Ms \^ $fBi 1# ^hl ^|!J^ ■1 mM^ Mft THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA PRESENTED BY PROF. CHARLES A. KOFOID AND MRS. PRUDENCE W. KOFOID l^'f'iiL Z in en M tn o H '"^ 6 < c ?i W u > '-' en -w C/5 P C nj IM 5l ^ 6 -S .1:; tuo Sb -5 ^ ^ OJ -5 P J Q AMCEBIC OR TROPICAL DYSENTERY ITS COMPLICATIONS AND TREATMENT BY W. CARNEGIE BROWN, M.D. Member of the Royal College of Physicians ILonDon JOHN BALE, SONS & DANIELSSON, Ltd. OXFORD HOUSE 83-91, GREAT TITCHFIELD STREET, OXFORD STREET, W. 1910 PREFACE. Since Baly chose dysentery as the subject for the Goulstonian Lectures, sixty years ago, there have been many revolutionary changes- in our conceptions of disease. At that time dysentery was still prevalent in Great Britain, smouldering for the most part in the slums and hovels of the poorer classes, but occasionally blazing out into virulent epidemics which attacked all sections and grades of society. Thanks to hygienic reform and progress, domestic interest in the condition has considerably narrowed ; for, although infection still lurks in the western districts of Scotland and Ireland, and lingers with a strange persistence in many of our most efficient lunatic asylums, dysentery has been practically banished from the general life of England. From an Imperial and Colonial point of view, however, the study of this disease still remains a subject of pre-eminent importance. The recent development of industrial and agri- cultural activities in our tropical possessions and the increased facilities for communication have resulted in an enormous demand for the services of Europeans, and within the last thirty years the white population has multiplied five-fold. Of the pro.tean climatic diseases which they have still to face, dysentery is second in prevalence only to malaria, and from all classes and races it annually claims an appalling number of victims. The discovery that dysentery itself is not a single disease may be regarded as one of the most remarkable advances in modern medical science ; for, although in medicine it is impossible to claim that any theory of disease has been immutably settled, or that the r-:«-»r- rf^M»^KS/9 IV. AMCEBIC DYSENTERY final word has been spoken, our conception of amoebic dysentery as a distinct and specific affection is definite and assured, and the pathology of the disorder is now a chose jugee. The literature of the subject, already very extensive, is rapidly increasing, and almost every month important additions are being made to our knowledge. The very scope and volume of these contributions is indeed so great that it tends to diminish their practical value ; for, published as they are in all languages and in all parts of the world, and scattered through an enormous number of scientific journals, most of them are accessible only to those who make a special study of the subject. It is believed, therefore, that a general survey of the information which has recently been acquired with regard to amoebic dysentery and other protozoan infections of the human intestine may not be devoid of interest and utility. For an accurate appreciation of the pathology of amoebic dysentery, a knowledge of the cardinal facts in the life-history of the specific organisms and of their relations to other intestinal protozoa is essential ; and it is endeavoured in these pages to set forth as clearly as possible the outstanding features in the natural history of the entamoebae. But no attempt has been made to give a complete account of this important group, or to trespass on the domain of pure zoology, and only those events in the develop- ment and reproduction of the parasites which have a direct bearing on amoebic dysentery have been fully considered. It is not pre- tended that the biological section is more than a narrative of the prominent phenomena for which a special relation to a distinct morbid process is claimed ; and, as far as possible, the intricacies of detailed zoological description, which occasionally tend to obscure medical issues, have been avoided. The book is, indeed, chiefly intended for the practising physician, and its principal aim is to emphasize the necessity of early diagnosis PREFACE V. and to lay down precise and comprehensible directions for the treatment of the various clinical types of amoebic dysentery. An attempt has been made to take into account the varying conditions under which the disease may have to be treated, and special regard is paid to the remedial measures which are best suited to the require- ments of warm climates. The object of the work will be more than achieved if the instructions for the general management of cases and for the selection and use of suitable remedies prove of practical value and assistance. I am indebted to Mr. A. Engel Terzi for the care and artistic skill which he has devoted to the illustrations, and to Miss May Sinclair for many valuable suggestions and much helpful criticism during the revision of the proofs. 32, Harley Street, London, W. August, 1 9 10. CONTENTS. CHAPTER I. PAGE Introductory 3 CHAPTER II. History and Literature of Amoebic Dysentery 7 CHAPTER III. Epidemiology and Geographical Distribution 24 CHAPTER IV. Classification and General Relations of Protozoa to Intestinal Diseases ... 41 CHAPTER V. The Entamoebae of the Human Intestinal Tract 44 CHAPTER v. The Entamoebae of the Human Alimentary Tract — Morphology and Struc- tural Comparison 5° CHAPTER VII. The Entamoebae of the Human Alimentary Tract — Reproduction 64 CHAPTER VIII. The Entamoebae of the Human Alimentary Tract — Cultivation 71 CHAPTER IX. Other Protozoan Infections of the Human Alimentary Tract 79 CHAPTER X. The Symptoms of Amoebic Dysentery 93 CHAPTER XI. Diagnosis 108 CHAPTER XII. Morbid Anatomy 1^9 Vlll. AMCEBIC DYSENTERY CHAPTER XIII. The Case for the Pathogenicity of Entamoeba Histolytica CHAPTER XIV. The Causes of Amcebic Dysentery CHAPTER XV. Hepatic Abscess CHAPTER XVI. Other Sequelae of Amoebic Dysentery CHAPTER XVII. The Prophylaxis of Amoebic Dysentery CHAPTER XVIII. The Treatment of Acute Amoebic Dysentery CHAPTER XIX. The Treatment of Chronic Amcebic Dysentery CHAPTER XX. Diet in Chronic Amoebic Dysentery CHAPTER XXI. The Treatment of Amoebic Dysentery by Drugs CHAPTER XXII. Local Medication CHAPTER XXIII. Surgical and other Methods of Treatment CHAPTER XXIV. The Treatment of Amoebic Abscess of the Liver— Prophylaxis Index PART I.— GENERAL. AMCEBIC DYSENTERY. CHAPTER I. Introductory. For many centuries, several different infections, similar in their clinical manifestations, but distinct in specific character, have been described by the single term Dysentery. The symptoms common to these disorders are definite and characteristic, and clearly separate the condition from other morbid processes of the alimentary tract ; but, within the last few years, the suspicion — originally raised by marked variations in clinical type — that dysentery might itself be more than a single pathological unit, has been fully confirmed. The number of individual diseases which may rightly be com- prised in the group is still uncertain, but at least two have now been definitely differentiated, and the pathogenic nature of the micro-organisms in which they originate has been completely established. Of these infections, one is protozoan, and the other bacterial ; the varieties of dysentery, of which they are respectively the causes, being known as amoebic and bacillary. Strong claims have been advanced for the further subdivision of these types, and especially for the recognition of additional forms of protozoan dysentery ; but although the evidence which has been adduced is highly significant, it is at present insufficient to warrant 4 AMCEBIC DYSENTERY a new classification, or to incriminate other microbial organisms as pathogenic. There is, however, abundant proof of the etio- logical relation of the rhizopod — Amceba dysenterice (Councilman and Lafleur), Entamoeba coli (Casagrandi), E. histolytica (Schaudinn) — to amoebic dysentery ; and of the connection between one or more species of bacteria — of which the variety known as Shiga-Kruse is the most familiar — and the bacillary variety of the disease. It is with the first of these infections — Amoebic Dysentery — that this work is principally concerned ; and an endeavour will be made to describe the biological relations of the organism, the history of, its discovery, the epidemiology and distribution of the disease, the pathological results of amoebic infection, and the most effective methods of prevention and treatment. DESCRIPTIVE DEFINITION.— Amcebic Dysentery is a disease which originates in penetration and subsequent destruction of the intestinal walls by a specific protozoan micro-organism — Entamoeba histolytica ; the lower segment of the alimentary tract, viz. : — the colon, sigmoid flexure and rectum being the favourite sites of invasion. The signs of acute infection are fever, sickness, pain, and tenesmus, with frequent calls to stool. The dejecta are scanty, and consist principally of mucus and blood. The commencement of amoebic dysentery is, however, generally very insidious, and active dysenteric symptoms seldom develop for some time after infection. The course of the disease is protracted, and it has a marked tendency to recurrence and chronicity. The later stages are often characterized by toxaemia ; and, not infre- quently, they are complicated by hepatic suppuration. NOMENCLATURE. — Alternative Terms : Tropical Dysentery — Amgebiasis — Amcebic Enteritis — Amcebic Colitis — Amobenruhr — Dysenterie Amibienne — Dysenterie a amibes. INTRODUCTORY 5 As infection by a specific micro-organism of the Amoeba family is not only the cause of a definite train of symptoms but also serves to distinguish the type of disease, the term Amoebic Dysentery is, perhaps, more applicable than any other title. It is eminently desirable that a disorder of widespread prevalence should be known by a distinctive and practical name, and one which is readily comprehensible by laymen as well as by physicians. Amoebic Dysentery fulfils these indications satisfactorily ; and it has, besides, the conspicuous advantage that it has already secured general adoption. Considerable confusion has, however, arisen in the nomenclature of the disease by a difference of opinion as to the use of the term " Tropical " dysentery. By many writers that name is applied^ irrespectively of the nature of the infection, to any variety of dysentery which has originated in the tropics ; while by others its application is strictly confined to the amoebic type of the disease. Amoebic dysentery is, indeed, regularly described by many authorities as " Tropical " dysentery, although the reference is to an infection contracted in a cold climate, and although the patient may not have been in the tropics. This indiscriminate application of the term " Tropical " is some- what unfortunate. Bacterial dysentery is common in the tropics ; indeed, although it has become endemic in many temperate regions, it is, essentially, a tropical disease ; and many, if not most, of the European invalids who return from warm climates suffering from a chronic flux of mucus and blood exhibit no trace of amoebic infection. Amoebic dysentery, on the other hand, is by no means a distinctively tropical affection ; it is prevalent in most sub-tropical countries, and it is of common occurrence in many districts of the temperate zone. Strictly speaking, therefore, " Tropical dysentery" is an inappro- 6 AMCEBIC DYSENTERY priate title ; but greater confusion undoubtedly results from its employment in a geographical sense than by its retention as a synonymous term for amoebic dysentery. In the latter relation, the name "tropical" has, to a certain extent, been sanctioned by custom ; and, provided that it is applied only to cases of amoebic dysentery, there can be no serious objection to its use. Amcebiasis — a word recently introduced to denote amoebic disease generally — has been adopted by several authors as an alternative title for amoebic dysentery. In this sense, however, it is vague and unsatisfactory ; it does not express the dysenteric state, and it should be confined to cases in which symptoms other than those of dysentery have been produced by amoebic infection. Further confusion is caused by the fact that " amoebiasis " is often applied to the condition in which non-pathogenic amoebae are harboured in the intestine without hurt to their host ; but its use in this sense is unjustifiable and misleading. On the other hand, " amoebiasis " accurately and conveniently expresses a morbid state in which amoebic infection is followed by symptoms of which dysentery is not a predominant feature. Such an event is unusual ; but hepatic and cerebral amoebic abscesses, and other consequences of infection, without precedent dysentery, are by no means unknown. The term Amcebic Colitis is sometimes employed by physicians who find a distinction between colitis and dysentery. In rare instances the development of pathogenic amoebae may be arrested before the ulcerative stage of inflammation is reached, and "amoebic colitis" would then be descriptive of the pathological condition. But amoebic colitis is, after all, only a stage of dysentery, and a multiplication of names for a single disease is undesirable. CHAPTER II. History and Literature of Amcebic Dysentery. Although various protozean organisms had previously been described as occasional habitants of the human alimentary tract, the history of amoebic dysentery definitely begins with the dis- covery by Lambl of a rhizopod in intestinal mucus, taken from a Jewish child, who died of infantile diarrhoea at the Kinder Spitale in Prague, in 1859. This organism he regarded as a monad — the term then generally used for unicellular protozoa — and his description states that it measured '009 mm. by '016 mm. At rest, it was roughly spherical in shape, but when in motion the body became elongated, and the animal progressed by throwing out club-shaped pseudopodia, which were homogeneous with the body substance. Lambl further noted the characteristic mole- cular vibration of granules in the protoplasm, which, he stated, was most active near the roots of the pseudopodia. Vacuoles were also seen in the body substance, and, in some specimens, delicate nuclear vesicles were visible. The movements, both protoplasmic and granular, were active at first, but within a few hours after the collection of the intestinal mucus they gradually ceased. These organisms were subsequently demonstrated by the same observer in many other cases of dysenteric diarrhoea. Lambl does not appear to have received the credit which he deserved for these important observations. It is generally stated that he attached no pathological significance to the presence of 8 AMCEBIC DYSENTERY amoebae, but that is incorrect. If his original paper is consulted, the following words will be found : "It is an established fact that minute organisms, which appear to be closely related to the rhizopoda, are present in the human intestinal canal, and their importance in regard to the concomitant pathological processes in children should certainly not be under-rated." ^ Not only, there- fore, did Lambl first describe the morphology of an intestinal amceba, but he demonstrated the organism in association with a definite form of disease, and although he naturally hesitated to express the view that pathogenicity had been proved, he clearly realized that it was probable. Lambl's researches were published in a somewhat inaccessible series of reports, and, although noted ^ by Leuckart (who also found parasitic amoebae in the human intestine), his paper failed to reach other investigators. In India, Lewis, while examining cholera dejecta in 1870, observed living amoebae, but attached no importance to their presence, and although his description of the organisms is full and distinctive, it is not clear that he even recognized them as protozoa. He seems rather to have regarded them as some variety of normal cell, the morphology and develop- ment of which resembled that of an ordinary leucocyte. There can be little doubt, however, that if Lewis had been aware of Lambl's paper, he would have taken a different view, and would have made further inquiry into the subject of amoebic infection. Five years later, intestinal amoebae were again demonstrated and described by Dr. F. LOSCH, clinical assistant to Professor Eichwald, of St. Petersburg. The patient was a young peasant * Lambl, " Beobachtungen und Studien aus dem Gebiete der pathologischen Anatomic und Histologic." Prague: i860, Fricdrich Tempski. * F. Leuckart, " Die menschlichen Parasiten." 1863. HISTORY AND LITERATURE OF AMCEBIC DYSENTERY 9 of Archangel, who was suffering from dysentery which, after persisting intermittently for two years, ultimately proved fatal. During his illness, amoebae were repeatedly found in the mucus passed with the dejecta ; but just before death, which was actually the result of a terminal pleuro-pneumonia, the organisms entirely disappeared. At the post-mortem examination, however, they were shown to be present in enormous numbers in the intestinal contents, and in numerous ulcers on the mucous membrane of the colon and sigmoid flexure. LusCH, who had seen Lambl's paper and was much impressed by his researches, fully appreciated the pathological importance of the discovery. But, clear as was the evidence, it was supplied by a single instance of the disease, and was still insufficient to establish a claim for pathogenicity. He accordingly limited himself to the conclusion that a superimposed infection of amoebae had possibly only aggravated an ordinary case of ulcerative colitis. His own belief is, however, clearly indicated by the fact that he undertook experiments to test the biological relations of the organisms. Some mucus containing amoebae was injected into the rectal cavities of four dogs, and in one case this attempt to reproduce the disease was successful, for dysentery supervened, and amoebae were recovered from the dejecta. The infected dog, when killed, was found to be suffering from extensive, although superficial, ulceration of the lower part of the colon. There can be no doubt that LOsch's case was a typical instance of amoebic infection, and his careful study of the condition,^ illus- trated as it is by a large number of excellent plates, which show the development of the amoeba and its power of ingesting red ^ F. Losch, " Massenhafte Entwickelung von Amoben im Dickdarm," Virchow's Archives^ Ixv., 156. lO AMCEBIC DYSENTERY blood corpuscles, remains one of the best, as it is the first important contribution to the literature of amoebic dysentery. Closer attention was naturally directed to the subject of intes- tinal amoebae by the publication of Losch's report, and during the next few years numerous papers on the development and life- history of parasitic protozoa appeared in medical and scientific journals. Among the more important were those of Grassi,* who, so early as 1879, showed that intestinal amoebas passed through a cystic stage, and that, when the conditions of life were unfavour- able, cysts were formed in greater numbers. He found intestinal amoebae in healthy persons as well as in those affected by dysentery, and he accordingly opposed the theory advanced by LOSCH that they might be the cause of the disease. About the same time, amoebae were reported by Leuckart ^ as having been found in healthy human dejecta, by Perroncito ^ as occurring in the contents of an otherwise normal colon, and by SONSINO ^ (who, however, did not regard them as causative) in the intestinal mucus of a child who died of dysentery at Cairo. From that city also came the next important addition to the knowledge of the subject. While examining sections made from the intestinal walls of victims of the cholera epidemic of 1893, Professor Koch observed a species of amoeba embedded in the tissues. This he regarded as possibly pathogenic, but, being fully occupied with bacteriological work, he was unable at the time * Grassi, " Die protozoi parasiti e specialmente di quelle che sono nell'uomo,'' Gazeta Med. Italiatm, 1879, P- 445 '■> and other papers in the Proceedings of the Societa Italiana di scientia naturale, Milan, 1882 ; and in the Aiii de R. Accadejnia di Lincei, 1888. ' Leuckart, " Die Parasiten des Menschen." Leipzig, 1879. •^ Perroncito, " I Parasiti." Milano, 1881. ' P. Sonsino, " Davidson's Hygiene and Diseases of Warm Climates.'' 1893. HISTORY AND LITERATURE OF AMOEBIC DYSENTERY II to investigate the question, and he asked Dr. S. Kartulis to determine, if possible, whether the organism had any definite relation to a morbid process. During the next two years, Kartulis examined, post mortem, a large number of fatal cases of intestinal disease, and, as a result of his observations, published ^ several papers in which he stated that amoebae were invariably found in Egyptian dysentery ; and he further recorded his belief that they were undoubtedly the patho- genic agency in that disease. In a consecutive series of 150 autopsies, which he made at the Greek and Arab hospitals in Cairo, Kartulis found amoebcc in every instance in which there had been marked dysenteric symptoms, w^hilst in patients who had died from other causes they were never once discovered. He thought that in severe dysentery the amcebic infection was excessive, and that in mild cases it was slight, and he claimed that a direct relationship between the number of organisms and the intensity of the symptoms could always be demonstrated. Of twelve fatal cases of dysentery in which sections of the colon were made, amoebae were found in every one ; while similar specimens prepared from the intestines of thirty persons who had died of typhus, tuberculosis, enteric fever, and Bilharzia disease, contained not a single amoeba. Kartulis was unable at the time to cultivate the amoeba, or to reproduce the disorder in guinea-pigs and rabbits ; but his experiments in this direction were on a scale insufficient to give reliable results. * Kartulis, " Ueber Riesen-Amoben bei chronischer Darmentziindung der Aegypter," Virchow's Archives^ 1885, xcix., 145. Ideitty "Zur Aetiologie der Dysenteric in Aegypten," Vtrchow's Archives, 1886, cv., 521. Idetn, " Einiges iiber die Pathogenese der Dysenteric," Centralbl. ^iir Bakt., 1891, ix., 365. 12 AMCEBIC DYSENTERY There can be no question of the importance of those observa- tions, and of the influence which they exercised on the views then current as to the nature of the disease. Since the days of Hippo- crates, dysentery had been regarded as a "phlegmonous" or " sthenic " inflammation ; and the proper method of dealing with it was believed to be depletion and the continued action of depressant drugs. The introduction of ipecacuanha had lessened, to some extent, the appalling mortality which had long been con- sidered inevitable, but which, it was now realized, was a direct consequence of treatment. Still, although blood-letting to faint- ness and huge doses of calomel had given place to more rational remedies, the conception that dysenteric symptoms might originate in various causes, and that at least one variety of dysentery was parasitic, came as a revelation. The ultimate establishment of amoebic dysentery as a distinctive disease is largely due to Kartulis's pioneer work in Egypt ; and he may justly claim the greatest share of the credit for this notable advance in medical science. Kartulis has elaborated and confirmed these researches by many further observations. In 1887 he pointed out the definite association of Amoeba coli with hepatic suppuration ; and he has since published ^ numerous important papers on amoebic dysentery and its sequelae. The recent article, " Die Amoben Dysenteric," in KOLLE and Wassermann's " Handbuch " — an excellent and comprehensive review of the subject — is from his pen. Kartulis's observations were promptly confirmed by Hlava^^ " See among others: (i) " Ueber weitere Gebreitungsgebiete der Dysenterie- Amoben,'' CentralbL f. Bakt. unci Parasitenkunde, 1891, ix. ; (2) "Ueber patho- gene Protozoen bei dem Menschen," Zeitsch. f. Hygiene, Bd. xiii., F. 2 ; (3) "Gehirn Abszesse nach Dysenterie Leber Abszesse," CentralbL f. Bakt., 1904, xxxvii., 527 ; (4) Kolle and Wasserniann : G. Fischer, Jena, 1907. '" Hlava, CentralbL f. Bakt., 1887, i., 527, Ungarn. HISTORY AND LITERATURE OF AMCEBIC DYSENTERY 1 3 at Prague ; but in Europe and the tropics they attracted little attention. In America, however, the articles in Virchow's Archives had been noted by Osier, who thereupon instituted a search for amoebae in the cases of dysentery which happened at the time to be under his care. One patient who had returned from Panama, and who was being treated for chronic dysentery in hospital at Baltimore, was found to be passing large numbers of amoebae ; and several other instances of amoebic infection were subsequently reported from different parts of the United States. Further cases in Professor Osler's wards at Baltimore fur- nished material for a very complete study of amoebic dysentery by Drs. Councilman and Lafleur.^^ Their account of the disorder, published in 1891, combines an excellent description of the symptoms and pathology of amoebic infection with a compre- hensive and critical review of the literature of dysentery — the post-mortem records left by Indian and other tropical pathologists being specially subjected to examination with reference to the indications they afford as to the possible duality of the disease. There is much evidence to that effect scattered through the writings of the older medical authorities. So long ago as 1828, Annesley,^^ of Madras, divided dysentery into several different classes ; and, noting the frequent association of thickening and ulceration of the great intestine with inflammation of the liver, he named one of the most familiar types "Hepatic dysentery." He, however, misinterpreted the pathological connection, and regarded the dysenteric condition as a consequence of disordered secretion of bile. DUTROLAU,^^ also, had insisted that tropical dysentery ^' Councilman and Lafleur, Johns Hopkins Hospital Reports, 1891, ii. '^ Annesley, "Researches into the Diseases of India." London, 1841. " Dutrolau, "Maladies des Europeens en Pays chauds." Paris, 1868. 14 AMCEBIC DYSENTERY differed widely, both in symptoms and pathology, from the haemorrhagic flux of temperate climates. In this view he was supported by most of his contemporaries ; and there are numerous other indications that, in certain parts of the world, amoebic dysentery has, from the earliest times, been a prevalent, although unsuspected disease. Not the least important of Councilman and Lafleur's results was an observation which indicated the existence of two varieties of amoebae, differing in appearance and in pathogenic virulence. These they named A. dysenteria; and A. coli. Their closely reasoned argument that amoebic dysentery deserved recognition as a separate disease was widely read and discussed, with the result that the whole subject was carefully re-investigated ; and numerous important articles by zoologists and physicians were published during the next two or three years. Some of these writers ^* con- firmed and extended the views of Councilman and Lafleur ; but others ^^ — and, indeed, the greater number — refused to accept their work, and vehemently opposed the theory of pathogenicity in any variety of amoeba. In this controversy, which was carried on with much vigour both in America and on the Continent, English physicians, who formed the great majority of tropical workers, took no definite side ; but it is a curious fact that, while foreign pathologists, as a rule, favoured the doctrine of specific pathogenicity, biologists (with the notable exception of Schaudinn), almost to a man, denied that the parasitic amoebae exercised any pathological influence on their hosts. " See, among others : A. Kovacs, " Beobachtung und Versuche ueber Amoben Dysenterie," Zeitsch. f. Heilk., 1892, xiii., p. 509. '* See, among others : A. Schuberg, " Die parasitischen Amoben des mensch- lichen Darms," Centralb. f. Bakt.^ 1893, xiii., pp. 18, 22. HISTORY AND LITERATURE OF AMOEBIC DYSENTERY 1 5 Much of the adverse criticism was naturally based on the facts — already noted by Cunningham, Perroncito, Grassi, Massiutin, and others, that amoebae were frequently present in the contents of the normal intestine ; and that experiments, such as those of Calandruccio,^^ showed that encysted amoebae might be swallowed without ill-effect, although an abundant development of living amoebae took place immediately after they were ingested. In 1893, Maggiora,^^ after a careful review of all the evidence then available, concluded that no cause had been shown for the incrimination of Amoeba coli as the pathogenic agent in any variety of dysentery; and Gasser,^^ by the injection of garden mould, not only induced active colitis in cats, but recovered amoebae, apparently identical with those of LosCH and Kartulis, from their excreta ; while SoRGA further showed that the introduction of dysenteric matter, which had been proved to be free from amoebae, could induce dysentery both in man and animals, and that amoebic organisms might sometimes be found in the resultant dejecta. Further light was thrown on the question of pathogenicity by H. Quincke and E. Roos,^^ whose work, at Kiel, to some extent anticipates the later discoveries of SCHAUDINN. In two cases of chronic dysentery, one of which had been contracted at Palermo, or, possibly, in Egypt, and the other certainly in Schleswig-Holstein, they found amoebae, which varied in appearance, both in their active and encysted state, and which differed also in their method of reproduction. The organisms harboured by the first patient '* Calandruccio, Atii. Accad. Giorn., 1890, ii., p. 95. " A. Maggiora, Centralbl. f. Bakt. und Parasitenkunde, Jena, 1892, 173. '^ J. Gasser, " Note sur les causes de la dysenterie," Archives de Medecine exp. et dAnat. path., 1895, ii., 198. ^® Quincke and Roos, " Ueber Amoeben Enteritis," Berlin, klin. Wochenschr . 1893, 1089. l6 AMCEBIC DYSENTERY were apparently identical with those described by COUNCILMAN and Lafleur, and the dysenteric symptoms were severe ; in the second instance the amoebae were larger, the nucleus being less clearly defined, and they were associated with flagellated protozoa. In this case the disorder was comparatively trivial. As a result of these observations, Quincke and Roos concluded that there were at least two varieties of pathogenic amoebae, one of which — the tropical or Egyptian — was more virulent than the other. The latter organism they believed to be a species peculiar to cold countries, and productive of a milder type of dysentery. They further claimed that still another variety of amoeba could be differentiated, and that it was composed solely of parasitic, but non-pathogenic organisms. Amoebae recovered from the dejecta of nine out of twenty-four healthy persons to whom a purgative had been previously administered, were found to be different from either of the species noted in dysentery ; and Quincke and Roos sup- ported this observation by experiments which showed that, when injected into the rectum, their first organism was highly pathogenic to cats, but that the second and third varieties failed to cause dysentery. Soon afterwards. Dr. W. Kruse, of the Hygienic Institute in Berlin, and Staff-Surgeon Alessandro Pasquale, of the Royal Italian Navy, undertook a journey to Egypt in order to test the theory of pathogenicity by further investigation and experiment. Working principally at the Greek Hospital in Alexandria, Drs. Kruse and Pasquale were able^*' to corroborate almost the whole of Councilman and Lafleur's observations. They specially verified the statements of these authors as to the existence of both ^" W. Kruse and A. Pasquale, "Eine Expedition nach Egypten zum Studium der Dysenteric und Leberabzess," Deutsch. nied. Wochenschr, 1893, 354* HISTORY AND LITERATURE OF AMCEBIC DYSENTERY 17 a pathogenic and a harmless species of intestinal amoeba ; and it is interesting to note that their description of the former closely agrees with that of Entamoeba histolytica afterwards given by SCHAUDINN. In the hands of Kruse and Pasquale, reproduction experi- ments, which had previously given somewhat ambiguous results, were highly successful ; and they were the first to prove that amoeba-containing pus from a hepatic abscess (although otherwise sterile), if injected into the lower intestines of cats, may induce true amoebic dysentery. The result of their detailed investigation of fifty cases of the disease was to give an unqualified confirmation to the clinical and pathological work of LoscH, Kartulis, Council- man and Lafleur. Further experiments, however, were less conclusive. A contem- porary observer, Zancarol of Alexandria, showed ^^ that not only could amoebic dysentery and liver abscess be successfully transferred to the domestic animals, but that hepatic pus which had been ascer- tained to contain no amoebje, if injected into the rectum of a cat, might set up acute dysentery. He argued from these results that the origin of the disease was streptococcal, and not proto- zoan. Soon afterwards Professor Celli,^^ working in collaboration with R. FiOCCA, published several important memoirs on intestinal protozoa. The amoebae parasitic in man were divided by these authors into no fewer than six species, none of which were considered to be actually pathogenic. In their review of the work which had been carried out in Egypt and in Italy, Celli and -'Zancarol, " Pathogenic des Absces du Foie," Revue de Chirurgie, 1893, 677. '- A. Celli, Centralbl. f. Baki., xv. Cf. ibid.^ 1902, I. Abt. 2 1 8 AMOEBIC DYSENTERY FioCCA 2' maintained that all dysentery was really bacterial in origin ; and as Bacillus coli and Amoeba colt were so frequently found in symbiosis, they suggested that these organisms exercised a definite influence on each other, and that the development of amoebae possibly effected a metamorphosis of B. coli into B. dysenteria'.^^ Moreover, although generally favouring the claim for patho- genicity, physicians and pathologists were by no means unanimous. In a report,^^ communicated to the Verein fi'ir innere Medicin, of Berlin, in January, 1896, Dr. I. Boas stated that, as the result of a large number of experiments by himself and others, he had come to the conclusion that pathogenicity had not been established. He considered that both the experimental animals and the material used by previous observers were unsatisfactory, and that the results, in consequence, were unreliable. Soon afterwards — in 1897 — Dr. W. JANOWSKI, of Warsaw, contributed a series of papers^" to the Centralhlait jiir Bakieri- ologie, which contains an excellent catalogue raisonne of previous researches on the etiology of amoebic dysentery. His own obser- vations and experiments to determine the actual pathogenicity of the amoeba were somewhat inconclusive, but Janowski considered that the distinction between bacterial and amoebic dysentery had been clearly proved, and that the weight of evidence favoured the view that the latter disease was caused by the combination of a definite species of amoeba with bacterial organisms. *^ Celli and Fiocca, An7iali digiene speriment,, 1896, vi., 204; " Ueber die Aetiologie der Dysenteric," and other papers in the Centralbl. f. Bakt., xv., xvi., xvii. ; " Intorno alia Biologia delle Amcebe," Bull. R. Accad. Med., Rome, 1894-5, and other journals. 2^ Cf., " La Metamorphose dans les Microbes," A. Rodet. Paris : Bailliere. '■■* I. Boas, " Amoeben Enteritis," Deutsch. med. Wochenschr., 1896, 214. 2® Janowski, Centralbl. f. Bakt., 1897, xxii., 88, 151, 194, 324. HISTORY AND LITERATURE OF AMCEBIC DYSENTERY 19 About the same time (1897) Drs. O. Casagrandi and P. Barbagallo, of the Zoological Department of the University of Catania, who had already published 2' several articles on the same subject, issued^^ a full account of their researches into the life- history and relations of the intestinal amoebae. This important study attracted general attention ; and, among others, it was noticed by Schaudinn, who, although he differed from the main conclusion of the authors that no species of amoeba was pathogenic, declared it to be an exact statement of biological fact. In a further article,^^ Drs. Casagrandi and Barbagallo dealt with the artificial reproduction of the organisms, and stated their belief that no parasitic amoeba had yet been successfully cultivated. The amoebae which other observers claimed to have grown were, they thought, the result of accidental contamination of cultures by cysts or spores of free-living species. In the following year (1898) TsuJiTANl'" claimed that although he had been unable to obtain a pure culture, he had successfully grow^n intestinal amoebae in symbiosis with the spirillum of cholera ; and, as the result of an experiment by which he showed that cysts, sown on a medium on which pathogenic bacteria, while growing, had been previously killed by drying over sulphuric acid, would develop in three to five days, he suggested an interdependent relationship between specific protozoa and virulent bacteria. " Casagrandi and Barbagallo ; see " Ricerche suU' Amoeba Coli (Losch)," Atti Academ. Medic, di Catania., 1895, and other papers. ^^ Idem., "Entamoeba Hominis (Amoeba Coli), Losch, Studio biologico e clinico," Annali igien. speritnefital., 1897 and 1899. See also idem., "Sulla sterilitd del pus degli ascessi epatici dei climi caldi," Gaz. Ospedale Mila?to, 1896. ^^ Idem., " Ueber die Cultur von Amoben," Centralbl. f. Bakt., iSgj, xxi,, 579 ^"Tsujitani, " Ueber die Reincultur der Amoben," Centralbl. f. Bakt.y 1898, xxiv., 666. 20 AMOEBIC DYSENTERY The next paper of note was a clinical and pathological review of thirty-five cases of amoebic dysentery — all of them originating in the Southern United States — which was published ^^ by Professor H. F. Harris, of the Jefferson Medical College. Harris's descrip- tion of the symptoms, morbid anatomy and distinctive character- istics of the disease corresponds closely with the accounts of OSLER, and Councilman and Lafleur ; and his opinions as to its specific nature are in accord with those of most other American authorities. During the next few years a considerable number of clinical and pathological observations, generally corroborative of the theory of pathogenicity, were recorded from various parts of the world ; but, with the exception of a detailed description of the disease ^^ by Jurgens, which appeared in 1902, no important addition was made to the literature of amoebic dysentery until the publication of Fritz Schaudinn's memoir,^^ "Die parasitaren Amoben des mensch- lichen Darmkanals." The incidents which surround Schaudinn's work during his short stay on the shores of the Adriatic are full of interest. Pending the completion of the Institute of Protozoology in Berlin, of which he had been appointed first director, he was placed in charge of the zoological station at Rovigno, where he immediately under- took an extended series of researches into the life-history and biological relations of the parasites of malaria and dysentery. In the neighbouring villages both diseases were endemic, and very prevalent ; and with the abundance of clinical material which was thus continuously at his disposal, SCHAUDINN was able to '' Harris, "Amoebic Dysentery," Atner. Journ. of Med. Science., 1898, cxv., 384. See also "Experim. bei erzeugte Dysenteric," Virchow's Archives, 1901. " Jurgens, "Zur Kentniss der Darmamoben und der Amoben-Enteritis." Veroffentlichen aus dem Gebiete des Militdr-Sanitdtswesen, H. 20, p. 1 10. Berlin : Hirschwald, 1902. " F. Schaudinn, Arbeiten aus dem Kaiserlichen Gesuitdkeiisatnte, 1903. HISTORY AND LITERATURE OF AMCEBIC DYSENTERY 21 follow his favourite method of investigation by the simultaneous observation of large numbers of fresh specimens. In this way he ascertained almost at once that the conjectures of former observers were correct, and that at least two species of amoeba, which differ widely in their morphological characters, in their life-cycles, and in their modes of reproduction, may be parasitic in the human colon. He also showed that one of these organisms, termed by him Entamceba coli, was entirely harmless ; and that the other, which he named Entamoeba histolytica, was the definite cause of amoebic dysentery. Schaudinn's work at Rovigno will be remembered not only for its scientific importance, but also on account of the melancholy interest which attaches to one of his investigations. While engaged in testing and comparing the pathogenicity of the different species of amoeba, he did not hesitate to infect himself by swallowing the developmental cysts of the organisms ; and he had, in consequence, two serious attacks of dysentery. It is, indeed, only too probable that his untimely death was a direct consequence of this disastrous experiment; for, after his return to Germany, he suffered inter- mittently from dysenteric seizures, and four years later deep suppuration round the sigmoid flexure was attended by a fatal result. Schaudinn's observations removed the chief obstacle to the recognition of amoebic dysentery as a distinct disease, and proved that the pathology of LosCH, Councilman, and Kartulis was established on an accurate and scientific basis of fact. His dis- covery explained why a parasite, for which pathogenicity was claimed, had apparently been shown, in many instances, to be merely an innocuous commensal, and to be of frequent occurrence in perfectly healthy individuals ; and it satisfactorily answered every argument which had been adduced to prove that intestinal amoebae played no part in the production of specific disease. The scientific 22 AMCEBIC DYSENTERY differentiation of the organisms into two zoological species entirely transformed the significance of all previous observations and experi- ments, and finally determined the role of amoebae in the causation of dysentery. Subsequent research has confirmed the accuracy of Schaudinn's work in every important particular. After a careful re-investigation of the whole subject, C. F. Craig who with most other American observers, had at first believed ^* that there were insufficient grounds for the specific distinction of entamoebae, expressed ^^ his full con- currence in a biological and clinical differentiation. Craig's later researches, indeed, corroborate and extend Schaudinn's con- clusions in a very remarkable manner; and his report constitutes an excellent introduction to a study of our present knowledge of the life-history of the intestinal amoebas. In the tropical foyers of the disease, Schaudinn's discoveries, although at first regarded with incredulity, are now accepted by the great majority of scientific observers. Much of the previous work in Manila had, indeed, to some extent at least foreshadowed his results. Musgrave and Strong ^^ had differentiated the pathogenic from the innocuous amoebae of the intestine by repro- duction experiments in cats, and had shown that free-living amoebae grown in straw infusion were incompetent to produce specific infec- tion. They had also noted morphological differences, and Shiga ^^ had claimed that Amceba dysenterice was distinguished from other varieties by its larger size. ^* C. F. Craig, "The Life - cycle of Amceba colt,'' American Medicine, February 20, 1904. " Ibid., American Medicine, May 27, June 3 and 10, 1905. ** R. Strong, article, " Amoebic Dysentery," " System of Medicine," Osier and McCrae, vol. i. Musgrave and Clegg, "Amebas: their Cultivation and Etiological Signifi- cance," No. 18, Bureau of Government Laboratories, Manila. '' K. Shiga, Centralbl.f, Bakt., xxxii., 352. HISTORY AND LITERATURE OF AMCEBIC DYSENTERY 23 MusGRAVE, however, still finds himself unable to accept in their entirety Schaudinn's views as to the specific distinction of Entamoeba histolytica, and, whilst admitting the general accuracy of his statements, he and Clegg ^^ hold staunchly to their original opinion that all species of intestinal amoebae are potentially patho- genic ; that every individual who harbours amoebae of any variety may be regarded as suffering from amcebiasis ; and that all or any of these organisms, irrespective of their morphological charac- teristics, are possible causes of amoebic dysentery. No material addition to our knowledge of the disease has been made since the publication of Schaudinn's article in the Arbeiten aiis dent Kaiserlichen Gesundheitsatnte, but important papers, most of them confirmatory of his work, have been issued in India by Rogers,^^ Anderson,'"^ and others ; by Clegg, Woolley," (both of them in collaboration with Musgrave), and Flexner ^^ in America ; by Dopter,*^ Prues,** and other writers in France ; by Viereck,^^ Jurgens,^** and Kartulis *^ in Germany ; and by Saundby,^^ Miller, and others in England. " Musgrave and Clegg, Philippine Journal of Science, ix., i. ^* L. Rogers, Brit. Med. Journ., November, 1905, and June, 1906. ^" A. R. S. Anderson, Indian Medical Gazette, April, 1907 ; Brit. Med. Journ. 1908, ii., 1243. ■•' WooUey and Musgrave, y^«r«. Amer. Med. Assoc, 1905. *^ S. Flexner, article, " Amoebic Dysentery," Clifford Allbutt's " System of Medicine." 1907. *^ Ch. Dopter, " Les Dysenteries," Paris, 1908 : Octave Doin. Also Archives de Midecine Experimentale, July, 1907. *^ Henri Prues, " Dysenteric Amibienne." Toulouse, 1905. ^* H. Viereck, "Studien liber in dem Tropen erworbene Dysenterie," Beihefte. Earth, Leipzig, 1907. '* Jurgens, " Die Amoben-Enteritis," Zeitsch. f. exp. Path., December, 1907. *' S. Kartulis, "Die Amoben-Dysenterie," Kolle and Wassermann's " Hand- buch." Jena : G. Fischer, 1907. *' Saundby and Miller, "A Case of Amoebic Dysentery," Brit. Med. Journ:, March, 1909. 24 CHAPTER III. Epidemiology and Geographical Distribution. Only in very few places has there been any scientific investi- gation of the epidemiology of amoebic infection, but a good idea of the general distribution and preferential tendencies of the different types of dysentery may be gained by a comparison of the relative frequency of the amoebic and bacillary forms of the disease in Japan and the Philippine Islands. In both of these endemic centres the subject has been carefully studied, and, as a large body of statistical evidence is now available, the results may be regarded as accurate and reliable. The extreme southern districts of Japan reach to within 22° of the Line ; but this tropical area is of limited extent, and the con- tinental part of the Japanese archipelago lies almost entirely in the temperate zone. The Philippine Islands, on the other hand, are altogether tropical. Both countries offer unusually favourable con- ditions for the development and spread of epidemic dysentery ; population is everywhere dense, sanitation defective, and pollution of food and water supplies widespread and continuous. In the Philippines, amoebic dysentery is perhaps the commonest of all the serious diseases which affect the inhabitants of the islands. Its frequency relatively to other types of dysentery is probably higher than in any other part of the world, and, although all classes of the community are attacked, Europeans are especially EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 2$ liable to infection. Dr. CoOK, of the Government Civil Hospital in Manila, states that 30 per cent, of the patients treated at that institution suffer from amoebic infection. Fifty out of every thousand native inhabitants annually contract dysentery, and five of that number succumb to the disease. An estimate of the relative incidence of the different types may be formed from the following statistics : At autopsies made in Manila, during the year 1900, on 147 fatal cases of dysentery, it was proved that 67 per cent, of them were amoebic ; whilst, of 1,327 patients examined by Strong and Musgrave, 561 or 42 per cent, were found to be suffering from the same infection. The incidence, indeed, appears to be increasing, for the average proportion of amoebic cases is, at present, no less than 80 per cent., and in 90 out of every 100 fatal cases of dysentery amoebic lesions may be demonstrated.^ Amoebic disorders of the intestines appear to be especially prevalent among the American forces stationed in the Philippines. A series of 300 observations carried out at the Cana^ao Naval Hospital by E. R. HOYT, in 1907,* showed that of all the officers and men admitted for treatment (cases diagnosed as dysentery excluded), 30 per cent, harboured motile entamcebcc, and 15 per cent, intestinal flagellates. In 14 or 70 per cent, of the 20 cases admitted as dysentery, motile entamoebae were present, and in 20 per cent, of the remainder encysted organisms were found. Prolonged service on the station appeared to increase the liability to infection. To these figures Japan presents a marked contrast. There, also, ' R. Strong, " Amoebic Dysentery," Osier and McCrae's " System of Medicine," i., 488, and other articles. * E. R. Hoyt, Philippine Journal of Science, iii., No. 5 (1908). 26 AMCEBIC DYSENTERY dysentery has long been rampant, and the older histories of the Empire contain numerous references to calamitous epidemics of the disease, which visited the country at more or less regular intervals and carried off innumerable victims. These traditions are by no means imaginary, and they have recently been corro- borated in a remarkable manner by the accurate statistics which are being collected for the Japanese Government. In a Report on the Epidemiology of Dysentery in Japan, Shiga ^ has shown that from time to time within the last thirty years the disease, ever present in endemic form, has suddenly and periodically assumed a grave epidemic type. On these occasions extension was always in a definite direction, and almost invariably from south to north. In the earlier periods of the outbreaks, the ratio, both of case incidence and of fatality, was appalling, but after some time the fastigium appeared to be reached, and statistics again assumed a more normal level. The cycle of recurrence is stated by Shiga to be about ten years. In Japan, the normal incidence of dysentery is about 50,000 cases annually, with 11,000 or 12,000 deaths ; but when the disease becomes epidemic these figures are greatly increased. In 1883, and again in 1893, severe outbreaks occurred in Kiushu, Shikoku, and the central provinces. During the latter year there were, in Kiushu alone, 50,000 deaths ; and in Shikoku 135,000 cases. Throughout the whole of Japan, the enormous number of 875,000 cases of dysentery are stated by Shiga to have been reported during the decade 1890-1900 ; and of these no less than 231,000 were fatal, a case mortality of over 26 per cent. * K. Shiga (translated by Thoinot), *' Epidemiologic Dysenterique en Japon," Archives de Mddecine Navales, Octobre, 1906. See also K. Shiga, " Epidemio- logische Betrachtungen iiber die Dysenterie in ]?i^a.n " Zeits.f. Hyg. utid Infekt. Krankh.^ 1908, 75-92, and Philippine J ourn. of Science, 1906, 396. EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 27 There can be no doubt as to the type of dysentery which is responsible for those epidemics. Japanese observers are unanimous in declaring that it is always bacillary, that amoebic dysentery is never seen in epidemic form, and that, except in * Formosa and the extreme southern provinces, the latter disorder is rare in Japan. In North and Central China, although accurate statistics are unobtainable, it is probable that the epidemiology of the disease is closely similar to that of Japan. Dysentery is always prevalent ; periodically it becomes epidemic, and the clinical type is acute and virulent. In these districts, the usual infection is, no doubt, bacil- lary ; but, on the other hand, the endemic dysentery of South China, Hong Kong, and the Treaty ports, in the great majority of instances, is amoebic.^ The chronic dysentery from which European residents on the China coast so frequently suffer is almost invariably of the latter type. In Cochin China, in the French dependencies in Further India, and in Siam, dysentery is responsible for more than a third of the total number of deaths. Considerable difference of opinion, how- ever, exists ^ as to the actual nature of the affection. It is certain that many deaths which are reported as being due to dysentery are, in fact, the result of sprue — the endemic diarrhoea of Cochin China — and that many others are caused by bacillary infections ; but it is significant that, when amoebic dysentery is looked for, it is generally * Nakagawa, "Ueber Urheber der in Formosa endemischen Dysenteric," Mitteil. de medicin. Gesell. Tokio, 1907. Also Shiga, Centralbl. f. Baki., various papers, 1898, 1902. - Jiirgens, Veroffi a. d. Gebtei, d. Militdr Sanildtswesen, 1902, H. 20; "Die Amoben-Enteritis und ihre Bez'iehungen zur Dysenterie," Zeiis. /. exfi. Path., 1907, 4. 3- * See Pfiihl, Archives de Medecine JS/avales, 1906, 401, and many other French writers on the Endemic Diarrhoea of Cochin China. Also, Ruga in Mense's " Tropenkrankheiten.'' 28 AMCEBIC DYSENTERY found, and a careful examination of a recent series of cases of dysentery, which occurred amongst the crews of the French Naval Squadron stationed in these waters during the years 1904-05, resulted in 30 per cent, being classed as amoebic. Of the invalids suffering from dysentery who are sent home to France for treat- ment, a still greater proportion are affected by the amoebic form of the disorder ; and more than half of all the cases which occur in Europeans in civil employment are of amoebic origin. In Siam, amoebic disease is very prevalent. Of fifty cases of dysentery which were examined in the prison hospital at Bangkok, WOOLLEY found ^ amoebae in eleven,-or 22 percent. ; and he further reports that of a total population of eight Europeans in a small town of 4,000 inhabitants in Lower Siam, four suffered from amoebic dysentery in one season. The British and Dutch East Indies are noted endemic centres of dysentery ; and the amoebic form of the disease is especially prevalent throughout the whole of the tropical districts of Eastern Asia and the Eastern Archipelago. Here, as in South China, the clinical characteristics of the different varieties are exceptionally well marked, the chronic and recurrent types being, almost in- variably, amoebic ; the acute and malignant cases, bacillary. The amoebic variety, too, is the more fatal ; for, although large numbers of deaths occur during acute attacks, a still greater proportion of fatalities must be ascribed to toxaemia and exhaustion, induced by protracted illness and repeated relapses. In the Malay Peninsula and Sumatra, 50 per cent, of all cases of dysentery are amcebic ; whilst in Java, Celebes, and the islands of the East Indian Archipelago the proportion is even higher. ^ Paul G. Woolley, Journ. of the Avier. Med. Assoc, October 9, 1906, and private communication. EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 29 In India, amoebic dysentery, although less prevalent than in Eastern Asia, is widely but irregularly distributed, some districts being much more severely affected than others. In Madras, Pondicherri, Mysore, Travancore, Haidarabad, and Malabar^ it is very common; whilst, in Bombay, Powell states^ that it is more often seen than any other type. In the Central and Northern Provinces, the incidence of the disorder is less marked; and in Lower Bengal, where dysentery furnishes a larger contribution to the mortality returns than any other single disease, the amoebic variety appears to be comparatively rare. Statements as to its frequency, however, vary considerably. Of seventeen patients in the Campbell and Police Hospitals at Calcutta, who were suffering from dysentery, ROGERS, in 1902, found ^'^ amoebic infection only in one ; but his later work indicates that this was an exceptionally low proportion. Viereck states" that, of twenty cases of amoebic dysentery treated at the Seamen's Hospital in Hamburg, the infection had been acquired at Calcutta in eleven instances, in two instances at other Indian ports, five times in China, once in Japan, and once in Cochin China. In Rajputana and the drier parts of the Punjab and North- West Provinces, amoebic dysentery is infrequent,^^ but many cases have been reported from the upper Gangetic Provinces ; and in the planting districts of Northern and Central Bengal it is un- doubtedly very common. * C. F. Fearnside, " Dysentery in the Prisons of the Madras Presidency," Indian Medical Gazette^ July, 1905. ® Powell, British Medical Associatioti Report, 1908. '° L. Rogers, Brit. Med.Journ.., and various papers, 1902, 1903, 1905. " H. Viereck, " Studien liber die in Tropen erworbene Dysenterie " (Beihefte). Leipzig : J. A. Earth, 1908. 1^ A. Duncan, Brit. Med. Journ., 1902, ii., 242. 30 AMCEBIC DYSENTERY Throughout Assam and Burmah the disease is endemic, and it appears to be equally prevalent in the seaports and country districts. In Dacca, Comilla, and Rajshaki, in Eastern Bengal, Major Anderson found amoebic organisms in 50 per cent, of all cases of dysentery, and identified the great majority of these as Entamceba histolytica}^ The high rate of mortality which prevails among the coolies employed in the tea gardens and plantations in Eastern Bengal is largely due to amoebic infection, introduced, in most cases, from Southern India. In Tenasserim, the Mergui Archipelago, and the Western Provinces of Siam, an acute form of dysentery is very prevalent ; but a large number of cases which were examined there by the writer showed that the disorder was almost invariably of amoebic origin. An interesting research also carried out by Major Anderson, at the penal settlement of Port Blair in the Andaman Islands, showed ^^ that a very large proportion of the prisoners harboured intestinal Protozoa. During the year 1905, 2,539 cases of dysentery w^ere admitted to hospital, and in 920 of these, special investigation as to the nature of the disease was instituted. In 455 cases amoebae were found in combination with flagellates (Trichomonas and Lamblia), and in twenty-nine they were the only protozoan para- sites ; in four instances Balantidium was present in combination with flagellates and amoebae, and once only was it found alone. Of 210 patients, not suffering from dysentery and admitted for other diseases, seven were shown to harbour intestinal amoebae alone ; fifty-four, amoebae and flagellates ; and eighty, flagellates alone. Thus, in only 167 out of 920 cases of dysentery could " Anderson, Bri'f. Med. Journ.^ 1908, ii., 1244. " Anderson, Indian Medical Gazette, April, 1907. Idem, Brit. Med. Journ.y 1908, ii., 1243. EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 31 none of these Protozoa be demonstrated ; while less than a third of all the other patients were free from protozoan infection. The type of dysentery is mild, for of 4,719 cases treated in 1904-5 only 298 were fatal ; and as the patients, almost without exception, belonged to the criminal and poverty-stricken classes, this proportion indicates a non-malignant form of disease. Major Anderson's statistics are, moreover, instructive, inasmuch as the convict population of the Andamans is representative of almost every race and province of the Indian Empire, and the ratio of infection of new arrivals may, therefore, be regarded as fairly reflecting the conditions which prevail throughout India. In Ceylon, where dysentery of a malignant type is extremely prevalent, the amoebic variety of the disease is uncommon. Castellani,^-^ who examined the dejecta of 150 dysenteric cases in the Government hospitals, found entamoebas in two only ; and although one writer states ^^ that amoebic dysentery is prevalent in the hill districts, amoebic infection appears to be comparatively rare. In both of Castellani's cases the disease was complicated by hepatic abscess, but in neither instance could entamoeba be found in the pus. An additional point of interest in Castellani's report is that both patients were included in a series of twenty- three cases of dysentery in which a special bacteriological examina- tion was carried out, and that neither showed a Shiga-Kruse infection, although the specific bacillus was successfully demon- strated in nineteen of the others. No definite statistics as to the prevalence of amoebic dysentery in Asia Minor and Arabia are available, but infection is now known to be more general than has been supposed. The dysenteric •* CasteWam, /ourn. of Hygiene, 1904, iv., 495. '® Fernando, Brit. Med. Journ., 1905, i., 875. 32 AM(EBIC DYSENTERY diarrhoea by which pilgrims returning from Mecca are so frequently attacked, and which in Semitic countries sometimes assumes an epidemic form, is declared by Drs. RuFFER and Zirolia ^^ of the International Sanitary Commission to be true amoebic dysentery. Kartulis states ^^ that the Hedjaz acts as the medium of distribu- tion, and that the pilgrim-diarrhoea — so frequently seen at the quarantine stations of Egypt — is a typical example of the epidemic occurrence of the disease. The fact that an enormous number of pilgrims from infected countries annually flock to Mecca, where they live under most unhygienic conditions, sufficiently explains these outbreaks ; but there is also good reason to believe that amoebic dysentery is endemic and very prevalent in the country itself. Throughout tropical and subtropical Africa, amoebic dysentery is ubiquitous. It is exceptionally prevalent in alluvial districts along the courses of the great rivers, where floods are frequent, and where surface drainage is often defective. In Egypt the case- incidence of amoebic dysentery is higher, in proportion to popula- tion, than in any other country in the world ; but the occurrence of the disease is limited almost entirely to the low-lying tracts of land adjacent to the Nile. On the other hand, in the oases and desert regions of Egypt amoebic infection is infrequent ; but in parts of Tunis, Algiers, and Morocco^^ it appears to be very prevalent. In South Africa, amoebic infection is uncommon on the dry uplands of the interior, although in the coast towns, and especially in the Portuguese and German ^^ colonies, and in Natal, it is of '^ Zirolia, Bulletin Quarantenaire. Alexandria, June 9, 1904. '* Kartulis, KoUe and Wassermann's " Handbuch." Jena, 1907, p. 352. '* Marchoux, Comptes rendus ; Soc. Biol.^ 1899, p. 870. 20 Hillebrecht, "Ueber Ruhr-artige in Deutsch. Sud-West KinkZy" Archiv.f. Schiffs find Tropen- Hygiene, 1906. EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 33 frequent occurrence. The camp dysentery which proved so fatal in the Transvaal and Orange Free State during the war of 1901 was almost wholly of the bacillary type ^^ ; but fifteen out of the thirty-seven cases identified as amoebic dysentery in the Hamburg Seamen's Hospital were contracted in South African ports. According to RiJGE, it is endemic in Madagascar. Throughout the equatorial provinces and in the Western Territories of Africa, acute dysentery, although by no means infrequent, is apparently less prevalent than in most other parts of the tropics. Prout states ^^ that in the Gold Coast Colony the commonest clinical variety of the disease is a subacute form of dysenteric diarrhoea, which is rarely fatal, but which shows a marked tendency to become chronic. Entamoebae, however, can seldom be demonstrated, and hepatic abscess is rare. In Senegal, on the other hand, Marchoux^^ reports that amoebic dysentery is endemic. At the Settlement of St. Louis, where the disorder is unusually prevalent, it frequently assumes an epidemic type ; and, almost every year, during the months of July and August, the case incidence rises rapidly. In 1898, forty-seven cases, of which two were fatal, occurred in the French garrison. The principal clinical features of this outbreak of dysentery were mildness of type and protracted course, whilst the specific nature of the infection was clearly indicated by the fact that entamoebae were found in the dejecta of every one of the patients. Hepatic abscess was, however, a rare complication. Little exact information is available as to the prevalence of amoebic dysentery in other provinces of Central Africa, but the *^ Report of the Commission of Inquiry, South African War, 1903. ^^ Transactions of the Society of Tropical Medicine and Hygiene^ 1908. ^^ Marchoux, " Note sur la dysenteric des pays chauds," Cotnptes rendus Soc. Biol., 1899, 870. 34 AMCEBIC DYSENTERY disorder is stated to be moderately frequent in Lagos, in the Niger and Congo valleys and deltas, in Kamerun,^* and throughout the lake regions in Uganda, and in the East Coast Protectorate. Creighton Wellman has informed the writer that at Angola he repeatedly verified the existence of both types of dysentery, and that hepatic abscess is often seen as a sequela of the amoebic variety of the disease. A malignant form of epidemic dysentery — probably bacillary — is prevalent on the caravan routes, but it occurs only during the dry season. Amoebic dysentery is endemic in Benguella. In the Western Hemisphere, relatively to latitude, amoebic dysentery is, perhaps, even more prevalent than it is in the Old World. Most of the tropical States of North and South America are endemic centres of the disease ; whilst in the temperate regions of both continents it is also extensively disseminated. In the West Indies, although hepatic abscess is rare, the flux which is so prevalent and fatal throughout Central America has been shown to be mostly of amoebic origin. In the Panama Canal region, amoebic dysentery was formerly very prevalent ^^ ; whilst in Florida ^^ and in Texas,^^ it is stated to be more common than any other variety of severe illness. Throughout Brazil,^^ Venezuela, Chile, and the Amazon valley, amoebic dysentery is also very prevalent ; but in Argentina amd the other Southern Republics, although cases are occasionally recorded,^^ ^* A. Plehn, "Die Dysenterie in Kamerun," Archiv. f. Schiffs und Tropen- Hygiene, 1898, 125. -' Osier, Medical News^ 1902, and other papers. '^ Nasse, Z>^«/j«:/«. med. Wochenschr., 1891, 881. " Dock, Texas Medical Journal^ 1891,419. ^^ Fajardo and others, see Centralbl.f. Bakt., 1896. -* Dessy and Marotta, " Sobre la existencia de la enteritis disenterica y del absceso del higado en Argentina," Ann. Med. Circ, 1905. EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 35 it is infrequent. In the mortality returns published by the Govern- ment of Brazil,^'' a fatal issue is ascribed to amoebic dysentery once for every three times that the bacillary type is certified as the cause of death ; and it is noteworthy that, in Rio de Janeiro at least, children and young adolescents appear to be affected much more frequently and severely than in other countries.^' In Polynesia and the tropical districts of Australia, amoebic dysentery is responsible for a large share of the excessive mortality from intestinal diseases which prevails throughout the whole of these regions. It has been repeatedly identified in Fiji ; and a recent epidemic disorder which occurred in that colony was shown to be due to amoebic infection. Similar outbreaks appeared at the same time in several of the European stations of New Guinea and New Caledonia, and at the latter settlement the affection was conclusively proved to be true amoebic dysentery. Although preferentially a tropical or subtropical disease, amoebic dysentery is not uncommon in cold countries, and it is widely dis- tributed throughout the temperate zones of both hemispheres. It is endemic in many parts of Southern Europe, and is excep- tionally prevalent in Italy, Sicily, Malta, and the Balkan Peninsula. Kruse and Pasquale observed numerous cases in Naples, Aquila, and Calabria ; whilst Celli and FiOCCA showed that Rome, Siena, Belluno, and Forli were deeply infected, and Schaudinn found it in abundance at Rovigno. The occurrence of the disease is by no means limited to South Europe. It is not uncommon in Austria-Hungary,^^ Poland, ^ Boletim Estatistica. Rio, 1907. ^^ O. De Oliveira, " Dysenteria amebica na infancia," Brazil Medicina. Rio, 1904, 321. ^- Hlava, Centralbl.f. Bakt. (Ungarn), i., 537. 36 AMCEBIC DYSENTERY Bavaria, and most of the Northern States of Germany.^^ In 1901,^* amoebic dysentery appeared in epidemic form among troops stationed in East Prussia, and similar outbreaks have been noted ^^ in garrison towns throughout Russia and Siberia. Numerous instances of purely indigenous origin have been seen in France and in England ; and a careful study of a case of amoebic dysentery, followed by hepatic abscess, in a man who had always lived in Birmingham, appears ^^ in a recent issue of the British Medical Journal. A case lately described ^^ by Messrs. Caussade and Joltrain before the Societe des Hopitaux in Paris, is so typical of amoebic infections as they are seen in Europe, that it appears to be worthy of citation. The patient was a man who had never been out of France, or, so far as he knew, in contact with anyone who had dysentery. He was attacked by diarrhoea, the dejecta soon becoming dysenteric in character. Subsequently, a hepatic abscess with a pulmonary vomica developed. No amoebae could be found in the excreta, nor could dysentery bacilli be grown from them. The blood, moreover, did not agglutinate cultures of the Shiga-Kruse or Flexner bacillus, but there was marked eosinophilia. Amoebae were ultimately found in the pus from the lung cavity, and at the autopsy, sections made from ulcers in the colon showed the amoebic infection to be severe and typical. In no country have so many reports of cases been published as in the United States ; and there can be no doubt that amoebic *' Steffenhagen, " Amcebendysenterie mit sekundar Leber Abscess." ^^ Jagers, " Ueber Amoebenbefunde bei epidemischen Dysenterie," Berl, klin. Wochenschr., 1901, xxxvi., 917. " Voroshilski, Protok. Omsk. Med., 1935. ^' Saundby and Miller, Brif. Med. Journ.., March, 1909. ^ Lancet, 1907, i., 694. EPIDEMIOLOGY AND GEOGRAPHICAL DISTRIBUTION 37 dysentery is much more prevalent in the temperate districts of America than in the isothermal zones of the Old World. Professor OSLER declares it to be by far the most common type of dysentery in that country, and he further states that at Baltimore the other varieties of the disease are seen but rarely. Musser, ^^ of Phila- delphia, says that the great prevalence of amoebic dysentery there is a conclusive argument against its being regarded as a tropical disease, or as having any special affinity for the tropics. Dock ^^ met numerous instances of amoebic dysentery in Georgia, but when he removed to Ann Arbor, in Michigan, he searched for amoebae in vain. The occurrence of amoebic dysentery has recently been noted by Nydegger ^^ at New York, by Lamb *^ at Washing- ton, by BOGGS ^* in Virginia and other Southern States, by Ellis ^^ in Texas, by Waugh ^* at Chattanooga, by Tuttle *^ in Ohio, and by C. F. Craig,^^ Fitz and Gerry,*^ and many other writers in most of the Northern States of the Union. '^ Musser, BrU. Med. Journ.^ 1902, ii., 242. '■ Dock, Medical Record, July, 1891. <" J. A. Nydegger, West Virginia Med. Journ., 1907, ii., p. 15. <' Washington Medical Annual, 1907. " T. R. Boggs, Virginia Med. Semi-Monthly. Richmond : 1908. *' Texas Cour. Record Medical. Fort Worth : 1906, 7, xxiv., i. ** VJaxxgh, Southern Med. and Surg. Journal. Chattanooga: 1905. " J. P. Tuttle, Lancet Clinic, Cincinnati, 1905 ; an6 Jour, of the Amer. Med, Assoc, Chicago, 1904. *® C. F. Craig, "The Pathology of Chronic Specific Dysentery,'' Journ, of the Assoc, of Military Surgeons, 1904, &c. " Fitz and Gerry, Boston Med. and Surg. Journal, 1891. PART II.— BIOLOGICAL. 41 CHAPTER IV. Classification and General Relations of Protozoa to Intestinal Diseases. Although important information as to the life-history and pathological relations of the Protozoa has recently been acquired by the study of human and comparative parasitology, the zoo- logical position of the group is still uncertain. From a medical point of view most of the illnesses which originate in infection by pathogenic Protozoa bear a close analogy to bacterial diseases, and if a classification on a clinical basis were possible, these organisms might reasonably be included in the vegetable world ; but, so indefinite are the biological features dividing them from unicellular plants on the one hand, and from metazoan organisms on the other, that most zoologists regard Protozoa as distinct from both kingdoms, and consider their establishment as a separate Class to be essential to an exact appreciation of their place both in Medicine and Natural History. In classifying primitive organisms it is now, however, usual to rely on the indications afforded by their habits of life rather than on morphological characters ; and it is therefore generally agreed to accept Protozoa as a separate sub-kingdom of the animal world ; their constitution being roughly defined by including within the group all organisms which, although consisting structurally of but a single cell, maintain an independent existence, and perform the functions usually associated with animal life. 42 AMCEBIC DYSENTERY The great majority of the Protozoa are free-living, and parasitism is the exception ; but in each of the four orders into which the sub-kingdom is divided, viz. (i) Rhizopoda, (2) Sporozoa, (3) Flagel- lata, and (4) Infusoria, parasitic forms are found ; and the second division, Sporozoa, belongs altogether to that category. From the standpoint of general pathology, also, the Sporozoa are of greatest importance, as the order includes most of those Protozoa which find their natural habitat in the circulation. The Rhizopoda, on the other hand, take first rank as intestinal parasites, in that they include the organisms which are responsible for the causation of amoebic dysentery ; but numerous Sporozoans, Flagellates, and Infusorians are also found in the alimentary canal, and some of them have more or less well-defined pathogenic functions. In the zoological scale the Rhizopoda are the lowest division of the sub-kingdom, and, regarded as animals, they are, perhaps, the simplest of all forms of life ; for the complete organism consists of nothing more than an uncovered cell of protoplasm, which moves and encloses food particles by means of temporary extrusions of its own body substance. They are subdivided into a large number of sub-classes, orders, and genera ; but most of them are free-living, and only one order — that of Amoeboea — comprises organisms which are parasitic in man. The order Amoeboea is further divided into three genera, Amceba, ChlantydopJirys, and Leydenia — all of them parasitic. Of these, however, Amoeba is alone worthy of special notice : for, of the other two — both of which contain but one species — Leydenia has been found only in the peritoneal fluid, and Chlamy- dopJirys enchelys, although its occurrence is not unusual in the human intestine, has no pathogenic function. As to the further sub-division of the Amoebae there is much dif- ference of opinion, but the system which is now generally adopted RELATIONS OF PROTOZOA TO INTESTINAL DISEASES 43 is that of SCHAUDINN. The classification, was not, however, originally made by that observer, for although it is known by his name, it is based on previous rearrangements of the genus by Casagrandi, Barbagallo, and Jurgens. In this scheme, the genus Amoeba is divided into two sub-genera — viz., Amoeba and Entamoeba. The use of the former term to denote first a genus, and, again, a sub-genus of the order, is confusing, and the nomenclature will no doubt be altered ; but in the meantime it stands, and is generally adopted by zoologists. Of these subgenera. Amoeba has many species, some of which are occasionally found as parasites of the digestive system and its accessory structures, but none of them possess any definite patho- logical importance. Entamoeba, again, is subdivided into two species — Entamoeba histolytica, the pathogenic organism of amoebic dysentery, and Entamoeba coli, a harmless intestinal parasite. 44 CHAPTER V. The Entamoeba of the Human Intestinal Tract. Technique and Methods of Demonstration. Fresh Specimens. — At all stages of the disease, the dejecta of a patient suffering from amoebic dysentery usually contain living entamcebae ; and if a drop of the excreted mucus is placed under a microscope, one or two organisms may generally be observed. As a rule they are easily seen ; and, after a little experience, there is seldom any difficulty in determining, almost at once, whether a given specimen contains entamoebae. Like other Protozoa, how- ever, they are apt to be elusive, and for their successful demonstra- tion certain precautions are necessary. It not infrequently happens that in the portion of material which is subjected to examination, no entamcebae can be discovered, although there may be considerable numbers of them in other parts of the stool ; and care must be taken to secure a specimen in which organisms are likely to be found. The mucus passed as the result of straining usually contains entamoebae ; and they are almost invariably present in the gelatinous matter and flakes of disinte- grating membrane which form the latter part of a dysenteric motion. There is no more likely situation than the edges of a small shred of sloughed mucosa ; and, if it is taken from freshly passed excreta, placed with some of the mucus in which it is suspended on a slide, and quickly examined, specific entamoebae will almost certainly be seen. THE ENTAMCEB.E OF THE HUMAN INTESTINAL TRACT 45 It is, further, important that nothing be allowed to interfere with the natural movements of the organisms. Their normal refractive index varies but little from that of thick mucus, and their outlines, in consequence, are sometimes almost invisible. In such cases, if not in motion, they are easily overlooked; but the characteristic changes of shape and position afford material aid in identification. Excreta intended for examination should, therefore, be preserved from contact with urine and disinfectants ; and it is desirable that the patient should not have been recently treated by calomel or other intestinal antiseptics. In cold weather the receptacle should be warmed ; and if that is done by boiling water accidental contamination by free-living amoebae will at the same time be avoided. In the tropics, and in ordinary circum- stances at home, a warm stage is unnecessary, for entamoebas are usually quite active at a temperature of from 15° to 20° C. A suitable fragment having been selected, it should be placed on the centre of a clean cover-glass. For this purpose a platinum loop is generally unsatisfactory ; the exact particle which is wanted can seldom be picked up, and smooth blunt forceps, with a pair of scissors to divide strings of mucus, are more useful. The specimen may be examined as a film or in a hanging drop. If the former method is adopted the cover-glass is gently lowered on to a slide, and lightly pressed down ; when a hanging drop is preferred, the edges of the cover are vaselined, and it is placed on a hollow-ground object-glass in the usual way. Should the mucus be exceptionally viscid, dilution with normal saline solution, slightly warmed, facili- tates observation ; as, apart from the fact that movements are then freer, the refraction of the medium corresponds less closely to that of entamoebse. The specimen should be examined with a full illumination, and in the first instance by a moderately low power. For making a 46 AMCEBIC DYSENTERY search a magnification of 80 to 100 diameters is most serviceable ; but in order to distinguish species, higher powers are desirable, while for detailed structural observation an immersion lens (^2"i"' or x\-in.) is necessary. In examining dysenteric dejecta, one of the first things to strike an observer is the fact that there is no definite relation between the severity of the symptoms and the number of organisms which are excreted ; often, in acute attacks, only one or two may be seen, while in mild cases they may be abundant. There is, besides, great irregularity in their frequency ; a copious infection may be noted at one time, and without obvious change in the condition of the patient or in the characters of the dejecta, organisms, at the next search, may be very rare. Fixing and Staining. — For purposes of diagnosis stains are generally unnecessary and whenever possible, intestinal protozoa should be examined fresh. Apart from the aid to identification afforded by their movements, the organisms are often so contracted and altered by fixing and colouring processes, that they present but a faint resemblance to their natural appearance, and definite information as to their life processes can only be gained by the study of fresh specimens. Both Entamoeba histolytica and E. coli, however, stain readily with most of the aniline dyes, and assistance in distinguishing them rapidly from each other, and from other cells in fresh dejecta, may be obtained by adding a small quantity of weak aqueous solution of acid fuchsin to the specimen. By this method, detritus and epithelial cells are coloured red, whilst the entamoebas are left almost unstained ; they are, however, much shrunken and altered in appearance by the action of the reagent. For permanent preparations, one of the simplest and best methods is to fix a film on a slide by gently rubbing a small piece THE ENTAMOEBA OF THE HUMAN INTESTINAL TRACT 47 of slough or mucus on the glass, which, when dried in the air, is placed in the vapour of osmic acid for twenty minutes, and after- wards washed with tapwater. Another well-known method of fixing entamoebae is the process recommended by Schaudinn. After spreading and drying a film on a cover-glass, it is floated (preparation down) in a watch-glass containing a mixture of two parts of saturated watery solution of perchloride of mercury with one part of absolute alcohol. The fixative is then heated to 70° or 80° C, over wire gauze, for ten minutes, at the end of which time the film is washed in 70 per cent, alcohol, flushed with water, and dried. The ordinary fluid fixatives, such as the solutions of Orth, Flemming, and Heidenhain, alcohol, chromic acid, &c., should not be employed for films or streak preparations of entamoebae, as they distort the organisms and often render them quite unrecogniz- able. Fixing fluids, however, act well when the entamoebae are in the tissues, and sections of intestine which have been hardened in Heidenhain's mercuric salt solution, or in Mxjller's fluid con- centrated in an incubator for three days, give satisfactory views of the organisms in situ. Specimens so fixed may be stained in various ways. A simple method is to dip the film for one minute in a 50 per cent, solution of tincture of iodine, afterwards clearing by washing it in 90 per cent, alcohol. Although they take the colour slowly, entamoebae may also be well stained by haematoxylin and eosin. Solutions of haematin in alcohol, and of alum in the proportions recommended by Daniels,^ having been matured and tested, a small quantity of the unfiltered stain is placed on the film for ten minutes, at the end of which time it is flushed off, and the specimen is dried after ' C. W. Daniels, " Studies in Laboratory Work." London, 1903, p. 53. 48 AMOEBIC DYSENTERY washing in tapwater. The film may then be counterstained by placing it in a i per cent, solution of eosin for half a minute, after which, it is finally washed and dried. Heidenhain's iron haematoxylin process^ is one of the best general stains for intestinal Protozoa, and Mallory's modification' of his technique is simple and effective. Nigrosin also secures good definition of structure, and has been much employed by German observers, many of whom regard this stain as more permanent and suitable for this class of work than any other. For differential chromatin colouring, Romanowsky's process is generally advisable, and the best specimens of entamoebas, both in film and in tissue, may be obtained by Giemsa's effective modifica- tion of that stain. In this method, Giemsa's fluid (Grubler) is slowly added to distilled water until the translucency of the mixture is approximately that of dark port wine, and the film or section is at once immersed in the solution. The specimen must remain in contact with the dye for twenty-four hours, after which time it may be dried, washed, and mounted. Many of the stains in ordinary use lack permanency ; and a specimen of entamcebae, especially when mounted in Canada balsam, is often quite invisible in less than a month. Films show less tendency to fade when put up without a cover-glass, and if kept dry will last indefinitely. The best specimens, too, are secured by light staining ; for structural detail can be seen clearly only when the organisms are faintly coloured. In faecal films, moreover, bacteria are sometimes excessively numerous, and when deeply stained they may obscure everything else. Bacteria-free films may sometimes be obtained from hepatic abscesses. * For particulars of the application of this process, see a paper by Captain Hamerton, " Methods of Study," &ic.,Journ. Royal Ar7ny Medical Corps, 1908. ' Mallory and Wright, " Pathological Technique," 1901, p. 397. THE ENTAMCEB^E OF THE HUMAN INTESTINAL TRACT 49 When E. histolytica is stained lightly in Giemsa, the homo- geneous ectoplasm remains almost uncoloured and appears as a clearly differentiated, slightly tinted area, whilst the granular endo- plasm assumes a deeper blue shade. The scanty chromatin of the nucleus, if at all visible, is seen as minute scarlet points or fibrils, and the ingested blood corpuscles are pale pink. The whole of the body substance of E. coli, when subjected to the same process, stains dark blue, the outer zones being, however, somewhat fainter in colour. The nucleus, on account of the abundance of its chromatin, shows numerous deep purple-red fibrils and spots. 50 CHAPTER VI. The Entamceb^ of the Human Alimentary Tract — Morphology and Structural Comparison. Entamceba Histolytica. — In the living condition, the patho- genic agent of dysentery assumes an endless variety of form. When at rest it tends to become globular, and is seen as an irregularly shaped spherical or ovoid mass ; but, on account of almost incessant motion in the cell protoplasm, the appearance is continually changing. With the commencement of movement, the organism elongates in one direction, becoming pear-, sausage-, or kidney- shaped ; but after further extrusion of pseudopodia from the circumference, irregularity becomes still more marked, and, in its active state, the amoeba appears as a multiform body of infinite diversity and complexity of outline. Similar movements are common to most rhizopoda, although in E. histolytica structural peculiarities in the formation of the pseudopodia are distinctive of the species ; and, in the cell itself, the following specific characteristics may generally be readily identified : — {a) A clear homogeneous field of jelly-like protoplasm, usually known as ectoplasm, which, when the organism is at rest, occupies about a third of the whole area. (6) A roughly granular endoplasm, which constitutes the remaining two-thirds of the total contents. (c) A faintly defined nucleus and nucleolus. THE ENTAM(EB^ OF THE HUMAN ALIMENTARY TRACT 5 1 (d) Inclusions of blood corpuscles, bacteria, and food particles. The cell-organism itself is enclosed by a thin line of tissue, which is, however, almost imperceptible where the granular endoplasm reaches the margin, and is well-defined only at the periphery of the homogeneous field. Even there it cannot be identified as a definite membrane, for no characteristic structure can be distinguished ; and it varies in clearness with the specific gravity of its surroundings. In a thick medium, which presumably approximates to the density of the clear zone, the line is hazy and indistinct ; but in thin fluid, or in normal saline solution, it stands out with sharp definition. Further, as granules and other objects readily pass out and in at all points of the periphery, and as the organism is known to contain no cellulose, it is practically certain that the body substance is not enclosed by a true cell-wall, and that the line which is seen is merely the limit of the protoplasm rendered perceptible by difference of refraction. The Homogeneous Transparent Protoplasm, or Ecto- plasm, is generally described as forming a complete zone round the granular endoplasm, but during life that distribution is of very rare occurrence. It varies in size and position with the condition of the organism, and, in ordinary circumstances, the so-called ectoplasm is situated at one or both ends of the cell. When pseudo- podia are thrown out, hyaline protoplasm invariably collects behind the periphery at the point where the extrusion is taking place, and there is always, therefore, a clear field at the anterior pole of the entamoeba, in the direction in which movement is taking place. The arrangement of the ectoplasm is, in consequence of that disposition, segmental rather than circumferential, and the granular endoplasm is usually in direct contact with the periphery at one or more places. In these situations no clear area can be seen to intervene between it and the edge of the cell ; and, except that the 52 AMCEBIC DYSENTERY ectoplasm is never enclosed by granular matter, nor completely cut off from the periphery, it has little claim to its title. The area which the ectoplasm occupies also varies with the digestive activity of the organism. V/hen food particles are englobed by the entamoeba, they are thrust at once into the granular matter, which may thus become so distended as to fill up the whole of the body space, the homogeneous area being pushed aside, and com- pressed until it becomes almost invisible. With the absorption of the nutritious matter and the expulsion of refuse, the hyaline proto- plasm appears to expand, until, in the fasting condition, it again occupies half or one-third of the organism. Although no structure can be made out, and although neither vacuoles nor food particles can be seen in the homogeneous proto- plasm, there is no doubt that it is, nevertheless, strictly specialized in composition as well as in function. The highly refractive appearance suggests that it is of infinitely greater tenacity and hard- ness than the rest of the cell ; and the disposition indicates that it subserves the purposes of motion and prehension rather than those of digestion. It is, moreover, definitely connected with the patho- genic function of the species ; for it is by means of the long and sharp pseudopodia of hyaline material that E. histolytica is able to thrust itself between the cells of epithelial and glandular structures, and to tear asunder the connective tissue fibres. The Granular Protoplasm varies considerably in appearance and opacity. In some specimens it is pale and finely granulated, and, not infrequently, its limits can be differentiated from those of the homogeneous protoplasm only by a slightly deeper shading. In the majority of cases, however, it is coarse, densely opaque, and sharply separated from the hyaline protoplasm ; and it is often so closely packed with clumps of granules that the nucleus and included bodies which it contains are quite invisible. THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 53 It is difficult to explain these variations, for, even under the highest powers of the microscope, the granular protoplasm appears to be structureless ; no fibrillar tissue, nor any appearance sugges- tive of an areolar network, can be distinguished. The colour varies with the food which has been ingested, and with the number of granules; but, in ordinary circumstances, the endoplasm of E. histolytica has a pale, greenish-yellow tint — that of E. coli being brownish-grey — and the general formation is that of a thick gelatinous fluid, in which particles of granular matter are em- bedded. The granular endoplasm is also much less viscid than the homogeneous ectoplasm, for distinct currents and streams may often be seen in it, and Harris states that motile bacilli which have been ingested continue to move about freely. There can be no doubt that it is contractile and resilient ; and its capacity for varied and rapid movement is shown not only in locomotion, but by the way in which food particles are thrust deeply into the interior, and their debris afterwards expelled from the periphery. The granular endoplasm also possesses marked assimilative functions, and it is able to deal with an astonishing quantity of food. Entamceba coli. — In E. coli there is no separation of granular from hyaline area. Granular protoplasm fills the whole of the organism ; and although here also there is sometimes a little variation in the intensity of the shading, no distinction can be drawn between the protoplasm of which the pseudopodia are formed and the rest of the cell contents. When locomotion takes place, the absence of the clear field at the anterior pole is especially noticeable ; and this marked characteristic is one of the most important indications in the identification of species. A trans- parent ectoplasm is, practically, peculiar to E. histolytica, and the formation of hard and powerful pseudopodia differentiates that 54 AMCEBIC DYSENTERY organism from E. coli and from all other cells that are found in the intestinal contents.^ Another notable point of distinction between E. histolytica and E. coli is that the granular endoplasm of the former almost Fig. I. — Enta7>io!ba histolytica. X 375 (semi-diagrammatic). £, Ectoplasm or hyaline protoplasm; 6^, granular endoplasm; N, nucleus and nucleolus; B.C., ingested blood corpuscles. (The nucleus is placed more centrally, and is larger and more distinct than it usually appears.) Fig. 2. — Entamoeba coli. x 500 (semi-diagrammatic), a, Commencing movement ; 3, in motion (nucleus obscured) ; c, at rest ; N, nucleus ; V, vacuoles. invariably contains considerable quantities of ingested blood. It is by no means unusual to find twenty or thirty englobed corpuscles in one organism ; and in many cases the whole of the interior is closely packed with these cells. Ingested blood corpuscles are never ' Prowazek states that Amceba buccalis also possesses a hyaline ectoplasm, but that it is distinguished from E. histolytica by its nucleus, which is central, and more defined. {Arbeiten aus dem Kaiserlichen Gesundheitsatnte Leiisatnie, xxi., 42.) THE ENTAMOEBA OF THE HUMAN ALIMENTARY TRACT 55 seen in E. coli ; but the vacuoles, which are of common occurrence in the endoplasm of that species, must be carefully distinguished from blood cells. In other respects, the protoplasm of E. coli differs but little from the granular endoplasm of E. Jiistolytica. It is, however, somewhat finer and lighter in texture and the granules are smaller. Fig. 3. — Entarnceba hisiolyiica. Organisms in dysenteric mucus. X 400. The granular protoplasm occupies almost the entire cell, and is distinguished from the ectoplasm only by a slight difference in shading. In both species the endoplasm generally contains numerous minute fragments of solid matter — apparently foodstuff and bacteria. The structural granules themselves are derived from two sources ; they may be nuclear, that is to say, they may be fragments of chromatin extruded from the nucleus, or they may be metaplastic — residue from the digestion of food. The former resemble shreds of a fibrillar structure ; the latter are more angular, 56 AMCEBIC DYSENTERY and look like grains of pigment. These varieties of granules are easily distinguished from each other. The process by which blood corpuscles are ingested by E, histolytica, and their ultimate fate after being included in the endoplasm of that organism, are imperfectly understood ; for although living entamoebas have been watched for long periods in fluid media in which blood cells were plentiful, and to which fresh blood was from time to time supplied, and although the conditions were as nearly as possible normal, the actual enclosure of a red blood corpuscle by an organism has never been observed. So far at least as specimens of entamoeba which are under the microscope are concerned, it is, moreover, very doubtful whether any absorption takes place ; and, as it is certain that there is no expulsion of residue, many observers have claimed that the process has no place in the nutrition of the organism. It can scarcely be doubted, however, that blood corpuscles are captured by entamoebae in the same way that bacteria and smaller particles are englobed by leucocytes, and that they are afterwards assimilated by a process akin to phagocytosis. Digestion seems to be temporarily arrested when the organism is placed in the light, but the appearances are so distinctive as to leave little room for any other conclusion. In both varieties of entamoeba a nucleus may be seen ; but there are marked differences in its position and structural arrange- ment in the respective species. In E. histolytica, the nucleus, although a constant structure, is generally ill-defined, easily mistaken for an ingested blood corpuscle, and often very difficult of identification. It is about 4 to 6 /i, in diameter, ovoid or elongated in shape, and it is generally placed eccentrically to the granular protoplasm, lying almost on the periphery of that substance. It contains very little chromatin, THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 57 and, in consequence, stains badly, no definite nuclear structure, filaments, or chromidia being apparent. A small bladder-like nucleolus, in which lies a grain of pigment, is always present. When the endoplasm is opaque, and crowded with granules, blood corpuscles, or other ingested matter, the nucleus may be completely obscured, but the addition of dilute acetic acid to the specimen generally brings it into view. Fig. 4. — Entaniaba histolytica. X 500. Fixed in osmic acid vapour, and stained by safranin. (After Jiirgens.) The nucleus and nucleolus are slightly coloured. There are no freshly ingested corpuscles, but the granular endoplasm contains debris and matter suggestive of the remains of blood cells. The hyaline ectoplasm is well seen. Fig. 5. — Entamceba coli. X 500. Fixed, while in motion, by osmic acid vapour and stained with safranin. The nucleus, which is rich in chromatin and has a shaded areola, is well seen. V, vacuole. In E. co//the nucleus is generally deeply placed in the interior of the endoplasm. It is clearly defined, and, in most cases, easily seen ; in shape it is spherical, and apparently vesicular, and it is separated from the endoplasm by a line, usually of remarkable sharp- 58 AMCEBIC DYSENTERY ness, and by a definite areola. Unlike the nucleus of E. histolytica, it contains a large quantity of chromatin, and it stains deeply with any nuclear stain. A small nucleolus may sometimes be seen. The presence of Vacuoles is an important feature in the differentiation of species. Briefly stated, the distinction is that E. histolytica contains blood cells and no vacuoles ; and that E. coli contains vacuoles and no blood corpuscles. Round, trans- parent, faintly coloured discs, from 3 to 5 /^ in diameter, are not infrequently observed in the interior of E. histolytica, and they are often described as cavities in the granular matter. The nature of these bodies is, however, doubtful ; the general appearance and a characteristic yellowish tint suggest that they may be partially digested blood corpuscles ; but, if that is so, it is difficult to explain why, although considerably smaller than red cells, they are always uniform in size. They have, however, nothing in common with protoplasmic vacuolation, for they can be seen to react to pressure and to the influence of movement in exactly the same way ag semi-solid structures. In E. coli several well-developed vacuoles can generally be seen, but their presence is not invariable. They vary greatly in size and in distribution, and they are usually scattered all through the protoplasm, two or three large ones being often grouped near the nucleus. They are easily obliterated by pressure. Size of Intestinal Entamoebce. — E. histolytica is usually described as being considerably larger than E. coli ; and difference of size is regarded by many writers as an important specific distinction* In neither species, however, is size a constant character, and it is, therefore, of little diagnostic value. The usual diameter of E. histolytica is from 20 to 30 /i, and specimens measuring 40 fi are by no means rare ; but, on the other hand, undoubted examples no more than 10 to 12 /x in breadth are frequently seen. THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 59 It is also the case that, in different patients and in different attacks of amoebic dysentery, the specific organisms vary con- siderably in size. In some infections they are almost all large, in others almost all small ; and although no relation has been shown to exist between size and the severity of the seizure, it is probable that different " strains " of E. histolytica vary in virulence as they do in bulk. Apparent size is, moreover, influenced by different conditions, and especially by the density of the surrounding fluid. In the same way that the periphery becomes more clearly defined in a thin fluid, the whole entamoeba appears to increase in size after the addition of normal saHne to the medium in which it is living. E. colt usually measures from 12 to 25 /i in diameter, and as it very rarely exceeds the latter figure, the statement that the organism is smaller than E. histolytica is so far correct. Movement and Locomotion. — In favourable conditions entamoebae are seldom or never at rest ; and when not in active movement from one place to another, alterations in their outline and in the arrangement of the endoplasm are continually taking place. The manner in which these changes in shape and position are effected is, moreover, characteristic of the species ; and valuable aid in the distinction of E. histolytica from E. coli is afforded by observation of the movements and by the conformation of the pseudopodia. If a living specimen of E. histolytica is watched for some time, it will be seen that at some particular point the periphery bulges, and that hyaline protoplasm collects under the protuberance. This swelling subsides almost as soon as it forms, but immediately reappears in another segment of the circumference, the process being repeated again and again almost without intermission. It may also be observed that these continuous movements, though apparently confined to the ectoplasm, begin in the centre of the organism, and 6o AMCEBIC DYSENTERY that they are invariably preceded by a change in the granular protoplasm. The first indication of commencing motion is that the granules, nucleus, and foreign bodies in that substance are momentarily swayed backwards and forwards as if by a current of liquid protoplasm. Movement towards one point of the periphery ultimately predominates, and the subsequent change in outline takes place at that spot ; but the granular protoplasm does not reach the periphery, and a thick cushion of hyaline matter always intervenes between it and the protuberance which is formed. In both species locomotion is effected merely by an extension of the pseudopodia in one direction. In E. coll, the gray protrusion which is pushed out from one pole of the elongated organism becomes longer and larger, the body protoplasm flowing in until nothing is left behind. In E. histolytica the pale-coloured pseudo- podia appear at first structureless, glassy and homogeneous ; and for an appreciable time after their formation they are without granular endoplasm. Ultimately, however, that substance pours steadily into their interior until the whole of the organism is gradu- ally transferred into what was once only a protrusion of hyaline ectoplasm. The pseudopodia of E. histolytica are generally somewhat thicker and stouter than the finger-shaped protrusions of E. coli, although this is by no means a distinctive characteristic. The ends of the projections in both species are rounded and sometimes club- shaped ; but those of E. coli are soft and flaccid, whilst the terminal extremities of E. histolytica appear horny and resistant, their forma- tion and movements suggesting great tenacity and strength. In a thin fluid locomotion is, naturally, more active than in dense surroundings, but the rapidity with which E. histolytica moves through a tenacious medium, and the ease with which it can push aside obstructions, are very remarkable. The movements of E. coli, THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 6l on the other hand, are limited in scope and lacking in vigour, and outside the body they quickly fail and cease. When entamcebae are in motion a considerable quantity of debris adheres to the back part of the organism, and as in E. histolytica the granular endoplasm collects in the posterior end, it is often very difficult to determine whether the matter is really adherent, or whether some of the protoplasm is not escaping. Fig. 6. — Entatnxba histolytica. Dying and dead forms. In some the clear ectoplasm and the nucleus can still be seen ; in others, structural disintegration has already set in. " Mulberry " knobs well shown, x 4CX). (After Kartulis.) Death of the Organism. — The duration of life is unknown. When conditions are favourable, as in the alimentary canal, both species undoubtedly live for a considerable time — probably for some weeks, or for one or even two months — but, outside the body, even although a suitable temperature and other essential conditions are maintained, vitality soon begins to fail. E. histolytica 62 AMOEBIC DYSENTERY is much more tenacious of life than E. coli ; the latter dies almost at once, but, on a stage with a regulated temperature, the former sometimes lives for three or four days. After death, both species contract in size and assume a spherical shape. In E. histolytica the granular endoplasm becomes lighter and less opaque ; the nucleus takes up a more central position, and, in consequence of increased transparency, both it and the nucleolus can generally be easily made out (see fig. 4). This clear structural definition is, however, of short duration, for within twenty-four hours decomposition sets in, and soon afterwards nothing can be seen but a granular mass. At death, E. coli also becomes paler, the change in shade being especially noticeable near the periphery, and suggesting the forma- tion of a separate ectoplasm. When death takes place suddenly, it is often preceded by violent agitation of the endoplasm and spasmodic movements of the whole organism. Short, irregular, and malformed pseudopodia are thrust out at various points of the periphery, and these extrusions some- times persist as rounded mulberry-like knobs on dead entamoebae of both species. Distinction of Entanioebce from other Objects. — Free-living amoebae, leucocytes, and epithelial or other organic cells may be readily mis- taken for entamoebae. The contamination of faecal matter by free- living amoebae after it has been selected for examination is by no means rare. In the Tropics especially, there is often abundant oppor- tunity for the development of these organisms in the water which is used to clean vessels and receptacles, and unless care is employed they may easily find their way into specimens selected for examination- The resemblance between entamoebae and many free-living species is, moreover, sometimes very close, and it is to be noted, as Viereck points out, that several of the latter have resting stages which can scarcely be distinguished from those of parasitic forms. THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 63 As a rule, free-living amoebae can be recognized by the fact that almost all of them are furnished with a pulsating or contractile vacuole. This, however, is not an absolute characteristic, for several free-living amoebce have been described which ■ have no contractile vacuole ; but, so far as is known, that structure is never seen in parasitic entamoebas; and if in dysenteric dejecta an organism is found in which there is a contractile vacuole, it may safely be regarded as a result of accidental contamination. From large leucocytes entamoebae may usually be differentiated by their greater size, by the characteristic formation of their pseudo- podia (especially noticeable in E. histolytica), and by their wider activity and freedom of movement. It happens, not infrequently, that, as a result of catarrhal in- flammation of the colon, an extensive desquamation of the epithelial layers takes places, and that numerous degenerating cells are shed into the intestinal contents. Many of them are water-logged and swollen, and in this condition they sometimes present a superficial resemblance to entamoebae. Observation, however, reveals almost complete lack of structure and general disintegration ; and, apart from these differences, epithelial cells are easily distinguished from living entamoebae by the fact that they exhibit no change of outline or position. 64 CHAPTER VII. The Entamceb^e of the Human Alimentary Tract — Reproduction. So far, the examination of the intestinal entamoebae presents no serious obstacle, and the morphological characters which differen- tiate species may generally be identified during the routine observa- tion of a case of amoebic dysentery. The methods by which the organisms multiply, although still more distinctive of species, are on the other hand exceedingly complex and difficult to follow, so much so that for clinical purposes they are practically unavailable. Their importance, however, is so great that a brief statement of the prominent features in the processes of reproduction is necessary. Our knowledge of the reproductive stages, and especially of the sexual multiplication of intestinal entamcebae, is almost entirely due to the researches of Schaudinn.' He showed that in the case of E. histolytica the facts are as follow : — Multiplication may occur during the active life of the organism within the intestine, in which case it is generally, if not always, asexual. This sometimes takes the form of binary fission, that is to say, the whole entamoeba after cleavage of the nucleus divides into two equal parts ; but more often asexual multiplication is effected by means of budding. In the latter case, after dispersion of the nuclear contents in the endoplasm, an indefinite number of F. Schaudinn, Arbetten aus dem Kaiserlichen Gesundheitsamte, 1903. THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 65 daughter entamoebae, each containing fragmentary chromatin, are irregularly extruded from the periphery of the parent organism, to which, however, they remain joined by a narrow neck. A nucleus having been formed by the collection of the included chromosomes, this attachment ruptures and the young entamoebae are set free. These processes correspond to the schizogony of other protozoa. Fig. 7. — Entamoeba histolytica. Asexual multiplication by budding. x 900. a, b. Dispersion of nuclear contents in the granular endoplasm ; c, collection of chromatin for the nuclei of the young entamoebse ; d, formation of buds. (After Schaudinn.) More frequently, however, multiplication takes place by spore formation or sporogony. At a certain period in the life of the organism it becomes mature, and it then enters on a resting or quiescent stage of existence. Schaudinn states that he is entirely unable to trace the influences that determine maturity in any species of amoeba ; but the condition should be distinguished from the formation of resistant cysts, which is induced by unfavourable external conditions. In the latter state E. histolytica is usually seen as a spherical body, lo to 20 yu, in diameter, with a clearly defined envelope. The cell contents are of a uniform pale grey colour, and present no appearance of structure. No nucleus is visible. In the sexually mature organism, the division between 5 66 AMCEBIC DYSENTERY hyaline and granular protoplasm is readily distinguishable, and the nucleus is easily seen. After a special form of nuclear division and subsequent conjuga- tion, most of the indistinct chromatin of the nucleus is shed into the endoplasm ; the nucleus consequently degenerates, and the residue is expelled. The fragments of chromatin afterwards collect at various points of the periphery, and form themselves into an un- certain number of minute spherical cysts, each 3 to 7 /a in diameter, by the aid of a filamentous membrane derived from the hyaline ectoplasm. These small bodies subsequently separate from the organism and .form resistant spores which are able, probably after passing through another phase, to develop into new individuals. The parent entamoeba thereupon rapidly degenerates and dies. Fig. 8. — Entamaba coli. Asexual multiplication by binary fission. x 900. (After Craig.) In comparison with these progresses, and with the indefinite formation and number of buds and spore-cysts in E. histolytica, the reproduction of E. coli is more typical and regular. In this species, multiplication by schizogony, which also occurs only during the intra-intestinal life of the organism, may take the form either of binary fission or of a special type of multiple division. In the first process, there is no diffusion of the chromatin through the cell protoplasm, and the nucleus simply splits up into two halves. When nuclear separation is almost complete, the cell protoplasm constricts, opposite the point of separation, and the organism divides into two equal segments. THE ENTAMCEB^ OF THE HUMAN ALIMENTARY TRACT 6? When schizogony by multiple fission takes place, the nuclear chromosomes, after dispersion through the body substance, collect at eight separate and almost equally distributed points to form the -^c/,; Fig. 9. — Entamceba coK. Schematic representation of asexual and sexual reproduction. 7- 1904. 190 AMCEBIC DYSENTERY The appearance of the cavities is characteristic. In contradistinction to the greenish-tinted and extremely offensive pus found in cerebral abscesses which are a result of cranial disease, the contents of amoebic abscesses of the brain are generally odourless, and of a deep yellowish or brownish-red colour. There is also, in most cases, a true pyogenic membrane ; and sections through the abscess Fig. 30. — Amoebic suppuration of the brain. Section of a minute abscess. The cavity contains numerous entamoebae and pus corpuscles. The nuclei of both are deeply stained. (After Legrand and Dopter.) X 300. reveal the presence of large numbers of entamoebas floating free in the pus or embedded in the walls and surrounding tissues. Legrand states^ that amoebic abscesses of the brain are seldom sterile, and that besides entamcebaj various bacteria, both aerobic and anaerobic, may be recovered from the interior. Legrand, Deutsch. med. Woch., p. 1905. OTHER SEQUELS OF AMCEBIC DYSENTERY 191 Abscess of the brain, as a sequela of dysentery, has long been familiar to physicians, and the following notes of a case which was treated by Habershon in Guy's Hospital over fifty years ago, supply an interesting clinical and post inorteui record of metastatic cerebral suppuration, and are, indeed, a typical example of a fairly common tropical condition. Chronic Dysentery. Hepatic Abscess. Pyamia. Abscess in the Brain and Lung. — Thomas D., aged 25, was admitted February 14, and died March 19, 1855. He was a sailor, and had been for two years in the East Indies. In Burmah he had ague and dysentery, and was ill for several weeks ; and for two months he had had pain in the side- On admission, he was sallow and generally cachectic. There was pain in the right side ; the chest was dull ; and it was supposed from the history that he had abscess in the liver. On February 21, when sitting by the fire, he fell down in a fit, and was convulsed ; for several days he continued in a semi-conscious con- dition. On the 28th, he could speak and give his name ; he continued apparently to improve till the 14th, when he again fell into a semi-con- scious state. On the i6th he was able to sit up and take his breakfast, but shortly afterwards he became quite insensible, and had stertorous breathing which continued till death. It was observed throughout that the right leg was weak, and that at last it was paralysed. The right pupil was smaller than the left, but a few hours before death it became widely dilated. On inspection twenty-four hours after death the outside of the brain was dry, and at the base there were slight adhesions between the surfaces of the arachnoid. In the posterior lobe of the left hemisphere there was an abscess about the size of a hen's egg, containing thick, tenacious pus, which nearly reached the surface, and was surrounded with softened brain substance ; at its anterior part there was a clot of blood, also surrounded by softened tissue. The abscess had broken into the posterior corner of the left lateral ventricle, which was filled with pus ; the right contained about an ounce of clear serum, and the fourth ventricle was healthy. In the chest old and recent adhesions were found at the bases of 192 AMCEBIC DYSENTERY both pleural cavities. The bronchi were slightly inflamed, and con- tained muco-purulent secretion. The base of the left lung contained a small abscess, the base of the right was in a state of incipient pneumonia. In the right lobe of the liver at the upper surface there were two chronic abscesses, containing about three ounces of pus ; it was viscid and green, and the walls of the abscess, which were very thick, were bounded by a smooth cyst and firm tissue about one eighth of an inch in thickness ; on the circumference of the abscess a compressed vein was observed. In the colon the mucous membrane was thickened ; several well- marked cicatrices were found in the ascending colon ; the mucous mem- brane was puckered ; and in some parts it was of a slate colour, the muscular coat being slightly hypertrophied. Unless located and opened at an early stage, cerebral abscesses are almost inevitably fatal, although in some instances, if the suppurating area is limited in extent, encystment may take place. When the amoebic cavities are numerous and small they tend to coalesce and to form worm-eaten channels on the surface of the brain ; but suppurative meningitis appears to be very uncommon. Abscess of the Spleen. — Suppuration of the spleen is generally regarded as a rare complication, but several instances have lately been described in which splenic abscesses developed as a result of amoebic infection, and many typical specimens of the condition are to be found in museums of tropical pathology. In a recent case reported to the Society of Tropical Medicine and Hygiene by Preston Maxwell/ of Amoy, an abscess of exceptional size developed in the spleen of a young Chinaman a month after the first symptoms of dysentery. The swelling completely filled the left half of the epigastrium and projected over to the right of the mesial line ; there were daily rigors which simulated a double infection of benign tertian" malaria, and, in the dejecta, which were * Society of Tropical Medicine and Hygiene, Transactions^ Julyi 1909. OTHER SEQUELS OF AMOEBIC DYSENTERY 193 dysenteric in character, Entamoeba histolytica was found. The spleen was incised through the abdominal wall, and 80 oz. of yellow pus and blood were evacuated, the patient making a good recovery. Large numbers of entamoebae were present in the contents of the abscess cavity. The liver w^as healthy. When suppuration takes place in the spleen it is generally exten- sive, and, in the great majority of instances, is fatal. The route of infection is uncertain : in a few of the cases which have been reported the organisms appeared to invade the viscus directly from the splenic flexure of the colon, but the blood-stream is probably the usual channel. Amcebic Appendicitis. — The appendix is obviously liable to be involved in the organic lesions ®f all varieties of dysentery, although, except as part of the general morbid process, amoebic appendicitis is rare. That mestastatic appendicitis, strictly so called, occasionally originates in amoebic infection, and that peri-appendi- cular suppuration may be secondary to insignificant amcebic lesions in the colon there can, however, be no doubt. Entamoeba histolytica has frequently been demonstrated in the walls of excised appen- dices and in pus from the region of the caecum, although there has been no history of dysentery and nothing to indicate amoebic infection. On the other hand, the results of careful searches for entamcebae in a large number of consecutive cases of appendicitis have been negative.* Differentiation between amoebic and non- amoebic disease of the appendix is generally impossible, and as the treatment is practically the same it is unimportant. Early surgical intervention is advisable in every instance in which a definite diagnosis of appendicitis has been made. * See papers by Leo Schredel {Wiener, klin. Rundschau., March 14, 21, 28, 1909) ; also, Report by Sozo Nishiyama {idetn). 13 194 AMCEBIC DYSENTERY Intestinal Hemorrhage. — Dangerous bleeding from the intestine, although rare, is occasionally encountered in the course of amoebic dysentery ; and Haasler,^ and Strong*^ have shown that this grave complication is especially liable to occur during the formation of a hepatic abscess. The frequent combination o( the two conditions is now fully confirmed, and numerous instances of their association have been reported by Futcher, MuGLiSTON, Freer,'' and other observers. The nature of the relationship is somewhat obscure, but Strong has recently pointed out that in the cases in which it was noted there was a marked diminution in the coagulability of the blood. Fever was also a prorriinent and persistent symptom, and jaundice occurred more frequently than in simple abscess of the liver. The evidence indicates that predisposition is an important factor, and that the condition is probably one of failure of resistance to septic infection. In view of the great destruction of the vascular coats of the intestine, severe bleeding might have been expected to be a more general symptom of amoebic dysentery than is actually the case. Alarming haemorrhage from amoebic ulcers, for instance, is less frequent than it is from the smaller necroses of typhoid fever, or of duodenal ulcer ; and the explanation of this comparative immunity is by no means clear. It is true that the type of disease is more chronic, and that endarteritis, infiltration, and thrombosis usually precede tissue destruction ; but in many instances of amoebic dysentery ulceration is both rapid and extensive, although only an insignificant amount of blood is passed in the dejecta. As has been seen, the blood-vessels often show a remarkable resist- ance to ulcerative processes. ^ Haasler, Deutsche, tned. Wochen., 1902. * Strong, Publications of the Biological Laboratory, Manila, 1905. '' Mugliston and Yr&tr, Jourft. Trop. Med.., iQOS- OTHER SEQUEL.^ OF AMCEBIC DYSENTERY 195 Gastro-intestinal Complications. — Except in cases of pro- foundly impaired nutrition, the mouth is seldom affected in amoebic dysentery ; but, in the poorest class of patients, cancrum oris is a somewhat frequent complication. Malignant stomatitis is, how- ever, more commonly seen as a concomitant of the bacterial form of the disease and of the dysentery which, in the tropics, so frequently precedes the fatal issue of tuberculosis, nephritis, diabetes and other chronic dyscrasias. It can, therefore, scarcely be regarded as a complication, for the association is with general malnutrition rather than with specific infection. Non-malignant stomatitis is very rare. The distinctive eroded ulcers of sprue have no relation to amoebic dysentery, and are found only when the disorder of which they are symptomatic has become established. Gastralgia, gastric catarrh, and dyspepsia are often described as late complications of amoebic dysentery ; but although some degree of digestive incompetence generally persists after the active symptoms have subsided, affections of the stomach rarely appear as true sequelae of the disease. In most cases, dyspeptic troubles are undoubtedly the result of remedial measures. Pain, nausea and vomiting are frequently induced by persistent attempts to irrigate the lower bowel ; and, when there is a tendency to gastric derangement, these symptoms are always increased by the use of copious injections. That various forms of neurosis originate in this way, there can be no question ; and absorption of toxin is especially liable to take place in young subjects. In a recent instance, two children who were being treated for chronic amoebic dysentery were severely affected, and rectal irrigation had to be abandoned, as it was invariably followed by violent sickness, and on one occasion by tetany. Gastric ulcer is very rare, but hyperchlorhydria and subacidity 196 AMCEBIC DYSENTERY are often remarked during convalescence, and in the quiescent stages of dysentery. So frequent are those symptoms, indeed, that it is almost reasonable to assume a definite connection between them and amoebic infection. The condition which is described as chronic amoebic enteritis is, in the great majority of cases, sprue. Except by direct extension upwards, the small intestine is seldom affected in amoebic dysentery, and permanent lesions or sequelae are certainly very rare. An affection of the upper bowel consequent on amoebiasis is said to be prevalent in Cochin China and in other parts of the Eastern tropics, but when a patient is carefully examined, mouth sores, contraction of the liver, and other distinctive signs of sprue are generally found. The morbid changes of the great intestine which result from amoebic dysentery have already been described. Together with the concurrently - formed peritoneal adhesions, these structural alterations of the colon give rise to permanent pain and tenderness, and are of so constant a character that they may fairly be included among the distinctive sequelae of the disease. The pain is generally persistent rather than severe, and it is aggravated by movement, by the erect attitude, by a full meal, or by any cause of intestinal distension. It ceases on the patient lying down ; but tenderness, although insignificant when standing, is generally increased in the recumbent position. If accidental diarrhoea comes on, or if a purgative is taken, the pain is altogether disproportionate to the intestinal disturbance ; but purgation is usually followed by a corresponding measure of relief. The condition is always chronic, and it is often combined with manifestations of persistent intestinal auto-intoxication. In such cases, the countenance is sallow or muddy ; and there is generally great vital depression with marked secondary anaemia and emacia- tion. Not infrequently, also, there are evidences of splanchnoptosis OTHER SEQUELS OF AMCEBIC DYSENTERY 197 and other visceral neuroses, the symptoms then chiefly affecting the nervous system. At this stage, neurasthenia, loss of mental tone, and melancholia are not unusual. Nervous Diseases. — Apart from mental impairment, it is now generally admitted that various derangements of the nervous system may originate in amoebic disease; and the interdependence of gastro-intestinal and nervous function on which neurologists lay so much stress is, perhaps, nowhere better illustrated than in the circumstance that disorders like chorea and epilepsy have, in many instances, been definitely traced to attacks of amoebic dysentery. Peripheral neuritis is also an occasional sequela, especially after middle age ; but the connection is often difficult to establish, as in countries where amoebic dysentery is endemic other causes are generally responsible for the condition. Chorea is a frequent consequence in young subjects ; and inco- ordination and spasm are extremely liable to be induced by an attack of dysentery if the patient suffered during early youth from these forms of nervous weakness. Musgrave has published ^ two cases which indicate the close association of the disorders. In one of them an attack and a relapse of amoebic dysentery were followed in each instance by chorea, although, after typhoid fever the patient had no nervous symptoms. * Musgrave, " Amoebiasis : Complications and After Effects," Philippine Jourfi. of Science^ June, 1906. PART VII.— TREATMENT. 201 CHAPTER XVII. The Prophylaxis of Amcebic Dysentery. It has been shown that every case of amoebic dysentery originates in the ingestion of the pathogenic entamoeba, and that, unless there is contamination of water or food by the dejecta of infected persons there can be no occurrence of the disease. It follows, therefore, that the first step in prevention is the destruction or efficient disinfection of the excreta of patients who are suffering from dysentery. Further, as it is apparent that infection, in the great majority of instances, is waterborne, the most effective measure of general prophylaxis must be to secure a public water- supply which is absolutely beyond suspicion. In several of the more important cities and settlements of the tropics the installation of a pure water supply has been satis- factorily accomplished, and, in practically every instance, the effect on the public health has been immediate and striking. In these places, amoebic dysentery has lost its endemic character, and, although by no means wholly eradicated, the disorder now occurs only in sporadic form, and as a consequence of infection by vege- tables, fruit, and other less important agencies. On the other hand, most of the great tropical centres of population are still without reliable drinking water ; and, in many cases, the public provision of a plentiful supply of pure water appears to be almost impossible. The difficulties are mainly geographical, and are 202 AMOEBIC DYSENTERY chiefly felt in districts where there are no hills, and where a river furnishes the only available source of supply ; for although, in ordinary circumstances, water may be effectively purified during a comparatively short flow in a stream, river valleys in the tropics are generally so densely populated that freedom from pollution is unattainable. Even when a town supply is collected from an uninhabited jungle catchment area, and is stored in an impounding reservoir, adequate supervision is extremely difficult ; and it is always advis- able, in districts where amoebic dysentery is or has been endemic, to take further precautions. Almost everywhere in the tropics sterilization of the domestic supply is necessaiy ; and it is a sound principle to make it an invariable rule to boil all drinking water ; and, after boiling, to keep it as far as possible sterile. Enough has been said about the growth of amoebic organisms on filters to show that, unless carefully looked after, these appliances may constitute a source of serious danger. When there is much sediment in water, a filter should be employed as a preliminary measure ; but filtration in itself is useless for sterilization, and may, indeed, prove a source of fresh contamination. As a rule, filters are unnecessary ; and on no account should drinking water be filtered after it has been boiled. With reference to milk, although its freshness and nutritive value are to some extent impaired by boiling, the risks of pollution are again so great and so insuperable that cow's milk should also be sterilized in the same way. The utility of Pasteurization, or the employment of lower temperatures than 212° F., is doubtful. Entamoeba cysts are highly resistant to heat, and experiments show that they are capable of surviving a temperature which will kill most varieties of encysted bacteria. Special precautions should also be employed with regard to THE PROPHYLAXIS OF AMCEBIC DYSENTERY 203 certain articles of common consumption. Lettuces, radishes, tomatoes and salads, unless grown under reliable supervision, are dangerous, and should be rigorously excluded from the household dietary. Even when sanitary cultivation is assured, uncooked vegetables are always suspect ; for nothing is more difficult than to convince a native gardener that vegetables will grow without plentiful supplies of liquid manure, and nothing is harder than to dissuade him from its use. Cold meat, fish, chicken, &c., must be carefully protected from contamination. Many families in the tropics make it a rule to have no meat on the table unless it has been brought direct from the fire ; but this stringent regulation excludes a large number of desirable and economical dishes, and if meat safes and wire-gauze covers are kept scrupulously clean and are judiciously used for the storage of cold meat, bread and similar things, they afford sufhcient protection. Cold meat should never be garnished with raw vege- tables or green herbs. In most tropical cities, the manufacture of aerated waters is now an industry of considerable importance, and soda water, lemonade and other beverages of the sort are largely utilized as table waters. In most cases, they are quite safe ; but their source should always be known, and if there is any suspicion of insanitary manufacture or of misrepresentation as to their origin they should be carefully avoided. The same caution applies to ice ; unless made from absolutely pure water, it may be highly dangerous, and there is no doubt that sherbet and other drinks displayed on booths in native bazaars are frequent sources of infection. Apart from special methods of prevention, resistance to the invasion of entamcebas depends, to a great extent, on adequate digestion and unimpairment of the general health. When vitality is lowered by exposure, improper food, and fatigue, infection is easy 204 AMCEBIC DYSEXTEKY and frequent ; when the normal tone of the system is maintained by regular habits, suitable diet, and adequate exercise, infection is difficult and rare. It is always necessary to guard against chills, which in the tropics are among the most frequent causes of intestinal catarrh. After exercise, a dry jersey, or sweater, should be put on and moist underclothes should be changed as soon as possible. In places where there is a marked fall in the atmospheric temperature during the night, a woollen abdominal belt should be worn ; and, generally speaking, exposure to damp and cold should, as far as possible, be avoided. In the tropics, as elsewhere, measures designed for the pre- vention of intestinal disease must be systematic and continuous ; and it is essential that they should conform as far as possible to the arrangements and comforts of everyday life. If prophylaxis ceases to be reasonably pleasant as well as practicable it will not be carried out. The continued use of distilled or boiled water at meals is always distasteful, and frequent change is necessary. Barley water, China tea (with fresh limejuice instead of milk), and aerated waters, with some variety of fruit extract, provide an agreeable and welcome change. The alcoholic drinks which are least likely to predispose to intestinal catarrh and consequent liability to specific infections are weak dilutions of spirits or some variety of white v\'ine in soda- water. Hock, Moselle, Sauterne, Graves, and Chablis of good quality can generally be easily obtained, and these wines are more suitable for hot climates than claret and burgundy. In British tropical settlements whisky or brandy and soda is in general use as a table beverage ; and if well matured, freely diluted with good aerated water, and taken in moderation, it is fairly innocuous. Liqueurs, bitters, and concentrated wines, such as sherry, port, and Madeira, should be avoided. THE PROPHYLAXIS OF AMCEBIC DYSENTERY 205 There is no foundation for the assertion that the free use of alcohol tends to produce immunity ; the chronic gastritis insepar- able from alcoholism actually predisposes to infection ; and the statement is, moreover, entirely contrary to clinical experience. As a matter of fact, alcoholic subjects are especially liable to amoebic dysentery. The beneficial influence which may be exercised by keeping men in good physical condition, by looking after their general hygiene without fuss or unnecessary irritation, and by carrying out reasonable precautions with regard to their food and drinks, is well exemplified by the decrease in the case incidence of amoebic dysen- tery among the American troops in the Philippine Islands since special sanitary regulations for the prevention of the disease were introduced. As compared with white civilians resident there, of whom from 15 to 20 per cent, are annually affected by amoebic dysentery, not more than 3 per cent, of the soldiers of the army of occupation are now treated for the disorder in the garrison hospitals. The general prophylaxis of amoebic dysentery may almost be summed up in one word — cleanliness. If domestic arrangements are closely supervised, if a plentiful supply of hot water is provided in the kitchen, if plates and dishes are scalded when washed, and afterwards dried with clean cloths, if water and milk are boiled, if food is kept from contamination by flies and other carriers of pollution, if larders and meat safes are systematically cleansed — in short, if the sanitary routine of a well-arranged house is made compulsory, there is little danger of contracting amoebic dysentery, even in places where endemic infection is intense and persistent. 206 CHAPTER XVIII. The Treatment of Acute Amcebic Dysentery. It has been seen that in a considerable proportion of cases of amoebic dysentery the periods of onset and relapse are attended by clinical manifestations of marked severity, and that the disorder is then liable to assume a grave and malignant aspect. It follows that during these attacks prompt attention and careful management are of special importance, not only in relieving the urgency of the symptoms, but in averting the occurrence of dangerous complica- tions. At this stage, however, active specific treatment is seldom practicable, and remedial measures are chiefly designed to mitigate the severity of the seizure and to tide the patient over an illness, which, although only an incident in the course of a chronic infection, may at any time induce a crisis of imminent danger. The general indications are to relieve pain, to keep fever in control, and to check the incessant attempts at defaecation ; and in order to effect these objects, absolute rest in bed and efficient and capable nursing are essential. During the exacerbations of amcebic dysentery it is specially important that all unnecessary movement should be avoided and that the systematic use of a bedpan should be made imperative. When there is much pain and tenesmus, treatment ought to commence with the hypodermic injection of i gr. of morphia, and a careful abdominal and rectal examination should then be THE TREATMENT OF ACUTE AMCEBIC DYSENTERY 207 made. If sc3'bala are present, or if, as is generally the case, there is evidence of irritation from retained faecal matter, a large intestinal douche (2 to 3 pints) of warm (98° F.) solution of boracic acid (2^ gr. to the ounce) should be administered. If necessary, this may be repeated ; and after the colon and lower bowel have been emptied in this way, a small enema of starch, mucilage of acacia, or some other demulcent, generally affords effective relief to the rectal spasm and irritability. It is inadvisable to inject ano- dynes, such as laudanum and cocaine, into the rectum, as in acute dysentery absorption is extremely irregular and uncertain, and serious symptoms are not infrequently produced by apparently small doses. If the stomach contains undigested food, an emetic of mustard and hot water should be given at once. In most cases, the purging and distress consequent on con- tinuous efforts at evacuation are immediately relieved by the morphia ; but, if the hypodermic injection is not repeated within a few hours, the tenesmus and other symptoms usually recur with undiminished violence. Unless the pain is excessive, it is, however, inadvisable to push the morphia farther ; and, at this stage, the best -effect may generally be obtained by giving a cachet containing 2^ gr. of calomel with | gr. of pulv. opii. This combination should be repeated every two hours until four doses have been taken. An old, although latterly somewhat discredited remedy, calomel is often of very great service in acute amoebic dysentery ; and, unless there are cogent reasons which forbid the use of mercury, no hesitation need be felt in ordering it. The principal indications against the employment of the drug are idiosyncrasy — which is especially frequent in persons of East Indian birth — marked anaemia or prostration, stomatitis, and oesophagitis. The huge doses (20 or 30 gr.) in which calomel was formerly prescribed are responsible for the disrepute into which it has fallen, for although there is 208 AMCEBIC DYSENTERY abundant testimony that, in the hands of Annesley, Morehead, and many of the older physicians, excellent results were often obtained by the use of the drug, it is not surprising, in view of the enormous quantities which they gave, that its administration was occasionally followed by collapse. There does not, however, seem to be any ground for the belief expressed by Habershon and WiLKS (who opposed the employment of mercury in all intestinal diseases), that in dysentery calomel always increases the inflamma- tion of the mucosa. On the contrary, in moderate doses, it un- doubtedly acts promptly and satisfactorily by hastening the removal of retained matter, by stimulating the biliary and intestinal secre- tions, and, possibly, by the exercise of its powerful antiseptic and germicide properties. When calomel cannot be taken, small and frequently repeated doses of sulphate of magnesia or sulphate of soda generally prove an efficient substitute. A concentrated solution — i drachm in an ounce of aq. chloroformi or aq. cinnamoni — should be given every two hours, until an ounce of the salt has been taken. The best effect is obtained if water and fluid nourishment are withheld for half an hour before and half an hour after the administration of the medicine. Opium should never be combined with saline remedies ; but, if necessary, morphia may be used hypodermically. In the earliest stage food must be reduced to a minimum, and for the first twenty-four hours the diet should be restricted to albumin water (the whites of two raw eggs to lo oz. of water), whey, barley water, toast water, or weak milk and soda (milk i, soda 3). Solids must not be given, nor should any food, such as undiluted milk, which is likely to form a bulky residue in the colon, be allowed. During the exacerbations of amoebic dysentery in the tropics, thirst is always intense ; it may be relieved by small quan- tities of ice, or iced water; and cold tea, with fresh limejuice instead of milk and sugar, often proves an effective remedy. THE TREATMENT OF ACUTE AMCEBIC DYSENTERY 209 At the end of twenty-four hours, if the symptoms show some abatement, a large cupful of strong chicken broth or meat juice may be given, and if the improvement is maintained, soups, eggs, and fluid meat, may be tried and should form, practically, the sole food until the end of the attack. Minced chicken, fish, sweetbread, &c., may usually be given about the fourth day. Farinaceous foods and undiluted milk generally disagree with patients in the acute stages of amoebic dysentery. When pain is an urgent symptom, hot fomentations should be applied to the abdomen. The most effective method of preparing a fomentation is to fold a length of flannel in eight or twelve layers, and after soaking in boiling water to wring it out in a twisted towel. Before application a few drachms of linimentum opii or turpentine are sprinkled on to the surface, and the flannel is then packed, as hot as the patient can bear it, firmly on to the abdomen, where it is allowed to remain until it begins to cool. When properly prepared and carefully applied at short intervals, the amelioration of all the symptoms of acute amoebic dysentery — and notably of the tenesmus and straining — which follows the appli- cation of these stupes is often very remarkable, and should a relapse occur they are generally the first remedy to be asked for. During acute attacks the temperature must be carefully watched, and if a tendency to hyperpyrexia is observed, a concomitant in- fection of malaria should be suspected. If parasites are found in the blood, and especially if the small ring forms of malignant tertian are discovered, an intramuscular injection of quinine should be given at once. For this purpose, 15 grains of bi-hydrochloride of quinine are dissolved by heating in a test-tube with 100 minims of distilled water, the whole of the solution being then injected into the gluteus maximus muscle. It is unnecessary to add that on every occasion on which injections are used, the syringe and needle 210 AMOEBIC DYSENTERY should be sterilized, and the skin carefully cleansed and disin- fected. In such cases administration of quinine by the mouth is inadvisable ; for, apart from the fact that vomiting is generally an urgent symptom, absorption is always defective, and the action of the remedy may be delayed until it is too late. Cold packs are generally necessary in malarial, and are alw^ays indicated in non- malarial hyperpyrexia. Fever is almost invariable during exacerbations of amoebic dysentery, but a moderate degree of pyrexia (102° to 104° F.) seldom calls for active treatment, and the temperature generally subsides with the administration of calomel and free action of the bowels. Frequent sponging with tepid water — part only of the body being uncovered at a time, and other precautions being taken against chill — is often effective in reducing the temperature and in pro- moting the general comfort of the patient. Warm sponging is, moreover, generally successful in soothing the nervous system, in controlling excitement, and in inducing sleep. If the fever does not yield to these simple measures, acetanilide (in 2|-grain doses) may be tried. When moderate pyrexia is accompanied by severe headache, with high vascular tension — a frequent condition in acute dysentery — antipyrin is the best remedy. Stimulants are rarely necessary, and in ordinary cases are harmful ; but if collapse threatens, brandy should be given freely. The best effect is generally obtained by a moderately small dose — a tablespoonful in half a tumblerful of very hot water — repeated three or four times at intervals of half an hour. If there is much sickness stimulants may be administered by the rectum, but sub- cutaneous injection of normal saline is preferable (see p. 212). As intense prostration often supervenes unexpectedly and is a frequent cause of death during acute exacerbations, stimulants and normal saline should always be available, although there may appear to be no immediate necessity for their use. THE TREATMENT OF ACUTE AMCEBIC DYSENTERY 211 Mental complications are rare, but they occasionally develop during an acute attack of amoebic dysentery, and naturally occasion much anxiety. Delirious excitement is one of the most usual forms of derangement, and it is generally connected with a previous malarial infection. When pyrexial delirium appears to be imminent, a hypodermic injection of quinine (lo grains) to which 2 minims of solution of hyoscine (i grain to 200 minims) have been added, must be given at once. If the temperature falls without relief to the mental excitement, the hyoscine may be cautiously repeated until the patient falls into a deep sleep. When hyoscine is unavailable, morphia is preferable to other sedatives. In the only instance in which I have seen bromides prescribed, they appeared to exercise an unusually depressant and unfavourable influence ; for exhaustion set in almost at once, and the case terminated fatally within a few hours. Vomiting is seldom a prominent symptom unless there is high fever ; but in some instances it is persistent, and it always demands special attention. Counter-irritation is generally the best remedy ; mustard or strong turpentine stupes should be applied to the stomach, while the patient is kept lying down and is supplied with small pieces of ice to suck. When anything can be retained, tablets of cocaine, 2^^ of a grain (repeated every quarter of an hour until five have been taken), relieve the intense nausea more effectively than any other remedy. Hiccough, which is sometnnes very dis- tressing, and is often indicative of approaching meteorism and collapse, may be arrested by an ounce of the following mixture, repeated every hour : — ^ Liq. trinitrini (i per cent.) ... ... in. viii. Spt. chloroformi ... ... 5 i- Aq. ... ... ... ad 3 iv. M. Alarming haemorrhage from the bowel may take place at a very 212 AMCEBIC DYSENTERY early period of the disease. It is, however, a comparatively infre- quent complication, although there are few cases of amoebic dysentery in which ulceration does not, at some time or other, involve a blood-vessel of moderate size. As a rule, the true nature of the condition is easily apparent, but serious haemorrhage may occur without the passage of blood by the rectum. When haemorrhage supervenes the patient should be kept at absolute rest, and if not already under the influence of morphia a full dose should be injected hypodermically. All nourishment, except sips of iced water, should be withheld; and 15 minims of adrenalin chloride solution (i in 1,000) should be given by the mouth, and repeated at intervals of half an hour as long as may be necessary. If collapse appears to be imminent, resort must be had to stimulants, or to ether and strychnia. Shock and prostration, due to haemorrhage or to other causes, are effectively combated by the subcutaneous injection of normal saline solution. When this is indicated, a transfusion needle, to which a rubber tube and funnel have been attached, is inserted over the pectoral m.uscle, and a pint of the solution is allowed to flow slowly into the connective tissue below each clavicle. Remedies which should not be given during Acute Attacks. ipecacuanha, although sometimes of great value in the chronic stages of amoebic dysentery, is inadmissible during acute exacerba- tions. It is especially contra-indicated when the patient is anaemic and enfeebled, when there is high fever, and when there is a tendency to sickness ; for in such circumstances, accentuation of all the symptoms, with consequent prostration and collapse, are liable to follow its administration. MusGRAVE states that, in Manila, he saw at least three cases in which death was directly THE TREATMENT OF ACUTE AMOEBIC DYSENTERY 213 attributed to the improper use of ipecacuanha ; and most tropical physicians will agree that this was by no means an uncommon experience. Astringents. — As the object of treatment is to promote rather than to diminish the intestinal secretions, astringents should never be given in acute amoebic dysentery. They invariably fail to check the distressing efforts at defaecation, and by inducing retention of the intestinal contents, they occasionally give rise to very serious symptoms. The recently introduced tannin derivatives, tannigen, tannoform, &c., which are stated to pass unchanged through the stomach, and are, doubtless, effective remedies in many other con- ditions, appear to be even more unsuitable than catechu, haema- toxylin, and the older astringents of the Pharmacopoeia, for they undoubtedly exercise a more powerful influence on secretion, and, consequently, on assimilation and absorption. Intestinal Antiseptics. — The reputed intestinal germicides almost invariably do harm ; and, although the opportunity would seem to be a favourable one, attempts to arrest the symptoms, and to cut short the progress of amoebic dysentery in its earlier and more acute stages by the energetic use of intestinal antiseptics invariably end in failure. Formerly, tropical physicians made it a routine practice to treat all cases of acute dysentery by large doses of the combination of free chlorine and quinine, which was suggested by Professor Burney Yeo, and which has proved a valuable remedy in typhoid and many other conditions ; but, although the patient generally experienced some benefit from the relief of flatulence and distension, the mixture had no effect in allaying the pain or in checking the urgency of the rectal symptoms. The antiseptic is, in fact, unable to survive the long passage of the alimentary canal, and it certainly fails to check the development of entamoebae. Even after much larger doses than those recommended by Yeo, the 214 AMCEBIC DYSENTERY characteristic odour of chlorine can never be detected in the dejecta, and the vitaHty of the organisms remains unaffected. Experience with other intestinal antiseptics has been equally disappointing. Salol, benzosol, and acetozone, which are largely used in the treatment of chronic amoebic dysentery, and are, indeed, considered by many authorities to be superior to any other remedy, are badly tolerated in the acute stages of the disorder. Prescribed in large doses, they invariably upset the digestion, and increase the severity of the symptoms ; when ordered in small quantities, they are inert. It is highly improbable, however, that there is any real difference in the therapeutic action of intestinal germicides at different periods in the course of amoebic dysentery ; and their failure in the acute stage is, doubtless, attributable to the greater irritability of the stomach, and to the fact that comparatively lengthened administration is necessary for their action to become apparent. Antiseptic irrigation of the bowel should not be attempted during an exacerbation of amoebic dysentery. After the colon has been cleansed by a preliminary douche of warm boracic solution, further direct medication is best deferred until fever and other acute symp- toms have subsided ; and local treatment should be restricted to soothing injections of small quantities of starch or mucilage. Even these remedies are of questionable value ; for, although they relieve tenesmus and induce a marked sense of comfort, it is undoubtedly true that, in acute dysentery, reflex vomiting and other symptoms of severe gastric disturbance frequently originate in the use of rectal injections. The general management of the acute phases of amoebic dysen- tery may be summed up in the statement that the best results are obtained by the simplest measures. If during exacerbations the patient is kept at rest, carefully fed, and treated with small doses of THE TREATMENT OF ACUTE AMOEBIC DYSENTERY 215 calomel and opium, the periodic crises are notably of shorter dura- tion and less intensity than when a multiplicity of remedies is employed. Energetic measures, or, in other words, the simul- taneous administration of powerful antiseptics, pei' os and per rectum, and combinations of antidysenteric drugs with active cholagogue purgatives, have naturally passed into disuse ; whilst sedatives, such as opium and morphia, disparaged and condemned by the older authorities, are now regarded as almost indispensable aids to treatment. 2l6 CHAPTER XIX. The Treatment of Chronic Amcebic Dysentery. General. With the subsidence of the marked symptoms characteristic of invasion and relapse, amcebic dysentery passes into its chronic or latent stages, and an entirely different line of treatment is now indicated ; but although, as in the acute form of the disorder, con- siderable modifications may be necessary to meet the varying requirements of individual cases, the management of the condition is again based on definite general principles. As a rule, expectant therapeutics are now abandoned in favour of specific remedies ; active medication — internal and local — is undertaken ; sedatives and anodynes are withheld ; the aid of a strict dietetic regime is invoked ; and remedial measures generally are directed to the extermination of the specific parasites. When the disease is of some duration, these organisms, as might be anticipated, are firmly established ; and notwithstanding the fact that the virulence of the infection tends gradually to diminish and natural resistance to increase, a prolonged course of treatment is, almost invariably, essential to a cure. To a great extent, moreover, the principles of treatment are unaffected by the clinical condition. Necessarily, symptoms vary considerably ; in a certain proportion of cases they are moderately acute, whilst in others they may be almost imperceptible; but, THE TREATMENT OF CHRONIC AMCEBIC DYSENTERY 217 whether the course of the disorder has been long or short, whether it has been attended by numerous and severe exacerbations, or whether the manifestations of infection are of a mild and insidious type, the indications for the treatment of chronic amoebic dysentery are always the same. They are, first, to arrest the development of entamoebas and the consequent destruction of the intestinal walls ; secondly, to main- tain the general nutrition and to inhibit systemic toxaemia ; and, thirdly, to prevent serious complications, and more especially the formation of metastatic abscesses. These objects are best attained by maintenance of the general health and nutrition, by careful regulation of the diet, by precau- tions against chill and other possible causes of relapse, and by the administration of antidysenteric and germicide remedies. Apart from specific treatment, the relative importance of these measures varies with circumstances ; in the tropics, the question of nutrition generally presents the most serious difficulties, whilst in cold climates the danger of chill is usually the source of greatest anxiety. When a patient suffering from chronic amoebic dysentery applies for treatment, a history of the symptoms, with special reference to the mode of onset, should be obtained ; and the condition of the intestines, the liver and the dejecta should at the same time be carefully investigated. In this way, important information may almost invariably be gained as to the position, the extent and the nature of the lesions. The physical deterioration, the progress of emaciation, the degree of anaemia, and the presence of toxaemia, if any, should also be noted ; a weighing machine should be provided, and a record of the weight should be made once or twice a week. The question of clothing requires particular attention. When treatment is carried out in a cold climate, woollen garments should be worn next the skin by day and by night; and special precau- 21 8 AMGEBIC DYSENTERY tions should be taken against changes of temperature. It is im- portant to keep the hands and feet warm ; and recreations which involve exposure to cold, such as motor-driving, fishing, boating, &c., should be forbidden. Bathing must be restricted to a hot bath every second or third night at bed-time; warm baths during the day are unadvisable. In the tropics, also, the possibility of cold must not be over- looked. Light flannels are the most suitable clothing, and an abdominal belt should always be worn. Serious relapses are not infrequently attributed to chills induced by sitting under a punkah ; and, especially after bathing, draughts and currents of cool air should be avoided. It is seldom necessary to send a patient, during treatment, from a cold to a warmer climate ; but, in the temperate zone, sudden falls in the thermometer not infrequently correspond to exacerba- tions of the symptoms ; and the question of transferring an invalid to a milder climate may have to be considered. On the other hand, in the tropics, the issue of the disease often depends on a patient being able to come home for treatment ; and in the case of Europeans, repatriation is not only generally advisable, but is often essential to cure. Whenever possible, return to a temperate climate should be made a rule of -tropical practice; for although treatment can be, and often is, successfully carried out in the endemic centres of the disease, the prospect of permanent relief is greatly enhanced by a complete change of surroundings. Not only can more suitable diet be obtained, but the benefit which accrues from the feeling of being at home is always of marked therapeutic value. When return has been definitely settled, the patient should go at the earliest opportunity, and, if necessary, hasten his departure in order to arrive at a mild season. It is a mistake to temporize THE TREATMENT OF CHRONIC AMCEBIC DYSENTERY 219 or to try half measures. Removal to a hill station is unadvisable ; for the high sanatoria of the tropics, invaluable as they are in other conditions, are in most cases unsuited to the treatment of chronic dysentery. Before advising a patient to return to a cold country, it is, how- ever, necessary to ascertain that his circumstances admit of adequate provision being made for comfort on the voyage, and for treatment when he arrives at home. The facilities which invalids from the tropics find at their disposal on reaching England are, too often, inadequate for their requirements. The sick poor haye unrivalled opportunities of receiving satisfactory care during illness ; so also have the rich, who can afford to pay high charges for treatment in nursing homes ; but for the middle classes — who represent, to a large extent, the average tropical patient — little skilled assistance can be obtained at a reasonable cost. Tropical invalids, moreover, require special care, and in most cases special treatment ; and if that cannot be procured, it is infinitely better for them to remain in the tropics. Unless the aid which is indispensable to recovery is at his command, the consequences of sending a patient in an advanced stage of amoebic dysentery to Europe are generally disastrous. Exercise plays a prominent part in the maintenance of the general health while treatment is being carried out ; and, whenever it is practicable, some form of outdoor recreation should be advised. During the latent phases of amoebic dysentery rest in bed is generally unnecessary and undesirable; and, although a patient may have to lie up at intervals, general and regular exercise in the open air has a marked influence in preventing toxaemia and pro- moting ultimate recovery. Over-exertion and fatigue, on the other hand, must be avoided ; for there is no more frequent and potent cause of relapse than exhaustion. When the patient is confined 220 AMCEBIC DYSENTERY to bed, daily general massage should be practised. In the tropics excessive exposure to the sun often induces a return of acute dysenteric symptoms ; but, provided that the condition warrants it, a game of golf, walking, and, if more active movement is impossible, driving in the morning and evening are important items in the general management of chronic cases. When treatment is conducted on right lines the results are more satisfactory than might have been anticipated. Cure is seldom radical or unretarded by relapse, but chronic amoebic dysentery is far from being an intractable affection. On the contrary, compared with other progressive intestinal disorders, it is exceptionally amenable to treatment. When the morbid process has not gone too far, the adoption of appropriate measures is almost invariably followed by surprising improvement, and, in many cases, the patient is restored to complete and permanent health. On the other hand, when the disorder is established, neglect or inability to carry out the necessary treatment generally results in chronic invalidism, and, only too frequently, the illness terminates in death. 221 CHAPTER XX. Diet in Chronic Amcebic Dysentery. In the treatment of chronic amoebic dysentery, as in that of other intestinal diseases, the question of diet occupies a place of pre-eminent importance. The postulates are : First, the food must be sufficiently nutritious to make good the loss of tissue which results from a protracted illness of an exceptionally wasting nature ; secondly, it must be of such a character that the residues of digestion do not act as fresh sources of irritation to an ulcerated and inflamed colon ; thirdly, in order to counteract the tendency to toxsemia, intestinal digestion must be free from excessive putre- faction and fermentation ; and, further, if the development of para- sitic entamoebas is to be checked, an effort must be made to establish permanent acidity in the contents of the lower bowel. It ought, also, to be borne in mind that the necessary regime has in most cases to be followed for a considerable length of time, and the food, therefore, should be capable of some variation, and should be tolerably agreeable to the patient. Meat Diets. As a rule these indications are best fulfilled by a diet in which meat greatly preponderates. In many cases of chronic amoebic dysentery a course of meat, absolutely without farinaceous food, continued for several weeks, not only affords sufficient nourishment 222 AMCEBIC DYSENTERY but acts as a powerful remedial agent ; and the somewhat anomal- ous type of amoebiasis, usually known as " planters' diarrhoea," to which reference has already been made, and which is regarded by many authorities as a connecting link between dysentery and sprue, is specially benefited by a diet consisting solely of large quantities of meat (see p. 226). There are several reasons why meat is preferable to a milk diet in dysentery. It is more easily assimilable, the residuum more closely approaches the natural dejecta of an adult, and it is less likely to set up constipation. Pawlow and others have shown that meat normally excites a greater flow of the gastric and intest- inal secretions than any other food; there is, in consequence, a diminished tendency to fermentation, and there is less delay in peptonization and absorption. Moreover, in the tropics animal food is almost always obtainable, either freshly killed or frozen and imported, in a more or less satisfactory condition. On the other hand, there are two drawbacks to the employ- ment of meat in chronic amoebic dysentery. The first is that, as considerable quantities have to be taken, a diet in which flesh greatly preponderates is apt after a short time to become distasteful and nauseous ; and the second, that the resultant dejecta are generally alkaline. Frequent changes in the variety and preparation of animal food, however, help to relieve monotony and prevent satiety ; fish, chicken, game, &c., cooked in different ways, may be advantageously substituted for beef and mutton ; and although, as a rule, carbohydrates must be excluded from the diet farinaceous foods in which proteids predominate, such as macaroni and gluten bread, are specially suited to the treatment of amoebic dysentery. Oranges, peaches, apricots, tomatoes, rhubarb, and green vegetables are admissible additions to a meat diet. Glandular tissues such as liver, kidneys, sweetbreads, &c., and all salted or preserved food, should be avoided. DIET IN CHRONIC AMOEBIC DYSENTERY 22$ The alkalization of the intestinal contents by a meat diet is an even stronger objection, as it tends to encourage the development of the specific cause of the disease ; but, in most cases, it is readily counteracted by intestinal germicides or other antidysenteric remedies. Slight but sufficient acidity may generally be established by ipecacuanha, benzosol, or sulphate of copper (see pp. 235-239) ; and when a patient is limited to animal food, one or other of these drugs should be taken regularly. In the tropics as elsewhere, the prolonged consumption of animal proteids and the exclusion of carbohydrates from the diet of healthy men is apt to be followed by derangements of the renal, hepatic, and circulatory systems. It is a remarkable fact, however, that during the treatment of chronic amoebic dysentery these effects are seldom induced ; and, after a protracted illness, the quantity of meat which may be taken with impunity for a lengthened period is astonishing. If the supply of fluid is kept up by copious draughts of hot water — a precaution which should never be neglected — the urine rarely shows any marked excess of nitrogen, the liver and kidneys act freely, and gastric efficiency is unimpaired. Moreover, disordered appetite and unnatural craving for injurious food which are frequent symptoms of the toxaemic stages of chronic amoebic dysenteiy, are almost invariably alleviated by a diet of meat. The spasms of acute hunger and the irresistible impulse to consume large quantities of food which the patient knows to be deleterious cease, and marked relief is generally afforded to the other gastric neuroses. The form in which meat should be given necessarily varies with the general condition. In subacute or in advanced and asthenic cases, it may be desirable to confine the patient to bed, and to commence treatment with soups and jellies, or even to restrict the diet to raw meat juice, liquid peptones, &c. ; but, in most instances, 2 24 AMOEBIC DYSENTERY rest in bed is unnecessary. It is further imperative that, except in these special cases, all meat should be lightly and plainly cooked. There are many objections to the use of raw meat, not the least serious being the danger — an imminent one in the tropics — of superimposing a taenia infection on the disorder under treatment. Preferably, also, meat should be given in solid form. Minced or pounded beef or mutton, or thin slices from a lightly cooked joint, are almost as digestible and infinitely more nutritious than consommes or liquid extracts. A general rule as to quantity is that as much meat as can be assimilated without discomfort may be allowed; but, in practice, the amount suitable for individual patients must be carefully esti- mated for each case — the normal body weight, the natural taste or disinclination for animal food, and the effects of the diet being the best guides to a decision. Men of big build and powerful physique, when restricted almost exclusively to animal food, require 2 lb. of fresh meat daily, and even this quantity is seldom sufficient for adequate nutrition for more than ten days or a fortnight. It is, however, for the time, a full allowance; and, except in special circumstances, it should rarely be necessary to exceed it. Women are generally unable to tolerate much animal food, and nausea is more readily induced by a meat diet than it is in men. A shorter course of treatment is, on the other hand, usually sufficient ; and female patients who are not naturally robust, do better on modified meat diets, combined with intestinal germicides, than on a purely proteid regime. In such diets, carbohydrates are strictly limited, although eggs and various albu- minous compounds, such as solid peptones, casein, gluten, &c., may often be substituted with advantage for animal proteids. Of late years, considerable advances have been made in the manufacture of these special products, and several of them are DIET IN CHRONIC AMCEBIC DYSENTERY 225 excellently adapted for tropical practice. As an auxiliary to a modified meat diet, somatose, a granular tasteless powder which is soluble in water, easily digested, and, for its bulk, highly nutritious, is one of the most useful of the solid peptones ; whilst, of the casein preparations, the best known are protene, which appears to be practically pure casein ; plasmon, in which there is over 80 per cent, of proteid ; and sanatogen, which is composed of casein and about 5 per cent, of added glycerophosphate of soda. Apart from their alimentary value — casein, bulk for bulk, is more nutritious than meat proteid — these preparations are often of remarkable service in the treatment of the later stages of amoebic dysentery, and are specially effective in counteracting fermentation and checking the absorption of intestinal toxins. The following is a specimen of a modified meat diet suited to the treatment of an average case of chronic amoebic dysentery : — 7.30 a.m. — Tea, with milk and a little sugar; no bread. An orange, a few grapes, or a pear. 9 a.m. — Two lightly boiled eggs. Tea or weak coffee and milk ; a limited quantity of toast and butter. If eggs cannot be taken, fresh fish may be substituted ; and protene or sana- togen may be given instead of tea or coffee. No bacon, ham, or preserved fish is allowed. 11.30 a.m. — Ten ounces of clear soup, with plasmon, or some other proteid preparation. 1.30 p.m. — Six ounces of underdone roast beef or mutton, minced beef, chicken, rabbit, calf's head or game, with macaroni, green vegetables, or tomatoes. Any stewed or fresh non- carbohydrate fruit in season. Strawberries and rhubarb are specially suitable. Apollinaris or Perrier water. 5 p.m. — Tea, with a limited quantity of brown bread and butter 7.30 p.m. — Clear or Julienne soup ; a little dry toast. Fresh fish 15 226 AMCEBIC DYSENTERY cooked in any way, but without flour. For convalescents (in addition) : A little cold meat, chicken or game. A pear or other fruit in season. Apollinaris or other table water. ID p.m. — Ten ounces hot water. In the tropics many of the articles indicated are, of course, unprocurable, but eggs, fowls, and meat can generally be readily obtained, and many tropical fruits, such as papaya, melon, pumelo, rambutans, avocado pears, &c., are excellent substitutes for European varieties. Whenever possible, fresh bael sherbet should be given twice daily, preferably instead of the other nourishment, at 11.30 and 5 p.m. The exclusively meat diet, which is so effective in cases of " planter's dysentery," involves complete withdrawal of carbo- hydrates, total abstinence from all stimulants, a copious supply of mineral waters, or, preferably, of hot water, and an abundant diet of meat. The food consists entirely of fish, eggs, meat (principally underdone chops and beefsteaks), without bread, but with small quantities of fruit and green vegetables. If the patient cannot satisfy his appetite by meat alone, as frequently happens, he is told that the only permissible course is to eat more meat, and meat only, until he ceases to be hungry. When plenty of fluid is taken this drastic regime may be kepi up for a month or more, generally with the best results to the intestinal condition and with little discomfort beyond the annoyance which is caused by a persistent alkaline taste in the mouth — an almost invariable consequence of a purely meat diet. Milk Diets. Although, in the treatment of chronic amoebic dysentery meat must always be the diet of preference, it may be advisable in certain circumstances to restrict the patient, temporarily at least, DIET IN CHRONIC AM(EBIC DYSENTERY 22/ to a regime of which milk is the sole or principal constituent. The residuum from a milk diet, it is true, is bulky, heavy, and apparently unsuited to an inflamed colon, but, in comparison with normal dejecta, it shows a marked diminution in microbic activity and an almost complete lack of putrefaction. In special circum- stances, therefore, and in general whenever meat proves unsuitable, milk should be regarded as the first alternative diet ; and in these cases it is advisable to begin with milk alone. On such a diet muscular exertion is impossible, and when the patient is taking nothing else he should be strictly confined to bed. Treatment by a diet consisting solely of milk is, however, a procedure which should not be undertaken lightly or without recognition of the fact that a further serious strain is to be thrown on the vital resources. One of the first effects is a marked and occasionally alarming decrease in weight, and the patient generally complains bitterly of insufficiency of nourishment ; but, assuming that the milk is of good quality, and that instructions are carefully followed, there is seldom or never any real danger. On commencmg the treatment it is advisable to give a pre- liminary dose of castor oil, and after the aperient has acted no food except milk is allowed. The usual quantities are : 60 oz. every twenty-four hours during the first three days ; 70 oz. during the next three days, and so on until the maximum, 120 oz. every twenty-four hours, is reached. Unless otherwise directed the milk should not be sterilized or boiled ; it should be sipped slowly in small quantities or sucked through a straw. In cold weather it should be slightly warmed. No other restrictions are necessary. Exertion must, of course, be avoided ; but the patient may be per- mitted to get up for a short time every morning and evening and occasionally to have a sponge bath. Unless smoking irritates the mouth it should not be stopped, for sudden discontinuance often causes so much discomfort as to interfere with digestion. 228 AMCEBIC DYSENTERY During the continuance of a milk diet laxatives are generally necessary, and it is advisable to give a dose of pulv. glycyrrhizae co. or liquid extract of cascara on alternate days. The general improvement which is effected in cases of advanced putrefactive dysentery and toxaemia by the substitution of milk for a mixed diet is often very remarkable. Disinclination for food disappears, lassitude gives place to alertness and a sense of bien-etre, movement is freer and easier, the complexion freshens, the skin becomes firm and elastic, and there is a marked increase in vascular and muscular tone. As the patient progresses, a little fruit — straw- berries or grapes for preference — may be permitted, and beef tea, veal broth, or vegetable puree may be added to the food ; but as long as milk forms the principal source of nourishment no meat or other solid food should in any circumstances be allowed. Soured Milk. — In view of recent researches on intestinal toxaemia, and on the germicidal action of lactic acid -forming bacteria, the possibilities of soured milk as a remedial agent have naturally attracted much attention. It is claimed that at least one variety, now generally known as the bacillus of Massol, when swallowed along with milk, passes with it almost directly to the colon and lower bowel, and that it there produces large quan- tities of fresh lactic acid, with a consequent acidifying and anti- septic effect on the intestinal contents. It is, therefore, argued that, in this so-called Bulgarian milk, we possess a remedy which is specially adapted to the treatment of amoebiasis ; but, clinically, the results have been somewhat disappointing, and recent observa- tion indicates that the therapeutic value of the lactic acid fermen- tation has been greatly exaggerated. It is possible, however, that this conclusion goes too far, and that soured milk has been too hastily discredited as a dietetic remedy in the treatment of chronic amoebic dysentery. DIET IN CHRONIC AMCEBIC DYSENTERY 229 The truth is that, although in at least half of all the instances in which it has been tried, soured milk has failed to exercise any definite germicide or antitoxaemic effect, in a certain proportion of cases it has given excellent results ; and when combined with a suitable diet it certainly assists the action of local antiseptic remedies. It is, undoubtedly, often effective in advanced cases of amoebic dysentery, when ulceration and putrefactive change are prominent features ; but, on the other hand, it is generally useless in the commoner form of the disease when toxaemia is attended by inefficient carbohydrate digestion. No doubt, many of the failures have been due to the fact that, in this country at least, it is by no means easy to obtain properly soured milk. Practically all the solid preparations of lactic acid bacilli now on the market are unreliable. Personal experience, moreover, indicates that fresh cultures are also often unsatisfactory ; as, in this country at least, it seems impossible to keep up a con- tinuous strain of Massol's bacillus without special cultures; and, if soured milk is prepared in England in the Bulgarian way — by adding a teaspoonful of the previous day's soured milk to fresh scalded milk — it will generally be found after a few transplantations that, although a soured milk is produced, the original and effective bacillus has been replaced by other organisms. It is, therefore, at present unadvisable to attempt the treatment of septic conditions of the lower bowel by this method unless the soured milk is obtained from a dairy which is equipped with a bacteriological laboratory where the proper strains are kept up, and used for cultivation. The usual method of administration is to give a pint and a half of soured milk daily, in three quantities of half a pint each. At first, food must be restricted, and for the first day or two little or nothing should be taken besides the soured milk and considerable 230 AMCEBIC DYSENTERY quantities of water, to each pint of which two teaspoonfuls of milk sugar have been added. During the continuance of the treat- ment, an ordinary hght mixed diet is advisable ; carbohydrates, such as sugar, rice, cornflour, &c., ought to be well represented, and meat should be allowed only once a day. A purely vegetable diet is, however, unsuitable ; and fat and butter ought to be limited in quantity. No intestinal antiseptics should be given by the mouth, and alcohol in any form is prejudicial to the success of the treatment. Alcohol in Chronic Amcebic Dysentery. Alcohol is, indeed, essentially antagonistic to the action of most specific remedies ; and during active treatment abstinence from all forms of wine and spirits is advisable. In certain cases, however, stimulants may be required ; and when there is marked failure of strength, loss of appetite, and depression — a condition which not infrequently follows complete deprivation — it is generally necessary to prescribe alcohol. In such circumstances, limited quantities of cognac, or malt whisky, freely diluted with soda-water, are less likely to be harmful than other forms of stimulant. 231 CHAPTER XXI. The Treatment of Amcebic Dysentery by Drugs. Antidysenteric Remedies. — There is no subject in the history of therapeutics on which there has been greater diversity of teaching than the treatment of chronic dysentery by internal remedies. To a considerable extent, the conflict of opinion has been in respect of the utility of ipecacuanha ; but essential principles and methods have been almost equally in dispute. Moreover, although an endless number and variety of drugs have been employed, there is still no general consensus of authority as to their curative value ; and most of the remedies now in use have, on the one hand, been vaunted as specifics by their adherents, while, on the other, they have been condemned as worthless by at least as many detractors. Ipecacuanha. — The tendency on both sides has, no doubt, been to speak too dogmatically ; but it is significant that, in spite of much hostile criticism, ipecacuanha has successfully maintained a definite reputation as an antidysenteric for two hundred and fifty years, and that it is still generally regarded as the first remedy to be tried in an ordinary case of chronic amoebic dysentery. It is, indeed, the most important example of a class of drugs which are believed to possess special antidysenteric properties, and which have long been accepted as standard remedies for the disorder. The truth is that ipecacuanha, although a medicine of great efficacy in certain varieties and phases of dysentery, has very definite 232 AMCEBIC DYSENTERY limitations, and that it is actually harmful unless the conditions under which it may be given are clearly recognized. It is, for instance, contra-indicated during acute attacks, or when there is marked elevation of temperature ; it has little, if any, remedial value in bacillary dysentery ; whilst in sprue and other intestinal dis- orders which are apt to be confused with amoebic infections it is always deleterious. On the other hand, in certain cases of chronic amoebic dysentery, the effect which is produced by full doses of ipecacuanha, properly administered, is often surprising ; and although the encomiums which the drug has received from Delioux de Savignac, MacLean and others are unwarranted, it may fairly be described as a remedy of moderate but definite practical utility. Originally brought to France from Brazil by Piso, in 1648, and introduced under the name of Radix antidysenterica, ipecacuanha immediately gained a remarkable vogue from the circumstance that it was successfully prescribed for the Dauphin ; but it appears to have afterwards fallen into comparative disrepute, for although dysentery was everywhere rife, little more was heard of it in Europe. In India, however, ipecacuanha continued to be employed with more or less success, and Surgeon Docker of the 7th Fusiliers again brought it into prominent notice in 1858 by publishing an important paper in which he showed that at least one cause of failure was the fact that the remedy had been given in insufficient doses. Another reason for the frequent inefficacy of ipecacuanha is that in hot climates the root is apt to deteriorate, and samples of the drug, especially those which have been kept for some time in powdered form, are often inert. The Brazilian variety of the plant — Psychotria ipecacuanha — has, however, been successfully introduced into the Eastern tropics, and the root-bark of this species can generally be obtained in a "recent" condition. When fresh THE TREATMENT OF AMCEBIC DYSENTERY BY DRUGS 233 ipecacuanha is unprocurable, the Hquid extract of the British Pharmacopeia may be used ; it keeps well, is fairly active, and is free from most of the disadvantages of the older preparations. Docker, whose mode of administration is still widely used, prescribed the powdered root-bark in 25 or 30-grain doses ; but the following modification of the so-called Brazilian method is more effective, and is less apt to induce vomiting. The patient is temporarily confined to bed, and after a light dinner, consisting only of soup or veal broth, he takes at 9 p.m. half an ounce of castor oil. At 7 a.m. the following morning, a cup of tea with a thin slice of toast may be given, but no breakfast is allowed. At 9.30 a mustard plaster is applied to the epigastrium, and at 10.30, an ounce of decoction of ipecacuanha is taken, and is repeated every hour for four hours. The decoction is prepared in the following way : A drachm of fresh root bark is bruised and boiled for five minutes in 4 ounces of water ; after straining through fine muslin, it is allowed to cool, and 2 drachms of tincture of cinnamon are then added to the decoction. During the administration of the remedy, the patient lies perfectly still in bed, and takes no food or other liquid ; the head is kept low, and talking is strictly prohibited. If nausea supervenes, the medicine is stopped, and the inclination to vomit is resisted as long as possible. An hour and a half after the last dose, a wine- glassful of iced chicken jelly is given, and later a basin of Benger's food may be retained. The treatment should be repeated daily for three days. Personal experience shows that, if directions are carefully followed, ipecacuanha given in this way seldom induces vomiting, that no opium is necessary, and that, if fresh root-bark only is used, a satisfactory result is obtained without further medicinal treatment in from 30 to 40 per cent, of all cases. When Docker's method is 234 AMCEBIC DYSENTERY employed, a bolus of 30 grains of powdered root-bark is adminis- tered after a preliminary dose of 30 minims of laudanum ; but, although the opium doubtless controls the tendency to nausea, it also arrests the intestinal secretions, and thereby limits the curative action of the ipecacuanha. Moreover, when vomiting does occur, it is of an unusually distressing type, and the experience of most physicians is that the nausea which follows a combination of ipecacuanha and opium is so intense that a patient can rarely be persuaded to make another attempt to take the remedy. Various procedures have been devised to obtain the antidysent- eric action of ipecacuanha without the emetic effect of the drug, and of these continued administration in fractional doses for three or four days is perhaps the most successful. One such method, usually known as Le Dantec's, is extensively employed in Cochin China, and has gained a considerable reputation in the French Colonies as an easily tolerated and effective treatment of chronic amoebic dysentery. The ipecacuanha is prescribed in the following way : Successive watery extracts are prepared from 2 drachms of bruised root-bark: (i) By soaking it in 6 ounces of cold water for twenty-four hours ; (2) by infusing the root-bark after exhaustion in this way in 6 ounces of boiling water for two hours, and (3) by afterwards boiling it for half an hour in a similar quantity of water. The three solutions are given in their proper order in dessert-spoonful doses on three following days, the whole of one solution being taken each day. During the administration of the remedy, no food except soup, arrowroot, &c., is allowed. The alkaloids and pharmaceutical preparations of ipecacuanha are much less effective than powdered root-bark, and the so-called de-emetinized ipecacuanha certainly lacks the antidysenteric proper- ties of the entire drug. The Effects of Ipecacuanha. — When successful, the action of THE TREATMENT OF AMCEBIC DYSENTERY BY DRUGS 235 ipecacuanha is at once apparent. In most instances, a copious loose motion of characteristic yellow colour and acid reaction is passed within three or four hours, and the patient experiences a marked sense of relief. Similar discharges, almost entirely free from mucus and blood, are voided during the next two or three days ; the intestinal functions gradually become normal, and the patient is soon convalescent. Apart from careful dieting, further treatment is generally unnecessary. Ipecacuanha doubtless acts by stimulating secretions which are prejudicial to amoebic life in the intestine. A decoction prepared as directed for internal administration, when diluted to i-ioo, applied to living entamoeb?e on a slide, arrests their movements ; but it does so less promptly and effectively than a weak solution, (1-5000) of quinine hydrochlorate — a drug which has no antidysen- teric action. Further, it is difficult to see how organisms in the intestinal coats can be destroyed, as in many cases they undoubtedly are, by ipecacuanha, unless there is more than a merely local action, and unless the circulation in the tissues has been materially modified by the addition of an internal secretion. There are few contra-indications to the use of ipecacuanha. It is true that in pregnancy and other conditions, which are accom- panied by severe vomiting, the remedy may aggravate the symp- toms, and that, when there is marked anaemia or prostration, the administration of ipecacuanha may be attended by some risk ; but personal experience indicates that it can be given to young children and delicate subjects without the slightest danger. In a recent case of chronic amoebic dysentery complicated with severe and persistent vomiting of hysterical type, decoction of ipecacuanha was retained without difficulty, and the patient who, in the tropics, had been seriously ill at intervals for fifteen months, made an excellent recovery. 236 AMCEBIC DYSENTERY Other Antidysenteric Remedies. — Definite anti dysenteric virtues have been attributed to many other tropical products of vegetable origin ; but although some of them are useful as alternatives to ipecacuanha, none are equal, and most are distinctly inferior to that drug. Four, however, deserve a word of notice ; they are simaruba, ailanthus, kho-sam, and the fruit of the bael tree. Suuariiba, the root-bark of the mountain damson {Simariiha officinalis) is a popular remedy in Java and the East Indies, and is ofHcially recognized in the Dutch and other Continental pharmaco- poeias. Like ipecacuanha, it ought to be freshly prepared. The usual method of administration is to soak ^ oz. of root-bark in a pint of boiling water for a quarter of an hour, the whole of the infusion being taken in doses of 2 or 3 oz., at short intervals, within twenty-four hours. Simaruba occasionally induces nausea, but in most cases it may be continued for a week or more without ill- effect ; patients like its bitter and slightly astringent taste, and the antidysenteric action is sometimes very remarkable. The infusion may also be used as an intestinal injection. Ailanthus, although frequently confused with simaruba, has, in fact, no connection with that product. It is the root-bark of Ailanthus glandidosa, a terebinthine tree, indigenous in the Far East ; and it has been used by the Chinese as a remedy for chronic dysentery from time immemorial. Native physicians, indeed, re- gard ailanthus as a far more reliable antidysenteric than ipecacuanha or any other drug ; and personal experience is to the effect that, in some instances at least, an infusion of ailanthus prepared by mace- rating 2 oz. of root-bark in ^ pint of boiling water is a medicine of great efficacy. Two ounces of the infusion are taken at intervals of not less than six or eight hours. In large doses ailanthus has marked depressant and nauseating effects, and as it has also a. cumulative action caution must be THE TREATMENT OF AMCEBIC DYSENTERY BY DRUGS 237 exercised in continuing the drug for more than two or three days. Matignon, who regards it as a specific in chronic amoebic dysentery, records an instance in which an overdose of infusion of ailanthus was followed by a fatal result. Kho-sarn. — The dried seed of Brucea snmatrana — generally known by the Japanese name of kho-sam — enjoys a wide celebrity in the Eastern tropics as an antidysenteric, and highly successful results have recently been obtained by its use in the treatment of chronic amoebic dysentery. The fruit is a greyish almond-like nut, and the kernel contains a large quantity of a powerful chola- gogue and emetic alkaloid — chosamine. Mougeot, of Saigon, who treated 879 cases by kho-sam, states that it was successful in no fewer than 871 instances, whilst Schneider, of Teheran, Pro- fessor Lemoine, of Val-de-Grace, and many others who have investigated its therapeutic properties bear emphatic testimony in its favour. The drug can now be obtained in the form of com- pressed tablets, known as Elkossam, each of which represents one kernel. Five or six tablets are taken daily. Bael Fruit. — The bael (Acgle inarmdos) flourishes abundantly in Bengal and Southern India, and the fruit is prized throughout the tropics as an antidysenteric and antiscorbutic remedy of great value. The pulp of the ripe bael may be sliced and eaten with pounded sugar ; but the best effects are obtained by preparing a "sherbet" from the unripe fruit in the following way : The pulp is cut into cubes of an inch square, and placed with a little white sugar in an earthenware jug. To this a pint of boiling water is added, and the contents after being well stirred are allowed to cool. This infusion or sherbet is drunk ad libitiuii, from 30 to 60 oz. being taken in the twenty-four hours. Bael is an excellent tonic and restorative at all periods of amoebic dysentery, but is specially valuable during convalescence and when the patient is returning to a normal diet. 238 AMCEBIC DYSENTERY Protozoan Germicides. — Several of the synthetic remedies which are known as internal germicides, and which have proved useful as intestinal antiseptics in typhoid and similar conditions, have of late years been largely employed in the treatment of chronic amoebic dysentery. Most of them exercise a directly destructive influence on entamoebas, and as they seldom induce nausea, they are excellently adapted for the treatment of cases in which ipecacu- anha is badly tolerated. Of these drugs, benzosol, salol, and acetozone are the most reliable remedies for all varieties of protozoan dysentery. Their marked antiseptic properties are but little affected by their passage through the upper part of the intestine, and in the colon they still retain at least the greater part of their original activity. Opinions differ as to their relative merits, but a considerable personal experi- ence indicates that benzosol is the most promising and generally useful of the three. Apart from its undoubted efficacy as a germi- cide, it produces no constitutional or local reaction, and its marked therapeutic value in the treatment of intestinal amoebiasis has been abundantly confirmed. Benzosol (benzoate of guaiacol) occurs in minute acicular white crystals, which, although soluble in chloroform and hot alcohol, are almost insoluble in water. On coming in contact with the gastric juice it is saponified ; the benzoic acid disappears from the molecule, and the drug ultimately reaches the colon as uncombined guaiacol. The doses recommended in therapeutical guide-books are much too small ; to produce a definite antiseptic action in the intestine, benzosol must be ordered in substantial quantities — 40 to 60 gr. daily. Five-grain doses are quite ineflective for an adult ; and the best results are obtained by giving 20 gr. in the morning, 10 gr. in the middle of the day, and 20 gr. in the evening. Tablets of benzosol are apt to become hard and insoluble, and it is advisable to prescribe the remedy in cachet. THE TREATMENT OF AMCEBIC DYSENTERY BY DRUGS 239 Benzosol has slightly laxative properties, and at first it occa- sionally induces marked looseness of the bowels ; but, in the treatment of amoebic dysentery, this is seldom disadvantageous ; and although the action of the remedy must be carefully watched, a little diarrhoea is beneficial rather than otherwise. The dejecta passed after full doses have nothing of the appearance of ipecacu- anha motions ; they are dark and bilious looking ; they seldom contain mucus or blood ; and the reaction is strongly acid. Benzosol is especially suitable for the treatment of the latent phases of amoebic dysentery, as during its administration rest in bed is generally unnecessary. After ascertaining that it agrees with the patient, benzosol ought to be continued for a month or six weeks without interruption ; and then, after a pause of two or three weeks, it may be resumed if necessary ; but, in many cases, the dysenteric symptoms entirely disappear after a short course of the drug, and there are no subsequent recrudescences. Benzoyl-acetyl-peroxide — a synthetic preparation which may be regarded as hydrogen peroxide, in which half of the hydrogen has been replaced by benzoyl, and the other half by acetyl — is a favourite remedy in the garrison hospitals of the U. S. Government in Manila. It is commended as an exceptionally powerful intestinal germicide by Drs. STRONG and Freer ; and an important point in its favour is that, although in some instances it has been given in larger doses than are necessary for antiseptic purposes, no unfavourable physiological effects have been observed. Benzoyl-acetyl-peroxide is used both internally and locally. Five grains are given by the mouth, in a celloidin or keratin capsule, three times a day ; and, once daily, two quarts of i-iooo dilution are allowed to flow into the colon by a long rectal tube. The treatment is continued for two or three weeks. A solution of benzoyl-acetyl-peroxide of similar strength may be used at the same 240 AMCEBIC DYSENTERY time instead of drinking water ; and patients who have taken it ad libitum in this way for several weeks have found it an effective and agreeable beverage. The recorded results of this method of treatment are excellent ; but at present the drug is often difficult to obtain ; and, in the tropics at least, it is an unstable compound. It is, moreover, too expensive for general use. Salol (phenyl-salicylate) has been recommended ' by numerous writers on amoebic dysentery as a useful intestinal antiseptic ; and, in many cases, it undoubtedly exercises a marked beneficial influence. It appears, however, to act on the bacteria of the alimentary tract more effectively than on parasitic protozoa ; and compared with benzosol it has many drawbacks. Like that drug, it must be given in full doses in order to secure its germicide action ; and, as the phenyl radicle is excreted by the urinary tract, nephritis is apt to be set up unless the kidneys are perfectly sound and capable of withstanding a considerable strain on their powers of elimination. The effects of salol, moreover, are less marked in the colon than in the small intestine ; and although inferior as a germicide to benzosol it cannot with safety be continued for so long. Cases in which the dejecta are extremely offensive and putrid often do better on salol than on any other drug ; and when its use appears to be desirable, at least 15 gr. should be ordered three times a day. When the patient is taking solid food, even that quantity is insufficient to secure moderate asepsis ; and unless there is evidence of intolerance the dose in such cases should be increased to 20 gr. Salol is generally ordered in cachet, but it appears to be more effective when prescribed as an emulsion. The following formula, suggested by Martindale, provides an excellent and con- \ See R. Strong and others : Bulletin of the Biological Laboratory. Manila, 1904. THE TREATMENT OF AMOEBIC DYSENTERY BY DRUGS 241 venient intestinal disinfectant for routine use : Dissolve 20 gr. of salol in a fluid drachm of liquid paraffin by the aid of heat : while hot, triturate vigorously, and add 30 gr. of powdered gum acacia, afterwards making up to i fluid ounce with distilled water. Salophen has been recommended as a satisfactory substitute for salol ; and, as it contains a smaller proportion of phenyl, it seldom or never acts as an irritant to the renal epithelium. Like salol, it is unaffected by the gastric juice, and dissolves only when it meets the pancreatic ferments in the alkaline tract of the small intestine. Salophen has gained a considerable reputation in the Dutch East Indies as a remedy for typhoid and other septic con- ditions of the intestine, and has recently been largely prescribed for amoebic infections. A limited personal experience is, on the whole, favourable. Not less than 30-gr. doses should be ordered. Acetozone (benzoyl-acetyl-peroxide) has also been extensively employed in America and in the Philippine Islands. Like most of -the other synthetic remedies, it is but sparingly soluble in water and in acid solutions, although in the small intestine it splits up into acetyl hydrogen and benzoyl hydrogen, both of which are powerful germicides. MusGRAVE states^ that the best results are obtained by prescribing large quantities of a dilute solution of acetozone to be drunk freely at intervals during the day. For this purpose he recommends aerated water as being more palatable and convenient for tropical use, and says that three or four pints of solution of acetozone in soda water (1-2,500 or 1-5,000) may be taken every twenty-four hours. There is some difference of opinion as to dosage, but it is ^ W. E. Musgrave, "Treatment of Amoebic Dysentery in the Tropics," Manila, Bulletin of the Biological Laboratory, 1904. 16 242 AMCEBIC DYSENTERY generally agreed that acetozone should always be given either in weak solution or with large potations of water. Thirty grains dissolved in four pints of water were given by Llewellyn^ without ill effect, but Charles Wray, who ordered it to be taken in capsules, followed by copious draughts of water, considered* that ^ grain was a sufficient dose. Musgrave, who has used it extensively, states that he has seen unfavourable symptoms follow the administration of acetozone in celloidin-coated capsules, and he believes that they were due to premature rupture of imperfect coverings, with con- sequent liberation of the drug in a concentrated form in the stomach. On the whole, acetozone may be regarded as a reliable pro- tozoan germicide, but one which must be used with great circum- spection. It should only be prescribed in very dilute solution, and in doses of not more than 5 grains. My own experience is to the effect that, unless given with an aperient, acetozone is somewhat constipating — a distinct disadvantage. It is also very expensive. Oil of Turpentine. — In the tropics these synthetic germicides, although rapidly coming into general use, are frequently unpro- curable, and it may be necessary to have recourse to simple remedies. Oil of turpentine often gives excellent results in the treat- ment of chronic amoebic dysenteiy ; and, as Sir Joseph Fayrer pointed out many years ago,^ it is specially useful in the more chronic forms of the disease, when the type of ulceration is indolent and extensive. The administration of turpentine is attended by considerable difficulty. Like other intestinal antiseptics, it must be given in full ^ Llewellyn, Australian Medical Gazette, February 20, 1905. ' Medical Afinual, 1909, p. 387. Wright, Bristol. '^ "Tropical Dysentery and Chronic Diarrhoea." Churchill, 1881. THE TREATMENT OF AMOEBIC DYSENTERY BY DRUGS 243 doses, 30, 40 or even 60 minims, three or four times daily ; and its pungent odour and acrid taste are serious disadvantages. Many- patients, indeed, are quite unable to take turpentine in any form. Capsules containing the liquid oil either become hard and insoluble or they rupture too readily ; and in hot climates they are specially unsatisfactory. An emulsion prepared as follows may, however, often betaken without difficulty : 30 grains of powdered gum acacia are rubbed up, first with a fluid drachm of turpentine and afterwards with an equal quantity of water, the mixture being gradually made up to an ounce by trituration with mist, amygdalae. Half an ounce to an ounce is a suitable dose. When large doses of turpentine can be tolerated, the germicide action is at least equal to that of benzosol, and the soothing and healing effects which it produces are often very remarkable. In haemorrhagic dysentery, turpentine generally acts promptly and satisfactorily as a haemostatic ; and in malignant cases it may be instrumental in saving life by arresting the tendency to tympanites and meteorism. Combined with castor oil it is an effective remedy in those cases of chronic amoebic dysentery in which constipation and the passage of large masses of mucus are prominent symptoms. A better effect is secured by administering turpentine in single large doses than by giving it frequently in small quantities, and whenever possible it should be ordered in that way. There are few contra-indications to its use, but it is always inadmissible when there is albuminuria. Sulphate of Copper and Opimn. — In certain cases of chronic amoebic dysentery highly satisfactory results are obtained by the use of sulphate of copper and opium. The combination is specially adapted to the treatment of that latent form of the disorder to which attention has already been directed and which is generally known as "planters' dysentery." The following formula may be used : — 244 AMCEBIC DYSENTERY 9 Cupri sulph. ^ gr. Pulv. opii ... ... i; „ Massa paraffini 2 ,, Ft. pil. Such a pill should be taken three times daily after food, and the diet should be limited almost entirely to meat. In these doses, sulphate of copper rarely produces any feeling of nausea and in cases of long standing surprising cures are often effected. Without the sulphate of copper or without the opium the remedy is of little value, and the remarkable efficacy of the pill is due to the com- bination of the drugs. Saline Aperients. — The treatment of acute dysentery by saline aperients, originally introduced by French physicians about the middle of last century, has now for many years been a general and approved method of practice. Dujardin-Beaumetz, writing of acute tropical dysentery (which, however, was probably of the bacillary variety) said, "When we see bile again in the dejecta the patient is cured " ; and he believed that this object could be best attained by the regular and continued administration of the sulphates of magnesia and soda. In India the saline treatment of acute dysentery has always been favoured, and of late years the method has also been largely utilized in the chronic stages of the amoebic variety of the disease. Here, however, the results have been by no means always satisfactory. It is undoubtedly true that Epsom and Glauber's salts may be given with marked benefit ; but the action of salines is extremely irregular and uncertain ; and they are unsuitable for routine employment. Given in small and frequently repeated doses, salines render the contents of the alimentary canal strongly alkaline, and consequently promote a rapid growth of amoebic organisms, with a corresponding increase in the dysenteric symptoms. In certain cases, however, they may prove to be of great service. THE TREATMENT OF AMCEBIC DYSENTERY BY DRUGS 245 The beneficial results which follow their use appear to be due to their purgative effects, and to their action in dissolving the viscid mucus which adheres to the surface of the colon. Not only is a protozoan breeding-ground of exceptional fertility frequently broken down and removed, but the inflamed mucosa is made more readily available to the remedial action of intestinal germicides. For this reason salines are likely to be of utility when local medication is employed. Aperients of all sorts, and particularly alkaline sulphates, often prove effective in cases in which dysenteric symptoms are combined with chronic dyspepsia, portal congestion, and functional derange- ment of the liver ; and they are generally indicated in the chronic amoebic dysentery of plethoric and alcoholic subjects. Many of these cases do well when a course of treatment at a mineral spa is undertaken ; and salines are systematically employed in com- bination with the Plombieres system of cure. In cases of marked anaemia, depletion, and emaciation, they are contra-indicated. When prescribed in chronic amoebic dysentery, salines must generally be continued for a considerable time ; and one of the best methods of administration is to order a drachm of sulphate of soda, in 6 oz. of hot water, three times a day before food. After a week or ten days, the midday draught is omitted ; and ultimately no more than one dose in the early morning is necessary. 246 CHAPTER XXII. Local Medication. The direct application of germicide remedies to the inflamed and ulcerated intestine is of special importance in the chronic stages of amoebic dysentery. Indolent sores and putrid centres of toxin formation are frequently restored to healthy action by means of rectal injections after all other methods of treatment have failed ; and the specific micro-organisms — on which the persistence of the disease depends — are more effectively destroyed in this way than by any other form of medication. Doubts have been expressed as to the utility of germicide douches on the ground that anatomical and physical conditions make it impossible for rectal injections to reach the seat of disease in the colon, and that, in any case, these solutions cannot possibly affect entamoebas which are developing in the sub-mucosa and the deeper tissues of the intestinal wall. But it has been repeatedly shown by skiagrams, and in many other ways, that local applications properly introduced encounter no serious obstacle until they arrive at the ileo-caecal valve; and practical results abundantly attest their efficacy and value. No therapeutical fact is more fully confirmed than that deeply-seated organisms may be destroyed by flushing the colon with suitable germicides, and that direct medication is the most rapid and effective method of dealing with protracted and obstinate amoebic infections. The local treatment of chronic amoebic dysentery generally LOCAL MEDICATION 247 necessitates the administration of at least ten or twelve intestinal douches — one or two being given daily — and as during this period the diet must be carefully regulated, and the bowel prepared for the reception of each injection, the patient should, if possible, be placed in a nursing home. To a great extent success is dependent on efficiency of method and technique ; and the best results can only be attained when continuous attention is given to the details of treatment. Practice, moreover, must be regulated by the general condition. In most cases absolute rest in bed is unnecessary, and a certain amount of movement and distraction is desirable. After irrigation the patient may sit up in an easy chair, or move about from room to room. In exceptionally mild cases, germicide douches may be employed without interference with the usual occupations, but active movement or exertion, except in the intervals of local treat- ment, should be forbidden. Absolute rules for this as for other details of treatment are, however, undesirable, and each case should be treated on its own merits. The introduction of a germicide solution is best effected by means of a soft but substantial rubber tube, one and a half to two yards in length, attached to a glass reservoir of two quarts capacity, from which, solely by force of gravity, fluid may flow freely and steadily into the intestine. On account of their tendency to excite peristalsis, Higginson's and other forms of pump syringe are unsuitable ; funnels are apt to admit air ; and rubber reservoirs decompose and are difficult to keep clean. The rectal portion of the tube, although flexible, must be sufficiently rigid to keep a direct course to the upper curve of the sigmoid flexure under the gentle force which is necessary to overcome the obstruction offered by an infiltrated and often constricted passage ; the nozzle should be rounded, with only one opening at the extreme tip ; and the 248 AMCEBIC DYSENTERY body of the tube should be perfectly smooth, of uniform calibre, and not more than five-eighths of an inch in diameter. Suitable irrigation tubes are difficult to obtain, and although a serviceable appliance may be fitted up by connecting a soft rubber pipe to a stomach tube, a special apparatus is desirable. An in- testinal irrigator has been constructed for me by Messrs. Allen and Hanbury which has the following advantages : It can be thoroughly and rapidly sterilized ; the distal end is hardened and slightly contracted, so that if it becomes clogged with mucus or other matter, it may be readily cleared by a little manipulation and compression of the tube ; it cannot kink or turn back in the bowel ; and the flow of fluid into the intestine may be accurately observed and regulated. Before the administration of a germicide injection the lower intestine should be washed out by a preliminary douche of 50 or 60 oz. of warm water, or a weak solution of boric acid (i gr. to the ounce). For cleansing purposes mucilaginous vegetable infusions, such as linseed, are unsuitable ; and as soap, bicarbonate of soda and other alkalines may counteract subsequent acidity they should also be avoided. While an injection is being administered the relations of the rectum to the other abdominal viscera are important. The pelvis should be raised on a hard pillow 8 or 10 in. above the level of the bed, and the patient should be placed across the elevation in the left prone position ; that is to say, he should lie on the left side with the right thigh flexed on the abdomen, and the face and chest turned down to the mattress. In this attitude the highest part of the colon — the splenic flexure — will be 5 or 6 in., and the lowest — the hepatic flexure — 8 or 9 in. below the sigmo-rectal junction. The tube, well lubricated with unmedicated vaseline, is then care- fully introduced as far as it will go without undue pressure, and LOCAL MEDICATION 249 30 or 40 oz. of solution, warmed to 96° — 98°, are allowed to flow steadily into the bowel. During the operation the patient must keep perfectly still, and the same position should be maintained for five minutes after the injection. Given m this way, a remedial application readily penetrates to all parts of 'the colon, and is usually retained without difficulty ; whereas, if the patient is rolled or swayed about, as is often recom- mended, spasm and the accumulation of flatus are generally induced, and the desire to evacuate the injection becomes uncontrollable. Although the left prone attitude is generally preferred, many physicians advocate the dorsal or the knee-elbow positions, and provided the pelvis is well raised they are almost equally satis- factory. In cases where the intestinal reflexes are abnormally excitable and the mucosa hyper-sensitive, rectal irritability may be overcome by raising the end of the bed 18 in., or if that is ineffec- tive by placing the patient in the Trendelenburg position ; but in ordinary circumstances these proceedings are unnecessary. Flatulent accumulations in the alimentary tract are by far the most frequent cause of intolerance of injections. If they are not brought away by the preliminary douche, intestinal gases may some- times be successfully expelled by abdominal massage, or by giving a second douche of normal saline solution containing 20 m. of liquor opii sedativus before the injection. In cases of persistenf fermentation and irritability, Pil. asafoetidae co. is a useful and reliable remedy. The rectal tube and connection should be freed from air before introduction. Even when every precaution is observed, a certain amount of reflex spasm is almost invariably excited by the inflow of fluid. In some instances a rapid stream seems to be less irritant than a slow trickle ; in others, only complete cessation can avert imme- diate expulsion of the injection. In such circumstances the condi- 250 AMCEBIC DYSENTERY tions best suited to each case must be determined by changes in manipulation, in the strength and temperature of the injection, or in the position of the patient. TuTTLE states that he treated amoebic dysentery successfully and with almost complete freedom from discomfort or spasm by large enemas of ice-water ; and as he had previously claimed that cold — which affects free-living amoebag scarcely at all — was fatal to parasitic forms he believed that the germicide action was a result of the low temperature. Mus- GRAVE, Harris and others who agree to the soothing effects of cold, have, however, shown that frozen dysenteric dejecta, when thawed and injected into cats, still induce true amoebic dysentery. There is, moreover, great variation in capacity to tolerate large quantities of fluid. Most patients are able to retain three pints, but four or even more are frequently introduced without causing the slightest inconvenience. The female abdomen is, naturally, more tolerant than the male. The point is of some importance, for the local medication of chronic amoebic dysentery can be satisfac- torily carried out only by copious quantities of fluid, and it should be an invariable rule of practice to make injections as large as they can be borne. Numerous experiments have been undertaken to test the exact germicide values of different preparations, but in vitro results are by no means reliable guides to treatment, and clinical experience indicates that the selection of a remedy presents fewer difficulties and is of less practical importance than efficiency of technique and method in administration. Provided it is an active germicide, con- stitutionally innocuous and properly administered, success may be attained by almost any one of a large number of drugs ; but, in practice, solutions of the salts of silver and of quinine are generally regarded as the most useful preparations. Silver compowids. — On account of their unirritating effects the LOCAL MEDICATION 251 proteid compounds of silver are preferable to inorganic salts of the metal ; and personal experience has shown that argyrol — a soluble combination of silver with a wheat proteid — is better adapted to the local treatment of chronic amoebic dysentery than any other remedy. After a preliminary cleansing douche, 2 pints or more of a freshly prepared i per cent, solution of argyrol at 95° to 98° F. are allowed to flow into the colon and are retained as long as possible. This injection should be repeated once daily for ten days or a fortnight, and if it is well borne the strength of the solution may be gradually increased to 2 per cent, and the quantity to 3 or 4 pints. When properly administered, argyrol injections cause little irritation, and practically no pain. Patients generally say that at first only a pleasant feeling of warmth is induced by the inflow of the solution ; but when the higher strengths are employed and ulceration is recent, there may be a little sharp tingling. In respect of pain, however, argyrol compares very favourably with the nitrate and other salts of silver. Protargol — in which there is a much smaller proportion of silver — is more liable to cause irritation ; and, relatively to argyrol, is unsatisfactory and ineffective. Solutions of quinine, originally proposed by LOSCH in 1875, have been extensively employed in the local treatment of amoebic dysentery, and when used with discrimination, give excellent results. Harris claims that the bisulphate has a higher germicide value than any of the other preparations of quinine, but its special efficacy is more than doubtful. The fact is that all the salts of quinine are almost equally potent, and that the rapidity and extent of their action depend, in a great measure, on the acidity of the solution. Insoluble salts dissolved in a slight excess of acid are more effective, and should always be employed in preference to soluble preparations of quinine. High concentrations of quinine generally cause considerable 252 AMCEBIC DYSENTERY pain, and not infrequently a strong injection is followed by acute suffering. In no case should the proportion exceed i in 750, and this strength should only be gradually reached. Twenty grains of bisulphate of quinine, dissolved in 40 min. of dilute sulphuric acid, with 60 ounces of warm water (approximately i in 1,500), make a suitable solution for the first injection, the quinine being increased t>y 5 grains every third day. Like other germicide douches, the solution should be introduced at a temperature of 96° F. or a little over; and if there is pain, a hypodermic injection of morphia should be given. The insertion of a cocaine suppository (^ grain) five minutes before a quinine injection is recommended by many physicians. The bionomic relation of intestinal bacteria to entamoebae has a definite therapeutic interest, and the germicidal effects of various solutions on organisms growing in symbiosis have been studied by several observers. Thomas ^ obtained the following results with sym- biotic cultures of amoebae and reputed spirilla of Asiatic cholera : — (i) Boric acid, eucalyptus, ichthyol, and oil of cassia had little or no effect on either organism. Harris has also shown that strong solutions of boric acid cause a temporary cessation of vitality but have no destructive action. (2) Tannic acid i in 100, copper sulphate i in 2,000, potassium per- manganate I in 4,000, and bisulphate of quinine i in 1,000, partially destroyed both amoebic organisms and spirilla. (3) Potassium permanganate i in 2,000, quinine bisulphate i in 500, nitrate of silver i in 2,000, argyrol i in 500, and protargol i in 500, promptly killed the spirilla, but failed to affect some of the amoebae. All life was, however, destroyed by doubling the strength of these solutions. ' American Journal of Medical Sciences , January, 1906. LOCAL MEDICATION 253 (4) Thymol i in 2,500 destroyed the amoebae without ajffecting the spirilla. Other germicides. — General experience indicates that, in practice, excellent results may be obtained by the use of solutions of perman- ganate of potash, of sulphate of copper, and of thymol in the strengths indicated. The two latter, however, occasionally give rise to considerable pain ; and the residues left by permanganate injec- tions simulate decomposed blood so closely that the intestinal condition is often obscured. Personal observation has, further, confirmed the value of strong solutions of creosote in the treatment of haemorrhagic amoebic dysentery, advocated - by MM. Chantemesse and Rodriguez. In their case, that of a patient from Guatemala, whose motions con- sisted of almost pure blood, and contained large numbers of Entamoeba histolytica, douches of creosote, of a strength of 5 grammes to a litre of water (| per cent.), rapidly effected a complete cure. In a somewhat similar case, in which considerable quantities of blood and mucus were passed periodically at intervals of two or three months, and which had resisted treatment by ipecacuanha and argyrol injections, the symptoms yielded almost at once to injections of creosote of a similar strength. Although the breath smelt strongly of creosote for some time, the evidences of absorption were inconsiderable and the urine remained unaffected. Other varieties of protozoan dysentery are treated locally in the same way as amoebic infections. For balantidian dysentery, rectal douches are generally sufficient, and the administration of drugs is unnecessary. Bulletin, Societe, de Pathologic Exotique^ ii., 1909. 254 CHAPTER XXIII. Surgical and other Methods of Treatment. In the treatment of chronic amoebic dysentery surgical inter- vention is seldom desirable ; but it may be necessary to have recourse to an operation in the following circumstances : (i) When a crisis, such as perforation, occurs ; (2) to provide a more effective method of dealing with the lesions in the great intestine ; (3) to relieve a patient from the permanent discomfort which is consequent on incurable disease, fibrosis, or dilatation of the colon. Trans- peritoneal operations are, however, justifiable only in extreme cases; and, except in the first instance, only after other means have failed to ameliorate an obstinate and possibly dangerous condition. Three principal methods of remedial surgical treatment have been advocated. They are : (i) The formation of a temporary artificial anus in the caecum, through which the dejecta may be passed for several weeks. It is presumed that, complete rest being thus assured to the colon, the ulcerated and disorganized mucosa will heal rapidly, and that the opening may then be successfully closed. (2) Lavage of the intestine through the appendix vermiformis. An incision is made into the groin over the appendix, which is brought to the surface and anchored by silk sutures to the edge of the wound. The end having been cut off, the lumen is kept open, and a rubber catheter is passed through it into the intestine. In this way the colon may be freely and repeatedly douched by SURGICAL AND OTHER METHODS OF TREATMENT 255 medicated solutions, and the opening can be afterwards closed by resection of the appendix. (3) Excision of the whole of the large intestine and anastomosis of the cut end of the ileum with the rectum. The first operation — that of forming a comparatively large open- ing into the caecum — although it provides an excellent oppor- tunity for intestinal irrigation, and although numerous successful cases have been published,^ is attended by so many disadvantages that it has now been practically abandoned. The irritation is greater and the general condition of the patient is even more piti- able than when an artificial opening is made into the sigmoid from the left groin ; and extreme difficulty is almost invariably experienced in closing the opening. In cases of chronic and apparently incurable dysentery Steiner- has recently employed the following method with marked success. After a large opening into the caecum has been established, the colon is washed out daily from below with a weak solution of argyrol, the injection being continued until it flows clear from the Ccecal incision. When the colon is healed the artificial anus is temporarily closed by tampons, and the dejecta are allowed to pass through the natural channel, the closure being afterwards made permanent if there is no return of symptoms. The second method, in which the appendix is used as an opening for irrigation only — no attempt being made to divert the intestinal contents — is frequently adopted for the relief of malignant and other conditions of the colon, and has also been successfully employed in the treatment of amoebic dysentery. Unless there are ' See among others, Dr. Simpson and Mr. Keith, Medical Press and Circular, July 29, 1896. ^ Berliner klinisch Wochenschrifi, February 8, 1908. 256 AMCEBIC DYSENTERY extensive adhesions, the operation presents no difficulty, and the appendix may generally be drawn out through a small wound. It is better to defer opening the appendix until union with the abdominal parietes is complete, generally about four days after- wards, but irrigation two or three times daily may then be under- taken almost at once. A cleansing douche of warm water should hrst be injected, and after it has been passed, two to three pints of argyrol, copper sulphate, or permanganate solution should be allowed to flow slowly into the cascum. Both injections generally reach the rectum within ten minutes, but in order not to unduly hasten their transit the patient should be kept perfectly still. The rubber tube must be retained in situ so long as the appendix is open. Keetley, Arthur, and others, who have employed appendi- costomy in numerous cases of chronic dysentery, speak^ highly of the applicability and utility of this operation as a general method of treatment ; but Milton Holt, who is equally convinced of the efficacy of the procedure, considers^ that it should be undertaken only when entamoebae persist in the dejecta after a year's trial of rectal irrigation. With this view most tropical physicians will agree ; but it may be admitted that high ulceration in the ascending colon, which cannot be reached by injections from below, warrants earlier intervention than lesions which are situated in the sigmoid flexure. The somewhat formidable operation of excision of the whole colon has been followed by brilliant results in the hands of Mr. Arbuthnot Lane and a few other surgeons, but there has been insufficient time for the accumulation of evidence as to the per- manency of the relief which it affords. Those who are familiar ^ Medical Record, March 25, 1905. * New York Medical Jour?ial, November 16, 1907. SURGICAL AND OTHER METHODS OF TREATMENT 257 with the extremity of suffering to which a toxsemic patient may be reduced, and with the structural disorganization of the colon caused by advanced and neglected amoebic dysentery, will, however, have no difficulty in agreeing that this heroic measure may be the only alternative which offers any prospect of saving life, and that in such conditions it is eminently justifiable. The recorded mortality of the operation is abnormally high, for it is seldom undertaken before the patient is in extremis, and there can be no question that if excision of the colon is carried out earlier there will be a marked reduction in the percentage of fatalities. It occasionally happens that amoebic infection persists in limited areas after the rest of the colon has healed ; and single ulcers which obstinately resist all treatment are by no means infrequent sequelae of tropical dysentery. Callous ulceration of this type is generally attended by periodic attacks of acute pain ; in some instances, these are so severe that it may become necessary to explore the con- dition of the colon by laparotomy, and, if the diagnosis is con- firmed, to excise the ulcer. Operative interference is, of course, unjustifiable unless the sections can be made through healthy intestine. In view of their powerful amoebicide action in vitro, an attempt to destroy entamoeba in the tissues by means of x-rays would appear to be a rational and feasible procedure. Numerous external affections dependent on the growth of trichophytons and other pathogenic organisms are now regularly treated in this way, and it is believed that deeper structures may be similarly influenced by radio-therapy. It is for instance claimed^ that the progress of leukaemia, both splenic and myelogenous, may be arrested by the * Ledingham and McKerron, Lancet, January 14, 1905. Kienbock, Lancet, June 20, 1907. 17 258 AMCEBIC DYSENTERY direct application of x-rays to the spleen and bones, and that many other diseases/ including leprosy, may be similarly relieved. There are as yet insufficient data to establish the therapeutic value of x-rays in amoebic dysentery, but at least one patient appears to have been cured in this way. It must not be forgotten that degeneration in healthy tissues is frequently induced by exposure to the rays, and De Courcelles states^ that not only the testes and ovaries, but the whole of the intestinal lymph glands, may become atrophied as a result of this treatment. See Heinecke, Miinchener med. Wochens.^ May 3, 1904 ; Senn, and others. Foveau de Courcelles, La Semaine Med.^ IQOS) P- 364: 1905, p. 116. 259 CHAPTER XXIV. The Treatment of Amcebic Abscess of the Liver. Prophylaxis. With improved methods of treatment, the case incidence and the mortaHty of hepatic suppuration have, in recent years, shown marked diminution, and still further progress in the prevention and cure of the gravest of all the sequelae of intestinal amoebiasis may be anticipated in the future. It is now fully established that early identification of amoebic infection of the colon is the most impor- tant consideration in the prophylaxis of liver abscess ; and that, when suppuration has taken place, timely surgical intervention is the surest means of effectively reducing the appalling fatality of the complication. The amelioration in the incidence of metastatic abscess has, however, been materially assisted in other ways. Many factors contribute to the predisposition of liver tissue to suppuration ; personal habits, tendency to dietetic and alcoholic excess, exposure to unwonted climatic conditions, psychic and mental causes, all exercise a powerful influence ; and it is no doubt due in a great measure to changes in the methods of life which formerly prevailed in the tropics that there has been such a marked decrease in the frequency of the complication. Hepatic suppuration is, however, still far too common ; and it is by no means the case, as is fre- quently asserted, that it occurs only when amoebic dysentery has been neglected or improperly treated. 26o AMOEBIC DYSENTERY A notable advance in the prevention of liver abscess has been recently made in Calcutta, where ROGERS has shown that remark- able reduction in the case incidence may be attained by the system- atic employment of ipecacuanha as a prophylactic in the earliest stage of hepatic invasion.^ Although the dysenteric symptoms were sometimes so mild as to be almost imperceptible, ROGERS found that, in 90 per cent, of his cases, there was a definite connec- tion between the two conditions ; and that the occurrence of poly- nuclear leucocytosis almost invariably foreshadowed the formation of an amoebic abscess. Therefore, whenever hepatitis, however slight, was attended by a marked excess of leucocytes, he concluded that he had to deal with a pre-suppurative stage of infection of the liver by intestinal amoebae, and he prescribed ipecacuanha in large doses with the following results : — In three cases of inflammation of the liver with leucocytosis, in all of which there was a history of dysentery, the fever and other evidences of hepatitis disappeared after from two to four days' treat- ment by ipecacuanha, although these symptoms had previously persisted for two, five, and six weeks, respectively. In three similar instances where the patients were not treated by ipecacuanha, fever subsided only after several weeks ; whilst, in a further series of five cases in which large doses of the drug were administered, the temperature, which had been continuously high for more than a month, fell to normal in from one to six days. Further, three cases of fever, with polynuclear leucocytosis and slight enlargement of the liver, which exhibited no other evidence of amoebic infection, were cured by ipecacuanha in from two to fifteen days, after five, eight, and nine weeks' illness. ' L. Rogers : Paper read at the Annual Meeting of the Philippine Islands Medical Association, February 29, 1908. TREATMENT OF AMCEBIC ABSCESS OF THE LIVER 261 Later results have confirmed the utiHty of this method of treat- ment, which — ahhough previously recommended by Chevers, Maclean, and others — it has remained for Rogers to bring into general use. In the Calcutta General Hospital for Europeans, no case of liver abscess occurred as a sequela of dysentery during two years after the introduction of the ipecacuanha treatment ; and an equal measure of success has been attained in many other centres of amoebic infection. So far, no clinical evidence has been adduced to show that similar methods of preventive treatment may be equally efficacious ; but there can be no question that the success of the remedy depends on the destruction of the specific entamoebae ; and when ipecac- uanha cannot be tolerated, benzosol and other germicides may be confidently expected to produce similar results. Palliative measures, such as the application of fomentations and counter-irritation over the liver, almost invariably fail to effect the slightest permanent improvement or to arrest the progress of suppuration ; and the obvious indication afforded by these experiences is that in all cases of amoebic infection, especially when there is evidence of hepatic complication, or when obscure intestinal symptoms are combined with leucocytosis, specific antidysenteric remedies (both internal and local), should be prescribed early and continuously. Operative Treatment. On the formation of an abscess, steps must be taken to evacuate the pus ; and thereafter to maintain free drainage of the cavity until it is healed. The determination of the actual condition is some- times very difficult, and suppuration must be diagnosed rather by the general symptoms than by the physical signs. In no case should an operation be delayed until fluctuation can be elicited ; for when that sign is obtained it is often too late to save the patient. 262 AMCEBIC DYSENTERY No reliance can be placed on aspiration as a method of treat- ment. In rare instances it may be sufficient to effect a cure, and combined with subsequent injection of quinine solution it is sometimes useful in dealing with small abscesses ; but in the vast majority of cases free incision is necessary. Moreover, employed merely as a means of diagnosis, aspiration is by no means free from objection. Apart from the fact that irremediable damage may be done by injury to blood-vessels, hepatic pus is often so viscid that it will not flow through a needle, although it may afterwards extra- vasate along the track of the instrument into the peritoneal cavity. Two operations are in common use — the first, or abdominal, being employed when the abscess is situated in the lower segments of the liver ; the second, or transthoraciCy when the cavity lies in the external or superior portions of the gland, or extends upwards towards the thorax. Besides the appliances usually required for laparotomy, the following instruments should be provided : An exploring syringe or aspirator, a large trocar and cannula, a Paquelin's cautery, a periosteal elevator, a rib saw, a bone forceps, several large fully-curved threaded needles, and stout rubber drainage tubes. All surgical procedures are, of course, carried out with strict antiseptic precautions. The Abdominal Operation. — After the usual preparation the patient is placed on the back, or when lateral incision is necessary, on the left side ; and in order to raise the liver close up to the external wound a hard pillow or sandbag is inserted under the hollow of the spine. An incision through skin and subcutaneous tissue, 3 to 4 inches in length, is carried directly downwards from the lower border of the costal margin across the most prominent part of the swelling, and is gradually deepened until the peritoneum is reached. The existence of adhesions, less frequent in this position than where there is resistant rib-pressure, may now be TREATMENT OF AMCEBIC ABSCESS OF THE LIVER 263 determined. If the tissues are thickly matted together and the peritoneal cavity is thus shut off from the wound, the abscess may be evacuated as soon as its nearest point is located. On the other hand, when there are no adhesions, the peritoneum must be care- fully opened, the liver being freely exposed by drawing asunder the edges of the incision. Flat sponges are gently packed between the liver and the abdominal walls so as to form a complete circle round the opening and dam off the cavity of the peritoneum from con- tamination by the contents of the abscess. The liver must not be incised until this has been done. Incision of inflamed liver tissue is always attended by the risk of severe haemorrhage, and it is important that the abscess should be reached at the point where it is most superficial. Before section, therefore, an endeavour should be made to determine as closely as possible the actual position of the cavity, an exploring syringe or trocar being, if necessary, used for the purpose. When found, the abscess is opened by the trocar, the aperture being afterwards carefully enlarged by the blades of a dressing forceps ; or if deeply situated in liver tissue, by a Paquelin cautery at a dull red heat. During evacuation the abdominal walls must be kept gently pressed down on the liver, so as to maintain complete occlusion of the peritoneum and assist the discharge of pus. Free drainage can seldom be secured in the case of a large abscess, unless the opening in the liver admits two fingers ; and when the incision has been increased to that size, a fairly rigid rubber drainage tube of large calibre should be passed in, the cavity being freely irrigated by hot water, or by a solution (i in 2,000 water) of bisulphate of quinine dissolved in weak sulphuric acid. So far as is practicable, the cavity ought also to be explored by the finger, and its extent and the existence of other abscesses determined. The most important part of the operation — the provision of 264 AMCEBIC DYSENTERY drainage without peritoneal contamination — still remains to be accomplished. The rubber tube being left in situ, the whole length of the wound in the liver is packed round it with a single ribbon of iodoform gauze, so that although free exit is provided for the pus through the lumen there can be no leakage along the outer circumference of the pipe. The flat sponges are now carefully removed, after irrigation of their surfaces, and the wound is filled up with gauze. The drainage tube may with advantage be cut short, and its mouth anchored by two stitches to the edges of the skin. The wound is afterwards covered by a large pad of absorbent wool and protective tissue. If, after packing the tube, there is still danger of leakage, the margins of the abdominal and liver incisions should be united by a ring of interrupted silk sutures placed not more than a quarter of an inch apart. Satisfactory union may generally be effected by entering curved threaded needles deep in the hepatic tissue, and directing them upwards and outwards so as to reach the surface of the liver half an inch from the opening ; they are then carried directly onwards through the abdominal wall until they emerge close to the edge of the external incision, when the sutures are released from the needles, and the ends are tied. If the abscess is small, packing the cavity by soft gauze may be substituted for a rubber drainage tube. A gauze dressing has, in itself, many advantages; it is unlikely to injure the liver during sharp movements such as are caused by coughing or vomiting, and its own capillary attraction assists in maintaining drainage. In many cases, as, for instance, when there is a tendency to haemor- rhage from the wound or from the abscess walls, gauze packing may be indispensable, for by no other means can bleeding or oozing be so promptly and completely arrested. The use of gauze, however, entails frequent irrigation and changes of deep dressing, TREATMENT OF AMCEBIC ABSCESS OF THE LIVER 265 and when the cavity is large these procedures are so tedious and exhausting that better results can generally be obtained by tube drainage. Transthoracic Operations. — Abscesses situated in the upper portion of the liver can seldom be satisfactorily treated unless part of a rib is resected, as, with the evacuation of the cavity, the intercostal spaces rapidly decrease in size, and drainage tubes are occluded by pressure. The natural width of these spaces, however, varies considerably. In some cases a rigid metal tube of moderate size causes little or no inconvenience, and I have successfully treated many high abscesses by means of a simple pattern of silver irrigating cannula, kept permanently in sitn between the ribs. The cannula slides stiffly through a shield by which it is retained in position, being thus shortened at will ; and after irrigation of the cavity it is attached to a syphon drainage tube which discharges into a jar of carbolic solution placed below the patient's bed. When there is extensive disorganization of hepatic tissue, however, trocar-drainage affords little prospect of providing suffi- cient exit for the discharges, and it is necessary to have recourse to more radical measures. In such circumstances, excision of part of one or more ribs is generally advisable ; and, when the abscess appears to be a large one, that operation should be undertaken without waiting for the result of an attempt at relief by less effective methods. The incision may be made above the insertion of the diaphragm, in which case the opening is actually transthoracic ; but it is usual to include in the same term operations which involve resection of a rib below that level. Whether the pleural or peri- toneal cavity is traversed, the procedure is practically the same. Tlie Operation. — The hepatic area is fully exposed by placing a sandbag under the hollow of the spine, and turning the patient across it in a semi-prone position to the left. After determining the 266 AMCEBIC DYSENTERY probable position of the abscess by inspection and palpation, the rib which appears to be most widely separated from its fellows by bulging intercostal spaces is selected ; and an incision, 3^ to 4 in. in length, is made parallel to the edges of the bone, and along its median line. The incision should be clean and deep ; that is to say, it should divide skin, muscular tissue, fasciae, and periosteum. Bleeding points having been arrested by pressure forceps, the edges of the wound are held apart, and the periosteum is freely separated from both aspects of about 3 in. of bone by means of a periosteal elevator. The rib is then cut across at each end of the denuded space by a bone forceps, or preferably by a small saw. After removal of the divided segment, the costal pleura is opened by a probe-pointed director and the blades of a dressing-forceps, the visceral pleura being thus brought freely into view. At this stage, air pressure from without generally causes partial collapse of the exposed lung, and the pleura overlying the diaphragm may be clearly seen. In most cases, also, the pressure of pus in the liver causes it to bulge up into the wound, and there is then no difficulty in determining the position of the abscess; but, in some instances, the use of an aspirator may be necessary. Before incising the diaphragm, however, the thoracic cavity (if uninfected by pus) must be shut off from the wound by uniting the margins of the costal and diaphragmatic pleura. Closely-set interrupted sutures of fine silk are passed through an incision in the deeper serous layer corresponding to the opening in the costal pleura, and the stitches, after being carried through that structure, are tied in a complete circle round the track of the wound. If the pleural cavity is already suppurating, no attempt should be made to close it; but, on the contrary, free exit should be given to the purulent fluid by gentle irrigation, the insertion of a soft drainage TREATMENT OF AMCEBIC ABSCESS OF THE LIVER 267 lube, and the application of large pads of absorbent gauze. The diaphragm should not be attached to the thoracic wall, as the stitches are apt to be torn asunder by sudden movements such as are induced by coughing or retching. As a rule there is no necessity to cut or tie the intercostal arteries. These vessels lie well away from the periosteal sheath ; and if the elevator is kept inside that structure they can scarcely be injured when a portion of only one rib is removed. It sometimes happens, however, that in order to secure a sufficient opening, two ribs must be resected, and it is then necessary to cut away the periosteum as well as the bone. In such a case, the larger branch of the artery, which lies between the outer and inner intercostal muscles, behind the lower sharp border of the rib, should be tied at both ends of the proposed incision by a ligature passed round it by means of an aneurism needle. The smaller branch — on the upper border of the rib — may generally be secured by pressure or by a twist from an artery forceps. The diaphragm being thus exposed, and the pleural cavity shut off from the wound, an incision is made directly into the hepatic tissue, and is gradually deepened until the cavity is reached. The abscess may then be evacuated and drained in the usual way. Although in most cases the structures heal rapidly, convalescence after an operation for abscess of the liver is prolonged and unsatis- factory. The exhaustion and secondary anaemia incident to pro- tracted suppuration of the hepatic tissue is of an unusually severe type, and recovery is generally tedious and marked by frequent interruptions. European patients on whom the operation has to be carried out in the tropics should be sent home as soon as they are able to travel ; and in such circumstances it is more than questionable whether they should ever again attempt to live in a hot climate. 268 INDEX. Abscess, Cerebral, 189 Hepatic, 169 et seq. Diagnosis of, 187 Etiology of, 171 Evidence of its Amoebic Origin, 173 Facies in, 184 Modes of Termination, 185 Morbid Anatomy, 179 Period of Development, 174 Prognosis of, 188 Prophylaxis of, 2i;9 Routes of Invasion, 176 Situation, Size, and Number of, 174, 175 Statistics of, 171 Symptoms and Course, 181 Treatment of, 259 Splenic, 191 Acetozone as an Antidysenteric, 241 Adhesions, Peritoneal, 196 Africa, Dysentery in, 32 et seq. Age, Influence of, 157 Ailanthus as an Antidysenteric, 236 Alcohol and Dysentery, 204, 205, 230 America, Central, Dysentery in, 34 North, Dysentery in, 37 South, Dysentery in, 34 Amceba gingivals, 80 undulans, 8 1 Amoebiasis, use of the term, 6 Amoebic Colitis, use of the term, 6 Anaemia, Secondary, in Amoebic Dysentery, 97 Andaman Islands, Dysentery in, 30 Animals, Experimental Amoebic Dysentery in, 147 Ankylostome Infection, Diagnosis of, 114 Antidysenteric Remedies in Chronic Amoebic Dysentery, 231 Antiseptics, Intestinal, in Acute Amoebic Dysentery, 213 Anus, Artificial, Formation of, 254 Apparatus, for Intestinal Douches, 247 Appendicitis, Amoebic, 193 Appetite, Capricious, 96 Arabia, Dysentery in, 31 Argyrol, the Best Local Germicide, 251 Assam, Dysentery in, 30 Astringents, not to be given in Acute Amoebic Dysentery, 213 Australasia, Dysentery in, 35 Bacillary Dysentery, Diagnosis of, 108 Morbid Anatomy, 120 Bael Fruit as an Antidysenteric, 237 Balantidian Dysentery, 87 Treatment of, 253 Balantidium colt, 84-86 minutum, 90 Benzosol as an Antidysenteric, 238 Benzoyl-acetyl Peroxide as a Germicide, 239 Bilharziosis, Diagnosis of, from Amcebic Dysentery, 113 Binary Fission in Entamoeba histolytica, 65 Biology of Entamceba, 41 et seq. Blood Changes in Amoebic Dysentery, 96 et seq. in the Dejecta, lOl in E. histolytica, 55, 56 Boas, Experiments of, 18 Brazilian, Modification of Method of giving Ipecacuanha, 233 " Budding" in E. histolytica, 65 Burmah, Dysentery in, 30 Calomel in Acute Amoebic Dysentery, 207 Casagrandi and Barbagallo, Researches of, 19 Celli and Fiocca, Experiments of, 17 INDEX 269 Ceylon, Dysentery in, 31 Chilodon dentatus, 90 China, Dysentery in, 27 ChlamydophrySi 81 Chorea, as a Sequela, 197 Chronic Amcebic Dysentery, Morbid Anatomy of, 134 Symptoms of, 105 Climates, Influences of, in Predisposition, 160 Clothing, Importance of Proper, 217 Coagulation Necrosis, 126 Coccidia in the Alimentary Canal, 82 Cochin China, Dysentery in, 27 Cold, Precautions against, in Treatment, 218 Colour of Endoplasm, 53 Combined Infection of Typhoid and Amoebic Dysentery, iii Complications, The, of Amoebic Dysentery, 169 Constipation in Amoebic Dysentery, 113 Copper, Sulphate of, as an Antidysenteric, 243 Councilman (with Lafleur), Observations of, 13 Craig, Confirmation of Schaudinn's work, 22 Creosote, as a Local Germicide, 253 Cultivation Experiments, Evidence of, 143 of Entamcebse, Tx et seq. Cysts, formation of resistant, in E. histolytica, 65 Death of Entamoebze, Morphology, &c., 61 Definition of Amoebic Dysentery, 4 Dejecta, the, in Amoebic Dysentery, 100 Demonstration of Entamoebje, 44 Diagnosis of Amoebic Dysentery from : Bacillary Dysentery, 108 Chronic Intestinal Catarrh, 112 Hemorrhagic Typhoid, no Intussusception, 112 Pernicious Malaria, no Diet in Acute Amoebic Dysentery, 208, 209 Chronic Amoebic Dysentery, 221 et seq. Milk in Chronic Amoebic Dysentery, 227 Diets, Meat, in Chronic Amoebic Dysentery, 221 Modified Meat, 225 Docker's Method of giving Ipecacuanha, 233 Dopter's Observations on E. histolytica in tissue, 123 Douches, Intestinal, in Treatment, 247 Drinking Water and Amoebic Dysentery, 162 et seq. Drug Treatment ot Chronic Amoebic Dysen- tery, 231 Ectoplasm of E. histolytica, 51 Endoplasm of E. coli, 53 E. histolytica, 52 Entamceba histolytica in tissue, 122 et seq. tetragetia, 80 Eosinophilia, in children, 97 Epilepsy as a Sequela, 197 Epithelial Cell Simulating Entamcebse, 63, loi Epithelioid cell in Dejecta, 102 Etiology of Amoebic Dysentery, 156, 162 Europe, Amoebic Dysentery in, 35, 36 Excision of a Callous Ulcer, 257 of the Large Intestine, 255, 256 Exercise in Treatment, 219 Experiments, Kartulis's Feeding, 154 Schaudinn's Feeding, 151 Strong's Feeding, 154 Feeding Experiments, 150 Fever, Treatment of, in Acute Dysentery, 210 Fibrosis of Intestine, 134 Flagellates, Intestinal, 82 Floods and Dysentery, 161 Fomentations in Acute Amoebic Dysentery, 209 Gastric Symptoms in Amcebic Dysentery 96, 195 Gauducheau's Cultivation Experiments, 77 Germicide Remedies, 238 H/5;morrh AGE, Intestinal, as a Complication, 194 Treatment of, 212 Harris, Clinical and Pathological Observations, 20 Ulcer of, 131 Hartmann's Entamceba, 79 270 AMOEBIC DYSENTERY Healthy Persons, Entamoebse in, 139 Helminthiasis, Diagnosis of, from Amoebic Dysentery, 1 13 Hepatic Infection, Routes of, 176, 177 Hiccough, in Amoebic Dysentery, 96 Treatment of, 21 1 Hyperpyrexia, Treatment of, 209, 21 1 Ice-water Enemas, 250 Immunity, possibly obtained by Cultures, 78 Incubation, Period of, 93 India, British, Dysentery in, 29 Indies, East, Dysentery in, 28 West, Dysentery in, 30 Infection, Artificial, of Animals, Evidence from, 1 45 Iiifectivity of Amoebic Dysentery, 142, 143 Intestinal Irrigation, Apparatus and Procedure, 248 Lavage through Surgical Openings, 254 Invasion, Stage of, 93 I pecacuanha in Acute Amoebic Dysentery, 212 in Chronic Amoebic Dysentery, 231 et seq. Irrigation of the Colon, Steiner's Method, 255 Janowski, Experiments and Views of, 18 Japan, Dysentery in, 24 et seq. Jiirgens, Work of, 20 Kartulis, Observations and Experiments of, II Kho-Sam, an Antidysenteric Remedy, 237 Koch, Observations of, 11 Kruse (with Pasquale), Observations of, 16 Lafleur (with Councilman), Work of, 13 Lambl, Observations of, 7 Lmiiblia intestinalis , 82 Latent Amoebic Dysentery, 103, 104 Le Dan tec's Method of giving Ipecacuanha, 234 Lesage's Cultivation Experiments, 74 Leucocyiosis, a result of Intoxication by Drugs, 97 in Chronic Dysentery, 98 Leydenia gemmipara, 81, 82 Localization of Amoebic Lesions, 136 Local Medication in Acute Amoebic Dysen- tery, 214 Chronic Amoebic Dysentery, 246 etseq. Losch, Work of, 8 Malaya, Dysentery in, 28 Malignant Disease of Sigmoid, Diagnosis, 115 Type of Amoebic Dysentery, 94, 119 Maturity in E. histolytica, 65 Measurements of Entamoebae, 58 Meat Diet in Chronic Amoebic Dysentery, 221 et seq. Mild Type of Amoebic Dysentery, 103 Milk Diet in Chronic Amoebic Dysentery, 226 Soured Milk in Chronic Amoebic Dysentery, 228 Moisture, Influence of, in Causation, 160 Morbid Anatomy, 119 of Experimental Dysentery, 148 et seq. Morphology of Entammba coli, 53 E. histolytica, 50 Mouth Lesions in Amoebic Dysentery, 195 Movements of Entamoeboe, 59 Mucosa, The, in Amoebic Dysentery, 125 Musgrave, Views of, on Pathology, 23, 140 Nervous System in Amoebic Dysentery, 94, 197 Noc's Entamoeba, 78 Nomenclature of Amoebic Dysentery, 4 Nuclear Changes in Reproduction of Ent- amoebse, 66, 68 Nucleus, The, in Entamoebae, 56 Nyctotherus africanus, 90 faba, 90 Operations for Hepatic Abscess, 261 Opium, Sulphate of Copper and, 243 Osier, Observations of, 13 Osier's Ulcerative Colitis, III Pasquale (with Roos), Observations of, 15 Pathogenicity, the Case for, 138 Perforation, Morbid Anatomy of, 135 Philippine Islands, Dysentery in, 25 et seq. INDEX 271 Physical Signs of Amoebic Dysentery, 103 " Planters' Dysentery," Diet in, 226 Prophylaxis, The, of Amoebic Dysentery, 201 Protozoa, Classification of, 42 Pseudopodia, Morphology of, 60 Pulse, The, in Amoebic Dysentery, 96 Pus in Dejecta, 102 Qdincke (with Roos), Observations of, 15 Quinine, as a Local Germicide, 251 Race, Influence of, in Predisposition, 159 Rays, X-, as Intestinal Germicides, 257 Repair of Ulcerated Tissue, 133 Repatriation, Precautions to be Observed, 219 Reprodaction of Entamcehce, 64 Respiration in Amoebic Dysentery, 96 Rogers' Method of Hepatic Abscess Preven- tion, 260 Roos (with Quincke), Observations of, 15 Salines in the Treatment of Chronic Amoebic Dysentery, 244 et seq. Salol as an Antidysenteric, 240 Salophen as an Antidysenteric, 241 Schaudinn, Fritz, Discoveries and Work at Rovigno, 20 Schistosome Infection, Diagnosis of, 113 Schizogony in E. colt, 66, 67 E. histolytica, 65 et seq. Scybala in Amoebic Dysentery, 113 Seasons, Influence of, in Predisposition, 161 Senegal, Dysentery in, 33 Sex, Influence of, in Predisposition, 159 Siam, Dysentery in, 28 Simaruba, as an Antidysenteric, 236 Skin, The, in Amoebic Dysentery, 95 Smoking, Allowable during Treatment, 227 Spirillar Dysentery, 84 Spirochsetes, Intestinal, 84 Sporogony in E. colt, 68 E. histolytica, 65 et seq. Stains for Entamoeboe, 46 et seq. Stimulants in Acute Amoebic Dysentery, 211 Stomach, Condition of, in Amoebic Dysentery, 96 Stomatitis, as a Complication, 195 Submucosa in Amoebic Dysentery, 125 Sumatra, Dysentery in, 28 Suppuration in the Intestinal Coats, 128 Surgical Treatment of Chronic Amoebic Dysen- tery, 254 et seq. Symbiosis of Entamoebse and Bacteria, 72 Symptoms of Amoebic Dysentery, 93 Technique, and Methods of Demonstration, 44 Temperature in Amoebic Dysentery, 98 Tenesmus, Vesical and Rectal, 94 Thymol, an Effective Local Germicide, 253 Tongue, The, in Amoibic Dysentery, 95 Toxaemia, 97, 106 Treatment, The, of Acute Amoebic Dysentery, 206 of Chronic Amoebic Dysentery, 216 "Tropical" Dysentery, Limitations of the Term, 5 Tsujitani, Experiments of, 19 Tuberculosis, Intestinal, Diagnosis of, 114 Turpentine, Oil of, as an Antidysenteric, 242 Ulceration in Sigmoid, 104 Morbid Anatomy of Amoebic, 129 et seq. 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