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 THE NEW SYDENHAM 
 
 SOCIETY. 
 
 INSTITUTED MDCCCLV1I1. 
 
 VOLUME CXLVI.
 
 PALUDISM. 
 
 BY 
 
 DE. A. LAVEEAN, 
 
 PROFESSOR OP MEDICINE IN THE SCHOOL OP VAL DE GRACE. 
 
 TRANSLATED BY 
 
 J. W\ MARTIN, M.D., F.R.C.P.E. 
 
 LONDON: 
 THE NEW SYDENHAM SOCIETY. 
 
 1S93. 
 
 Med.
 
 w
 
 \ GO 
 
 TRANSLATOR'S PREFACE. 
 
 The work of which a translation is now offered to the members 
 of the New Sydenham Society may be considered as the chief of 
 a series of most valuable treatises which M. Laveran has written 
 upon the subject of paludism. It deals with and summarises the 
 important investigations he has conducted, and describes his dis- 
 covery of the malarial haeinatozoon which has made his name 
 famous. The accuracy of his description of the different forms 
 of the organism, and his account of the long series of cases in 
 which it was found, confirm its reality as a factor in the malarial 
 process. When it is demonstrated that these organisms disap- 
 pear pari passu with the cure of the disease M. Laveran's position 
 is very considerably strengthened. 
 
 It is too much to say that the discovery of these parasites puts 
 an end to all future investigations of paludism. Far from it ; the 
 composition of the blood, coupled with that of the possible pro- 
 ducts developed by these organisms, must be further examined 
 and explained. Thus the full knowledge of their bearing upon 
 the malarial process will entail further and elaborate investi- 
 gation. I do not think, however, that anyone can peruse 
 M. Laveran's work without it being at once apparent that his 
 discovery is in all likelihood the correct one. 
 
 His researches have been confirmed by many other observers. 
 Such able writers as Vandyke Carter and Hehir fully substantiate 
 them, as do various authorities in America. At the seventh Inter- 
 national Congress of Hygiene, held in London in 1 891, Professor 
 Cruikshank spoke to the presence of Laveran's organisms in man 
 as evidence of the existence of malaria, and their detection as in- 
 valuable as a diagnostic sign. 
 
 It is to be hoped that before long the whole life-history of 
 these parasites may be demonstrated, and, moreover, that charts 
 will be published showing the areas of distribution of the
 
 vi translator's preface. 
 
 malarial process with greater accuracy than has at present 
 been attempted. 
 
 I have endeavoured to render M. Laveran's views as accu- 
 rately as possible, without adhering too rigidly to a literal 
 translation. 
 
 J. W. MARTIN. 
 
 Edinbuhgh.
 
 PREFACE. 
 
 At the end of the year 1880 I pointed out the existence of new- 
 parasites in the blood of patients suffering from palustral fever, 
 and I have returned at different times to the description, of these 
 parasites to confirm my first observations, and on some points 
 to make them complete. 
 
 The parasites which I described as being those of marsh fever 
 differed very much from those which had been previously de- 
 scribed, and they did not belong to the class of schizophytes, to 
 which all pathog-enic microbes seem to belong; consequently my 
 first assertions were received everywhere with much scepticism. 
 
 Since 1880 investigations confirmatory of mine have been 
 multiplied, and I believe I can say without exaggeration that 
 to-day the existence of the haeniatozoon of paludism is admitted in 
 all parts of the globe where the disease is endemic. 
 
 In 1889 the Academy of Sciences conferred the very high honour 
 upon my work of bestowing upon me the Breant prize. 
 
 I shall be pardoned, I hope, if I quote here a part of Professor 
 Bouchard's report, as it constitutes a document too important in 
 the history of the hasmatozoon of paludism to be omitted. 
 
 "The Commission 1 by a unanimous vote bestow the Breant 
 prize (interest of the endowment) on M. A. Laveran, Professor in 
 the School of Val de Grace, for his discovery of the hgematozoon of 
 paludism. This discovery, which was made ten years ago, has 
 been verified by observers of the most different views in almost 
 every country where intermittent fever prevails. The parasite, 
 which is the pathogenic agent of an endemic the most ancient, 
 the most extensive, and the most serious of all that scourge 
 humanity, differs fundamentally from the parasites which are at 
 present known of other infectious diseases. It is at least the first 
 example of a disease being caused in man by a sporozoon. N<> 
 
 1 Commissioners: MM. Marey, Itichct, Charcot, Brown-Si'quard, Wrnouil ; 
 Bouchard, reporter.
 
 
 viii PBEFACE. 
 
 one to-day will support the ideas formerly held which attributed 
 palustral disease to various forms of algas or to bacteria. 
 
 " The discovery of M. Laveran comprises the whole patho- 
 genesis of intermittent fever ; it may be said that it has changed 
 the pathological anatomy of this disease. In fact, the character- 
 istic pigment of the lesions of palustral infections is effected by 
 the parasite, and is contained in the parasite itself." (Academy 
 of Sciences, public meeting of December 30th, 1889, p. 65.) 
 
 The existence of the hsematozoon of paludism is no longer 
 seriously disputed, but several points concerning the history of 
 this parasite are still obscure and require to be re-examined, taking 
 into consideration the numerous works which have been pub- 
 lished within the last few years. 
 
 What I have proposed to do in this new work is as follows : 
 Introduction. — Brief resume of researches anterior to mine on 
 the parasitic nature of paludism, and state of the question in 
 1880. 
 
 Chapter I. — Description of the hsematozoon of paludism. 
 Chapter II. — Eeview of researches subsequent to mine. 
 Chapter III. — Nature of the parasites of palustral blood. 
 A nalogous ksematozoa found in different animals. 
 
 Chapter IV. — The haematozoon which I have described is 
 really the agent of paludism. This parasite is polymorphous, but 
 unique. 
 
 Chapter V. — Pathogenesis of the phenomena of paludism. 
 Chapter VI. — Means of protection on the part of the organism. 
 Treatment and prophylaxis. 
 
 In the first chapters I have reproduced in part some articles 
 which appeared in 1889 and 1890 in the ' Archives of Experi- 
 mental Medicine and Pathological Anatomy.' I had only to com- 
 plete that work with the help of the most recent publications. 
 
 I have not thought it necessary to return to the clinical 
 description of the phenomena which paludism produces ; there 
 would be but little to add to the chapters devoted to this question 
 in my ' Traite des fievres palustres.' 
 
 Terminology is of great importance in science, and it must be 
 admitted that, in general, medical terminology leaves much to be 
 desired. There are more than twenty different terms for the 
 phenomena produced by palustral endemia. It seems to me that 
 it is high time to make a choice from among these terms, and no 
 longer leave the matter to individual taste. The word paludism, 
 proposed by Professor Verneuil, appears to me excellent. It is 
 short j it recalls the chief origin of the fevers, and does not give
 
 PREFACE. ix 
 
 a false idea of the nature of the phenomena, as some other terms — 
 for example, intermittent fever. 
 
 One might hesitate between palustral and paludal. Paludal 
 might be perhaps more exact, but the word palustral has been 
 accepted long ago, and for this reason I have adopted it, em- 
 ploying it generally as a qualifying adjective — thus, palustral 
 anasmia, palustral cachexia, &c. ; sometimes as a substantive, a 
 palustral designating a patient suffering from paludisro. 
 
 Apart from the figures interspersed in the text, several plates 
 represent the hasmatozoon of paludism under the different aspects 
 which it has in fresh blood, or in preparations of dried and 
 stained blood. 
 
 The haamatozoa of tortoises and of birds, which approach more 
 than any other the haainatozoa of paludism, are also represented 
 in several plates. 
 
 The photographs reproduced in Plates V and VI have been taken 
 by M. Yvon, from my preparations. The photographs of haenia- 
 tozoa are difficult to execute, and I thank M. Yvon very sincerely 
 for having so kindly placed at my disposal his great experience 
 of microscopic photography. 
 
 A. LAVERAN. 
 
 Paris; March ist, 1891.
 
 CONTENTS. 
 
 PAGE 
 
 Introduction ........ i 
 
 CHAPTER I. 
 
 Description of the hsematozoon of paludism — Different aspects under which 
 it is seen — Methods of examining the blood — Attempts at cultiva- 
 tion and inoculation in animals ...... 9 
 
 CHAPTER II. 
 
 Researches subsequent to mine — The hsematozoon of paludism has been dis- 
 covered by a large number of observers — Remarkable agreement of the 
 descriptions that have been given of it in all countries . . . 31 
 
 CHAPTER III. 
 
 The hsematozoon which I have discovered in palustral blood is a sporozoon — 
 
 Similar hsematozoa exist in different animals, and principally in birds . 55 
 
 CHAPTER IV. 
 
 The hsematozoon which I have described is the pathogenic cause of palu- 
 dism — The parasitic elements of palustral blood represent the different 
 stages of the evolution of the same polymorphic hsematozoon — Relation 
 of these different stages to the febrile types . . . .74 
 
 CHAPTER V. 
 
 In what form is the hiematozoon of paludism found in external media, 
 and how is the infection produced ? — Meteoric and tellui'ic conditions 
 which favour the development of paludism — Individual predisposing 
 •auses — Influence of race and age— Congenital paludism — Incubation — 
 Pathology of the phenomena of paludism . . . .96
 
 Xll CONTENTS. 
 
 CHAPTER VI. 
 
 PAGE 
 
 Means of defence of the organism — Spontaneous cure of paludism — Role of 
 the phagocytes — Tonic treatment — Specific action of quinine — Dif- 
 ferent modes of its administration — Prophylaxis of paludism . .115 
 
 Addendum . . . . . . . . .181 
 
 Literature . . . . . . . . .183 
 
 Index . . . . . . . . .193
 
 ON MARSH FEVER AND ITS ORGANISM. 
 
 INTRODUCTION. 
 
 The conditions which favour the development of paludism, and 
 those which are necessary to the multiplication of most of the 
 lower animal and vegetable organisms, are exactly the same ; and 
 the parasitic nature of paludism has long been suspected, as the 
 writings of Vitruvius, of Varron and Columellus show. 
 
 Laucisi and Rasori admitted that paludism was produced by 
 certain animalcules, which, engendered by the putrefaction of 
 the marsh, are found in suspension in the air of marshy places, 
 and are capable of penetrating the blood. These ideas were so 
 common in Italy at the beginning of this century, that the fever- 
 producing animalcules had received from the people a name — 
 that of serafici (death-producing). 
 
 According to Virey, infusoria are the principal cause of the 
 insalubrity of a marsh. Boudin considered it due to the vegetable 
 organisms which abound in marshy localities, and principally to 
 the marsh-flower, the vegetable species giving off into the atmo- 
 sphere toxic volatile principles which are capable of giving rise 
 to paludism. 
 
 Bouchard attributed these phenomena to a species of poison 
 secreted by some of the animalcules which abound in a marsh. 
 
 This is pure hypothesis, without more foundation than the 
 opinion of Boudin ; it has been observed that the marsh-flower, 
 in especial, could not account for the occurrence of paludism. 
 
 According to J. K. Mitchell, Miihry, and W. A. Hammond, 
 the spores which abound in the air of marshy localities are the 
 cause of paludism. 
 
 J. Lemaire, who published in 1864 f Researches upon the Micro- 
 scopic Organisms found in the Air of Marshes/ was obviously 
 
 1
 
 2 MARSH FEVER AND ITS ORGANISM. 
 
 inclined to think that the microphytes and the microzoa which 
 exist in the air of marshy localities are the cause of paludism, 
 but he does not name any one species in particular. 
 
 Similarly, Massy of Ceylon, Cunuingham of Calcutta, and 
 Corre of Senegal attribute it to the microscopic organisms in the 
 air or in the water of marshes as a whole, and do not specify 
 what is the pathogenic micro-organism. 
 
 From 1866 to 1880 these researches were conducted with more 
 precision, and on several occasions it was announced that the 
 parasite of paludism had been discovered. 
 
 The observers who look for the microbe of paludism in the 
 air, the water, and in the soil of unhealthy localities are natui'ally 
 led to attribute it to the micro-organisms which predominate 
 where the observations are made. 
 
 In 1866 Salisbury described little vegetable cells of the species 
 of Palmella as the cause of paludism ; these, he said, he had 
 found constantly in the urine and in the sweat of patients suffer- 
 ing from fever in the Ohio or Mississippi district. 
 
 In 1867 Binz pointed out the existence of bacteria in the 
 blood of patients suffering from palustral fever, and he announced 
 that he had induced paludism in animals by injecting into their 
 veins putrid matters of vegetable origin. 
 
 In 1869 Balestra described an alga found in the water of the 
 Pontine marshes as the pathogenic cause of palustral fever. 
 
 In 1876 Lanzi and Terrigi, following up experiments made on 
 animals, in the blood of which they injected water taken from 
 the marsh of Ostia, arrived at the conclusion that paludism is due 
 to a brownish bacterium which might be the cause of the pig- 
 mentation of the organs of those attacked. 
 
 In 1878 Eklund described, under the name of Limno'ph.y salts 
 hyalina, a micro-organism which he had often met among the 
 algge of marshy and fever-producing places, and which appeared 
 to him as deserving to be considered the parasite of paludism. 1 
 
 In 1879 Klebs and Tommasi Crudeli, following up researches 
 which were undertaken to verify the assertions of Lanzi and 
 Terrigi, arrived at the conclusion that the cause of paludism is 
 a bacillus. 
 
 I consider that it is unnecessary to describe here all the micro- 
 organisms which have been successively honoured with the title of 
 the parasite of paludism, not one of which has stood the test of 
 control researches ; the works of Klebs and Tommasi Crudeli are 
 the only ones that deserve our attention, the Bacillus malarise 
 1 For more details see ruy • Traite des fievres palustres,' pp. 31 — 51.
 
 INTRODUCTION. 3 
 
 having, in fact, been admitted by a great number of observers 
 when I began my researches. 
 
 Klebs and Tommasi Crudeli, after having established the pre- 
 sence of the bacillus in the air, in the water, and in the soil of 
 palustral localities, tried to cultivate these bacilli. Mud from 
 a marsh was exposed to the free air at a temperature of 36 to 
 40 C. in a manner so as to dry only the surface and leave the 
 subjacent layers humid, which appeared to be the condition most 
 favorable to the development of the agent of paludism ; a small 
 quantity of this mud was introduced into a cultivation fluid, and 
 this first culture served to inoculate other liquids which were 
 injected into the subcutaneous tissue of rabbits. Klebs and 
 Tommasi Crudeli were said to have succeeded by this process in 
 setting up in the animals under experiment phenomena analogous 
 to those of paludism. 
 
 According to these observers, the bacillus which is found in 
 
 the soil under the appearance of oval spores, mobile and strongly 
 
 refractile to light, is developed in cultui-e fluids and in the bodies 
 
 • of inoculated animals under the form of long filaments, at first 
 
 homogeneous, afterwards transversely segmented. 
 
 These experiments, and the conclusions to which Klebs and 
 Tommasi Crudeli came, are subject to numerous and grave 
 objections. The cultivation liquid was evidently very impure ; 
 the bacillus described as being the pathogenic cause of paludism 
 presented no single characteristic to distinguish it from the 
 numerous bacilli of the soil ; and further, the assertions of the 
 authors with regard to the phenomena produced in animals are 
 very questionable : the therrno metric tracings given as being 
 those of intermittent fever were very little characteristic — the 
 same applies to the anatomical lesions observed in the rabbit ; 
 and it must also be added that at the present time it still remains 
 to be demonstrated that these animals are susceptible to paludism. 
 
 Researches, undertaken in Italy by Perroncito, Ceci, Cuboni, 
 Marchiafava, Valenti, Ferraresi, Piccirilli, appeared at first to 
 confirm those of Klebs and Tommasi Crudeli. 1 
 
 Cuboni affirmed that this bacillus was peculiar to paludism, 
 and that he had succeeded in cultivating it ; Mai'chiafava and 
 Ferraresi were said to have established that the blood of patients 
 suffering from intermittent fever examined during the cold stage 
 
 1 Klebs and Tommasi Crudeli, " Studien ueber die Ursache des Wecheelfiebers 
 u. ueber die Natur der Malaria" ('Arch, f. expor. Pathol, u. Pharmakol.,' vol. 
 xiii). Tommasi Crudeli, tbe 'Practitioner,' November, 1S80, p. 321. Cuboni 
 and Marchiafava, 'Arch. f. exper. Pathol.,' vol. xiii, 1881.
 
 4 MARSH FEVER AND ITS ORGANISM. 
 
 contained always, and at times in great quantity, the Bacillus 
 mal arise at its stage of complete development, while during the 
 height of the fever the bacilli disappeared from the blood, and 
 only their spores were found. 
 
 In 1882 Ceci published the results of experiments made in the 
 laboratory of Klebs ( f Archiv f. experim. Path. u. Pharm.,' vols. 
 xv, xvi), and the conclusions of his work agreed with those of 
 Klebs and Tommasi Crudeli ; the author was said to have suc- 
 ceeded in setting up the phenomena of palustral fever in dogs 
 and rabbits by injecting into their veins the culture fluids pre- 
 pared from palustral earth. 
 
 Such was the state of the question at the time when I pub- 
 lished the first results of my observations on the parasites of 
 paludism ; it is, I believe, useful to recount it at the beginning 
 of this work in order to let the reader appreciate the results of 
 my work, and to judge of the progress which has been made 
 since 1880 in the knowledge of the nature and causes of paludism. 
 
 Another problem remained very obscure in 1880 — that of 
 palustral melanaemia. As the study of palustral rnelanremia was 
 the cause of my researches, and as it is intimately connected with 
 the history of the parasites of paludism, it merits some attention. 
 
 The brown coloration of the spleen, of the liver, and of the 
 brain has been pointed out by all observers who have had the 
 opportunity of making autopsies on subjects who have died of 
 pernicious attacks ; but the first observers being deprived of the 
 aid of the microscope did not know to what to attribute this 
 particular coloration, which they noticed only in those cases 
 where it was very pronounced. 
 
 Lancisi, Stoll, Bailly, Monfalcon, demonstrated that there often 
 existed in persons who had died of paludism an abnormal pig- 
 mentation of the liver and brain. Popken and Fricke, Chisholm, 
 Thnssinck, Anderson, Prick, Drake, Annesley, Stewardson, attri- 
 buted the abnormal pigmentation of the spleen, liver, and brain 
 to the alterations most associated with paludism. 1 Maillot 
 pointed out on several occasions the brown tint of the spleen in 
 those suffering from fever, and he rightly compared this colora- 
 tion to that of chocolate and water. Out of twenty-two autopsies 
 of pernicious fever mentioned in his ' Traite des fievres inter- 
 mittentes ' (Paris, 1836, pp. 285 — 287), the dark tint of the grey 
 suljstimce of fche brain is mentioned eight times ; in five cases 
 tli;it coloration had assumed almost a blackish hue. 
 
 According to Haspel, the pigmentation of the spleen, the liver, 
 1 See my ' Traite des fievres palustres,' p. 100.
 
 INTRODUCTION. 5 
 
 and the brain is one of the most constant changes in paludism 
 (' Malad. de l'Algerie,' Paris, 1850, t. i, p. 335 ; t. ii, p. 318). 
 
 Meckel first recognised that the brownish tint of certain 
 viscera in patients who had died of palustral fever was the result 
 of an accumulation of pigment in the blood. 
 
 Virchow, Heschl, Planer, and Frerichs in especial have given 
 good descriptions of palustral rnelaneeniia. Frerichs described 
 well the changes produced by melansemia in the different organs — 
 liver, spleen, lungs, kidneys, brain. He even shows in the brain, 
 besides particles of pigment, colourless and hyaline concretions 
 which obstruct certain capillary vessels (' Traite des malad. du 
 foie/ French translation, p. 493). Frerichs had never thought of 
 the parasitic nature of these latter elements, which are, moreover, 
 indistinguishable in the conditions in which he studied them, that 
 is in organs examined at least twenty-four hours after death. 
 
 According to Frerichs, it is in the spleen that the most part 
 of the pigment is produced ; the stagnation of the blood in the 
 venous sinuses of the spleen is, he thinks, the principal cause of 
 that alteration. 
 
 Frerichs, and after him Griesinger, gave to the accumulation 
 of pigment in the capillary vessels of the brain an important part 
 in the pathogenesis of the brain-changes in paludism — pernicious 
 fevers with delirium, somnolence, and coma. 
 
 The articles on melanasmia (' Dictionnaire encyclopedique des 
 sciences medicales '), and of the f Dictionnaire ' of Jaccoud, 
 written by B. Ball and by Hallopeau, show that although when 
 they were written (1873 — 1876) the study of the pathological 
 anatomy of melansemia was well understood, the causes and 
 nature of the lesion were still very obscure. Melanasmia was 
 considered neither as a constant lesion of paludism nor as a 
 lesion peculiar to this malady ; as for the formation of pigment, 
 there are several theories, which I think it unnecessary to 
 give here. 
 
 In two treatises on palustral inelanasmia (' Arch, de Physiol./ 
 1875, and ' Arch. gen. de Med.,' 1880) Kelsch came to the 
 conclusion that raelanaemia was a lesion peculiar to paludism ; 
 according to this observer the pigment was formed in the blood, 
 but the mechanism of this formation was still obscure, and the 
 question was now more important than ever, Why does palustral 
 fever produce pigment, while other fevers more dangerous — e. g. 
 typhoid, typhus — are not accompanied by inelanasmia ? 
 
 On arriving at Bona in 1878 I had the opportunity of making 
 several autopsies on subjects who had died from pernicious
 
 6 MARSH FEVER AND ITS ORGANISM. 
 
 attacks, and I was struck with the fact that melanaemia was a 
 lesion peculiar to and very characteristic of paludism; my attention 
 was naturally directed to this lesion, Avhich I had never met in 
 any other disease. 
 
 Melanaemia is specially very pronounced in individuals who died 
 from acute paludism (pernicious attacks) ; the colour which it 
 gives to certain organs, particularly to the spleen, the liver, and 
 the grey substance of the brain, is almost always sufficient to 
 show from microscopic examination if death is the result of 
 paludism. 
 
 I shall state here shortly the alterations which are observed 
 in acute paludism : in chronic paludism lesions are complex ; the 
 alterations of the blood are complicated with congestions and 
 inflammations which, in palustral cachexia, are highly noticeable. 
 These inflammatory lesions, principally the vascular cirrhoses, are, 
 moreover, well explained by the existence in the blood of para- 
 sitic elements. 
 
 Some observers have been able to maintain that occasionally 
 no single characteristic alteration was found in individuals who 
 had died of pernicious fever. 
 
 This assertion does not stand a strict examination, and could 
 only be put forward at a time when the importance of melanasmia 
 was not known. It might be affirmed, on the contrary, that in 
 these cases there always remain lesions specially pronounced in 
 the spleen and liver. The spleen increases in volume and weight, 
 but the increase is not always considerable ; in one patient who 
 died of a pernicious attack the spleen did not weigh more than 
 400 grammes. The shape of the organ is modified, the edges 
 are rounded ; the spleen tends to take a globular form, which 
 is explained by the softening, the pulpiness of the splenic 
 parenchyma. It often happens that the mere act of grasping 
 the spleen to pull it out from the abdomen causes rupture of the 
 distended and thin capsule ; the fingers sink into the splenic 
 pulp. 
 
 The colour is characteristic ; instead of the normal red colour 
 the spleen shows in the inner parts, as well as on the surface, a 
 brownish tint which has been compared to chocolate and water. 
 
 If you examine a drop of splenic fluid with the microscope 
 you will find in the midst of the blood, and the elements proper 
 to the spleen which are separated, the existence of pigmented 
 elements in great numbers, and free granules of pigment; the 
 pigmented elements are either leucocytes loaded with pigment, or 
 hyaline bodies of irregular shape : one finds in those preparations
 
 INTRODUCTION. 7 
 
 of the spleen pigmented granules much more numerous than in 
 blood taken from the vessels of other organs. 
 
 The liver is generally increased in volume and weight ; its 
 consistence is often diminished, but the only constant and 
 characteristic alteration consists in a greyish-brown or slate- 
 coloured tint which is taken by the hepatic parenchyma. 
 
 By histological sections of a piece of the liver made after 
 hardening, it is easy to see that the blood-capillary vessels enclose 
 pigmentary elements in great numbers, which distend them more 
 or less. 
 
 Histological examination of the kidneys reveals also the exist- 
 ence of pigmentary elements, especially in the Malpighian glome- 
 ruli ; a certain number of pigmented elements circulating with the 
 blood are evidently arrested there. 
 
 Melansernia is often sufficiently well marked in the grey 
 substance of the brain to allow one to see it with the naked eye ; 
 the grey substance of the convolutions takes a dark grey or violet 
 tint, which can be compared to that of certain dark-coloured 
 hortensias. The histological examination of the sections of the 
 brain after hardening by the ordinary process shows that the 
 capillaries enclose a large number of pigmented elements ; the 
 pigmented granules are in some cases regularly disposed along 
 the length of the brain capillaries, the appearance of which is 
 quite characteristic. 
 
 In the other parts of the brain, in the pons, in the medulla, the 
 capillaries also enclose numerous pigmented elements. If the 
 grey tint is more apparent in the grey substance of the convolu- 
 tions, it evidently depends on the abundance of the capillaries in 
 that substance. The medulla of the bones has a brownish tint due 
 to the presence of pigmented elements, similar to those found in the 
 spleen. The other tissues have a normal tint, but by histological 
 sections it is easy to see that the capillary vessels contain pig- 
 mented elements more or less numerous, and that melanaomia is 
 really, as the etymology implies, a general alteration of the blood, 
 which is only more pronounced in the spleen, in the medulla of 
 bones, and the liver than in the other viscera, which is naturally all 
 the more apparent as the tissues are more vascular. 
 
 When one examines a drop of blood taken from the dead body of 
 a palustral subject in the ordinary conditions of autopsy — that is 
 to say, twenty-four hours after death — one sees in the midst of the 
 blood numerous pigmented bodies. Many of these elements are 
 melaniferous leucocytes, the nuclei of which can be coloured and 
 stained with carmine ; but beside these leucocytes, hyaline pig-
 
 8 MARSH FEVER AND ITS ORGANISM. 
 
 merited irregular bodies are seen, which can only be coloured 
 slightly, or not at all, by carmine, and which do not contain 
 any nuclei. These latter elements have great analogy in their 
 dimensions, and often in their shape, with melaniferous leucocytes, 
 and it can easily be understood that they may have been con- 
 fused with them. If the blood is taken shortly after death the 
 parasitic elements characteristic of paludism can be recognised.
 
 CHAPTER I. 
 
 Description of the hsematozoon of paludism — Different aspects under 
 which it is seen — Methods of examination of the blood — Attempts 
 at cultivation and inoculation in animals. 
 
 In 1880, as I was trying to account for the mode of formation 
 of the pigment in the palustral blood, I was led to see that 
 besides melaniferous leucocytes, spherical hyaline corpuscles with- 
 out nucleus could be seen, and also very characteristic crescent- 
 shaped bodies. 
 
 I had proceeded thus far with my researches, and was still 
 hesitating whether these elements were parasites, when on 
 November 6th, 1880, on examining the pigmented spherical bodies 
 mentioned above, I observed, on the edge of several of these 
 elements, moveable filaments or flagella, whose extremely rapid 
 and varied movements left no doubt as to their nature. 
 
 I published in 1881 the observation of the patient in whose 
 blood I saw the flagella for the first time (' De la nature para- 
 sitaire des accidents de l'impaludisme,' Paris, 1881, p. 58) ; this 
 observation is given at the end of this book (Observation 22). 
 
 The very fact that I can quote the day on which I observed 
 the flagella for the first time shows how characteristic these 
 elements are. It was natural to suppose that these parasitic 
 elements, for the most part pigmented, were the cause of palus- 
 tral melangemia, and also the cause of the phenomena of paludism. 
 Numerous facts soon came to confirm this hypothesis. 
 
 The parasite of palustral blood is seen under rather varied 
 forms, which may be classed under the four following types : 
 
 1st. Spherical bodies. 
 
 2nd. Flagella. 
 
 3rd. Crescent-shaped bodies. 
 
 4th. Segmented bodies and rose-shaped bodies. 
 
 1st. Spherical bodies. — This is the most common form, and the 
 one most often met ; I have noticed it, in the examination of 
 palustral cases, 389 times out of 432. These elements often 
 possess amoeboid movements which alter their shape more or
 
 10 
 
 MARSH FEVER AND ITS ORGANISM. 
 
 less. They are composed of a hyaline, colourless, and very 
 transparent substance, and have variable dimensions : the 
 smallest have scarcely i fi } the largest have a diameter equal to 
 or even greater than the diameter of a red blood-corpuscle ; some 
 of the elements have a diameter twice as large as that of blood- 
 corpuscles. 
 
 The contours are shown by very fine lines ; on preparations 
 stained with osmic acid and colouring reagents, a double contour 
 may be found, which is not seen in elements observed in fresh 
 blood. The smallest only contain one or two granules of pig- 
 ment, or even none at all. They have the appearance of little 
 colourless clear spots in the blood-corpuscle. 
 
 
 Fig. i. — a. Normal red blood-corpuscle. B, c. Blood-corpuscles with spherical 
 bodies of very small size not pigmented. D, E, F. Blood-corpuscles with 
 spherical bodies of small size pigmented, g. Blood-corpuscle with a spherical 
 body distorted by amoeboid movements. H, I. Blood-corpuscles with several 
 spherical bodies pigmented, k. Spherical body, pigmented, fully deve- 
 loped, l. Spherical body containing grains of pigment in movement. 
 M. Spherical body on which a double contour is distinguished, n. Free 
 spherical bodies, o. Spherical bodies massed together. (X iooo.) 
 
 In proportion as these elements enlarge the number of gran- 
 ules of pigment increases ; these granules make a fairly regular 
 circle, or else they are arranged irregularly, and often possess very 
 rapid motion. This motion has neither the constancy nor the 
 regularity of the Brownian movement, with which, in other 
 respects, it has a certain analogy ; it diminishes or increases 
 in rapidity, it stops sometimes, to commence again, without the 
 physical condition of the preparation being modified. On their 
 first appearance one is inclined to believe that the pigmented 
 corpuscles possess a movement of their own; but it seems almost 
 certain that it is a movement imparted to them. 
 
 The amoeboid movements of spherical bodies coincide often with 
 the motion of the granules or pigment ; these distortions, which
 
 DESCRIPTION OF THE H^MATOZOON. 11 
 
 take place rather slowly like those of anicebas, are easy to see 
 when the same element is in the centre of the field of the micro- 
 scope, and is drawn say every minute. These spherical bodies 
 are at times free in the serum (k, l, n, o, Fig. 1), at times 
 adherent to the red blood-corpuscles (b, c, d, e, f, g) ; on the 
 same blood-corpuscle sometimes two, three, or four of these bodies 
 are found (h, i). 
 
 These parasites evidently live at the expense of the blood- 
 corpuscles, which grow pale in proportion as the parasitic elements 
 which adhere to them increase in size ; there is a time when the 
 blood-corpuscle is only distinguished by its contour ; its charac- 
 teristic colour has disappeared, its transparency is the same as 
 that of the parasite, and soon the corpuscle disappears com- 
 pletely. 
 
 The red blood-corpuscles attacked by parasites have often a dia- 
 meter considerably larger than that of the normal blood-corpuscle ; 
 the characteristic yellowish colour and their disc-like shape also 
 disappear, the blood-corpuscles becoming, so to speak, dropsical. 
 Are, then, the parasites enclosed in the blood-corpuscles, or are 
 they simply adherent to them ? This question, which after all is 
 secondary, is difficult to answer by direct observation. 
 
 Our knowledge of the structure and composition of the blood- 
 corpuscles in man makes it difficult for us to understand how 
 these parasites can enter them. The probability is that they 
 simply adhere to the blood-corpuscles by pressing upon them. 
 What makes this supposition more likely to be true is that the 
 parasitic elements are often found in the blood in a free state, and 
 that at all periods of their development. 
 
 The spherical bodies may be multiplied by means of segmenta- 
 tion or by budding. 
 
 On examining minutely one of these elements possessing 
 amoeboid movements, it sometimes happens that this body is seen 
 to divide into three or four similar but smaller elements ; these 
 elements separate themselves and become free. Some kinds of 
 sarcoid balls are sometimes formed on the edges. 
 
 After a variable time, seldom extending over half an hour or 
 three quarters of an hour, the movements of the granules of 
 pigment stop, and the spherical bodies take their cadaveric form ; 
 the contours are more or less irregular, the pigment collects in 
 certain points ; the bodies are still easily distinguished from the 
 melaniferous leucocytes by the absence of a nucleus. 
 
 Some observers have described a nucleus in the spherical 
 bodies; if it exists (which is not yet proved), this nucleus is
 
 12 MARSH FEVER AND ITS ORGANISM. 
 
 very difficult to see, and is not coloured by the methyl aniline 
 blue, as is the case with the nuclei of leucocytes. 
 
 Figs. 2 to 1 8, PL I, inserted at the end of this book, represent 
 diseased red blood-corpuscles to which from one to four spherical 
 bodies adhere, first without pigment, then with black granula- 
 tions. The red corpuscle increases in size and becomes pale 
 (15, 16), then completely disappears. Figs. 19 and 20 show 
 free spherical bodies in their complete development ; figs. 21 and 
 22 show small spherical bodies, free, isolated, grouped, and massed 
 together. 
 
 In fig. a, PI. II, I have represented spherical bodies free or 
 adherent to blood-corpuscles, just as they are seen in fresh blood. 
 Fig. b in the same plate shows spherical bodies in the different 
 degrees of their development, with the appearance they present 
 in the preparation of blood, di'ied and stained by methyl aniline 
 blue. Lastly, fig. a in PI. Ill shows spherical bodies in their 
 different stages of development, either free or adherent to the 
 blood-corpuscles, as they appear in preparations of dried blood 
 submitted to the double staining of eosine and methyl aniliue blue. 
 
 Marchiafava and Celli make claims in relation to the discovery 
 of these elements, to which I must refer in analysing works 
 which are subsequent to mine. These observers assume that I 
 had not seen the largest pigmented forms of spherical bodies, and 
 that I had not described the amoeboid movements ; on that account 
 I think it my duty to reproduce here some passages from my 
 earlier publications. 
 
 In a communication to the Academy of Sciences (sitting 
 October 24th, 1881), after having spoken of crescent-shaped ele- 
 ments, of spherical bodies containing mobile pigmented granules, 
 with or without flagella, and of free flagella, I also mentioned as 
 parasitic elements of palustral blood small elements which scarcely 
 measure the sixth part of the diameter of one blood-corpuscle, and 
 which only enclose one or two granules of pigment. I add that these 
 bodies, sometimes isolated, sometimes grouped together in threes 
 and fours, now free in the blood, now adherent to blood-corpuscles, 
 seem only to represent one of the phases in the development of 
 larger spherical bodies. 
 
 I also mention the red blood-corpuscles which seem fenestrated, 
 and are nothing but blood-corpuscles to which small hyaline 
 bodies without pigment adhere, making colourless spots on the 
 blood-corpuscles (Acad, des Sciences, ' Comptes rendus/ t. xciii, 
 p. 628). 
 
 In a communication made to the Medical Society of the Paris
 
 DESCRIPTION OF THE H.EMATOZOON. 13 
 
 hospitals on April 28th, 1882,1 pointed out the existence of small 
 transparent elements, the smallest of which only measured 1 /n } and 
 only contained one or two granules of 'pigment. These bodies are 
 sometimes free, sometimes adherent to red blood-corpnscles, sometimes 
 three or four of these bodies are found on the same blood-corpuscle. 
 At an ordinary temperature these elements show amoeboid move- 
 ments. 
 
 A coloured plate accompanying this work, which was communi- 
 cated in 1882 to the Medical Society of Hospitals, represents small 
 elements, free, isolated, or grouped together, and other elements, 
 one, two, and three in number, which adhere to blood-corpuscles. 
 
 In the 'Revue scientifique ' of April 29th, 1882, the small 
 elements, which only measure 1 fi } are also described and repre- 
 sented in a free state or within the red blood-corpuscles ; in this 
 work I also show that these elements present amoeboid move- 
 ments at an ordinary temperature. 
 
 In the second edition of the ' Nouveaux Elements de Patho- 
 logie medicale ' (in conjunction with Teissier, Paris, 1883) these 
 small elements are also described and represented (op. cit., t. i, 
 p. 93, and fig. 12). 
 
 In my ' Traite des fievres palustres ' (Paris, 1884), fig. 7 
 represents small elements free or adherent to blood-corpuscles ; 
 the smallest do not even measure 1 ft, and only contain one 
 granule of pigment ; one of them does not contain any at all. I 
 point out (p. 1 67) the frequency of red blood-corpuscles which show 
 small colourless spots, at p. 168. I note the amoeboid move- 
 ments of the bodies which I then described under the name of 
 body No. 2. Fig. 1 1 also represents small elements free or 
 adherent to red blood-corpuscles. 
 
 At p. 203 (op. cit.) I write, " The primitive embryonic form 
 of the parasites of paludism seems to be represented by the little 
 spherical transparent bodies which I described under the name of 
 body No. 2, of small volume, and which are presented in fig. 7. 
 These little bodies are free or adherent to red blood-corpuscles, at 
 the expense of which they evidently live, for the red blood-cor- 
 puscles which support them grow paler in proportion as they in- 
 crease in size, and at last disappear. At first these elements ai*e 
 hyaline, transparent, and non-pigmented, and the blood-corpuscles 
 to which they adhere simply show little clear spots; soon a granule 
 of pigment is formed within, then two and three, and very soon 
 the pigmented granules become so numerous that it is difficult 
 to count them." 
 
 The existence in the blood of the smallest of these elements is
 
 14 
 
 MARSH FEVER AND ITS ORGANISM. 
 
 frequently noticed in the course of clinical observations published 
 in this book ; particularly Obs. 21, 32, 35, 36, 41, and 42, which 
 were collected in 1881 and 1882. 
 
 We shall see further that in 1884, after the publication of 
 my ' Traite des fievres palustres/ Marchiafava and Celli still 
 maintained that the elements which I had described were only 
 degenerated red blood-corpuscles. This fact alone should enable 
 people to estimate fairly the claims of these authors. 
 
 2nd. Flagella. — When a preparation of blood is carefully 
 examined, in which spherical bodies of ordinary size are found in 
 a free state, mobile filaments or flagella are often seen upon the 
 edge of these elements ; these flagella move very quickly, and 
 give to the neighbouring blood-corpuscles very varied move- 
 ments : the blood-corpuscles are diminished, folded, and yet they 
 always resume their form as soon as the flagella are a little 
 removed. These movements can be compared to those of small 
 eels which are fixed by their tails and seeking to get free. The 
 flagella are so fine and so transparent that in spite of their 
 length for microbes, three or four times the diameter of the 
 blood-corpuscles, it may be 21 to 28 f.i, it is very difficult to see 
 them when they are at rest. The flagella are liberated from the 
 spherical bodies ; the act of their freeing themselves can sometimes 
 be seen. 
 
 The number of flagella which adhere to one spherical body is 
 variable : sometimes only one of these elements is distinguished 
 (c, Fig. 2) ; at other times two, three, or four (a, b) : the move- 
 
 Fig. 2. — a. Spherical body with four flagella. B. Spherical body with 
 three flagella, one of which shows a slight swelling, c. Spherical body 
 d. Flagellum free. (About X 1000.) 
 
 with one flagellum. 
 
 ments of each flagellum are independent of those of neighbouring 
 flagella. 
 
 When the flagella are three or four in number they are
 
 DESCRIPTION OF THE HJiMATOZOON. 15 
 
 sometimes rolled up, so that it is very difficult to say what their 
 number aud dimensions are. 
 
 The movements of flagella may be seen in the blood after it 
 is taken from the vessels, especially when the outside temperature 
 is very high, bnt generally it is much easier to make the obser- 
 vation after fifteen to twenty minutes. Perhaps the movements 
 stop under the influence of the cooling of the blood on coming out 
 of the vessels. 
 
 The free end of the flagellum often presents a little pyriform 
 swelling, only discernible when this very mobile end is exactly in 
 the line of vision. These swellings at the extremities have been 
 shown in all the flagella a and b (Fig. 2). 
 
 Besides these, small swellings sometimes appear which seem to 
 move along the flagella (b, Fig. 2) ; I have several times seen a 
 pigmented particle which seemed to come from the interior of the 
 spherical body and moved along the flagellum, causing a slight 
 swelling as if the flagellum had been hollowed out of a canal. 
 
 Sometimes the flagella are placed symmetrically, at others they 
 are grouped together at one point of the spherical body. 
 
 In observing a spherical body provided with flagella, such as 
 a and b in Fig. 2, it is difficult not to think that it is an 
 animalcule provided with pseudopodia, all the more so because 
 the flagella often give more or less extensive movements to the 
 spherical body. It is generally an oscillating movement in one 
 place without the spherical body leaving its place, but if the 
 layer of blood is rather thick it undergoes a real movement of 
 transition. 
 
 The varying number of flagella and their irregular disposition 
 do not accord with the idea of a parasite provided with pseudo- 
 podia, but the real reason for giving up that idea is that at a 
 given time the flagella leave the spherical bodies and circulate 
 among the blood-corpuscles. The flagella when they have become 
 free are difficult to follow ; instead of moving in one particular 
 place, as when they were adherent to the spherical bodies, they 
 move rapidly in the field of the microscope : the fixed point 
 furnished by the pigmented spherical body is also missed. It is 
 evident that each flagellum then lives an independent life. 
 
 After the flagella have become free, the pigmented bodies to 
 which they adhered alter their shape and remain motionless, the 
 granules of pigment accumulating in one or more points. 
 
 It has been attempted to minimise the importance of flagella 
 by saying that they are very rare in palustral blood. It is certain 
 that these elements are observed more rarely and with more diffi-
 
 16 MARSH FEVER AND ITS ORGANISM. 
 
 culty than the spherical and crescent-shaped bodies ; the flagella 
 are only produced in one phase of the evolution of the parasites 
 of paludism, they are invisible in a state of rest, and in addition 
 they rapidly disappear under the influence of quinine. Out of 
 432 palustral patients whom I examined, I found flagella in 92 only. 
 
 Flagella are represented in PI. I (figs. 29 — 32) ; PI. II (fig. a) 
 gives a fairly exact idea of the very characteristic appearance 
 which these elements take when they move in fresh blood among 
 the blood-corpuscles which they displace. 
 
 The flagella are always found in the blood at the same time as 
 the spherical bodies described above, and also often at the same 
 time as the crescent-shaped bodies which will be described later 
 on. I have never succeeded in seeing flagella come out of a 
 crescent-shaped body ; but these latter may, as we shall see, go 
 through a slow transformation from an oval to a spherical form, 
 and it is very probable that these spherical bodies give rise to 
 flagella, as do the spherical bodies themselves. 
 
 The flagella, although rather rare in the peripheral blood 
 (according to the researches of Councilman they are to be found 
 much more frequently in the blood taken directly from the spleen), 
 are not the less on that account the most characteristic elements 
 among the different forms which are taken by the parasites of 
 paludism. 
 
 I have often been asked to examine parasites, and I have always 
 noticed that when I had only spherical elements or crescent-shaped 
 bodies to demonstrate, there remained some doubts in the mind of 
 the observer; if I succeeded in finding flagella all hesitation dis- 
 appeared : an examination of a few minutes was sufficient to 
 remove all doubts. 
 
 It is after having verified the existence of flagella in fresh 
 blood that Professor Bouchard said, in the Academy of Sciences, 
 " A recent note by M. Laveran leads me to point out the impor- 
 tance of a discovery which now goes back ten years, which, 
 although contradicted for a long time, seems to me now unassail- 
 able " (Academy of Sciences, sitting January 21st, 1889). 
 
 Professor Straus has also been satisfied of the parasitic nature 
 of the elements found in the blood of palustral patients from the 
 day when he was able to observe the flagella ; I had shown him 
 previously the spherical and crescent-shaped bodies without suc- 
 ceeding in completely convincing him. 
 
 " I confess," says M. Straus, " that I was amongst those who 
 still entertained some doubts of the truth of M. Laveran's dis- 
 covery, so much is one inclined to mistrust new ideas which do
 
 DESCRIPTION OF THE HiEMATOZOON. 17 
 
 not belong to the ordinary stock of information ; but these doubts 
 have been completely dissipated. M. Laveran has kindly shown 
 me at Val-de-Grace preparations of blood taken from a soldier 
 suffering from an attack of intermittent fever, who had returned, 
 from Tonquin. The several forms of the parasite described by 
 him could be seen there very distinctly, specially the flagellated 
 bodies, which are eminently characteristic ; these spherical bodies, 
 provided with vibrating flagella which possess extremely quick 
 movements, and displace red corpuscles after the maimer of whips, 
 form one of the most striking pictures which can be seen under 
 the microscope. This picture is as distinct and as characteristic 
 as that of the blood of anthrax, or the blood of an individual 
 suffering from filaria " (' Soc. de Biologie/ November 24th, 1888). 
 
 The observers, numerous at the present time, who have suc- 
 ceeded in finding flagella in palustral blood are unanimous in 
 declaring that seeing the flagella in movement is absolutely 
 characteristic, and that once seen it is impossible to doubt that 
 these elements are living. The flagella are not generally seen 
 in preparations of dried and stained blood. I have, however, 
 seen some in these preparations, which proves that the flagella 
 existed in fresh blood, the drying taking place very quickly on 
 separation from the vessels. 
 
 3rd. Crescent-shaped bodies. — These are cylindrical elements 
 more or less pointed at their extremities, and usually bent in 
 crescent form (a, Fig. 3) ; the substance of these bodies is trans- 
 parent, colourless except towards the middle, where granules of 
 pigment similar to those of the spherical bodies are found. 
 
 The length of these elements is generally a little greater than 
 the diameter of the blood-corpuscles, i. e. from 8 to 9 jx ; it 
 is worthy of note that one never finds crescent-shaped bodies 
 of small size or of a size much greater than that just mentioned ; 
 the breadth is about 2 li towards the middle. The extremities 
 of the crescent are sometimes very pointed, sometimes rounded. 
 
 Their appearance in fresh blood is shown by a single very 
 fine line, but it is easy to see in certain preparations Avhich have 
 undergone the action of osmic acid, or of colouring reagents, 
 that there exists a double contour. 
 
 The granules of pigment whose presence is constant are almost 
 always massed towards the middle, they are more or less heaped 
 together ; in exceptional cases the pigment is to be found at 
 one of the horns. 
 
 A very fine line is usually seen on the side of the concavity, 
 and this joins the two extremities of the crescent (b, Fig. 3). 
 
 2 '
 
 18 MARSH FEVER AND ITS ORGANISM. 
 
 These elements are free in the blood ; when one is adherent 
 to the blood-corpuscles (c, Fig. 3) it is by accident ; if the cover- 
 glass is struck ever so lightly so as to displace the blood-corpuscles, 
 the crescent-shaped body is generally displaced and becomes free. 
 Spherical bodies adherent to red blood- corpuscles, on the contrary, 
 adhere very strongly to them, and it is impossible to free them 
 in the way just mentioned. 
 
 By setting up a small current in a preparation of blood it is 
 easy to ascertain that the crescent-shaped bodies have really the 
 cylindrical form mentioned above ; they turn on their own axis 
 following the current, and show their different phases. 
 
 Fig. 3. — a, b. Crescent-shaped bodies, c. Crescent-shaped body joined 
 to a blood-corpuscle. r>. Crescent-shaped body. E. Oval body. (About 
 X 1000.) 
 
 Besides these crescent-shaped elements others are also found 
 which are scarcely curved, or even whose main axis is straight, 
 and which have more or less the oval form represented by e 
 (Fig. 3). By leaving a crescent-shaped body in the field of the 
 microscope, it may be seen that after a certain time this body 
 assumes an oval form. The oval body itself is changed after a 
 variable time to a round body. 
 
 These elements do not possess motion ; the pigmented granules 
 which they contain are motionless, the changes in form mentioned 
 above take place slowly, and have nothing in common with the 
 amoeboid movements ; lastly, one never finds flagella on the sides 
 of the crescent-shaped bodies. 
 
 The shape of these elements, their dimensions, which are always 
 about the same and which are nearly equal to those of the red 
 blood-corpuscles, the fine line which often unites the horns of 
 the crescent, and which seems to belong to a blood-corpuscle 
 which has been almost entirely destroyed, lead one to think that 
 they are blood-corpuscles invaded by the haematozoa of paludism. 
 
 Sometimes this origin of the crescent-shaped bodies is very 
 apparent; the fine line which unites the two ends of the crescent 
 makes with the outward edge of the crescent a regular circle, 
 which has exactly the dimensions of a red blood-corpuscle. It is 
 to be noticed that no small crescent-shaped bodies are ever found 
 in the blood-corpuscle in a state of development as may be ob-
 
 DESCRIPTION OF THE HiEMATOZOON. 
 
 19 
 
 served in the case of certain hasrnatozoa in animals (Drepanidium 
 ranarum, for example). 
 
 Some observers admit that the crescent- shaped bodies have 
 nuclei. 
 
 The crescent-shaped bodies are shown in Plate I, figs. 33 and 
 34, as well as the oval and spherical bodies which are derived from 
 them (figs. 37, 38). 
 
 Fig. a in Plate II shows crescent- shaped bodies as they appear 
 in fresh blood ; and fig. b in the same plate shows their appear- 
 ance in a preparation of blood dried and stained with methyl 
 blue. 
 
 Fig. a in Plate III shows the same elements in a preparation 
 of dry blood and submitted to double staining (eosine and methyl 
 blue). 
 
 4th. Rose-shaped or segmented bodies. — Beside the spherical 
 bodies and flagella and crescent-shaped bodies, spherical elements 
 pigmented in the centre and regularly segmented may be some- 
 times found in the blood of palustral patients. In my ' Traite 
 des fievres palustres' this variety of parasitic elements is mentioned 
 on p. 177. This segmentation is represented in d, e, g, h, in 
 Fig. 4. These elements were drawn at Constantine in Septem- 
 ber, 1 88 1, and observed during an attack of quartan fever. I 
 have also noticed these elements in some cases of quotidian fever; 
 they seem to me very rare in tertian fever. 
 
 Fig. 4. — a, b, c. Hyaline bodies pigmented, motionless, and mis-shapen. 
 D, E. Segmented and rose-shaped elements, pigmented at the centre. 
 G, H. Elements resulting from the segmentation of rose-shaped bodies. 
 1, K, L. Melaniferons leucocytes whose nuclei have been brought out by 
 carmine. (About X 1000.) 
 
 This rose shape has, according to Golgi, a great importance; 
 it represents the principal mode of multiplication of the parasite 
 of paludism ; moreover this mode of segmentation is different in 
 the tertian and quartan fevers. I shall return later to this ques- 
 tion ; for the present it is sufficient to say that I have not often 
 had the opportunity of meeting this rose-shaped form in palustral 
 blood, which explains the very secondary place which I have 
 assigned to it.
 
 20 MARSH FEVER AND ITS ORGANISM. 
 
 We have seen above that the spherical bodies may be multiplied 
 by a kind of budding or by segmentation ; the regular segmented 
 bodies would therefore only represent one of the methods of 
 multiplication of the hasmatozoa. 
 
 The different phases of the segmentation of a spherical body 
 are shown in Plate I (figs. 23 to 28) ; the segmentation, which at 
 first is only shown by a slight indentation of the outline of the 
 element, grows larger and larger; at last the small spherical bodies 
 resulting from the segmentation become free. 
 
 Fig. a, Plate III, shows a rose-shaped body in the preparation 
 of dried blood and submitted to the double staining (eosine and 
 methyl blue). 
 
 Lastly, irregular pigmented hyaline motionless bodies are found 
 in palustral blood (a, b, c, Fig. 4) ; these evidently are only the 
 dead forms of the parasites above described, and melaniferous 
 leucocytes differing from them by their more regular form and 
 by the presence of a nucleus which can easily be stained by 
 carmine (1, K, L, Fig. 4). 
 
 Melaniferous leucocytes are presented in Plate I (figs. 39, 40, 
 41) with dead forms of parasitic elements (figs. 42, 43, 44) ; and 
 in Piute II, fig. a, with the appearance they have in fresh blood. 
 
 Out of 480 palustral patients examined in Algeria, I have 
 noticed the existence of parasites described above 432 times ; 
 negative facts were collected at the beginning of my researches, 
 when I did not know exactly under what conditions to observe 
 the parasites, and refer to some patients who had been submitted 
 to quinine treatment, or else had not had any attack for some 
 time — conditions very unfavorable to the search for parasites, as 
 I have since discovered. 
 
 It was interesting to know if the parasites were more or less 
 numerous in the blood before, during, or after the attacks. Out 
 of 79 examinations made a little time before the attack, I have 
 observed parasites 79 times. Out of 286 examinations made dur- 
 ing attacks I have observed them 273 times. Out of 164 exa- 
 minations made a few hours after the onset of fever I have ob- 
 served them 141 times (' Traite des fievres palustres/ p. 197). 
 
 It is, therefore, a little before the attacks or at the beginning 
 that the examination of the blood should be made. 
 
 In certain patients, and particularly in certain cachectics who 
 seem to have acquired very great tolerance for the parasites, the 
 latter are found not only during the whole duration of the 
 paroxysms, but also in the interval of the attacks, and certain 
 forms (crescent-shaped bodies) only disappear slowly even when
 
 DESCRIPTION OF THE H.EMATOZOON. 21 
 
 the patient is submitted to treatment with quinine. On the 
 whole there exist great individual differences. 
 
 I had the opportunity of examining in Paris a number of 
 soldiers who had returned from the colonies, and were passing 
 through or on furlough in Paris. These men came from Algeria, 
 Tunis, Tonquin, Cochin-China, Senegal, and Madagascar. Every 
 time I was able to make the examination of the blood under good 
 conditions, i. e. at the beginning of an attack, I found parasitic 
 elements, and the elements were the same whatever the native 
 origin of the fever. Certainly these elements were often few in 
 number, and it was consequently more difficult to observe them than 
 in Algeria. It should be taken into account that the palustral 
 patients seen in Paris have always been treated in a more or less 
 systematic way. I have also found the parasites in some patients 
 who had contracted paludism in France, in Eochefort principally. 
 
 Out of 432 cases in Algeria in which I ascertained the pre- 
 sence of parasites, I noticed — 
 
 Spherical bodies alone .... 266 times. 
 
 Crescent-shaped bodies alone 
 
 Spherical and crescent-shaped bodies 
 
 Spherical bodies and flagella 
 
 Spherical and crescent-shaped bodies and flagella 
 
 43 
 3i 
 59 
 33 
 
 The spherical bodies alone or associated with other elements 
 have therefore been observed 389 times out of 432. 
 
 The crescent-shaped bodies alone or associated with other 
 forms, 107 times. 
 
 The flagella, always associated with spherical elements, have 
 been seen in 92 patients. 
 
 In most of the cases (95 times out of 107) the crescent-shaped 
 bodies have been observed in the blood of patients suffering from 
 palustral cachexia or recurring intermittent fever ; when, as has 
 been done in Paris, patients are observed who came from a 
 distance and who have had numerous relapses of fever, or who 
 are cachectic, it was to be expected that the crescent-shaped 
 bodies would be more frequently found than in the palustral 
 countries, in which there is often the opportunity of observing 
 fevers in their primary attack. 
 
 If I do not modify the figures given in my ' Traite des fievres 
 palustres ' concerning the frequency of the different elements, 
 taking into account facts which I have observed since I left 
 Algeria, it is because my first figures refer to all the forms of 
 paludism, whilst in Paris I only observed one class of patients 
 (those suffering from a relapse of intermittent fever ) ; the intro-
 
 22 MARSH FEVRR AND ITS ORGANISM. 
 
 duction of these facts into my statistics of Algeria might therefore 
 have affected the conclusions at which I had arrived. 
 
 What relations exist between the different parasitic elements 
 above described ? I expressed as far back as 1862 the opinion 
 that these elements, in spite of the variety of their shapes, con- 
 stitute not parasites of different kinds, but successive states of 
 the same polymorphic parasite. 
 
 The hyaline corpuscles, not yet pigmented, which make small 
 clear spots on the red blood-corpuscles, represent probably the 
 embryonic stage of the parasite ; little by little their bodies 
 increase, and their size is completed when they are equal to or 
 even a little larger than that of the blood-corpuscle ; at the same 
 time the number of the granules of pigment increases. These 
 elements, which possess amoeboid movements, exist in a free state 
 in the serum of the blood, or adhere to the red blood-corpuscles, 
 at the expense of which they live, and which supply them with the 
 pigment. The flagella are developed within the spherical bodies, 
 and at a given time they become free. 
 
 The explanation of the crescent-shaped bodies remains still 
 rather obscure, but the relation of these elements to the spherical 
 bodies and to the flagella does not seem doubtful. 
 
 We shall see in the next chapter that several Italian observers 
 admit the existence of two or three species of hasmatozoa of 
 paludism, one being characterised by the crescent-shaped bodies. 
 
 Examination of palustral blood; technical details for the pre- 
 paration and staining of the parasitic elements. — In studying the 
 parasites of paludism, it is necessary that the choice of patients 
 should be made under the most favorable circumstances. The 
 parasites are most often absent from the blood of those palustral 
 patients who have not had any attack for some time, or who have 
 just been undergoing quinine treatment ; a patient should there- 
 fore be chosen who is actually suffering from fever, or who is just 
 affected, and who has not taken any quinine recently. 
 
 The easiest and most practical method for the search of the 
 parasites of palustral blood, consists in the examination of the 
 fresh blood obtained by pricking the finger. 
 
 Councilman and Golgi, who have examined the blood of the 
 spleen in a certain number of patients, have noticed that the blood 
 obtained in this way contained parasitic elements in larger num- 
 ber than peripheral blood. Hypodermic puncture of the spleen 
 made with antiseptic precautions is not dangerous, but it is too 
 delicate and painful an operation to bring into practice generally.
 
 EXAMINATION OF THE BLOOD. 23 
 
 The preparation of the recent blood is made by the ordinary 
 method ; it is important that it should be very thin. It may be 
 surrounded with paraffin, but this precaution may be dispensed 
 with. The blood which coagulates on the edges of the prepara- 
 tion in contact with the air is a sufficient seal ; it remains liquid 
 in the centre for a variable time, but at any rate for a few hours, 
 which is quite sufficient for ordinary examination. When it is 
 wished to make an examination of the blood with high powers, or 
 to study the movements of the parasitic elements, it is well to 
 ring with paraffin in order to stop the movements which the 
 drying of the blood gives to the blood-corpuscles. 1 
 
 At the beginning of my researches I took minute precautions 
 to prevent the introduction of all extraneous matters into the 
 preparation. In practice these precautions are not necessary ; 
 the parasitic elements are too characteristic for one to compare 
 them with the dust in suspension in the air. 
 
 The finger of the patient which is to be pricked must be 
 clean, it must be washed very carefully in order to prevent the 
 entrance of dirt into the preparation, which might interfere 
 with the examination. The finger should be washed first with 
 water, then with alcohol, and care should be taken to dry it 
 completely before pricking. If the skin is ever so little damp, the v 
 blood spreads, mixes with the water, and the red blood-corpuscles 
 are disfigured ; on the contrary, when the skin is very dry the 
 blood which comes out of the wound makes the drop very defined 
 and very prominent ; it is easy to collect, and the blood-cor- 
 puscles are not changed if the operation is quickly performed. 
 I usually examine pure blood without the addition of any re- 
 agent. 
 
 At first after making the preparation the search for the para- - / 
 sitic elements is sometimes difficult ; the blood-corpuscles form 
 rouleaux, and often present their edges ; in these conditions most 
 of the parasitic elements, and particularly those which adhere to 
 the blood-corpuscles, are invisible. If the preparation is suffi- 
 ciently thin the blood-corpuscles will soon lie flat, which makes 
 the search for the haematozoa much easier. 
 
 The parasitic elements are often in small numbers in the peri- \y 
 pheral blood, therefore the observer who undertakes to find them 
 must be patient, and repeat the examination of the blood several 
 times before declaring the examination to be negative. 
 
 1 Preparations may be sent to the R. C. P. Laboratories of either Edinburgh 
 or London, the directors of each having kindly engaged to examine the specimens. 
 — [Trans, note.]
 
 24 MARSH FEVER AND ITS ORGANISM. 
 
 A power of 400 diameters is sufficient for the investigation of 
 the ha3inatozoa of paludism. I ordinarily use the oculars 1 or 2, 
 and the objectives 7 or 9 of Verrick ; I have also used the objec- 
 tives 10 and 13 with oil immersion by the same maker. The 
 examination of the fresh blood must be made in daylight ; artificial 
 light and the Abbe condenser make the parasitic elements too 
 transparent. The parasitic elements being usually pigmented, the 
 black granules of pigment will give a useful point to start from. 
 By adding a drop of water to the blood the blood-corpuscles 
 are destroyed, without altering, at least for some time, certain 
 parasitic elements, specially the crescent-shaped bodies, which 
 may easily be discovered by this means. 
 
 It is in the pure and fresh serum in the midst of the blood- 
 corpuscles that the parasites are best studied ; if the presence 
 of the blood-corpuscles is sometimes inconvenient it often makes 
 the observation easier, especially so far as flagella are concerned, 
 these being so transparent that it is difficult to see them in the 
 serum. The very varied movements which these elements give 
 to the blood-corpuscles serve to show their presence, and to make 
 their particular movements more apparent. 
 
 The very rapid movements of the granules of pigment in the 
 spherical bodies, and the amoeboid movements of the latter, can 
 also only be studied in fresh blood ; and in preparations of 
 fresh blood, by means of a prolonged observation of a spherical 
 body, some of the transformations it undergoes may be followed. 
 A hot stage (37 to 38 C), useful for observing amoeboid move- 
 ments and flagella, is not necessaiy. All my observations in 
 Algeria Avere made at the temperature of the laboratory. 
 
 The rapid drying of the blood by heat is an excellent means 
 of preserving the blood and the parasitic elements which it 
 contains. The cover-glasses with the blood spread in thin layers 
 on their surface may be preserved a long time, sent away a 
 distance, and stained a long time after the blood was collected ; 
 thanks to this method, I can examine in Paris blood which I 
 obtained in Algeria. I am glad to have the opportunity of 
 thanking those of my colleagues who have kindly sent me dried 
 palustral blood, and specially M. Soulie, assistant professor in the 
 school at Algiers, and M. Geschwind. 
 
 Heat in this case seems to me preferable to the vapours of 
 osmic acid, which have also been recommended to fix the blood- 
 corpuscles in their shape. Osmic acid is much more difficult to 
 use than heat ; a bottle containing a solution of osmic acid cannot 
 be carried about, and it would be dangerous to leave that re-
 
 EXAMINATION OF THE BLOOD. 25 
 
 agent in the patient's room. Besides, osmic acid is not 
 satisfactory in these cases on account of its staining the fat 
 granules black, consequently they might be confused with the 
 granules of pigment in the parasites. 
 
 In making preparations of dry blood the following plan may 
 be followed with advantage : 
 
 ist. A few cover-glasses are cleaned with great care, first in 
 water and if necessary in water mixed with hydrochloric acid, 
 then in alcohol. 
 
 2nd. The finger of the patient it is intended to examine is 
 rendered physiologically clean and dried completely, then pricked 
 with a needle passed through the flame. 
 
 3rd. A cover-glass is made to impinge on the drop of blood 
 which escapes from the pricking ; the drop of blood thus adheres 
 to the glass. 
 
 4th. A second glass is applied immediately to the first glass 
 so that the blood spreads in a thin and uniform layer between 
 these two glasses. 
 
 5th. The two cover-glasses are then made to slide over one 
 another and separated, and the blood, which makes a very thin 
 layer on the surface of each glass, is rapidly dried. 
 
 6th. Each cover-glass is taken with the forceps and passed 
 three times through the flame of a spirit lamp, care being taken 
 not to turn the surface covered with blood downwards. 
 
 The cover-glasses thus prepared may be wrapped in paper and 
 examined subsequently ; the name of the patient and the date 
 when the blood was taken should be written on the paper. 
 
 The blood, dried as we have just described, may be examined 
 without any other preparation, without staining, and this method 
 gives excellent results for the crescent-shaped bodies. The 
 cover-glass is placed on a slide and surrounded with paraffin ; 
 the preparation is mounted dry, as they say ; Canada balsam will 
 make the elements much too transparent. 
 
 In some preparations of blood preserved for six or seven years 
 by this pi'ocess the crescent-shaped bodies are still quite visible : 
 in time the elements become a little disfigured ; they broaden out 
 and become granular. 
 
 The pigmented spherical bodies, either free or adherent to the 
 red blood-corpuscles, are also seen in preparations of dry blood 
 when one is practised in these methods ; but for the study of 
 these elements in dry blood there is some advantage in using 
 colouring reagents — namely, methyl blue or double staining with 
 eosine and methyl blue.
 
 26 MARSH FEVER AND ITS ORGANISM. 
 
 Before submitting a preparation of blood to the colouring 
 reagents, it is useful, in order to retain the blood-corpuscles in 
 their shape better than they were simply by heat, to use (following 
 the advice of Roux) a mixture in equal parts of alcohol and 
 ether ; a few drops of this mixture is poured on the glass and 
 allowed to dry. 
 
 In order to obtain a staining with methyl blue, a few drops of 
 concentrated aqueous solution of methyl blue is poured on the glass 
 covered with dry blood ; after thirty seconds it is washed with 
 distilled water and the preparation dried, and also mounted dry. 
 
 The preparations mounted dry are surrounded with paraffin 
 and wax, so as to prevent the dampness of the atmosphere 
 affecting them; they may thus be preserved a long time. 
 
 The parasitic elements (spherical bodies free or adherent to 
 red blood-corpuscles, the crescent-shaped bodies, the oval bodies 
 and segmented bodies) take, in these preparations, a blue tint 
 much paler than that of the nuclei of leucocytes; the blood- 
 corpuscles preserve their normal colour (fig. b, PI. II). 
 
 The double coloration of blood by eosine and methyl blue 
 by the process of Metschnikoff gives very good results for the 
 study of the hosmatozoa of paludism, and for that of the 
 haematozoa of those animals which approach the parasites of 
 paludism. 
 
 The blood is dried and the globules fixed as has been described 
 above ; the cover-glass on which the blood has been dried is 
 put in an aqueous concentrated solution of eosine for thirty 
 seconds, then washed with distilled water and dried ; the cover- 
 glass is afterwards placed in the concentrated solution with 
 methyl blue for about thirty seconds, washed again with dis- 
 tilled water, and dried. It is mounted dry or in Canada balsam, 
 after ascertaining that the double staining is satisfactory. 
 
 In the blood of birds, and of batrachians or reptiles, the nuclei 
 of the blood-corpuscles are deeply stained blue ; the haamatozoa 
 assume a tint of much paler blue than that of the nuclei of the 
 leucocytes and of the blood-corpuscles, sometimes a faint violet, 
 due to the mixture of the tints of eosine and methyl blue. 
 
 The blood-corpuscles altered by the presence of the ha3ma- 
 tozoa are coloured less deeply by eosine than the healthy blood- 
 corpuscles. 
 
 Figs, a and B on PI. Ill show the appearance of palustral 
 blood and birds' blood containing hamiatozoa on preparations 
 submitted to the double staining with eosine and methyl blue. 
 I have not yet succeeded in staining flagella ; some flagella may
 
 EXAMINATION OF THE BLOOD. 27 
 
 at times be so differentiated in preparations of blood, but this is 
 very rare. 
 
 In studying' palustral blood, and specially iu the study of the 
 blood which has been dried and submitted to the action of 
 different reagents, invariably some effects are produced ; the acci- 
 dental alterations must be taken into account, thereby avoiding 
 the risk of confusing these alterations with those which are 
 characteristic of the presence of hasmatozoa. 
 
 Ehrlich and Foa have observed that in certain cases the 
 normal red blood-corpuscles, dried and submitted to the action of 
 methyl blue, showed bluish tints or granulations stained by 
 methyl blue. 
 
 Celli and Guaruieri, who point out this source of error ('Annali 
 di Agricoltura,' 1889), have tried to stain fresh blood on its 
 coming out of the capillaries with methyl blue dissolved in serum 
 coming from serous effusion ; the coloration of parasitic elements 
 takes place slowly, the preparation must be left for an hour or 
 even three hours in the damp chamber. 
 
 According to Celli and Guarnieri, the amoeboid bodies stained 
 in this way show a clear central space in which one or two 
 corpuscles more highly stained are found ; the peripheral part is 
 stained rather quickly. 
 
 In this process, as in the process by drying, sources of error 
 exist; the long stay in the coloured serum and the wet chamber 
 may easily give place to alterations in the normal or parasitic 
 elements. 
 
 A good method of staining, says Soulie, consists in collecting 
 the blood to be examined on a piece of glass which bears a drop 
 of an alcoholic solution of evaporated methyl blue ; the colouring 
 matter is slowly dissolved in the serum, the white corpuscles and 
 other elements are stained without alteration ( c Bull. nied. de 
 l'Algerie/ 1890, p. 230). Care must be taken to use a suffi- 
 ciently dilute solution, without which the methyl blue cannot be 
 dissolved in the serum. Feletti has recommended a method of 
 staining similar, if not identical (Congress of the Italian Society 
 of Mediciue, 1890). 
 
 Attempts at cultivation. — When pure blood is taken from a 
 palustral patient and the presence of ha^matozoa ascertained, some 
 drops should be put in broth, in gelatine, or jelly, or on potato, 
 and it will be noticed that after a few days the broth is limpid, 
 and no colony has been raised in the solid substances, even 
 if these substances have been kept in an incubator at a tempera- 
 ture of 37 to 40 C.
 
 28 MARSH FEVER AND ITS ORGANISM. 
 
 In water and sterilised earth the results of the sowing- are not 
 absolutely negative. 
 
 As the ordinary media did not succeed for the cultivation of 
 paludism, it might have been expected that these parasites could 
 be cultivated in the blood. 
 
 The attempts I have made in this direction have, up to the 
 present, given only negative results. One of these attempts at 
 cultivating Tneinatozoa in pure blood kept at a temperature of 
 38 C. has been made by M. Roux in the laboratory of M. Pasteur — 
 that is to say, under the best conditions. 
 
 A very simple way of trying this culture in the blood consists 
 in taking a drop of palustral blood with precautions on a cover- 
 glass which is placed over one of the excavated slides which are 
 used for the study of microbes in suspended drops ; the slides 
 are first sterilised in the flame. A little vaseline placed between 
 the cover-slip and the slide prevents drying ; for further security 
 the preparation between various examinations may be left in the 
 damp chamber. 
 
 On examining a drop of blood which has been taken on a cover- 
 glass care should be taken to spread it a little ; the parasitic 
 elements are visible at the places where the layer of blood is 
 thinnest, and principally at the periphery. 
 
 I have thus been able to preserve, for ten days or longer, 
 preparations of palustral blood in which I distinguished parasitic 
 elements in the middle of the blood-corpuscles scarcely altered. 
 Once it seemed to me that the pigmented amoeboid bodies had 
 increased in number; but that was, perhaps, only an illusion 
 which might be explained by the fact that the blood-corpuscles, 
 having become paler, allowed the parasitic elements to be seen 
 more easily. 
 
 Since I have adopted this procedure I have unfortunately had 
 but few oppoi'tunities of studying fresh palustral blood ; there 
 are, on this point, further researches necessary : it is possible 
 that by carefully examining blood in the suspended drops, and 
 keeping the preparation at a temperature of 38 C. with the hot 
 stage, one may succeed in following the changes of the parasite, 
 and in finding out more exactly than has been possible till now 
 the relations existing between its different foi-ms. 
 
 Attempts at inoculation in animals. — Many veterinary surgeons 
 agree in denying the existence of paludism in animals (Verheyen, 
 art. " Fievres Interm." du ' Dictionn. de Medecine veterinaire ' 
 de Bouley et Raynal).
 
 EXAMINATION OF THE BLOOD. 29 
 
 Certain epizootic diseases have been attributed to paludisra 
 because they have been observed in marshy districts. This is 
 evidently quite insufficient as a proof. Marshy districts favour 
 the propagation of many diseases besides paludisra. 
 
 The watery cachexia or rot, which often makes great havoc in 
 herds which graze in marshy fields, has nothing to do with 
 palustral cachexia ; it is said that it results from the presence of 
 distoma or flukes in the bile-ducts. 
 
 Obedenare has compared an epizoon fairly common in oxen 
 in the Danubian provinces to paludism ; this epizoon is charac- 
 terised by fever and hematuria. 
 
 Babes has recently studied that disease under the name of 
 Hemoglobinuria epizootique du betail ( f Arch. f. path. Anat. u. 
 Physiol.,' 1889) ; according to him the disease is caused by a 
 diplococcus which penetrates into the blood-corpuscles and 
 destroys them : the diplococci are specially found in great 
 numbers in the kidneys, which explains the frequency of the 
 hematuria. 
 
 The presence of the pentastomata in the bowels (very common 
 in oxen in Danubian provinces) would favour the diplococcus 
 penetrating into the blood. 
 
 The diplococcus described by Babes is evidently a parasite 
 very different from the hsematozoa of paludism. 
 
 Smith has described alterations in the blood in the Texan 
 fever of the ox, which is probably of a parasitic nature, but 
 which appears to have nothing in common with the hasmatozoon 
 of paludism (Pfeiffer, ' Les Protozoaires pathogenes,' p. 57). 
 
 When I was in Algeria I often asked veterinary surgeons to 
 send me parts of the liver and spleen of animals suspected of 
 paludism ; I made a histological examination of those parts in a 
 small number which were sent to me, and I never noticed the 
 lesions of paludism. 
 
 The facts of experimental paludism quoted by Klebs and Tom- 
 masi Crudeli, and Ceci, and Schiavuzzi will not stand criticism. 
 
 In 1883, when at Constantine, I tried to induce palustral 
 fever in a rabbit by injecting into its veins culture fluids prepared 
 with palustral earth (according to the method of Klebs and 
 Tommasi Crudeli, and Ceci). The injection of these liquids, 
 or of those directly collected from pools of water in marshy 
 localities, into the veins easily produces an attack of fever in the 
 rabbit, but the attack is not repeated ; the animals recover very 
 soon, and when killed, after a certain time, the alterations which 
 are characteristic of paludism are not observed.
 
 30 MARSH FEVER AND ITS ORGANISM. 
 
 I was not more fortunate in my attempts at inoculating- 
 paludism in rabbits when I used blood taken from palustral 
 patients for intra-venous injections. 
 
 "We shall see further (Chap. III.) that some observers have 
 likened certain hasmatozoa of birds to the parasites of paludism. 
 These certainly resemble them very much, but should not be mis- 
 taken for them ; this question will be more carefully discussed 
 when the hsematozoa of birds are studied. 
 
 The fact that up to the present the parasite of paludism has 
 not been cultivated in natural or artificial media, nor inoculated 
 into animals, has been quoted more than once by the authors 
 who disputed the existence of the new parasite. The argument 
 would have some value if the question were about a schizophyte ; 
 but the hasmatozoon of paludism not belonging to that class, it is 
 not surprising if they should behave otherwise than micrococci 
 or bacilli. It is impossible to cultivate the filaria of human blood 
 in artificial media, yet nobody attempts to dispute the parasitic 
 nature of filariosa. 
 
 We now possess, thanks to the work of men like Pasteur and 
 Koch, an excellent method for the study of schizophytes. Ought 
 one to be surprised if this method does not apply to sporozoa ? 
 Evidently not. These new parasites require new methods of 
 observation and experimentation. The study of the hasmatozoa 
 of animals is naturally the preface to the more difficult study of 
 the hasmatozoa of paludism. It will be necessary to choose 
 species which are readily available for experiment, and in which the 
 hasinatozoa are easy to observe ; it will be particularly interesting 
 to see how the haernatozoa of birds, for instance, so akin to those 
 of paludism, are reproduced and propagated.
 
 CHAPTER II. 
 
 Researches subsequent to mine — The hsematozoon of paludism has 
 been discovered by a large number of observers — Remarkable 
 agreement of the descriptions that have been given of it in all 
 countries. 
 
 Investigations based on my researches on the parasites of 
 paludism, which were very rare from 1881 to 1886, have become 
 more and more numerous in subsequent years. 
 
 In mentioning the researches which confirm mine I shall not 
 follow the chronological order exactly. Several observers have 
 published papers on that question which correct or supplement 
 one another, and cannot be examined separately. The annual 
 bibliography which will be found at the end of this volume 
 will enable the reader to see the chronological order of these 
 works. 
 
 At the end of 1880 I communicated the first results of 
 my researches to my colleague, Dr. E. Richard, fellow-professor 
 at Val-de-Grace, asking him to verify them. M. Richard soon 
 wrote to me that he had succeeded in discovering the parasites 
 which had been observed at Constantine, in the blood of 
 palustral patients at Philippeville (Province of Constantine) . 
 
 In an article in the ' Revue scientifique ' of January 27th, 1883, 
 Richard gives a good description of the different appearances 
 under which the parasitic elements are found in the blood of 
 palustral patients, and concludes thus : — "After a year of research 
 we are now strongly convinced that M. Laveran is right, and 
 that the real microbe of paludism has been discovered by him." 
 
 We saw (p. 5) that the name of Marchiafava was in 1880 
 among those of the observers who defended the so-called Bacillus 
 malarias. From that time Marchiafava has completely given 
 up that opinion, and has published in collaboration with Celli 
 several works on paludism, on the analysis of which we will 
 dwell at some length. From 1884 to 1889 the opinions expressed 
 by these authors have varied very much, and it is essential to know 
 the history of their variations in order to appreciate the value of 
 certain claims made by Marchiafava or in his name.
 
 32 MAESH FEVER AND ITS ORGANISM. 
 
 In 1884 Marcliiafava and Celli, in the treatise 'On the Alterations 
 of the Bed Blood-corpuscles in Malarial Infection and on the Cause 
 of Melansemia,' assert that all the parasitic elements which I have 
 jvist described as found in the blood of palustral patients must be 
 considered as degenerated blood-corpuscles. Marchiafava and 
 Celli deny absolutely that the new elements which I had the 
 opportunity of showing them in Rome in 1882 are of a parasitic 
 nature ; they wish to explain the flagella themselves by a 
 degeneration of the red blood-corpuscles. 
 
 Marchiafava and Celli are now inclined to believe that the 
 cause of paludism is a micrococcus. 
 
 In a letter dated Rome, April gth, 1884, M. Marchiafava, in 
 thanking me for sending him my ' Traite des fievres palustres ' 
 and forwardiug me the above-mentioned treatise, is very careful to 
 draw my attention to the fact that he and his colleague have 
 arrived at conclusions very different from mine. 
 
 "In our view/' writes Marchiafava to me, " the only elements 
 that may be suspected of being parasites are corpuscles deprived 
 of pigment analogous to micrococci, which are often found in large 
 numbers in red blood-corpuscles, and are only visible in prepara- 
 tions of blood dried and stained with methyl blue. We believe 
 that the pigmented forms which you have described are nothing 
 but degenerated and pigmented red corpuscles." 
 
 At the Congress of Copenhagen in 1884, Marchiafava and Celli 
 together with Tommasi Crudeli still urged that the elements I 
 have described as the parasites of paludism only repi'esented 
 retrograde changes of red blood-corpuscles. 
 
 Thus there can be no doubt of this point : after the publication 
 of the ' Traite des fievres palustres,' four years after the publication 
 of my first works on this question, Marchiafava and Celli refused 
 to admit the parasitic nature of the elements which I had described 
 in the blood of palustral patients, that of the spherical bodies as 
 well as of the crescent-shaped bodies and flagella, and they 
 considered then that the parasite of paludism was a micrococcus. 
 
 In 1885 Marchiafava and Celli in a second treatise, under the 
 title of ' New Researches on Malarial Infection ' ( f Annales itali- 
 ennes de 1' Agriculture,' Rome, 1885), agree that parasitic elements 
 may be found in palustral blood which affect the form I had 
 previously described — pigmented bodies free or adherent to the 
 blood-corpuscles, crescent-shaped bodies, and flagella endowed 
 with movements extremely characteristic ; they still insist on the 
 small unpigmeuted elements, described in their previous publica- 
 tion, being a species of micrococci, but they confess that, contrary
 
 SUBSEQUENT RESEARCHES. 
 
 33 
 
 to what they had first asserted, many of these elements are visible 
 in fresh blood and contain granules of pigment ; out of forty- 
 seven parasitic elements represented, forty are pigmented. 
 
 It is sufficient to cast one's eyes on the figures given below 
 (Fig. 5) from that treatise of 1885 to ascertain that the parasitic 
 elements described by these authors are really those whose pre- 
 sence I had shown in palustral blood several years before ; it is 
 easy to recognise the spherical bodies adherent to the blood- 
 corpuscles (included in blood-corpuscles, say Marchiafava and 
 Celli), the elements with flagella, and the crescent-shaped bodies. 
 
 Fig. 5. — a, B, c. Blood-corpuscles containing plasmodia. d, e. Hyaline 
 bodies, pigmented, with flagella. F. Crescent-shaped body. g. Oval- 
 shaped body. (Figures taken from the treatise of Marchiafava and Celli.) 
 
 In 1886 a new treatise by the same authors was published in the 
 same contributions as the previous one. They insist very strongly 
 on the description of the elements endowed with amoeboid move- 
 ments and deprived of pigment, to which they propose to give the 
 name of plasmodia, or malarial hsbmojplasmodia. This name of 
 plasmodia applied for the first time to parasitic elements of 
 palustral blood may have induced some persons to believe that 
 Marchiafava and Celli have found new parasites ; in reality 
 these authors have merely described under this new name (the 
 unsuitability of which has been shown) 1 some elements which 
 I showed as far back as 1880 and 1882. In order to prove 
 their claims Marchiafava and Celli insisted on these two con- 
 siderations, — that the plasmodia were non-pigmented elements, 
 and were endowed with amoeboid movements. I had said before 
 them (see p. 18) that the elements described in my first publica- 
 tion under the name of bodies No. 2, and which correspond to 
 plasmodia, were endowed with amoeboid movements, and that the 
 smallest of these elements did not contain any pigment. Marchia- 
 fava and Celli besides, in order to prove their case, have much 
 
 1 Naturalists mean by the name of plasmodia a collection of similar entities 
 which frequently may be observed in one of the phases of the development of 
 the Protozoa ; the hsematozoa of paludism arc not found in the state of plasmodia, 
 so the generic name cannot apply to them. 
 
 3
 
 34 MARSH FEVER AND ITS ORGANISM. 
 
 exaggerated the frequency of the non-pigmentation of these 
 elements ; it is exceptional to find non-pigmented amoeboid 
 elements of the same size as some of those represented in the 
 above-mentioned treatise. 
 
 In 1887, in a communication on malarial infection made to the 
 Eoyal Academy of Rome, Marchiafava and Celli again assert 
 that the elements endowed with amoeboid movements and 
 deprived of pigment (plasmodia) are the real parasites of 
 paludism, whilst admitting that the pigmented elements are also 
 parasitic ; and it is not a question, as they have previously main- 
 tained, of a degeneration of red blood-corpuscles. 
 
 In 1888, in the ' Archives italiennes de biologie,' the same 
 observers once more try to show that plasmodia are the real 
 parasites of paludism, and that the plasmodia are very different 
 from the parasites I have described. 
 
 In 1889 Celli and Guarnieri published, in the ' Annales 
 italiennes de l'agriculture/ a work which is evidently a sequel 
 to the preceding treatises although it does not bear the signature 
 of Marchiafava. 
 
 This work shows a new evolution in the opinions of Celli ; 
 the authors classify as follows the parasitic elements of palustral 
 blood : 1st, amoeboid bodies ; 2nd, sickle-shaped bodies, which 
 they say give origin to flagella. 
 
 We have seen that in their treatises of 1886 and 1887 
 Marchiafava and Celli described, as being the parasites of 
 paludism, small amoeboid elements, non-pigmented (plasmodia), 
 which, according to them, had nothing in common with my para- 
 sites ; these authors had, till then, refused to admit that the 
 plasmodia were, as I have always held, nothing but the first 
 degree of development of the pigmented spherical bodies. Now 
 Celli and Guarnieri accept this combination as demonstrated, the 
 pigmented spherical bodies are put into the class of amoeboid 
 bodies with the small elements deprived of pigment ; in the 
 plate set apart to amoeboid bodies, the elements are represented 
 as being pigmented 27 times out of 30. 
 
 Celli and Guarnieri admit that some vacuoles, artificially made 
 on dried red blood-corpuscles, have been more than once mistaken 
 for the micrococci which Marchiafava and Celli suspected, in 
 1884, to be the agents of paludism; they admit, lastly, that the 
 amoeboid bodies, either pigmented or not, either free or adherent to 
 red blood-corpuscles, the crescent-shaped bodies, and the flagella 
 only represent different phases of the same parasites, probably 
 a sporozoon.
 
 SUBSEQUENT RESEARCHES. 35 
 
 There was only one admission remaining for Celli and 
 Guarnieri to make, namely, that Marchiafava had been quite 
 wrong in disputing so long the facts which I had advanced, and 
 that the claims of that observer concerning plasmodia had no 
 longer any foundation. 
 
 In spite of logic and truth Celli and Guarnieri again tried to 
 maintain these claims. They are willing to admit that I was the 
 first to discover the crescent-shaped bodies and the flagella, but 
 if we are to believe them the largest share in the discovery of 
 amoeboid bodies was due to Marchiafava, seeing that I had only 
 described (so they say) those that are free and motionless. 
 Being unable to deny that I have spoken of amceboid move- 
 ments, Celli and Guarnieri affect to believe that I mentioned 
 them in connection with the crescent-shaped bodies, which is 
 utterly wrong. I always said that the crescent-shaped bodies 
 were motionless, and I only spoke of amoeboid movements in 
 connection with elements indicated in my first publications under 
 the name of bodies No. 2, and which are no other than the 
 amceboid elements of Celli and Guarnieri. 
 
 It may have been noticed (p. 19) that I have described as far 
 back as 1882, not only free amceboid bodies, but also those 
 among these elements which adhere to red blood-corpuscles ; the 
 latter elements are principally described and figured in a treatise 
 printed in 1882 and presented to the Medical Society of Hospitals; 
 it is sufficient to look at the plate published in that work to be 
 convinced of the inaccuracy of the assertion of Celli and Guarnieri. 
 Far from ignoring the importance of the elements which Celli 
 and Guarnieri call amceboid bodies, I have always said that 
 these were the forms oftenest found in palustral blood ; it will be 
 seen in my ' Traite des fievres palustres ' that I have observed 
 these elements 389 times out of 432 cases. 
 
 Celli and Guarnieri say that they have seen crescent-shaped 
 bodies being transformed into oval elements, afterwards into 
 spherical elements, which gave out flagella. I have often tried 
 to follow the changes of the crescent-shaped bodies ; I have 
 seen these elements take, after a variable time, an oval or 
 rounded form; but I never saw flagella escaping from a body 
 which, at the beginning of the observation, presented the form 
 of a crescent. 
 
 Without disputing the fact pointed out by Celli and Guarnieri, 
 I think that these authors were much too hasty in generalising 
 and coming to the conclusion that the flagella were always 
 derived from crescent-shaped bodies. 1 have often observed
 
 
 36 MARSH FEVER AND ITS ORGANISM. 
 
 flagella in blood which did not contain any crescent-shaped 
 bodies, and I have seen the flagella escaping from bodies 
 endowed with very apparent amoeboid movements, belonging, no 
 doubt, to the first class of the elements described by Celli and 
 Guarnieri. 
 
 In a treatise on summer and autumn fevers, published in 1889, 
 Celli and Marchiafava have admitted the importance of the 
 crescent-shaped bodies, which they had till then disputed ; 
 according to them these bodies were only very seldom met with 
 in palustral blood — once in 200 cases, according to a note in 
 one of their works. Now these authors maintain that the 
 crescent-shaped bodies are often found in the blood of patients 
 suffering from autumnal fevers. Pietro Canalis had already 
 pointed out this fact, which agrees with what I have said about 
 the frequency of these elements in cachectics from paludism, or, 
 at least, in patients who had had several relapses of fever. 
 
 In their last work on winter fevers (Rome, 1890) Celli and 
 Marchiafava, discussing the question whether the parasitic 
 elements of palustral blood belonged to one or to several species, 
 conclude by saying that they adhere to the belief in the 
 existence of a polymorphic parasite ; " an hypothesis and sup- 
 position/' they say, " which has always been upheld by us." 
 This word always will undoubtedly appear strange to the reader 
 who has just read the abstract of the works of MM. Celli and 
 Marchiafava ; I leave him to form his own opinion about it. 
 
 If we recapitulate the history of the works of Marchiafava 
 and Celli we see that in 1884 these authors did not concede the 
 parasitic nature of the elements described by me, and that they 
 incline to believe that the cause of paludism was a kind of 
 micrococcus. 
 
 From 1885 to 1888 Marchiafava and Celli tried to prove that 
 the elements described by them in 1886, although under the 
 name of plasmodia, are the real parasites of paludism, and that 
 these plasmodia are very different from my parasites. At least 
 in 1890 Celli, Marchiafava, and Guarnieri admit the existence of 
 all the parasitic elements described by me, and to them as to me 
 these elements only represent the different states of the same 
 parasite, which is that of paludism. 
 
 One conclusion I think is that Marchiafava and Celli have 
 simply been brought to verify, in 1890, the facts which I men- 
 tioned from 1880 to 1882. 
 
 Sternberg published in 1886 ('The Medical Record/ New York, 
 1886) a paper on the parasite of paludism, the conclusions of
 
 OBSERVATIONS OF VARIOUS AUTHORS. 37 
 
 which support those which we have just expressed in connection 
 with the works of Marchiafava and Celli. 
 
 In 1 88 1 Sternberg had undertaken some researches at New 
 Orleans to prove those of Klebs and Tommasi Crudeli ; he has 
 remained in doubt as to the role of the Bacillus malarias of these 
 observers ; in 1884 Sternberg had not, he says, much confidence 
 in the new parasite which I had just described. In the meantime 
 he went to Rome, saw the parasitic bodies whose existence I had 
 demonstrated in the laboratory of Marchiafava, and he returned 
 to America convinced that these new parasites were really those 
 of paludism ; he was not long in finding them himself in the 
 blood of palustral patients in America. Sternberg has no doubt 
 that the plasmodia are the same elements as those described by 
 me in my first works under the name of bodies No. 2. 
 
 Golgi has published several treatises on the parasites of 
 paludism, and he has studied particularly the segmented forms. 
 
 In a work published in 1886 ('Archives italiennes des sciences 
 medicales ') he gives the first results of his researches, which 
 were carried on at Pavia, principally on patients suffering from 
 quartan fever. Golgi asserts that he has found in the blood of 
 nearly all his patients the hyaline corpuscles endowed with 
 amoeboid movements which are described in my first works under 
 the name of bodies No. 2, and he admits that the plasmodia of 
 Marchiafava and Celli only represent the first stage in the develop- 
 ment of these elements. The figures given in that treatise do 
 not leave any doubt about the identity of the elements observed 
 at Pavia and those described by me ; the hyaline bodies possessed 
 of amoeboid movements and the crescent-shaped or oval bodies 
 are exactly represented. 
 
 Golgi emphasises the rose-shaped form. The parasitic element 
 undergoes segmentation regularly, while the pigmented granules 
 collect towards the central part ; these segments detach them- 
 selves, assume the appearance of rounded corpuscles, and becoming 
 free, are changed iuto amoeboid spherical bodies. The rose-shaped 
 bodies consequently would represent one of the methods of the 
 multiplication of parasitic elements. 
 
 Golgi has seen in most of the patients a direct relation 
 between the number of the parasites and the intensity of the fever. 
 
 Blood taken from the spleen in the different stages of the 
 attacks of fever has enabled him to ascertain that the number 
 of parasites was much larger in the splenic blood than in the 
 peripheral blood. 
 
 In a paper which appeared in the ' Archives italiennes des
 
 38 MARSH FEVER AND ITS ORGANISM. 
 
 sciences medicales ' in 1889 under the title of " The Development 
 of the Parasites of Paludism in Tertian Fever " and in a more recent 
 work published in the ' Archives italiennes de biologie/ t. xiv, 
 fasc. 1, 2, Golgi showed the differences which, according to him, 
 exist between the parasites of tertian fever and those of quartan 
 fever. These differences could be summed up much as follows : 
 the parasite of tertian fever accomplishes its evolution in two 
 days, that of quartan fever in three days. 
 
 The amoeboid bodies of tertian fever have much quicker move- 
 ments than those of quartan fever. 
 
 The parasites of tertian fever cause the decoloration of the red 
 blood-corpuscles, which they attack easily and rapidly, whilst in 
 quartan fever the red blood-corpuscles invaded by the parasites 
 keep their characteristic coloration until their destruction is almost 
 completed. 
 
 In quartan fever the corpuscles of the affected blood have a 
 great tendency to lessen, whilst in tertian fever the affected 
 corpuscles have often a larger diameter than healthy ones. 
 
 In tertian fever the protoplasm of the parasites is very trans- 
 parent, the contours are very slightly differentiated ; in quartan 
 fever the protoplasm appears less delicate, the contours of the 
 parasites being more apparent. 
 
 In quartan fever the pigment presents itself under the shape 
 of granules or bundles, larger than in the tertian ; the colour of 
 the pigment may also be a little different. 
 
 Lastly, and that is what constitutes the principal difference, 
 the segmentation of the rose-shaped elements is not made in the 
 same way in the tertian as in the quartan. In the tertian the 
 number of rounded corpuscles which come from the segmentation 
 of pigmented elements is larger than in the quartan. Fig. 6, 
 taken from Golgi, shows this difference well ; the number of seg- 
 ments would be about twice as large in the tertian as in the quartan. 
 
 In the quotidian fever, now the parasite of the tertian, now 
 that of the quartan is found ; which Golgi explains by admitting 
 that the quotidian does not represent a particular type, but only 
 a complicated form of the tertian or the quartan, double tertian 
 or triple quartan. This hypothesis can only be admitted with 
 difficulty by clinical observers, especially by those who have 
 practised in hot countries, where the quotidian is much the most 
 common of the intermittent fevers. 
 
 According to Golgi the crescent-shaped bodies are met with in 
 the fevers of an irregular type ; for my part I have very often 
 met with them in regular intermittent fever.
 
 OBSERVATIONS OF OTHER AUTHORS. 
 
 39 
 
 Golgi succeeded in finding flagella, and he observed that these 
 elements only showed themselves in the blood at the time of the 
 febrile attacks and for a few hours before those attacks. 
 
 4?% 
 
 S(g)B 
 
 
 n 
 
 '0® U Q0 
 
 Fig. 6. — a. i, 2, 3, 4. Segmentation of a pigmented element in tertian 
 fever. The outline of a blood -corpuscle may still be seen in figures 
 1 and 2. In figure 4 the separation of the corpuscles resulting from 
 segmentation is complete, b. i, 2, 3, 4. Segmentation of a pigmented 
 element in a case of quartan fever. In figure 4 the separation of cor- 
 puscles resulting from segmentation is complete. 
 
 We shall see later on that a certain number of Italian 
 observers, following Golgi, have admitted the existence of 
 several species of parasites of paludism. 
 
 It is to be noticed that several authors who defend the theory 
 of Golgi are much more confident than himself ; Golgi, whilst 
 admitting several varieties of parasites, has never, to my know- 
 ledge, asserted that these parasites belong to absolutely dif- 
 ferent species, without relation to each other. It even appears, 
 from the following paragraph in the last work by Golgi 
 (' Archives italiennes de biologie/ 1890), that he admits the 
 possibility of the passage of the parasite from one form to 
 another. 
 
 In 1884 Councilman and Abbot had expressed doubts concern- 
 ing the parasitic nature of the elements described by me ; their 
 investigations had been made on the cadavera, i. e. in very bad 
 conditions so far as the examination of parasites is concerned, 
 they being rapidly defaced after death. 
 
 However, in 1887, in a communication to the Pathological 
 Society of Philadelphia, Councilman announced that he had 
 succeeded in finding hasmatozoa in all the palustral patients 
 whom he had had the opportunity of examining (' Fortschritte 
 der Medicin,' 1888, No. 12, pis. v and vi).
 
 40 MARSH FEVER AND ITS ORGANISM. 
 
 In a first series of examinations of Wood obtained by pricking 
 the finger, Councilman established the existence of flagella 1 1 
 times out of 80. 
 
 In a second series the examination was made on blood extracted 
 directly from the spleen, and the flagella were found 16 times 
 out of 21 patients. This is a very remarkable result, which 
 shows that the rarity of flagella in the peripheral blood should 
 not be made a pretext for disputing the importance of these 
 elements. 
 
 According to Councilman, the crescent-shaped bodies and the 
 oval bodies which spring from them are only to be found in 
 patients suffering from palustral cachexia ; the segmented forms 
 being found in the shivering stage of the attacks of intermittent 
 fever. 
 
 Lastly, Councilman found that the action of quinine, very 
 decided on the amoeboid elements and the flagella, is much less 
 marked on the crescent-shaped bodies, thus agi'eeing with my 
 own observations (' Traite des fievres palustres/ p. 201). 
 
 The works of W. Osier, like those of Sternberg and Council- 
 man, are confirmatory of mine. Like them, Osier at first accepts 
 my descriptions of the parasites of paludism with much scepticism, 
 in particular that of flagella; the existence of such elements in 
 the blood seems to him unlikely. However, he undertook control 
 researches, and was not long in being convinced of the truth of 
 my descriptions (communic. to the Pathol. Society of Philadelphia, 
 'The British Medical Journal/ 1887). 
 
 In 70 patients suffering from different forms of paludism Osier 
 succeeded in finding the haematozoa 63 times; the negative 
 observations are, moreover, explained by the fact that the patients 
 had been submitted to treatment by quinine. 
 
 In the acute forms of paludism Osier principally met the small 
 hyaline elements, possessing amoeboid movements and often 
 pigmented, described in my first works by the name of bodies 
 No. 2. The crescent-shaped bodies were found almost always 
 in persons suffering from palustral cachexia, or at least from 
 recurring intermittent fever. The flagella were noticed in seven 
 cases (six chronic and one acute) ; the segmented or rose-shaped 
 figures in six cases. 
 
 The accompanying figures (Fig. 7), taken from Osier's work, 
 leave no doubt about the identity of the parasitic elements 
 observed by him and myself. Concerning the relation of the 
 parasites to attacks of fever Osier has come to the same conclusions 
 as I did ; it is before and during the beginning of the attack
 
 OBSERVATIONS OP OTHEIi AUTHORS. 
 
 41 
 
 that the parasitic elements are found in the blood, though this 
 rule has exceptions. 
 
 Fig. 7. — Some aspects of parasitic elements of palustral blood, from the 
 
 work of W. Osier. 
 A, B, c. Blood-corpuscles to which pigmented spherical bodies of small 
 
 size adhere. D, E. Pigmented spherical bodies with flagella. F, g, h. 
 
 Crescent-shaped bodies. 1, K. Oval bodies. 
 
 Quinine causes the parasitic elements to disappear more rapidly 
 in acute than in chronic forms. 
 
 In a second communication to the Pathological Society of 
 Philadelphia, in 1887, Osier confirms his first conclusions, and calls 
 itttention to the remarkable similarity which exists between the 
 descriptions of authors who have studied the hsematozoa of 
 paludism in different parts of the world. 
 
 Osier has noted the existence of the flagella less frequently 
 than Councilman, but he has not examined the blood from the 
 spleen taken directly by puncture as was done by Councilman. 
 Osier noticed that the amoeboid bodies which adhere to the red 
 blood-corpuscles can be detached and become free in the blood ; 
 this is one of the arguments on which I relied in maintaining that 
 these parasites are only attached to the red blood-corpuscles, that 
 they have a depression, more or less, at the point of adherence, 
 and are not an integral portion of the red blood-corpuscles, as 
 some authors maintain. 
 
 Maurel, who has made many investigations of the micro- 
 organisms of the air, of the water and the soil of marshy 
 countries, at first doubted the existence of my ha3matozoon, which 
 he had not succeeded in finding. At the end of his ' Micro- 
 scopical Researches upon the Etiology of Paludism ' (Paris, 1887) 
 he declares that he is now convinced of its existence. 
 
 In a paper read before the New York Society of Pathology, 
 in 1 888, James is said to have discovered the existence of the 
 haernatozoa in 34 out of 35 examinations of patients suffering 
 from palustral fever. 
 
 James made experiments in vain for parasitic elements
 
 42 MARSH FEVEE AND ITS OEGANISM. 
 
 analogous to those of palustral patients in the blood of a great 
 number of patients not infected with paludism ; therefore he 
 insists upon the importance of searching for heematozoa from a 
 diagnostic point of view. 
 
 He always met crescent-shaped bodies in the chronic forms of 
 paludism, and the segmented bodies during the febrile paroxysm, 
 and gives the following propositions as proved. 
 
 ist. Parasitic elements, which have been described as hsema- 
 tozoa of paludism, are uniformly found in the blood of palustral 
 patients. 
 
 2nd. The crescent-shaped bodies are only met in the chronic 
 forms of paludism. 
 
 3rd. The segmented forms are observed only before and during 
 the paroxysms. 
 
 4th. Under the action of large doses of quinine the parasitic 
 elements disappear rapidly from the blood, with the exception 
 of the crescent-shaped bodies. 
 
 We therefore see that Councilman, Osier, and James agree in 
 attributing the crescent-shaped bodies specially to the palustral 
 cachexia. As a general rule this agrees with my own observa- 
 tion, but I think that James, in particular, has formulated his 
 view too absolutely. 
 
 Vandyke Carter discovered the existence of haeruatozoa in the 
 blood of a great many palustral patients in India. I regret 
 not having succeeded in procuring his original work. 
 
 Evans, surgeon to the Hospital at Mandalay, found the small 
 hyaline elements, generally pigmented, in the blood of palustral 
 patients ; these bodies live either in a free state or in a state of 
 parasitism on the red corpuscles (communic. to the Clinical Society 
 of London, 1888 ). 
 
 Soulie succeeded in showing the presence of parasites in the 
 blood of palustral patients at Algiers, notably the bodies pro- 
 vided with flagella. Concerning these elements Soulie writes as 
 follows : 
 
 " It is impossible, when you have once seen them distinctly, not 
 to be convinced of their existence and of their animated and 
 parasitic nature. It is a curious sight to watch those long 
 arms moving with such vigour round the sphere which supports 
 them, capable of drawing in all directions and giving all manner 
 of forms to one or more blood-corpuscles, situated in their 
 neighbourhood. Sometimes one of the flagella detaches itself, 
 and continues its march in the shape of a corkscrew in the 
 serum, turning aside the blood-corpuscles which it meets in its
 
 OBSERVATIONS OF OTHER AUTHORS. 43 
 
 passage ; it assumes the shape of a spirillum or of a spiro- 
 cheta. After a few hours the movements grow slower, and 
 finish by stopping at a temperature of 15 to 20 C. Like the 
 crescent-shaped corpuscles, they do not stain well with aniline 
 colours" ( f Comptes rendus de la Societe de Biologie/ 1888, 
 p. 168). 
 
 Soulie adds, it is true, that the examination of the blood has 
 often been negative. 
 
 It is difficult to understand the meaning of these words nega- 
 tive examination in relation to the study of the parasites of 
 paludism. 
 
 The result of the examination depends to a, large extent on the 
 method of making the investigations, and on the time given to 
 them. It has very often happened that I found parasitic elements, 
 sometimes in great numbers, in preparations of blood the examina- 
 tion of which had been pronounced negative. 
 
 The hsematozoa are easily concealed in the middle of red blood- 
 corpuscles, especially at the beginning of the examination of the 
 preparations, when the red blood-corpuscles are piled together ; 
 it is therefore necessary that the examination should be extended, 
 and also resumed several times. 
 
 Special stress should be laid on the state of the patient and 
 the treatment he has undergone. We have seen that it is a little 
 before and at the beginning of the attacks that there were 
 more chances of finding the parasites of paludism in peripheral 
 blood. 
 
 In a new work ('Bulletin rued, de l'Algerie/ April 1st, 1890) 
 Soulie says that in thirty patients suffering from paludism whom 
 he examined during the months of October and November, 1889, 
 the haematozoa were found fourteen times ; and he adds that many 
 patients were only examined once after being treated with quinine, 
 which explains the rather larger number of cases in which the 
 examination of the blood proved negative. 
 
 In Russia, Metschnikoff, Sacharoff, and Bartoschewitsch have 
 succeeded in discovering the hcematozoon of paludism : moreover 
 Danilewsky and Metschnikoff have shown the existence of a similar 
 parasite in the blood of various animals, and specially of some 
 birds ; this question will be referred to in the next chapter. 
 
 Sacharoff found the haematozoon in almost all the patients he 
 had examined. He describes the five following forms (communic. 
 a la Societe de Medecine de Tiflis) : 
 
 1st. Rounded or irregular-shaped corpuscles, with contours not 
 well defined, possessing amoeboid movements, enclosed in red
 
 44 MARSH FEVER AND ITS ORGANISM. 
 
 blood-corpuscles ; the outline of these elements may be brought 
 out by a concentrated solution of methyl blue. 
 
 2nd. The same elements containing (principally in pernicious 
 attacks) numerous granules of pigment ; the methyl blue stains 
 these bodies entirely. 
 
 3rd. The same corpuscles, free in the blood and pigmented, 
 showing sometimes the rose-shaped segmentation ; the corpuscles 
 resulting from the segmentation may enter the red blood-cor- 
 puscles and give rise to the forms No. 1. 
 
 4th. Crescent or oval forms, pigmented; Sacharoff also remarks 
 that this form is particularly frequent in palustral cachexia, and 
 that it resists quinine treatment more than the others. 
 
 5th. Haematozoa with flagella endowed with rapid movements. 
 
 In 1889 Sacharoff published a pamphlet in Russian with the 
 title 'Paludism in the Transcaucasian Railway/ which is interest- 
 ing principally on account of the micro-photographs appended 
 to the text. Several of these photographs give these crescent- 
 shaped bodies perfectly, and even the spherical bodies adherent 
 to red blood-corpuscles. 
 
 The treatise of Khenzinsky entitled ' Contribution to the Study 
 of the Micro-organisms of Paludism ' (Odessa, 1889) deserves 
 mention here ; a plate representing different aspects of the 
 hasmatozoa of paludism is added to this work. 
 
 Enrique Morado and Tomas Coronado found the haematozoon 
 of paludism with its different forms at Havana, both the crescent- 
 shaped bodies and the spherical bodies and flagella (' Cronica 
 medico-quirurgica de la Habana/ October, 1889). 
 
 In a work published in 1890 in the same journal Coronado 
 first describes the alterations which take place in normal blood 
 after its coming out of the vessels, alterations which he says are 
 very important to Havana on account of the high temperature of 
 the atmosphere ; and he shows conclusively that these alterations 
 must not be confused with 'those which are produced by the 
 presence of haamatozoa. He afterwards describes the haematozoa 
 of paludism. 
 
 In seventy-one patients suffering from palustral fever whom 
 he examined, the spherical bodies were met thirty-six times, the 
 crescent-shaped bodies twenty-nine times, the flagella eleven 
 times ; the last were always associated with spherical bodies. 
 
 Coronado shows mobile corpuscles free in the serum, which 
 would be embryonic forms of the haematozoa. The parasitic nature 
 of these corpuscles does not seem well proved. Mobile corpuscles 
 similar to those described by Coronado are often seen in the
 
 OBSERVATIONS OF OTHER AUTHORS. 45 
 
 blood of patients suffering from affections other than paludism, 
 and even in that of healthy people (see Chap. III). 
 
 Coronado concludes from his investigations that several kinds 
 of haainatozoa do not exist causing the different clinical varieties 
 of paludism, but one simple polymorphic hasmatozoon. 
 
 The hasmatozoon of paludisni has also been found in Mauritius 
 by Elie Anderson, and at Hong-Kong by J. M. Atkinson. 
 
 Pietro Canalis published several interesting works on the 
 haematozoa of paludism, dating since 1889. 
 
 In sixty-three patients suffering from palustral fever, who were 
 examined with great care and often at very short intervals in 
 the military hospital at Rome, the haematozoa of paludism were 
 discovered in every case, but were never seen in the blood of 
 patients suffering from affections other than paludism. 
 
 P. Canalis admits with Golgi that the parasites of paludism 
 present a different evolution in the tertian and quartan fevers; 
 he also tries to show that there exists a third variety, to which 
 he gives the name of half-moo7i-sJiaped bodies, which ]s the most 
 characteristic form of the evolution of these parasites. This 
 last variety is met with in lengthened attacks of quotidian 
 fevers or subintrants, being able in the continued forms to 
 rapidly produce cachexia in certain pernicious fevers and in the 
 irregular fevers. 
 
 According to Canalis, the cycle of development of this third 
 variety may be divided into four phases : the amoeboid bodies, 
 half-moon or oval bodies, rounded bodies and flagella, and 
 segmented bodies. The semi-lunar bodies are developed in the 
 red blood-corpuscles at the expense of the amoeboid bodies ; they 
 transform themselves into oval bodies, then into spherical bodies 
 from which flagella emerge. The semi-lunar forms usually only 
 appear in the blood after repeated attacks from the fifteenth to 
 the thirtieth day after a first attack. Canalis found these ele- 
 ments only once in the blood on the seventh day of the disease. 
 
 Among these phases of evolution there is only one characteristic 
 body — the crescent-shaped body. Canalis confesses that in the 
 first phase (amoeboid bodies) the third variety which he wishes 
 to be admitted is not to be distinguished from the other two ; the 
 flagella also are not peculiar to this variety ; lastly, the author, 
 who admits that the crescent-shaped bodies, after being trans- 
 formed into spherical bodies, may undergo segmentation or 
 spor ulation, does not say how the segmentation differs from that 
 which is observed in tertian and quartan fevers. 
 
 It should be noticed that Canalis has not seen this segmenta-
 
 46 MARSH FEVER AND ITS ORGANISM. 
 
 tion take place in the course of a microscopic observation, and it 
 is by induction that he has been led to admit it. 
 
 The crescent-shaped bodies remain, which surely are very 
 characteristic. Are these bodies always found in certain clinical 
 forms of paludism, exclusive of others ? That is a question 
 which we shall examine further on. 
 
 Feletti and Grassi (' Sur les parasites du paludisme/ Catane, 
 1889, and 'Riforma medica/ March, 1890) have succeeded in 
 finding the haematozoa of paludism at Catania, and they do not 
 hesitate to admit that the elements which I have described are 
 really parasites — a fact all the more interesting because Professor 
 Grassi was at first little favorable to this opinion. Feletti and 
 Grassi said that, by modifying the methods of research hitherto 
 used, they had noticed the existence of a nucleus inside the 
 spherical bodies ; the name of amibules is proposed by them to be 
 given to the smallest of these bodies, and the name of amibse to 
 the others. The nucleus of the amoeboid bodies is of great size, 
 and most often eccentric ; it resembles that which is found in 
 many Rhizopods. A nucleolus is found in the nucleus. Feletti 
 and Grassi do not describe the alteration of the method of 
 observing which they have used. 
 
 The semi-lunar bodies would also seem to contain a nucleus 
 with a nucleolus. 
 
 According to Feletti and Grassi, two species at least of hasma- 
 tozoa of paludism should be distinguished ; the first giving birth 
 to regular fevers, and the second to irregular ones. The para- 
 sites of the irregular forms are characterised by the crescent 
 shape, as Golgi and Canalis had already mentioned. Feletti 
 and Grassi noticed a very marked difference between the two 
 species of parasites in all cases of fever studied at Catania since 
 September, 1889, the crescent-shaped bodies never having been 
 met by them in the tertian or quartan fevers. 
 
 Feletti and Grassi must have seen at Catania, as may be seen 
 everywhere, fevers which change their type, and after having 
 been continued or quotidian assume the quartan type ; it should 
 be admitted that in these cases, which are very frequent, the 
 two varieties of parasites co-exist in the blood. 
 
 According to these authors, the flagella only represent one 
 phase of the alteration of the hseniatozoon. They acknowledge, 
 however, that flagella may be found in the blood of certain 
 patients only a few minutes after the blood is taken from the 
 vessels. 
 
 The researches of E. Antolisei and Angelini are, on most
 
 OBSEEVATIONS OF OTHER AUTHORS. 47 
 
 points, confirmative of those of Golgi and Canalis (' Riforma 
 medica,' January, 1890, and ' Archivio Italiano di Clinica 
 Medica,' 1890). 
 
 The ha3matozoon of the quartan fever is, according to these 
 observers, the one least chai'acterised among the parasites of 
 paludism, and the one whose evolutions are most regular and 
 consequently easiest to study. 
 
 On the first day of the intermission, pigmented spherical bodies 
 are found in the blood of patients suffering from quartan fever ; 
 on the second day these elements, having grown larger, are found 
 in the blood-corpuscles or free in the plasma, but the free 
 elements are rarer than in the tertian. On the day of the attack 
 segmented forms appear in the blood six, eight, or ten hours 
 before the beginning of an attack. During the febrile attack 
 the examination of the blood reveals principally amoeboid bodies 
 without pigment, and segmented bodies become more and more 
 scarce ; Antolisei has not witnessed the change of the spores 
 into amoeboid bodies as a result of segmentation. 
 
 Sporulation would seem to be the determining cause of the 
 attack of fever, which, according to Antolisei, is severe in 
 proportion to the number of forms in process of segmentation. 
 
 In no case of quartan fever has Antolisei met any crescent- 
 shaped bodies or flagella. 
 
 If there exist in the blood two generations of parasites, the 
 one being one day older than the other, a double quartan fever 
 is the result ; three generations may produce a triple quartan, 
 i. e. a fever with the symptoms of a quotidian ; but it is rare, 
 according to Antolisei, for the quotidian to be due to such trans- 
 formation of the quartan. 
 
 In certain swfr-continued fevers the same parasitic elements 
 may be met as in the quartan. 
 
 The parasitic forms which are met in the blood of patients 
 suffering from tertian fever are complex and much more difficult 
 to understand, in the opinion of Antolisei, than those of the 
 quartan fever. In many cases, writes this authority, elements 
 have been found which were not expected, and which did not 
 seem to have any relations with the febrile cycle in which the 
 observation is made ; in a certain number of cases of tertian 
 fever it has been impossible to find segmented bodies in spite of 
 frequent examination of the blood. 
 
 In the first few hours which follow an attack of tertian fever, 
 a,moeboid bodies with or without pigment, and free or enclosed 
 within the red corpuscles, may be generally observed. On the
 
 48 MARSH FEVER AND ITS ORGANISM. 
 
 day of the apyrexia the pigmented bodies appear more and more 
 large and numerous, being found in largest numbers in the 
 blood eight or ten hours before the attack. The flagella have 
 often been discovered in the blood of patients suffering from 
 tertian fever. 
 
 The number of spores is larger in the segmented bodies of 
 the tertian than in those of the quartan fever, as has been shown 
 by Golgi. 
 
 Antolisei admits that most quotidian fevers are produced by 
 the hasmatozoa of the tertian type, but he does not consider that 
 the observation of the facts will allow any opinion to be 
 formulated as to the existence of two generations of parasites, 
 which would come to maturity after an interval of twenty-four 
 hours. 
 
 The principal characteristics of the hasmatozoa of irregular 
 fevers seem to be the following : — At the beginning of the 
 infection induced by this variety of parasites there are often 
 only amoeboid bodies to be found in the blood, at least in peri- 
 pheral blood ; after a variable time the crescent-shaped bodies 
 appear ; the appearance of these elements cannot always be 
 waited for ; on account of the severity of the fever, administra- 
 tion of quinine is necessary. The patients may have several 
 recurrences of fever without the crescent-shaped bodies being 
 observed ; these, however, show themselves at last, and are cha- 
 racteristic of this variety of parasites (Antolisei and Angelini). 
 
 When only amoeboid movements are observed in the blood, it 
 is impossible to say whether it is a tertian, or quartan, or 
 irregular fever. 
 
 The crescent-shaped bodies come from amoeboid bodies ; the 
 sporulation is made as with the other varieties of rounded cor- 
 puscles (Canalis) . From these spores the amoebae proceed which 
 in turn produce a new generation of parasites. 
 
 The amoebae, at a certain point of their development, instead 
 of following the evolution common to the other forms and 
 reproducing themselves with the rounded form, assume the 
 semi-lunar form. There is no direct observation which shows 
 the passage of one amoeba, with or without pigment, into the 
 semi-lunar form, but there are many reasons for believing that 
 this is their mode of development (Antolisei and Angelini). 
 
 The semi-lunar bodies take the oval form, then the rounded 
 form, and from this rounded form flagella often proceed. 
 Antolisei and Angelini have not seen the flagella in the act of 
 liberating themselves.
 
 OBSERVATIONS OF OTHER AUTHORS. 49 
 
 The other processes which are observed in the semi-lunar 
 forms are the following : 
 
 ist. The budding, which may take place on the crescent- 
 shaped, oval, or rounded forms. 
 
 2nd. Disintegration (death) ; the protoplasm is broken up into 
 irregular hyaline fragments with a simple contour. 
 
 3rd. The sporulation ; this takes place as in the quartan fever, 
 the pigment accumulates in the centre ; soon the spherical body is 
 segmented and gives rise to rounded corpuscles with a double 
 outline, eight, ten, or twelve in number. 
 
 These bodies in process of sporulation are not very common in 
 peripheral blood, the internal organs appear to be the seat they 
 prefer. 
 
 When the blood of a patient suffering from h-regular palustral 
 fever only shows spherical bodies, it is certain that after a variable 
 time, should the patient have a relapse, the crescent-shaped 
 bodies will be found (Autolisei and Angelini). 
 
 Quinine causes the amoeboid bodies to disappear from the 
 blood, but not the crescent-shaped bodies, which persist for a 
 variable time. 
 
 The flagella do not appear to represent a necessary phase of 
 the crescent-shaped bodies, but only an accidental phase. 
 
 In another work ( f Eiforma medica/ April, 1890) Antolisei writes 
 concerning the variety of the hasmatozoa characterised as crescent- 
 shaped bodies, " The biology and morphology of this entity 
 vary with the intensity of the infection it sets up, with the 
 season in which the infection takes place, and with the individual 
 conditions of the patients who suffer from it." 
 
 The differential characters attributed by Antolisei and Angelini 
 to the three species of haematozoa recognised by them are, as 
 we see, wanting in precision. 
 
 G. Terni and G. Giardina (' Kivista d' Igiene e Sanita Pubblica/ 
 May 1 6th, 1890) have examined the blood of eighty -five patients in 
 the military hospital at Rome during the months of October, 
 November, and December, 1889. Inmost of the irregular fevers 
 and of the palustral cachexias they found the crescent-shaped 
 bodies, which confirms the theories of Golgi and Canalis. 
 
 Terni and Giardina have observed the flagella twenty-fivo 
 times in eighty-five cases, and they found, as I did, that the 
 flagella are more likely to be found in the blood of individuals 
 in danger of an attack, and also that they are always associated 
 with the spherical bodies. 
 
 A. Bignani has studied the distribution of the parasitic elements 
 
 4
 
 50 MARSH FEVEE AND ITS ORGANISM. 
 
 in the different organs of patients who have died from pernicious 
 attacks ( f Accad. med. di Roma/ anno XVI, t. v, ser. 2) ; he has 
 come to the following conclusions : — The parasites are always 
 found in much larger numbers in the small arteries and the 
 capillaries than in the vessels of average or large size. The 
 adult forms of the parasites and the bodies in process of segmen- 
 tation have a great tendency to accumulate in some capillary 
 network, especially in that of the brain, the lungs, the spleen, 
 the medulla of the bones, the liver, and the intestines ; in some 
 cases of pernicious fever with bilious symptoms, the capillary 
 network of the intestines was richer in parasites than all other 
 organs. The crescent-shaped and oval bodies are more abun- 
 dant in the spleen and the medulla of the bones than anywhere 
 else. 
 
 The parasites accumulate where the circulation is sluggish, as 
 in the brain capillaries, and they cause, according to Bignani, the 
 endothelial lesions which increase the difficulty of circulation still 
 more. In the veins, the parasites (amoeboid forms) are often 
 adherent to the walls like leucocytes. The perniciousness, as 
 Bignani rightly observes, always coincides with a very great 
 abundance of parasites ; but these parasites, although in very 
 large numbers in the viscera, may be scarce enough in the blood 
 taken from the finger. 
 
 The search for the parasites of paludism in cadavera is difficult 
 because these parasites are rapidly deformed and are confused with 
 melaniferous leucocytes ; this confusion has been made by all the 
 authors who previously to me had studied the anatomic lesions 
 of paludism. Bignani made his post-mortems only a few hours 
 after death, which explains why he has been able to find the 
 parasites with their characteristic appearance. 
 
 Bignani recommends the following plan for the study of the 
 hasmatozoa in the tissues taken from the cadavera : 
 
 1 st. As a means of fixing, absolute alcohol and solution of 
 sublimate of 1 per cent., to which he adds 0*75 per cent, of 
 chloride of sodium, and from 0*50 to 1 per cent, of acetic acid ; 
 the preparations remain in this liquid from a quarter of an hour 
 to a few hours, according to their size. 
 
 2nd. For the staining of these sections : the aqueous solution 
 of safranin, the solution of methyl blue with one per 10,000 
 of potash, vesuvin in aqueous solution, Bismarck brown and 
 Grubler's red magenta. These last two colouring substances 
 are those which have given the best results. 
 
 The German authors at first received the Bacillus malarise of
 
 OBSERVATIONS OP OTHER AUTHORS. 51 
 
 Klebs and Tommasi Crudeli with much favour, ignoring- my 
 haematozoon ; but the recent works by Paltauf, Kahler, Plehn, 
 Bamberger, and of Quincke corroborate mine. 
 
 Paltauf has found the haematozoon of paludism ten times out of 
 ten, and Kahler five times out of five (' Societe de Medecine de 
 Vienne/ December 20th, 1889). 
 
 Bamberger has established the presence of these parasites in 
 all palustral patients whom he has examined, and he has never 
 found similar organisms in individuals suffering from diseases 
 other than paludism (' Societe de Medecine de Vienne/ May 2nd, 
 1890). 
 
 Plehn ( f Societe de Medecine de Berlin/ March 5th, 1890) has 
 observed the haematozoa of paludism in the blood of several 
 patients who had intermittent fever in Germany, and principally 
 in the blood of workmen who had contracted the fever in the 
 neighbourhood of Potsdam. Plehn, who has ascertained that 
 these hsematozoa were never met with except in paludism, and 
 disappeared under quinine treatment, has no doubt that they are 
 the pathogenic cause of paludism. 
 
 Quincke (Kiel, 1890) has had the opportunity of examining 
 eight patients suffering from palustral fever ; six of these patients 
 had worked in digging the canal from the North Sea to the 
 Baltic, the other two cases came from the Lower Elbe and Kiel. 
 In one case only was the fever quotidian ; in the other cases it 
 had a tertian type. In the eight patients the examination of the 
 blood showed the existence of the haematozoa of paludism. 
 
 Quincke had not observed the constant relations which, accord- 
 ing to Golgi, would exist between the nature of the parasitic 
 elements in the blood and the febrile type. He points out that 
 pseudo-vacuolated alterations of the red blood-corpuscles, which 
 have nothing in common with the parasites of paludism, are oft 1 11 
 observed in the blood of palustral patients, and are also scon in 
 iarge numbers of diseases, and even in the blood of healthy 
 persons. 
 
 The works of Plehn and Quincke are interesting, although 
 they are founded on a small number of facts. It w;is useful to 
 ascertain that intermittent fever, which was contracted in the 
 neighbourhood of Potsdam or Kiel, was accompanied with the 
 presence of the same parasites in the blood as the levers of 
 Algeria and the hot countries. 
 
 Pfeiffer has also observed the luematozoa of paludism (' Les 
 Protozoaires pathogenes/ Jena, 1890). 
 
 As to the numerous works recapitulated above, all of tin in
 
 52 MARSH FEVER AND ITS ORGANISM. 
 
 (except for a few differences on secondary points) agree with 
 my observations, only a small number can be set against them 
 with different conclusions. 
 
 Only a single work confirmatory of the opinions expressed by 
 Klebs and Tominasi Crudeli on the existence of a Bacillus malarise 
 has been published since 1882, that of Schiavuzzi. 
 
 On April 4th, 1886, Tommasi Crudeli announced to the Medical 
 Academy of Rome that B. Schiavuzzi had succeeded in obtaining 
 a pure culture of a bacillus collected in the air of the marshes in 
 the neighbourhood of Pola in Istria, and that this bacillus was 
 identical with the one which had been previously described by 
 Klebs and himself. 
 
 A new communication was made on that subject to the Medical 
 Academy of Rome at the sitting of December 5th, 1886; lastly, 
 Prof. Ferdinand Cohn, who had followed the researches of 
 Schiavuzzi at Pola, published the result, in 1886, in his paper 
 (' Beitrage zur Biologie des Pflanzen/ 1888). 
 
 The bacillus isolated by Schiavuzzi is found in the earth of 
 palustral districts under the shape of oval spores, mobile, 
 refracting light strongly ; in the body of animals inoculated, 
 and in the cultivation fluids, it would appear to be developed in 
 long filaments, first homogeneous, afterwards transversely seg- 
 mented. 
 
 It is somewhat surprising to find in the treatise of Schiavuzzi, 
 as the proof of his assertion that this bacillus is the agent of 
 paludism, only four experiments on rabbits which had been 
 inoculated with the cultivation fluid of the bacillus found there 
 (Pola). Moreover these experiments do not prove much. The 
 thermometric tracing from the rabbits inoculated by Schiavuzzi 
 differ very little from those of healthy rabbits ; the temperature 
 of animals, and of rabbits in particular, undergoes variations of 
 temperature at night, consequently the oscillations of some tenths 
 of a degree cannot be considered as showing a diseased state. In 
 one of these observations a well-marked rise, which also was 
 not repeated, may be explained by local accidents, even the 
 puncture of inoculation. As Golgi says, Schiavuzzi, Tommasi 
 Crudeli, and Colin must have had a vei*y extraordinary imagina- 
 tion to see authentic examples of intermittent fever in the 
 rabbits in these facts (Golgi, ' Intorno al Preteso Bacillus malarise 
 di Klebs, Tommasi Crudeli, e Schiavuzzi/ Torino, 1889). 
 
 The post-mortem changes found in the rabbits under experi- 
 ment are not more characteristic than the thermometric tracings. 
 
 The treatise by Schiavuzzi, far from confirming the opinions
 
 NO CHARACTERISTIC BACILLUS FOUND. 53 
 
 held by Klebs and Tommasi Crudeli, on the contrary shows the 
 weakness of the foundation for the belief in the Bacillus malarias. 
 
 Golgi has tried to verify the assertions of Schiavuzzi, and has 
 made experiments on rabbits with cultures of the bacillus pre- 
 pared by Schiavuzzi himself. 
 
 The conclusion arrived at from these experiments is that the 
 injections of the bacillus of Schiavuzzi have never produced inter- 
 mittent fever in rabbits ; after inoculation an observer can 
 scarcely notice the slight elevation of temperature, which is not 
 repeated on the following days, and which has been also noticed 
 after the inoculation of cultivated liquids of non-pathogenic 
 organisms. 
 
 Golgi has carefully examined the blood of rabbits inoculated 
 with the culture fluid of the bacillus of Schiavuzzi. That 
 examination only showed him a few of those commonplace 
 alterations of the red blood-corpuscles which take place even in 
 normal blood after it comes out of the vessels ; he has never met 
 any elements similar to the parasitic elements of palustral 
 patients. 
 
 Golgi comes to the conclusion that the bacillus of Klebs, 
 Tommasi Crudeli, and Schiavuzzi has nothing to do with pa- 
 ludism. 
 
 Another Italian author, as far back as 1887, in a review of 
 the parasites of paludism, recapitulated the history of the bacillus 
 described by Klebs and Tommasi Crudeli as follows: "From 
 the moment of its discovery, the Bacillus malarias has been con- 
 tinually losing its ground to such an extent that to-day it is 
 completely abandoned' 5 (U. Arcangeli, 'Rivista Clinica,' No. 1, 
 1887). 
 
 The place of the Bacillus malarias seems to be among the 
 vaunted parasites of paludism which have no longer anything but 
 historic interest. 
 
 In 1886 Von Sehlen published a work on the etiology of 
 paludism, in which he announces that he has found micrococci 
 about 1 fx in diameter in the blood of patients suffering from 
 intermittent fever, who were examined during the cold stage. 
 By cultivating the blood taken from these patients in gelatine 
 he obtained colonies of micrococci, whilst other cultivations 
 made with blood taken during the intermission did not produce 
 anything. The earth of marshy localities seems to have yielded 
 colonies of micrococci similar to those of palustral blood 
 (Sehlen, "Ueber die Aetiologie der Malaria/' ' Arch, do Virchow,' 
 May, 1886, p. 319).
 
 54 MAltSH FEVER AND ITS ORGANISM. 
 
 The attempts made by different observers to reproduce these 
 experiments have only given negative results. Palustral blood, 
 does not contain any micrococci, that name would not describe the 
 embryonic forms of the haematozoa of paludism ; the smallest 
 of these elements, it is true, resemble by their dimensions the 
 micrococci described by Sehlen, and it might be supposed that 
 he had noticed these embryo forms and mistaken them for micro- 
 cocci were it not for the question of cultivation. 
 
 Up to the present time the attempts at the cultivation of 
 the hasrnatozoon of paludism have only given negative results. 
 For my part I have made numerous attempts in that direction 
 without the smallest success (Chap. I, p. 29), and other observers 
 have not been more fortunate than I. 
 
 Schwalb (' Reunion des medecins allemands a Magdebourg,' 
 September, 1884, and ' Virchow's Arch.,' September, 1886, p. 486), 
 having succeeded in setting up lesions similar to those of 
 palustral melanaemia in rabbits by giving repeated doses of 
 sulphur or oxysulphide of carbon (COS) to these animals, has 
 come to the conclusion that paludism is a poisoning by oxy- 
 sulphide of carbon. 
 
 I mention this chemical theory of paludism for completeness' 
 sake, but I consider it is useless to discuss it. Intermittent fever 
 has not been observed, so far as I know, in workmen exposed to 
 the vapours of sulphide of carbon, and the existence of oxysul- 
 phide of carbon in the countries in which paludism prevails has 
 still to be demonstrated. 
 
 The haematozoon of paludism is difficult to observe, especially 
 in our climate, and in subjects already under treatment, and 
 also when its different appearances are unfamiliar ; it is not 
 surprising, therefore, that investigations undertaken under these 
 conditions have been sometimes negative. A large number of 
 observers, after having at first denied the existence of the 
 hiematozoon of paludism, have become convinced of the reality of 
 this parasite after new researches. 
 
 I think I may conclude, from this review of works subsequent 
 to mine, that the existence of the pai*asites described by me 
 in palustral blood is well established. These parasites have been 
 found in the most distant parts of the globe, and, as Osier has ob- 
 served, there is a remarkable coincidence between the descriptions 
 which have been given in Europe, Africa, Asia, and America. 
 
 How are these new parasites to be classified ? Are they really 
 the pathogenic cause of paludism ? These questions will be 
 examined in the following chapters.
 
 CHAPTER III. 
 
 The hsematozoon which I have discovered in palustral blood is a 
 sporozoon — Similar hsematozoa exist in different animals, and 
 principally in birds. 
 
 The parasitic nature of the elements described in the first 
 chapter is no longer disputed at the present day ; however, I 
 think it would be well to say a few words about the investiga- 
 tions of Mosso and Maragliano, which aimed at proving that 
 altered blood-corpuscles might take the appearance of some 
 of the parasitic elements of palustral blood. 
 
 Mosso injected the blood of a dog into the peritoneal cavity 
 of a bird, and for three or four days after the injection he 
 noticed some changes of the red blood-corpuscles, which he tried 
 to compare to the changes in palustral blood. 
 
 Observers who undertook to confirm these researches have, 
 after studying the parasites of the palustral blood, come to con- 
 clusions diametrically opposed to those of Mosso. 
 
 A. Cattaneo and Monti injected the blood of a dog eighteen 
 times into the peritoneum of birds (fowls and pigeons), after 
 Mosso's plan, and examined the contents of the peritoneum at 
 different times varying between the first and fifteenth day after 
 the operation. 
 
 In this experiment the blood injected is separated during the 
 first few days into a liquid part and a coagulum ; in proportion to 
 the length of time since the injection, the liquid part grows less 
 and the coagulum becomes firmer. 
 
 Red corpuscles (of bird and dog) more or less altered are found 
 in the liquid part and in the coagulum ; also normal or granular 
 white corpuscles, globuliferous or pigmented cells similar to those 
 which have been described by Bizzozero as found in the medulla 
 of the bones, which seem to be derived from the peritoneal 
 endothelium. These bodies of the changed blood must not bo 
 confused with the parasitic bodies of palustral blood. 
 
 Plates produced in Cattaneo and Monti's work show the
 
 56 MARSH FEVER AND ITS ORGANISM. 
 
 different appearances which the changed red and white corpuscles 
 of Mosso's experiment take ; it is sufficient to glance at these 
 plates to be convinced that the haematozoa of paludism have 
 nothing in common with these changes of the blood. 
 
 Marchiafava and Celli, who have repeated the experiment of 
 Mosso, have arrived at the same conclusions as Cattaneo and 
 Monti. This fact deserves the more notice, because at the 
 beginning of their researches these authors declared that my 
 parasites were nothing but the normal elements of the blood more 
 or less changed. 
 
 Maragliano has studied the changes which are seen in human 
 blood when subjected to drying, heat, and different reagents. 
 
 According to Maragliano, in a preparation of normal blood 
 surrounded with paraffin, some changes of red blood-corpuscles 
 may be found which have a close relation to some of the altera- 
 tions described in palustral blood, specially the clear spaces, 
 non -pigmented, on which Marchiafava and Celli have specially 
 insisted. Some plates which accompany the treatise of Maragliano 
 show the alterations of the red blood-corpuscles observed. 
 
 It appears evident, after examination of these figures, that 
 Maragliano has observed neither the pigmented spherical elements 
 nor the crescent-shaped bodies nor the flagella of the palustral 
 blood ; none of the bodies represented by him contain pigment, 
 none show even vaguely the appearance of the flagella. The 
 only doubtful point is that concerning the small clear spaces non- 
 pigmented. It is certain that, under the influence of heat and 
 drying, clear spaces are often made in the red blood-corpuscles, 
 and it is possible for these to be confused with the blood-cor- 
 puscles to which some small hyaline spherical bodies, not yet 
 pigmented, adhere. 
 
 This source of error can be avoided by examining fresh blood 
 at the ordinary temperature, and in any case it should not be 
 used as a proof in regard to the other parasitic elements of the 
 palustral blood. 
 
 Cattaneo and Monti, who have repeated the investigations of 
 Maragliano, conclude that the alterations described by him have 
 no relation to those of palustral blood. Such is also the con- 
 clusion of Dr. Tomas Coronado of Havana, who has studied both 
 the alterations just described and those of palustral blood, com- 
 paring them one with another. 
 
 For my part, I have often been in a favorable position to 
 examine the blood under the conditions stated by Maragliano, 
 and I have never seen any of the elements which I consider
 
 NATURE OF THE ORGANISM. 57 
 
 characteristic of paludism when the blood was taken from a 
 patient suffering from paludism. 
 
 In a recent discussion at the Congress of the Italian Society 
 of Internal Medicine, Maragliano admitted the existence of the 
 hasmatozoa of paludism, whilst maintaining that the plasmodia 
 (i. e. the spherical bodies deprived of pigment) might be confused 
 with the corpuscular changes (' Semaine medicale,' 1890, p. 
 394). Brought down to these limits, the criticism of Maragliano 
 seems to me quite just. 
 
 The changes which heat produces on the red corpuscles of the 
 blood must also be put out of the question. It is known that 
 when a preparation of normal blood is heated to 57 C, distinct 
 changes of the red blood-corpuscles may be seen taking place. 
 Projections of little sarcoid balls, which are endowed with the 
 Brownian movement, appear on their edges. 
 
 Talamon again called attention last year to these alterations 
 of the red blood-corpuscles, and particularly to what he called 
 the flagellar disfiguration (' Societe Medicale des Hopitaux,' 
 February 26th, 1890, and ( Journal de la medecine moderne,' 
 March 6th, 1890). 
 
 Talamon brings about these changes by placing the prepara- 
 tion of fresh blood 8 or 10 centimetres distant from a very hot 
 coke fire, ten to twelve seconds being sufficient to produce the 
 changes ; the slide placed on the back of the hand at that instant 
 gives a fairly severe sensation of burning. 
 
 This experimental process is bad for two reasons : first, if 
 the preparation is heated too much all the blood-corpuscles are 
 destroyed ; secondly, the temperature at which the changes are 
 produced cannot be ascertained. By using the hot stage it 
 is easy to notice that a temperature of 56 to 57 C. at the 
 minimum is necessary for the alterations in the red blood-corpuscles 
 to take place. As soon as the temperature reaches that degree, 
 little sarcoid balls are formed on the circumference of the red 
 blood-corpuscules ; these sarcoid balls are often transformed into 
 prolongations of variable length, which are endowed with a move- 
 ment more or less rapid but little varied : the sarcoid balls 
 which leave the red blood-corpuscles are endowed with Brownian 
 movement. 
 
 These facts have been very well studied by MM. Schultzo and 
 Ranvier. Talamon made his observations with a very strong 
 power (objective 12 in the immersion of Verrick), therefore the 
 phenomena have been described by him in much brighter colours 
 than by Schultze and Ranvier ; an enlarged representation of a
 
 58 MARSH FEVER AND ITS ORGANISM. 
 
 phenomenon which is common, or at least can be produced at 
 will, is found in his description. 
 
 The differences which exist between the flagella of paludism, 
 and the sarcoid projections of the normal blood-corpuscles sub- 
 mitted to the action of heat, are numerous. 
 
 i st. The flagella of the hsematozoon of paludism maybe observed 
 at the ordinary temperature of the laboratory ; I have often 
 observed them at a temperature not even 15 C. The sarcoidal 
 protrusions on the red blood-corpuscles are only developed when 
 the blood is heated from 56 to 57 C. 
 
 2nd. The flagellae of the haematozoa have never been seen except 
 in patients suffering from paludism ; they are always joined in 
 the blood of these patients with other parasitic elements — the 
 pigmented spherical bodies from which they appeared to spring; 
 the flagella never spring from red blood-corpuscles, as is always 
 the case with sarcoidal protrusions, whose formation is brought 
 about by strongly heating the blood. 
 
 3rd. The flagella of paludism differ from the sarcoidal pro- 
 trusions in their shape and dimensions, being always more 
 uniform than those of the prolongations ; also by the rapidity 
 and variety of their movements. None of the observers who have 
 watched the flagella move in all directions, roll up, then unroll, 
 giving the most varied movements to the blood-corpuscles (which 
 at times they appear to seek to penetrate), will admit that these 
 movements may be mistaken for those of the sarcoidal protu- 
 berances produced by heat. The flagella sometimes move so 
 quickly that they give a transitory movement to the spherical body 
 to which they are attached. When they have become free they 
 retain the same rapidity and the same variety of movements. 
 
 Hayem (" De la contractilite des globules rouges et des pseudo- 
 parasites du sang dans Fanemie extreme/' ' Soc. Med. des 
 Hopitaux,' February 21st, 1890) has called attention to some 
 alterations in the shape of the red blood-corpuscles which are 
 found in pernicious anaemia ; these alterations have been clas- 
 sified by him under the four following types : 
 
 1st Type. — Certain red corpuscles, sometimes of great size, 
 which have the capacity of altering their shape on the spot 
 (amoeboid contractility). 
 
 2nd Type. — Certain red corpuscles which show prolongations 
 in the shape of a finger of a glove, mobile or motionless ; the 
 movements of these projections are most often simple oscilla- 
 tions ; sometimes a very sharp tentacular prolongation takes 
 place.
 
 NATURE OF THE ORGANISM OP PALUSTRAL BLOOD. 59 
 
 3rd Type. — Oscillatory movement of the very small corpuscles 
 which remain suspended in the plasma. 
 
 4th Type. — Bodies out of focus in the preparation (pseudo- 
 parasites). Most generally these latter elements present the 
 appearance of small knotty sticks, narrow and of a variable 
 length. 
 
 " These pseudo-parasites possess a continuous oscillatory 
 movement round their vertical axis, and in addition an inflexion 
 movement following their facets. The result of this double 
 movement and of their irregularity of contour is that each of 
 them, considered individually, changes its shape constantly, a 
 peculiarity which alone would be sufficient to distinguish these 
 mobile bodies from the parasites with which they might be 
 confounded. 
 
 " Such a body, which has at a given instant the appearance 
 •of a small stick, suddenly assumes that of a small rounded mass 
 carrying a sort of flagelluni. At other times the small stick, 
 resembling a bacterium, takes a curve and assumes the shape of 
 a V or of a small triangle. In other cases the element assumes 
 the shape of a diplococcus. 
 
 " Whatever their form may be, all these small bodies move 
 about rapidly in the preparation " (' Bulletin de la Soc. Med. 
 des Hopitaux/ 1890, p. 119). 
 
 The different characteristics of the pseudo-parasites of the 
 blood, and of the flagella of the palustral blood, are easy to 
 trace ; the flagella do not develop themselves on the sides of the 
 blood-corpuscles like the pseudo-parasites of Hayem ; they do not 
 resemble those knotty prolongations of very unequal length 
 which have the appearance of bacteria or of diplococci. Lastly, 
 the very complicated movements of the flagella cannot be com- 
 pared to those of these debris of red corpuscles, which, possessing 
 the Brownian movement, are also carried about by the currents 
 which always occur in the plasma of fresh blood — currents which 
 are due to the differences of temperature and to the evaporation 
 which takes place at the edges of the cover-slip. 
 
 The movements of the red corpuscles described by Hayem, with 
 the exception of those of the first type, do not seem to be those 
 of living bodies. They persist for a few days in preparations 
 made aseptically, and may be excited at will by suddenly raising 
 the temperature of the blood, which evidently alters the vitality 
 of the blood-corpuscles (Browicz, ' Neuvieme congres de medeeino 
 interne,' Vienna, 1890). 
 
 A. Edington (" Report on the Morphology and Development of
 
 60 MAKSH FEVER AND ITS ORGANISM. 
 
 the Blood/' in 'Brit. Med. Journ.', May 31st, 1890) has pointed 
 out the existence of elements to which he gives the name of albo- 
 cytes, which are found in normal blood. They are colourless cor- 
 puscles, spherical, about the size of a third of the diameter of a red 
 blood-corpuscle, which would seem to be formed in the interior 
 of a special white corpuscle or matricyte. The albocytes, at first 
 colourless, increase in size little by little, become loaded with 
 haemoglobin, then become biconcave, and thus reach the state 
 of adult red corpuscles. 
 
 Talamon considers that the albocytes of Edington are no 
 other than the hasmatoblasts "of Hayem (' Medecine moderne,' 
 1890, p. 728). 
 
 At the Congress of Berlin, 1890, Kollmann, of Leipsic, again 
 called attention to the pseudo-organisms of the normal human 
 blood. When normal human blood gathered with antiseptic 
 precautions is examined, a number of little bodies, says 
 Kollmann, can be seen resembling micrococci or bacilli ; these 
 corpuscles, the largest of which measure 0*5 /n in diameter, are 
 endowed with very quick movements. Examination by staining 
 reagents shows that these are artificial products resulting from 
 blood-corpuscles or leucocytes ; the cultivations on gelatine are 
 neutral. 
 
 These pseudo microbes of the blood have been mistaken, as 
 Kollmann saj's, more than once for real micro-organisms. 
 
 The confusion of these elements, or blood-corpuscles having 
 undergone alterations with the heematozoa, could only be 
 possible in the first phase of the evolution of the parasites, i. e. 
 at the time when they present themselves under the aspect of 
 small non-pigmented elements making clear spots in the blood- 
 corpuscles. We must confess that certain altered blood- 
 corpuscles have, especially in dried blood, a great analogy with 
 red blood- corpuscles invaded by haematozoa in the first stage of 
 their development. 
 
 Celli and Guarnieri have admitted that the vacuoles artificially 
 produced in dried blood-corpuscles have been more than once de- 
 scribed as parasitic bodies ; the confusion is all the more easily 
 understood because on the stained preparations the colouring 
 matter, e. g. methyl blue, may be accumulated in the vacuoles 
 as if it had an affinity to a parasitic element. 
 
 E. Antolisei notices that the blood coming from persons free 
 from paludism, sometimes presents alterations which remind one 
 much of the first phases in the development of the haematozoa of 
 paludism (' Gazzetta degli Ospitali/ 1889, No. 77). When only
 
 NATUKE OF THE ORGANISM. 61 
 
 these non-pigmented forms are found in the blood of a patient 
 paludism must not be too hurriedly diagnosed. 
 
 Several observers, deceived by these resemblances, have thought 
 that they had found alterations identical with those which charac- 
 terise paludism, in the blood of patients suffering from other 
 affections. This confusion, I say, is only possible in the first phase 
 of the hasmatozoa, and it is difficult to make when examining 
 fresh blood which has not been submitted to the action of heat, 
 nor to that of reagents capable of altering the shape of the 
 blood-corpuscles ; it was in order to avoid these sources of error 
 that in my first researches I always examined the blood when 
 fresh and pure, without the addition of any reagent. 
 
 Kceuig, of Berlin, shows the following method of distinguishing 
 the amoeboid bodies from the pseudo-vacuoles : — the diaphragm 
 of the microscope is taken away suddenly, leaving the mirror 
 in its place, with the result that the amoeboid bodies disappear, 
 while the vacuoles remain and are still more easily distinguished 
 (Tito Gualdi, Congress of Berlin, 'Seniaine medicale,' 1890, p. 305). 
 
 What is the nature of the parasite of palustral blood ? What 
 place should be assigned to it in the scale of beings ? 
 
 This polymorphic parasite belongs evidently to a species other 
 than the schizophytes, among which all the pathogenic microbes 
 known up to the present time have been included ; most authors 
 admit that it should be classified among the sporozoa, but this 
 opinion has found some few opponents. 
 
 According to Feletti and Grassi the hasmatozoa of paludism 
 should be placed among the Rhizopods (' Riforma medica,' March, 
 1890), and they should be divided into two different species. 
 
 1 st. Hsemameba, with three varieties : 
 
 a. H. prsecox, which produces the quotidian fever, with attacks 
 tending to repeat each other at shorter intervals ; 
 
 b. H. vivax (simple and double tertian) ; 
 
 c. H. malarise (simple double or treble quartan). 
 
 2nd. Laverania, 1 producing irregular fevers which in a few 
 days change their character : continued, subcontiuued, quotidian, 
 tertian, &c. 
 
 Antolisei has attempted to show that the haematozoon of palu- 
 dism had some relation with the monadines of Cienkowski, or 
 the proteomixita of Lankester (' Riforma medica,' April, 1890). 
 
 A certain number of sporozoa are now known, which evidently 
 belong to species akin to the haematozoa of paludism. 
 
 1 I first described the luemamiba as a crescent-shaped body, I do not see then - 
 fore why my name should be given to one of these species more than another.
 
 62 MARSH FEVER AND ITS ORGANISM. 
 
 Balbiani has divided the sporozoa into, ist, gregarinse ; 2nd, 
 oviform psorospermiae or coccidia ; 3rd, tubuliforrn psorospermiae 
 or sarcosporidae ; 4th, myxosporidae ; 5th, microsporidae (' Lecon 
 sur les sporozoaires,' Paris, 1884). 
 
 The polymorphism of coccidia, their parasitic state in the 
 living cells, the complicated phenomena which are present at their 
 development, occur in the life-history of the parasites of paludism. 
 
 It is indeed among the coccidia that the hsematozoa of palu- 
 dism should be classfied according to Metschnikoff, whose autho- 
 rity in such matters is so important. 
 
 According to Kruse, the haematozoon of paludism should be 
 considered as a hsemogregarina and not as a coccidia. 
 
 Besides the coccidia, Giard has mentioned among the sporozoa 
 having some affinity with the parasites of paludism, the micro- 
 aporon of the silkworm, and the Lithocystis Schneideri, a con- 
 stant parasite of the interior of the sea-urchin. This latter 
 parasite has a plasmodial form and polysporous cysts ; crescent- 
 shaped bodies are formed in variable numbers in each spore, and 
 produce the amoebae which are transformed into flagella. 
 
 Eimer discovered a coccidium in 1870 in the intestine of a mouse, 
 which was studied by Schneider afterwards, who proposed to call 
 it Eimeria falciforme. According to Eimer, this parasite is seen 
 under several aspects : first, a cystic form enclosed in the epithe- 
 lial cells of the intestines ; second, falciform corpuscles enclosed 
 in the epithelial cells or free in the intestines : these latter possess 
 a rather rapid movement, and the bend of the crescent becoming 
 emphasised, the sudden straightening of the crescent afterwards 
 takes place ; third, amoeboid bodies which, after having wandered 
 for several days on the surface of the intestines, appear to pene- 
 trate into the epithelial cells and thus re-assume the primitive phase. 
 
 A coccidium is found in the intestines of the salamander, which 
 has great analogy with the Eimeria falciforme of the mouse. 
 This coccidium is developed in the nucleus of the epithelial cells of 
 the intestines, under the appearance of a rounded granular body 
 which segments itself and gives rise to crescent-shaped bodies 
 arranged in bundles. These latter elements, when free, are 
 animated w T ith movements identical with those of the Eimeria falci- 
 forme : the bend is exaggerated, then the crescent straightens 
 suddenly. In May, 1889, I noticed the presence of these parasites 
 in the intestines of several salamanders in the laboratory of 
 M. Metschnikoff at the Pasteur Institute. According to Metsch- 
 nikoff, these parasites assume the flagellated form at a certain 
 phase of their development. J. Steinhaus has given a good
 
 SIMILAR ORGANISMS FOUND IN ANIMALS. 63 
 
 description of these coccidia under the name of Karyophagus 
 salamandrse ('Arch, de Virchow/ 1889, t. cxv). 
 
 It is not much more surprising to see parasites developed in 
 or upon the corpuscles of the blood than in the epithelial cells of 
 the intestine, as is the case with the Eimeria folciforme. Never- 
 theless this comparison would have doubtless appeared a little 
 strange if parasites, which are still more akin to those of palu- 
 dism, had not been found in the blood of different animals. 
 
 As far back as 1843, Gruby pointed out the presence of an 
 organism with flagella in the blood of a frog, which was called 
 by him Trypanosoma sanguinis. 
 
 In 1880, Griffith Evans described a disease which rages in 
 India among horses, mules, and camels, and which is called surra. 
 This disease, which has the character of a remittent fever, is 
 caused by heematozoa which have been described under the 
 name of spirilla (by Evans), then under the name of Spirochasta 
 Evansii by Steel. Steel and Evans have been successful in 
 transmitting this disease to dogs, horses, and mules. 
 
 Lewis observed hasmatozoa in the rats of India, which he thinks 
 are identical with those of the surra disease, while Crookshank 
 found these parasites twenty-five times out of one hundred in the 
 blood of the European rat. It is a polymorphic organism, which 
 is seen at times under a globular form, at others under the form 
 of an organism with flagella, and again under the form of 
 crescent-shaped bodies. 
 
 Gaule has described a hasmatozoon of the Rana esculenta under 
 the name of cytozoon ('Arch. f. Physiol.,' 1880-81, and 'Revue 
 d'hygiene/ 1885, p. 686). This cytozoon is found in the red blood- 
 corpuscles in the shape of an elongated body with a nucleus 
 or in a free state in the plasma ; it then possesses very rapid 
 movements. The body of the cytozoon is vermiform, and very 
 thin at the extremities, its length on the average being equal to 
 the half of the long axis of a red blood-corpuscle. Cytozoa of 
 the largest size have been found in the blood of the triton. 
 
 These parasites of the blood of the frog have been described 
 by Ray Lankester, Wallerstein, and Grassi under the name of 
 Drepanidium ranarum, and by Kruse under that of Ilxmogregaruia 
 of frogs. 
 
 At the same time as drepanidium, amoeboid bodies enclosed in 
 red blood-corpuscles are often found in the blood of the frog, which 
 seem to be only one phase of the development of the drepanidium ; 
 these amoeboid bodies sometimes contain certain kinds of bacilli, 
 which are multiplied there, and are not met in a free state in the
 
 64 JVIARSH FEVER AND ITS ORGANISM. 
 
 serum. The real significance of these latter parasites in the 
 blood of a frog is still rather obscure (Gabritchewsky, ' Annales 
 de l'lnstitut Pasteur/ 1890, p. 440). 
 
 The existence of the hastnatozoa in fishes was demonstrated in 
 1 84 1, for the first time, by Valentin. 
 
 In 1883, Mitrophanow described flagellated infusoria in the 
 blood of a carp and roach ; these parasites, at one phase of 
 their development, are seen in the state of amoeboid bodies without 
 flagella. 
 
 Chalachnikow has very often observed haematozoa in fishes 
 coming from the provinces of Kherson and Kharkov, the Dneiper 
 and the lakes around Tobolsk ; these haematozoa have great 
 analogy with the trypanosma of the frog and rat. 
 
 Organisms provided with flagella may be observed frequently 
 in the blood of the tortoise (Emys lutaria) and of the frog (Rana 
 esculenta), and are also found in the lymph, the urine, and even 
 in the bile. 
 
 These parasites, which correspond to the Hexamitus of Dujardin, 
 possess six flagella, four anterior and two posterior, and make a 
 way for themselves with much rapidity through the blood-corpus- 
 cles, by pushing them aside or driving them before them. 
 
 The hexamitus also lives in a free state in the intestinal duct 
 of tritons, frogs, lizards, and tortoises. The alterations in the 
 structure in the intestinal wall in inanition favour the entrance 
 of this parasite into the blood ; the intestinal mucous membrane 
 becomes more permeable for the young forms of the hexamitus, 
 which afterwards spread into the whole vascular and lymphatic 
 system. 
 
 In examining the blood of lizards {Lacerta viridis, Lacerta 
 ogilis) taken at Kharkov and its neighbourhood, Danilewsky and 
 Chalachnikow have frequently found that a large number of red 
 blood-corpuscles were invaded by parasitic elements. These 
 haetnatozoa are nearly always enclosed in the blood-corpuscles, 
 though some that are free and move slowly in the serum amongst 
 the blood-corpuscles may be met at times. 
 
 This parasite in the blood of the lizard, or haemocytozoon, is 
 oftenest seen under the appearance of a little worm, whose 
 extremities are more or less thin ; its dimensions are variable, 
 from 10 to 1 5 ^u in length, and each parasite contains one nucleus. 
 The invaded blood-corpuscles increase in size and become dis- 
 coloured. 
 
 The ha;mocytozoon sometimes possesses a rudimentary move- 
 ment, consisting of a flexion in the direction of the bend, fallowed
 
 SIMILAR ORGANISMS FOUND IN ANIMALS. G5 
 
 by a straightening ; elevation of the temperature (30 to 38 C.) 
 augments the intensity of that movement, cold having the opposite 
 effect. 
 
 The free haemocytozoa have the appearance of little worms 
 endowed with movements similar to those above described ; some 
 small constrictions may also be distinguished. 
 
 Little protoplasmic elements, which have scarcely a quarter of 
 the volume of a leucocyte, may also be observed in the blood of 
 lizards; these probably represent the hagmatozoa in the first phase 
 of their development. 
 
 The frequency of the haernatozoa varies very much according 
 to the habitat of the animals. Out of five lizards taken from a 
 garden at Kharkov, in August and September, there was one at 
 least whose blood contained these parasites, while in the lizards 
 taken at 15 kilometres from the town the haernatozoa were much 
 scarcer. 
 
 The haematozoon of the lizard probably enters through the 
 digestive tracts, but nothing is proved on this point. 
 
 The blood of the marsh-tortoise frequently contains parasites 
 free or enclosed in red blood-corpuscles ; these were observed for 
 the first time by Danilewsky in 1884. 
 
 Plate IV, fig. a, reproduces some of the appearances of the 
 haernatozoa of the tortoise according to Danilewsky's observations. 
 
 The parasites enclosed in the red blood-corpuscles or cytozoa are 
 first seen under the appearance of a rounded colourless spot, some- 
 times oblong, which enables them to be distinguished easily from 
 the substance of the blood-corpuscles : the cytozoon is situated 
 at the side of the nucleus ; it contains a few shining granules, 
 but no pigment (1 — 5, fig. A, PI. IV). 
 
 At a more advanced stage of its development the cytozoon is 
 seen inside the red blood-corpuscle under the shape of a trans- 
 parent, colourless, immobile little worm (6, 7, 8, fig. a, PI. IV). 
 
 This little worm grows, takes a greyish hue, and a nucleus 
 makes its appearance towards the middle of the worm ; one of 
 the extremities becomes curved so much that the parasite, which 
 is folded upon itself, may have a length twice the diameter of the 
 blood-corpuscle which contains it. 
 
 The structure of the little worm is extremely simple ; it is a 
 cylindrical body rather thin at its extremities, representing a 
 single cell with one nucleus. 
 
 At its state of complete development the parasite becomes 
 mobile and escapes from the blood-corpuscle, which it drags along 
 for some time afterwards (9 — 12, fig. a, PI. IV). 
 
 5
 
 66 MARSH FEVER AND ITS ORGANISM. 
 
 The elements 9, 10, n, are interesting from the point of view 
 of the interpretation of the very fine line which very often joins 
 the crescent at its two ends in the crescent-shaped bodies of 
 palustral blood ; this line represents the edge of the blood-cor- 
 puscle altered and become very transparent. On the blood- 
 corpuscle of the tortoise the presence of the nucleus is very 
 characteristic. 
 
 The little worm after becoming free moves with large helicoid 
 circular undulations ; later, transverse constrictions which change 
 their place during the movements of progression, and which may 
 be compared to contractions, are seen. 
 
 Danilewsky has found gregarine cytocysts in the medulla of the 
 bone of tortoises (15, 16, fig. a, PI. IV). Inside the red corpuscles, 
 which are pale and distended, oval bodies with a mammillated 
 surface may be seen ; these are muriform, and soon are segmented 
 more completely and give birth to embryos (fig. a, 17, 18, 
 PI. IV). 
 
 According to Danilewsky, the adult parasite is encysted in a 
 red corpuscle, and an intra-cellular metamorphosis of the gregarina 
 is produced, similar to that of Monosporea (A. Schneider) in 
 cytoplasma ; the protoplasm is afterwards divided into mobile 
 embryos. 
 
 The cytocysts of the haematozoa of the tortoise are interesting 
 to compare with the segmented elements or rose-shaped elements 
 of the palustral blood. 
 
 The haematozoa of the tortoise have a great analogy with those 
 of the lizard. 
 
 The haematozoa of birds are still more akin than the preced- 
 ing to those of paludism. 
 
 Danilewsky found haematozoa in the blood of several species of 
 birds, which he has described under the following names : — 
 Pseudovermicules, pseudovacuoles, polimitus sanguinis avium,, 
 pseudospirilla, trypanosoma. 
 
 The first four of these forms appear to correspond to the dif- 
 ferent phases of a polymorphic parasite, which has a very great 
 analogy to the haematozoa of paludism. 
 
 The pseudovacuoles or cytozoa (1 — 4, PI. IV, fig. b) are seen 
 under the appearance of clear spots of variable shape and dimen- 
 sions inside the red blood-corpuscles; the smallest of these elements 
 are from 2 to 4 fi in diameter, the largest reach the size of the 
 blood-corpuscles. Several cytozoa are often found in the same 
 blood-corpuscle. 
 
 The hsemocytozoon of birds contains black granules of pigment
 
 SIMILAR ORGANISMS FOUND IN ANIMALS. 67 
 
 in variable number, which seem to be the product of a trans- 
 formation of the haemoglobin like the pigment of the parasites 
 of paludism. 
 
 It should be noticed that in cold-blooded animals (frogs, 
 lizards, tortoises) the hasmatozoa do not give rise to the forma- 
 tion of pigment as is the case in the hot-blooded animals 
 (Danilewsky). 
 
 The pseudovacuoles or haeniocytozoa appear to be the young 
 and temporary forms of the haamatozoa of birds. 
 
 The granules of pigment enclosed in the cytozoa are sometimes 
 endowed with a very quick movement similar to that which I 
 have described in certain elements of palustral blood. 
 
 The pxeudovermicules have an elongated form 14 /.i to 17 fi in 
 length ; the substance of the parasite has a greyish colour ; in 
 the centre a nucleus is always found ; the body of the vermicule 
 is very thin at its extremities, one of which is generally more 
 rounded than the other. These elements are mobile ; the move- 
 ments are slow, being quickened by heat ; the pseudovermicule 
 usually advances in a curved line or in a larger spiral, trans- 
 verse constrictions being made during these movements (5, fig. 
 b, PL IV). 
 
 The polimitus presents the most interesting form of the 
 haematozoaof birds; it was described in 1884 by Danilewsky, and 
 has been observed by several others, especially by Metschnikoff. 
 
 The polimitus is developed in the red blood-corpuscles; its form 
 is generally spherical ; in its interior flagella are in motion which 
 give a movement to the polimitus and alter its form ; after a 
 certain time the capsule opens and the flagella escape, showing 
 energetic movements. 
 
 The excapsulated polimitus (which proceeded from the blood- 
 corpuscle at first enclosing it) measures on an average 6 fx, some- 
 times 12 li, and even 15 li in diameter (8, 9, fig. b). 
 
 The flagella, which have variable lengths, are independent of 
 each other in their movements ; one will often stop while the 
 others continue to move. 
 
 The free end of the flagella is usually a little swollen, but 
 that is not an invariable characteristic. The excapsulated poli- 
 mitus shows oscillatory movements which are given to it by the 
 flagella ; sometimes it is segmented. 
 
 Danilewsky found the polimitus in the blood of the magpie, 
 the jay, and the owl ; he made observations on birds who had 
 been recently caught, and also on those who had been captive ful- 
 some time.
 
 68 MARSH FEVER AND ITS ORGANISM. 
 
 The polimitus of birds is always developed in the red blood-cor- 
 puscles, and it is only exceptionally to be met in a free state in 
 the serum. It may be ascertained by collecting blood in a 
 pipette which contains a solution of osmic acid, or else by drying 
 the blood rapidly ; under these conditions no free polimitus is 
 found in the preparations. The cooling to which the blood is 
 submitted when taken from the vessels favours the excapsulation ; 
 by heating the preparation to 40 C. the excapsulation may be 
 prevented. No free polimitus is observed at that temperature, 
 whilst in the same preparation cooled to 20 C. many may be 
 seen (Danilewsky). 
 
 The polimitus is composed of a capsule and fluid contents, in 
 which are found black granules (melanin) often possessing very 
 quick movements. The flagella move first inside the polimitus, 
 then liberate themselves from the interior, move about for some 
 time before severing their attachment to the polimitus, and at 
 last become free ; they constitute then the pseudospirilla. 
 
 The pseudospirilla are endowed with very rapid movements, 
 which may last for an hour or even longer. 
 
 Swelling sometimes takes place on the pseudospirilla of birds 
 as on the flagella of palustral blood, which is explained by the 
 protoplasmic nature of those elements. 
 
 Danilewsky has not succeeded in cultivating the small pseudo- 
 spirilla of the blood of birds, also he has not observed their 
 division, and thinks that they cannot multiply in a free state. 
 
 Beside the polimitus and the pseudospirilla, organisms are met 
 with sometimes in the blood of birds which are similar to the para- 
 sites observed in the blood of the rat and of the hamster (cricetus), 
 and which have been described under the name of Herpetomonas 
 Lewisii. Danilewsky found these organisms for the first time 
 in the blood of several birds (owl, jay) in 1885, and gave them 
 the name of trypanosoma sanguinis avium. In 1861, Eberth noticed 
 the existence of a trypanosoma in the gullet of birds. 
 
 The trypanosoma sanguinis avium has a cylindrical shape, the 
 posterior end is thinner than the anterior ; the body is a greyish 
 colour, half transparent, homogeneous, and of a soft consistence. 
 The anterior extremity is extended into a flagellum of variable 
 length which becomes thinner and thinner, a vibrating membrane 
 makes a hyaline border. The vibrations of the flagellum and 
 those of the membrane correspond in rapidity, extent, and 
 direction. 
 
 The trypanosoma has a spirilliform movement, the flagellum 
 being directed forwards.
 
 SIMILAR ORGANISMS FOUND IN ANIMALS. 69 
 
 In the interior of the trypanosoma a greyish homogeneous 
 nucleus may be found, having a nucleolus. 
 
 The trypanosoma is multiplied by longitudinal division. 
 
 According to Danilewsky these haernatozoa are found in birds 
 which are fed by their parents after having been hatched, and 
 not in those which find their food themselves. It seems proved, 
 in the case of the trypanosoma at least, that this parasite is de- 
 veloped in the digestive canal and especially in the crop, and 
 that the youug are infected by their parents. 
 
 Generally the presence of the hasrnatozoa does not cause any 
 morbid disturbance in the birds. In more than 300 birds examined 
 by Danilewsky containing haauiatozoa, death only occurred in 
 four or five ; in these cases an extraordinary number of parasites 
 were present in the blood ; the liver and the spleen were enlarged, 
 and the rnelaneemia was very pronounced. 
 
 Danilewsky proposes the two following hypotheses in order to 
 explain the habitual harmlessness of the heematozoa of birds : 
 there is perhaps in birds a tolerance transmitted by heredity; 
 perhaps also the temperature of the blood of birds is too high 
 for the parasitic elements to be set free. 
 
 In a recent work (' Annales de FInstitut Pasteur,' December, 
 1890) Danilewsky says that he has found rose-shaped bodies, 
 similar to those which are seen in palustral blood, in the blood 
 of certain birds ; these bodies, resulting from the segmentation 
 of the endocorpuscular parasities, give rise to eight, ten, and 
 often twenty spores, which become free. These spores, even 
 when not separated, present a nucleus, and are easily stained 
 by methyl blue or by safranin. 
 
 The free spores are seen under the appearance of oval cor- 
 puscles, very small, with well-defined and thick contours, having a 
 great resemblance to the spores of the microsporidse. 
 
 The birds in whose blood these rose-shaped bodies are met with 
 are often diseased, the temperature rises from i° to i'5°, the bird 
 no longer eats but grows thin, sometimes it is attacked by con- 
 vulsions and dies ; generally the illness ends by recovery in from 
 four to six days. 
 
 These facts supplied Danilewsky with new arguments to prove 
 that these parasites in the blood of birds are the same as the 
 parasites of paludism. 
 
 The differences which exist between the haamatozoa of palus- 
 tral blood and those of the blood of birds may, according to him, 
 be explained by the difference of the surroundings in which the 
 parasites live.
 
 70 MARSH FEVER AND ITS ORGAN[SM. 
 
 Besides the haamatozoa described above, Danilewsky has found 
 leticocytozoa in the blood of certain birds (owl) ; these are para- 
 sites which, instead of penetrating into the blood-corpuscles, 
 enter the leucocytes and are developed there. " One part of 
 these germs evidently perishes in the struggle against the 
 activity of the phagocytes, whilst the other part keeps the vital 
 capacity and consequently the power of subsequent development. 
 Very probably the same struggle takes place during the malarial 
 infection of man, especially in the spleen and medulla of the 
 bones" (' Aunales de l'Institut Pasteur/ 1890, p. 427). 
 
 The leucocytozoa of the owl have been met with principally 
 in the medulla of the bones ; they appear to represent only 
 one of the phases in the development of the polimitus avium. 
 Danilewsky has often noticed the excapsulation of the polimitus 
 and the energetic movements of the flagella in the spring of the 
 year. 
 
 The same parasites which Danilewsky describes in the blood 
 of the jay, the magpie, and the owl were found in Sicily by B. 
 Grassi and Feletti in the blood of several species of birds, and 
 principally in that of the sparrow and domestic pigeon. As 
 Grassi aud Feletti point out (' Communication a l'Academie des 
 Sciences naturelles de Catane,' March 23rd, 1890), it is interesting 
 to notice the presence of the hasmatozoon in species so common as 
 the sparrow and the pigeon. The birds in whose blood Grassi and 
 Feletti found hasmatozoa came from parts of Sicily in which 
 paludism is endemic. 
 
 Up to the present I have sought in vain for the hasmatozoa in 
 the blood of sparrows and pigeons which I have been able to 
 procure in Paris. 
 
 Besides the trypanosoma, which has nothing to do with the 
 parasites of paludism, Grassi and Feletti have observed in the 
 blood of birds — 
 
 1st. A form akin to the crescent-shaped bodies of palustral 
 blood. 
 
 2nd. A form of amoeba akin to the amoeboid bodies of palustral 
 blood (my spherical bodies), to which Grassi and Feletti propose to 
 give the name of hxmamvebse. 
 
 Usually the amcebaa occupy the extremities of the red blood- 
 corpuscles, and the semi-lunar bodies the sides. 
 
 The crescent-shaped bodies of birds possess a nucleus easily 
 discerned ; on reaching a certain phase of their development 
 they take the spherical form and shoot out flagella. 
 
 In February and the first half of March, at Catania, the
 
 SIMILAR ORGANISMS FOUND IN ANIMALS. 71 
 
 sparrows infected with parasites were in proportion of 20 per 
 cent. After that time the number of infected birds went on 
 increasing, and at the end of April all the birds examined were 
 infected. Most had only semi-lunar bodies ; very few had 
 haemamcebae at the same time. In previous researches Grassi and 
 Feletti noticed, on the contrary, that amoebae always existed at 
 the same time as the crescent-shaped bodies. 
 
 In May and June the hatching took place. No parasites 
 were found in the embryos or in the young still without feathers ; 
 some were sometimes found in the young ones which were still 
 in the nest, but already capable of flying; much oftener still in 
 the young ones which had already left the nest. 
 
 Grassi and Feletti consider that the disease is not hereditary, 
 and that it is not transmitted by the parents which feed their 
 young. 
 
 In their opinion the infection is produced in the surrounding 
 media ; it seems always to begin with the semi-lunar bodies with- 
 out haemamcebaa. Grassi and Feletti show the co-existence of the 
 haematnoebae and the semi-lunar bodies, but this does not prove 
 the identity of these parasites ; the semi-lunar bodies exist in 
 almost all birds, and it is not surprising that they are associated 
 with other parasites. Grassi and Feletti do not hold that the 
 hasmamoebse and the semi-lunar bodies represent two forms of a 
 polymorphic parasite, but the arguments which they advance 
 against this opinion do not seem to me convincing. 
 
 The semi-lunar bodies multiply in the blood of the bird. If 
 birds whose blood contains numerous adult semi-lunar bodies 
 are systematically obseiwed, after eight days the existence of very 
 small semi-lunar bodies may be noticed, which grow larger little 
 by little, and become full grown ; the multiplication appears to 
 be by division. It should be noticed in passing that nothing 
 similar is seen in palustral blood ; the semi-lunar or crescent- 
 shaped bodies have always very approximately the same dimen- 
 sions, and nothing shows that they can be multiplied by division. 
 
 Kruse has observed these haematozoa in the blood of the 
 rook and the crow. 
 
 During the summer of 1889, in Paris, I succeeded in finding 
 the parasites described by Danilewsky in the blood of the jay. 
 A summary of the observations made repeatedly during the 
 months of May, June, and July, 1889, on one of these birds 
 follows. 
 
 A large number of red blood-corpuscles were altered and con- 
 tained pigmented elements ; there were often five or six altered
 
 72 MARSH FEVER AND ITS ORGANISM. 
 
 blood-corpuscles at the same time in the microscopic field (oc. i 
 and obj. g of Vei'rick). 
 
 The altered blood-corpuscles presented clear spaces of variable 
 dimensions, which could easily be distinguished by their trans- 
 parency from the substance of the blood-corpuscles, which was, 
 however, of a paler tint than that of normal red blood-corpuscles. 
 
 The hyaline elements, which appear as if enclosed in the 
 blood-corpuscles, had a rounded, or more often elongated shape, 
 in the direction of the long axis of the blood-corpuscle. 
 
 With but very few exceptions these elements were pigmented ; 
 some were curved, and extended nearly the complete circle of 
 the nucleus. In the smallest only one granule of pigment 
 could be found, in the others the number and position of the 
 granules of pigment were very variable. 
 
 The granules of pigment enclosed in the largest elements were 
 sometimes endowed with a very rapid movement. 
 
 The blood-corpuscles which contained the parasites grew paler 
 and paler, so that a time came when only the nucleus of the 
 blood-corpuscle could be discerned at the side of the parasite ; 
 at last the nucleus itself disappeared, and the parasite was found 
 free in the blood. The liberated parasites were rare exceptions 
 compared with the parasites enclosed in the blood-corpuscles. 
 
 Several times I saw pigmented elements breaking down ; nu- 
 merous mobile and short pseudospirilla escaped from them, which 
 were difficult to observe, and which seemed to me very different 
 from the flagella of palustral blood. 
 
 The spherical elements, containing mobile pigmented granules, 
 were sometimes endowed with a quick oscillatory movement, 
 similar to the movement of the analogous elements in palustral 
 patients. 
 
 The jay which was the subject of this observation did not 
 show any apparent disease even when the parasitic elements 
 were very numerous in the blood ; it recovered spontaneously. 
 The examination of the blood made several times from August, 
 1889, to April, 1890, did not reveal the existence of any of the 
 parasitic elements above described. 
 
 On April 19th the bird died by accident. The examination of 
 the blood taken from the heart showed the existence of 
 large-sized nematoids, but no endocorpuscular parasite was found. 
 The examination of the spleen was also negative. 
 
 Plate III, fig. b, represents some of the parasitic elements 
 observed in this bird ; the dry blood has been treated with eosine 
 and methyl blue.
 
 SIMILAR ORGANISMS FOUND IN ANIMALS. 73 
 
 The haematozoa of birds are evidently near akin to those of 
 paludism, but the identity of the two species is not proved. By 
 the side of the analogies important differences are noticeable : 
 the pseudovermicules, mobile and presenting constrictions, do not 
 seem to me comparable to the crescent-shaped bodies of palustral 
 blood. The pigmented cytozoa have certainly a great similarity 
 to the pigmented spherical bodies of palustral blood, which adhere 
 to blood-corpuscles ; it must, however, be noticed that in the blood 
 of birds the cytozoa are almost always enclosed in the red blood- 
 corpuscles, while the spherical elements are often free in palustral 
 blood. The amoeboid movements of these elements are more pro- 
 nounced in palustral blood than in the blood of birds. Finally, the 
 pseudospirilla which escape from the cytozoa of birds seem to me 
 very different from the flagella of palustral blood. 
 
 Because of the analogies which exist between the haematozoa 
 of birds and those of palustral blood, it was interesting to know 
 if it were possible to inoculate these latter parasites into birds. 
 In June, 1889, I injected a few drops of palustral blood rich in 
 parasitic elements into the brain of a young jay whose blood was 
 normal. After this operation I did not notice any alteration in 
 the blood of the bird ; the examination of the blood made several 
 times during the months of July, August, and October was always 
 negative. In December, 1890, I repeated the experiment ; a few 
 drops of palustral blood containing crescent-shaped bodies were 
 injected into the veins of a jay without any result. 
 
 Before coming to any conclusion on this subject it will be 
 necessary to multiply these investigations and to experiment on 
 different species of birds ; it is possible that certain haematozoa 
 of birds belonging to palustral districts are identical with those 
 of paludism, but that has not yet been proved. 
 
 To sum up : the parasites of palustral blood are not now as V 
 isolated as they seemed to be when I gave my first description 
 of them ; they are found to belong to a group the importance of 
 which inci-eases every day. Perhaps there may be occasion to 
 create a special division in the class of sporozoa to contain, 
 along with the coccidia, the haematozoa of paludism and the 
 analogous haematozoa which have been discovered in different 
 animals. I leave to naturalists the task of solving this question.
 
 CHAPTER IV. 
 
 The hwmatozoon which I have described is the pathogenic cause of 
 paludism — The parasitic elements of palustral blood represent 
 the different stages of the evolution of the same polymorphic 
 hsematozoon — Relation of these different stages to the febrile 
 types. 
 
 The haematozoon which I have described is found in palustral 
 patients in Europe, Asia, Africa, and America, with the same 
 characteristics; this is a great presumption in favour of its 
 pathogenic role, especially if it be added that this parasite has 
 never been found except in paludism. 
 
 This latter proposition does not admit of any exception ; the 
 presence of a single one of the parasitic elements previously 
 described is pathognomonic of paludism, and allows the diagnosis 
 to be made as certainly as the presence of the echinococcus or 
 debris of echinococci in a fluid allows us to diagnose a hydatid cyst. 
 
 In Algeria I very often made a histological examination of 
 the blood of anaemic patients who were free from paludism — of 
 dysenteric patients especially ; I have never noticed in these 
 cases the presence of hsematozoa. This result has been confirmed 
 by all the observers who have tested my researches. 
 
 Before the presence of the heematozoa had been noticed in 
 palustral blood, melanasmia was considered as the most character- 
 istic lesion of paludism ; but nobody could explain why this 
 lesion took place in paludism and not in other febrile diseases. 
 
 At present we know that inelanaemia is the consequence of the 
 development of the hsematozoa, and it seems logical to conclude 
 from it that the agents of melanamiia are also those of paludism. 
 
 Under the influence of quinine treatment the hsematozoa 
 disappear at the same time as the fever disappears, which is an 
 
 1 Tims the histological examination of the blood is very useful in all cases 
 where the diagnosis of paludism offers difficulties ; it allows the separation o£ 
 diseases which appear with almost identical clinical forms, though they may be as 
 different in nature as typhoid fever and palustral continued fever with typhoid 
 state ; sun-stroke, and certain pernicious attacks, &c. In our climates these grave 
 forms of paludism are rarely met, nevertheless the question of the palustral 
 nature of such accidents arises rather frequently.
 
 INJECTION EXPERIMENTS. 75 
 
 important proof of the cause and effect relation which exists 
 between these parasites and the phenomena of paludism. The 
 crescent-shaped bodies resist quinine treatment better than the 
 other elements. Why wonder at this ? Numerous facts of the 
 same kind could be brought forward in the history of parasites, 
 which are often much more difficult to destroy under one par- 
 ticular form than under any other. In this particular case the 
 resistance of certain elements even gives a good explanation of 
 the recurrence which is so common in intermittent fever. 
 
 It has sometimes been brought forward that as paludism is not 
 a contagious disease, its parasitic nature was doubtful. The dis- 
 eases produced by parasites which live on the surface of the body 
 are easily transmissible ; it is also the same with diseases which, 
 like typhoid fever or cholera, cause the elimination of products 
 containing pathogenic microbes. It can be easily understood 
 that it would be different in the case of diseases which are due to 
 the presence of parasites in the blood or in the tissues, and in 
 which there is no elimination of the parasitic elements into the 
 external media. 
 
 Persons suffering from trichiniasis or filariosis are not dangerous 
 to their surroundings; they do not communicate their disease 
 any more than do palustral patients. 
 
 Moreover it is possible to inoculate paludism from man to 
 man. As far back as 1881 I was able, from my knowledge of 
 the Imsmatozoa of paludism, to give the conditions of success for 
 this experiment. 
 
 Gerhardt injected palustral blood (about one gramme) into the 
 connective tissue of patients with chronic affections other than 
 paludism, and he says he twice succeeded in setting up inter- 
 mittent fever (' Zeitsch. f. klin. Med.,' Bd. vii) ; these results 
 are weakened by other facts in which injections of blood into the 
 connective tissue have given only negative results. It is probable 
 that, in the two cases in which Gerhardt succeeded in inoculating 
 fever, the blood injected into the connective tissues had entered 
 small vessels. 1 
 
 Mariotti and Ciarocchi have inoculated paludism in four 
 patients under treatment in the hospitals of Home for chronic 
 affections non-palustral ( f Lo Sperimentale,' 18S4). These ob- 
 servers always failed when they made subcutaneous injections of 
 
 1 As far back as 1880, Dochmann had tried to inoculate paludism from man to 
 man with serous fluid of herpetic vesicles of a palustral patient. The observations 
 of Dochmann are by no means conclusive (V. J. Chassiu, ' Sur ['inoculation do la 
 fievre intermittente,' These de Paris, 1885).
 
 76 MARSH FEVER, AND ITS ORGANISM. 
 
 palustral blood ; on the contrary, they noticed that intra-veuous 
 injections were very efficacious. 
 
 Marchiafava and Celli also succeeded in transmitting paludism 
 by an intra-venous injection of palustral blood, while subcutaneous 
 injections only gave them negative results ; they have seen 
 haematozoa appear in the blood of persons inoculated by intra- 
 venous injection, at the same time as regular and well-charac- 
 terised attacks of intermittent fever took place, which yielded to 
 quinine. 
 
 Marchiafava and Celli operated in the following manner : — A 
 Pravaz syringe was used to make the intra-venous injections; it 
 was sterilised every time after having been enclosed in a glass 
 tube closed with wadding, the syringe being taken from the tube 
 only at the moment of using it ; the operator's hands were washed 
 in a solution of sublimate, and then, with the same solution, he 
 washed the skin of the fold of the elbow of the palustral patient 
 from whom the blood was to be taken, and also that of the patient 
 in whom the injection was to be made. The point of the cannula 
 was driven into one of the veins at the bend of the elbow of the 
 palustral patient, a small quantity of blood was aspirated, then 
 immediately injected into one of the veins of the bend of the elbow 
 of the subject who lent himself to the experiment ; the quantity 
 of blood thus transferred was at most one gramme. 
 
 I summarise the Observations i and 3 (Marchiafava and 
 Celli, "Nuove ricerche sulla Infezione Malarica,' ; ' Annali di Agri- 
 coltura,' 1885). 
 
 Obs. 1. — Young man of 17, suffering from transverse myelitis, 
 free from paludism. A first experiment was made of two sub- 
 cutaneous injections in this young man with blood taken from a 
 palustral patient ; these injections did not produce any effect. 
 
 On August 21st and 26th, 1884, intra-venous injections were 
 made with palustral blood containing many parasitic elements, 
 and particularly flagella j on the day following the last injection 
 an attack of fever resulted, which was repeated on the following 
 day ; the patient suffered from well-marked quotidian fever, which 
 yielded to sulphate of quinine, but which reappeared several times. 
 The spleen became enlarged, — in short, the examination of the 
 blood revealed the existence of the parasitic elements which 
 characterise paludism. 
 
 Obs. 3. — Man aged 32, suffering from ccrebro-spinal sclerosis, 
 free from paludism. 
 
 On September 6th subcutaneous injection of palustral blood 
 was made, which had no effect.
 
 INJECTION EXPERIMENTS. 77 
 
 On September 13th he received an intra-venous injection of 
 one gramme of blood taken from a patient suffering from palustral 
 cachexia with irregular attacks of fever ; on September 20th 
 (seven days after the injection) he had an attack of fever which 
 was repeated on the following days. The temperature chart 
 published with this observation is exactly that of the quotidian 
 intermittent fever ; at the same time the spleen was enlarged, 
 and the examination of the blood revealed the hasmatozoa of 
 paludism. The fever yielded easily to sulphate of quinine. 
 
 T. Gualdi and Antolisei communicated two cases of palustral 
 fever to the Royal Academy of Medicine of Rome in 1889 ; the 
 fever was induced experimentally in two healthy individuals by 
 the intra-venous injection of palustral blood. 
 
 Antolisei, Gualdi, and Angelini published in 1889 (' Ri forma 
 medica,' September and November, 1889) four other cases of 
 experimental paludism. It is needful to dwell shortly on the 
 examination of these facts, which are interesting not only from 
 the point of view of the transmission of paludism from man to 
 man, but also because they give important data as to the duration 
 of the incubation of paludism, and also for the discussion of the 
 theory which allows the existence of several species of heematozoa 
 of paludism. 
 
 It is important to know if, by inoculating blood of the tertian 
 or quartan type, these types could be reproduced in the individual 
 inoculated, and it was specially in order to solve this question 
 that Gualdi and Antolisei made the experiments which I will here 
 summarise. 
 
 First fact. — Intra-venous injection into a neurasthenic patient, 
 who has never had palustral fever, of three cubic centimetres of 
 blood taken from a patient with quartan fever five hours before 
 the attack. Ten days after the injection the temperature rose 
 slowly to 40*8° C; in three days the patient had, in fact, a continued 
 fever, the spleen enlarged ; on the following days the fever 
 reappeared without regular type, the blood contained amoeboid 
 bodies. 
 
 The patient had several relapses of fever in September, 1889 
 (the intra-venous injection had been made in May, [889) ; the 
 examination of the blood revealed semi-lunar bodies as well as 
 amoeboid bodies (Gualdi and Antolisei, " One quarte experi- 
 ment ale/ 3 ' Ril'orina medica,' November, 1889). 
 
 Therefoi-e in this patient, who was inoculated with blood of 
 the quartan fever, a fever was induced which was at first con- 
 tinuous, then irregular, with amoeboid bodies but without crescent-
 
 78 MARSH FEVER AND ITS ORGANISM. 
 
 shaped bodies, and when the relapse occurred four months after 
 the iujection, crescent-shaped bodies were found. 
 
 Second fact. — Patient of 42, suffering from traumatic hemiplegia. 
 For ten years he had had no fever : on May 17th an injection 
 was made of palustral blood taken from a patient with quartan 
 fever five hours and a half before the attack j twelve days 
 afterwards an irregular fever appeared, with enlargement of 
 the spleen. Examination of the blood revealed pigmented 
 spherical bodies ; in the case of the patient who had supplied 
 the blood many forms in endogenous multiplication could be 
 found. 
 
 The incubation lasted ten days in one case, twelve in the 
 other. 
 
 In neither was the febrile type reproduced in the subjects 
 experimented upon. 
 
 Third fact. — Intra- venous injection made with the blood from a 
 tertian fever patient. The blood was taken at the beginning of 
 an attack and injected on July 17th into a man of twenty-four, 
 suffering from cerebellar tumour. On July 27th an attack of 
 fever resulted, which returned on the 29th ; on the 27th the 
 examination of the blood did not show anything abnormal. 
 During the second attack pigmented spherical bodies were found, 
 with mobile pigmented granules. 
 
 The attacks came at shorter intervals, attacks on the 2nd and 
 3rd August with hypertrophy of the spleen. 
 
 This fever was arrested by quinine, the parasitic forms dis- 
 appearing rapidly from the blood. 
 
 Fourth fact. — Patient of 52, suffering from diffuse cerebro-spinal 
 sclerosis. On July 1 7th an injection was made, as with the 
 previous patient, with blood from the same subject with tertian 
 fever. 
 
 On July 27th an attack of fever; apyrexia on 28th and 29th; 
 slight attack on the 30th (the fever would consequently be of a 
 quartan type). 
 
 On August 2nd an attack of fever ; new attacks on August 3rd 
 and 4th (quotidian type) ; on the 5th no fever ; on the 6th last 
 attack j on August 14th and 15th subcutaneous injections of 
 quinine. 
 
 The examination of the blood of this patient from August 2nd 
 to 7th, spherical bodies with or without pigment ; no segmented 
 forms were found in this or the first case. 
 
 In the last two patients the incubation lasted ten days, and 
 the fever produced was irregular.
 
 INJECTION EXPERIMENTS. 79 
 
 Fifth fact. — The blood was taken on October 7th, 1889, from 
 a patient with quartan fever of first invasion, in whose blood 
 bodies in process of segmentation were very abundant. 
 
 Two cubic centimetres of blood taken from the basilic vein 
 were injected into the same vein in a subject suffering from 
 softening of the brain who had never had fever. On October 19th 
 the patient, into whom palustral blood had been injected, had an 
 attack of fever, the blood containing spherical bodies with or with- 
 out pigment. 
 
 On October 20th and 21st apyrexia occurred, and the spherical 
 bodies increased in number and size, and on the 22nd many of 
 the elements were in process of segmentation. 
 
 On October 22nd, attack of fever, the temperature rising to 
 38'9° C. ; on the 25th another attack. 
 
 In this case quartan fever was produced with the blood of a 
 patient himself suffering from quartan fever, and the parasitic 
 elements observed in the blood of the two patients showed a 
 great resemblance ; but it is also open to question whether, had 
 the patient been examined later, at the period of relapse, crescent- 
 shaped bodies would not have been found, as was the case in 
 the subject of the first observation. 
 
 Sixth fact. — A man of 45, suffering from paralytic dementia. 
 On September 25th two cubic centimetres of blood were in- 
 jected into his veins ; this blood contained only crescent-shaped 
 bodies. 
 
 On October 3rd a slight attack of fever resulted, but nothing 
 abnormal was found in the examination of the blood. 
 
 On October 4th 0*75 gramme of sulphate of quinine was given 
 by mistake ; during the night of October 4th a very severe attack 
 of fever occurred ; on the morning of October 5th the temperature 
 was 40*5° C. 
 
 In the examination of the blood amoeboid bodies were seen. 
 
 New attacks of fever came on the 5th during the day ; on 
 October 6th, 7th, 8th, 9th, there was slight rise of temperature. 
 
 During the night of October 9th the patient had a rather 
 severe attack of fever; on the 10th two attacks; on the nth 
 and 12th slight attacks ; on the 13th an examination was made 
 of the blood, showing, besides amoeboid bodies, a small number 
 of semi-lunar bodies. Apyrexia from October 14th to 19th. 
 
 On October 21st a slight attack of fever; on the 22nd semi- 
 lunar bodies and flagella were found ; on October 23rd the last 
 attack, which was slight. 
 
 In this case the incubation lasted thirteen days.
 
 80 MARSH FEVER AND ITS ORGANISM. 
 
 The fever was irregular, but its development was stopped by 
 the administration of a dose of sulphate of quinine. 
 
 I shall return to these facts later on when speaking of the 
 plurality of the parasites of paludism, and of the duration of the 
 incubation of palustral fever ; for the present I only point out 
 that paludism can be transmitted at will from man to man by 
 intra-venous inoculation, and that the pai-asites of paludism can 
 be seen appearing in the blood of the inoculated subject as soon 
 as the fever declares itself. 
 
 To sum up : ist. The haamatozoa have been found in the 
 palustral patients of all countries with the same characteristics, 
 and there is a remarkable agreement between the already 
 numerous descriptions which have been given of it. 
 
 2nd. These hasmatozoa have never been found in persons who 
 were not suffering from paludism. 
 
 3rd. The development of the haematozoon is intimately con- 
 nected with the production of melanaemia, which is the most 
 characteristic lesion of paludism. 
 
 4th. Quinine causes the hasmatozoa to disappear from the 
 blood at the same time as it cures the palustral fever. 
 
 5th. It has been possible to transmit paludism from man to 
 man by injecting a small quantity of blood, taken from the 
 veins of a palustral patient and containing haematozoa, into the 
 veins of a subject free from paludism. 
 
 The conclusion that the haematozoa are the pathogenic agents 
 of paludism appears to me to be indisputable. 
 
 From the point of view of general pathology, this unexpected 
 fact, that a sporozoon is the cause of one of the most important 
 diseases among those which lately were classed in the group of in- 
 fectious diseases, deserves to be emphasised as a new proof of the 
 diversity of the pathogenic agents, and of the risks which might be 
 run in generalising too rapidly and drawing inferences from the 
 nature of some of these agents as to the nature of others. 
 
 Is paludism the only disease produced in man by the presence 
 of parasites belonging to the class of sporozoa ? We are still 
 ignorant about the real nature of a great many pathogenic 
 agencies, and it is very probable that some of these agencies are 
 of the same nature as palustral fever. 
 
 It is very likely that yellow fever, which is an infectious 
 disease, endemic like paludism, may have a parasite similar to 
 that of paladism for its pathogenic cause. 
 
 Goitre, which is a type of endemic disease, might also be 
 caused by a protozoou, which should be carefully looked for in
 
 THE SPOROZOA OP OTHER DISEASES. 81 
 
 the hypertrophied thyroid, its seat of election, as the spleen is 
 the seat of election of the hasmatozoa of paludism. 
 
 We see from the researches of Darier, conBrmed by those of 
 Malassez and of Wickham, that Paget' s disease of the mamma 
 is due to sporozoa of the order of Coccidia or Psorospermiae. 1 
 
 The cutaneous psorospermosis must be placed along with Paget's 
 disease, the vegetating follicular psorospermosis, and probably 
 the molluscuvi contagiosum of Bateman. 
 
 According to Sacharoff, the parasite of relapsing fever is near 
 akin to the hasmatozoa of paludism (' Communication a, la 
 Societe de Medecine de Tiflis,' 1888). This parasite, which it is 
 easy to see in the blood after the defervescence of the fever, 
 seems to be twenty times the diameter of a red blood-corpuscle in 
 length ; made up of an amoeboid protoplasmic mass, containing 
 granulations and almost always a nucleus ; it emits prolongations 
 which, when free, take a spiral form; these prolongations appear 
 to be no other than the elements which are described by 
 Obermeyer under the name of spirilla. 
 
 Sacharoff notices that these hasmatozoa of recurrent fever 
 have a great analogy to those of paludism, and proposes to give 
 them the name of hasmatozoa of relapsing fever. 
 
 Danilewsky admits with Sacharoff that the spirilla of relapsing 
 fever have a great analogy to the pseudospirilla of the blood of 
 birds, and he gives as a proof of that opinion the fact that the 
 spirilla of relapsing fever cannot be cultivated in artificial media 
 any more than the pseudospirilla of birds. 
 
 Loesch (' Archives de Virchow/ t. lxv), Grassi, Perroncito, 
 Sonsino, Kartulis (meme recueil, 1886, t. cv, p. 521), have 
 described some amoebae of the large intestine which may play 
 an important part in the etiology of the dysentery of hot 
 countries, and in the pathogenesis of abscess of the liver. 
 
 Is the haematozoon of paludism unique ? Is there a single 
 polymorphic parasite, or are there several species of parasites 
 giving rise to different clinical manifestations of paludism ? 
 
 From the beginning of my researches I put this question 
 to myself. The clinical manifestations of paludism are very 
 varied, and, on the other hand, the pai'asites of paludism are seen 
 
 1 Darier, ' Societe de Biologie,' April 13th, 1889, and ' (.'omnium au Congres 
 International de Dermatologie de Paris,' August 8th, 1S89. L. Wickham, " Anat. 
 path, et nature de la maladie de Paget du mann-lon " (' Arch, de rued, exper. et 
 d'anat. pathol.,' 1890, p. 46). Malassez, " Sur les nouvelles psorospermoses clu-/. 
 l'liornme " (meme recueil, 1890, p. 302). L. Wickham, '('ontiih. ?i L'£tude des 
 psorospermoses cutanees,' Paris, 1890. 
 
 G
 
 82 MARSH FEVER AND ITS ORGANISM. 
 
 in the blood under several forms ; it was therefore natural 
 to ask if such and such form of parasite did not correspond 
 to such and such clinical variety (' Traite des fievres palustres/ 
 p. 196). 
 
 In order to solve this problem I increased the number of my 
 observations, and since 1884 the results given by the analysis of 
 432 cases of paludism have been published by me. 
 
 I have only promulgated the two following general rules con- 
 cerning the relations which exist between the febrile type and 
 the parasites observed in the blood : 
 
 1st. Often only the elements described in my first publication 
 under the name of bodies No. 2, and in my subsequent publica- 
 tions under the name of spherical bodies, are found in the blood 
 of patients suffering from palustral fever of first invasion (con- 
 tinued or quotidian) ; and sometimes all the parasites observed 
 in these fevers belong to the first degree of development of these 
 elements (spherical bodies of very small volume, non-pigmented 
 or containing only one or two granules of pigment). 
 
 2nd. The crescent-shaped bodies are usually found in the blood 
 of patients suffering from relapses of fever or palustral cachexia. 
 
 Even these rules admit of exceptions ; for instance, the crescent- 
 shaped bodies have been met at times in the blood of patients 
 attacked with a fever of first invasion. 
 
 In 400 observations analysed from the point of view of the 
 existence of crescent-shaped bodies, these elements have been 
 found 107 times in the following manner (' Traite des fievres 
 palustres/ p. 196) : 
 
 Intermittent fever, first invasion 
 Intermittent fever, recurrent 
 Pernicious attack . 
 Palustral cachexia 
 
 Total 
 
 10 times. 
 
 5° » 
 
 2 „ 
 
 45 » 
 
 107 times. 
 
 I have also studied the relations which exist between the 
 parasitic elements of the blood and the febrile paroxysms, and I 
 have shown that it is specially before and at the beginning of the 
 attacks of fever that the most characteristic parasitic elements 
 are found in the blood in the greatest number. 
 
 I arrived, in 1884, at the conclusion that the different forms in 
 which the haBmatozoa of paludism present themselves belong to 
 one and the same polymorphic parasite ; since then I have always 
 upheld this opinion. 
 
 For the last few years several Italian observers have tried to
 
 ONLY ONE POLYMORPHIC H51MATOZOON. 83 
 
 prove that the haematozoa of paludism belonged to several species, 
 and that there was a constant relation between such and such 
 species of parasite and such and such clinical manifestations of 
 paludism. 
 
 I have shown in the preceding chapter the differential charac- 
 ters which have been ascribed by Golgi, Canalis, and Antolisei to 
 the parasites of the tertian and quartan types, and we have seen 
 that the most important of these characteristics was supplied by 
 the mode of segmentation of the elements. 
 
 In the theory of Golgi, quotidian fever would be now a tertian, 
 now a double quartan ; consequently sometimes the parasites of 
 the tertian, sometimes those of the quartan type would be found 
 in the blood of patients suffering from quotidian fever. 
 
 Golgi and Canalis have admitted more recently a third variety 
 of parasites of irregular fever, characterised by the crescent- 
 shaped bodies. 
 
 The haematozoa of paludism would therefore be of three kinds : 
 
 ist. Haematozoa of the tertian; 
 
 2nd. Hasmatozoa of the quartan ; 
 
 3rd. Haematozoa of the irregular fevers. 
 
 Gualdi and Antolisei and Angelini have published investiga- 
 tions which confirm those of Golgi and Canalis ; these researches 
 have already been summarised (Chap. II, p. 68). 
 
 Terni and Giardina, who have specially studied the irregular 
 palustral fevers, agree with the foregoing observers that these 
 fevers are produced by a haematozoon which differs from the 
 haematozoon of the tertian and of the quartan types, and which is 
 characterised by the crescent-shaped bodies. 
 
 Under this title of irregular palustral fevers must be com- 
 prised the continued and subintrant 1 fevers, the irregular and 
 intermittent fevers with long intervals of apyrexia, and also the 
 palustral cachexia ; these constitute, it must be confessed, not a 
 very homogeneous group. 
 
 Feletti and Grassi admit the existence of two varieties of 
 parasites, as has been already remarked. 
 
 ist. The haemamibse (corresponding to my spherical bodies), 
 these being the parasites of the regular fevers. 
 
 2nd. The Laverania (characterised by crescent-shaped bodies), 
 these being the parasites of the irregular fevers. 
 
 Feletti and Grassi affirm that at Catania the palustral fevers 
 were always from the beginning of the attack very exactly classified 
 
 1 [An example of a subintrant fever is a double quartan or a double tertian. — 
 
 Trans.]
 
 84 MARSH FEVER AND ITS ORGANISM. 
 
 in these two divisions of the regular and irregular fevers, and 
 that the same varieties of parasites always corresponded to the 
 same variety of fever. I was somewhat surprised at this asser- 
 tion, to prove which Feletti aud Grassi have not so far given 
 any definite facts. 
 
 When one has studied paludism in hot countries, and repeatedly 
 seen its different manifestations succeed each other in the same 
 subject, it is difficult to understand how these manifestations 
 can be so easily grouped under the two titles of regular and 
 irregular fevers. 
 
 The theory of the plurality of the haematozoa of paludism raises 
 numerous objections. 
 
 The unity of paludism, from a clinical and anatomico-patho- 
 logical point of view, is indisputable. Such or such forms in such 
 or such conditions are oftener met ; the tertian and the quartan 
 types, e. g., are much more common in our climates than in hot 
 countries, but it cannot be said that here there is a home for 
 tertians, here a home for quartans or for irregular fevers ; it is in 
 the same endemic centres that fevers of different types are con- 
 tracted, and these types vary in a regular manner with the season 
 and with the climate. 
 
 The pathological anatomy also shows the unity of paludism ; 
 melanaemia and hypersplenia are lesions common to all palustral 
 fevers. 
 
 Lastly, the same treatment can be applied to all the types of 
 fever. 
 
 It is a well-known fact that the fever often changes its type 
 in the same patient ; it is rare, especially in hot countries, for a 
 fever to begin with the tertian or quartan type ; more generally 
 it is first continued or quotidian, and at the time of a relapse is 
 transformed into tertian or quartan. The type of fever may 
 even modify itself when patients have left the palustral countries 
 in conditions which exclude the idea of a new infection. If these 
 facts are to be explained on the hypothesis of the plurality of 
 parasites, it will be necessary to admit that the different species 
 of haematozoa must generally co-exist in the same patient, and 
 are in turn predominant. 
 
 According to Golgi, the quotidian intermittent fever may be 
 at times a double tertian, at times a treble quartan, which is 
 very convenient for the theory he defends, but very unlikely. 
 Quotidian fever is the most common clinical form in the principal 
 homes of paludism, and doctors who have practised in hot 
 countries will have difficulty in admitting that it springs from
 
 ONLY ONE POLYMORPHIC H^EMATOZOON. 85 
 
 the tertian or quartan type, that is, from types comparatively rare 
 in these countries. 
 
 The morphological characters ascribed to the three species 
 (Golgi, Canalis, Gualdi, and Antolisei), or to the two species 
 (Grassi and Feletti) of haematozoa of paludism, are insufficieut 
 to allow each of these species being recognised in the different 
 phases of its evolution. 
 
 The hasmatozoa of the tertian and of the quartan and of 
 irregular fevers show themselves in the blood first under the 
 aspect of small amoeboid elements, which have the same appear- 
 ance in the three species of paludism ; the segmentation and 
 sporulation are also made in an almost similar manner, the differ- 
 ence being that in the quartan the number of spores is generally 
 smaller than in the tertian. The segmented bodies, as Antolisei 
 admits, are often absent, especially in the tertian, which deprives 
 that characteristic of much of its importance. 
 
 The crescent-shaped bodies are, it is ti'ue, very characteristic ; 
 and were it proved that they are always present in the irregular 
 fevers and never in the regular fevers, we might admit the two 
 varieties described by Grassi and Feletti. But the relations 
 which exist between the appearance of crescent-shaped bodies 
 in the blood and such or such types of paludism are far from 
 being so simple. The exceptions to the rule, if there be any rule, 
 are very numerous. 
 
 The supporters of Golgi's theories are obliged to make many 
 concessions. Thus it is that Gualdi and Antolisei are obliged 
 to acknowledge that the type of fever does not depend only on 
 the variety of parasites, but also on individual conditions, so 
 that the same variety of parasites may produce different febrile 
 attacks. 
 
 The same observers admit that the haematozoa of the irregular 
 fevers may be evolved in certain cases without passing through 
 the phase of crescent-shaped bodies. Now, as this phase is the 
 only characteristic one, it does not appear what there is in these 
 cases to distinguish this variety of haematozoa. The admission 
 that the haematozoa of irregular fevers may or may not pass 
 through the phase of crescent-shaped bodies approaches very 
 closely to the opinion of those authors who, agreeing with me, 
 hold that the parasite is unique, but that its development is 
 variable. 
 
 If the three species of haematozoa were distinctly separated, 
 and always in exact relation to the febrile type, by injecting 
 blood taken from a patient suffering from tertian or quartan
 
 86 MARSH FEVER AND ITS ORGANISM. 
 
 fever into a subject free from paludism, the tertian or the 
 quartan type ought always to be produced in the inoculated 
 patient. Gualdi, Antolisei, and Angelini have tried to supply 
 this experimental proof of the plurality of the haematozoa of 
 paludism. It has been noticed (p. 77) that these observers 
 have six times injected blood coming from palustral patients into 
 the veins of subjects free from paludism, for the purpose of 
 ascertaining whether they could reproduce the type of fever of 
 the patient supplying the blood in the inoculated person. 
 
 In one case only this result (which should be the rule if the 
 theory of the plurality of the haematozoon of paludism were true) 
 was obtained. One person inoculated with blood of quartan fever 
 had two attacks of the quartan type ; in the other cases the 
 results were either unfavorable to Golgi's theory, or at least 
 proved very little. For instance, the intra- venous injection of 
 quartan blood caused in one case a fever, first continued, then 
 irregular, and after a relapse the appearance of crescent-shaped 
 bodies was observed. The blood of a patient with quartan 
 fever producing an irregular fever, and giving rise to crescent- 
 shaped bodies, is, it seems to me, the exact opposite of Golgi's 
 theory. 
 
 In order to explain these facts Antolisei suggests the hypothesis 
 that the germs of the different varieties of paludism may co-exist 
 in the same patient; the forms belonging to the evolving cycle 
 of the hsematozoon which is in activity, if I may thus speak, 
 being only visible in certain patients ('Riforma medica,' April, 
 1890). If in the experiment just mentioned the blood of quartan 
 fever produced an irregular fever, it was because the patient 
 suffering from the quartan type of fever had in his blood — 1st, 
 the parasite of the quartan type; 2nd, the parasites of the 
 irregular fevers in a latent state. 
 
 In certain patients suffering from irregular fevers, crescent- 
 shaped bodies are found in the blood taken directly from the 
 spleen, whilst the blood obtained by pricking the finger contains 
 none ('Riforma medica,' March, 1890); Gualdi and Antolisei 
 give this fact as a fresh proof of the relation which exists between 
 the irregular fevers and crescent-shaped bodies. Before coming 
 to any conclusion it would be necessary to examine the blood 
 obtained by puncturing the spleen in patients with tertian or 
 quartan fevers; perhaps crescent-shaped bodies would sometimes 
 be found there. 
 
 Terni and Giardina admit that the crescent-shaped bodies are 
 absent in certain cases of irregular fevers, and that the parasites
 
 FURTHER OBSERVATIONS. 87 
 
 of the regular and irregular fevers are sometimes combined in 
 the same individual ; they advance the hypothesis that this 
 combination is frequent in the fevers of hot countries. 
 
 " In Algeria/' say Terni and Giardina, "the cases in which 
 all the varieties of haematozoa of paludism are associated perhaps 
 predominate ; this would be in keeping with the gravity of the 
 infection and the frequency of remittent and quotidian fevers in 
 tropical countries. These cases, which are rare in Rome, are still 
 more so in Northern Italy" ('Hi vista d' igiene e sanita pubblica/ 
 May 1 6th, 1890). 
 
 It thus appears that the upholders of the plurality of the 
 haernatozoon of paludism are obliged to heap up hypotheses in 
 order to meet the objections which facts are constantly bring- 
 ing to bear against their theories. 
 
 With the purpose of testing the assertions of the writers who 
 have assumed the existence of several species of haematozoa of 
 paludism, I have selected from among my observations, either 
 already or not yet published, those which seem to me to present 
 most interest from the special point of view of the relations 
 which exist between the parasitic forms and the febrile types, and 
 I have grouped them in five series, as follows : 
 
 1 st. Palustral fevers by first invasion : continued, regular 
 quotidian, or with subintrant attacks. 2nd. Quotidian intermittent 
 fevers (relapses). 3rd. Tertian fevers. 4th. Quartan fevers. 
 5th. Patients observed on several occasions, often at long in- 
 tervals, and who have presented fevers of different types. 
 
 1st. Palustral fevers of first invasion. — In my ' Traite des 
 fievres palustres ' I have published a certain number of observa- 
 tions which show that in palustral fevers of first invasion, either 
 spherical bodies or crescent-shaped bodies may be met with in 
 the blood. The following table shows some of these facts. 
 
 Obs. 23. 1 — Clinical form : Quotidian fever of first invasion 
 ('Traite des fievres palustres,' p. 255). Result of examination of 
 blood : Crescent-shaped bodies, spherical bodies, flagella. 
 
 Obs. 24. — Clinical form : Quotidian fever of first invasion (op. 
 cit., p. 256). Result of examination of blood: Spherical bodies, 
 flagella ; no crescent-shaped bodies. 
 
 Obs. 31. — Clinical form: Continued fever at the beginning, 
 afterwards quotidian, of first invasion (op. cit., p. 266). Result 
 of examination of blood : Spherical bodies of very small volume in 
 
 1 In order to avoid confusion between the observations of my ' Traite" <lrs lirvics 
 palustres' and the observations given in this work 1 have used Roman figures to 
 designate the new observations.
 
 88 MARSH FEVER AND ITS ORGANISM. 
 
 great numbers, often three or four of these elements adhere to 
 the same blood-corpuscle ; no crescent-shaped bodies. 
 
 Obs. 32. — Clinical form : Continued fever at the beginning, 
 afterwards quotidian, of first invasion (op. cit., p. 268). Result 
 of examination of blood : Small spherical bodies in great numbers, 
 either free or adherent to the blood-corpuscles ; no crescent- 
 shaped bodies. 
 
 Obs. 35. — Clinical form : Palustral continued fever with typhoid 
 state; eight days of invasion (op. cit., p. 296). Result of exam- 
 ination of blood : — First examination : spherical bodies of average 
 or small size (the latter are very numerous) ; no crescent-shaped 
 bodies. Second examination : after the subsidence of the fever, 
 spherical bodies, crescent-shaped bodies (rare). 
 
 Obs. 36. — Clinical form : Quotidian fever of first invasion ; 
 grave attacks with typhoid state (pernicious phenomena). Result 
 of examination of blood : Spherical bodies of small volume in 
 great numbers ; no crescent-shaped bodies. Relapse : Regular 
 quotidian fever (op. cit., p. 295). Result of examination of blood : 
 Spherical bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 42. — Clinical form : Quotidian fever of first invasion, 
 pernicious phenomena (op. cit., p. 318). Result of examination 
 of blood : Spherical bodies of small size in great numbers, 
 either free or adherent to the blood-corpuscles ; no crescent- 
 shaped bodies. 
 
 Obs. 43. — Clinical form : Quotidian fever, acute cachexia 
 (op. cit., p. 328). Result of examination of blood : Crescent- 
 shaped bodies, spherical bodies, flagella. 
 
 The new observations which are found at the end of this 
 volume, and concern palustral fevers of first invasion, are sum- 
 marised in the following table on the special point now under 
 consideration : 
 
 Obs. 1. — Clinical form: Palustral continued fever of first 
 invasion. Result of examination of blood : Spherical bodies ; no 
 crescent-shaped bodies. 
 
 Obs. 2. — Palustral fever of first invasion. Result of examina- 
 tion of blood : Spherical bodies of very small volume ; no crescent- 
 shaped bodies. 
 
 Obs. 3. — Clinical form : Palustral fever of first invasion. Result 
 of examination of blood : Spherical bodies of very small volume ; 
 no crescent-shaped bodies. 
 
 Obs. 4. — Cliuical form : Palustral continued fever or quotidian 
 intermittent fever with subintrant attacks. Result of examina- 
 tion of blood : Spherical bodies ; no crescent-shaped bodies.
 
 FURTHER OBSERVATIONS. 89 
 
 Obs. 5. — Clinical form : Palustral continued fever of first inva- 
 sion. Result of examination of blood : Spherical bodies of very- 
 small size ; no crescent-shaped bodies. 
 
 Obs. 6. — Clinical form : Quotidian intermittent fever of first 
 invasion. Result of examination of blood : Spherical bodies, 
 flagella; no crescent-shaped bodies. 
 
 Obs. 7. — Clinical form : Palustral fever of first invasion. Result 
 of examination of blood : Spherical bodies, flagella ; no crescent- 
 shaped bodies. 
 
 Obs. 8. — Clinical form : Quotidian fever of first invasion. 
 Result of examination of blood : Spherical bodies, flagella ; no 
 crescent-shaped bodies. 
 
 Obs. 9. — Clinical form : Quotidian fever of first invasion. 
 Result of examination of blood : Crescent-shaped bodies, spherical 
 bodies. 
 
 Obs. 10. — Clinical form : Quotidian fever of first invasion. 
 Result of examination of blood : Crescent-shaped bodies, spherical 
 bodies. 
 
 Obs. 11. — Clinical form : Palustral fever of first invasion; con- 
 tinued or quotidian form with subintrant attacks. Result of 
 examination of blood : Crescent-shaped bodies ; no spherical 
 bodies. 
 
 Obs. 12 and 13. — Clinical form : Quotidian fever of first inva- 
 sion. Result of examination of blood : Crescent-shaped bodies ; 
 no spherical bodies. 
 
 These facts prove that the authors who wished to formulate 
 absolute rules concerning the parasitic forms which are met with 
 in the blood of patients suffering from palustral fever of first 
 invasion, and who asserted that no crescent-shaped bodies were 
 found in these cases (James), or, on the contrary, that the crescent- 
 shaped bodies characterise the palustral continued fevers and the 
 quotidian fevers with subintrant attacks (Canalis), have too hastily 
 drawn a general conclusion from insufficient facts. 
 
 Spherical bodies of small volume, and often in very great 
 numbers, are usually observed in recent fevers (summer or 
 autumn), but spherical bodies of average size and flagella, 
 spherical bodies with crescent-shaped bodies, and even crescent- 
 shaped bodies alone may be seen (Obs. 11, 12, and 13). In my 
 ' Traite des fiovres palustres ' I point out that the crescent-shaped 
 bodies have been observed ten times in patients suffering from 
 fevers of first invasion, twice in patients from pernicious attacks, 
 and ninety-five times in patients from palustral cachexia or re- 
 current fever (op. cit., p. 196).
 
 90 MARSH FEVER AND ITS ORGANISM. 
 
 2nd. Quotidian intermittent fever (relapses). — (a) Observations 
 already published in my ' Traite des fievres palustres.' 
 
 Obs. 14. — Clinical form : Quotidian intermittent fever (relapse) 
 (op. cit., p. 245). Result of examination of blood : Crescent- 
 shaped bodies, spherical bodies, flagella. 
 
 Obs. 18. — Clinical form : Quotidian intermittent fever (relapse) 
 (op. cit., p. 249). Result of examination of blood : Spherical 
 bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 21 and 25. — Clinical form : Quotidian intermittent fever 
 (relapse) (op. cit., pp. 252 — 257). Result of examination of blood : 
 Spherical bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 26. — Clinical form : Quotidian intermittent fever (relapse) 
 (op. cit., p. 258). Result of the examination of the blood : 
 Spherical bodies of average or small size, flagella ; no crescent- 
 shaped bodies. 
 
 Obs. 29. — Clinical form : Quotidian intermittent fever (re- 
 lapse) (op. cit., p. 263). Result of the examination of the 
 blood : Crescent- shaped bodies in great numbers ; spherical 
 bodies. 
 
 Obs. 40. — Quotidian intermittent fever (relapse), pernicious 
 accidents (op. cit., p. 313). Result of the examination of the 
 blood : Spherical bodies of average or small size ; no crescent- 
 shaped bodies. 
 
 Obs. 44, 45, 46. — Clinical form : Quotidian intermittent fever, 
 rapid cachexia (op. cit., pp. 330—31). Result of the examination 
 of blood : Crescent-shaped bodies, spherical bodies, flagella. 
 
 (b) New observations. 
 
 Obs. 14. — Clinical form : Quotidian intermittent fever (re- 
 lapse). Result of examination of the blood : Spherical bodies ; 
 no crescent-shaped bodies. 
 
 Obs. 15. — Clinical form : Quotidian intermittent fever (relapse). 
 Result of the examination of the blood : Spherical bodies, seg- 
 mented bodies ; no crescent-shaped bodies. 
 
 Obs. 16. — The same. 
 
 Obs. 18, 19, 20, 21. — Clinical form : Quotidian intermittent 
 fever (relapse). Result of the examination of the blood : Spherical 
 bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 22. — Clinical form : Quotidian intermittent fever (re- 
 lapse). Result of the examination of the blood : Crescent- 
 shaped bodies, spherical bodies, flagella. 
 
 Obs. 23. — Clinical form : Quotidian intermittent fever, rapid 
 cachexia. Result of the examination of the blood : Crescent- 
 shaped bodies, spherical bodies.
 
 FURTHER OBSERVATIONS. 91 
 
 Obs. 24. — Clinical form: Quotidian intermittent fever (relapse). 
 Result of the examination of the blood : Crescent-shaped bodies, 
 spherical bodies, flagella. 
 
 In the blood of palustral patients suffering from relapses of 
 quotidian intermittent fever we may therefore find, 1st, spherical 
 bodies of small or average size, without flagella or crescent- 
 shaped bodies ; 2nd, spherical bodies and flagella without cres- 
 cent-shaped bodies ; 3rd, crescent-shaped bodies and spherical 
 bodies with or without flagella j 4th, spherical bodies and seg- 
 mented bodies, — that is to say, all the varieties of shapes of the 
 hsematozoa. 
 
 I might have multiplied the observations of quotidian fever 
 in which I have noticed only spherical bodies with or without 
 flagella, and which show that the crescent-shaped, bodies are very 
 often absent from the quotidian fevers. Golgi and Canalis admit, 
 it is true, that the quotidians are the double tertian or triple 
 quartan, and this is an ingenious theory, since, thanks to it, all the 
 quotidian fevers — that is to say, most of the fevers observed in hot 
 countries — would be lost sight of. I have already said that this 
 hypothesis seems to me inadmissible. The quotidian type is the 
 most common febrile type in hot countries ; and when a fever 
 reappears several times always with the same type, as in the 
 Obs. 14, I do not at all see the grounds for saying that 
 it is a double tertian or triple quartan. We shall see, besides, 
 that the crescent-shaped bodies have been noticed in patients 
 suffering from well-marked tertian or quartan fevers, which 
 completely ruins the theory of the two or three species of hasrna- 
 tozoa. 
 
 3rd. Tertian fevers. — (a) Observations published in my ' Traite 
 des fievres palustres.' 
 
 Obs. 19. Clinical form : Tertian intermittent fever (relapse) 
 (op. cit., p. 250). Result of the examination of blood: Spherical 
 bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 20. — Clinical form : Tertian intermittent fever (relapse) 
 (op. cit., p. 251). Result of the examination of blood: Spherical 
 bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 27. — Tertian intermittent fever (relapse) (op. cit., p. 259). 
 Result of the examination of the blood : Crescent-shaped bodies, 
 spherical bodies, flagella. 
 
 Obs. 28. — Clinical form : Tertian intermittent fever (relapse) 
 (op. cit., p. 261). Result of the examination of the blood : 
 Spherical bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 30. — Clinical form: Tertian intermittent fever (relapse)
 
 92 MAESH FEVEK AND ITS ORGANISM. 
 
 (op. cit., p. 265). Eesult of the examination of the blood: 
 Spherical bodies of medium or small size, flagella; no crescent- 
 shaped bodies. 
 
 (b) New observations. 
 
 Obs. 25. — Clinical form : Tertian intermittent fever (relapse). 
 Eesult of the examination of the blood : Spherical bodies, flagella J 
 no crescent-shaped bodies. 
 
 Obs. 26. — Clinical form : Tertian intermittent fever (relapse). 
 Result of the examination of the blood : Spherical bodies, flagella ; 
 no crescent-shaped bodies. 
 
 Obs. 27. — Clinical form : Tertian intermittent fever (relapse). 
 Result of the examination of the blood : Crescent-shaped bodies ; 
 no spherical bodies. 
 
 Obs. 29. — Clinical form: Tertian intermittent fever (relapse). 
 Result of the examination of the blood : Crescent-shaped bodies, 
 spherical bodies, flagella. 
 
 Obs. 30. — Clinical form : Tertian intermittent fever, sixth 
 relapse (tertian type). Result of the examination of the blood: 
 Crescent-shaped bodies ; no spherical bodies. Seventh relapse 
 (tertian type) . Result of the examination of the blood : Spherical 
 bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 31 and 32. — Clinical form : Tertian intermittent fever 
 (relapse). Result of the examination of the blood: Crescent- 
 shaped bodies, spherical bodies, flagella. 
 
 Spherical bodies, with or without flagella or crescent-shaped 
 bodies, may, therefore, be met with in the blood of patients suf- 
 fering from tertian intermittent fever. The crescent-shaped 
 bodies have been found alone several times (Obs. 27 and 30). 
 This latter observation is particularly interesting. During the 
 sixth relapse of fever of tertian type I found only crescent- 
 shaped bodies in the blood ; at the seventh relapse, again with 
 the tertian type, the blood contained spherical bodies and flagella 
 without crescent-shaped bodies. In the fifth series of facts 
 further examples of the co-existence of crescent-shaped bodies 
 with tertian fever will be found. Obs. 46 especially deserves 
 notice, and we shall return to it. 
 
 4th. Quartan fevers. — The observations of quartan fever 
 which are found at the end of this volume are summed up exactly 
 as follows, from the point of view of the relation which exists 
 between the clinical form and the parasites : 
 
 Obs. 33. — Clinical form : Quartan fever (relapse) . Result of the 
 examination of the blood: No crescent-shaped bodies; spherical 
 bodies.
 
 FURTHER OBSERVATIONS. 93 
 
 Obs. 34 and 35. — Clinical form : Quartan fever (relapse). Re- 
 sult of the examination of the blood : Spherical bodies, segmented 
 bodies ; no crescent-shaped bodies. 
 
 Obs. 36. — Clinical form : Quartan fever (relapse). Result of 
 the examination of the blood : Crescent-shaped bodies, spherical 
 bodies, flagella. 
 
 Obs. 37. — Clinical form : Quartan fever (relapse). Result of 
 the examination of the blood : Here again it must be noticed 
 that the crescent-shaped bodies have been found in the blood, 
 either isolated or joined together. In Obs. 37 the crescent- 
 shaped bodies have been found to the exclusion of other parasitic 
 elements. The segmented bodies have been noticed in Obs. 
 34 and 35. 
 
 I have never observed quartan fever but as a relapse, and all 
 authors agree that this fever seldom begins with the quartan 
 type. If there existed a special parasite for the quartan, it seems 
 evident the quartan fever would be produced from the beginning 
 of the attack. 
 
 5th. Palustral fevers ivith variable type; patients observed at 
 long intervals. — Observations of this series may be summed up 
 in the following table : 
 
 Obs, 33. — Clinical form: Tertian fever (relapse). Result of 
 the examination of the blood : Crescent-shaped bodies, spherical 
 bodies, flagella. New relapse of fever with quotidian and after- 
 wards tertian type. Result of the examination of the blood : 
 Crescent-shaped bodies, spherical bodies, flagella. 
 
 Obs. 39. — Clinical form : Intermittent quotidian fever. Result 
 of the examination of the blood : Crescent-shaped bodies, spherical 
 bodies, flagella. Relapse (pernicious phenomena). Result of 
 the examination of the blood : Spherical bodies. 
 
 Obs. 40. — Clinical form : Tertian fever. Result of the examina- 
 tion of the blood: Spherical bodies, flagella. Relapse (quotidian 
 attacks). Result of the examination of the blood : Crescent- 
 shaped bodies. 
 
 Obs. 41. — Clinical form: Tertian, afterwards quotidian fever. 
 Result of the examination of the blood : Crescent-shaped bodies, 
 spherical bodies. 
 
 Obs. 42. — Clinical form : Quotidian fever. Result of the 
 examination of the blood : Crescent-shaped bodies, spherical 
 bodies. Relapse (tertian type). Result of the examination of 
 the blood : Spherical bodies ; no crescent-shaped bodies. 
 
 Obs. 43. — Clinical form : Palustral continued fever. Result of 
 examination of the blood : Spherical bodies of small size ; no
 
 94 MARSH FEVER AND ITS ORGANISM. 
 
 crescent- shaped bodies. Relapse (with the tertian, afterwards 
 quotidian type). Result of the examination of the blood : Spherical 
 bodies ; no crescent-shaped bodies. 
 
 Obs. 44. — Clinical form : Quotidian fever. Result of the exam- 
 ination of the blood : Spherical bodies ; no ci*escent-shaped bodies. 
 Relapse of fever. Result of the examination of the blood : Spherical 
 bodies, flagella ; no crescent-shaped bodies. 
 
 Obs. 45. — Clinical form : Quotidian (relapse). Result of the 
 examination of the blood : Crescent-shaped bodies, spherical 
 bodies. Relapse (with the tertian type, and new relapse, quoti- 
 dian attack). Result of the examination of the blood : Both 
 relapses, spherical bodies ; no crescent-shaped bodies. 
 
 Obs. 46. — Clinical form : Quotidian (relapse). Result of the 
 examination of the blood : Spherical bodies, segmented bodies ; 
 no crescent-shaped bodies. Relapse (of fever, tertian type). 
 Result of the examination of the blood : Crescent-shaped bodies ; 
 no spherical bodies Second relapse. Result of the examination 
 of the blood : Spherical bodies ; no crescent-shaped bodies. 
 
 Obs. 47. — Clinical form : Irregular fever (relapse). Result of 
 the examination of the blood: Spherical bodies, segmented bodies; 
 no crescent- shaped bodies. 
 
 It has been known for a long time that the type of fever is 
 often modified in the same patient ; it was interesting to know 
 if the nature of the parasitic elements of the blood was modified 
 at the same time as the type of the fever. Some of the observa- 
 tions of this fifth series would be favorable to this opinion, 
 principally Obs. 40 and 42. In these two cases relapses with 
 tertian type were accompanied with the presence of spherical 
 bodies in the blood, and relapses with the quotidian type by the 
 presence of crescent-shaped bodies. But Obs. 46 shows that the 
 inverse ratio may be met ; here it is the tertian fever which is 
 marked by the presence of crescent-shaped bodies, and the 
 quotidian fever with that of spherical bodies. 
 
 In Obs. 38 and 43 we see that the type of fever changes 
 without the nature of the parasitic elements of the blood being 
 modified. 
 
 Obs. 47 relates to an irregular fever, the type of which 
 I have not been able to ascertain. Now in this case the presence 
 of the crescent-shaped elements has never been noticed ; this 
 is contrary to what ought to have taken place in these circum- 
 stances if these elements were the parasites of the irregular 
 fevers. 
 
 All these facts tend to prove that there exists no direct and
 
 CONCLUSIONS. 95 
 
 constant relation between the forms under which the haematozoa 
 are seen in the blood, and the clinical manifestations of 
 paludism ; all we can say is that certain parasitic forms are 
 oftener found in certain patients, — the crescent-shaped bodies, 
 e. g., in the relapsed fevers and in the cachectics, as I demon- 
 strated long ago. 
 
 That several species of haamatozoa of paludism exist does not 
 receive more support from zoological theories than from clinical 
 observation ; but all the zoological theories which we possess at 
 present concerning these parasites are very incomplete. 
 
 Is it, then, so difficult to understand that the same sporozoon 
 may take different shapes ? 
 
 I have quoted already (Chap. Ill) several examples of spo- 
 rozoa which are seen under very different aspects, — Lithocystis 
 Schneideri, Eimeria falciforme, Depranidium ranarum ; and it 
 would be easy to multiply examples. 
 
 In the laboratory of M. Metschnikoff, at the Pasteur Institute, 
 I examined some parasites of the Apus which are fixed in the 
 mobile gills ; these parasites evolve by producing now amoeboid, 
 now crescent-shaped bodies ; M. Metschnikoff, in showing me 
 these facts, added that probably it was the same process that 
 occurred with the haematozoa of paludism. The type of the 
 fever is very probably much more likely to be determined by 
 individual conditions than by the variety of the parasitic ele- 
 ments of the blood ; we shall return to this point in the following 
 chapter.
 
 CHAPTER V. 
 
 In what form is the hssmatozoon of paludism found in the exterior 
 media, and how is the infection produced ? — Meteoric and 
 telluric conditions which favour the development of paludism 
 — Predisposing individual causes — Influence of race and age — 
 Congenital paludism — Incubation — Pathology of the pheno- 
 mena of paludism. 
 
 It might have been hoped that, as the different appearances 
 which are taken in the blood by the parasites of paludism were 
 known, it would be easy to find them in the surrounding media. 
 
 From the beginning of my investigations I endeavoured to 
 find the forms under which the hrematozoon of paludism existed 
 in water or in earth ; I have examined numerous samples of the 
 water or soil of localities in Algeria where palustral disease 
 prevails, and I have several times noticed the presence of organ- 
 isms which have some analogy with the haematozoaof paludism in 
 the stagnant water of the fever localities ; chiefly amoeboid bodies 
 having one or several flagella similar to the spherical bodies of 
 p:ilustral blood, — with this difference, that the arrangement of the 
 flagella was more regular in the Protozoa found in water. These 
 organisms were not pigmented, but as the hgematozoa of paludism 
 probably borrow their pigment from the red blood-corpuscles, it 
 was not to be expected that they would be found pigmented in 
 the exterior media. 
 
 Maurel, who has met with these amoeboid bodies or analogous 
 organisms in an ordinary vegetable infusion, has pointed out the 
 analogies which exist between them and the parasites of the 
 palustral blood (Maurel, ' Recherches microscopiques sur l'etio- 
 logie du paludisme,' Paris, 1887, pp. 202 — 204). 
 
 Grassi and Feletti have noticed the existence of very small 
 amoebae with pseudopodia without contractile vacuoles in the soil 
 of palustral countries ; this amoeba is encysted rather easily, and 
 in that state may probably be carried by the atmospheric air, 
 and it has been found in the nasal cavities of healthy young 
 pigeons which had been placed for two nights in a palustral
 
 HOW THE INFECTION IS PRODUCED. 97 
 
 locality, at a height of six feet from the ground. Nine days 
 after, these pigeons had crescent- shaped bodies in their blood. 
 
 Grassi and Feletti compare this amoeba with those described 
 by Maurel, and seem disposed to believe that it is under this 
 form that the parasite of paludism is found in the exterior 
 medium. 
 
 The moi'phological resemblances are far from being complete, 
 and the identification of these organisms with the ha)matozoa of 
 paludism seems to me very rash. If the haBmatozoon of paludism 
 lived in water and in the soil under forms identical with those 
 which it possesses in the blood, there seems no reason why it 
 should be difficult to cultivate it in the exterior medium by 
 putting a few drops of the blood of a palustral patient in a little 
 water or sterilised earth, a culture of the parasitic elements being 
 then obtained ; these attempts at cultivation have, so far, given 
 only negative results. 
 
 It seems to me probable that the hasniatozoon of paludism 
 exists in the palustral media in the state of a parasite on some 
 animal or plant. 
 
 According to James, parasites which have a certain analogy to 
 the haomatozoon of paludism may be found in the vegetable king- 
 dom; they are amoeba? provided with flagella at one phase of their 
 development, and contain chlorophyll. This same fact has been 
 pointed out to me by M. Certes. 
 
 We saw (Chap. Ill) that parasites near akin to the haematozoon 
 of paludism are found in the blood of birds, and it is possible that 
 the hsematozoon of paludism itself exists in the blood of certain 
 animal species. 
 
 Mosquitoes are always abundant in palustral countries, and it 
 has been found that the drainage of the ground, which suppresses 
 the fever, also drives away mosquitoes (Lamborn, ' La destruction 
 des moustiques,' analysis in ' Revue scientifiquc/ 1890, p. 498). 
 Possibly these insects play a part in the propagation of paludism 
 as in that of filariosis. 
 
 For a long time the mode of propagation of filariosis was un- 
 known. The filaria), because of their size and the comparatively 
 elevated group to which they belong, are, however, easier to 
 study than the Luematozoa of paludism; it is now known thai 
 the filaria) of man undergo one phase of their development, in the 
 bodies of mosquitoes. The mosquitoes, by sucking the blood of 
 patients suffering from filariosis, absorb embryo filarieB, which 
 develop themselves in the body of these insects. When the 
 mosquitoes die and fall into the water, the filariffl escape and the 
 
 7 
 
 /
 
 98 MARSH FEVER AND TTS ORGANISM. 
 
 infection takes place through drinking water. Out of 140 female 
 mosquitoes examined by Lewis, twenty were literally filled with 
 filariae. 
 
 Findlay, of Havana, thinks that mosquitoes are the principal 
 agents of dissemination of yellow fever, and Hammond is of the 
 same opinion. 
 
 The fact that it is difficult to find a form under which the 
 haematozoon of paludism is met in the exterior world is not sur- 
 prising when we know that it is ajquestion of sporozoa ; the history 
 of the development of these entities is yet to be written (Balbiani). 
 
 Do the parasites get into the system with the water that is 
 drunk or with the inspired air ? 
 
 It seems to be a common opinion in the present day that air 
 is seldom the vehicle of pathogenic agents, and that it is water 
 which in most cases should be blamed. So far as paludism is 
 concerned, both modes of infection seem possible ; but while the 
 infection through the air is generally admitted, so much so that 
 the words maV aria (bad air) have become synonymous with 
 palustral fever, the infection through water is disputed by some 
 authors. 
 
 Persons who have contracted paludism have almost always 
 made use of the water of palustral localities, at the same time 
 breathing the air, consequently it is difficult to say which has 
 been the mode of infection. 
 
 Numerous facts tend to prove that the infection may take place 
 through drinking water. 
 
 ist. It has been found repeatedly that in the same localities, 
 among persons living under the same conditions, but drinking 
 water from different sources, some were severely attacked by 
 palustral fever while others escaped. (See principally my 
 ' Traite des fievres palustres,' pp. 458 — 464.) 
 
 2nd. In certain localities which were formerly insalubrious it 
 has been sufficient to place pure water at the disposal of tho in- 
 habitants, instead of the stagnant water which was formerly used, 
 for palustral fevers to disappear. 
 
 3rd. In some localities, otherwise very healthy, people may 
 contract fever, whose drinking-water comes from unhealthy 
 localities, and the persons most exposed to infection in these con- 
 ditions are those who consumed most water. 
 
 4th. Travellers passing through unhealthy countries often 
 succeed in escaping fevers by only drinking water that has been 
 boiled, while people who do not take that precaution suffer 
 severely. 
 

 
 CONDITIONS FAVOHAULE TO ITS DEVELOPMENT. 
 
 99 
 
 It has been objected that the infusoria and the amoebae are 
 destroyed by the digestive apparatus. 
 
 The protecting action of the normal digestive juices is indis- 
 putable, but it often happens that this action, for some cause 
 or other, takes place under unfavorable conditions, and loses 
 much of its efficacy. The properties of the digestive juices may 
 explain why a great number of persons escape from fever, whilst 
 others, living in apparently identical conditions, are severely 
 attacked. 
 
 In the case of the first, the digestive juices whose secretion 
 was normal destroyed the parasites brought by the water ; whilst 
 in the others, alterations of the digestive apparatus and weaker 
 activity of the digestive juices enabled the parasites to multiply 
 and penetrate the system. 
 
 Bouchard and Legendre have laid stress on the predisposition 
 to infectious diseases, and particularly to typhoid fever, which is 
 the consequence of the alteration of the digestive apparatus, and 
 principally of the dilatation of the stomach (Bouchard, ' Lecons 
 sur les auto-intoxications dans les maladies/ 1887, and 'Therapeu- 
 tique des maladies infectieuses,' 1889, P- 9 1 )- 
 
 The following fact seems to me sufficiently convincing con- 
 cerning the infection through water : Palustral fever is rarely 
 contracted inside the town of Constantine, particularly at the 
 Casbah, which is the highest point. During the summer of 1882 
 I received into my service several Government workmen employed 
 in the Commissariat department, inside the Casbah ; these men 
 were suffering from palustral fever for the first time, and they 
 asserted that for a long time they had not been out of Constan- 
 tine. Having been employed at the oven, they had suffered much 
 from heat, which outside reaches from 35 C. to 40 C. in the shade, 
 and in the room adjoining the oven was over 50 C. ; on account 
 of this these workmen drank from six to seven litres of plain water 
 every day between meals. It was natural that the digestive 
 juices being diluted by the great quantities of water, taken 
 without food, whilst the secretion was almost nil, were no pro- 
 tection to the system. 
 
 If the form under which the parasite of paludism is found 
 in the exterior world and its method of penetrating the system 
 are not yet understood, at least the causes which favour its 
 development and its penetration into the blood arc known ; the 
 study of these causes is most important, as it is the basis of 
 prophylaxis. 
 
 Paludism is essentially an endemic discaso ; it is possible to 

 
 100 MARSH FEVER AND ITS ORGANISM. 
 
 trace the regions in which it prevails, in the same way as natu- 
 ralists show the regions in which such and such a plant is 
 found and in which such and such an animal species has its 
 habitat. 
 
 Paludism may appear in localities which for centuries have 
 been free from it ; in the Mauritius and the Isle of Bourbon, 
 palustral fevers, formerly almost unknown, have greatly increased 
 since 1867. 
 
 Fortunately it is more usual to see it decrease ; the list is 
 long of localities, of whole countries, which have been made 
 healthy through cultivation of the soil. 
 
 In the eighteenth century palustral fevers were very common 
 and very severe in Holland (Pringle). The immense works exe- 
 cuted in order to protect the coast against invasion of the sea 
 have considerably reduced the field of the palustral endemic. 
 
 We know by the writings of Morton, Willis, and Sydenham 
 that palustral fevers were formerly prevalent in London, but 
 the drainage of a marsh caused the disappearance of the fever. 
 
 Graves points out the happy results of the drainage of the 
 ground in Ireland, and shows that in many places it has put 
 an end to the palustral endemic ( f Clinique/ t. i, traduction 
 fran9aise, p. 3). 
 
 At Strasburg in 1832 not only intermittent fevers were still 
 prevalent, but severe palustral fevers, complicated with pernicious 
 phenomena ; the dyking of the Hie and the Rhine, and the de- 
 struction of marshes have greatly reduced the fever. 
 
 In the Bresse, the Sologne, the Landes, and the Moi'bihan 
 palustral fever is much less serious than formerly. 
 
 In Algeria paludism has almost completely disappeared from 
 some localities where it raged at the beginning of the conquest ; 
 in all places the regular cultivation of the soil has caused it 
 to recede. 
 
 The damp uncultivated marshy localities are those which offer 
 to paludism a favorable medium. The existence of marshes, 
 properly speaking, is not necessary; and, on the other hand, all 
 marshes do not cause fever even in hot countries. At Tahiti, 
 in Australia, and in New Caledonia palustral fevers are rare, 
 in spite of the existence of marshes having all the objective 
 characters of fever marshes, as Boudin has rightly remarked. 
 Pommay has pointed out the innocuousness of marshes in the high 
 plateaus of South Oranes (South Algeria) ('Revue d'hygienc,' 
 1884, t. vi, p. 184). 
 
 If the marsh, properly speaking, is not necessary, there must
 
 CONDITIONS FAVORABLE TO ITS DEVELOPMENT. 101 
 
 at least be humid soil. Palustral fevers are not generated on 
 ships at sea far from land ; while in tropical countries, where 
 ground has been dried for some time, the fevers disappear, 
 though rain, especially when it does not last long, brings back 
 the fever-giving qualities to the soil. The small rains which take 
 place towards the end of the summer in hot countries, and which 
 are soon dried up by the sun, are known to be very dangerous ; 
 the abundant rains which last a long time do not produce such 
 ill effects, especially if at the same time the temperature falls. 
 
 The influence of heat is shown by the distribution of palu- 
 dism on the surface of the earth. Palustral infection, unknown 
 in cold countries, increases in intensity in proportion as one 
 advances towards the equatorial regions ; in the temperate and 
 warm zones it only prevails in the hot season: it reappears every 
 year with the same regularity, as is the case with certain animal 
 and vegetable species. 
 
 At Rome the first case of reappearance of fever is observed 
 every year almost exactly on the same day at the beginning of 
 July (Mayer L. Colin, 'Traite des fievres intermittentes/ 1870). 
 
 It is the same in Algeria ; at Constantine for three consecu- 
 tive years I saw the first cases of reappearance of palustral fever 
 take place towards the end of June, and the last during 
 November ; from December to the following June I only observed 
 relapsed fevers. From July to October the cases of fever are 
 rapidly multiplied, which explains and justifies the expression of 
 endemo-epidemic, often employed by authors who have written 
 on Algerian fevers. 
 
 Thus during the winter the germ of paludism is in abeyance ; 
 like some animals it has its hibernating period, and, like them, 
 it awakens at the beginning of summer. 
 
 The influence of altitude, of which there is no doubt, is explained 
 by the lowering of the temperature to a large extent, and also by 
 the fact that on high ground the waters having an easier fall, 
 the soil naturally drains itself. Experience taught this happy 
 influence of altitude long ago to the populations of palustral 
 countries; the Arabs and the inhabitants of the Koman Gampagna 
 always retreat from the plains towards the mountains during the 
 fever season. 
 
 The altitude which is sufficient to protect from fever is not 
 very great, and this fact is extremely important for the prophy- 
 laxis of paludism. I mentioned before that in the interior of 
 the town of Constantine fever is very rare; about one hundred 
 yards below, however, near the gates of the city, on the banks of
 
 102 MARSH FEVER AND ITS ORGANISM. 
 
 the Hummel, paludism is botli frequent and dangerous. It is the 
 same at Bona ; the upper town is spared, while in the lower part 
 attacks of paludism often occur. It would be easy to multiply 
 such examples. In a palustral country persons living in the 
 upper storeys of a house are less exposed than those who live on 
 the ground-floor. The germs of paludism, it would appear, rise 
 with some difficulty into the atmosphere. 
 
 The winds which blow over a marshy district may carry the 
 germs along, but not to a great distance. On the shores most 
 infected with paludism the sailors escape as long as they remain 
 in their ships ; the sea air it is known is very pure, and the 
 atmospheric dust soon disappears in the great mass of sea 
 water. 
 
 Predisposing individual causes. — The influence of age and sex 
 is small ; if it is a fact that adult men are more frequent victims 
 to paludism than women, young and very old people, this may be 
 explained by the influence of their occupations, about which we 
 shall speak later on. 
 
 Children are often attacked by paludism ; according to 
 Brun they are attacked in Egypt in a larger proportion than 
 adults. 
 
 Men of all races are subject to paludism, but in a variable 
 degree ; the blacks, for instance, offer a much greater resistance 
 than the Caucasians, a resistance which, however, does not go 
 as far as conferring immunity, as was thought by Boudin. 
 Palustral cachexia is not uncommon among the negroes, principally 
 at Gaboon, Ceylon, and the Antilles, though very numerous facts 
 show that when blacks and whites are transplanted into a palus- 
 tral district the whites are attacked in a much larger proportion 
 by paludism and present much graver forms of the disease than 
 do the blacks, consequently negroes are valuable auxiliaries in a 
 palustral country. 
 
 In the Mexican war the negroes who were brought from the 
 Soudan were very useful in Terres Chaudes, owing to the remark- 
 able immunity which they enjoyed, not only from the palustral 
 fevers, but also from yellow fever. 1 
 
 The Indians and the Creoles are not spared ; during the Mexican 
 war a company of volunteer Creoles was levied in the Antilles for 
 
 1 Consult on this question: Graves, 'Clinique mcdicale,' trad. franc, de Jaccoud, 
 3me edit., t. i, p. 483. Boudin, " Acclimatement des races humaines," ' Rec. de 
 iiu'111. de nu'd. mil.,' 3ine serie, ts. xii, xiii, and xv. Laveran, article "Antago- 
 nisme " du ' Dictionn. encyclop. des sc. me*d. Dutroulau, ' Traite des maladies des 
 Kuropuens dans les pays chauds,' ame edit., Paris, 1868, p. 147. Corre, " De 
 1'influence de la race dans les mal, infect,," ' Gaz. liebdom.,' 1869.
 
 PREDISPOSING CAUSES. 103 
 
 the Terres Chaudes, which was wasted rapidly under the influence 
 of palustral fevers. 
 
 In Algeria I have often noticed paludism among the natives, 
 but nearly always in forms milder and less acute than among the 
 Europeans j the Arab has evidently a greater tolerance, either 
 personal or hereditary, for the agent of paludism than has the 
 European. 
 
 The most unhealthy occupations in palustral countries are those 
 which bring man most often and most directly in contact with the 
 soil. The workmen employed in drying up marshes, in digging 
 harbours or ditches, navvies, gardeners, agricultural and harvest 
 labourers, afford the largest number of victims to paludism. 
 
 Paludism is essentially a disease of the country, as typhoid 
 fever is a disease of towns. In the central parts of Rome 
 people are exempt from the fever which rages with violence in 
 the Campagnia and even up to the gates of Rome (L. Collin, of>. 
 cit.). All weakening causes, for instance, fatigue, mental or 
 physical strain, anaemia resulting from privation or previous dis- 
 ease, predispose to paludism. 
 
 It was long ago noticed that the parasites are developed by 
 preference in weakened constitutions whose vitality is already 
 lowered, just as mosses and lichens invade the trunks of sickly 
 trees. It seems, says Pasteur, that life repels the life which 
 wishes to graft itself on it ; it is when an individual grows weak 
 that it becomes an easy prey to the parasites which besiege it. 
 
 The results of the experiments made by Charrin and Roger, 
 also by Canalis and Morpurgo, to determine the part of fatigue and 
 fasting in the etiology of infectious diseases, agree entirely with 
 the results of observation. 
 
 Rats which have been fatigued fall easy victims to an attenu- 
 ated anthrax virus, which has no power on them in their normal 
 state (Charrin and Roger, " La fatigue et les maladies micro- 
 biennes," in ' Semaine medicale, 5 1890, p. 29). 
 
 In researches which were recently published by Canalis and 
 Morpurgo (Rome, 1890) it is shown that by starving animals 
 they can be made liable to diseases which they resist in their 
 normal state ; pigeons and hens deprived of food lose their 
 immunity from anthrax. During the time of fasting the number 
 of leucocytes in the blood is diminished (Canalis and Morpurgo), 
 which might perhaps explain the disappearance of the exemp- 
 tion. 
 
 A first attack of paludism confers no immunity ; on the con- 
 trary, individuals who have once had palustral fever are more
 
 104 MARSH FRYER ANP ITS ORGANISM. 
 
 liable to contract it. It may be said that relapses are the rule ; 
 these relapses, however, do not imply a new infection, the agent 
 of paludism being able to remain in a latent state for a long time. 
 
 Paludism can be inoculated by intra-venous injection, as Ave 
 have seen, but it is not propagated by contagion from man to 
 man. 
 
 " Congenital 'paludism. — A certain number of scientific observa- 
 tions exist which tend to prove that paludism may be congenital ; 
 these observations were made by Sue and Hawelka (Bouchut), by 
 Playfair and by Duchek (Griesinger), by Bohn and by Bureau 
 (Leroux, ' Eevue de medecine,' 1882, pp. 569 — 575). 
 
 " Playfair reports the obervation of a woman who, during her 
 first pregnancy, was repeatedly attacked every foi^tnight with 
 remittent fever; the child at its birth showed so liypertrophied a 
 spleen that its edge reached the umbilicus ; the child had no 
 fever till the age of two, but was pale and sickly. Duchek 
 has observed a case exactly similar ; the child died shortly after 
 its birth, and presented a pigmented splenic tumour and pigment 
 in the blood of the vena porta " (Griesinger, ' Traite des maladies 
 infectieuses/ 2me edit., trad, franc., 1877, p. 20). 
 
 The observations of Chiarleoni show that the germ of paludism 
 may attack the foetus, and it often kills it when the mother is 
 not submitted to quinine treatment. The children born at full 
 time from mothers who have suffered during their pregnancy 
 from attacks of palustral fever, but who have been treated by 
 quinine, on the contrary, most generally show a normal develop- 
 ment and the signs of good health (" Le paludisme et la fonction 
 de la generation chez la femme," in 'Ann. univers. di Medicina/ 
 April, 1886). 
 
 It was believed until recently that the placenta formed a per- 
 fect filter which prevented the microbes passing from the mother 
 to the foetus, and the existence of congenital paludism might 
 appear in opposition to the parasitic nature of the disease (Leroux, 
 f Revue de medecine, 1882, p. 661). 
 
 Straus and Chamberland have shown that the microbes of sym- 
 ptomatic anthrax, of fowl-cholera, and of experimental septicaemia, 
 passed from the mother to the foetus (< Societe de Biologie,' Nov. 
 nth, 1881), and that the anthrax bacillus itself is not always 
 stopped by the placenta ('Societe de Biologic/ Dec. 16th, 1882), 
 contrary to the opinion of Davaine. 
 
 It can be understood that the hasmatozoa of paludism, which in 
 their first phase of development are in the state of amoeboid cor- 
 puscles, very small, free or intimately adherent to the blood-cor-
 
 INCUBATION. 105 
 
 puscles, may be able to pass through the placenta. The trans- 
 mission of paludism from the mother to the fcotus may easily be 
 reconciled with the ideas concerning the parasitic nature of dis- 
 ease which exist at the present day. 
 
 In order to dispel all doubts concerning congenital paludism 
 it would be interesting to examine the blood of the newly born 
 child of a mother suffering from paludism, and thus to ascertain 
 the existence of the hoematozoon. 
 
 Guarnieri and Bignami experimented twice for haematozoa in 
 the blood of foetuses of three and six months respectively from 
 cachectic mothers ; in both these cases the examination was nega- 
 tive. No conclusions can be drawn from these negative facts ; 
 new researches are necessary. 
 
 Incubation. — A few authors have expressed the opinion that 
 the invasion of paludism might be very rapid ; the case has been 
 often quoted of travellers attacked suddenly with pernicious sym- 
 ptoms while crossing a marshy district. In order for this fact 
 to prove anything, it would be necessary to show, ist, that the 
 travellers had not already been for some time under the influence 
 of paludism ; 2nd, that the phenomena observed were really due 
 to paludism, and not to other causes — as, for instance, heat apo- 
 plexy. Up to the present time this proof has not been forthcoming. 
 I myself hold that there always exists a period of incubation, 
 whose minimum duration may be from six to ten days. 
 
 "I have seen," says Maillot, " a large number of soldiers fall 
 ill, who only left camps near the marshes ten or twelve days 
 previously" ( ( Traite des fievres/ p. 263). 
 
 I have already pointed out the following fact which I had 
 occasion to observe : — A body of French troops landed at Bona 
 in the summer, and marched by stages from Bona to Con- 
 stantine, traversing localities well known to be unhealthy ; on 
 the march no case of paludism occurred. However, only a few 
 days after the arrival at Constantine, where the men were located 
 in very healthy barracks, symptoms of paludism appeared in a 
 large number of the men ; certain patients were seized a month 
 or more after their arrival, whilst others were attacked seven or 
 eight days after crossing the marshy districts. 
 
 Sorel has reported similar facts : " The encampment of Taki- 
 tount, which is at an altitude of 1051 metres, and situated 
 outside the ordinary zone of paludism, received on August 8th, 
 1 88 1, a reinforcement of eighteen soldiers, who having landed at 
 Bougie on August 3rd, started on the 6th. On the 18th twelve 
 men of that detachmont fell ill, and were admitted to the
 
 10n MARSH FEVER AND ITS ORGANISM. 
 
 hospital at Setif on the 19th. On August 21st and 24th two new 
 patients of the same detachment were also sent into hospital, and 
 in all the symptoms of paludism were unmistakably present." 
 
 As Sorel remarks, "it is evident that these men had contracted 
 the germs on the road from Bougie to Takitount (one of the 
 stations is very unhealthy), which would give from seven to nine 
 days as the duration of the incubation in most cases " ( f Archives 
 de med. militaire,' 1884, t. iii, p. 293). 
 
 In recent years paludism has been inoculated several times from 
 man to man, as already has been mentioned (Chap. IV, p. 75) ; 
 these facts of the experiments concerning paludism are interest- 
 ing from the point of view of the incubation of paludism. 
 
 It is shown by the experiments of Mariotti and Ciarocchi, Celli 
 and Marchiafava, Gualdi, and Antolisei and Angelini, that when 
 palustral blood containing hrematozoa is injected into the blood of 
 a man free from paludisnf, the fever appears in the inoculated 
 subject on an average ten days after the injection. These ex- 
 periments were made in conditions very favorable to the infec- 
 tion, since the ha3tnatozoa were introduced directly into the 
 blood. 
 
 The duration of the incubation given by the experimental 
 process agrees exactly, as we see, with the data of observation. 
 
 The period of incubation may be very long ; it should rather 
 be called the latent period ; it is not rare to meet people who 
 never had fever in Algeria, but who shortly after their return to 
 France suffered from very characteristic symptoms (Maillot, op. 
 cit., p. 263). 
 
 Dutroulau ( f Traite des maladies des Europeens dans les pays 
 chauds,' 2tne edit., Paris, 1868, p. 233), after having given several 
 examples of prolonged incubation of paludism, adds, " I might 
 multiply greatly these examples, which all have the same signifi- 
 cation, namely, a variable period of latency of the miasma before 
 the onset of the fever. How far can this period extend ? Up 
 to the present time it is impossible to determine this." 
 
 The haematozoa of paludism may remain latent in subjects who 
 have never had any symptoms of paludism, as well as in those 
 who have been attacked once or several times. 
 
 Verneuil and De Brun have shown that this period of latency 
 may be very long. De Brun gives the case of a man of fifty- 
 one who had a relapse of African fever seventeen years after his 
 return to France, and nineteen years after his last attack of 
 fever ; the surroundings in which this patient lived rendered a 
 fresh infection impossible.
 
 PATHOGENESIS OF THE DISEASE. 107 
 
 Any morbid cause, however — for example, a traumatism — may on 
 occasions be the cause of the return of attacks ; the traumatisms 
 affecting the spleen more especially provoke fever (De Brun, 
 " Les causes individuelles au somatiques de l'inipaludisnie," in 
 1 La medecine moderne/ May 8th, 1890). 
 
 A period of latency as long as that shown by De Brun seems 
 a priori very extraordinary. In order that the case quoted by 
 this author should be unassailable, it would be necessary for the 
 presence of the haematozoa of paludism to have been noticed in 
 the blood at the time of the relapse ; the appearance of attacks 
 of fever more or less regular is not sufficient to characterise 
 paludism. A nervous fever may at times be observed, which 
 almost exactly resembles intermittent fever; this I have ob- 
 served frequently in old palustral patients. This nervous fever, 
 which is observed in anaemic and neurotic patients, is not much 
 influenced by quinine ; it disappears after a few days without 
 any treatment being necessary. 
 
 How do the haematozoa when once introduced into the blood '< 
 produce the phenomena of paludism ? 
 
 The phenomena of paludism, it seems to me, maybe attributed 
 in great measure, 1st, to the alterations of the blood produced 
 by the haematozoa ; 2nd, to circulatory disturbances, and the 
 irritation which the presence of these parasites causes in the 
 tissues, and principally in the nerve-centres. 
 
 The haematozoa live at the expense of the normal elements of 
 the blood. The invaded red blood-corpuscles grow paler and paler 
 in proportion as the parasites develop, and even their contours 
 at last disappear. It may be said that no anaemia, except the 
 anaemia resulting from haemorrhage, can be better explained than 
 palustral anaemia. 
 
 The pigment, which is so abundant in the small vessels of all 
 the organs in subjects who have died from pernicious attacks, 
 also shows that the haematozoa are extremely destructive to the 
 red blood-corpuscles. 
 
 Moreover anaemia is the most constant symptom of paludism. 
 All the authors who have desci-ibed palustral phenomena have 
 insisted on the rapidity with which anaemia takes place. A few 
 grave attacks are sufficient to inake a patient unrecognisable, 
 so marked does the anaemia become. Certain patients become 
 anaemic and fall into cachexia without having any fever. Anaemia 
 constitutes with them the principal and, so to speak, solitary 
 symptom of the infection. 
 
 Frcrichs, who had been struck with tho abundance of the
 
 108 MARSH FEVER AND ETS ORGANISM. 
 
 pigment in the capillaries of the brain of subjects who had died 
 from pernicious fever, was the first to advance the theory that the 
 thi'ombosis produced by the accumulation of the pigment plays 
 an important part in certain phenomena of paludism. 
 
 This opinion has been the subject of severe criticism ; it was 
 indeed difficult to understand how these thrombi, formed of pig- 
 ment, should rapidly vanish and give rise sometimes to inter- 
 mittent symptoms. There were also objections on account of the 
 action of quinine, which did not very well agree with the theory 
 of pigmentary thrombosis. 
 
 The fact that the thrombus is formed not of inert material, as 
 Frerichs thought, but of parasitic elements, allows of the possi- 
 bility of the obstruction being removed tolerably quickly (though, 
 after all, this is not always the case) ; also it explains why quinine 
 has often great efficacy. 
 
 The paralysis and transient aphasia which are sometimes 
 observed during the paroxysms of the fever may be satisfac- 
 torily explained by temporary obstructions limited to certain 
 vascular areas of the brain. 
 
 The capillary haemorrhage, which is not rare (especially in the 
 brain) in subjects who have died from pernicious attacks, would 
 appear to result from the same cause. 
 
 The obstruction of the capillary vessels by the haematozoa is 
 not an hypothesis ; it is a fact easily verified, especially by the 
 examination of the brain-capillaries of subjects who have died 
 from pernicious attacks with delirious or comatose symptoms. 
 
 Bignami found very extended parasitic thrombosis of the intes- 
 tinal and gastric mucous membrane in certain subjects who had 
 died from choleraic pernicious attacks. 
 
 It may be easily understood that the presence of the haematozoa 
 provokes hyperaemia, vascular congestions, and inflammations. 
 When patients recover rapidly the congested organs soon resume 
 their normal size. In the long run the irritation produced by 
 the presence of the parasites and by the repeated congestions 
 accruing from it ends in chronic inflammation, whose seat 
 of election is naturally the viscera which are more specially the 
 habitats of the parasites. 
 
 It is thus that the spleen in old palustral patients constantly 
 shows inflammatory alteration, interstitial splenitis, and peri- 
 splenitis. Chronic hepatitis and nephritis follow in order of 
 frequency ; I have also sometimes noticed chronic pneumonia. 
 
 The lesions of chronic inflammation once established in a 
 viscus persist, oven grow worse, after recovery from paludism.
 
 INTERMITTENCY NOT PECULIAR TO PALUDISM. 109 
 
 For this reason cirrhosis of the liver or chronic nephritis 
 continue to develope in patients who have not had any attacks 
 of fever for a long time. 
 
 The presence of haematozoa in the small vessels of the cerebro- 
 spinal centres furnishes a satisfactory explanation of the nervous 
 symptoms, headache, pain in the back, delirium, convulsions, 
 and coma (pernicious attacks). The initial cold of the onset is 
 essentially a nervous phenomenon ; as for the rapid elevation of 
 temperature, the opinions now held concerning the physiology of 
 the spinal cord shows that symptom also to be attributed to the 
 irritation of this organ. 
 
 In filariosis accompaniments of fever identical with those of pa- v 
 ludism may be observed, but they do not answer to a regular type. 
 
 Intermittency is very far from constituting a constant charac- 
 teristic of paludism, and it is often wrong to employ the expres- 
 sion intermittent fever to designate this malady. 
 
 Palustral irregular continued fevers, cachexias of the first onset, 
 intermittent fevers with variable types, &c, are often observed 
 alongside intermittent fever with a regular type, especially in 
 the hot countries where paludism prevails with intensity. 
 
 On the other hand, intermittency is not peculiar to the phe- 
 nomena of paludism ; it has been noted frequently in neuralgias 
 Avhich were not of palustral origin, and even in traumatic nephritis 
 (W. Mitchell, ' Des lesions des nerfs et de leurs consequences,' 
 trad, de Dastre, Paris, 1874). 
 
 The hectic fever of tubercular disease is a quotidian inter- 
 mittent fever, the difference being that the paroxysms occur in 
 the evening and, unlike quotidian fever of palustral origin, resist 
 treatment by quinine. 
 
 Certain affections of the liver may also provoke intermittent 
 symptoms (J. Cyr, " De la periodicite de certains symptomes 
 hepatiques," ' Arch. gen. de med.,' May, 1883). 
 
 Verneuil and Mathon have shown that wounds of the spleen 
 in subjects free from paludism and living far from palustral 
 centres might give rise to periodic attacks of fever (Verneuil, 
 ' Du paludisme considers au point de vue chirurgical/ 1883, p. 4 ; 
 Mathon, ' De la splenite traumatique/ These, Paris, 1876). 
 
 " It is certain that the contusions of the spleen are sometimes 
 followed by periodic fever, but that symptom does not belong 
 more exclusively to palustral intoxication than does delirium to 
 alcoholic intoxication, or the paralysis of the radial extensors 
 to saturnine poisoning. Moreover the liver and kidneys, together 
 with the spleen, possess the property of creating a febrile eon-
 
 110 marsh eever and its organism. 
 
 dition with regular returns. Lastly, every one knows there is a 
 specific intermittence and a symptomatic intermittence in very 
 varied morbid states " (Verneuil, op. cit., p. 5). 
 
 The knowledge of the fact that injuries of the spleen often 
 produce intermittent symptoms is very important, for with palustral 
 patients it is certainly the spleen which is the most affected of all 
 the viscera by the presence of the pai'asites, aud there is nothing 
 exaggerated in comparing the invasion of this organ by the 
 myriads of parasites to an injury. 
 
 Observers who, like Councilman and Golgi, have examined the 
 blood of the spleen in patients with paludism, have noticed the 
 parasitic elements in much greater abundance than in the blooci 
 taken at the periphery ; thus Councilman succeeded sixteen times 
 out of twenty-one in finding the flagella in the blood of the spleen, 
 these bodies being much rarer in the blood obtained by the prick- 
 ing of a finger. 
 
 Pathological anatomy also shows that the spleen is the hot- 
 bed, if I may so say, of the parasites of paludism. Whether 
 death occurs after acute symptoms or as the result of cachexia, it 
 is always the spleen which shows the most characteristic lesions 
 in palustral patients. 
 
 In the individuals who succumb rapidly to pernicious attacks 
 the spleen is found to be softened and often reduced to a jelly ; 
 the softening is such that the splenic pulp is fluid to the touch. 
 The increase of volume is sometimes small, but the spleen always 
 presents a characteristic brownish hue due to the abundance of 
 the pigmented parasitic elements. When making the histological 
 examination of the splenic pulp a few hours after death parasitic 
 elements are again found, and specially the crescent-shaped bodies; 
 but these hacmatozoa soon lose their shape, and are easily con- 
 founded with melaniferous leucocytes. 
 
 In palustral cachexia the splenic hypertrophy is constant and 
 often enormous. 
 
 What is difficult to explain is not the intermittency, but the 
 regularity of the intermittency ; the existence of different regular 
 types of palustral fevers makes the question still more compli- 
 cated. 
 
 The first idea which comes to one's mind is that the hajmatozoa 
 which are developed in the spleen and in the medulla of the 
 bones migrate at times into the general circulation, and there give 
 rise to the febrile paroxysms, or else that successive generations 
 of these parasites are produced. 
 
 Filariosis and recurrent fever offer very curious examples of
 
 PATHOGENESIS OF THE PHENOMENA. Ill 
 
 parasites which are only seen intermittently in the general 
 circulation. 
 
 During the day the filarial retire into the deeper vessels ; it is 
 only towards six or seven o'clock in the evening that the parasites 
 appear in the small subcutaneous vessels, with a military punctu- 
 ality, as Cobbold remarks. 
 
 In patients suffering from relapsing fever the spirilla in the 
 blood obtained by pricking a finger will be observed only during 
 the febrile paroxysms ; in the intervals of apyrexia the spirilla are 
 only found in the spleen, and they are generally enclosed in the 
 cells of this organ (Metschnikoff). 
 
 It is a little before and at the beginning of the febrile 
 paroxj'sms that the kasrnatozoa are seen in great numbers in the 
 blood of the peripheral capillaries. 
 
 When these parasites are found in abundance in a patient 
 who has not had any attack for a long time, one may infer with 
 certainty that a relapse is imminent. 
 
 It is therefore reasonable to suppose that a direct relation exists 
 between the febrile paroxysms of paludism and the multiplication 
 of ha3matozoa in the blood, but the appearance and disappearance 
 of the parasites in the general circulation do not correspond suffi- 
 ciently exactly with the paroxysms and the intervals of apyrexia 
 to explain the intermittence. 
 
 The hasmatozoa do not disappear from the general circulation 
 after each attack, very far from it; I have often met them in 
 abundance and with their most characteristic forms in the in- 
 tervals of apyrexia. 
 
 Some authors have admitted the existence of different parasites 
 for the tertian, quartan, and irregular fevers ; we have seen 
 (Chap. IV, p. 128) that this hypothesis, which was advanced 
 by Golgi, is anything but proved, and that the existence of a 
 single polymorphic parasite was much more probable : this ques- 
 tion will not require further comment. 
 
 Experiments show that after febrile paroxysms the hajinatozoa 
 disappear in part from the general circulation, and that the metalli- 
 ferous leucocytes which result from the destruction by the haonia- 
 tozoa are then found in considerable numbers in the blood. The 
 absorption of the haeinatozoa by the phagocytes, which become 
 more active during the attacks of fever, is, as I said in [884, 
 probably one of the causes of the iutermittency. 
 
 lloux and Chamberland proposed a theory in order to explain 
 the intermittency of recurrent fever, which might also apply to 
 the other palustral attacks. After having remarked that during
 
 112 MAKSH FEVER AND ITS ORGANISM. 
 
 the febrile paroxysms free spirilla are found in the blood which 
 disappear in the intervals of apyrexia, Roux and Chamberland 
 add, " The body of a patient acts as a medium of culture 
 favorable at certain times and unfavorable at others. Might 
 not the fact of the intermittence be partly explained by the 
 presence in the tissues after each abundant culture (i. e. moment 
 of the attack) of substances elaborated by the parasite, and through 
 which by their accumulation its development is obstructed ? The 
 spirilla which are hindered in their evolution are the prey of the 
 phagocytes, while the antiseptic matter being eliminated or de- 
 stroyed in the blood, the medium of culture is again favorable, 
 and the spirilla multiply and the attack returns at the same time 
 that free spirilla reappear in the blood " (" Immunity against 
 Septicaemia conferred by Soluble Substances," c Annales de 
 Flnstitut Pasteur,' 1887, p. 572). 
 
 In his very remarkable " Essai d'une theorie de l'infection " 
 (' Congres de Berlin/ 1890) Professor Bouchard writes, "One 
 thing seems certain to me ; it is that the bacteria act on animals 
 by the matters which they secrete :" and further, " The fever of 
 the infectious diseases is toxic ; it is provoked by diastases such 
 as that studied by Roussy, by ptomaines such as the amidaleine 
 of Brieger." 1 
 
 The general laws which are so well formulated in this work 
 only concern the bacteria. As I have had occasion to remark 
 before, the haematozoa are too far removed from the schizophytes 
 for it to be possible to infer the mode of action of the one from 
 the other. 
 
 The investigations of Brousse, of Roque, and of Lemoine tend 
 to prove that the urinary toxicity is increased in paludism after 
 attacks of fever. 
 
 Brousse arrived at the following conclusions : 
 
 1st. The uro-toxic coefficient calculated with the formula of 
 Bouchard, the average coefficient being 0*464, rises during the 
 attack ; and the physiological effects observed are those which 
 are generally noticed after the injection of urine : dyspnoea, 
 myosis, fall of temperature, exophthalmia, and, even, convul- 
 sions. 2nd. This toxicity decreases during the period of conva- 
 lescence of the intermittent fevers, and is very inferior to that of 
 the urine during the attack, and besides weaker than that of 
 
 1 See also on this subject : Bouchard, ' Actions des produits secretes par les 
 microbes pathogencs,' Paris, 1890. Roussy, ' Communic. a l'Acad. de Med.,' Feb., 
 12th, 1889. Du memo, "Bechcrchcs expcriui. sur In pathogenic de la fievre," 
 Arch, de physiologic,' Paris, 1890, p. 355.
 
 PATHOGENESIS OF THE PHENOMENA. 113 
 
 the normal urine (' Societe de Med. et de Chir. pratiques de 
 Montpellier,' May 14th, 1890). 
 
 Roque and Lemoine are still more affirmative than Brousse ; 
 according to these observers the urinary toxicity would rise to a 
 much larger proportion after the attacks of palustral fever, and 
 the alteration of the kidneys and the liver increases the gravity 
 of the attacks by hindering the elimination of the toxic pro- 
 ducts (" Recherches sur la toxicite urinaire dans l'impaludisnie," 
 ' Revue de med./ 1890, p. 926). 
 
 The facts quoted by Roque and Lemoine are very few in 
 number, and the general conclusions which they draw from them 
 do not seem sufficiently justified. 
 
 The toxicity of the urine after an attack of intermittent fever 
 ought to be compared not only to the toxicity of normal urine, 
 but also to the toxicity of the urine after attacks of fever of equal 
 intensity to the palustral attacks, but depending upon other 
 causes. 
 
 In the urine of all fever patients an increase of the normal 
 toxicity is found, as well as new toxic properties, principally the 
 convulsion-causing property (Bouchard, e Lecons sur les auto- 
 intoxications,' Paris, 1887, p. 256). 
 
 I made lately some experiments on the toxicity of the urine 
 voided after an attack of intermittent fever, and I have not 
 noticed the great toxicity of such urine pointed out by Roque 
 and Lemoine ; however, I can conclude nothing from this. Before 
 giving any decided opinion on the degree of toxicity of the 
 urine in patients with palustral fevers, it will be necessary to 
 collect a large number of data. 
 
 Certain patients become cachectic without having had any 
 attack of fever, which renders the secretion by the hasmatozoa of 
 a substance analogous to pyretogenine very improbable. 
 
 We see from the researches of Nuttall and Buchner that the 
 blood and the serum of the blood have in some cases a destruc- 
 tive action on the microbes, apart from all influence of the leuco- 
 cytes. This action is soon exhausted ; it disappears when the 
 blood or the serum is heated to 55 C. (Buchner, ' Centralbl. f. 
 Bacter.,' June 14th and 28th, 1889; ' Anal, in Arch, de Med. 
 experimentale/ 1889, P* 872. 
 
 Fodor and Lubarsch have Bhown the bactericidal action of the 
 blood of the rabbit on the anthrax bacilli. In order to explain 
 that, in spite of this action, the rabbit remains very susceptible 
 to anthrax, these observers suggest that it is the parenchymatous 
 organs which allow the bacilli to escape the destroying influence 
 
 8
 
 114 MARSH FEVER AND ITS ORGANISM. 
 
 of the blood ; in other words, the bacilli meeting a hurtful 
 influence in the blood of the vessels take refuge in the spleen, 
 the liver, and medulla of the bones, where conditions much more 
 favorable to their development would be found. 
 
 Perhaps something similar takes place in the case of the 
 haematozoa of paludism, whose seat of election is in the spleen, 
 liver, and medulla of bones ; this would explain why parasites 
 cannot be cultivated in the blood outside the organism. The 
 degree of irritability of the nervous system, which varies with 
 individuals and with the date of the infection, seems to play an 
 important part in determining the type and form of the fever. 
 If it is a strong person who has palustral fever for the first time 
 the nervous system reacts strongly against a morbid agent to 
 which it is not accustomed, and a continued fever, or at least a 
 quotidian, is observed. If the patient is already anasmic, or 
 weakened by several attacks of fever, the nervous system having 
 become less sensitive, a fever with long intermissions then takes 
 place. 
 
 The nervous system gets accustomed to the presence of the 
 haematozoa, and reacts less and less. Among persons who have 
 lived for a long time in palustral countries, or who have had 
 several attacks of paludism, the attacks of fever are generally 
 rare and slight, though those who have newly come suffer from 
 fever of great frequency and severity.
 
 Q CHAPTER VI. 
 
 Means of defence of the organism — Spontaneous cure of paludism 
 — Role of the phagocytes — Tonic treatment — Specific action* of 
 quinine — Different modes of its administration — Prophylaxis 
 of paludism. 
 
 When morbid germs have succeeded in entering the blood the 
 human organism is not absolutely at their mercy, as would be 
 the case with an inert medium of culture in which these germs 
 have been sown ; the living organism continues to defend itself 
 against their action. 
 
 This law of general pathology applies well to paludism. 
 Patients with palustral fever, even when the properties of 
 quinine were not known, did not all die — far from it ; while to- 
 day cures called spontaneous, that is, without the use of quinine, 
 are not rare. 
 
 In this struggle of the organism against the haematozoa the 
 leucocytes seem to play an important part. 
 
 It has been known for a long time that if a substance in- 
 soluble in the serum and finely pulverised be injected into the 
 blood of an animal, the leucocytes seize this powder rapidly and 
 eliminate it from the blood (Ponfick, Hoffmann, Langerhans). 
 By mixing some frog's lymph with cinnabar powder and examin- 
 ing under the microscope the leucocytes may be seen attacking the 
 coloured granulations and absorbing them. The phenomenon 
 becomes more apparent if by the help of a hot stage the tempera- 
 ture of the preparation be raised. 
 
 We learn from the investigations of Metschnikoff that the leu- 
 cocytes seize not only the inert dust and the dead microbes, but 
 also in a great many cases the living pathogenic microbes, and 
 consequently this property of the leucocytes, or phagocytosis, 
 plays a very important part in the evolution of the infectious 
 diseases and the phenomenon of immunity. The cells of tin 
 splenic pulp, the cellules of the endothelium, of the subcutaneous 
 tissue, and of the pulmonary epithelium, take part in this work. 
 The name of macrophages has been proposed by Metschnikoff to
 
 116 MARSH FEVER AND ITS ORGANISM. 
 
 distinguish these latter elements, which are in general much 
 larger than the leucocytes or microphages} 
 
 Metschnikoff thinks that the phagocytes are the principal 
 agents of recovery in relapsing and palustral fevers ; in other 
 words, they are the principal agents of the destruction of 
 the parasites in the blood which are the cause of these two 
 diseases. 
 
 In relapsing fever the spirilla of Obermeyer, which are found 
 in very large numbers in the blood at the time of the attack, 
 disappear during the apyrexia. Metschnikoff has been able to 
 study this disease in the case of the monkey, which is easily 
 inoculated with the spirilla. 
 
 " At the beginning of the attack, when spirilla are found in 
 every drop of blood taken from the peripheral vessels, the spleen 
 is still entirely free from them. 
 
 "In a more advanced stage of the disease the number of the 
 spirilla in the spleen is very much smaller than in that of the 
 blood. This state of things changes radically towards the end 
 of the attack, for at that time all the spirilla are transported 
 into the spleen. But at the beginning of the apyrexia only a 
 very small number of microbes are free ; most of the spirilla are 
 absorbed by the leucocytes having multiple nuclei, which are 
 abundant in the substance of the spleen. All the contents of the 
 microphage are often found to be filled with spirilla, which 
 makes them a shapeless heap of filaments. I have never been 
 able to find any spirilla inside the macrophages or in the lym- 
 phoid cells having a single nucleus, which constitute the 
 corpuscles of Malpighi. 
 
 " In a more advanced stage of the apyrexia it was much more 
 difficult to find the spirilla again, but I have been able to ascer- 
 tain their existence within the microphages of the spleen thirty- 
 two hours after the crisis." 
 
 To sum up, " the attack lasts as long as the spirilla are 
 living free in the blood, and ends when these parasites become 
 the prey of the phagocytes" (Metschnikoff, ' Annales de l'Institut 
 Pasteur/ 1887, pp. 329, 330). 
 
 1 Metschnikoff, "Maladies parasitaires et digestion intra-cellulaire " ('Revue 
 scientifique,' 1886). The same, " Sur la lutte des cellules de l'organisuie contre 
 l'invasion des microbes " ('Ann. de l'Institut Pasteur, 1887, p. 321). The same, 
 "Etudes sur l'immunitc " (meme recueil, 1889, p. 289; and 1890, pp. 67 
 and 193). Gamalcia, " Sur la destruction des microbes dans les organismes 
 febricitants " (meme recueil, 1888, p. 229). Bouchard, ' Therapeutique des 
 maladies infectieuses,' 1889, pp. 92 — 95. The same, " Essai d'une theoriede l'in- 
 fection" (' Congres de Berlin,' 1890).
 
 MEANS OF DEFENCE OF THE ORGANISM. 117 
 
 l< In studying the internal organs of two fatal cases of mala- 
 rial fever I have been able to convince myself/' writes Metschnikoff 
 (loc. cit., p. 328), "in a very marked manner of the action of 
 the phagocytes in this disease. It is principally the macrophages 
 of the spleen and the liver which absorb quantities of malarial 
 parasites, often in surprisingly large numbers, which belong to 
 the neighbouring group of Coccidia." 
 
 The description of the researches of Metschnikoff concerning 
 the phagocytes in the parasitic disease of the Daphuia, in the 
 septicaemia of mice, and in anthrax would take me too far. It 
 is sufficient to say that these works seem to me quite conclusive 
 concerning the important role which has been assigned by 
 Metschnikoff to the phagocytes. 
 
 Wyssokowitsch ('Zeitsch. f. Hyg./ 1886, Analyse par Netter 
 in 'Bulletin med.,' 1887, No. 12) has experimented on eighteen 
 varieties of microbes, principally on the staphylococci, the strep- 
 tococci, the anthrax bacillus, the bacillus of typhoid fever, the 
 comma bacillus, the pneumococcus, and the tetragonus. Whatever 
 may be the nature of the microbes injected into the blood of an 
 animal, their number soon decreases. If it is microbes non- 
 pathogenic to the animal under experiment they are not found 
 in the blood for more than three hours after the injection ; if the 
 microbes are pathogenic their number, after having diminished, 
 increases very much in proportion as the symptoms induced by 
 their presence manifest themselves. 
 
 The microbes are deposited in the capillaries of the organs 
 which have a slow circulation — the spleen, liver, medulla of bones 
 — and they are absorbed and slowly digested by the cells of the 
 endothelium. 
 
 The resistance of the microbes deposited in the spleen or in 
 the medulla of bones may be long. Wyssokowitsch found that 
 some spores of the Bacillus subtilis which were in the spleen were 
 still alive after three months — a fact which is interesting in the 
 study of latent microbism. 
 
 I explained in my first publications the destruction of the para- 
 sites during the febrile attacks by the action of the leucocytes. 
 " It is known that under the influence of artificial heat the leuco- 
 cytes acquire a very great activity ; the amoeboid movements are 
 exaggerated, and if the pigmented granules are placed in contact 
 with leucocytes it is found that they seize and absorb them very 
 rapidly. Febrile heat certainly acts in the same way as artificial 
 heat in this experiment; in the fever patient the activity of the 
 leucocytes is exaggerated, and the parasitic elements become their
 
 118 MARSH FEVER AND ITS ORGANISM. 
 
 prey more easily than in the individual whose temperature is 
 normal" (' Traite des fievres palustres,' p. 479). 
 
 Since then Metschnikoff, Golgi, Gamaleia, have laid stress on 
 the role of febrile heat in the destruction of microbes. 
 
 Golgi, in his work on ' Le Phagocytisme dans le Paludisme/ 
 which dates from 1888, allows, as I did in 1884, that the destruc- 
 tion of the parasitic elements by the leucocytes plays an important 
 part in the phenomenon of the intermission, and that the febrile 
 process increases the activity of the white corpuscles, and con- 
 sequently makes the destruction of the parasitic elements more 
 rapid. 
 
 Gamaleia, in a treatise on f La destruction des Microbes dans 
 les Organismes febricitants,' arrived at the conclusion that the 
 febrile period of the infectious diseases accompanies the destruc- 
 tion of the bacteria — a conclusion which applies well to the 
 parasites of paludism. 
 
 On the contrary, the activity of the phagocytes is lessened by 
 cold. 
 
 It is seen from the researches of Wagner that if fowls kept 
 in the cold can take anthrax disease, as the celebrated ex- 
 periment of Pasteur proves, this is caused by the fact that in 
 them the leucocytes lose a part of their activity. The same effect 
 may be obtained by lowering the temperature of the fowls by 
 means of antipyrin. 
 
 According to Alexander the number of spirochete in recurrent 
 fever increases when the temperature is lowered by antipyrin 
 ( f Bresl. arztl. Zeitsch./ 1884, No. 11). 
 
 The existence of melaniferous leucocytes, which are often 
 numerous after attacks of intermittent fever, and specially after 
 grave attacks, shows that the leucocytes take possession of the 
 debris of the parasitic elements, and the pigment which they 
 contain. 
 
 But the leucocytes do not only seize on the dead parasites, 
 they also take possession of the living ones ; this sometimes may 
 be ascertained by direct examination of the blood. The leuco- 
 cytes which are attached to the parasitic elements are in process 
 of absorbing them. 
 
 Golgi, who has made a series of punctures in the spleen at 
 the different stages of attacks of fever, and also during the 
 apyrexia, observed that the phagocytic forms are much more 
 numerous in the splenic pulp than in the blood of the general 
 circulation, especially during the initial stage of the attacks. 
 
 Danilewsky has noticed that phagocytosis has an important
 
 TREATMENT. 11 
 
 role in the destruction of the haematozoa of birds (" Contrib. 
 a l'Etude des Phagocytes/' 'Ann. de FInstitut Pasteur/ 1890, 
 
 P- 43 2 )- 
 
 The organism, therefore, may triumph over the hasmatozoa 
 
 when left to its own resources ; it contends with all the greater 
 advantage when it is placed in satisfactory general conditions ; 
 therefore all weakening causes hinder the cure of paludism, while 
 a tonic treatment favours it. I have observed the same fact in 
 the animals whose blood contains hasmatozoa. Under the in- 
 fluence of abundant food the hasmatozoa were seen to disappear, 
 whilst want of food favoured their development. 
 
 Patients who have become anaemic, who are worried, badly fed, 
 have constantly relapses of fever, quinine itself becoming, so to 
 speak, powerless to prevent these relapses ; on the contrary, 
 under the influence of good regimen and rest alone, the state of 
 palustral patients frequently improves ; the anasmia disappears, 
 the relapses are rarer, and recovery may be obtained without any 
 more active treatment by the simple fact that the organism has 
 been placed in good hygienic conditions. All tonics have, there- 
 fore, a favorable action on the disease, wine, coffee, and arsenious 
 acid taking the first place. Arsenic taken in small doses does 
 great service in treatment of obdurate fevers and of palustral 
 cachexia ; on the contrary, when given in strong doses, accord- 
 ing to Boudin's method, thereby provoking gastric troubles 
 (diarrhoea or vomiting), relapses of fever often take place, and the 
 state of the patient becomes worse. 
 
 Hydrotherapeutics are of great value, always as a tonic treat- 
 ment ; it sometimes succeeds when other treatment has failed : 
 it must be remembered, however, in having recourse to this 
 method, that the first trial may provoke a relapse. It is necessary 
 to act with prudence, and it is always advisable to begin by short 
 and tepid douches before trying the cold douche ; the spleen 
 should not be douched at first, and a few doses of quinine should 
 be prescribed at the same time as the douche. It can be easily 
 understood that a cold douche, especially if brought to bear on 
 the splenic region, may be followed by an attack j the vessels of 
 the spleen being contracted, the hasmatozoa are again put in 
 circulation. 
 
 Palustral patients who have taken the waters as baths at hot 
 springs — Vichy, for instance — also often have relapses at the 
 beginning of the treatment unless care is exercised. 
 
 The fact that a change of climate is extremely favorable to 
 patients who have contracted fever in hot countries is explained
 
 120 MARSH FEVER AND ITS ORGANISM. 
 
 by the strengthening influence of colder climates ; severe heat is 
 very weakening ; the abundant perspiration, sleepless nights, 
 dyspepsia which is almost continuous, weakens the organism ; 
 and it is not surprising that a very rapid improvement should 
 take place in the state of patients who are able to leave the hot 
 countries for the temperate. 
 
 The tonic treatment, which is very efficient in the chronic 
 forms of paludism, is evidently insufficient in the grave fevers 
 which may rapidly cause death. Fortunately we possess a remedy 
 really and truly specific, marvellously efficacious in paludism — 
 quinine. 
 
 The action of quinine on patients suffering from pernicious 
 attacks, distressed by noisy delirium or sunk in coma, must be 
 watched in order to have a just idea of the services of quinine 
 in the treatment of paludism. In the simple intermittent fevers 
 one or two doses of quinine are sufficient to cut short the fever ; 
 this expression — cut short the fever — is very appropriate here. 
 It can be ascertained by examining the thermometric tracings of 
 patients suffering from intermittent fever, who have had several 
 attacks and have taken quinine ; after doing so the fever stops 
 suddenly ; the line which was so irregular during the attacks 
 becomes suddenly horizontal. No other fever is thus cut short 
 by quinine, which is really the specific of paludism. 
 
 Cinchona was known and much appreciated in England as far 
 back as 1660, under the name of Peruvian bark ; but the cinchona 
 powder was very difficult to administer, especially in grave fevers ; 
 at any rate, the slowness with which the absorption of cinchona 
 took place was very detrimental to the treatment of these fevers. 
 Pelletier and Caventou have rendered an immense service to 
 therapeutics by isolating quinine. 
 
 Although the febrifuge properties of quinine have been known 
 for a long time, it has not so far been known how this medicine 
 acts ; the numerous experiments made on animals or on healthy 
 persons in order to solve this question have really, it may be 
 said, only obscured it the more. To attempt to demonstrate the 
 action of quinine in paludism by experimenting on healthy men 
 or animals is the same as studying the action of the pomade 
 d'Helmerich on the itch by rubbing this pomade on men or ani- 
 mals not suffering from that disease. Experimenting on the 
 physiological action of quinine could not possibly show how this 
 medicine cures paludism. 
 
 In 1867 Binz published experiments which showed that palu- 
 dism was produced by bacteria, and that sulphate of quinine cured
 
 THE ACTION OF QUININE. 121 
 
 palustral fever by killing- the bacteria (Binz, * Arch, de Max 
 Schultze,' 1867). 
 
 The conclusions of Binz did not stand criticism ; the bacteria 
 described by him had no particular characteristic. On the other 
 hand, Vulpian and Bochefontaine showed that bacteria are very 
 slightly sensitive to the action of quinine. According to Vulpian, 
 in order to destroy bacteria in the blood it would be necessary 
 to give fever patients more than 30 grms. of hydrochlorate of 
 quinine for a dose ('Cours d'Anat. pathol., 1871). 
 
 The numerous experiments of Bochefontaine show that the 
 vibriones are destroyed with difficulty by quinine (' Arch, de 
 Physiol. / 1873, 1st series, t. v, p. 390) ; in frogs made bacteri- 
 haeinic by the injection of cyclamine under the skin, sulphate of 
 quinine does not destroy the bacteria which multiply in the 
 blood. 
 
 Quinine does not kill the alga? nor the fungi which have often 
 been assigned as being the cause of paludism. The palmella? 
 also are easily developed in a solution of sulphate of quinine 
 (Wood, 'American Journal of Medical Science/ 1868). 
 
 The penicillium can live and flourish in a concentrated solution 
 of sulphate of quinine (Bochefontaine). In the military hospitals 
 in Algeria the bottles which contain a solution of sulphate of 
 quinine, at a strength of 1 in 20, are almost always covered with 
 fungi on their inner surface if they are not frequently and care- 
 fully cleaned. 
 
 These objections, quite justifiable as to the bacteria of Binz 
 and the palmellae of Salisbury, have no force when it is understood 
 that the parasites of paludism belong not to the Schizophytes nor 
 to the Algae, but to the Protozoa. 
 
 It has been known for a long time that the Protozoa are very 
 susceptible to the action of quinine. It is sufficient to add a very 
 small quantity of quinine to any infusion containing a large number 
 of infusoria, for them to be killed in a few minutes (Bochefon- 
 taine, op. cit., 404). 
 
 On the other hand, it is well known that the haeruatozoa dis- 
 appear rapidly in patients submitted to quinine treatment. One 
 conclusion only remains, namely, that quinine cures the fever by 
 killing the haomatozoa. 
 
 The action of quinine on the hajmatozoa may be studied directly 
 by mixing a drop of solution of sulphate or hydrochlorate of qui- 
 nine to a drop of palustral blood j in these conditions it can be 
 noticed that the movements of the flagella are no longer observed, 
 and that the haematozoa assume their dead forms. The disap-
 
 122 MARSH FEVER AND ITS ORGANISM. 
 
 pearance of the parasites in the blood of patients submitted to 
 quinine treatment is another clear proof that quinine destroys 
 the hasmatozoa. 
 
 It may be objected that many substances have antiseptic and 
 antiparasitic properties superior to those of quinine without being 
 antidotes of paludism. 
 
 If parasiticides like iodine or mercury could be introduced 
 into the blood in sufficient doses, these medicines would no doubt 
 destroy the hasmatozoa of paludism as well, and even much better 
 than quinine ; but these agents are very strong poisons to man 
 himself, and therefore cannot be made use of to kill the parasites 
 living in the upper part of the digestive tube. 
 
 The particular sensibility of the haematozoa to quinine is, after 
 all, nothing very surprising. Certain parasites are sensitive to 
 the action of substances which do not act on others. The root 
 of the pomegranate tree and the ethereal essence of male fern, so 
 useful against taenia, have no effect on ascarides ; while santonine, 
 which is efficient against ascarides, has no influence on taenia. 
 
 Raulin has shown that in order to prevent the development of 
 the Aspergillus niger in a liquid, it was sufficient for the liquid to 
 contain -iqUoWoo °^ nitrate of silver. If the Aspergillus niger 
 were a parasite capable of developing itself in the blood of man 
 it would be sufficient to administer 40 milligrammes of nitrate of 
 silver in order to stop its multiplication in the blood of a man 
 weighing about 150 lbs. (Duclaux, 'Ferments et Maladies/ Paris, 
 1882, p. 47). 
 
 A continued observation of the blood of palustral patients 
 submitted to quinine treatment affords the opportunity of ascer- 
 taining the effect of the treatment ; the parasitic elements imme- 
 diately become scarcer ; the spherical bodies and the flagella dis- 
 appear first, the crescent-shaped bodies resisting much longer. 
 
 This variable resistance of the parasitic elements explains the 
 frequency of the relapses. If the hasmatozoa of paludism were 
 all found in the blood in the same stage of development, it would 
 be difficult to understand why quinine destroys some and not the 
 others. 
 
 The bodies which have resisted quinine give rise to a remulti- 
 plication of parasites which it is necessary to check by repeated 
 treatment without waiting for the relapses. 
 
 This method of treatment may be compared to the sterilisation 
 of the liquids of cultivation by the intermittent heating to ioo° 
 C. By heating to ioo° C. most of the microbes enclosed in the 
 liquid are destroyed, but some spores resist ; by heating again to
 
 TREATMENT BY QUININE. 123 
 
 ioo° C. after twenty -four hours the spores which are developed, 
 and which in their new form have become more sensible to the 
 influence of heat, may be killed. Thus it is sufficient to heat a 
 cultivation liquid three times to ioo° C. at twenty-four hours' in- 
 terval in order to bring about a complete sterilisation. 
 
 It has been seen that the phagocytes play an important part in 
 the destruction of the hasmatozoa ; the question may therefore be 
 asked whether the efficacy of the quinine treatment is not partly 
 due to the fact that under the influence of quinine the action of 
 the phagocytes is exaggerated. 
 
 Some experiments by Binz seem to prove that quinine paralysed 
 the amoeboid movements of the leucocytes ; Hayem and Bochefon- 
 taine have ascertained, on the contrary, that these movements 
 were not impeded by the quinine. 
 
 Probably the phagocytes take up the hsernatozoa when these 
 have been killed or paralysed by quinine, but the activity of 
 the phagocytes is most likely not directly influenced by quinine 
 treatment. 
 
 How should quinine be prescribed in paludism ? — under what 
 form and in what dose ? 
 
 As a general rule it may be said that in ordinary cases of 
 simple intermittent fever quinine should be prescribed internally 
 by the mouth, whilst in grave forms requiring a rapid interven- 
 tion recourse should be had to the hypodermic method ; the latter 
 mode of treatment must also be adopted when patients who are 
 suffering from simple fevers do not easily stand quinine ad- 
 ministered by the mouth, also when vomiting occurs. 
 
 The endermic method, which consisted in the absorption of 
 the salts of quinine by the skin deprived of the epidermis, and of 
 enemata of the sulphate of quinine, was useful at times before the 
 hypodermic method was known, but is now out of date. 
 
 In prescribing enemata of quinine one can never be sure 
 that the dose will not be rejected before the absorption of the 
 medicine has taken place, and it is always impossible to gauge 
 exactly how much has been absorbed. 
 
 The hydrochlorate of quinine should be prescribed in preference 
 to the sulphate of quinine. It contains 81 per cent, of quinine, 
 while the bisulphate itself only contains 59 per cent.; it is more 
 stable, more soluble, and easier to obtain pure than the sulphate 
 of quinine (Dujardin-Beaumetz, 'Societe de Therapeutique,' March 
 23rd, 1887). 
 
 According to the researches of Beurmann, of Regnauld, and of 
 Villegean quinine should be classified as follows : 1st, from its
 
 124 
 
 MARSH FEVER AND ITS ORGANISM. 
 
 contents in alkaloid ; 2nd, its solubility (' Bulletin gen. de 
 Therapeutique,' 1888, t. cxiv). 
 
 Quinine Salts classified in terms of their Alkaloid. 
 
 IOO 
 
 parts 
 
 of basic hydrochlorate of 
 
 quinine 
 
 contains . 
 
 8171 
 
 quinine 
 
 JJ 
 
 jj 
 
 neutral ,, 
 
 >» 
 
 >> 
 
 8r6i 
 
 ?) 
 
 JJ 
 
 >> 
 
 basic lactate 
 
 jj 
 
 
 > 
 
 78*26 
 
 )» 
 
 JJ 
 
 »> 
 
 ,, hydrobromate 
 
 j» 
 
 
 5 • 
 
 7660 
 
 jj 
 
 )) 
 
 >> 
 
 „ sulphate 
 
 JJ 
 
 
 ? • 
 
 74 3 1 
 
 jj 
 
 JJ 
 
 >> 
 
 ,, sulphovinate 
 
 J» 
 
 
 ? • 
 
 7216 
 
 j> 
 
 JJ 
 
 JJ 
 
 neutral lactate 
 
 JJ 
 
 
 )? ■ 
 
 6230 
 
 )» 
 
 »> 
 
 51 
 
 „ hydrobromate 
 
 J J 
 
 
 >> • 
 
 60*67 
 
 J? 
 
 JJ 
 
 )> 
 
 „ sulphate 
 
 JJ 
 
 
 * • 
 
 59- 1 2 
 
 jj 
 
 JJ 
 
 JJ 
 
 „ sulphovinate 
 
 JJ 
 
 
 ») • 
 
 56-25 
 
 jj 
 
 Quinine classified in order of their Solubility , after J. Regnauld 
 
 and E. Villegean. 
 
 1 part of neutral hydrochlorate of 
 
 quinine is 
 
 soluble in 
 
 o'66 water. 
 
 >> 
 
 JJ 
 
 sulphovinate 
 
 )? 
 
 ») * 
 
 o'yo „ 
 
 >> 
 
 JJ 
 
 lactate 
 
 s> 
 
 jj 
 
 2'00 
 
 >) 
 
 JJ 
 
 sulphovinate 
 
 3) 
 
 J? 
 
 3'3° .. 
 
 JJ 
 
 JJ 
 
 hydrobromate 
 
 JJ 
 
 j» 
 
 6'33 » 
 
 » 
 
 JJ 
 
 sulphate 
 
 )> 
 
 jj 
 
 900 
 
 JJ 
 
 basic 
 
 lactate 
 
 JJ 
 
 jj 
 
 10*29 
 
 JJ 
 
 >> 
 
 hydrochlorate 
 
 JJ 
 
 ? j 
 
 . 21'40 „ 
 
 JJ 
 
 j> 
 
 hydrobromate 
 
 JJ 
 
 jj 
 
 • 45'° 2 
 
 JJ 
 
 >> 
 
 sulphate 
 
 *J 
 
 jj 
 
 . 581-00 
 
 The salicylate of quinine, so much praised by Antouesco 
 (' These/ Paris, 1886), is very little soluble (one part is dis- 
 solved in 1430 parts of water at 20 C.) ; moreover 100 parts of 
 salicylate only contain 70' 12 per cent, of quinine. 
 
 The hydrochlorate of quinine is a little more expensive than 
 the sulphate of quinine, but it is prescribed in a smaller dose. 
 
 The hydrochlorate of quinine is, because of its solubility, the 
 best quinine salt to be employed for hypodermic injections ; the 
 basic hydrochlorate of quinine is only dissolved in 21 times its 
 weight of water, but the neutral hydrochlorate is much more 
 soluble ; one part of basic hydrochlorate of quinine is dissolved 
 in 21*40 parts of Avater, one part of neutral hydrochlorate of 
 quinine in o*66 of water. 1 
 
 1 Quinine is considered to-day as a diacid alkali ; the neutral salt is the body 
 which results from the combination of a molecule of quinine with two molecules 
 of monobasic acid. It is through the application of this rule that the old acid 
 hydrochlorate of authors has become the neutral hydrochlorate, although its re- 
 action on turmeric paper is strongly acid (De Beurmann and Villegean, op. cit., 
 p. 205).
 
 TREATMENT BY QUININE. 125 
 
 De Beurmann and Villegean recommend for the hypodermic 
 injections the following solution : 
 
 Bihydrochlorate of quinine . . 5 grammes. 
 
 Distilled water . . . . q. s. to make 10 cubic centimetres. 
 
 A cubic centimetre of this solution represents exactly 50 centi- 
 grammes of bihydrochlorate. 
 
 In the absence of solid bihydrochlorate, the basic hydro- 
 chlorate of commerce may be utilised by the following method : 
 — Dissolve a certain quantity of pure hydrochloric acid with dis- 
 tilled water until the liquid has a specific gravity of 1*045 a ^ 
 -f-15 C. Place 5 grms. of basic hydrochlorate of quinine in a 
 graduated burette, add 5 c.c. of the acid solution ; then add dis- 
 tilled water to make up to 10 c.c, and filter. 
 
 The solution of bihydrochlorate of quinine is clear and of an 
 almost syrup consistency ; after some time it assumes a brownish 
 tint, without, however, being decomposed (De Beurmann and 
 Villegean, op. cit., and ' Tribune inedicale,' Sept. 18th, 1890). 
 
 The solution of bihydrochlorate of quinine although very acid 
 to turmeric paper, is not caustic ; I have not observed any eschars 
 or gangrene in the patients treated with this solution, but very 
 acute pain at the time of the injection, which lasted sometimes 
 for several hours. 1 
 
 I have also employed the following formula, which is given in 
 the ' Formulaire des Hopitaux Militaires : ' 
 
 Monohydroehlorate of quinine .... I gramme. 
 
 Alcohol at 6o° C 3 grammes. 
 
 Distilled water 6 „ 
 
 If required a few drops of hydrochloric acid may be added in 
 order to obtain a complete solution. 
 
 At a temperature of -+- 15° C, a cubic centimetre of this so- 
 lution contains very nearly one decigramme of quinine. 
 
 In the injections made with this solution, as with the solution of 
 bihydrochlorate, it is necessary, it is true, to inject a larger quan- 
 tity of liquid ; if 1 grm. of hydrochlorate of quinine is needed, 2 
 cubic centimetres of the solution is injected with the ordinary 
 Pravaz syringe through each puncture by filling the syringe twice 
 and five punctures being made. In these conditions the absorp- 
 tion of the quinine is easy and rapid. 
 
 Kobner has used the following formula (' Bulletin gen. de 
 Therap.,' 1890, p. 506) : 
 
 1 The addition of a little carbolic acid will prevent the pain in most cases {Trans.).
 
 126 MARSH FEVER AND ITS ORGANISM. 
 
 Hydrochlorate of quinine from . . . 0*50 to 1 gramme. 
 Pure glycerine . . . . . .2 grammes. 
 
 Distilled water ...... 2 „ 
 
 Prepare without acid and inject the solution tepid. 
 
 In order to avoid the possible confusion of the hydrochlorate 
 of quinine with the hydrochlorate of morphia — a confusion which 
 might cause very grave accidents — Vigier and Delpech have 
 rightly proposed to write on the prescriptions and on the labels 
 the name of the alkaloid first, as follows : 
 
 Morphia (hydrochlorate) 
 Quinine ,, 
 
 instead of — 
 
 Hydrochlorate of morphia 
 ,, of quinine. 
 
 That would be indeed a very useful precaution. 
 
 The following formula, given by Vinson, is very good for the 
 hypodermic injections, and very useful, as hydrochlorate of qui- 
 nine is not always to be obtained : 
 
 Sulphate of quinine . . . . .1 gramme. 
 
 Distilled water . . . . . .10 grammes. 
 
 Tartaric acid . . . . . .50 centigrammes. 
 
 The neutral sulphovinate of quinine is almost as soluble in 
 water as the neutral hydrochlorate (one part of the neutral sul- 
 phovinate is dissolved at an ordinary temperature in 0*70 water), 
 but the solutions of sulphovinate of quinine have a serious incon- 
 venience since they decompose rather quickly, and the hypodermic 
 injections made with the decomposed solutions cause local compli- 
 cations, e.g. acute pain, abscess, gangrenous spots (Marty, f Societe 
 de Pharmacie de Paris,' 1887; ' Bulletin med.,' 1887, No. 12). 
 
 I have used the sulphovinate of quinine in subcutaneous injec- 
 tions to compare it with hydrochlorate of quinine, and I have 
 noticed that the local complications were much more frequent 
 with the first than with the second. 
 
 Lactate of quinine has been praised by Vigier (' Gaz. hebdom./ 
 1885, p. 83). 
 
 The crystallised lactate of quinine, as found in commerce, is 
 not sufficiently soluble for hypodermic injections. 
 
 The hydrobromate of quinine is only soluble in 60 parts of 
 water, but a solution of this salt, 1 in 10, may be obtained by 
 substituting distilled water and alcohol in place of pure water, as 
 in the following formula : 
 
 Hydrobromate of quinine . . . .1 gramme. 
 
 Alcohol 1*50 grammes. 
 
 Water 7-50
 
 TREATMENT BY QUININE. 127 
 
 The solution of hydrobromate of quinine often gives rise to local 
 complications. 
 
 When making hypodermic injections of quinine, it is neces- 
 sary to be very careful to plunge the point of the needle of the 
 Pravaz syringe deeply into the subcutaneous tissue ; the injec- 
 tions made in the thickness of the dermis almost invariably cause 
 local complications. 
 
 The solution must be perfectly clear, and have neither crystals 
 nor spores in suspension. 
 
 Injections should be made into the limbs and not into the 
 trunk, in view of the local complications which may take place, 
 and which are specially likely to occur in cachectic patients. 
 
 The injection is generally followed by acute pain. A small nu- 
 cleus of induration forms at the level of the puncture ; most gene- 
 rally that nucleus vanishes or becomes absorbed, but sometimes 
 an abscess or dry eschar about the size of a sixpence or a shilling 
 takes place, and slowly separates. Sometimes larger eschars or 
 even diffuse inflammation have been observed, but these grave 
 complications are quite exceptional, and it is not the injection 
 itself that is to blame, but the way of making it. 
 
 Baccelli lately praised intra-venous injections of quinine ( f Gaz- 
 zetta degli Ospitali/ No. 12, Feb., 1890). 
 
 Baccelli injected from 40 to 60 centigrammes of hydrochlorate 
 of quinine into a vein at the bend of the elbow, using the follow- 
 ing solution : 
 
 Hydrochlorate of quinine .... 1 gramme. 
 
 Chloride of sodium 75 centigrammes. 
 
 Distilled water .10 grammes. 
 
 Twenty-four hours after the injection almost all the parasitic 
 elements had disappeared from the blood. 
 
 To prepare Baccelli 5 s solution neutral hydrochlorate of quinine 
 should be used, which gives an acid solution. By mixing blood 
 with one drop of this solution it is easy to ascertain that the 
 blood coagulates, and that the blood-corpuscles are altered, first 
 becoming pale and then disintegrated. 
 
 The hypodermic method allows quinine to be introduced into 
 the general circulation as quickly as the intra-venous injection, 
 and without any danger. I do not see, therefore, why intra- 
 venous injections should be preferred to it, for they are more 
 difficult to perform, and may give rise to very grave local or 
 general complications. 
 
 The intra-venous injections seem to me only to be justifiable in 
 the most grave pernicious attacks, when it might be feared that
 
 128 MARSH FEVER AND ITS ORGANISM. 
 
 the hypodermic method itself would not allow the quinine to be 
 introduced quickly enough into the blood — as, for instance, in 
 choleraic or pernicious attacks. 
 
 Are quinine salts toxic, and at what dose do they give rise to 
 symptoms ? 
 
 On this subject many incorrect theories have been advanced, 
 and even to-day sulphate of quinine is blamed by the public for 
 many mishaps which are caused by paludism alone, — for instance, 
 most of the palusti-al cachectics attribute the hypertrophy of the 
 spleen to the abuse of sulphate of quinine ; this, however, is met 
 to a much greater degree in patients who have never made use of 
 quinine than in persons who have used and abused it. 
 
 Certain people have a special susceptibility to quinine, which, 
 even in a small dose, causes rather alarming symptoms in them ; 
 but these are exceptional facts, and, for my part, I have never 
 met any example of them. 
 
 Trousseau and Pidoux mention having seen a young man at 
 the hospital of Tours who was mad for a whole day after having 
 taken a dose of 1*25 grammes of sulphate of quinine. 
 
 The same authors quote the following case : — A patient suffer- 
 ing from asthma, after having taken 3 grammes of sulphate of 
 quinine at one dose, was seized with ringing in the ears, giddi- 
 ness, vertigo, and excessive vomiting. Seven hours after taking 
 the medicine he was blind and deaf, and in delirium. These 
 symptoms disappeared of themselves (Trousseau and Pidoux, 
 ' Traite de Therapeutique/ 8th edit., t. ii, p. 487). 
 
 Kizu relates that every time one of his patients took sulphate 
 of quinine, even in a very small dose, she experienced con- 
 gestion of the face, and then a real attack of orthopncea and of 
 urticaria ( f Bulletin de la Societe des Medecins et Naturalistes de 
 Jassy/1887). 
 
 Floyer has quoted a similar case; a strong man could not take 
 sulphate of quinine even in a very small dose (0*15 grm.) with- 
 out having violent dyspnoea and some urticaria (' Brit. Med. 
 Journ./ 1886). 
 
 Kobner has seen symptoms in an infant after a hypodermic 
 injection of 30 centigrammes of sulphate of quinine — scarlatini- 
 form eruption, colic, bloody discharge from the anus. 
 
 Doses of sulphate of quinine six times weaker than the pre- 
 ceding, taken internally, produced similar results in this child 
 ('Bulletin gen. de Therapeutique/ 1890, p. 506). 
 
 Piskiris, of Athens, has published two cases of gastro-intestinal 
 haemorrhage in patients attacked with palustral anaemia follow-
 
 TREATMENT BY QUININE. 129 
 
 ing the administration of sulphate of quinine {' Galenos,' Athens, 
 1890). 
 
 Sulphate of quinine sometimes gives rise to hemoglobinuria or 
 hasmospherinuria : the urine becomes reddish or blackish ; it 
 contains albumen and hasnioglobin, but blood-corpuscles are not 
 found. This complication has been well studied and described 
 by Greek physicians, and in particular by Karamitzas and by 
 Pampoukis (Parnpoukis, ' Etude sur les Fievres palustres de la 
 Grece,' Paris, 1888). 
 
 Karamitzas gives the example of a student who was attacked 
 with hasmoglobinuria as soon as he took sulphate of quinine, even 
 in such a weak dose as 0*30 grm. 
 
 Pampoukis and Chomatianos have published several similar 
 observations. 
 
 Sulphate of cinchona will not give rise to hemoglobinuria 
 according to Pampoukis, and ought to be substituted for sulphate 
 of quinine in patients subject to this complication. 
 
 According to Tomaselli quinine might produce not only hasmo- 
 globinuria, but also an ictero-hasinaturic fever similar to the 
 ictero-hasmaturic fever of hot countries ( f Congres de la Societe 
 Italienne de Medecine Interne,' Rome, 1888). 
 
 Spyridon Canellis (of Athens) and Pasquale Muscato have pub- 
 lished recent examples of hemoglobinuria from quinine ("Analysis 
 of the Work of Spyridon Canellis," in ' Arch, de Med. navale,' 
 1888, p. 476; Pasquale Muscato, "Sur l'Hemoglobinurie paroxys- 
 tique par la Quinine/' 'Gaz. degli Ospitali,' 1890, Nos. 17 and 19). 
 
 For my part, I have not had occasion to observe hasmoglo- 
 binuria due to quinine, and I am unable to explain why this 
 complication, which appears so common in Greece, is so rare in 
 Algeria. 
 
 Lepine has studied the action of quinine upon the blood of the 
 dog and of the sheep and pig under the microscope. In these 
 animals quinine destroyed the blood-corpuscles largely. In the 
 living animal the cause of the destruction of the corpuscles is the 
 passage of the hemoglobin and of the inetheinoglobiu into the 
 plasma. In healthy subjects it is rare to observe its elimination by 
 the kidneys (hasmoglobinuria). It is possible that quinine destroys 
 the altered hasmatin of palustral patients more easily. 
 
 Manassein has pointed out an increase of the diameter of tho 
 blood-corpuscles — from 5 to 8 per cent, in different animals — 
 under the influence of quinine (Lepine, 'Arch, de Med. exper.,' 
 1890, p. 563). 
 
 At what dose is quinine toxic and the cause of death ? 
 
 9
 
 130 MARSH FEVER AND ITS ORGANISM. 
 
 Maillot aud Monnerat have prescribed up to 8 or 9 grnis. of 
 sulphate of quinine daily for pernicious fevers, and for intractable 
 neuralgias respectively. 
 
 Guersent relates that a lady, who had taken 41 grms. of 
 sulphate of quinine in the course of a few days, temporarily lost 
 sight, hearing, and speech, becoming deadly cold ; but all these 
 symptoms disappeared rapidly. 
 
 There exists to my knowledge, writes Briquet, a proved case of 
 intoxication by quinine followed by death. It was the case of an 
 insane physician who, to cure himself of a slight fever, took the 
 enormous dose of 220 grms. of sulphate of quinine in ten to 
 twelve days, and who succumbed to the prostration into which he 
 had fallen (Briquet, ' Traite therapeutique du Quinquina,' p. 585). 
 
 Giacomini, quoted by Briquet, gives the case of a man who 
 inadvertently swallowed 12 grms. of sulphate of quinine at one 
 time. There were symptoms of hyposthenia of the heart and of 
 the nervous system, but these symptoms were successfully com- 
 bated by the aid of stimulants. 
 
 The following facts show that a dose of 12 grms. of sulphate of 
 quinine could cause death in an adult. Two soldiers wishing to 
 take medicine mistook the bottle, and in place of sulphate of soda 
 took a solution of quinine, about 12 grms. of the salt each. Half 
 an hour after taking the medicine both men were seized with 
 vomiting, cramp in the stomach, pallor, dilatation of the pupils, 
 shallow respiration, shivering, small pulse, which was also irregular, 
 slow, and at times imperceptible. They also had ringing in the ears 
 and tendency to syncope. In one of these patients the symptoms 
 improved, but the other succumbed to syncope (Baills, " Deux cas 
 d'empoisonnement par le sulfate de quinine," in ' Archives de 
 Medecine militaire,' 1885, t. vi, p. 320). 
 
 These two facts show clearly that quinine is above all a poison 
 to the heart. They were cardiac symptoms which predominated 
 in both these cases, and caused death in one of them. 1 
 
 To sum up, excepting in a few subjects in whom quinine pro- 
 duces the appearance of symptoms more disquieting than really 
 dangerous, it may be said that the employment of quinine in doses 
 which are usually necessary to cure paludism presents no danger. 
 In Algeria — and in the gravest cases — I never exceeded the dose 
 of 3 grms. of sulphate or of hydrochlorate of quinine daily. In 
 ordinary forms, doses of 1 grm., o # 8o grin., and even o*6o hydro- 
 chlorate of quinine were quite sufficient. 
 
 1 Sec also Rosenbusch, " Un cas d'empoisonnement aigu par la quinine avee 
 un cxautheme acarlatiniforme " (' Wien. mediz. Presse,' April 13th, 1S90).
 
 TBEATMENT BY QUIXIXK. 131 
 
 Although quinine only rarely produces any ill effects, this possi- 
 bility ought not to be lost sight of; quinine intoxication, vomiting, 
 hyposthenia of the nervous system, may result. If these symptoms 
 are confounded with those of paludism, the dose of quinine might 
 be still increased, and as a consequence the symptoms of intoxi- 
 cation would be likewise increased. 
 
 It is specially necessary to be very prudent in administering 
 quinine for the first time to nervous persons. It should then not 
 be begun in large doses unless the gravity of the fever requires it. 
 
 It is often considered sufficient to cut short the fever with two 
 or three doses of quinine, waiting for a return of the fever to re- 
 commence the treatment. I consider this method to be bad, and 
 that the endeavour should be to prevent the relapse by the help 
 of repeated treatment ; unless this is done only a few attacks 
 are suppressed, as the parasites stopped for a time in their de- 
 velopment very soon increase, and all has to be gone over again. 
 
 Sydenham long ago understood the necessity of a prolonged 
 treatment by cinchona in intermittent fever. He wrote as follows: 
 
 " Cinchona, notwithstanding its efficacy, cannot be wholly de- 
 pended on to eradicate the disease. . . . The best means of 
 preventing the relapse is to repeat the febrifuge even after the 
 cessation of the fever " (Sydenham, in ' Encyclopedie des Sci. 
 med.,' p. i). 
 
 And further on, " In case the fever returns I never fail to 
 give the patient the same quantity as before, precisely on the 
 eighth day after the last dose of cinchona. For the patient to 
 be placed entirely out of danger of a relapse it is necessary to 
 repeat the treatment three or four times. " 
 
 Practice shows that two or three doses are sufficient to arrest 
 an ordinary intermittent fever, but that it often reappears at the 
 end of seven or eight days. After the fever is arrested the first 
 time the treatment should be recommenced six or eight days after 
 the last attack. 
 
 Quinine might without doubt be administered for a fortnight 
 or three weeks, but that would present enormous inconveniences 
 for the quinine gives rise to disagreeable nervous symptoms, espe- 
 cially in certain patients, such as ringing in the ears, deafness ; 
 moreover the treatment would become very expensive — a con- 
 sideration which is of importance to many patients, and which 
 ought to be remembered by doctors in hospitals. 
 
 It has not, however, been demonstrated that a continued treat- 
 ment with quinine has a greater efficacy over the interrupted 
 treatment which I speak of.
 
 132 MARSH FEVER AND ITS ORGANISM. 
 
 I have often pointed out that better results are obtained by 
 giving a few fairly strong doses of quinine than in prescribing it 
 for a lengthened time, but in small daily doses. 
 
 It is evident that if one gramme of hydrochlorate of quinine is 
 prescribed in a single dose the blood at a given time is found 
 much more charged with quinine, and as a consequence is much 
 more fatal to the ha3matozoa, than if 0*30 gramme of hydrochlo- 
 rate of quinine were prescribed for four days. 
 
 The type of the fever does not seem to me to require the 
 form of the treatment to be materially modified. After having 
 been assured, notably by the examination of the blood, that the 
 fever is really due to paludism, the following doses, for example, 
 would be prescribed for an adult man. 
 
 The first, second, and third days o'8o to 1 gramme of hydro- 
 chlorate of quinine daily. 
 
 The fourth, fifth, sixth, seventh days no quinine. 
 
 The eighth, ninth, tenth days o*6o to o*8o gramme of hydro- 
 chlorate of quinine. 
 
 From the eleventh to fourteenth days no quinine. 
 
 On fifteenth and sixteenth days o'6o to o*8o gramme of hydro- 
 chlorate of quinine. 
 
 From seventeenth to twentieth days no quinine. 
 
 On twenty-first and twenty-second days o"6o to o - So gramme 
 of hydrochlorate of quinine. 
 
 If the fever reappears during the course of the treatment it is 
 necessary to prolong it. 
 
 I certainly do not pretend to give a formula applicable to 
 every case of paludism. The preceding formula ought to be 
 modified very often, chiefly in the grave fevers of hot countries. 
 
 The question has been much discussed as to the right period 
 in intermittent fever that quinine should be taken. The majority 
 of authors admit that it ought to be administered during the 
 apyrexia. 
 
 Quinine is better tolerated at this time than during the attack 
 of fever ; it excites vomiting less often, and the absorption of 
 the medicine is probably more complete ; on the other hand, 
 it cannot be expected to cut short the evolution of an attack 
 of fever of normal duration when that attack has already 
 commenced. 
 
 Let it be ever kept in mind that in the grave and continued 
 levers the intermissions or even the remissions need not be waited 
 for before administering the quinine. 
 
 There was a time when the employment of quinine was con-
 
 TREATMENT. 133 
 
 sidered dangerous to patients suffering from continued fevers, and 
 was strictly limited to the intermittent fevers. Under the in- 
 fluence of this theory the mortality from paludism was enormous 
 in hot countries. Maillot deserves great credit for showing that 
 this opinion was erroneous, and that quinine should be adminis- 
 tered in continued as in intermittent palustral fevers. The the- 
 rapeutic reform which our illustrious master was the first to 
 describe has had the happiest results, and the opinions of Maillot 
 on continued palustral fever and its treatment are to-day uni- 
 versally admitted. 
 
 In serious cases hypodermic injections (1*50 to 2 grammes 
 daily) should be made without regard to the temperature. As 
 soon as the fever has yielded, the treatment for simple fever 
 given above should be followed. 
 
 Hydrochlorate of quinine should be prescribed internally in 
 solution or in the form of tabloids. In the military hospitals 
 of Algeria the patients swallow the solution of quinine, which is 
 prescribed and dealt out at the time by an attendant, during the 
 visit of the doctor and in his presence. It is an excellent plan, 
 seeing that it too often happens that when tabloids are prescribed to 
 be taken during the day the medicine is not taken, and a search dis- 
 covers the packets of quinine thrown into some corner of the ward. 
 
 In the grave pulustral fevers accompanied by pernicious 
 symptoms the first thing to attend to, and by far the most im- 
 portant of all, is to get the quinine taken ; but in addition to 
 this there is often occasion to prescribe some further aids to the 
 special treatment. 
 
 For the patients attacked with algid fever, friction either dry 
 or with evaporating camphor liniment should be used; hot stimu- 
 lating drinks — alcohol in tea, for example — diffusible stimulants, 
 ether, acetate of ammonia under the form of draught, or, better 
 still, hypodermic injections of ether (2 to 4 grms. of sulphuric 
 ether), must be prescribed. The hypodermic injections of ether 
 also render great service in patients attacked with choleraic com- 
 plications. 
 
 In the case of continued fever with typhoid state and high 
 temperature cold baths are sometimes indicated. 
 
 For the comatose symptoms when the individual is strong and 
 plethoric, and when signs of a severe encephalic congestion are 
 noticed, leeches may be applied to the mastoid processes in 
 order to prevent the consecutive congestion. Cold applications to 
 the head, counter-irritants to the extremities, and drastic purga- 
 tives are also useful.
 
 134 MARSH FEVER AND ITS ORGANISM. 
 
 All authors now agree in condemning the use of ordinary 
 bleeding in the treatment of paludism. 
 
 I have found chloral hydrate (3 to 4 grms. in a mucilaginous 
 solution) very useful in combating delirium in delirious pernicious 
 attacks, and in alcoholic palustral patients. 
 
 When vomiting is present, effervescing drinks, champagne, ice 
 may be given; a hypodermic injection of hydrochlorate of morphia 
 (1 centigramme) made over the epigastrium often succeeds in 
 soothing the vomiting. Opium should be prescribed internally if 
 there is excessive diarrhoea. 
 
 In bilious fever, ipecacuhana and calomel are very useful, but 
 here, again, the first thing is to prescribe quinine. 
 
 Formerly before giving quinine it was usual to prescribe laxa- 
 tives and emetics. Maillot has protested against this practice, 
 considering that if the purgatives and emetics are not in them- 
 selves hurtful, they have the great drawback of delaying the 
 administration of quinine (Maillot, op. cit., p. 361), and a perni- 
 cious attack may come on before quinine has been given. 
 
 None of the numerous medicines which have been patronised 
 till now as succedanea of quinine deserve this title, for none of 
 them possess efficacy comparable to that of quinine in the treat- 
 ment of paludism. 
 
 Arsenious acid acts specially as a tonic, and as such it may be 
 of service in the treatment of cachexia, but the method of Boudin 
 is insufficient and very dangerous in the treatment of the acute 
 symptoms. 
 
 Sulphate of cinchona is cheaper than sulphate of quinine, but 
 much weaker in its effects ; it would therefore require to be given 
 in larger doses than the sulphate of quinine, though its toxic 
 power is equal to that of quinine. 
 
 Sulphate of cinchonidine is more toxic than the sulphate of 
 quinine ; it is dangerous to exceed 2 grms., and in order to 
 obtain the necessary therapeutic effects this salt must be pre- 
 scribed in a dose double that of the sulphate of quinine, there- 
 fore it should not be employed (Marty, " Contrib. a l'etude du 
 Sulfate de Cinchonidine," ' Bull, gt-n do Therap.,' 1884, p. 335; 
 E. le Juge de Segrais, " Etude sur la Cinchonidine et ses sels 
 comme Succedanes de la Quinine," 'Arch. gen. de Med./ 1886, 
 t. ii, p. 420). 
 
 De Brun recently tried to revive the use of cinchonidine; 
 according to him the sulphate of cinchonidine, besides being 
 cheaper than that of quinine, is generally better borne by the 
 patient. De Brun prescribes 1 to 2 grms. of sulphate of cin-
 
 PROPHYLAXIS. 135 
 
 chonidine in doses of 0*50 to 1 grm. ; these doses may be enough 
 in slight cases, but would evidently be insufficient in grave 
 ones. 
 
 Analgesin or antipyrin does not cure palustral fever, it only 
 lessens the intensity of some symptoms, e. g. cephalalgia and fever ; 
 as such it may be useful in the treatment of continued palustral 
 fevers (Antony, ' Arch, de Med. milit.,' 1887, *• x > P- 2I )- 
 
 This is only a palliative treatment, and while prescribing 
 analgesin the patient should in addition be submitted to a qui- 
 nine treatment, quinine being the only real remedy, especially if 
 the fevers are those of hot countries, and if pernicious complica- 
 tions are dreaded. 
 
 Eucalyptus has found favour with some in the treatment of 
 paludism, taken in the form of the alcoholate or wine of eucalyptus. 
 The febrifuge properties of these preparations have been doubted, 
 and, at any rate, they are by no means comparable to those of 
 quinine. 
 
 Prophylaxis. — The prophylaxis of paludism comprises — 
 
 1st. The study of individual measures to be taken to escape 
 paludism when obliged to live in a country where the fever pre- 
 vails. 
 
 2nd. The study of measures to be taken in order to render the 
 localities where paludism is endemic healthy. 
 
 The prophylaxis will yet be founded on more precise data, 
 and may very probably be simplified, when it is known exactly 
 under what form the parasites of paludism are found in the 
 exterior medium. 
 
 At the present time rules may be framed which, being founded 
 on experience, are of indubitable usefulness and efficacy. 
 
 In most palustral countries there is a healthy and an unhealthy 
 season, or endemo-epidemic period. In Algeria, for example, 
 and in Italy, fevers are but seldom contracted from December to 
 May ; during these months paludism need not be dreaded. 
 The traveller who is master of his time should take advantage of 
 this season of the year to travel in palustral districts ; and this is 
 also the season which should be chosen to send troops into these 
 countries. 
 
 Breaking up the ground, earthworks, digging ditches or 
 ponds, draining of marshes, should not be undertaken during the 
 endemo-epidemic season. Any work of this kind which it is 
 impossible to delay in hot countries should as much as possible 
 be given to natives or negroes, who enjoy a remarkable immunity 
 from paludism.
 
 136 MARSH FEVER AND ITS ORGANISM. 
 
 The first advice to be given to a person who is about to travel 
 in a palustral country is to choose his residence carefully, and to 
 take advantage of the fortunate and remarkable influence of alti- 
 tude (see Chap. V, p. 101). 
 
 The site of the house should always be chosen on a height, 
 never in a hollow or in a damp or badly drained plain. The 
 altitude sufficient to preserve against paludism is, after all, not 
 very great. 
 
 In the same town very healthy districts often exist along with 
 particularly unhealthy quarters ; the highest part of the town, the 
 most central streets, and the most inhabited give the maximum of 
 protection. On the contrary, those dwellings which are situated 
 in the lower parts or on the muddy banks of a river should be 
 avoided ; also those which are isolated in the country, especially 
 if situated near marshes or irrigated land. 
 
 In all hot and unhealthy countries, as in India, it has been 
 necessary to establish sanitoria on the heights, where the fever 
 season is passed. 
 
 Those travellers and soldiers who are obliged to cross and live 
 in palustral localities during the endemo-epidemic season should 
 carefully choose their camps, and fix them not on the banks of 
 rivers or in the hollows, but on the highest ground available. 
 
 Persons should avoid travelling near the foci of paludism, and 
 especially avoid spending the night there duriug the endemo- 
 epidemic season. Workmen and reapers obliged to work in 
 unhealthy localities should return to settlements on the heights 
 for the night ; sailors will find an excellent shelter in their ships. 
 
 Drinking-water should be the object of scrupulous attention in 
 palustral localities, and especially during the endemo-epidemic 
 season. If it is not certain that water comes from springs 
 situated in localities free from paludism, it must be carefully 
 filtered or, better still, boiled. 
 
 We have seen that all debilitating causes favour the develop- 
 ment of paludism. 
 
 Great fatigue, excesses of all kinds should be avoided, espe- 
 cially during the endemo-epidemic season, and strengthening food 
 should be used. Alcoholic drinks, which are dangerous in hot 
 countries when taken to excess, are useful in moderate doses to 
 combat the weakening effects of heat. The same may be said of 
 spices and condiments, the use of which is made necessary by 
 the atony of the digestive apparatus, but when taken in excess 
 they may become injurious. 
 
 On account of its tonic properties coffee is an excellent drink
 
 PROPHYLAXIS. 137 
 
 in hot countries, therefore Eastern nations make a very great use 
 of it ; the infusions of coffee and tea have besides the advantage 
 of being made with boiling, and therefore sterilised, water. 
 
 Persons who have already had one or two attacks of fever 
 should redouble precautions to avoid a relapse, which is always 
 to be feared, especially if the anaemia persists. It is advisable to 
 take quinine wine or arsenious acid, or even to undergo a hydro- 
 therapeutic treatment, and on the slightest malaise to return to 
 sulphate of quinine. 
 
 It is not always possible to follow these rules. Many persons 
 are obliged to travel through very unhealthy regions, and even to 
 sojourn there during the fever season. 
 
 The utility of a preventive treatment of paludism is very ob- 
 vious when a person is living in localities where the paludism 
 prevails to such an extent that there is little chance of escaping 
 it, and there is fear that the attacks will become more and more 
 insidious and grave. 
 
 Since quinine can cure paludism and destroy the parasite 
 which has multiplied in the blood, it might be expected that cin- 
 chona and quinine administered as a preventative might hinder 
 the parasites from multiplying in the blood. 
 
 Numerous facts prove that cinchona and quinine which cure 
 paludism can also prevent it. 
 
 In the English navy quinine wine and sulphate of quinine are 
 often employed as a preventive. Each time that men are sent 
 ashore in the tropics they are obliged to take cinchona wine in 
 the morning when quitting the vessel and in the evening on their 
 return. 
 
 To demonstrate the salutary effects of this practice Bryson 
 mentions the following facts: — "Twenty sailors and one officer 
 were to be sent ashore at Sierra Leone to work during the day ; 
 cinchona bark was administered to the sailors, the officer refused 
 to take it, and he was the only one who took the fever. Later 
 two boats were dispatched from the ' Hydra ' to explore the river 
 Sherbo j they were absent a fortnight ; every day in conformity 
 with instructions the men took cinchona wine, and not a single 
 man was attacked with fever, although the region explored was 
 one of the most unhealthy on the coast. The crew of a third boat 
 remained for two days only in the same region and at the samo 
 period, the men had not taken cinchona, and all were attacked 
 except the officer who commanded the boat" (van Buren, "Rap- 
 port a la Commission Sanitairo des titats-Unis," in ' Essais 
 d'Hygiene et de Therapeutique militairos/ by Evans, Paris, 1865).
 
 138 MARSH FEVER AND ITS ORGANISM. 
 
 On the recommendation of Bryson sulphate of quinine has been 
 substituted for cinchona powder in stations on the west coast of 
 Africa. A strong alcoholic solution of sulphate of quinine is 
 poured into several casks of wine, so that 30 grms. of wine con- 
 tain about 0*25 grm. of sulphate of quinine. The reports of the 
 doctors of the Royal British Navy are in general favorable to 
 this new method. 
 
 Quinine and cinchona were employed as a prophylactic during 
 tho War of Secession as long as the troops were called to occupy 
 very unhealthy stations. 
 
 The reports of American military doctors are almost all favor- 
 able to this mode of treatment. 1 
 
 Chamberlain, Wilson, David Merrit, Maylert and Bache, Swift, 
 Thompson, confirm the good effects of quinine in preventing 
 palustral fever. 
 
 Warren gave to 200 men of his regiment 0*30 grm. of sulphate 
 of quinine per day during the fever season ; these 200 men 
 furnished only four cases of paludism. The rest of the regiment, 
 numbering about 400 men, which were not submitted to the pre- 
 ventative treatment supplied more than 300 cases of fever. 
 
 During the summer of 1863, in the campaign of South Carolina, 
 Samuel Logan caused a certain number of men in his regiment 
 to take 0*25 grm. of quinine per day, and he noticed the follow- 
 ing results: — The men who did not take quinine were attacked in 
 the proportion of 25 per cent., those who took it irregularly in 
 the proportion of 39 per cent., those who took it regularly in the 
 proportion of 19 per cent. 
 
 Jilek, of Pola, mentions the following : — " 736 soldiers were 
 lodged in the same barrack in an unhealthy locality ; 500 took 
 o*io grm. of sulphate of quinine each day; they were attacked in 
 the proportion of 18 per cent., whilst those who had not taken 
 quinine were attacked in the proportion of 28 per cent." 
 
 Hertz, of Amsterdam, has observed analogous facts. 
 
 " On the west coast of Africa the officers of the ' Penelope' made 
 an expedition up a marshy river ; all had taken the precaution of 
 taking sulphate of quinine, with the exception of one only who a 
 week after was seized with a violent attack of bilious inter- 
 mittent fever " (Gestin, quoted by Fonssagrives, ' Hygiene 
 navale/ p. 224). 
 
 1 'The Med. and Surg. History of the War of Rebellion,' 1888, vol. i, pp. 
 1 1 1 — 166. 
 
 Longuet, " La prophylaxie de la fievre intermittente par la quinine " (' Semaine 
 mddicale,' 1891, p. 5).
 
 PRornYLAxis. 139 
 
 Thorel has been able to pass through the most unhealthy 
 localities of Mekong, thanks to sulphate of quinine, taken in the 
 dose of o*6o to o"8o grm. each week ; 'and those of his com- 
 panions who took the same precaution likewise escaped palustral 
 fever (Thorel, ' These/ Paris, 1870). 
 
 Bizardel has given new examples of the efficacy of quinine as 
 a prophylactic of paludism. The small doses of quinine which are 
 advised by him cannot be expected to entirely prevent the infec- 
 tion, but much is gained if paludism can be prevented from mani- 
 festing itself in its gravest forms. 
 
 Bizardel repeatedly points out this fact, that even in the most 
 unhealthy regions persons who have taken quinine in prophy- 
 lactic doses have not manifested pernicious symptoms ; but these 
 are the very accidents which are to be feared by men who are 
 isolated and beyond the immediate help of a physician (Bizardel, 
 f De la Quinine comme Prophylactique du Paludisme,' These, 
 Paris, 1888). 
 
 Groeser, who has experimented on the preventative treatment 
 of paludism by quinine in Batavia — that is to say, in one of the 
 most unhealthy regions of the world, — decides in favour of this 
 method. The attacks of fever are much less frequent and much 
 less grave in the sailors who on landing at this dangerous port 
 are submitted to treatment by quinine than in those who neglect 
 this prophylactic measure (Groeser, c Berlin klin. Woch.,' 1888, 42, 
 p. 845 ; and 1889, 53, p. 1065). 
 
 The use of quinine as a prophylactic has been equally recom- 
 mended by Nicolas ( f Chantiers et Terrassements en Pays palu- 
 deens/ Paris, 1888). 
 
 Arsenic has been employed in Italy as a preventative medicine 
 of paludism. Experiments have been made repeatedly on work- 
 men and those employed on the railway and in the army. 
 
 Tommasi Crudeli says he has obtained favorable results with 
 this medicine ( f Rapport presente au Ministre de 1' Agriculture,' 
 Rome, March 18th, 1883). 
 
 In 1883 and 1884 interesting experiments were made in 
 Venetia upon the men of the second company of discipline who 
 had consented to submit themselves to it. Arsenic was taken 
 under the form of arsenical gelatine ; the dose of arsenious acid 
 was raised progressively from 1 to 8 milligrammes, and continued 
 at that dose unless there were gastro-intcstinal symptoms, in 
 which case the medicine was suspended. In 1883 and 1884 a 
 hundred soldiers who had never had fever, and were placed in the 
 same conditions, took part in the experiment. Fifty soldiers
 
 140 MARSH FEVER AND ITS ORGANISM. 
 
 submitted to the preventative treatment by arsenious acid 
 gave foui'teen cases of palustral fever, whilst the rest of the 
 fifty who had not submitted to the treatment furnished nineteen 
 cases. 
 
 The difference between these figures is insignificant, and the 
 sources of error are too numerous (it is impossible to be certain 
 that the conditions were strictly the same in all the individuals 
 in the experiment) for it to be possible to draw a conclusion 
 favorable to the preventative medication by arsenious acid 
 from these investigations {' Journal Italienne de Med. milit.,' 
 1886, 1). 
 
 Sanitary precautions. — It has been seen (Chap. V, p. 98) that 
 paludism has disappeared almost completely from a great number 
 of localities formerly very unhealthy. Examples of this happy 
 transformation abound, not only in Europe, but also in countries 
 where endemic paludism is very severe — for example, in Algeria. 
 
 Among the most efficacious measures of salubrity may be 
 quoted the drying of the morass, drainage, and cultivation of the 
 soil. 
 
 The drying the soil by di'aining it, by mechanical methods, or 
 by cultivatton obviously modifies the media in which the parasites 
 of paludism are developed, and the soil is rendered less susceptible 
 to the multiplication of these agencies. 1 
 
 The drying of a marsh ought only to be made with method and 
 with great precautions — above all in a hot country ; the season in 
 which the palustral epidemic does not prevail, or exists only 
 with least intensity, should be chosen, and care should be taken 
 not to uncover a great surface of the marsh during the hot season ; 
 the marsh is, indeed, much more dangerous when it begins to dry 
 than when it is covered with water. The example of Lancisi, 
 causing the ditches of Fort Saint Ange to be filled to assuage 
 the ravages of paludism is well known ; in Holland the same 
 means have been employed more than once with success. 
 
 During the drying of the marsh the workmen should not pass 
 the night in its midst, and they should be submitted to the pre- 
 ventative treatment with quinine during the fever season. 
 
 Regular cultivation at all times makes the soil healthy, but 
 certain trees and shrubs are particularly good for this purpose. 
 
 The plantations of eucalyptus which have been made during 
 
 1 Graves, ' Clinical Medicine,' vol. i, pp. 97-98. Colin, ' Traite des fievres 
 intermittentes,' 1870. Laveran, ' Traite des fievres palustres,' p. 521. Thevard, 
 ' De l'influence des transformations agricoles de la Sologne sur la diminution des 
 fievres intermittentes,' These, Paris, 1886.
 
 PROPHYLAXIS. 141 
 
 the last twenty years in a great number of palustral countries 
 have already rendered great service, notably in Corsica, in Al- 
 geria, and in Italy. 1 
 
 From 1 86 1, Kamel has considered eucalyptus to be capable of 
 combating paludism ; the credit belongs to him of having imported 
 the Eucalyptus globulus into our country. 
 
 Torelli has mentioned the following fact, which is a good ex- 
 ample of the great influence exercised by plantations of euca- 
 lyptus : — Near Rome, outside the gate of Ostia, in a place called 
 the Three Fountains, there is a convent which in 1868 had been 
 abandoned for a long time on account of its insalubrity, and 
 which bore the significant name of Tomba. Pope Pius IX gave 
 this convent to the Trappist monks who took possession of it, but 
 in these deplorable circumstances. For the first few years it was 
 so unhealthy that the monks could not sleep there, being obliged 
 to spend the night in Rome, not returning to Three Fountains 
 till after sunrise. 
 
 The first plantations of eucalyptus were made in 1869. In 
 1876 the improvement was such that the Trappists could stay the 
 night in the convent without being attacked by fever. In 1877 
 the number of trees exceeded 2500. A space of 988 acres was 
 then allotted to the Trappists, with the condition that they 
 should plant 100,000 trees in ten years. In 1879 the plantation 
 suffered much from frost, but during the following years the 
 Trappists planted 25,000 trees each year; and at the end of 1881 
 there were already 55,000 eucalyptus trees at Three Fountains, 
 and palustral fevers were becoming rarer. 
 
 The salubrity of the farm of Three Fountains has been disputed 
 by Tommasi Crudeli, but his assertions are contradicted by Torelli 
 and Baccelli and by the monks who live in the convent of Three 
 Fountains, and who are well able to judge in tho matter (' Bull, 
 de la Soc. Nationale d'Acclimatation/ Jan., 1885). 
 
 Michon has given two very interesting and convincing examples 
 of palustral localities being made healthy by the planting of euca- 
 lyptus ('Bull, de la Soc. Nat. d'Acclimatation,' Jan., 1885). A 
 great property situated on the east coast of Corsica, near to 
 Algeria and to the penitentiary of Casabianca, was uninhabitable 
 
 1 Ramel, 'Revue maritime et commerciale,' 1861. Regulus Carlotti, ' l>u 
 mauvais air en Corse,' Ajaccio, 1869. Ortal, 'De I'Eucalyptus globulus,' These, 
 
 Paris, 1874. Gimbert (de Cannes), ' Gaz. liebdoin.,' 1875, p. 340. Torelli, ' Kap- 
 port au Senat Italien sur ['amelioration ties regions an regno la malaria,' [880. 
 Charming, " Etiologie et prophylaxie de la malaria," ' Gazette mcdicalc de L'AlgeVie,' 
 April 30th, 1884. De Jardin-Beaumetz, article "Eucalyptus" in 'Dictionn.de 
 therapeutique.'
 
 142 MAllSH FEVEE AND ITS ORGANISM. 
 
 on account of fever ; even the warden himself refused to remain 
 there during the summer. The owner had planted before the 
 guard-house a small plantation of from 200 to 300 eucalyptus, and 
 from 400 to 500 along a river. These plantations have flourished, 
 and now the warden is able to live there with his family, summer 
 as well as winter. The workmen who come down from the moun- 
 tain to work in the vineyards on this same property, which was 
 formerly so unhealthy, do not contract the fever. 
 
 On the east coast of Corsica there is a small place of the name 
 of Solenzara, in which steel-works were established. When the 
 works were begun to be set up all the population were in the 
 habit of emigrating for four months — from July to October, — 
 which showed clearly how fearful the palustral endemic was. 
 One of the owners caused sixty acres to be planted with euca- 
 lyptus ; since then the fever has disappeared from Solenzara. All 
 the population are prosperous, and no one now thinks of emigrat- 
 ing during the summer. 
 
 In certain localities extremely favorable to the development 
 of paludism the plantations have not succeeded in completely dis- 
 pelling the fever. 
 
 Riviere, who has disputed the febrifuge properties of the euca- 
 lyptus plantations, giving as his argument the persistence of the 
 fever at Am Mokra and at the mines of Mokta (on the Lake of 
 Fetzara in the province of Constantine), has himself furnished the 
 explanation of their non-success, which is after all relative, be- 
 cause the plantations of eucalyptus have even at Mokra produced 
 an improvement in the sanitary condition. "We have planted 
 the banks of the Fetzara," writes Riviere, " but the plantation 
 was required to be kept at a certain distance from the maximum 
 limit of water, which inereases suddenly owing to the torrential 
 overflowing of the Oued-Zid and El-Aout into the immense basin. 
 The waters cover more than 34,580 acres, and are displaced by- 
 certain winds, but the natural escape and the loss produced by 
 rapid evaporation cause immense miasmatic surfaces to be laid 
 bare, thus producing, through an absolutely direct isolation and 
 rise of temperature, nioi'bific elements against which the recent 
 plantations on its banks are quite futile (' Bull, de la Soc. Nat. 
 d'Acclimatation,' January, 1885). Riviere considers that in 
 these conditions it would be advantageous to plant bamboos first, 
 in order to circumscribe and to reduce by degrees the central 
 basin. 
 
 The example of Ain Mokra cannot be quoted against the 
 eucalyptus; it is evident that it could not be expected to make
 
 OBSERVATIONS. 143 
 
 the region completely salubrious by planting eucalyptus upon 
 the banks of such an immense marshy surface as Riviere 
 speaks of. 
 
 The Eucalyptus globulus is the best known of the eucalypti ; 
 it is that which was first introduced into Europe, and is chiefly 
 used in the old plantations : in the new plantations the E. globu- 
 lus has been replaced by the E. rostrata, mainly in Algeria. The 
 E. globulus does not resist cold or great heat ; it requires good 
 ground, neither dry nor too wet, and perishes rapidly in too 
 marshy a soil. The E. rostrata is more hardy (Riviere, op. cit.) . 
 
 Does the eucalyptus act simply as other vegetation by draining 
 and drying the soil ? If the soil is rendered more rapidly salu- 
 brious by it than by other trees, is it only because its growth 
 is more rapid, or must it be admitted that it has special virtues, 
 and that it enjoys the property of destroying the parasites 
 of paludism ? This latter hypothesis is in itself not unlikely. 
 The eucalyptus, in fact, gives out aromatic vapours which possess 
 antiseptic properties ; besides, the leaves and the branches which 
 cover the soil contain a large proportion of eucalyptol, which may 
 prevent the development of the germs of paludism. 
 
 The influence of sulphur mines upon paludism has been pointed 
 out by d'Abbadie. It appears, from the facts quoted by him, that 
 the sulphurous emanations which are produced in the neighbour- 
 hood of sulphur mines have a favorable effect in palustral countries 
 (' Commun. a l'Academie des Sciences/ September 18th, 1882). 
 This action of sulphurous acid is easy to understand ; unfor- 
 tunately it does not seem that it can be used to render localities 
 healthy. 
 
 In speaking of the individual prophylaxis I have already said 
 that in palustral countries it is necessary to watch carefully the 
 drinking-water, which seems to serve as the vehicle of the germs 
 of paludism ; to the general rules for making a locality healthy 
 the necessity for providing that locality with water of good quality 
 must, therefore, be added. 
 
 OBSERVATIONS. 
 
 Obs. 1. — Continued palustral fever, first attack. Hsemato oa 
 of paludism ; spherical bodies. 
 
 Ven., aged 24, a soldier in the fifth train of artillery, admitted 
 to the military hospital of Constantine on August 8th, 1881. 
 
 Ven. has been in Algeria for eighteen months. He is in the 
 barracks at Bardo ; says he is ill for the first time.
 
 144 MARSH FEVER AND ITS ORGANISM. 
 
 Four days ago Ven. had severe shivering, which has not been 
 repeated since ; at the same time he felt very severe head- 
 ache, general malaise ; the fever would have persisted from that 
 moment without any very prominent remissions ; very strong sen- 
 sation of heat, great thirst, and anorexia. Before entering 
 hospital the patient has taken only one emetic. 
 
 On the evening of August 8th, when he was admitted, the 
 temperature was 40 C. (diet lemonade). 
 
 9th. — Severe fever continued; 40 C. in the morning, 41 ^C. 
 at four in the afternoon. Headache ; general malaise ; no stupor ; 
 no pronounced prostration ; great thirst ; tongue moist, a little 
 furred ; abdomen soft, without pain ; no diarrhoea. The splenic 
 dulness measures 7 centimetres vertically by 7 in width. Diet 
 lemonade ; sulphate of quinine o - 8o grm. morning and evening. 
 
 Examination of the blood made on morning of the gth : spherical 
 bodies of small or average size, free or adherent to blood- 
 corpuscles. 
 
 10th. — The fever persists ; 40* i° C. morning, 39*3° C. evening. 
 Sulphate of quinine o'8o grm. morning and evening. 
 
 nth. — The fever is falling; 36*8° C. morning; in the evening 
 the apyrexia persists. The general state is much improved ; 
 headache and the general malaise have disappeared (sulphate 
 of quinine o'8o grm. morning and o*6o grm. evening). 
 
 12th. — The apyrexia persists. The patient only shows weak- 
 ness. He begins to get up. (Half a dose of sulphate of quinine 
 o*6o grm. ; quinine wine.) 
 
 The sulphate of quinine is continued in doses of o*6o grm. until 
 the 1 8th. No relapse of fever. Appetite returns ; the patient 
 oats one ration, then two are given ; quinine wine, coffee. 
 
 Examination of blood made on September 2nd : I do not find 
 any more trace of parasitic elements. 
 
 The patient, who feels strong enough to resume service, goes 
 out on September 3rd, 1881. 
 
 Obs. 2. — Palustral continued fever, first attach. Hsematozoa 
 of pahidism ; spherical bodies of very small size. 
 
 Rud., aged 22, soldier in the fifth train of artillery, is admitted 
 to the hospital of Constantino on September 18th, 1881. 
 
 Rud. arrived in Algeria on December 10th, 1880. He has been 
 well till now ; is in the Bardo barracks. 
 
 On September 16th, at 4 in the evening, headache; general 
 malaise ; sensation of heat ; great thirst ; no shivering. 
 
 On 1 7th the fever persists. The patient has not taken sulphate 
 of quinine before entering the hospital.
 
 OBSERVATIONS. 145 
 
 18th. — The fever persists ; at 1.30 in the evening the axillary 
 temperature is 40° C. Headache ; general malaise ; anorexia ; 
 excessive thirst. The area of splenic dulness is 9 cm. in length 
 by 12 cm. in breadth. 
 
 19th. — 38 C. in the morning, 39 C. in the evening. 
 
 20th. — 39*8° C. in the morning. The patient has not taken 
 any sulphate of quinine since he came to the hospital. 
 
 The examination of blood made on 20th at 9 a.m. shows 
 spherical bodies of very small size, mostly non-pigmented, and 
 adherent to the blood-corpuscles, which look like pricked or 
 pierced corpuscles. Melaniferous leucocytes. Sulphate of quinine 
 r6o grm. on two occasions. 
 
 21st. — 36'4° C. in the morning. The apyrexia persists in the 
 evening. Sulphate of quinine o - 8o grm. in the morning and 
 evening. 
 
 22nd. — Another attack of fever, but very slight; the tem- 
 perature only rises to 38'6° C. Sulphate of quinine o'8o grm. 
 morning and evening. No return of fever. The sulphate of 
 quinine is continued in doses of o*6o grm. till 29th. 
 
 The patient leaves the hospital on October nth. 
 
 Obs. in. — Continued palustral fever, first attack. Hsematozoa 
 of paludism ; spherical bodies of very small size. 
 
 Fo., aged 22, a soldier in the third squadron of artillery, is 
 admitted to the Constantine Hospital on September 27th, 1881. 
 
 Fo. has been in Algeria five months. On the morning of the 
 25th shivering ; headache ; bilious vomiting. 
 
 On the 26th the vomiting repeated ; general malaise ; head- 
 ache ; weakness ; vertigo when standing ; great thirst. The 
 patient has not had any quinine before entering the hospital. 
 
 27th. — Very high fever, 40*2° C. in the morning, 40 C. in the 
 evening ; stupor without delirium ; jaundiced hue of the skin and 
 of sclerotic. The splenic dulness is 9 cm. by 9 cm. 
 
 28th. — 38"4° C. in the morning, 40*6° C. in the evening ; typhoid 
 state very pronounced, without abdominal symptoms. Examina- 
 tion of the blood at 2 p.m. shows very small spherical bodies, 
 having only sometimes 1 mm. diameter, adherent to the blood- 
 corpuscles, non-pigmented, or only containing one or two granules 
 of pigmcut ; melaniferous leucocytes; no orescent-shaped bodies. 
 Sulphate of quinine o'8o grm., the 28th, in the evening. 
 
 29th. — 39*2° C. in the morning, 39"3°C. in the evening; typhoid 
 state. Sulphate of quinine o'8o grm. morning and evening. 
 
 30th. — Apyrexia. The general state is more satisfactory, 
 Sulphate of quinine o'8o grin, morning and evening. 
 
 10
 
 146 MAESH FEVER AND ITS OBGANISM. 
 
 On October ist the temperature rises again to 39'3° C. in the 
 evening ; but from the 2nd the subsidence is complete, and 
 the general state improves rapidly ; the icteric hue disappears ; 
 strength and appetite come back. The sulphate of quinine is 
 continued till the gth. 
 
 The patient leaves the hospital on the 27th. 
 
 Obs. iv. — Continued palustral fever, first attach. Haematozoa 
 of paludism ; spherical bodies. 
 
 Quin., aged 22, soldier in the eleventh squadron of artillery, is 
 admitted to the hosptial of Constantine on October 11th, 1881. 
 
 Quin. has been in Algeria nine months ; says he is ill for the 
 first time; for a month he has not left the Bardo. On 11th he 
 came to the hospital ; four days before he had an attack of 
 headache ; lumbago ; general malaise ; heat without shiver ; 
 great thirst ; anorexia ; slight diarrhoea. The patient says he 
 has not taken any sulphate of quinine before he entered the 
 hospital. The patient was only admitted on 11th, and comes 
 through urgency. 
 
 11th. — I saw the patient at 4 p.m. The fever was very 
 high, 40 C. ; very great headache and much malaise ; moist 
 tongue, furred ; great thirst ; anorexia ; a little diarrhoea ; no 
 pain in the right iliac fossa ; no pink blotches ; the splenic dul- 
 ness is 12 cm. in height by 11 cm. in breadth (diet, lemonade). 
 
 12th. — The fever persists; at 6 a.m. the temperature still at 
 38*3° C. ; at 4 p.m. the thermometer in axilla registered 4i'2° C. 
 (diet, lemonade). Sulphate of quinine o - 8o grin, morning and 
 evening. 
 
 Examination of the blood made on the- 12th at 8*30 a.m. : 
 spherical bodies, of average or small size, free or adherent to 
 blood-corpuscles ; no crescent-shaped bodies. 
 
 13th. — In the morning the fever fell to 37*3° C, in the evening 
 another slight febrile movement was noticed ; at 4 in the evening 
 the temperature was 38'8° C. Broths ; sulphate of quinine o"8o 
 grm. morning and evening. 
 
 14th. — 37*7° in the morning, 36*9° C. in the evening. General 
 state very satisfactory ; a little appetite ; half a dose of sulphate 
 of quinine o - 8o grm. morning and evening. 
 
 The sulphate of quinine is continued in dose of o'6o grm. until 
 the 22nd. No relapse. 
 
 The patient went out on the 28th. 
 
 Obs. v. — Continued palustral fever, first attack-. Hsematozoa 
 if j>aludisvi ; spherical bodies of very small size. 
 
 Mor.j aged 24, soldier in the eighth company of mounted
 
 OBSERVATIONS. 147 
 
 troops, is admitted to the Constantino Hospital on August 7th, 
 1882. 
 
 Mor. has been nine months in Algeria. He works in the 
 company's garden. From August 1st general malaise; head- 
 ache. On the 4th general malaise and headache increased, which 
 obliged patient to go to bed. From that time fever seems to 
 have persisted without complete remissiou. There has been 
 no shiver ; headache ; great thirst ; complete anorexia. The 
 patient took before coming to the hospital o'8o grm. of suphate 
 of quinine. 
 
 7th. — High fever; 39/9 C. at 12 midday; same temperature 
 at 4 p.m. Typhoid state without abdominal symptoms ; very 
 severe headache ; prostration. The area of the splenic dulness 
 is 12 cm. by 13 cm. 
 
 The examination of the blood made on the 7th at 2 p.m. 
 showed very small spherical bodies in great numbers adherent to 
 the blood-corpuscles. Many of these bodies are not pigmented ; 
 the others only contain one or two granules of pigment. Two or 
 three of these bodies are often found in the same blood-corpuscle. 
 Melaniferous leucocytes. Sulphate of quinine 1 grm. at 7 p.m. 
 
 8th. — The fever persists, but is not so strong ; 38*4° C. in the 
 morning, 38'8° C. in the evening. Sulphate of quinine o - 8o grm. 
 morning and evening. 
 
 gth. — 36*8° C. in the morning, 39 C. in the evening. Sulphate 
 of quinine o*8o grm. 
 
 10th. — Apyrexia, which persists on the following days. 
 Sulphate of quinine is continued till the 18th, and resumed 
 from the 24th to the 30th. 
 
 The patient left the hospital on September 4th, 1882. 
 
 Ota. VI. — Quotidian intermittent fever, first attack, llaimatozoa 
 of pallidum, ; spherical bodies ; jlagella, 
 
 Yv., aged 23, soldier in the third zouaves, admitted to the 
 Constantine Hospital August 4th, 1881. 
 
 Yv. has been two years in Algeria. First attack of fever 
 July 28th last year. Headache ; general malaise ; great thirst ; 
 heat. 
 
 On August 3rd, for the first time, Yv. has had a very 
 characteristic attack of fever with initial rigors, heat, and per- 
 spiration. 
 
 4th. — New attack of fever at 10 a.m.; shivering; the axillary 
 temperature was then 41*3° C, at 4 p.m. 40 C. 
 
 Examination of the blood, made at 2.30 p.m., showed 
 spherical bodies free or adherent to blood-corpuscles. Many of
 
 148 MARSH FEVER AND ITS ORGANISM. 
 
 these elements are very small ; no crescent-shaped bodies. The 
 splenic dulness is n cm. by 14 cm. 
 
 5th. — 36'8° C. in the morning. At noon shivering ; at 1 p.m. 
 the axillary temperature is 40*4° C. ; at 4 p.m. it is still 40' 2° C. 
 Examination of blood, made on the 5th, 9 a.m, (before the 
 onset of the attack). Numerous spherical bodies, free or ad- 
 herent to blood-corpuscles ; spherical bodies containing mobile 
 pigmented granules ; flagella. Sulphate of quinine r6o grm., in 
 two doses. 
 
 6th. — Apyrexia morning and evening. Very pronounced 
 antemia ; general weakness. Sulphate of quinine 1*40 grm. 
 
 On the following days the apyrexia persists, The sulphate of 
 quinine is continued in doses of o"6o grm. until August 14th. 
 Examination of blood made on August 1 7th ; I do not find any 
 more traces of parasitic elements. The patient leaves the hos- 
 pital on September 5th. 
 
 Obs. vii. — Palustral fever, first attack. Hsematozoa of pain- 
 dism ; spherical bodies ; flagella. 
 
 Cour., aged 22, soldier in the 47th of the line, admitted to the 
 Constantine Hospital August 8th, 1881. 
 
 Cour. has been three weeks in Algeria. He says he has been 
 ill for three days ; shiverings at the commencement, headache, 
 vomitings, general malaise, intense thirst, anorexia. The patient 
 has not taken quinine before being admitted. 
 
 On August 8th, at 1 1 a.m. the axillary temperature is 39*8° C. ; 
 apyrexia at night. The splenic dulness measures 12 cm. by 11. 
 Examination of blood made August 8th at 3 p.m. at the end of the 
 onset of fever ; spherical bodies free or adherent to blood-cor- 
 puscles ; some of these elements contain mobile granules of 
 pigment, or show at their periphery flagella accompanied with 
 very rapid movements ; melaniferous leucocytes. Sulphate of 
 quinine o*8o grm. at 8 p.m. 
 
 9th. — Apyrexia. The patient does not show anything more 
 than weakness ; anaemia very marked. Sulphate of quinine 1*40 
 grm.; the sulphate of quinine is continued in doses of o"6o grm. 
 daily up to August 16th. There is no relapse. The patient 
 went out on August 26th, 1881. 
 
 Obs. vin. — Intermittent fever ; quotidian, first attack. Hsema- 
 tozoa of pal/udism ; spherical bodies ; flagella. 
 
 Sain., aged 23, soldier in the 3rd chasseurs of Africa, entered 
 the Constantine Hospital on September 20th, 1881. 
 
 Sain, lias been in Algeria twenty-three months. JMo former 
 grave illnesses. He was ill with fever the first time on September
 
 OBSERVATIONS. 149 
 
 6th, on coming back from accompanying a convoy to the Oued- 
 Athmenia. From September 6th to 20th the patient has been 
 attended to at the corps visit. 
 
 20th. — Fever very high ; at i p.m. 40'8° C. ; at 4 p.m. 39*4° C. 
 Headache ; thirst excessive. No abdominal symptoms. The 
 splenic dulness measnres 11 cm. by 14 cm. Profuse sweating 
 on the evening of the 20th (diet, lemonade). 
 
 2 1 st. — Fever has fallen; morning 36'3 C. The malaise and 
 the headache have disappeared. Sulphate of quiniue o'So grm. 
 at morning and evening. New attack during the day ; at 4 p.m. 
 temperature is 40 C. Examination of blood made on the 
 morning of September 21st (before taking sulphate of quinine) ; 
 spherical bodies free or adherent to blood-corpuscles ; spherical 
 bodies containing pigmented granules, mobile or provided with 
 fiagella ; free flagella ; spherical bodies of very small volume con- 
 taining sometimes only one or two pigmented granules, free or 
 adherent to the blood-corpuscles. 
 
 22nd. — 37 C. morning ; in evening apyrexia persists. Sulphate 
 of quinine o*8o grm. morning and evening. 
 
 23rd. — The apyrexia persists ; profound anaemia ; earthy look 
 on the face ; mucous membrane pale. General weakness ; tongue 
 moist ; neither diarrhoea nor constipation. A little appetite (one 
 dose; sulphate of quinine o"8o grm. ; quinine wine). 
 
 24th. — The apyrexia persists. Sulphate of quinine is con- 
 tinued in doses of o - 6o grm. each day to September 30th ; quinine 
 wine, coffee. No relapse. Went out October 3rd, 1881. 
 
 Obs. ix. — Quotidian intermittent fever, first attach. Hsematozoa 
 of paludism ; crescent-shaped bodies ; spherical bodies. 
 
 Coi., aged 23, soldier in the 3rd zouaves, entered the hospital 
 of Constantine July 20th, 1882. 
 
 Coi. has been eight months in Algeria. Was attacked with 
 fever for the first time six days ago ; intermittent, quotidian 
 fever very characteristic ; came on with initial shivering, re- 
 turned towards 10 a.m. The patient has taken three doses of 
 sulphate of quinine before he entered the hospital. 
 
 20th. — At 4 p.m. 30/2 C. Headache very marked ; general 
 malaise, feebleness, diarrhoea; tender spot in the region of the 
 spleen. The area of splenic dulness measures 12 cm. by 15 cm. 
 Sulphate of quinine o'8o grm. 
 
 2 1 st. — Apyrexia. Sulphate of quinine 0'8o grm. morning and 
 evening. Examination of blood made at 2 p.m. ; crescent- 
 shaped bodies ; spherical bodies of average size, some of these 
 elements contain mobile granules of pigment ; spherical bodies
 
 150 MARSH FEVER AND ITS ORGANISM. 
 
 of very small size, free or adherent to blood-corpuscles. Melani- 
 ferous leucocytes. 
 
 22nd. — The apyrexia persists. Anaemia very marked ; the 
 patient has vertigo whenever he attempts to l'aise himself ; ring- 
 ing in the ears. Sulphate of quinine is continued in doses of 
 o*8o grm., afterwards o*6o grm., till July 28th, and resumed from 
 August 6th to 10th. No relapse of fever. Patient went out on 
 August nth, 1882. 
 
 Obs. x. — Quotidian intermittent fever, first attach. Hsematozoa 
 of paludism ; crescent-shaped bodies; spherical bodies. 
 
 Del., aged 24, soldier in the eighth company of mounted 
 troops, admitted to Constantine Hospital on July 7th, 1882. 
 
 Del. arrived in Algeria in January, 1882. Was very healthy 
 till then. First attack of fever on July 1st at 9 a.m.; regular 
 attack with initial shivering at beginning ; new attacks on follow- 
 ing days. The patient took a dose of sulphate of quinine before 
 entering the hospital. 
 
 July 7th. — At 4 a.m. the axillary temperature 38 - 8° C. (end of 
 the attack). 
 
 8th. — New attack ; the axillary temperature rises to 40 C. The 
 area of splenic dulness measures 14 cm. by 15 cm. Apyrexia 
 from July gth to 10th, which might be attributed to the dose of 
 quinine taken before admission to the hospital. 
 
 nth. — Attack of fever; at 3.30 p.m. 39*5° C. ; at 6.30 p.m. 
 39-8° C. 
 
 12th. — Apyrexia. Sulphate of quinine 0*80 grm. morning and 
 evening. Examination of blood on the morning of July 12th; 
 numerous crescent-shaped bodies, sometimes three or four in the 
 field of the microscope ; spherical bodies of average size, but not 
 many. 
 
 13th. — New attack of fever; at 1.30 p.m. 39"6° C. ; at 6 p.m. 
 37*4 C. Sulphate of quinine was continued in doses of o*8o grm. ; 
 afterwards o-6o grm. till July 20th. No relapse. The patient 
 went out on July 20th. 
 
 Obs. xi. — Palustral fever, first attach ; continued form- of inter- 
 mittent fever witJt subintrant attachs. Hsematozoa of paludism ; 
 crescent-sliaped bodies. 
 
 N., soldier in the 3rd zouaves, aged 24, admitted to the 
 hospital of Constantine July 24th, 1881. 
 
 N. has been three years in Algeria ; says he is a patient for 
 the first time. On July 20th he felt some headache, general 
 malaise, a violent heat without shivering and without regular 
 jtttacks. According to the patient, the fever has persisted with-
 
 OBSERVATIONS. 151 
 
 out notable remission till admission to the hospital. At the time 
 when the illness took place the patient was drafted to Ain- 
 el-Bey, i. e. in a notoriously unhealthy locality. Before entering 
 the hospital N. took an ipecac, emetic ; no sulphate of quinine. 
 From July 23rd the patient has had several attacks of vomiting, 
 and without having taken any vermicide has vomited long frag- 
 ments of trenia. 
 
 24th. — Very intense fever ; 40*6° C. in the morning, 40*4° C. in 
 the evening. General malaise, great and intense headache, no 
 stupor, intense thirst, anorexia, no diarrhoea ; belly soft, without 
 pain. The spleen has notably increased in size (diet lemonade). 
 
 25th. — Fever persists ; 38*6° C. in the morning, 4r3° C. in the 
 evening. Headache, anorexia, intense thirst (diet, lemonade). 
 Sulphate of quinine o*8o grm. 
 
 26th. — 39' i° C. in the morning, 37*1° C. in the evening. Sul- 
 phate of quinine o # 8o grm. in the morning, 0'6o grm. in the 
 evening. 
 
 27th. — 37 C. in the morning. In the evening apyrexia persists. 
 Half a dose of sulphate of quinine o"6o grm. 
 
 28th. — Apyrexia in the morning. The patient takes o*6o grm. 
 sulphate of quinine. In spite of that he has an attack during 
 the day at 4 p.m. Axillary temperature is 39*7° C. Sulphate 
 of quinine o*8o grm. in the evening. 
 
 29th. — Apyrexia persists ; 37 C. in the morning. Examination 
 of blood on July 29th. Crescent-shaped bodies ; melaniferous 
 leucocytes. Sulphate of quinine o'8o grm. morning and evening. 
 
 30th. — Apyrexia persists. Appetite and strength come back. 
 One dose ; sulphate of quinine o*6o grm., cinchona wine. The 
 sulphate of quinine is continued in doses of o*6o gr. until August 
 5th. Cinchona wine, coffee. During all the month of August 
 the apyrexia persists. Aneemia disappears little by little. Exa- 
 mination of blood on August 31st. No more parasitic elements. 
 Patient went out September 1st, 1881. 
 
 Obs. xii. — Quotidian intermittent fever, first attack. Hsematozoa 
 of paludism ; crescent-shaped bodies. 
 
 P., aged 21, soldier in third zouaves, entered the Constantino 
 Hospital July 25th, 1882. P. has been eight months in Algeria ; 
 says he is ill for the first time since he came. On July 22nd ho 
 was attacked about 6 a.m. with shivering, accompanied by general 
 malaise, headaches, and bilious vomiting ; heat after the shivers ; 
 great thirst ; the fever persisted on July 23rd and 24th. The 
 patient took on the 24th, at Ain-el-Bey, ten pills containing 
 sulphate of quinine, and came to Constantine.
 
 152 MAESH FEVER AND ITS ORGANISM. 
 
 July 25th. — Attack of fever 3S'4° C. at 9.30 a.m. ; 30/8 C. at 
 noon ; 37*9° C. at 4 p.m. Very profound anaemia; general weak- 
 ness. Sulphate of quinine o - 8o grm. in the evening. 
 
 26th. — A new onset of fever which began at 5 a.m. ; at 6 a.m. 
 39*8° C. ; at noon 40 C. ; at 4 p.m. 38*4° C. Examination of 
 blood at 8 a.m. on July 26th. Crescent-shaped bodies; numerous 
 melaniferous leucocytes. Sulphate of quinine r6o grm. in two 
 doses. 
 
 27th. — Apyrexia ; general weakness very marked ; the patient 
 can only stand with difficulty. On the following days the apyrexia 
 persisted ; strength and appetite returned. Sulphate of quinine 
 was continued till August 4th, o*8o grm. ; afterwards o'6o grm. 
 doses. 
 
 August 1 8th. — A slight attack. Sulphate of quinine was given 
 again, and continued till August 27th. No fresh relapse. Patient 
 leaves hospital on August 29th on sick leave. 
 
 Obs. xiii. — Quotidian intermittent fever, first attack. Hsema- 
 tozoa of jialudism ; crescent-shaped bodies. 
 
 Vand., aged 29, a soldier in the third African battalion, entered 
 the Constantine Hospital on August 16th, 1882. 
 
 First attack of fever on August nth; daily attacks from 
 August 11th to 15th. The attacks were very characteristic; 
 they were i*epeated every day at about 8 a.m. The patient took 
 two doses of sulphate of quinine before entering the hospital. 
 
 August 1 6th. — Apyrexia; anaemia; general weakness; ano- 
 rexia. The splenic dulness measures n cm. by 13 cm. I pre- 
 scribed nothing but cinchona wine. Apyrexia persisted till 
 August 20th. 
 
 20th. — Attack of fever; 39*3° C. at 8 a.m. ; 41 C. at 1 1.30 a.m. ; 
 40*8° Cat 4 p.m. Examination of blood at 8.30 a.m Crescent- 
 shaped bodies. New examination of blood on the same day at 2 p.m. 
 Crescent-shaped bodies ; oval bodies derived from crescent-shaped 
 bodies ; melaniferous leucocytes. The sulphate of quinine was 
 prescribed from the evening of August 20th until August 28th. 
 On August 22nd the patient had another slight attack. The 
 patient left the hospital on September 1st on sick leave. 
 
 Obs. xiv. — Quotidian intermittent fever {relapse). Hoematozoa 
 of paludism ; spherical bodies. 
 
 Du., aged 22, soldier in second regiment of artillery, is admitted 
 to the hospital of Constantine on May 20th, 1882. 
 
 Du. has been in Algeria from April 10th, 1881. First attack 
 of fever at Bona on July, 1881, quotidian intermittent fever, 
 very characteristic, which was treated by sulphate of quinine.
 
 OBSERVATIONS. 153 
 
 Relapse of fever on April 28th, 1882, quotidian intermittent 
 fever. Sulphate of quinine. Fresh relapse on May 19th. Attacks 
 on May igth and 20th. 
 
 May 20th. — At 2 p.m. the axillary temperature is 40 C, at 4 
 p.m. 38*2° C. Examination of blood on May 20th at 2.30 p.m. ; 
 pretty numerous spherical bodies of average or small size, free or 
 adherent to blood-corpuscles. Melaniferous leucocytes. 
 
 21st. — Fresh attack of fever; at 7 a.m. shivering, when the 
 axillary temperature was 30/4 C, at 4 p.m. 38*8° C. ; sweating. 
 Examination of blood on May 21st at 8.30 a.m. gave the same 
 results as the examination on May 20th. Sulphate of quinine 
 o*8o grm. on May 21st in the evening. 
 
 22nd. — Apyrexia ; very marked anemia, general weakness, 
 anorexia. The area of splenic dulness is 14 cm. by 13 cm. 
 Sulphate of quinine o"8o grm. morning and evening. 
 
 On the following days the apyrexia persists ; the quinine was 
 prescribed in a dose of o*6o grm. till May 26th. The examination 
 of the blood made on June 2nd does not show the existence of 
 any parasitic elements. Relapse of fever on June 9th ; shiver- 
 ing at midday; at 1 p.m. the axillary temperature was 40^9° C. 
 
 Examination of blood made June gth at 2 p.m. ; spherical 
 bodies of small or average size, free or adherent to red blood- 
 corpuscles. As in the previous examination, no crescent-shaped 
 bodies were found. On June 9th, at 5.30 p.m., the axillary tem- 
 perature was 38*2° C. 
 
 June 10th. — 37 C. in the morning ; at midday new attack ; at 
 
 1 p.m. 40*9 C.° ; at 4 p.m. 38*2° C. Examination of blood at 
 
 2 p.m. ; same results as in previous examination. Spherical 
 bodies of small or average size, free or adherent to blood-cor- 
 puscles. Sulphate of quinine is prescribed from June 10th to June 
 19th, o*8o grm. first, then o'6o grm. No fresh attack of fever. 
 
 Obs. xv. — Quotidian intermittent fever (relapse). Hsematozoa 
 of paludism ; spherical bodies ; segmented bodies. 
 
 C, aged 32, soldier of the eighth squadron of artillery, ad- 
 mitted to Constantine Hospital on August 18th, 1881. 
 
 C. has been in Algeria from December nth, 1880, located at 
 Bardo. First onset of intermittent fever last July 20th. Quo- 
 tidian intermittent fever from July 20th to 30th. The patient 
 has been treated with sulphate of quinine. Relapse on August 
 15th; regular attacks on August 15th, 16th, and 17th at 10 
 a.m. Before coming to the hospital the patient has had several 
 doses of sulphate of quinine. 
 
 1 8th. — High fever ; 41° C. at midday ; 40*4° C. at 4 p.m. Very
 
 154 MARSH FEVER AND ITS ORGANISM. 
 
 severe headache. The splenic dulness was 7 cm. by 12 cm. Ex- 
 amination of blood on August 18th, at 2 p.m. showed amoeboid 
 bodies containing frequently mobile pigmented granules. These 
 spherical bodies of different sizes were free or adherent to blood- 
 corpuscles ; bodies of the size of a red blood-corpuscle showing in 
 the centre a heaping up of pigment and all around round shining 
 corpuscles (segmented bodies). Sulphate of quinine was pre- 
 scribed from the evening of August 18th to 26th. No new attacks. 
 
 September 3rd. — Anaemia was still very marked. The exami- 
 nation of the blood on September 3rd did not reveal any more 
 parasitic elements. The patient was discharged on September 
 10th, 1 88 1. 
 
 Obs. xvi. — Quotidian intermittent fever {relaj>se). Hsematozoa 
 of paludism ; spherical bodies ; segmented bodies. 
 
 Rob., aged 24, soldier in the third squadron of artillery, was 
 admitted to the Constantine Hospital November 15th, 1881. 
 
 Rob. has been two years in Algeria. First onset of fever in 
 August, 1 88 1 ; from that time the patient has had several re- 
 lapses of fever, and took for each several doses of quinine. 
 Since November 3rd regular quotidian attacks with initial rigors 
 beginning towards 4 a.m. The patient took several doses of 
 sulphate of quinine before entering the hospital. 
 
 15th. — Attack of fever at 4 p.m.; 30/7° C. Very marked 
 anaemia ; general weakness. The splenic dulness was 12 cm. 
 by 14 cm. 
 
 1 6th. — 37"9° C. in the morning. Examination of blood same 
 day in the morning ; spherical bodies in large numbers, free or ad- 
 herent to blood-corpuscles; some were very small, non-pigmented, 
 and gave to the blood-corpuscles to which they are adherent the 
 appearance of fenestrated blood-corpuscles ; the others of average 
 size contain mobile pigmented granules ; bodies segmented regu- 
 larly, with a heap of pigment in centre ; melaniferous leucocytes. 
 Another examination of the blood made the same day — at 1.30 
 p.m., at the time when the attack of fever begins — gave the 
 same results as the examination in the morning. On November 
 1 6th, at 3 p.m., rigors; at 4 p.m. axillary temperature 39*8° C. 
 
 17th. — 37 C. in the morning; during the day the patient had 
 another attack of fever; at 4 p.m. 39*3° C. Sulphate of quinine 
 o*8o grm. morning and evening. 
 
 On the following days the apyrexia continued. Sulphate of 
 quinine was continued in doses of o*8o grm., then of o"6o grm. 
 until November 27th. No relapse. The patient was discharged 
 on December 8th, 1881.
 
 OBSERVATIONS. 155 
 
 Obs. xvn. — Quotidian intermittent fever (relapse). Hxmatozoa 
 of paludism ; spherical bodies; fag ell a. 
 
 Vieu, aged 25, soldier in the eighth squadron of artillery, 
 entered the Constantine Hospital on March 18th, 1881. 
 
 First attack of fever in August, 1879 ; relapse in August, 1880 
 (quotidian fever), and in February, 1881. On March 18th the 
 patient entered the Constantine Hospital uuder different treatment 
 from mine. He had several attacks, and took a few doses of 
 quinine. On April 17th he was sent to me. 
 
 April 17th. — Apyrexia, very marked anaemia, earthy colour, 
 pinched ; general weakness ; anorexia. The splenic dulness 
 measured 11 cm. by 10 cm. Examination of blood on April 17th 
 in the morning. Spherical bodies ; flagella. 
 
 1 8th. — A regular attack of fever well marked, which was 
 repeated on April 19th. Sulphate of quinine was prescribed for 
 three days. The apyrexia persisted till April 23rd. Examination 
 of the blood on April 22nd. Spherical bodies. On April 23rd, 
 at 11 a.m., an attack of fever; at 3 p.m. 40*7° C. 
 
 25th. — A new attack during the day ; at 3.30 p.m. the axillary 
 temperature 39 C. Examination of blood on April 24th in the 
 morning (before the onset of the attack of fever). Spherical 
 bodies in rather large numbers, some showing mobile pigmented 
 granules ; others flagella ; free flagella were also found. Sulphate 
 of quinine o'8o grm. The quinine is continued on the following 
 days. The apyrexia persisted. 
 
 Ohs. xviii. — Quotidian intermittent fever (relapse). Exma- 
 tozoa of paludism ; spherical bodies ; flagella. 
 
 Al., aged 25, sergeant in the third rifles, is admitted to the 
 Coustantine Hospital on May 28th, 1881. 
 
 Al. has been in Algeria from December 17th, 1887. He had 
 intermittent fever for the first time in September, 1880, in the 
 neighbourhood of Jemmapes, and was treated during three weeks 
 at the hospital of Philippeville for quotidian intermittent fever. 
 Since that time the patient had remained weak, anaemic, and was 
 subject to palpitation of the heart. 
 
 On May 19th Al. felt headache; some general malaise; vague 
 pains in limbs. Nevertheless he continued his duties. On 
 May 24th the patient, who was at the butts, felt weaker than 
 on the previous days, and had great difficulty in coming back to 
 the barracks. On May 25th the general malaise and fever had 
 for the most part disappeared, but on May 26th Al. had a very 
 severe attack of fever, with initial rigors, during the night of 
 JNIay 27th to 28th; a new attack of very severe fever; he was
 
 156 MARSH FEVER AND ITS ORGANISM. 
 
 quite delirious. On the morning of May 27th the patient took 
 o'8o grm. sulphate of quinine. 
 
 28th. — Slight fever ; 38*2° C. in the morning, 38'3° C. in the 
 evening. The patient complains of very severe headache, pros- 
 tration, general weakness, very marked anaemia. Tongue white and 
 furry ; belly soft, painless ; no diarrhoea. The splenic dulness was 
 15 cm. by 14 cm. Examination of blood on May 28th in the morn- 
 ing. Spherical bodies containing pigmented granules, mobile or 
 with flagella. (Broth, lemonade). Sulphate of quinine i'20 grm. 
 
 29th, 36*6° C. in the morning; in the evening the apyrexia 
 persists. The general state is more satisfactory (half a dose ; 
 sulphate of quinine o'6o grm.). 
 
 30th. — The apyrexia persisted. Great anaemia ; earthy appear- 
 ance of the face ; general weakness (one dose ; sulphate of quinine 
 o'6o grm. ; cinchona wine) . Examination of blood made on May 
 30th. No more parasitic elements. The sulphate of quinine was 
 continued till June 8th in doses of o - 6o grm. a day. No relapse. 
 Cinchona wine; black coffee. From June 13th to 18th I still 
 gave sulphate of quinine. No relapse. The patient, who obtained 
 sick leave, was discharged June 18th. 
 
 Obs. xix. — Quotidian intermittent fever (relapse). Hsematozoa 
 of paludism ; spherical bodies ; flagella. 
 
 Mach., aged 23, soldier in the twenty-first section of the 
 workmen of administration, was admitted to the Constantine Hos- 
 pital on July 3rd, 1 88 1. 
 
 Mach. came to Algeria November gth, 1879. Had inter- 
 mittent fever for the first time in October, 1880, at Biskra. The 
 patient has had several relapses of fever. Admitted twice into 
 the hospital of Biskra. The fever returned a month ago at 
 Biskra, with the quotidian type. Last of all, during the journey 
 from Biskra to Constantine, there was another l'elapse. Last 
 week quotidian attacks came on at 2 a.m. Last attack on 
 July 3rd, when he came under my care. For a fortnight the 
 patient has not had any relapse of fever. 
 
 July 3rd. — The attack ended at the time he entered the hos- 
 pital. Very marked anaemia. The skin of the face had an earthy 
 tint. The mucous membrane is colourless. General weakness. 
 Pain in the region of the spleen. The splenic dulness was 8 cm. 
 by 8 cm. Sulphate of quinine o"8o gTni. on the evening of 
 July 3rd. Examination of blood on July 3rd at 4 p.m. (the attack 
 being over). Spherical bodies in large numbers, motionless or 
 with flagella (three flagella). Spherical bodies of small size. 
 
 4th. — Apyrexia. Sulphate of quinine o*8o grm. administered.
 
 OBSERVATIONS. 157 
 
 5th. — The apyrexia persisted. Strength and appetite earue 
 back (one dose sulphate of quinine, o*6o grm. ; cinchona wine). 
 The sulphate of quinine was continued in doses of o"6o grm. till 
 July 12th. No relapse of fever. Examination of blood on July 
 13th. No parasitic elements seen. The patient was sent home 
 on sick leave. 
 
 Obs. xx. — Quotidian intermittent fever {relapse). Hsematozoa 
 of paludism ; spherical bodies ; flagella. 
 
 Gra., aged 23, soldier in third Algerian rifles, admitted to 
 the Constantine Hospital November 1st, 1881. 
 
 Gra. had been in Algeria since November, 1879. During the 
 summer of 1880 he had been admitted on two occasions to the 
 hospital of Biskra for dysentery. Had not had fever till September 
 10th, 1881. The patient happened then to be in the bush. He 
 was admitted into the hospital of Millali on September 17th for 
 intermittent fever. He was discharged October 28th. On 
 October 30th relapse of fever and dysentery. 
 
 November 1st. — Fever rather severe at the time of entering the 
 hospital; 30/6 °0. at 4 p.m. 
 
 2nd. — Apyrexia in morning; towards 5 p.m. the patient had 
 another attack of fever ; at 6 p.m. the axillary temperature is 
 about 39*9° C. Anaemia ; general weakness ; dysentery, very 
 characteristic ; small stools, frequent, mucous and bloody, accom- 
 panied with severe colic and tenesmus. The splenic dulness 
 measured 8 cm. by 9 cm. Sulphate of quinine r6o grm.; 
 Seidlitz water two glasses in the morning; calomel 1*50 grm. in 
 the evening. 
 
 3rd. — 38*6° C. in the morning, 37*3° C. in the evening. The 
 colic was less severe. The stools were more abundaut, but they 
 still contained blood. Sulphate of quinine o'8o grm. ; Seidlitz 
 water a glass in the morning ; calomel 1 grm. in the evening. 
 
 4th. — Apyrexia. The stools were very loose ; did not contain 
 any more blood. The colic and tenesmus had disappeared (soups ; 
 sulphate of quinine o"6o grm. ; four pilules of Scgoud). The 
 days following the patient's state continued to improve. The 
 apyrexia persisted. The stools became normal. The sulphate of 
 quinine was continued in doses of o*6o grm. up to November 12th. 
 
 December 5th. — The state of the patient was very satisfactory. 
 The dysentery had disappeared completely, when the fever reap- 
 peared. Attack on the 5th towards midday ; at 1 p.m. 40-3° C. 
 Examination of blood made on December 5th at 2.30 p.m., that 
 is to say, during the attack ; spherical bodies, free or adherent 
 to the blood-corpuscles; spherical bodies of small size in great
 
 158 MARSH FEVKR AND ITS ORGANISM. 
 
 numbers, free or adherent to the blood-corpuscles. On December 
 5th, at 4 p.m., temperature 38*8° C. 
 
 6th. — 36*5° C. in the morning, 37 C. in the evening-. Sulphate 
 of quinine o*8o grm. morning and evening. Examination of blood 
 made December 6th at 8.30 p.m. ; spherical bodies in great 
 number ; the greater part of these contained mobile pigmented 
 granules, and were provided with flagella endowed with very 
 active movements ; melaniferous leucocytes (rare) . 
 
 7th. — 38*4° C. in the morning, apyrexia in the evening ; there 
 was another slight attack this morning (soups ; sulphate of qui- 
 nine o*8o grm.). 
 
 8th. — Apyrexia morning and evening. Profound anasmia ; 
 general weakness. The splenic dulness measured 9 cm. by 12 cm. 
 The dysentery did not reappear. A little appetite (one dose 
 sulphate of quinine o'6o grm. ; cinchona wine, coffee). The sul- 
 phate of quinine was continued in doses of o'6o grm. a day up to 
 December 16th. No recurrence of fever. The patient went out 
 on December 20th on sick leave. 
 
 Obs. xxi. — Quotidian intermittent fever (relapse). Hsemutozoa 
 of paludism ; spherical bodies; flagella. 
 
 Eng., aged 23, soldier in the 47th of the line, admitted to the 
 Constantine Hospital January 9th, 1882. 
 
 Eng. landed at Bona in the month of July, 1881. He came 
 by stages from Bona to Saint Charles, passing through very un- 
 healthy localities. At the end of July Eng. experienced the first 
 attack of fever (quotidian intermittent fever), very characteristic. 
 Since that time incessant relapses. The patient had not re- 
 mained more than a week without fever. He had been admitted 
 successively to the ambulance of Akbou, then to the hospital at 
 Bougie, latterly to the hospital at Ain-Beida. The last attack 
 took place on January 9th in the morning ; before being ad- 
 mitted to the hospital regular attack with initial rigors. The 
 patient said he had not taken sulphate of quinine for about a 
 fortnight. 
 
 January 10th. — Apyrexia morning and evening. Anaemia; 
 general feebleness. The splenie dulness measured 11 cm. by 14 
 cm. Slight bronchitis. 
 
 1 ith. — The patient said he had an attack of fever in the even- 
 ing which was not noticed. 
 
 12th. — Apyrexia (one dose cinchona wine). Examination of 
 blood made on January 13th at 9 a.m.; spherical bodies, free or 
 adherent to the blood-corpuscles ; melaniferous leucocytes. 
 
 26th. — The only medicine the patient has taken was cinchona
 
 OBSERVATIONS. 159 
 
 wine ; nevertheless there was no relapse of fever. Examination 
 of blood made on January 26th j spherical bodies of average or 
 small size, free or adherent to blood-corpuscles ; spherical bodies 
 provided with flagella. A relapse of fever seemed imminent. 
 
 28th. — The patient was seized with a rigor at midday ; at 2 
 p.m. the thermometer registered 38*9 C. in the armpit. Exami- 
 nation of the blood made on January 28th during the attack ; 
 spherical bodies, containing pigmented granules, mobile or pro- 
 vided with flagella. 
 
 29th. — Apyrexia in morning. New attack of fever during the 
 day ; at 2 p.m. axillary temperature 39"6° C. Sulphate of quinine 
 o*8o grni. morning and evening. 
 
 30th. — Apyrexia morning and evening (one dose sulphate of 
 quinine o*8o grin, morning and evening). 
 
 31st. — Apyrexia persists (one dose sulphate of quinine o'8o 
 grm. ; cinchona wine, coffee). The sulphate of quinine was con- 
 tinued in doses of o*6o grm. until February 8th. No return of 
 fever. Discharged February 18th. 
 
 Obs. xxii. — Quotidian intermittent fever {relapse). Hsematozoa 
 of paludism ; crescent-shaped bodies ; spherical bodies ; flagella 
 (Obs. 13 of my ' Traite des fievres paiustres ; ' it is in the blood 
 of this patient that I noticed, for the first time, the presence of 
 flagella). 
 
 D., aged 24, soldier in the eighth squadron of artillery, had 
 been in Algeria since December 5th, 1879, and entered the Con- 
 stantine Hospital November 4th, 1880. 
 
 The patient was at Bardo barracks, i. e. in a place notoriously 
 unhealthy on the banks of the Rummel. On October 10th he 
 had fever for the first time. He was admitted into the hospital 
 of Constantine on October 12th. He took several doses of sul- 
 phate of quinine ; the fever yielded readily, and the patient was 
 discharged on October 24th. Relapse of fever on October 26th ; 
 quotidian attacks came on about 10 a.m. 
 
 On November 4th I noticed that the patient had grown thin ; 
 was markedly amernic ; the skin had the earthy tint character- 
 istic of the cachexia of paludism. At 4 p.m. the axillary tem- 
 perature was 39*5° C. Tongue white, moist; great thirst. The 
 splenic dulness measured 12 cm. by 11 cm. Sulphate of quinine 
 o'8o grm. 
 
 5th. — Temperature is 38-5° C. in the morning, and 38-6° C. 
 in the evening. Examination of blood made November 5th in 
 the morning ; numerous crescent-shaped bodies. I prescribed 
 sulphate of quinine o"Go grm.
 
 160 MARSH FEVER AND ITS ORGANISM. 
 
 6th. — Apyrexia. 36'8° C. in the morning, 37*2° C. in the 
 evening. Examination of blood on November 6th ; crescent-shaped 
 bodies still numerous ; spherical bodies provided with mobile 
 flagella, whose existence I noticed for the first time. On November 
 6th the patient took again o'6o grin, sulphate of quinine. 
 
 7th. — Apyrexia. Examination of blood; crescent-shaped bodies 
 still numerous. I again noticed the existence of the spherical 
 elements provided with flagella. The patient again took, on 
 November 7th, morning and evening, o - 6o grm. sulphate of 
 quinine ; on the following days the quinine was omitted. The 
 apyrexia persisted. Examination of blood on November 9th ; 
 numerous crescent-shaped bodies ; spherical bodies with flagella. 
 The principal doctor, Aron, and MM. Petit and Troussaint, 
 army assistant surgeons, verified the existence of the flagella, 
 which were endowed with very quick movements. 
 
 From November 10th to 25th the apyrexia persisted. The 
 anEeniia was still very pronounced. Examination of blood on 
 November 1 7th ; crescent-shaped bodies still numerous ; sphe- 
 rical bodies also numerous ; flagella. I noticed that the flagella 
 end in a little knob at their free extremity. Examination of 
 the blood on November 25th ; crescent-shaped bodies ; spherical 
 bodies ; these were not so numerous, but larger than in the pre- 
 vious examinations ; the granules of pigment were endowed 
 with very quick movements within some of these elements. For 
 the first time I noticed that the flagella, at first adherent to 
 the spherical elements, detach themselves after a variable time, 
 and became free in the serum ; the free flagella continued to 
 move among the blood-corpuscles, to which they gave very free 
 movements. 
 
 26th. — Attack of fever at 10.30 a.m. Sulphate of quinine 
 o'8o grm. 
 
 From the 27th to the 30th the patient takes every day r6o grm. 
 of sulphate of quinine in two doses ; and from December 1st to 
 8th o"8o grm. quinine every day, or i2'8o grins, of quinine in 
 twelve days. The fever did not reappear. Examination of blood 
 on December 10th ; no parasitic elements found. 
 
 December 12th. — The patient left the hospital on sick leave. 
 
 It is worthy of notice that in this case the flagella had 
 resisted the sulphate of quinine several days, contrary to what 
 generally happens, and very large doses of quinine were neces- 
 sary to make them disappear. This was therefore a case excep- 
 tionally favourable for studying these bodies. 
 
 Oba. xxm. — Quotidian intermittent fever; acute palustral
 
 OBSERVATIONS. 161 
 
 cachexia ; hsematozoa of paladism ; spherical bodies ; cresceut- 
 shaped bodies. 
 
 B., aged 25, a soldier in the third squadron of artillery, 
 admitted to the Constantino Hospital August 22nd, 1881. 
 
 B. has been eighteen months in Algeria ; he was recently 
 employed at Ain-el-Bey. During the last five weeks general 
 malaise ; weakness ; pains in the limbs ; for the last fortnight 
 oedema, first of the lower limbs, then of the face. The patient 
 says he has not had any attack of fever, but on August 22nd, 23rd, 
 and 24th I noticed every evening considei'able fever of which the 
 patient is not conscious (there is no shiver at the commencement 
 of the attacks), and I am quite sure that this quotidian intermit- 
 tent fever has been existing a long time. The patient has not 
 taken any sulphate of quinine before entering the hospital. 
 
 August 22nd. — At 4 p.m. 39'8° C. 
 
 23rd. — 37*8° C. in the morning; at 4 p.m. 40 C. Great anaemia ; 
 earthy tint of skin ; the face is puffy ; a little oedema of the 
 lower limbs; no albumen in urine. The splenic dulness is 10 
 cm. by 12 cm. No diarrhoea. Slight laryngitis. Examination of 
 blood on August 23rd at 9.30 a.m. Crescent-shaped bodies ; 
 small spherical non-pigmented bodies, or containing a few granules 
 of pigment, adherent to red blood-corpuscles ; melaniferous leuco- 
 cytes. Examination of blood on August 23rd at 4 p.m. (during the 
 attack). Same results as in the morning. 
 
 24th. — 38'3° C. in the morning, 40"6° C. in the evening. Sul- 
 phate of quinine o'8o grm. morning and evening. 
 
 25th. — Apyrexia, which persists on the following days. The 
 sulphate of quinine is continued in doses of o - 8o grm., then o'6o 
 grm. till September 3rd. Strength and appetite return. The 
 oedema of the face and lower limbs disappears. The examina- 
 tion of blood on September 11th no longer shows the existence 
 of any parasitic elements. The patient leaves the hospital on 
 September 18th on sick leave. 
 
 Obs. xxiv. — Quotidian intermittent fever (relapse). Hsematozoa 
 of pahtdism ; crescent-shaped bodies ; spherical bodies; fiagella. 
 
 D., aged 24, soldier in first foreign regiment, enters the hospital 
 at Val-de-Cirace on October 23rd, 1888. 
 
 No serious previous illness. D. entered military service in 
 November, 1883; was seized with intermittent Fever in Tonquin 
 in April, 1887. On August 15th, 1S8S, he disembarked at 
 Algiers, and was treated at the Dey Hospital till September 
 1 st. He then returned to France on sick leave for two 
 months. The intermittent fever reappeared soon after his return 
 
 11
 
 162 MARSH FEVER AND ITS 0RC4ANISM. 
 
 to France. He had to enter the hospital at St. Martin, where 
 his fever was arrested after several doses of sulphate of quinine. 
 A new relapse of fever brought him to the Val-de- Grace on 
 October 23rd. Attacks of fever on October 23rd and 24th. The 
 morning temperature of October 24th is 39/8 C. The pulse 
 beats 100 per minute. 
 
 October 24th. — Apyrexia in the morning ; the patient is very 
 anasmic ; the skin has the earthy tint of palustral cachexia ; 
 the mucous membrane is pale ; the spleen is very much hyper- 
 trophied ; the splenic dulness is 12 cm. by 14 cm. Examination 
 of blood on the morning of 24th. Crescent-shaped bodies rather 
 numerous ; no amoeboid bodies or flagella. On the evening of 
 October 24th the patient has a little fever. 
 
 25th. — General malaise ; fever this morning ; pain at the 
 occiput. Examination of blood on the morning of October 
 25th. Crescent-shaped bodies ; pigmented spherical bodies, im- 
 mobile or provided with flagella ; free flagella. I inoculated with 
 the blood of this patient some tubes containing cultivation broth 
 and gelatine. The blood was taken with all the necessary precau- 
 tions to avoid the introduction of foreign germs. The tubes 
 are placed in the stove at 37 C. On the 25th during the day 
 the patient took 0*60 grm. of hydrochlorate of quinine. 
 
 26th. — The patient has another slight attack during the day ; 
 38 C. at 4 p.m. (hydrochlorate of quinine 60 centigrammes). 
 
 27th. — Apyrexia. I stop the hydrochlorate of quinine. Exa- 
 mination of blood on October 27th : crescent-shaped bodies ; 
 amoeboid bodies with or without flagella. The broth inoculated 
 with blood has remained limpid, and no growth had taken place 
 in the gelatine. The examination of these media of cultivation 
 was also negative on the following days. The attempts at culti- 
 vation on potato succeeded no better. 
 
 30th. — No new attack. Examination of blood; crescent-shaped 
 bodies rather numerous ; amoeboid bodies with or without flagella. 
 The latter are very rare. 
 
 November 2nd. — The patient shows great malaise and nausea, 
 which makes one think that a relapse is imminent. Examination 
 of blood on November 2nd in the morning, in the presence of 
 Professor Bouchard : crescent-shaped bodies ; amoeboid bodies 
 with or without flagella. The flagella are more numerous than 
 at examination on October 30th. 
 
 3rd. — Relapse of fever ; violent shivering at 2 p.m. At 3 p.m. 
 the axillary temperature is 39/8 C. 
 
 4th. — Apyrexia. Examination of blood on the morning of
 
 OBSERVATIONS. 163 
 
 November 4th, before Professor Straus and Dr. Hanot ; crescent- 
 shaped bodies; amoeboid bodies with or without flagella. MM. 
 Straus and Hanot have no doubt as to the parasitic nature of 
 these elements. 
 
 5th. — Vomiting ; attack of fever. Hydrochloratc of quinine 
 o*6o grm. 
 
 6th. — Apyrexia. Examination of blood; crescent-shaped bodies; 
 motionless spherical bodies. Only one of these elements presents 
 flagella, whose movements stop very quickly. Hydrochlorate of 
 quinine o'6o grm. 
 
 9th. — No fresh attack. Examination of blood ; crescent- shaped 
 bodies rather numerous ; a few amoeboid bodies. 
 
 12th. — The patient had a slight attack during the night; 
 general malaise ; sweating. Temperature still a little above 
 normal in the morning. Hydrochlorate of quinine o - 6o grm. Exa- 
 mination of blood ; crescent-shaped bodies ; amoeboid bodies, 
 motionless or provided with flagella. 
 
 13th. — Apyrexia. Hydrochlorate of quinine o*6o grm. 
 
 21st. — Apyrexia persists. The blood only contains some 
 crescent-shaped bodies very rare ; in two preparations of blood 
 examined with the greatest care I only found two of these ele- 
 ments, no amoeboid bodies or flagella. I prescribed two more 
 doses of hydrochlorate of quinine. The anaemia is much less than 
 when the patient came in ; his strength has partly returned ; the 
 spleen has remarkably diminished in size. The patient leaves the 
 hospital November 24th. 
 
 Obs. xxv. — Tertian intermittent fever {relapse). Hsematozoa of 
 paludismj spherical bodies; flagella. 
 
 Car., aged 20, soldier in the 3rd zouaves, enters the Constan- 
 tiue Hospital on December 5th, 1882. 
 
 Car., who is serving voluntarily, is in the military service, 
 and has been in Algeria one year. He says he had typhoid fever 
 in his infancy ; since then he has not had serious illness. He had 
 intermittent fever for the first time in July, 1882, at Ain-cl-Bey ; 
 he was readmitted at Constantine on July 29th ; ill for four days. 
 
 Quotidian intermittent fever. Car has been treated at the 
 infirmary twenty days, lielapse of fever early in September ; a 
 fortnight's treatment at the infirmary. New relapse at the be- 
 ginning of November. Third admittance to the infirmary ; 
 twelve days' treatment. On November 19th the patient returned 
 to service, and has continued till December 2nd. On December 
 2nd relapse of fever; attack about 5 a.m. with initial shivering. 
 Fresh attack on December 4th at same hour.
 
 164 MARSH FEVER AND ITS ORGANISM. 
 
 December 5th. — Apyrexia; profound ansenria, emaciation, gene- 
 ral feebleness, vertigo. The tongue is a little pale; anorexia; no 
 diarrhoea. The splenic dulness measures 11 cm. by 12 cm. (half a 
 dose ; sulphate of quinine 1 grm. in the evening). Examination 
 of blood made on December 5th, 8.30 a.m. Spherical bodies of 
 small or medium size in quite a large number, free or adherent to 
 the blood-corpuscles ; spherical bodies containing mobile pig- 
 mented granules and provided with flagella, flagella free; melani- 
 ferous leucocytes. 
 
 6th. — The patient takes another 1 grm. sulphate of quinine at 
 6 a.m. In spite of that he has an attack of fever; at 7.30 a.m. 
 the axillary temperature is about 40 C. ; he has not had initial 
 shivering; headache; much thirst; at 4 p.m. 37'3° C. Examina- 
 tion of blood made on December 6th in the morning, during the 
 attack. Spherical bodies of medium or small size, free or adherent 
 to the blood- corpuscles ; spherical bodies containing mobile pig- 
 mented granules ; melaniferous leucocytes. 
 
 7th. — 37'3° C. in the morning ; in the evening apyrexia persists 
 (a half dose of sulphate of quinine o - 8o grm. morning and even- 
 ing; cinchona wine). Examination of blood made on December 
 7th. Spherical bodies in very small numbers ; melaniferous leu- 
 cocytes. 
 
 8th. — Apyrexia persists (one dose ; sulphate of quinine o'8o 
 grm. ; cinchona wine, coffee). The sulphate of quinine is continued 
 in doses of o'6o grm. up to December 14th. No return of fever. 
 The patient goes out on December 21st on sick leave. 
 
 Obs. xxvi. — Tertian intermittent fever (relapse). Hsematozoa of 
 paludism ; spherical bodies, flagella. 
 
 Sim., aged 23, soldier in the second company of discipline, 
 admitted to the military hospital, Constantine, on April 27th, 
 1 88 1, after leaving the hospital of Soukharas. 
 
 Sim. had intermittent fever for the first time on July 20th, 
 1880. He was admitted to the hospital of Soukharas for 
 tertian intermittent fever ; he was afterwards sent on sick 
 leave to France. The patient returned to Algeria on February 
 4th last, and on February 5U1 had a relapse of fever. The 
 patient has taken several doses of quinine ; the fever disappeai*ed 
 for a week, then gave place to new attacks. For a month the 
 patient took only cinchona wine ; for a week regular attacks, re- 
 turning every two days towards 7 a.m. ; last attack April 27th. 
 The patient has had, moreover, for the last few days an area of 
 splenitis, very painful ; several blisters have been applied to 
 the left hypochondrium.
 
 OBSERVATIONS. 165 
 
 April 28th. — Apyrexia ; profound anosmia ; the skin has an 
 earthy tint, very marked on the face ; mucous membrane pale ; 
 great feebleness, vertigo in the upright position, sharp pains at 
 the side of the kidneys. The splenic dulness measures 10 cm. 
 by 14 cm. Tongue clean; a little appetite; no diarrhoea (half a 
 dose ; cinchona wine). Examination of blood made on April 28th 
 at 9 a.m. : spherical bodies containing mobile granules of pig- 
 ment, or provided with flagella. 
 
 29th. — At 6 a.m. attack of fever; at 7 a.m. 39*7° C. (diet, 
 lemonade ; sulphate of quinine o*6o grm. in the evening). 
 
 30th. — Apyrexia. Sulphate of quinine o'6o grm. 
 
 May 1st and 2nd. — Apyrexia persists. The patient is better; 
 a little appetite (one dose sulphate of quinine, o - 6o grm. ; cin- 
 chona wine). 
 
 3rd to 8th. — Apyrexia persists. Strength returns. Examina- 
 tion of blood made on May 6th : nothing abnormal. 
 
 9th. — Relapse of fever; shivering at 1 p.m. ; at 3 p.m. the axil- 
 lary temperature is about 40*3° C. 
 
 10th. — Apyrexia. Examination of blood made May 10th in 
 the morning : spherical bodies of average size provided with 
 flagella ; spherical bodies of small size. Sulphate of quinine 
 1 "20 grm. 
 
 1 ith. — Attack of fever ; at 7 a.m. shivering ; at 8 a.m. 4 1 • i° C. ; 
 at 3.30 p.m. the axilla^ temperature is still about 40 C. (sul- 
 phate of quinine o'6o grm. in the evening). 
 
 12th. — 36"5° C. in the morning. In the evening apyrexia per- 
 sists (sulphate of quinine 1*20 grm.). 
 
 13th. — 35*6° C. in the morning. The pulse is slower. Splenic 
 area very tender. In the evening apyrexia persists (sulphate of 
 quinine o'6o grm.; blistering over the region of the spleen). 
 
 14th to 24th. — No relapse. Sulphate of quinine is continued 
 in doses of o"6o grm. a day (one dose; cinchona wine). 
 
 21st to 31st. — No return of fever. Strength returns. Exa- 
 mination of blood made May 31st; nothing abnormal. 
 
 Reckoning from June 1st, I gave sulphate of quinine up to 
 June 6th (60 centigrammes a day) in order to prevent a relapse. 
 On June 3rd the splenic dulness measures no more than 7 cm. 
 by 8 cm. Patient went out June 11th, 1881. 
 
 Obs. xxvii. — Tertian intermittent fever. Hxmatozoa of pal n- 
 dism ; crescent -shaped bodies ; spherical bodies of small size. 
 
 Mont., aged 23, corporal in the 3rd zouaves, admitted to the 
 Constantine Hospital October nth, 1881. 
 
 Mont, has had fever for the first time September 4th. Regular
 
 166 MARSH FEVER AND ITS ORGANISM. 
 
 attack, quotidian at the beginning, since tertian type. Last attack 
 October 9th; again on October 10th. 
 
 October nth. — Attack of fever; 30/2 C. at 8 a.m.; 39'3° C. 
 at 4 p.m. Anaemia very marked ; earthy colour of the skin. The 
 area of splenic dulness measures 9 cm. by 10 cm. Examination of 
 blood made on October nth at 8.30 a.m.: crescent-shaped 
 bodies ; small spherical bodies not pigmented, adherent to blood- 
 corpuscles. Sulphate of quinine prescribed on leaving at 1 1 p.m. 
 No new attack. Patient leaves the hospital on November 2nd 
 on sick leave. 
 
 Obs. xxviii. — Intermittent fever tertian (relapse). H&matozoa 
 of paludism ; crescent-sliaped bodies. 
 
 Br., aged 22, overseer of military hospitals, admitted to the 
 Constantine Hospital on February 24th, 1881. 
 
 Br. was attacked with fever for the first time in the middle of 
 September, 1880, at Fort National. The fever took from the be- 
 ginning the tertian type. It is the sixth time that the patient 
 has been admitted to hospital for intermittent fever ; the last 
 relapse was February 23rd. The patient has not taken sulphate 
 of quinine for some time. 
 
 February 24th. — Apyrexia ; anaemia very marked, general 
 weakness. The area of splenic dulness measures 1 1 cm. by 1 1 cm. 
 Examination of blood on February 25th in the morning (before 
 the attack) : I demonstrated the existence of crescent-shaped 
 bodies in large numbers without other parasitic elements. 
 
 25th. — The patient had attack of fever. Examination of blood 
 on February 26th at 2 p.m. : crescent-shaped bodies. Sulphate 
 of quinine o'6o grm. from February 27th to March 4th. No new 
 attacks. Examination of blood made on March 6th : very few 
 crescent-shaped bodies. Examination of blood made on March 
 9th : crescent-shaped bodies in greater numbers than in preceding 
 examination. In the night of March 10th the patient had an 
 attack of fever. Examination of blood on March nth : crescent- 
 shaped bodies. Sulphate of quinine is prescribed for ten days ; 
 fever does not reappear. Examination of blood on April 3rd : I 
 find still some crescent-sliaped bodies. The patient goes out on 
 April 4th. 
 
 Obs. xxix. — Tertian intermittent fever (relapse). Hsematozoa of 
 paludism; crescent-shaped bodies; spherical bodies; flagella. 
 
 Gold., aged 26, soldier in the 4th hussars, admitted to the 
 Constantine Hospital on December 19th, 1881. 
 
 Gold, arrived in Algeria in the month of November, 1880. In 
 March, 1 88 1, he entered the hospital of Setif for bronchitis; in
 
 OBSERVATIONS. 1G7 
 
 April entered same hospital for typhoid fever. During the ex- 
 pedition of Kroumyrie, Gold, was admitted to the hospital for 
 dysentery. In October, during the march upon Kairouan, the 
 patient had intermittent fever for the first time. Since then he 
 has had several relapses, notably at Gafsa ; at the same time 
 there was dysentery. The patient was sent in succession to 
 Tebessa, then to Constantine. 
 
 December igth. — Apyrexia j profound anaemia, characteristic 
 earthy tint; lips pale; emaciation, general feebleness very great; 
 dysentery, the stools contain only blood ; fatty stools, colic, tenes- 
 mus. I prescribed milk diet and several doses of seidlitz water ; 
 afterwards the pilules of Segond. 
 
 22nd. — The stools have become normal. The patient eat 
 half a ration. No attack of fever since admission to the 
 hospital. 
 
 January nth, 1882. — Return of fever 39*5° C. at 3 p.m. 
 
 12th. — Apyrexia in the morning. In the evening the apyrexia 
 maintained. The spleen percusses out beyond the lower ribs about 
 two fingers' width. The splenic dulness measures 12 cm. by 
 12 cm. Examination of blood made on January 12th at 2 p.m. : 
 crescent-shaped bodies in large numbers, motionless spherical 
 bodies, or bodies provided with flagella, alive with very active 
 movements; oval bodies. 
 
 13th. — Apyrexia in morning at 2 a.m., onset of fever at 10.30 
 a.m., the thermometer registers 30/6 C. Examination of blood 
 made on January 13th at 2 p.m.: crescent-shaped bodies in great 
 number, oval bodies, spherical bodies. 
 
 14th. — Apyrexia morning and evening. Anoetnia, general 
 feebleness, small appetite (half dose sulphate of quinine, o*8o grin., 
 morning and evening). 
 
 15th. — The apyrexia persists (a half dose sulphate of quinine, 
 o*8o grm., cinchona wine, coffee). The sulphate of quinine is 
 continued up to January 18th. No return of fever. Strength 
 returns quite easily. The patient goes out on January 18th on 
 sick leave for three months. 
 
 Obs. xxx. — Intermittent fever. Sixth relapse [tertian type), 
 crescent-shaped bodies. Seventh relapse {tertian type), spherical 
 bodies, jlagella. 
 
 God., aged 23, soldier in the third squadron of artillery, entered 
 the Constantine Hospital Januai'y 25th, 1882. 
 
 God., who has been in Algeria for a year, had intermittent fever 
 for the first time in September, 1881. Five admissions to hospital 
 for intermittent fever. Last relapse was eight days ago ; tertian
 
 1G8 MARSH FEVER AND ITS ORGANISM. 
 
 fever very characteristic ; the patient has taken six doses of 
 sulphate of quinine of i grm. each before entering the hospital. 
 
 January 26th. — A pyrexia. Anasmia very marked. General 
 feebleness. The area of splenic dulness measures 14 cm. by 12 cm. 
 Examination of the blood made January 26th: crescent-shaped 
 bodies, oval bodies, melaniferous leucocytes. No new attacks. I 
 prescribe only cinchona wine. The patient goes out of the hospital 
 on February 8th. The fever reappears on February 8th, always 
 with the tertian type, and the patient re-enters the hospital on 
 March 24th. Last attack on March 22nd and 24th. Examina- 
 tion of blood made on March 24th, at end of attack : spherical 
 bodies of small and medium size, free or adherent to the blood- 
 corpuscles ; melaniferous leucocytes. 
 
 March 25th. — Apyrexia. Anasinia very marked ; earthy colour 
 of the skin; intellectual indifference very marked. The splenic 
 dulness measures 12^ cm. by 16 cm. Examination of blood made 
 March 25th : spherical bodies rare ; melaniferous leucocytes. 
 The patient has taken several doses of sulphate of quinine before 
 entering the hospital ; I prescribed only cinchona wine. 
 
 29th. — Attack of fever ; at 6 a.m. shivering ; at 7 a.m. 30/8 C. ; 
 at 3 p.m. the apyrexia is complete. Examination of blood made 
 at 9 a.m., at the end of the attack : spherical bodies of mean 
 size, free or adherent to blood-corpuscles ; some contain granules 
 of pigment in motion. 
 
 30th and 3 1st. — Apyrexia persists. Examination of blood made 
 March 31st at 9 a.m. : spherical bodies free or adherent to red 
 blood-corpuscles ; flagella. 
 
 The apyrexia continues the following days, though the patient 
 only takes cinchona wine. Examination of blood made April 
 4th : I still find some spherical bodies. The patient leaves the 
 hospital on April 10th, 1882. 
 
 Obs. xxxi. — Tertian intermittent fever contracted in Algeria. 
 Relapse after return to France; tertian type. Hosmatozoa of pahi- 
 dism ; crescent-shaped bodies; spherical bodies ; flagella. 
 
 Bel., aged 22, admitted to hospital of Val-de- Grace on October 
 15th, 1887, under Dr. Vaillard. 
 
 Patient contracted palustral fever in August last in Algeria ; 
 the fever had from the beginning the tertian type. On several 
 occasions the patient took quinine, but the fever reappeared not- 
 withstanding. 
 
 On admission to Val-de-Gruce profound anosmia; the skin and 
 mucous membranes pale ; ccdoma of the lower limbs ; the pulse 
 beats only 44 a minute. The spleen is markedly hypertrophied ;
 
 OBSERVATIONS. 169 
 
 the splenic dulness measures 16 cm. in height. Apyrexia re- 
 mains up to November 9th. Examination of blood made on 
 November 8th : crescent-shaped bodies in rather large numbers, 
 two or three are often in the field of the microscope. 
 
 November 9th. — Attack of fever very characteristic, with the 
 three stages of cold, heat, and sweating. 
 
 12th. — The attack of fever is not repeated. Examination of 
 blood : crescent-shaped bodies ; spherical bodies ; flagella. I 
 showed these objects to M. Vaillard. 
 
 12th and 13th. — The patient took o*8o grm. sulphate of quinine. 
 14th. — No fresh attack. Examination of blood : crescent- 
 shaped bodies as numerous as before. 
 
 1 oth. — No fresh attack. Examination of blood: crescent-shaped 
 bodies still as numerous as before. I showed them to Professor 
 Straus. 
 
 December 5th. — Attack of fever very characteristic. 
 6th. — Apyrexia. 
 
 7th. — Fresh attack of fever. These two attacks of December 
 5th and 7th leave no doubt about the type of fever. At the end 
 of these attacks the patient takes several doses of quinine, and 
 leaves the hospital on December 20th, 1887, in a satisfactory 
 state. The ana3mia is very much less marked than on entering 
 the hospital. The oedema of the lower limbs has disappeared, 
 and the spleen has diminished in size. 
 
 Obs. xxxii. — Tertian intermittent fever contracted at Tonkin, 
 (relapse) . Hsematozoa of paludism ; crescent-shaped bodies ; 
 spherical bodies ; flagella. 
 
 G., aged 22, soldier in second regiment of infantry of marines, 
 entered the hospital of Val-de-Grace on May 6th, 1887. 
 
 G. spent eleven months in Tonkin from June, 1885, to May, 
 1886. He was attacked with intermittent fever for the first time 
 at the end of September, 1885, at Haiphong. The fever showed 
 from the beginning the tertian type. Several relapses during 
 his sojourn in Tonkin. At each relapse patient took several 
 doses of quinine. 
 
 In May, 1886, G. embarked for Madagascar, and remained 
 there till the end of February, 1887. Several relapses of fever 
 during his sojourn in Madagascar, and on several occasions the 
 fever was complicated with pernicious symptoms. G. left Mada- 
 gascar at the end of February, and having a furlough of three 
 months he arrived in Paris on March 11th, 1887. From then to 
 May 6th, the day of entering the hospital, the patient had several 
 relapses of fever, which were treated witli sulphate of quiuine.
 
 170 MARSH FEVER AND ITS OBGANISM. 
 
 6th. — Anaemia very marked, no fever. The spleen is double 
 its size ; nervous complications ; loss of memory ; hesitancy of 
 speech. At the end of an attack of fever in Madagascar the 
 patient had aphasia for four hours. Slight nystagmus. The 
 apyrexia persists up to May 20th. 
 
 20th. — Attack of fever during the day. At 3 p.m. the axil- 
 lary temperature 39 C. Examination of blood made May 20th 
 during the attack : crescent-shaped bodies ; free spherical bodies. 
 
 21st. — Apyrexia morning and evening. The patient has not 
 taken quinine. Examination of blood made May 21st: crescent- 
 shaped bodies (rare) ; free spherical bodies, some show flagella. 
 I showed these specimens to Dr. Maurel. 
 
 22nd. — Attack of fever, 39° C. at 4 p.m. 
 
 23rd. — 36*2° C. in the morning. Examination of blood : free 
 pigmented spherical bodies, some flagella : crescent-shaped bodies. 
 I showed Dr. Roux a spherical body with a flagellum. 
 
 24th. — Attack of fever 39*2 C. in the morning (tertian fever 
 anticipated) . 
 
 28th. — The apyrexia continues. Examination of blood : pig- 
 mented spherical bodies rare. 
 
 June 1st. — There have been no new attacks. Examination of 
 the blood gives no new results. The patient has only taken 
 cinchona wine. The patient left the hospital. 
 
 Obs. xxxiii. — Intermittent quartan fever. Hsematozoa of palu- 
 clism ; spherical bodies. 
 
 Ben., aged 24, soldier in the fourth zouaves, admitted to Con- 
 stantine Hospital December 23rd, 1881. 
 
 Ben. had intermittent fever first at Aumale on August 10th, 
 1 88 1. He was for a month under treatment at the hospital of 
 Aumale for tertian intermittent fever. Relapses in September, 
 November, and December. 
 
 December 23rd. — Apyrexia ; anaemia very marked. The zone 
 of splenic dulness measures 9 cm. by 11 cm. 
 
 30th. — Attack of fever at 4 p.m. The axillary temperature 
 40*2° C. 
 
 31st. — Apyrexia. Examination of blood made on December 
 31st at 2.30 p.m. : spherical bodies of small or average size, 
 free or adherent to blood-corpuscles ; melaniferous leucocytes. 
 
 January 1st, 1882. — Apyrexia continues. 
 
 2nd. — Attack of fever at 3 p.m. ; at 3.30 the axillary tempera- 
 ture is about 39'6° C. Examination of blood made January 2nd 
 at 4 p.m. : spherical bodies of average size, free or adherent to 
 blood-corpuscles.
 
 OBSERVATIONS. 171 
 
 From January 3rd the patient took sulphate of quinine ; never- 
 theless on the 5th in the evening 1 he had a slight attack. 
 The sulphate of quinine is continued till January nth. No 
 relapse of fever. The patient left the hospital on January 18th 
 on sick leave. 
 
 Obs. xxxiv. — Quartan fever [relapse) . Hsematozoa of paludism ; 
 spherical bodies ; segmented bodies. 
 
 Dan., aged 25, soldier in the eighth company of mounted troops, 
 admitted to the Constantine Hospital on September nth, 1880. 
 
 Dan. had intermittent fever for the first time in September, 
 1880. Since March, 188 1, several relapses of tertian or quartan 
 type. The patient took on several occasions sulphate of quinine. 
 
 September 15th. — Apyrexia; anasraia very marked, earthy tint 
 of the face ; general feebleness, apathetic, very great indifference. 
 The zone of splenic dulness measures 9 cm. by 10 cm. 
 
 17th. — Attack of fever; at midday 40 C. ; at 4 p.m. 4i"3° C. 
 Examination of blood made September 17th at 2 p.m. (during 
 the attack) : segmented bodies, or rose-shaped bodies, in rather 
 large numbers ; melaniferous leucocytes. 
 
 1 8th. — Apyrexia. Examination of blood made September 
 1 8th: spherical bodies of small or average size; segmented 
 bodies are rarer than on September 17th. 
 
 19th. — Apyrexia continues. 
 
 20th. — Attack of fever, 40*6° C, at 7.30 p.m. 
 
 21st. — Apyrexia, which continues during September 22nd. 
 
 23rd. — Fresh attack; 39'6° C. in the morning, 40-9° C. at 6 p.m. 
 Examination of blood made September 23rd at 8.30 a.m. : spheri- 
 cal bodies in rather large number ; segmented bodies rare. From 
 September 23rd sulphate of quinine is prescribed in doses of o*8o 
 grm., then of o*6o grm. till October 3rd. No return of fever. Exa- 
 mination of blood made on October 2nd shows nothing abnormal. 
 The patient leaves the hospital on October 3rd on sick leave. 
 
 Obs. xxxv. — Quartan fever contracted in Tonkin (relapse). 
 Hsematozoa of paludism ; spherical bodies ; segmented bodies. 
 
 Pois., aged 24, soldier in the marine artillery, entered the hos- 
 pital of Val-de-Grace on March 15th, 1890. Patient has had 
 intermittent fever in Tonkin in September, 1888; relapse in 
 August, 1889. Pois. landed at Toulon on February 6th, and 
 obtained sick leave. New attack of fever since his arrival 
 in Paris; last attack March 13th. On admission the patient was 
 anasmic, but still fairly robust; apyrexia March 15th. The spleen 
 is increased in size ; the splenic dulness measures 8 cm. by 12 cm. 
 The patient has not taken sulphate of quinine since he was in
 
 172 MARSH FEVER AND ITS ORGANISM. 
 
 Paris. Examination of blood made on March 15th : some 
 spherical bodies, quite large, adherent to blood-corpuscles. 
 
 March 16th. — Attack of fever, which came on at 4 p.m. with 
 shivering; at 6 p.m. the temperature was 40*8° C. ; at 10 p.m. 
 it was still 39 C. (sweating). 
 
 1 7th. — Apyrexia. Spherical bodies, free or adherent to blood- 
 corpuscles ; segmented bodies. No quinine. 
 
 1 8th. — Apyrexia. Examination of blood made on March 18th 
 at 3 p.m. : spherical bodies of medium or small size, free or ad- 
 herent to blood-corpuscles. No quinine. 
 
 19th. — Apyrexia in the morning. Examination of blood made 
 at 2 p.m. : spherical bodies of small or medium size ; segmented 
 bodies. On March 19th at 4 p.m. shivering. Temperature rose 
 after this time, and at 8 p.m. is 40'4° C. ; at 10 p.m. it is not 
 more than 38 C. (sweating). 
 
 20th. — Apyrexia. Hydrochlorate of quinine o*6o grm. morning 
 and evening. Examination of blood made on evening of March 
 20th : I find no more parasitic elements. 
 
 On the 21st and 22nd the patient again took o*6o grm. hydro- 
 chlorate of quinine. 
 
 Obs. xxxvi. — Quartan intermittent fever (relapse). Hasmatozoa 
 of paludism ; crescent- shaped bodies; spherical bodies ; fagella. 
 
 Fet., aged 24, soldier in the fourth squadron of artillery, ad- 
 mitted to Constantine Hospital February 24th, 1881. 
 
 Fet. had intermittent fever first at Mondovi in August, 1880. 
 Several relapses during September, October, and November. 
 The fever reappeared in January, 1881, and remains in the 
 quartan type. Last attack on February 23rd. 
 
 February 24th. — Apyrexia. The patient is much weakened ; 
 anoemia, the skin has the characteristic tint. The area of splenic 
 dulness measures 10 cm. by 12 cm. Examination of the blood 
 made on February 24th in the evening : crescent-shaped bodies ; 
 spherical bodies. 
 
 26th. — Attack of fever during the day ; the quartan type is 
 then very characteristic. The patient has not taken quinine 
 since admission to the hospital. Examination of blood February 
 26th in the morning, some hours before the attack : spherical 
 bodies in rather large number ; flagella. 
 
 From February 27th I prescribed sulphate of quinine, which 
 is continued till March 5th. 
 
 March 10th. — No new attacks of fever. Examination of blood 
 does not show any parasitic elements. The patient leaves the hos- 
 pital without having any relapse.
 
 OBSERVATIONS. 173 
 
 Obs. xxxvu. — Quartan fever. Hsematozoa of paludism ; cres- 
 cent-shaped bodies. 
 
 Bon., aged 20, soldier in the 16th regiment of artillery, ad- 
 mitted to Constantino Hospital November 19th, 1882. 
 
 Bon. has been in Algeria for seven months. He first had 
 fever on October 8th, and has been treated at the hospital of 
 Philippeville for continued fever with typhoid state. 
 
 November 19th. — Profound auasmia, general weakness ; ver- 
 tigo ; emaciation; the zone of splenic dulness measures 13 cm. 
 by 15 cm. Attack of fever, 38 C. at noon, 38'8 C. at 4 p.m. 
 
 20th and 21st. — Complete apyrexia. 
 
 22nd. — Attack of fever; 38*8° C. in the morning, 36 C. in 
 the evening. Examination of blood made on November 23rd : 
 crescent-shaped bodies ; melaniferous leucocytes. Sulphate of 
 quinine is prescribed from November 23rd to 30th, and from 
 December 3rd to 7th. The fever does not reappear, and the 
 state of the patient improves rapidly ; he leaves the hospital on 
 December 9th. 
 
 Obs. xxxviii. — Tertian intermittent fever {relapse) . Hsematozoa 
 of paludism; crescent-shaped bodies; spherical bodies ; flagella. 
 Relapses with the quotidian, then with the tertian type ; crescent- 
 shaped bodies ; spherical bodies ; flagella. 
 
 Patient enters the Constantine Hospital for a relapse of inter- 
 mittent fever on November 12th, 1881. The fever shows the 
 tertian type. Examination of blood, made some hours before 
 the attack, shows crescent-shaped bodies, spherical bodies, and 
 flagella. 
 
 The fever disappeared under the influence of quinine. Relapse 
 on November 29th, with some quotidian attacks ; new relapses 
 on December 21st and 27th, with attacks of tertian type. I dis- 
 covered again in the blood crescent-shaped bodies in rather large 
 number, spherical bodies, and flagella (for details see Obs. 27 in 
 my ' Traite des fievres palustres,' p. 259). 
 
 Obs. xxxix. — Quotidian intermittent fever . Jl;vn\ato:.oa of palu- 
 dism ; crescent-shaped bodies ; spherical bodies ; flagella {relapse) ; 
 pernicious complications ; splierical bodies. 
 
 Patient admitted to Constantino Hospital November 7th, 1882, 
 for quotidian intermittent fever. Examination of blood made on 
 November 19th, 1882, during an attack: crescent-shaped bodies 
 in great number ; spherical bodies, flagella. Relapse of fever on 
 15th, 1883. Patient readmitted to Constantino Hospital on 
 March 20th, 1883, for palustral cachexia, with severe symptoms. 
 Examination of blood shows some spherical bodies of small or
 
 174 MARSH FEVER AND ITS ORGANISM. 
 
 medium size, free or adherent to blood-corpuscles. I do not 
 find more crescent-shaped bodies (for details see Obs. xlviii of 
 my c Traite des fievres palustres,' p. 334). 
 
 Obs. xl. — Tertian intermittent fever. Hsematozoa of paludism ; 
 spherical bodies ; flagella (relapse) ; quotidian attacks ; crescent- 
 shaped bodies. 
 
 Patient admitted to the Constantine Hospital on December 
 1 6th, 1882, for intermittent fever (relapse), with tertian type. 
 Examination of blood made in the interval of the two attacks. 
 Spherical bodies of medium or small size. Examination of blood 
 made during an attack. Spherical bodies of medium or small 
 size, free or adherent to blood-corpuscles ; flagella. Fever ceases 
 after sulphate of quinine. Return of fever on January 19th, 1883 ; 
 attack on the 19th and 20th (quotidian type). On examination 
 of blood I find only some crescent-shaped bodies (for more details 
 see Obs. xlix of my ' Traite fievres palustres/ p. 338). 
 
 Obs. xli. — Tertian intermittent fever, afterwards quotidian 
 (relapse). Hsematozoa of paludism ; crescent-shaped bodies; 
 spherical bodies. 
 
 Th., aged 23, soldier in the third squadron of artillery, entered 
 Constantine Hospital September 25th, 1881. 
 
 Th. has been in Algeria twenty-two months. He is said to 
 have had the fever first at Collo ; it lasted a fortnight. The 
 attack returned every two days. Patient has taken several 
 doses of sulphate of quinine. Last attack of fever on Sep- 
 tember 21st. 
 
 September 26th. — Apyrexia; profound anaemia ; general weak- 
 ness ; indifference very marked ; anorexia. The splenic dulness 
 measures 14 cm. by 15 cm. Examination of blood made September 
 26th at 2 p.m. : crescent-shaped bodies ; amoeboid bodies, con- 
 taining granules of pigment endowed with rapid movement. 
 
 27th. — Apyrexia in the morning. Examination of blood made 
 on September 27th in the morning : crescent-shaped bodies. 
 In the afternoon attack of fever without initial shivering ; at 
 4 p.m. the axillary temperature is 39' i° C. 
 
 28th. — 37^ C. in the morning. Examination of blood made 
 at 2.30 p.m. : crescent-shaped bodies ; spherical bodies of small 
 size; slight attack during the day ; at 4 p.m. 38*5° C. ; headache. 
 Sulphate of quinine o'8o grin, in the evening. On the following 
 days apyrexia. Sulphate of quinine is continued till October 7th, 
 o - 8o grm. first, then o*6o grm. The patient went out on October 
 17th. 
 
 Obs. xlii. — Quotidian intermittent fever. Hsematozoa of pain-
 
 OBSERVATIONS. 175 
 
 dism ; crescent-shaped bodies ; spherical bodies. Return of fever, 
 tertian type; new examination of the blood; spherical bodies. 
 
 Du., aged 30, gendarme, admitted to the hospital of Con- 
 stantine the 5th of August, 1882. He has been attacked with 
 intermittent fever for the first time ; he was twelve days at 
 Oued-Zenati. Quotidian fever attacks 3rd, 4th, 5th, Gth August. 
 
 August Gth. — 39'2° C. in the morning, 39*7° C. in the evening. 
 Aneernia very marked; the zone of splenic dulness measures n^ 
 cm. by 13^ cm. Examination of blood made on 6th August in 
 the morning : crescent-shaped bodies in great numbers ; oval 
 bodies ; spherical bodies very rare ; melaniferous leucocytes. 
 The fever yielded readily to sulphate of quinine ; the patient went 
 out 22nd August. 
 
 Du. had a return of fever in the month of October, 1882, 
 and a second relapse in the month of April, 1883, for which he 
 re-entered the hospital 25th April. The fever reappeared 16th 
 April ; slight attack at first, afterwards more and more severe, 
 returning every two days ; regular attacks with initial shivering. 
 From the 16th to the 24th there has been four attacks ; the patient 
 has taken 2 grms. sulphate of quinine before entering the hospital. 
 
 April 25th. — Apyrexia ; anasmia very marked ; earthy tint of 
 the face ; general feebleness ; want of appetite. The splenic dul- 
 ness is 8 cm. in height by 10 cm. in breadth. Examination of the 
 blood made 25th April : spherical bodies, free or adherent to the 
 blood-corpuscles, in small numbers ; melaniferous leucocytes. I 
 do not find any crescent-shaped bodies. No relapse. Examina- 
 tion of the blood made 4th May does not reveal any parasitical 
 elements. I prescribed in the meantime some doses of sulphate 
 of quinine. The patient leaves the hospital the 10th May. 
 
 Obs. xliii. — Continued palustral fever, first attack, llzema- 
 tozoa of ' paludism ; spherical bodies of small size ; relapse of fever. 
 Attack of tertian type, afterwards quotidian ; spherical bodies. 
 
 Mar., aged 23, soldier in 3rd zouaves, admitted to the hospital 
 at Constantine the 20th July, 1882. 
 
 The patient has taken fever for the first time 15th July at 
 Ain-el-Bey ; continued fever, which remains up to the time of 
 admission to the hospital. The 20th July at 4 p.m. the axillary 
 temperature is 39 C. General malaise ; headache, very acute 
 thirst, tongue dry and red at the point. The zone of splenic 
 dulness measures 9! cm. in height by \o\ in breadth. The 
 patient has not taken quinine before admission to the hospital. 
 Examination of the blood made 20th July at 4.30 p.m. : spherical 
 bodies of small size, free or adherent to some blood-corpuscles.
 
 J 76 MARSH FEVER AND ITS ORGANISM. 
 
 2 ist July fever remains 40*4° C. in the morning, 41*4° C. in the 
 evening. Typhoid state without abdominal symptoms. Examina- 
 tion of blood made 21st July at 2 p.m. : spherical bodies of small 
 or medium size, free or adherent to red blood-corpuscles. Some of 
 these bodies contain granules of pigment, endowed with very 
 quick movement. Sulphate of quinine r6o grins, on the 21st. 
 On the 22nd July 37*5° in the morning. General feebleness, 
 apathy, indifference, want of appetite. Sulphate of quinine 
 o*8o grm. morning and evening. The sulphate of quinine is con- 
 tinued in doses of o*8o grm., afterwards o'6o grm. until the 
 30th July. No return of fever. The patient goes out the 16th 
 August, 1882. The nth March, 1883, relapse of fever of the 
 tertian type. 29th March new relapse. The patient re-enters 
 the hospital of Constantine the 3rd April, 1883. 3rd April, 
 attack of fever ; 40 - 2° C. at midday ; 38*1° C. at 4 p.m. Examina- 
 tion of blood made 3rd April at 2 p.m. : spherical bodies of small 
 and of medium size, free or adherent to the red blood -corpuscles ; 
 spherical bodies containing granules of moveable pigment ; melani- 
 ferous leucocytes. Sulphate of quinine 1 grm. in the evening. 4th 
 April, 38 # 3° C. in the morning, 38'4° C. in the evening. Anaemia 
 very marked, earthy tint of the face, vertigo. The area of 
 splenic dulness measures 12 cm. in height, 13 cm. in breadth. 
 Examination of blood made 4th April : the same result as 3rd 
 April. Sulphate of quinine r8o grm. 
 
 April 5th. — Apyrexia, which is continued on the following days. 
 Sulphate of quinine is continued in doses of o*8o grm., then o"6o 
 grm. till April 12th, and again from April 15th to 19th. Examina- 
 tion of blood made on April 18th does not show existence of any 
 parasitic body. The patient leaves the hospital on April 20th 
 on sick leave. 
 
 06s. xliv. — Quotidian intermittent fever. Uxmatozoa of palu- 
 clism ; spherical bodies. Relapse of fever ; spherical bodies ; 
 flagella. 
 
 Eu., aged 22, soldier in the third zouaves, admitted to Con- 
 stantine Hospital August 21st, 1882. First attack of fever 
 August 15th at Ain-el-Bey, quotidian intermittent fever. 
 
 August 2 ist. — Apyrexia ; anaemia ; general weakness. The 
 zone of splenic dulness measures 1 1 cm. by 13 cm. Patient took a 
 dose of sulphate of quinine before entering the hospital. 
 
 29th. — Attack of fever at 1 1 a.m. ; at noon 41 C. ; at 4 p.m. 
 38*7° C. Examination of blood made August 29th at 2 p.m : sphe- 
 rical bodies free or adherent to blood-corpuscles. Sulphate of 
 quinine 1 grm. on 29th in the evening ; r6o grins, on August
 
 OBSERVATIONS. 1 77 
 
 30th ; o"8o grm. on August 31st ; o - 6o grm. from September 1st 
 to 7th. The fever did not reappear. Patient left the hospital 
 on September 16th on sick leave for two months. No relapse 
 during the furlough, which the patient spent in France. Eu. 
 returned to Algeria on November 21st, 1882. A slight relapse 
 of fever took place in December. On March 24th the fever re- 
 appeared with the tertiaii type. 
 
 April 1 6th. — Another relapse with quotidian type obtained 
 from April 16th to 19th. The patient re-entered the Constan- 
 tine Hospital on April 19th. 
 
 19th. — Attack of fever; at 10 a.m. 41 C. ; at 4 p.m. 38*5° C. 
 Examination of blood made on April 19th at 2 p.m. : spherical 
 bodies, free or adherent to some blood-corpuscles, in great numbers; 
 spherical bodies of small size ; fiagella. Sulphate of quinine 1 grm. 
 
 20th. — Apyrexia ; anaemia very marked ; earthy tint of the 
 face ; vertigo ; painful spot over the spleen. The zone of splenic 
 dulness measures 8 cm. by 10 cm. Sulphate of quinine i"8o grms. 
 Examination of blood made on April 20th at 2 p.m. : spherical 
 bodies very rare ; melaniferous leucocytes. Sulphate of quinine 
 was continued in doses of o - 8o grm. or o"6o grm. till April 27th. 
 No relapse of fever. The patient left the hospital on May 4th 
 on furlough. 
 
 Obs. xlv. — Quotidian intermittent fever {relapse). Heematozoa 
 of paludism ; crescent-shaped bodies ; spherical bodies. Relapse of 
 fever, tertian type ; spherical bodies of small or average size. Fresh 
 relapse, quotidian type ; spherical bodies of small or average size. 
 
 CI., aged 22, adjutant in the 3rd regiment of Algerian rifle- 
 men, admitted to Constantine Hospital on October 27th, 
 1882. First attack of fever September 3rd, 1881 ; quotidian 
 intermittent fever, which was stopped by several doses of sulphate 
 of quinine, but reappeared quickly. Last attack was on October 
 24th and 25th. 
 
 October 27th. — Apyrexia; anaemia very marked; general 
 weakness ; vertigo ; breathlessness ; palpitation of the heart on 
 the least effort ; slight trembling of the hands ; the splenic 
 dulness measured 13 cm. by 17 cm. Examination of blood made on 
 October 27th : crescent-shaped bodies ; spherical bodies. 
 
 From October 27th to 30th the apyrexia continued. I only 
 prescribed cinchona wine. 
 
 30th. — Slight attack; headache; at 3 p.m. temp. 38'4° C. 
 Examination of blood made on October 30th at 3 p.m. : crescent - 
 shaped bodies more numerous than on October 27th ; melaniferous 
 leucocytes. I prescribed sulphate of quinine from October 30th 
 
 12
 
 178 MARSH FEVER AND ITS ORGANISM. 
 
 to November 5th ; the fever did not reappear. The patient 
 went out November 9th on furlough. CI. passed his fur- 
 lough in France. The fever reappeared at several intervals 
 during the furlough. He returned to Algeria on February 17th, 
 1883. Eelapse of fever on March 10th; renewed attacks on 
 March 12th and 14th. The fever then took the tertian type. 
 
 CI. readmitted to Constantine Hospital on March 13th, 1883. 
 Apyrexia; anaamia very marked; general feebleness; vertigo; 
 anorexia. The area of splenic dulness measures 8 cm. by 9 cm. 
 Examination of blood made March 13th, in the morning: 
 spherical bodies small or of medium size, free or adherent to 
 blood-corpuscles ; melaniferous leucocytes ; no crescent-shaped 
 bodies. 
 
 March 14th. — Attack of fever at 4 a.m. ; at 6 a.m. axillary 
 temp. 40'4°C V at 4 p.m. 38*6°C. Examination of blood made March 
 14th, at 8.30 a.m. : sphei-ical bodies of small or medium size, 
 the latter in great number ; melaniferous leucocytes. Sulphate 
 of quinine is prescribed from March 14th to 23rd, and April 
 5th to 9th. No relapse. The patient went out on April 12th, 
 1883. 
 
 After leaving the hospital the fever reappeared on several 
 occasions; the last relapse June 12th; attacks on June 12th, 
 13th, 14th, and 15th, coming on in the morning. On June 
 15th the patient re-entered the Constantine Hospital. Attack at 
 7.30 a.m. ; at midday temp, was 40 , 6°C. ; at 4 p.m. it is only 37 # 8°C. 
 The area of splenic dulness measures 15 cm. by 17 cm. Examina- 
 tion of blood made on June 25th at 2 p.m. (at the end of the 
 attack) : spherical bodies of medium or small size ; melaniferous 
 leucocytes. Sulphate of quinine was prescribed from June 15th 
 to 23rd, o'8o grm. and o'6o grm. per day ; and from June 
 28th to July 3rd there was no relapse. Examination of blood 
 made June 17th: I did not find any parasitic elements. The 
 patient leaves the hospital on July 4th, 1883, on a furlough of 
 three months. 
 
 Obs. xlvi. — Intermittent fever. Several relapses, of which one 
 was of the tertian type. Hsematozoa of paludism ; spherical 
 bodies ; crescent -shaped bodies; segmented bodies. 
 
 G., aged 23, soldier in first foreign regiment, admitted to Val 
 de Grace January 4th, 1888. 
 
 G. had fever for the first time on August 18th, 1887, in the 
 province of Oran. Quotidian attacks ; the patient remained in 
 hospital fifty days ; he was sent afterwards on a furlough to the 
 island St. Marguerite, where the fever reappeared several times.
 
 OBSERVATIONS. 179 
 
 G. arrived in Paris on December 20th, 1887; ^he fever reappeared 
 on December 25th, and from then to January 4th (day of admis- 
 sion to the hospital) G. has had several attacks of fever. 
 
 January 3rd. — An attack of fever at 10 a.m. 
 
 4th. — Very well marked attack at hospital ; shivering at 1 1 a.m. ; 
 at 1.30 the axillary temperature is 41 C; the return to normal 
 was only complete at 7 p.m. Examination of blood made on 
 January 4th at 11 a.m., at the height of the attack : spherical 
 bodies in rather large number, pigmented, free or adherent to 
 blood-corpuscles; some segmented bodies (rose-shaped elements); 
 some melaniferous leucocytes. 
 
 5th. — 37 C. in the morning ; patient was very anaemic ; the skin 
 was earthy; the splenic dulness measured 16 cm. by 16 cm.; the 
 liveris not perceptiblyincreasedinsize. Examination of bloodmade 
 on January 5th in the morning, at beginning of attack : spherical 
 bodies in large number, pigmented, free or adherent to blood- 
 corpuscles ; segmented bodies ; several of these show a complete 
 segmentation, and the rounded corpuscles arising from this seg- 
 mentation were in part scattered. On January 5th at 9 a.m. severe 
 shivering; at 10 a.m. the axillary temperature was 41° C. The 
 attack ceased at 2 p.m. Hydrochlorate of quinine, o'6o grin., on 
 January 5th, 6th, 7th. The apyrexia continued till January 20th. 
 Examination of blood made on January 8th : not one single para- 
 sitic body found. Examination of blood made on January 13th : 
 some crescent-shaped bodies seen. 
 
 On the 20th and 22nd fresh attacks of fever. Complete apy- 
 rexia on January 21st; the quotidian fever was now changed into 
 tertian. I prescribed three doses of hydrochlorate of quinine 
 o - 6o grm. on January 22nd, 23rd, and 24th. 
 
 February 5th. — Slight attack of fever. 
 
 13th. — Relapse. Attack on February 13th, 14th, 15th. The 
 fever had now taken the quotidian type. Four doses of hydro- 
 chlorate of quinine o'6o grm. from February 14th. Examination 
 of blood made February 16th : crescent-shaped bodies found. 
 
 From the 25th to 27th three doses of hydrochlorate of quinine 
 were given. No relapse of fever. 
 
 From March 8th to 10th I again prescribed quinine. The gene- 
 ral state was improved. The splenic dulness measured only 10 cm. 
 by 10 cm. Patient left the hospital on March 18th. Kolapse of 
 fever in April. G. readmitted to Val de Grace on April 17th. 
 He had that day an attack of fever. Examination of blood made 
 April 17th. Spherical bodies of small or medium size, free or 
 adherent to blood-corpuscles ; some of the spherical bodies con-
 
 180 MARSH FEVER AND ITS ORGANISM. 
 
 tain granules of pigment alive with very active movement. I 
 did not observe flagella or crescent-shaped or segmented bodies. 
 
 April 1 8th. — Apyrexia. Examination of fresh blood : pig- 
 mented spherical bodies, free or adherent to blood-corpuscles. 
 Examination of the blood in suspended drop. On April 17th I 
 easily distinguished round the edge of the drop of blood spherical 
 bodies in the midst of blood-corpuscles. On April 20th the blood- 
 corpuscles were a little distorted (the preparation made on April 
 17th had been kept at the ordinary temperature of the labora- 
 tory) ; the spherical bodies were more or less distorted, motion- 
 less. On April 25th, eight days after the blood had been taken, 
 the spherical bodies could still be recognised in the midst of blood- 
 corpuscles. The patient took from April 18th several doses 
 of hydrochlorate of quinine, and left the hospital without 
 another attack. Examination of the blood made April 30th was 
 negative. 
 
 Obs. xlvii. — Irregular intermittent fever contracted in Tonkin 
 (several relapses). Hsematozoa of paludism ; spherical bodies; 
 segmented bodies. 
 
 Sp., aged 25, soldier in the first regiment of marines, admitted 
 to hospital of Val de Grace February 12th, 1890. 
 
 Sp. had spent two years in Tonkin, and has had several attacks 
 of intermittent fever. He had been admitted three times into 
 hospital for this cause, and sailed for France in August, 1889. 
 Since his return to France he has had sick leave. Several 
 relapses of fever since September, treated each time with sulphate 
 of quinine. 
 
 February 13th. — Apyrexia; anjeinia very pronounced. The 
 splenic dulness measured 8 cm. by 8 cm. Appetite good. 
 
 17th. — Slight attack of fever; temperature rose to 39° C. ; 
 following days malaise ; headache ; temperature rose a little in 
 the evening, on Februaiy 23rd 38*5° C. 
 
 24th. — 37*5° C. in the morning. The patient complains of 
 headache and sleeplessness. Examination of blood on February 
 24th in the morning : pigmented spherical bodies, rather large, free 
 or adherent to red blood-corpuscles ; segmented bodies. Attack of 
 fever, which began a little before the blood had been collected. At 
 1 p.m. the temperature was 39'6° C. Examination of blood made 
 on February 24th at 2 p.m during the attack. Pigmented spherical 
 bodies (rare) j melaniferous leucocytes; no more segmented bodies. 
 I prescribed three doses of hydrochlorate of quinine of r6o grms. 
 each. The fever reappeared on several occasions without regular 
 type.
 
 ADDENDUM. 
 
 This work was already out of the press when I received 
 Vandyke Carter's treatise of which mention is made on page 42. 
 I am happy to be able to give a resume of this very interesting 
 work, ' Note on some Aspects and Relations of the Blood Or- 
 ganisms in Agues by Vandyke Carter: Scientific Memoirs by 
 Medical Officers of the Army in India/ part 3, Calcutta, 1888) 
 from a translation, for which I am indebted to Dr. Anderson. 
 One will see by this resume that the researches of Vandyke Carter 
 are absolutely confirmatory of mine 
 
 Carter has examined the blood, 1st, in those subjects attacked 
 with different forms of paludism ; 2nd, in those subjects attacked 
 with other ailments. The haamatozoa have never been met with 
 in the second category of patients. 
 
 The author gives his observations on seven patients attacked 
 with paludism, in the blood of whom the presence of hasniatozoa 
 was demonstrated as follows : 
 
 1 st. Small spherical bodies, hyaline, adherent to blood-cor- 
 puscles, which represented the initial form of these parasites. 
 Carter says that the illusions by which the blood-corpuscles so 
 altered may be confounded with blood-corpuscles presenting 
 simply clear spaces, an appearance which is particularly fre- 
 quent when one examines blood in the tropics must be had 
 regard to. 
 
 2nd. Pigmented spherical bodies, free or adherent to blood- 
 corpuscles. These elements in the fresh state present amoeboid 
 movements. The pigmented granules included in the spherical 
 bodies are often alive with an intermittent movement more or 
 less rapid. 
 
 3rd. Spherical bodies with some flagella. 
 
 4th. Crescent-shaped bodies. 
 
 It follows from the descriptions of Carter, as from the plato 
 which accompanies his work, that the parasitic elements obsorved 
 by him ai'e identical with those which I have described. 
 
 The spherical bodies are those which have been met with 
 most frequently. 
 
 Carter has ascertained that the flagella, after being detached
 
 182 ADDENDUM. 
 
 from the spherical bodies, are in motion from ten to thirty 
 minutes ; they afterwards disappear, and the spherical body from 
 which they emanated remains motionless. 
 
 " It was with the greatest difficulty/' says Carter, " that I suc- 
 ceeded in preserving two or three of these flagella in preparations 
 of dried blood." 
 
 The crescent-shaped bodies remain often during several weeks, 
 even in patients under treatment with quinine. 
 
 It is very probable that the different parasitic forms indicated 
 above belong to one single species. These forms appeared under 
 the same conditions, and the order in which they follow one 
 another is in general the same. 
 
 The infection might be produced by means of drinking-water. 
 
 The spherical bodies and the flagella are destroyed by the 
 phagocytes, which do not attack the crescent-shaped bodies, 
 hence the persistence of these last elements ; the absorption of 
 the spherical bodies by the leucocytes is easy to prove. 
 
 The parasite of paludism ought to be ranked among the 
 hgematozoa ; they approach, on the one hand, the Trichomonades, 
 Trichomonas sanguinis (horses and rats), and on the other the 
 Sporozoa (crescent-shaped bodies). 
 
 There is not any constant relation between the nature of the 
 parasitic elements and the clinical form which the paludism 
 assumes. 
 
 The presence of parasitic elements in the blood of a patient 
 gives certainty to the diagnosis of paludism. 
 
 Quinine acts by increasing the activity of the phagocytes, and 
 not directly upon the hsecnatozoa.
 
 LITERATURE. 
 
 My intention is not to give the whole literature of paludism. 
 I propose merely to give a list, first, of the Avorks which have 
 appeared in recent years relating to paludism ; secondly, to 
 furnish a bibliography of the works relating to sporozoa in 
 general, and in particular to the heematozoa of animals which 
 resemble those of paludism. The study of these last parasites 
 has become inseparable from that of the hasmatozoa of paludism. 
 
 a. Hsematozoa of Paludism. 
 
 1880. 
 A. Lave ran. — Note sur un nouveau parasite trouve dans le sang 
 de plusieurs malades atteints de fievre palustre. Note 
 communiquee a l'Academie de Medecine, searice du 
 23 Nov. 
 
 — " Deuxieme note relative a un nouveau parasite trouve dans 
 
 le sang des malades atteints de fievre palustre : origine 
 parasitaire des accidents de l'impaludisme. Note com- 
 muniquee a l'Academie de Medecine, seance du 28 Dec. 
 
 — Sur un nouveau parasite trouve dans le sang des malades 
 
 atteints de fievre palustre : origine parasitaire des acci- 
 dents de l'impaludisme. Societe medicale des Hopitaux, 
 seance du 24 Dec. Bulletins et memoires de la Societe 
 medicale des Hopitaux, Memoires' p. 158. 
 
 1881. 
 A. Laveran. — Nature parasitaire des accidents de l'impaludisme : 
 description d'un nouveau parasite trouve dans le sang 
 des malades atteints de fievre palustre. Paris (chez 
 Bailliere), in-8vo, 104 pages, avec 2 planches. 
 
 — Troisieme note relative a la nature parasitaire des accidents 
 
 de l'impaludisme. Note communiquee a l'Academie de 
 Medecine dans la seance du 25 Oct. 
 
 — Communication a, l'Academie des Sciences sur la nature para- 
 
 sitaire des accidents de l'impaludisme, seance du 24 
 Oct. 
 
 1882. 
 E. Richard. — Communication a l'Academie des Sciences sur les 
 parasites de l'impaludisme, seance du 20 Fev.
 
 184 MARSH FEVER AND ITS ORGANISM. 
 
 A. Laveran. — De la nature parasitaire de Fiinpaludisme. So- 
 ciete medicale des Hopitaux, seance du 28 Avril, et 
 Revue scientifique du 29 Avril. 
 — Deuxieme communication a l'Academie des Sciences sur les 
 parasites du sang dans l'impaludisme, seance du 23 
 Oct. 
 
 1883. 
 A. Laveran. — Article Fievres palustres in 2me edition des Nou- 
 
 veaux Elements de pathologie et de clinique medicates de 
 
 Laveran et Teissier. Paris. 
 E. Richards. — Le parasite de Pimpaludisme. Revue scientifique, 
 
 p. 113. 
 
 1884. 
 A. Laveran. — Traite des fievres palustres. Paris, in-8vo (chez 0. 
 
 Doin). 
 E. Marchiafava et A. Celli. — Sulle alterazioni dei globuli rossi 
 
 nella infezione da malaria e sulla genesi della melanemia. 
 
 Reale Accademia dei Lincei. Roma. 
 Tommasi Crudeli. — Les Alterations des globules rouges du sang 
 
 dans l'infection malarique. Congres de Copenhague. 
 
 1885. 
 
 A. Laveran. — Du paludisme et de ses microbes. Societe medi- 
 cale des Hopitaux, seance du 24 Juillet. 
 
 E. Marchiafava et A. Celli. — Nouve Ricerche sulla infezione 
 malarica. Annali di Agricoltura, Roma, et Fortschritte 
 der Medicin. 
 
 Councilmann et Abbot. — A Contribution to the Pathology of 
 Malarial Fever, in American Journ. of Med. Sciences, 
 April. 
 
 Chassin. — Sur l'inoculation de la fievre intermittente. These de 
 Paris. 
 
 1886. 
 
 E. Marchiafava et A. Celli. — Studi ulteriori sulla infezione 
 
 malarica. Annali di Agricoltura. 
 Sehlen. — Ueber die Aetiologie der Malaria. Arch, de Virchow, 
 
 No. de Mai, p. 319. 
 Gr. Sternberg. — The Malarial Germ of Laveran. The Medical 
 
 Record, New York, Nos. du 1 et du 8 Mai. 
 Golgi. — SulP infezione malarica. Archivio yer le scienze mediche, 
 
 t. x, No. 4. 
 Councilmann. — Sur certains elements trouves dans le sang des
 
 LITERATURE. 185 
 
 sujets atteints de fievre intermittente, in Assoc, of 
 American Physic, 18 Juin, et Maryland Med. Journ., 
 Oct. 
 Metschnikoff. — Centralblatt f. Bacter., No. 21. 
 
 1887. 
 
 E. Marchiafava and A. Celli. — Sulla infezione malarica. Atti 
 
 delta R. Accad. med. di Roma. Travail reproduit en 
 
 francais dans les Archives italiennes de biologie, 1888, 
 
 t. ix, fasc. 3. 
 U. Arcangeli. — Le Ricerche moderne intorno Pagente dell' 
 
 infezione malarica. Rivista clinica, No. 1. 
 E. Marchiafava and A. Celli. — Hemoplasmodie rnalarique. 
 
 Association inedicale italienne, session de Pavie. 
 Metschnikoff Etude sur les affections malariennes. Russhdia 
 
 med., No. 12. 
 E. Maurel. — Communication au Congres de PAssociation medi- 
 
 cale pour Pavancernent des sciences. Toulouse. 
 — Recherches microscopiques sur Petiologie du paludisme in- 
 
 8vo de 210 pages (cliez 0. Doin). 
 Councilmann. — Nouvelles observations sur Petat du sang dans 
 
 les fievres malariales. Med. News. 
 Mosso. — Arch, de Virchow, p. 205, et Rend, della R. Accad. dei 
 
 Lincei, vol. iii, fasc. 7, 8. 
 Klebs. — Die allgemeine Pathologie, Ire pai'tie (Etiolog'ie). 
 Councilmann. — Reclierches complementaires sur le germe de la 
 
 malaria de Laveran. Communication a la reunion ami. 
 
 de la Societe pathologique de Philadelphie. 
 Laveran. — Les hematozoaires du paludisme. Annates de I' Inst. 
 
 Pasteur, 25 Juin. 
 Hallopeau. — Traite elementaire de pathologie geuerale, 2me edit., 
 
 P- 253- 
 W. Osler. — Communication a la Soc. pathol. de Philadelphie. 
 
 The Brit. Med. Journ., p. 556. Analyse in Semaine 
 
 medicate, 1887, p. 27. 
 E. Maragliano. — Sur la resistance des globules rouges du sang. 
 
 R. Accad. med. di Genova, et Berliner klin. Wochenschr., 
 
 No. 43. 
 E. Marchiafava and Celli. — Sui rapporti fra le altcrazioni del 
 
 Sangue di cane introdotto nel cavo peritoneale degli 
 
 uccelli e quello del sangue dell' uomo nella infezione 
 
 malarica. Bollett. della R. Accad. Med. di Roma, fasc. 7. 
 Pfeiffer. — Centralblatt f. Bacter.
 
 186 MARSH FEVER AND ITS ORGANISM. 
 
 Cohn. — Meme recueil, No. 12. 
 
 Tommasi Crudeli. — Deutsche med. Wochensch., Nov. 
 
 1888. 
 
 B. James. — The Micro-organisms of Malaria. Communic. a la 
 
 Societe pathol. de New York, 25 Jan. The Medic. 
 
 Record, p. 269. 
 A. Laveran. — Des hematozoaires du paludisme. Revue critique. 
 
 Annates de VInstitut Pasteur. 
 Schiavuzzi. — Untersuchungen ueber die malaria in Polen. 
 
 Miinchen med. Woch., No. 24 ; et Beitrdge zur Biologie der 
 
 PJlanzen Joum. de F. Cohn. Breslau. 
 Pampoukis. — Etude clinique et bacteriologique sur les fievres 
 
 palustres de la Grece. 
 E. Marchiafava and Celli. — Notes sur les etudes modernes de 
 
 l'etiologie de la fievre malarienne. Archivio per le scienze 
 
 mediche, t. xi ; et Archives italiennes de Biologie. 
 Codncilmann. — Neuere Untersuchungen ueber Laveran's Organ- 
 
 ismus der Malaria. Fortschritte der Medicin, Nos. 12 
 
 and 13. 
 Vandyke Carter. — Note on some Aspects and Relations of the 
 
 Blood Organisms in Ague. Scien. mem. by Med. Offic. of 
 
 the Army of India, Part III. Anal, in the Lancet, 16th 
 
 June, p. 1 20 1. 
 Golgi. — II fagocitismo nell' infezione malai-ica. Communic. a 
 
 la Soc. med.-chirurg. de Pavie, 19 Mai. Joum. la Riforma 
 
 medica, Mai. 
 Jeunhomme. — I/Etiologie de la malaria d'apres les observations 
 
 anciennes et modernes. Arch, de Med. militaire, t. xii, 
 
 pp. 57 et 145. 
 Evans. — Etat du sang dans les fievres intermittentes. Soc. 
 
 clinique de Londres. Analyse in Bulletin med., p. 608. 
 A. Cattaneo et A. Monti. — Les parasites du paludisme et les 
 
 alterations degeneratives des globules rouges. Com- 
 munic. au douzieme Congrcs med. de Pavie, et Arch, per 
 
 le scienze med., t. xii. 
 Celli et Guarnieri. — Sur la structure intimo du plasmodium 
 
 malarise. Riforma med., 7 Septembre et 12 Octobre. 
 N. A. Sacharofp. — Recherches sur le parasite de la fievre palustre. 
 
 C. r. des seances de la 80c. med. de Tijlis ; Gentralbl. f. 
 
 Bacteriol., 1889, p. 452; et Arch, denied, experim., 1 May, 
 
 1889. 
 — Sur l'analogie du parasite de la fievre intermittente avec celui
 
 LITERATURE. 187 
 
 de la fievre recurrente. C. r. des seances de la Soc. de 
 
 med. de Tiflis, No. xi ; Centralbl. f. Bacterial., 1889; et 
 
 Arch, de med. exper., May, 1889, p. 482. 
 Chenzinsky (Odessa). — Zur lehre ueber den Mikro-organismus der 
 
 Malaria-fiebers. Centralblatt f. Bacteriol., Bd. iii. 
 Soulie. — Etiologie du paludisme. Communic. a la Soc. de Biol. 
 
 G. r. de la Soc. Biologie, p. 766. 
 Giard. — Note sur l'infection paludeenne, Societe de Biologie, 
 • seance du 24 Novembre. 
 
 1889. 
 
 Nepveu. — Etude sur le sang des paludiques. Ass. francaise pour 
 PAvancement des Sciences, Paris, 14 Aout, 1889. 
 
 Golgi. — Intorno al preteso bacillus malaria di Klebs, Tommasi 
 Crudeli e Schiavuzzi. Torino. 
 
 — Sur le developpenient des parasites du paludisme dans la fievre 
 
 tierce. Fortschr. der Med., iii, et Arch, per le scienze med., 
 
 t. xiii, p. 173. 
 A. Celli and G. Guarnieri. — SulP etiologia dell' infezione ma- 
 
 larica. Ann. di Agricoltura. 
 P. Canalis. — Sopra il ciclo evolutivo delle forme semilunari di 
 
 Laveran et sulle febbri malariche irregolari e perniciose 
 
 die da esse dipendono. Roma. 
 Chenzinsky. — Contribution a l'etude des micro-orgauismes du 
 
 paludisme. Tbese de doctorat, Odessa. 
 T. Gualdi et E. Antolisei. — Due casi di febbre malarica speri- 
 
 mentale. Accad. med. di Roma, Anno xv (1888-9), 
 
 fasc. 6. 
 T. Coronado Cuerpos de Laveran. — Microbios del Paludismo. 
 
 Cronica medico-quirurgica de la Habana, No. x. 
 Golgi. — Communication sur les fievres intermittentes a long inter- 
 
 valle. Soc. medico-chirurgic. de Pavie, 6 Avril. 
 
 — Sur l'etiologie du paludisme. Ass. med. italiennes Congres de 
 
 Padoue. 
 
 P. Canalis. — Studi sulla infezione malarica. Sulla varieta paras- 
 sitaria delle forme semilunari di Laveran. Sulle febbri 
 mal. che da esse dipendono, Torino, 1889, et Giomale 
 medico del esercito et delta marina, December. 
 
 Celli. — Dei protisti citofagi. Hi for ma me.dica, May. 
 
 Marchiafava and Celli. — Sulle febbri mal. predominante noil' 
 estate e nelF autunno in Roma. Riforma medica, 13 
 September, 1889, et Atti delta R. Accad. med. di Roma, 
 Anno xvi, vol. v, serie 2.
 
 188 MARSH FEVER AND ITS ORGANISM. 
 
 R. Feletti et B. Grassi. — Sui parassiti della malaria (Nota pre- 
 liniinare). Catania, 22 Dec. 
 
 E. Antolisei and A. Angelini. — Due altre casi di f ebbre malarica 
 
 sperimentale. Riforma medica, September. 
 T. GrUALDi et E. Antolisei. — Una quartana sperimentale. Riforma 
 medica, November. 
 
 — Inoculazione delle forme semilunar di Laveran. Riforma 
 
 medica, November. 
 
 Paltauf et Kahler. — Communic. a la Soc. imperio-royale des 
 Medecins de Vienne, 20 Decembre, 1889. Semaine medi- 
 cate, 1890, p. 8. 
 
 Hayem. — Du sang et de ses alterations anatomiques, Paris, 1889, 
 
 P- 347- 
 N. A. Sacharofp. — Le Paludisme sur le chemin de fer de Trans- 
 
 Caucasie. Observations microscopiques, Tiflis, 1889. 
 Klein. — Examen des elements figures du sang au point de vue 
 
 clinique. College des docteurs de Vienne, December, 
 
 1889. Bull, med., 1890, p. 40. 
 W. Osler. — Valeur de l'organisme de Laveran dans le diagnostic 
 
 de la malaria. Johns Hopkins Hosp. Bull., No. 1, 1889— 
 
 90. 
 
 1890. 
 Jaccoud. — De la fievre intermittente, son traitement, sa nature. 
 
 Semaine medicale, p. 25. 
 Vallin. — Les heniatozoaires du paludisme. Revue d'hygiene,. 
 
 p. 97. 
 A. Celli et E. Marchiapava. — Intorno a recenti lavori sulla 
 
 natura della causa della malaria. Bullettino della R. 
 
 Accad. med. di Roma, 1889—90, Anno xv, fasc. 2. 
 
 F. Plehn. — Beitrag zur Lehre der Malaria-infection. Zeitsch. 
 
 fur Hygiene, p. 78. 
 
 — Communic. a la Soc. de Med. de Berlin, 5 Mars, et Berlin 
 
 klin. Wochensch., 31 Mars. 
 
 Hallopeau. — Traite elementaire de pathologie generale, 3me edit.,, 
 ire partie. 
 
 R. v. Jaksch. — Ueber Malariaplasmodien. Prager med. Wo- 
 chensch., 4. 
 
 P. Canalis. — Contributo alia storia degli studi moderni sulla in- 
 fezione malarica. Spalla/nzani. 
 
 — Intorno a recenti lavori sui parassiti della malaria. Lettera 
 
 al Presidente della R. Accad. med. di Roma. 
 
 — Etude sur l'infection palustre. Fortschr. der Med., Nos. 8 
 
 et 9, pp. 285, 325.
 
 LITERATURE. 189 
 
 R. Feletti and B. Grassi. — Sui parassiti della malaria. Riforma 
 
 medica, Mars. 
 Soulie. — Sur rhematozoaire du paludisme. Bull. med. de V Algerie, 
 
 p. 228. 
 E. Antolisei. — L'Ematozoa della quartana. Riforma medica, 
 
 January. 
 E. Antolisei et A. Angelini. — Osservazioni sopra alcuni casi 
 
 d' infezione malarica con forme semilunari. Arch, italiano 
 
 di clinica medica. 
 E. Antolisei. — SulP ematozoo della terzana. Riforma medica, 
 
 Janvier. 
 E. Antolisei et A. Angelini. — ISTota sul ciclo biologico dell' ema- 
 tozoo falciforme. Riforma medica, Mars. 
 Cornil et Babes. — Les Bacteries, 3me edit., t. ii, p. 163. 
 H. de Brun. — Les Causes individuelles ou somatiques de l'impalu- 
 
 disme. La Med. moderne, 8 May. 
 Bamberger. — De laplasmodie de la malaria. Soc. imperio-royale 
 
 des Medecins de Vienne, 2 May. 
 A. Celli et Marchiafava. — Sulle febbri predominanti nell' estat 
 
 e nell' autunno in Roma. Arch, per le Scienze med. di 
 
 Bizzozero, t. xiv, p. 117 (avec une planche). 
 E. Antolisei. — Considerazioni intorno alia classificazione dei 
 
 parassiti della malaria. Riforma medica, Avril. 
 A. Valenti. — Etiologia e patogenesi della melanemia e della in- 
 fezione malarica. Gaz. med. di Roma. 
 A. Laveran. — Au sujet de Fhernatozoaire du paludisme et de son 
 
 evolution. Soc. de Biologie, seance du 21 Juin. Comptes 
 
 rendus, p. 374. 
 Luzet. — Des agents infectieux du paludisme. Arch. gen. de Med., 
 
 t. ii, p. 61. 
 C. Terni et G. Giardina. — Sulle febbri irregolari da malaria. 
 
 Rivista d' igiene e sanita puhblica, 16 Mai. 
 — Meme travail avec analyse des observations. Publication 
 
 de la direction de la sante publique, Rome. 
 Paltaup. — Etiologie de la fievre intermittente. Wiener med. 
 
 Wochensch. 
 Dock. — Etude sur Petiologie de Finfection malarieuno et des 
 
 hematozoaires de Laveran. Med. News, 19 Juillet. 
 A. Laveran. — Des hematozoaires voisins de ceux du paludisme 
 
 observes chez les oiseaux. Communication a la Soc. de 
 
 Biologie, seance du 5 Juillet. Bull., p. 422. 
 T. V. Coronado. — El microbio de la malaria. Gronica medico- 
 
 quirurgica de la Habana, No. vi, p. 287.
 
 190 MARSH FEVER AND ITS ORGANISM. 
 
 Quincke. — Ueber Blutuntersuchungen bei Malaria-kranken (sur 
 l'examen du sang- dans le paludisme). Kiel et Mitth. d. 
 Verein. Schleswig Hoist. Aerzte, No. 4. 
 
 Rosenbach. — Deutsch. med. Wochensch., No. 16. 
 
 L. Pfeiffer. — Corresp. Bl. d. allg. arztl. Vereins v. Thuringen, 145. 
 
 — Les Protozoaires pathogenes. Iena. 
 
 Kollmann. — Les Pseudo-microbes du sang kuinain normal. Con- 
 gres de Berlin (Section de medecine interne). 
 
 T. Gualdi, Bozzolo. — Discussion de la communication precedents 
 Congres de Berlin. 
 
 GrOLGi. — Representation photograpliique du developpement des 
 parasites de Pinfection paludeenne. Congres de Berlin. 
 
 A. Bignami. — Reckerches sur l'anatomie patliologique des fievres 
 pernicieuses. Atti delta B. Accad. med. di Boma, Anno 
 xvi, t. v. 
 
 A. Celli and Marchiafava. — II reperto del sangue nelle febbri 
 malariclie invernali. B. Accad. med. di Boma, Anno xvi 
 (1889— go), fasc. 6. 
 
 Veronesi. — Yaleur clinique de l'examen du sang dans l'infection 
 paludeenne. Atti d. Accad. med. Perugia, ii, No. 1. 
 
 Dolega. — Etiologie de la malaria, ge Congres de medecine in- 
 terne de Vienne, 18 Avril. 
 
 — Blutbefunde dei Malaria (Etat du sang dans la malaria). 
 
 Fortsch. der Med., October 15. 
 Anderson. — The Malarial Fever in Mauritius. The Lancet, p. 3gi . 
 Golgi. — Sur le cycle evolutif des parasites malariques dans la 
 
 fievre tierce. Diagnose differentielle entre les parasites 
 
 endoglobulaires malariques de la fievre tierce et ceux de 
 
 la fievre quarte. Arch. ital. de biologie, t. xiv, fasc. 1, 2. 
 D. Reshelilo. — Etiologie de la malaria, St. Petersbourg. 
 Gr. Titov. — Importance diagnostique des protozoaires de la fievre 
 
 paludeenne, St. Petersbourg. 
 Grassi et Feletti. — Di un' ameba che si trova in vita libera e eke 
 
 potrebbe rapportarsi ai parassiti malarici (note prelimi- 
 
 naire), Juin. 
 Maragliano. — De la patkologie du sang. Congres de la Soc. 
 
 ital. de Med. interne, Rome, Oct. 
 
 — Sur les fievres intermittentes malariques a longs intervalles. 
 
 Fondements de la classification des fievres malariques. 
 
 Arch. ital. de biologie, t. xiv, fasc. 1, 2. 
 J. M. Atkinson. — Annual Beport on the Medical Department for the 
 
 year i88g, Hongkong, i8go. Appendix D. 
 A. Laveran. — De Pexamen du sang au point de vue de la reckercke
 
 LITERATURE. 191 
 
 de l'hematozoaire du paludisine. Soc. med. des Hopitaux, 
 
 seance du 28 Nov. 
 A. Laveran. — Au sujet des alterations des globules rouges du sang 
 
 qui peuvent etre confondues avec les hematozoaires du 
 
 paludisine. Soc. de Biologie, 27 Dec. 
 Danilewsky. — Sur les microbes de l'infection malarique aigue 
 
 et chronique chez les oiseaux et chez l'homme. Annates 
 
 de VInstit. Pasteur, Dec. 
 Romanowsky. — Sur la structure des parasites du paludisme. 
 
 Wratsch., No. 52, p. 1171. 
 L. Ppeiffer. — Vergleichende Untersuchungen ueber Schwarm- 
 
 sporen und Dauersporen bei den Coccidieninfectionen 
 
 und bei intermittens. Fortsch. der Medicin, 15 Dec, 
 
 1890. 
 
 b. Sporozoaires en general — Hematozoaires des animaux. 
 
 G. Valentin. — Ueber ein Entozoon im Blute von Salmo fario. 
 
 Miiller's Archiv, 1841, p. 435. 
 G. Gluge. — Ueber ein eigenthiimliches Entozoon im Blute des 
 
 Frosches. Mutter's Archiv, 1842, p. 148. 
 Grdby. — Sur une nouvelle espece d'heinatozoaires, Trypanosoma 
 
 sanguinis. Acad, des Sciences, 1843. Comptes rendus, 
 
 xvii, p. 1 134. 
 Gros. — Observ. et inductions microscopiques sur quelques para- 
 sites. Bull, de la Soc. imp. des Naturalistes de Moscou, 
 
 1845. 
 C. Wedl. — Beitrage zur Lehre von den Hematozoen. Denhschr. 
 
 der Wiener Ahad. der Wis sen., 1850. 
 E. Ray Lankester. — On Undulina. Quarterly Journal of Microsc. 
 
 Science, 1871. 
 A. Schneider. — Arch, de zoologie exper., t. x, 1878. 
 T.R.Lewis. — Flagellated Organisms in the Blood of Healthy Rats. 
 
 Quarterly Journal of Microsc. Science, 1879, p. 109. 
 J. Gaule. — Ueber Wurmchen welcha aus den Frosch-blut- 
 
 korperschen ausvvandern. Arch, fur Physiologic, 1880—81. 
 Wallerstein. — Ueber Drepanidium ranarum. Inaug. Diss., 
 
 Bonn, 1880. 
 W. Flemming. — Die Cytozoen. Biolog. Centralblatt, 1881. 
 Ray Lankester. — On Drepanidium ranarum. Quarterly Journal 
 
 of Microsc . Science, 1882. 
 Kunstler. — Recherches sur les infusoires parasites. Comptes 
 
 rendus de VAcad. des Sc, 1883, p. 755.
 
 192 MAESH FEVER AND ITS ORGANISM. 
 
 Grassi. — Sur quelques protistes endoparasites appartenant aux 
 classes des Flagellata, Lobosa, Sporozoa, et Ciliata. 
 Arch. ital. de biologie, 1882—3. 
 
 Mitrophanow. — Beitrage zur Kenntniss der hematozoen. Biol. 
 Gentralblatt, 1883. 
 
 Balbiani. — Lecons sur les sporozoaires, Paris, 1884. 
 
 E. M. Crookshank. — Flagellated Protozoa in the Blood of Dis- 
 eased and apparently Healthy Animals. Journ. of the R. 
 Microsc. Soc, p. 913, 1886. 
 
 Danilewsky. — Materiaux pour servir a la parasitologie du sang. 
 Arch, slaves de biologie, 1886—7. 
 
 — Contribution a, la question de l'identite des parasites patho- 
 
 genes du sang chez Phomme avec les hematozoaires 
 chez les animaux sains. Centralbl. f. med. Wiss., 1886—7. 
 
 — Recherches sur la parasitologie comparee du sang : Zoo- 
 
 parasites du sang des oiseaux. Kharkov, 1888 (Ouvrage 
 publie en langue russe). 
 R. Blanchard. — Art. " Hematozoaires " in Dictionn. encyclop. des 
 8c. med. 
 
 — Bibliographie des hematozoaires, Bull, de la 80c. zoologique 
 
 de France, t. xii, 1887. 
 Vandyke Carter. — Sur la maladie infectieuse du rat et du cheval 
 
 dans l'Inde. Extrait des Memoires scient. des medecins 
 
 militaires de Varmee des Indes. Calcutta, 1888. 
 Chalachnikov. Recherches sur les parasites du sang chez les 
 
 animaux a sangfroid et a sang chaud (en langue russe). 
 
 Kharkov, 1888. 
 Danilewsky. Nouvelles recherches sur les parasites du sang 
 
 des oiseaux. Kharkov, 1889. 
 
 — Recherches sur les hematozoaires des tortues. Kharkov, 
 
 1889. 
 J. Steinhaus. — Karyophagus salamandrse. Arch, de Virchow, 
 
 1889, t. cxv. 
 T. Smith. — Sur la fievre du Texas du bceuf. The Medical Record, 
 
 Dec, 1889. 
 Grassi and Feletti. — Les parasites du paludisme chez les 
 
 oiseaux. Bull, mensuel de V Acad, des 8c. naturelles de 
 
 Catane, 23 Mars, 1890. 
 W. Kruse. — Ueber Blutparasiten. Arch, de Virchow, 1890, t. 
 
 cxx, p. 541. 
 
 — Ueber Blutparasiten. Arch, de Virchow, 1890, t. cxxi, p. 
 
 359-
 
 LITERATURE. 193 
 
 Danilewsky. — Developpeinent des parasites malariques dans les 
 
 leucocytes des oiseaux (leucocytozoaires). Annates de 
 
 I'Institut Pasteur, 1890, p. 427. 
 Gabritchewsky. — Contribution a l'etude de la parasitologic du 
 
 sang. Annates de I'Institut Pasteur, 1890, p. 440. 
 Grassi et Feletti. — Ancora sui parassiti degli uccelli. Bull. 
 
 de I' Acad, des 8c. nat. de Catane, Juin, 1890. 
 Pfeiffer. — Les pi'otozoaires pathogenes. Iena, 1890. 
 
 1:;
 
 INDEX. 
 
 A. 
 
 Age, influence of, 102 
 Altitudes, influence of, 101, 136 
 Anaemia, 107 
 Angelini, 46, 77 
 Animals, hsematozoa in, 62 
 
 — inoculation of, 28 
 Antipyrin, 135 
 Antolisei, 46, 61, 77 
 Avsenious acid, 134 
 
 B. 
 
 Bacillus malariie, 31, 53 
 
 Bignani, 49 
 
 Birds, hsematozoa in, 66 
 
 Blood, palustral, examination of, 22 
 
 Canalis, 45 
 
 Carter, Vandyke, 42, 181 
 
 Cases, 143 
 
 Celli, 30, 56, 76 
 
 Chemical theory of paludism, 54 
 
 Chloral hydrate, 134 
 
 Cinchona, 120, 134 
 
 Climate, change of, in treatment of 
 
 paludism, 119 
 Conditions predisposing to paludism, 
 
 individual, 102 
 — meteoric and telluric, 100 
 " Congenital " paludism, 104 
 Coronado, 44 
 
 Councilman, 39 
 Crescent-shaped hodies, 17 
 Cultivation of the hsematozoon, 27 
 
 D. 
 
 Danilewsky, 65, 69, 81, 118 
 Defence of organism, means of, 115 
 Drugs in treatment, 134 
 Dysentery, 81 
 
 E. 
 
 Edington, 59 
 Emetics, 134 
 Eucalyptus, influence of, 135, 141 
 
 Feletti, 46, 61, 70, 83 
 Fevers, of first invasion, 87 
 
 — quartan, 92 
 
 — quotidian intermittent, 90 
 
 — tertian, 91 
 
 — with variable type, 93 
 Filariosis, 97, 109, 110 
 Flagella, 14 
 
 Forms of parasite, relation of, to febrile 
 types, 87 
 
 G. 
 
 German writers, 50 
 Giardina, 49
 
 190 
 
 INDEX. 
 
 Goitre, 80 
 
 Golgi, 37- 53, 84, 11S 
 Grassi, 46, 61, 70, 83 
 Gualdi, 77 
 Guarnieri, 34, 60 
 
 H. 
 
 Haernatozoon of paludism — 
 
 — action of, 107 
 
 — action of quinine on, 121 
 
 — cultivation of the, 27 
 
 — description of, 9 — 22 
 
 — forms of, in external media, 96 
 
 — inoculation of animals with, 28 
 
 — nature of, 55 
 
 — polymorphism of, 81 
 
 — relative frequency of forms of, 2 1 
 
 — the pathogenic cause of paludism, 
 
 74 
 
 — variations in numbers, in 
 
 — varieties of, 83 
 Hemoglobinuria due to quinine, 129 
 Hsemoplasmodia, malarial, 33 
 Hayem, 58 
 
 Heart, action of quinine on, 130 
 Heat, influence of, 10 1 
 Humid soil, influence of, 101 
 Hydrotherapeutics in treatment of 
 paludism, 119 
 
 Incubation, 105 
 Infection, mode of, 97 
 Injection experiments, 75 
 Inoculation, 75 
 
 — in animals, 28 
 Intcrmittency not peculiar to 
 dism, 109 
 
 James, 41 
 
 pain- 
 
 Latent period, 106 
 Literature, 183 
 
 M. 
 
 Maragliano, 56 
 Marchiafava, 30, 56, 76 
 Maurel, 41 
 Metschnikoff, 1 16 
 Mosquitoes, 97 
 Mosso, 54 
 
 O. 
 
 Observations, 87, 143 — 180 
 
 — of other writers, 30 — 54 
 Osier, 40 
 
 Kcenig, 6\ 
 
 Kollinium, 60 
 
 Paget's disease of mamma, 81 
 Parasitic theory of paludism, history 
 
 of, 1 
 Pathogenesis, 107 
 
 Pernicious symptoms, treatment of, 133 
 Phagocytosis, 115 
 Pigment, 107 
 Plasmodia, 33 
 Plehn, 51 
 Polimitus, 67 
 Precautions, sanitary, 140 
 Prophylaxis, 135 
 Pseudo-spirille, 68 
 Pseudo-vacuoles, 66 
 Pseudo-vermicules, 67 
 Purgatives, 134 
 
 Q. 
 
 Quincke, 51 
 
 Quinine, action of, 74, 120 
 
 — amount of alkaloid in salts of, 124 
 
 — as a prophylactic, 137 
 
 — dangers of, 128 
 
 — doses of, 132
 
 INDEX. 
 
 19: 
 
 Quinine, formulae of, 125 
 
 — history of, 120 
 
 — hypodermic injections of, 123, 125, 
 127 
 
 — influence of, on haematozoa, 121 
 
 — influence of, on phagocytes, 123 
 
 — modes of administering, 123 
 
 — precautions in administering, 131 
 
 — salts of, 123 
 
 — solubility of salts of, 124 
 
 — time of administration, 131 
 
 R. 
 
 Race, influence of, 102 
 Rose-shaped bodies, 19 
 
 S. 
 
 Sacharoff, 43, 81 
 Schiavussi, 52 
 Schwalb, 54 
 Segmented bodies, 19 
 Sehlen, 53 
 Site of house, 137 
 Soulie, 42 
 
 Spherical bodies, 8 
 Spleen in paludism, no 
 Sporozoa, classification of, 62 
 Sternberg, 36 
 
 Sulphur mines, influence of, 143 
 Sydenham, 131 
 
 Symptoms, mode of production of, 107 
 — treatment of, 133, 134 
 
 T. 
 
 Talamon, 57, 60 
 
 Terni, 49 
 
 Tonics, nse of, 119 
 
 Trypanosoma sanguinis avium, 68 
 
 U. 
 
 Unity of paludism, 84 
 Urine, toxicity of, 112 
 
 W. 
 
 Water, a cause of infection, 98 
 — precautions as regards, 136 
 Wyssokowitsch, 117 
 
 PRINTED BY AUUUD AND SON, 
 BAKTnOLOMKW CLOSK, LONDON, B.C., AND 20, HANOVKIt SQUAHE, W
 
 PLATE I. 
 
 i. Normal red blood-corpuscle. 
 
 2 — 6. Blood-corpuscles, to which are attached small spherical bodies without 
 pigment, numbering from i to 4. 
 
 7 — 13. Blood-corpuscles, to which are attached some pigmented spherical bodies, 
 numbering from 1 to 4. 
 
 14 — 18. Blood-corpuscles, to which are attached pigmented spherical bodies 
 which have almost completely destroyed the blood-corpuscles. 
 
 19, 20. Free spherical bodies at their full development. 
 
 21. Small free pigmented spherical bodies. 
 
 22. Spherical bodies massed together. 
 
 23 — 28. Different phases of development of segmented bodies. 
 
 2 9 — 3 1 - Spherical bodies with flagella, numbering from 1,3,01-4; the flagel- 
 lum of body 31 shows, towards its middle, a slight swelling. 
 
 32. A flagellum detached. 
 
 33 — 36- Crescent-shaped bodies ; one of the bodies (34) is adherent to a blood- 
 corpuscle, another (36) shows a double outline. 
 
 37, 38. Oval bodies derived from crescent-shaped bodies. 
 
 39 — 41. Melaniferous leucocytes. 
 
 42 — 44. Pigmented hyaline bodies representing dead forms of the haematozoon 
 of paludism. 
 
 All these bodies have been drawn under a power of about 1000 diameters.
 
 • © ® © @ © 
 
 
 10 
 
 11 
 
 
 13 
 
 14 
 
 15 
 
 16 
 
 17 
 
 18 
 
 P*i 
 
 
 
 
 y 
 
 29 
 
 22 
 
 31 
 
 < 
 
 : 
 
 23 
 
 25 
 
 m 
 
 27 
 
 24 
 
 • 
 
 26 
 
 ? 
 
 28 
 
 
 - 
 
 33 
 
 34 
 
 i 
 
 35 
 
 i 
 
 1 
 36 
 
 ft 
 
 37 
 
 ,, 
 
 -• 
 
 38 
 
 
 • 
 
 39 
 
 4-0 
 
 • 
 
 ••• 
 
 4-1 
 
 42 
 
 •.*&• 
 
 43 
 
 
 44 
 
 iverandel. 
 
 iletlibh
 
 PLATE II. 
 
 Figure A. 
 
 Haematozoa of paludism in fresh blood. In the midst of normal red blood- 
 corpuscles are seen the following bodies : 
 
 a. Group of three blood-corpuscles, to which ai*e attached small spherical bodies. 
 
 b. Small free spherical bodies. 
 
 c. Spherical body of medium size, adherent to a red blood-corpuscle. 
 >1. Spherical body come to its full development, free. 
 
 e. Spherical body with two flagella. 
 
 /. Detached flagellum. 
 
 g, </. Crescent-shaped bodies. 
 
 h. Melaniferous leucocytes. 
 
 i. Normal leucocyte. 
 
 ( X 500 diameters.) 
 
 Figure B. 
 
 Ila'inatozoa of paludism in the blood, dried and stained with methyl blue. 
 In the midst of normal blood-corpuscles the following bodies are seen : 
 
 a, a, a. Blood-corpuscles, to which are attached spherical bodies in different 
 stages of their development. 
 
 b, b, b. Detached spherical bodies. 
 
 c, c, c. Crescent-shaped bodies. 
 
 d, d. Leucocytes. 
 
 ( X 500 diameters.) 
 
 All the parasitic bodies in Figures A and B of this plate have been drawn 
 from nature; they have been grouped into the same field of the microscope in 
 order not to multiply the figures. The same applies to Figures A and B of 
 Plate III.
 
 A 
 
 B 
 
 eran del 
 
 Nicoletlit.li
 
 PLATE III. 
 
 Figure A. 
 
 Hsernatozoa of paludisin in the blood, dried and submitted to the double stain 
 of eosin and methyl blue. In the midst of normal red blood-corpuscles, stained 
 rose colour by eosin, the following bodies are seen : 
 
 a. a, a, a. Spherical bodies adherent to red blood-corpuscles. 
 
 b. Two free spherical bodies come to their full development. 
 
 c. Two crescent-shaped bodies. 
 
 d. Segmented bodies. 
 
 e. e. Leucocytes. 
 
 ( X 500 diameters.) 
 
 Figure B. 
 
 Hsernatozoa in the blood of birds, dried and double stained with eosin and 
 methyl blue. Among the normal red blood-corpuscles the following bodies are 
 seen : 
 
 a, a, a. Red blood-corpuscles containing cytozoa more or less developed. 
 
 b. Three free cytozoa. 
 
 c. Free vermicules ; to one of them the remains of a blood-corpuscle is still 
 attached. 
 
 d, d. Leucocytes. 
 
 (X 500 diameters.)
 
 Nicole!
 
 PLATE IV. 
 
 Figure A. 
 Different appearances of the hsematozoa of the tortoise (after Danilewsky). 
 
 i, 2, 3, 4. Red blood-corpuscles containing one or two hsemocytozoa of small 
 size ; by the side of the cytozoa, which form clear spots, the nuclei of the blood- 
 corpuscles can be recognised. 
 
 5, 6. The haemocytozoa take an elongated form in the interior of the blood- 
 corpuscles ; a nucleus in each vermicule is seen. 
 
 7, 8. Vermicules become enlarged ; they are folded on themselves. 
 
 9, 10, 11, 12. Vermicules with the remains of red blood-corpuscles. 
 
 13. Free vermicule. 
 
 14. Free vermicule, with the constrictions which they form when in motion. 
 
 15. Commencement of segmentation ; the parasitic mass has the appearance 
 of a raspberry. 
 
 16. Cytocyst, with its parasitic embryo. 
 
 17. Crushed cytocyst. 
 
 18. Mobile falciform embryo, with transverse constriction. 
 
 Figure B. 
 
 Some appearances of the hsematozoa of birds (after Danilewsky). 
 
 1, 2, 3, 4. Different forms of pseudo-vacuoles — that is to say, hsemocytozoa at 
 different phases of their incomplete development ; the red blood-corpuscles are 
 more or less distorted, some of them containing several hsemocytozoa. Bj r the 
 side of the hsemocytozoa, which form clear spots, are seen the nuclei of the blood- 
 corpuscles. 
 
 5. Mobile pseudo-vermicules, containing each a nucleus ; one of these pseudo- 
 vermicules shows a constriction produced during movement. 
 
 6. Red blood-corpuscle with cytozoon, from which are escaping spirilliform 
 bodies. 
 
 7. Spirilliform bodies under a high power. 
 
 8. 9. Polimitusof the blood of birds, with flagella. By the side of the polimitus 
 body the nuclei of the blood-corpuscles are still seen. 
 
 10. Pseudo-spirilla, or otherwise called flagella, detached.
 
 
 1 
 
 
 
 M<> 
 
 8 
 
 i/.a 
 
 10 
 
 3r; 
 
 
 -.•» 
 
 '•/* 
 
 
 13 
 
 
 
 16 
 
 17 
 
 18 
 
 
 
 
 
 
 
 
 Fig . 'Mnatozoa of torto 
 
 
 
 • i if;: 
 
 
 
 ; 
 
 ... 
 
 * 
 
 
 
 ? * 
 
 ; 
 
 
 
 
 
 ?r- 
 
 f 
 
 ;k 
 
 * I 
 
 f 
 
 
 del. 
 

 
 PLATE V. 
 
 (The photographs reproduced in this plate and in the following one have been 
 taken by Monsieur Yvon from my preparations.) 
 
 FlGURE I . 
 
 Hseniatozoa of paludism. Dried blood. In the midst of normal blood-cor- 
 puscles two bodies becoming pigmented may be distinguished towards the centre. 
 
 (Magnified 700 diameters.) 
 
 Figure 2. 
 
 Hseniatozoa of paludism. Dried blood doubly stained with eosin and methylene 
 blue. In the midst of normal blood-corpuscles a pigmented spherical body may 
 be distinguished. 
 
 (Magnified 500 diameters.) 
 
 Figure 3. 
 
 Section of the brain of a subject who died from an attack of pernicious coma. 
 The section made after hardening in the usual way has been stained with carmine 
 and mounted in Canada balsam. The capillary vessel found in the section shows 
 a very characteristic black piquete formed by the agglomeration of pigmented 
 parasitic elements (melanseniia). 
 
 (Magnified about 100 diameters.) 
 
 Figure 4. 
 
 Histological section of the liver of a subject who died from an attack of per- 
 nicious coma. Section made after hardening, stained with picro-carmine and 
 mounted in Canada balsam. The capillary network contains numerous pigmented 
 elements. The pigment forms black spots of variable size and shape (nielanseruia). 
 
 (Magnified about 100 diameters.
 
 Fiy / 
 
 
 ■^ 
 
 ; ;U 
 
 
 - 
 
 
 
 Plal 
 
 //■y '-.' 
 
 
 v.- 
 
 -; 
 
 ^.J' 
 
 Fiq.'l- 
 
 it 
 
 
 ■#*■* 
 
 iSson.Ediieur 

 
 PLATE VI. 
 
 Figure i. 
 
 Haematozoa of birds. Dried jay's blood. In the midst of normal blood-cor- 
 puscles there may be distinguished three corpuscles with pigmented rounded 
 parasites. The corpuscle which is in the centre of the preparation is deformed, the 
 parasite occupying its greater part, and pushing the nucleus aside. The two other 
 corpuscles invaded by the parasites are less deformed, the parasites twisting round 
 the nucleus. 
 
 (Magnified 500 diameters.) 
 
 Figure 2. 
 
 Dried pigeon's blood. In the midst of normal blood-corpuscles five corpuscles 
 may be distinguished containing rounded haematozoa. 
 
 Figure 3. 
 
 Dried jay's blood. By the side of normal blood-corpuscles there is seen a cor- 
 puscle with a pigmented rounded parasite, which is beginning by its extremities 
 to alter the shape of the nucleus. The part of the corpuscle which is not altered is 
 plainly distinguished from the part invaded by the parasite, the latter being paler. 
 
 (Magnified 1200 diameters.) 
 
 Figure 4. 
 
 Blood of the chaffinch. In the midst of normal blood-corpuscles there is a pig- 
 mented spherical body furnished with a flagellum (the preparation has been stained 
 with gentian violet).
 
 
 Fry J 
 
 Fig :/ 
 
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