key: cord-283979-1dn7at6k
authors: Portillo, Aránzazu; Ruiz-Arrondo, Ignacio; Oteo, José A.
title: Arthropods as vectors of transmissible diseases in Spain()
date: 2018-12-14
journal: Med Clin (Engl Ed)
DOI: 10.1016/j.medcle.2018.10.008
sha: 
doc_id: 283979
cord_uid: 1dn7at6k

Different aspects related to globalization together with the great capacity of the arthropod vectors to adapt to a changing world favour the emergence and reemergence of numerous infectious diseases transmitted by them. Diptera (mosquitoes and sandflies), ticks, fleas and lice, among others, cause a wide spectrum of diseases with relevance in public health. Herein, arthropod-borne disease are reviewed, with special emphasis on the existing risk to contract them in Spain according to different parameters, such as the presence of arthropod and the circulation or the possible circulation of the causative agents.

infectious agents. Most AVs belong to Insecta and Arachnida classes (Table 1) .

To review the broad subject of arthropod vector-borne diseases (AVBD) in Spain is a complex task. Just listing the arthropods that transmit diseases in our environment, such as dipterans (culicids and phlebotominae sand flies), fleas, lice, bed bugs and ticks, among others, and the diseases they transmit, or that they can transmit at any given time, would be a reason for one or several treatises. In any case, before discussing the subject, it should be remembered that the infections that they transmit are usually included in the socalled zoonoses. In this regard, the World Organization for Animal Health estimates that at least 60% of infections that affect humans have a zoonotic origin 2 and, according to the Pandemic Emerging Threats Program of the American Agency for International Development, almost 75% of current threats also have this origin. 3 One of the many known routes for the acquisition of zoonoses, apart from direct contact with animals or their products, faecal-oral or respiratory routes, bites or scratches, the consumption of undercooked 2387-0206/© 2018 Elsevier España, S.L.U. All rights reserved. products or the intake of milk, is AV transmission. 4 It is difficult to limit this issue to our country, since the setting is global and very dynamic, and diseases do not understand political borders. Only a few months ago new threats appeared, such as the re-emergence of yellow fever in Brazil or the epidemic of plague in Madagascar. 5 However, in this review we will put the focus on AVBD with greater risk to humans in our environment, without losing the "one health" perspective. AVBD are subject to complex interactions (demographic, social and cultural changes, climate change, wars and famine or evolution of microorganisms) among which, undoubtedly, global transport systems and the consequent invasion of exotic species 6 stand out. Generally speaking, travel, migration and globalization contribute to the emergence of infectious diseases. Its importance has been debated for many years and, possibly, dates back to ancient times. 7 Humans carry their usual microbiota, pathogens, ectoparasites and other possible vectors, the immunological history of past infections and vaccines, the genetic load (greater or lesser susceptibility), cultural preferences, behaviours, habits and customs, as well as luggage (pets, goods and others). 7 In the case of AVBD, the equation for the appearance of a certain disease would be the following: the presence of competent vector arthropods plus susceptible population, together with the presence of reservoirs and/or intermediate hosts (sick people), could give result an epidemic. The introduction of the tiger mosquito (Aedes albopictus) and the threat of its expansion could be a good example.

It is thought that A. albopictus was introduced in Europe in 1979 through Albania, by the trade of used tyres, although the first publication on its introduction in the European continent dates back to 1990 in Italy. 8 Since then, A. albopictus has expanded throughout the Mediterranean area. In Spain, this aggressive mosquito is well established in Catalonia, Levante, in the coastal area of Murcia and Andalusia. It has also been detected in Guipúzcoa, 9 and little by little it is introduced in other non-coastal areas such as Aragon, extending through travel routes (for example, motorways). 10 The last detection was carried out in the Community of Madrid 11 (Fig. 1) . A few months ago, the first specimens of this species were also identified in the North of Portugal. This mosquito has been incriminated as a vector of numerous arboviruses in different parts of the world, including Europe. A. albopictus, is the chikungunya virus vector. In this regard, most of the cases in Europe are imported, although in the last two decades there have been different epidemic outbreaks in Italy 12 and, recently, in France. 13 In Spain, only imported cases have been reported. 14 This mosquito (next to Aedes aegypti which, as will be detailed later, has been detected in a timely manner in Europe) can act as a vector of the dengue virus and with less effectiveness of the Zika virus. 15 In France, A. albopictus was responsible for the first autochthonous cases of dengue 16 and of those reported in the same country during the following years, one of them with a history of travel to Madeira, where a large outbreak had been reported (more than a thousand cases) between 2012 and 2013. 17 In 2011, the occurrence of autochthonous cases of dengue in Croatia were also attributed to A. albopictus, establishing the transmission by this mosquito in Europe. 18 In Spain we are only suffering from their annoying bites, for now. 19 Table 2 shows arbovirus infection and Table 3 shows other infections transmitted by dipterans worldwide, with the risk of transmission in Spain. We have evaluated the risk of emergence and/or re-emergence of these diseases in Spain according to the existing studies for each pathogen, the experience according to other diseases, previous immunity and other criteria, some of them subjective, that do not appear in the text.

A. aegypti is the main Zika vector and also a transmitter of yellow fever, dengue and chikungunya. In principle, this species is not a problem because it is not settled in Europe, although it has been detected in some areas, such as in an airport in the Netherlands and, more recently, in Fuerteventura 20 (Canary Islands) (Fig. 1) .

In view of the Zika epidemic in the Americas, the Ministry of Health, Social Services and Equality, in collaboration with the Carlos III Health Institute and the Autonomous Regions, has established a Zika virus disease surveillance in Spain. To date (last update in July 2017), 325 confirmed cases have been reported, all imported, except 4 congenital cases whose mothers were infected in the risk zone and 2 autochthonous cases of sexual transmission. 21 It should be noted that it is not necessary to resort to invasive or exotic species to refer to AVBD. Thus, Anopheles atroparvus is present in Spain, a good malaria vector. The official map of the distribution of this mosquito is not updated; however, although the risk of a malarial outbreak is low in our country, 22 recent events have involved this species in the two cases of autochthonous malaria registered in the north of the peninsula. 23 Spain was an endemic country of malaria until 1964, when WHO declared it a The risk of emergence/re-emergence is calculated based on three factors: (a) presence of cases of the disease in humans in the last 5 years in Europe, Mediterranean, Central and South American countries with a significant relationship with Spain; (b) presence of the vector in Spain; (c) pathogenicity of the virus for humans. Each factor is scored with one point (presence in the first two factors and low pathogenicity in the third factor) or with zero points (absence in the first two factors and high pathogenicity in the third factor). The first two factors are added and the third is subtracted. The total score can range between 0 and 2, with 0 being: low risk; 1: moderate risk; 2: high risk. free zone. In Europe, after the eradication of malaria, most cases are imported, although sporadic cases have recently been reported in many Mediterranean countries such as France, Italy, Greece. 24 The emergence of autochthonous cases in Greece between 2009 and 2017 has raised doubts about the real situation in Europe as a malaria-free zone. 25 Other diptera present in Spain which we cannot ignore are phlebotominae sand flies. The species Phlebotomus perniciosus and Phlebotomus ariasi, are the competent vectors of the leishmaniasis agent (Leishmania infantum). There are also other potential vectors of L. infantum in Spain, as they are Phlebotomus papatasi and Phlebotomus sergenti. Leishmaniasis is endemic throughout the Mediterranean basin in Europe and its geographic scope is spreading. Usually, the epidemiology of leishmaniasis was linked to the rural habitat with the presence of dogs. The great epidemic outbreak of Fuenlabrada with a high number of cases in an urban area, in which leishmaniasis was not common, showed the dangers of changing the urban model in Spain. Many houses were built in rural agricultural areas with gardens and peri-urban green spaces where wildlife was present. In these places the concentration of phlebotominae sand flies was high, and, in their environment, there were not only dogs but also other L. infantum reservoirs, such as hares and rabbits. This fact together with mild temperatures in recent years, decreasing the mortality of the vector, seems to be what caused the great outbreak. [26] [27] [28] Undoubtedly, the presence of phlebotominae sand flies throughout the Iberian Peninsula is a great threat, since not only do they transmit leishmania, but they are also Toscana virus vectors, which is causing numerous cases of meningoencephalitis in some areas of Spain 29 and other phleboviruses such as the Granada virus (without proven pathogenic power), the Naples virus or the Sicily virus. 30 Another species of mosquito to which special attention is to be paid is Culex pipiens. This species, which is distributed and well represented throughout the Iberian Peninsula, is capable of transmitting the West Nile virus (WNV). West Nile fever is becoming a serious problem in some areas of Europe, as in Greece, where there has been an outbreak with numerous neuroinvasive forms, 31 and in 2017 cases have been reported in France, Italy, Romania, Hungary, Croatia, Serbia and Austria. 32 In Spain, according to the data from the situation report and WNV risk assessment, published in 2013, there are several species of mosquitoes capable of virus transmission. For example, Culex modestus, Culex perexiguus and Culex theileri show a high vector competence, while C. pipiens and A. albopictus have a moderate vector competence. 33 The first human case of neuroinvasive disease due to WNV in our country was identified, retrospectively, in a patient diagnosed with meningitis in September 2004 who, in the days before the onset of symptoms, visited a village in Badajoz, Extremadura (Spain). 34 In 2010, the Ministry of the Environment reported the detection of WNV in 36 equine farms in the provinces of Cádiz, Sevilla and Málaga. 35 Through this active surveillance, 15 suspected cases were investigated and two human cases of WNV meningoencephalitis were confirmed. 35 Between 2011 and 2016, virus activity was detected in equines, suggesting that the virus is endemic in our country. 36 In addition, there was previous evidence about its circulation in birds that were considered for the development of a predictive virus circulation model in our country. 37

Another factor that clearly influences infections transmitted by arthropod vectors is climate change. In 2017 the International Conference on Climate Change and Health was held in Atlanta, which revolved around the idea that: "Health is the human face of climate change". Following this meeting, a special article was published in the New England Journal of Medicine which stated that the distribution of infectious diseases such as Lyme borreliosis, rickettsiosis or West Nile fever are expanding at the same rate as their AVs. 38 We know that climate variations and extreme weather events have a profound impact on AVBD. 39 Mosquitoes and ticks are devoid of temperature regulation mechanisms and, for this reason, fluctuations in temperature greatly affect their reproduction and survival. 40 In our country, it is more than possible that the great increase in the number of ticks in recent years is due to the fact that winters, in general, are much milder than years ago. Just to mention an example, Ixodes ricinus, the tick that most frequently bites people in the north of Spain, is very sensitive to climate warming. This, among other factors, is increasing its survival. 41 This species of tick transmits very prevalent diseases in Europe, such as Lyme disease or tickborne encephalitis, or others such as Rickettsia monacensis infection, human anaplasmosis, and babesiosis. 42, 43 In Spain, human cases of all of them have been described, except for tick-borne encephalitis. Although there is a high suspicion of the circulation of the virus in Spain, the molecular screening of hundreds of ticks has been carried out in our laboratory, with negative results. 43 In addition, other pathogens have been detected in I. ricinus specimens collected in Spain, such as Rickettsia helvetica, Candidatus Neoehrlichia mikurensis or Borrelia miyamotoi, which leads us to be alert to the possible occurrence of human cases. [44] [45] [46] As a consequence of climate change, the hypothesis about the probable changes in the distribution of another species of tick, Hyalomma marginatum, which is the Crimean-Congo hemorrhagic fever (CCHF) vector in Europe, has also been established. Under warmer climate conditions, according to prediction models, it is expected that the distribution of this tick species will extend to new areas which were previously free of the vector. In relation to this issue, the epidemiology of Mediterranean spotted fever seems clearly associated with climate change, especially with low rainfall values 47 and it has been shown that warming causes greater aggressiveness in its AVs. Table 4 shows the tick-borne diseases throughout the world, with the prediction of risk for Spain (subjective assessments).

To be able to show a perspective on the AVBD, it is essential to monitor and identify microorganisms in vertebrates and arthropods, designing strategies before their transmission to humans. Early detection and implementation of control strategies allow minimizing the impact on the population. Between 1990 and 2010, 91% of emerging infections spread from a wild-type focal point. 2 Occasionally, the infection is spread directly from reservoirs such as bats, rats or chimpanzees to domestic animals, which amplify the infection, or to people; other times, infection dissemination (spill-over) occurs through AV such as ticks, fleas or mosquitoes. In any case, it is essential to carry out a surveillance and to know the microorganisms carried by AV. A recent example in Spain is the detection of CCHFV in ticks of the species Hyalomma lusitanicum collected in deer a few years ago 48 in the province of Caceres and the explanation of one of the possible ways of the arrival of the virus to our country. 49 detection of the disease that appeared in 2016 as, to some extent, it was predictable. On September 1, 2016, the Ministry of Health issued a press release reporting the death of a man by CCHF and the contagion of the nurse who had taken care of him in the ICU of the Vallecas Hospital where he had been treated. The first two autochthonous cases of CCHF in Spain were confirmed 50 (Fig. 2) . In the last CCHFV situation report and transmission risk assessment in Spain, 51 52 The diagnosis of tick-borne diseases is not always easy. We must bear in mind that a tick bite history is usually absent in at least half of the cases and that incubation periods can be very long. Depending on the size of the tick, they can be very difficult to see (they can simulate a small mole), and their bite is painless. Unless there is awareness or a high index of suspicion when faced with certain signs and/or clinical symptoms, who is going to think of a tickborne disease? It is clear, "what is not sought, is not found". 52 In 2018, WHO revised the list of emerging pathogens that could cause serious epidemics in the future and those that need to be investigated, including CCHFV, Ebola/Marburg virus, Zika virus, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Lassa virus, Nipah virus and Rift Valley fever virus. In addition, this year the list is completed with disease X, referring to an international epidemic that could be caused by a pathogen whose pathogenic potential and route of transmission is unknown at the moment. This list takes into account the transmissibility between humans, the severity of cases and the percentage of mortality, the difficulty of control and diagnosis and the context of public health and global expansion. In addition, there are other diseases that need more attention as soon as possible: hemorrhagic fevers by other arenaviruses, chikungunya virus, diseases by other highly pathogenic coronaviruses or by emerging enteroviruses and febrile syndrome with severe thrombocytopenia. 53 Many of these diseases are AVborne. High High DEBONEL/TIBOLA: Dermacentor-borne necrosis, erythema and lymphadenopathy/tick-borne lymphadenopathy; LAR: rickettsiosis associated with lymphangitis. a In Spain, Borrelia hispanica relapsing fever. The risk of emergence/re-emergence is calculated based on two factors: (a) presence of cases of the disease in humans in the last 5 years in Europe, Mediterranean countries and Central and South American countries with a significant relationship with Spain; (b) presence of the vector in Spain. Each factor is scored with one point (presence in the two factors) or zero points (absence in the two factors) and both are added. The total score can range between 0 and 2, with 0 being: low risk, 1: moderate risk and 2: high risk.

Another AV that is said to have killed more people than all wars together is the body louse (Human pediculus), transmitting exanthematic or epidemic typhus (Rickettsia prowazekii), endemic recurrent fever (Borrelia recurrentis) and the trench fever (Bartonella quintana). Body lice have been a serious public health problem until recently. They live in the seams of clothes and multiply in cold weather, lack of hygiene and war conditions. A person can be infested with thousands of lice, and each specimen is capable of biting an average of five times a day. It is said that body lice were one of the main problems during the Russian Revolution, where three million people affected by exanthematic typhus died. Thus, Vladimir Ilyich Lenin (1870-1924) stated: Either Socialism defeats the louse, or the louse will defeat Socialism". Here in Spain, it was also a problem during the post-war period and was used as propaganda by Franco's regime. We can ask ourselves: Is there a risk of an epidemic or an epidemic outbreak of exanthematic typhus? It could happen, as it occurred in Burundi in 1996, when a large epidemic affected more than one hundred thousand patients. 54 All the alarms went off when a Red Cross nurse was diagnosed after returning from work in the affected country. Body lice are not seen on the body surface but live in the seams of clothing, in 20 ± 2 • C temperatures. Parasitism by body lice should be suspected in persons with signs of scratching and lack of hygiene, more frequently in cold times of the year. At present, body lice have reappeared in refugee camps in Europe, as in the Second World War. In November 2015, the European Center for Disease Prevention and Control reported the emergence of 27 cases of recurrent fever due to body lice at different points along the route followed by refugees arriving in Italy from the Syrian war. 55 In Western Europe, although we have not experienced any epidemic since the post-war period, and the fact that the condition had been eradicated, occasionally, there are R. prowazekii and B. quintana infection reports in homeless people parasitized by lice 56 and cases of Brill-Zinsser disease have been described in people who have suffered from exanthematic typhus which could lead to an epidemic outbreak in certain conditions. 57 Fleas are other bloodsucking insects of worldwide distribution with an impact in Public Health. Rickettsia can be transmitted to humans by at least two species: the rat flea (Xenopsilla cheopis), which is the endemic or murine typhus vector (caused by Rickettsia typhi), and the cat flea (Ctenocephalides felis), which is the key vector of Rickettsia felis and, occasionally, of R. typhi. As far as we know, rickettsias are not transmitted by the human flea (Pulex irritans). In Europe, murine typhus is a common AVBD in Mediterranean countries such as Greece, Cyprus, Croatia and Spain, including the Canary Islands. 58 It develops as a non-specific febrile disease, with or without rash, which is often underdiagnosed. In clinical practice, murine typhus should be included in the differential diagnosis of any patient with fever of intermediate duration, that is, in a patient with fever (more than 38 • C) of more than 7 and less than 28 days of progression, without focality to guide the diagnosis, which remains without a diagnosis after an initial evaluation that includes a complete clinical history, physical examination, complete blood count, chest X-ray and biochemical blood and urine tests. 59 R. felis infection is another rickettsiosis with characteristics similar to murine typhus, of which cases have also been published in Spain 60 and that should be considered in patients with fever and/or rash, with a history of contact with cats or flea bites. Despite the fact that there have been no reports of autochthonous Yersinia pestis infection transmitted by the rat flea (X. cheopis) in Spain, there is an alert for travellers at the time of writing this manuscript due to an epidemic outbreak in Madagascar that has affected several thousand people. 5 Finally, we should remember the phrase written by Hans Zinsser in 1934 in his book entitled: Rats, lice and history: "Nothing in the world of living creatures remains constant. Infectious diseases are constantly changing, new ones are in the process of development and the oldest ones are changing or disappearing".

Currently, ticks are considered the most dangerous AVs in the world, because of their ease in moving from animals to people, because of their ubiquitous nature (they are present on all continents, including Antarctica) and because of their capacity to agglutinate inside them a host of pathogenic microorganisms potentially transmissible through their hematophagous habits. The human tampering of ecosystems (deforestation, erosion of geographical limits to facilitate travel, etc.) or climate change are some of the factors that are favouring a greater contact between wild animals (with their ticks and the diseases they transmit) and people, facilitating the expansion of ticks to new previously unoccupied areas. Diptera, ticks or other AV may play the leading role in the next pandemic. Therefore, anticipating the next Public Health crisis is in our hands.

The authors declare no conflict of interest.

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Direct evidence of adult Aedes albopictus dispersal by car

Aedes (Stegomyia) albopictus (Skuse, 1894) (Diptera, Culicidae) primera cita para la Comunidad de Madrid

Chikungunya is back in Italy

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Zika virus: an updated review of comp or naturally infected mosquitoes

First two autochthonous dengue virus infections in metropolitan France

European Centre for Disease Prevention and Control. Dengue outbreak in Madeira, Portugal

Autochthonous dengue fever in Croatia

Initial distribution assessment of Aedes albopictus (Diptera: Culicidae) in the Barcelona, Spain, area

Identificación del mosquito Aedes aegypti en Fuerteventura

Casos diagnosticados en España

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Fauna de mosquitos (Diptera, Culicidae) presentes en el humedal de La Grajera (Logroño) y sus implicaciones en Salud Pública

Really malaria-free Europe?

Re-emergence of leishmaniasis in Spain

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Subdirección de Promoción de la Salud y Prevención. Dirección General de Atención Primaria

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We wish to thank Jorge García Labeaga, of URBE Ingeniería, for his collaboration in the preparation of Fig. 1 .