key: cord-0739100-kzk4i2j2 authors: Wong, Samson; Lau, Susanna; Woo, Patrick; Yuen, Kwok‐Yung title: Bats as a continuing source of emerging infections in humans date: 2006-10-16 journal: Rev Med Virol DOI: 10.1002/rmv.520 sha: a7e154d3a1aa97c79713cab03aea3bf49b6754ed doc_id: 739100 cord_uid: kzk4i2j2 Amongst the 60 viral species reported to be associated with bats, 59 are RNA viruses, which are potentially important in the generation of emerging and re‐emerging infections in humans. The prime examples of these are the lyssaviruses and Henipavirus. The transmission of Nipah, Hendra and perhaps SARS coronavirus and Ebola virus to humans may involve intermediate amplification hosts such as pigs, horses, civets and primates, respectively. Understanding of the natural reservoir or introductory host, the amplifying host, the epidemic centre and at‐risk human populations are crucial in the control of emerging zoonosis. The association between the bat coronaviruses and certain lyssaviruses with particular bat species implies co‐evolution between specific viruses and bat hosts. Cross‐infection between the huge number of bat species may generate new viruses which are able to jump the trans‐mammalian species barrier more efficiently. The currently known viruses that have been found in bats are reviewed and the risks of transmission to humans are highlighted. Certain families of bats including the Pteropodidae, Molossidae, Phyllostomidae, and Vespertilionidae are most frequently associated with known human pathogens. A systematic survey of bats is warranted to better understand the ecology of these viruses. Copyright © 2006 John Wiley & Sons, Ltd. Zoonoses are diseases and infections which are naturally transmitted between vertebrate animals and man [1] . Zoonotic pathogens are currently considered to be the major sources of emerging and re-emerging infections in humans and RNA viruses account for the overwhelming majority of emerging pathogens [2] . At the time of writing, the most important non-mammalian vertebrates associated with emerging infections in humans are the birds. The avian species have an enormous population: the estimated world poultry population in agriculture (chickens, ducks, geese and turkeys) in 2005 was over 18 billion [3] . Poultry birds often have large populations reared in relatively restricted environments. Wild birds have a tendency to gather in flocks and many species fly or migrate over long distances. All these are important attributes which allow them to harbour and disseminate infectious agents over vast geographical areas. Their impacts on public health and economy are best exemplified by the West Nile virus encephalitis in North America and the global influenza A H5N1 outbreaks. The latter carries major economic losses in agriculture and the potential to cause a pandemic associated with significant morbidity and mortality in humans. Infectious agents exist in commensal, mutual or parasitic relationships with their harbouring animal hosts. The relationship is often restricted to a limited number of host species owing to genetic adaptations that developed during co-evolution. This gives rise to the concept of species barrier in infectious diseases. However, spillage of infectious agents between different animal species does occur sporadically. This may result from accidental or deliberate intrusion by one animal species into the ecological niche of another, resulting in the direct exposure to the infectious agents from the original harbouring species or acquisition from the environment. Severe diseases often occur in the new animal hosts in the absence of genetic adaptations of the infectious agent to these new hosts. These new animals may become 'dead end' hosts when the infectious agent fails to cause further transmission under natural conditions (e.g. Japanese encephalitis in humans), or they may contribute to further transmissions resulting in an epidemic (e.g. SARS). The transmission dynamics of some important bat-associated viruses are summarised in Table 1 . Understanding the amplifying host, the routes of transmission, the type of susceptible human hosts, and the epicentres for zoonotic and human transmissions in crucial in the control of these infections. The relative probability of an infectious agent jumping from one animal species to another is often assumed to be related to the phylogenetic relatedness of the host species. However, experience from zoonoses acquired from birds shows that we should focus not just on those animals which are phylogenetically close to humans (such as the primates and rodents), but also on those which are more distantly related but have attributes that enable them to harbour and spread novel microbes. Hunting of non-human primates for bushmeat has been practised in tropical Africa for aeons. Such exposures have resulted in transmission of pathogens like Ebola virus, simian foamy viruses, simian immunodeficiency virus, and human immunodeficiency viruses to humans [4] [5] [6] . Rodents are not only the largest order of all mammals but also often exist in large numbers in urban and rural habitats. They are important sources of zoonotic pathogens including Sin Nombre and other hantaviruses. Bats are the only mammals possessing true flying ability. In recent years bats have increasingly been recognised to be potential reservoirs for various emerging infections. The bats and their associated viral pathogens will be discussed in this article. The bats represent the second largest order within the mammals. There are currently over 4600 known species of mammals (Class Mammalia) [7] . The largest order within Mammalia consists of the rodents (Order Rodentia) with over 2000 species, and there are over 930 species of bats (Order Chiroptera), or about 20% of all mammalian species. There are two suborders within Chiroptera, the Megachiroptera and Microchiroptera. Pteropodidae (flying foxes) is the only family within Megachiroptera (166 species) and they mainly feed on plant materials. There are 16 families within Microchiroptera (over 760 species) with diverse biology and ecology (Table 2) [7, 8] . Bats are found in all continents except the polar regions and a few oceanic islands. The nature of their diet is equally diverse, varying from plants, insects, animals and, unique among mammals, blood. The diversity of bat species and some of their unique biological and ecological features allow them to become the hosts for a large number of medically important infectious agents. Most bats are nocturnal animals and seek shelter in roosts during the day. A few species are diurnal. The roosting environment ranges from natural to man-made structures and they can be temporary or permanent (Figure 1 ). Natural roosts can be found in caves, rock crevices, nests of birds or ants and termites, cavities in trees, or exposed on tree branches and trunks [9] . Man-made habitats include mines, tombs, buildings, bridges and so on. The occupation of man-made habitats could bring the bats into closer association with humans and their companion animals or livestock. The significance of this is seen in the transmission of some pathogens, such as bat rabies viruses, from peridomestic bats to humans and livestocks. The number of bats in each colony varies greatly from less than 10 to over 200 000 individuals [9] . The large number of individuals, together with the social habits of the bats, such as mutual grooming and biting during courtship and mating, facilitates the transmission of infectious agents between them through direct contact, aerosols or arthropod vectors. The dietary habits of bats can broadly be divided into insectivorous, frugivorous, carnivorous, omnivorous and sanguivorous [10] . Predatory bats could potentially acquire infectious agents from other animal species, such as birds and insects. Sanguinivory in bats is limited to only three species of vampire bats, Desmodus rotundus, Diphylla ecaudara, and Diaemus youngi, all belonging to the [10] . Some species may utilise night roosts near feeding sites and distant from their day roosts. Despite their small sizes, bats have a relatively long life span and develop slowly. Many species live for over 10-20 years with some species living for over 30 years in the wild [10, 11] . Host longevity facilitates the persistence of infectious agents in When faced with winter and shortage of food supply, bats may either hibernate or migrate. The megachiropterans do not hiberbnate. Hibernation in microchiropterans involves substantial physiological changes during torpor, including an accumulation of brown adipose tissue. Hibernating bats can remain torpid continuously for up to 75 days, though many will have periodic arousal alternating with torpor periods lasting from 2 to 15 days [12] . Seasonal migration has been observed for bats living in both temperate and tropical environments, which demonstrate substantial seasonal changes in food supply and/or temperature. The maximal distance of migration of the studied bat species ranges from 200-300 km to almost 2000 km [13] . Of all the vertebrate hosts, bats are considered to be less important than ungulates, carnivores, rodents, non-mammals and primates in terms of the prevalence of zoonotic pathogens [2] . Nevertheless, bats do harbour a relatively large number of known or potential pathogens. Some of these appear to have co-evolved with specific bat hosts (e.g. lyssaviruses). Transmission of viruses carried by bats to humans can occur in a variety of ways, with direct contact through bites and scratches the most obvious example. Bats do not normally prey on humans. However, Desmodus rotundus has been known to feed on humans in Latin America when alternative animal hosts are scarce [14, 15] . Bites sustained from other bat species are usually the result of accidental encounters rather than deliberate attack on humans. Lyssaviruses are typical examples of direct bat-to-human transmission of pathogens. Another possible route of transmission involves inhalation of infectious particles by humans. These infective aerosols could arise from the secretions (e.g. saliva) or guano of the bats. This route of transmission may possibly occur in lyssavirus Bats and emerging infection Bats and emerging infection 71 71 infections. Arthropod vectors could serve as another mode of transmission of pathogens between bats and humans. Important categories of arthropods in this regard include mosquitoes, sand flies, and ectoparasites infesting bats such as bat ticks, bugs and bat flies. Insects, such as mosquitoes and sand flies may feed on both bats and humans as shown in entomological and virological studies [16, 17] . There is currently no evidence to implicate an active role of these vectors in disease transmission, presumably because of the lack of efficient vector-pathogen combinations or host specificity of the vectors. Vectorborne transmission is therefore a route that requires further study. The consumption of bat meat is practised in some parts of the world including China, Guam, and some parts of Asia where it is considered to have therapeutic effects against asthma ( Figure 1 ). Adequately cooked bat meat is unlikely to pose any risk for transmission of infections. However, capture and slaughtering of bats could expose the handler to the bats' blood and body fluids or bites and scratches. In situations where live bats are kept in captivity in game markets, they may come into close contact with other animals, which are susceptible to viruses carried by bats. This is one of the postulated mechanisms linking the finding of SARS-coronavirus (SARS-CoV) in bats and palm civets in southern China. The bats may have transmitted a SARS-CoV-like virus to the civets, which in turn act as amplifying hosts before transmitting the virus to humans. In some situations, transmission of bat pathogens to humans occurs via a secondary vertebrate host serving as an amplifying host. The outbreak of Nipah virus in Southeast Asia involved pigs as an efficient secondary host for multiplication of the virus and horses were involved in the transmission of Hendra virus to humans, while the palm civet is postulated to be the intermediate host for SARS-CoV. In an extreme example, another human host could be involved before such transmissions are clinically evident. This is exemplified by the transmission of the rabies virus to four organ transplant recipients from a donor who died of encephalitis of unknown aetiology who, in retrospect, was found to have been bitten by a bat [18] . The factors that promote the transmission of pathogens from bats to humans are incompletely understood. One aspect is environmental changes, either as a result of natural or climatic alterations or conditions related to human activities. Examples include a change of feeding hosts of the vampire bat Desmodus rotundus from livestock to humans due to a decline in the livestock population [14] . Another example is the Nipah outbreak in Malaysia in which the loss of the normal forest habitats of the bats forced them to reside in areas close to livestock and human inhabitation [19, 20] . The spread of the infectious disease within human communities was further augmented by trade in domestic animals, such as the transport of infected pigs in the spread of Nipah virus infection. Movement of bats over large geographical distances either as a result of natural migration, accidental or deliberate transport via artificial vehicles can occur and these may further facilitate the long-distance spread of potential pathogens [21] . The following section summarises the important viruses that have been found to be associated with bats. Emphasis is put on viruses that have clinical or veterinary significance and those that are better characterised. Supplementary Table summarises the viruses together with their main geographical distribution and natural hosts. Table 3 summarises their potential to be transmitted to humans based on current clinical, virological and epidemiological information. The detection of viruses in bats or other animals is problematic. Unequivocal evidence for natural infection can be obtained with a positive viral culture obtained from the animals. Another acceptable detection method is the use of direct immunofluorescent staining of bat tissues, most commonly used in the detection of lyssaviruses in the brains of bats. Nucleic acid amplification may offer similar confidence if the tests are performed competently without contamination. Unfortunately, many viruses are not readily cultivable in vitro. Consequently, a number of field studies employed serological tests to look for evidence of infection. While serology can offer valuable information, cross-reactivity between different members of the same family of viruses may be observed for some test formats (e.g. haemagglutination inhibition, complement fixation). Risk of bat-to-human transmission of the respective pathogens: A, documented direct bat-to-human transmission or through secondary hosts or definite epidemiological linkage; B, potential risk of transmission directly from bats or through secondary hosts or vectors because presence of known human pathogens documented and microbes present in relatively high frequency in bats; C, low risk of transmission directly from bats or through vectors because of low prevalence of pathogens in bats, inefficient vectorial capacity of bats or arthropod vectors, or insufficient epidemiological data to support a link; D, little risk of transmission because viruses not known to infect humans. them are arthropod-borne and have reservoirs in vertebrates. The Kaeng Khoi virus was initially isolated in 1969 from the wrinkle-lipped free-tailed bat (Chaerephon plicata) and Theobald's tomb bat (Taphozous theobaldi) in a cave in Thailand. Subsequent studies also found virological and serological evidence of infection in these two bats in Thailand [24] . The virus was recently isolated from Chaerephon plicata in Cambodia [25] . Interestingly, the virus was also isolated from bedbugs (Stricticimex parvus and Cimex insuetus) collected in the same bat caves, and these insects have been postulated to play a role in transmission of the virus between bats [24] . There is some serological evidence showing that Kaeng Khoi virus can infect humans entering bat caves to collect guano, and a seroprevalence of 29% among these workers has been described. Bedbug bites were incriminated to cause an influenza-like illness in the workers, which might be related to this viral infection. The Toscana virus is endemic in Mediterranean countries where it is a major cause of viral meningitis and encephalitis [26] . It has been isolated from the brain of a bat (Pipistrellus kuhli) once but the sandflies-rather than vertebrates-are considered to be its natural reservoir host [27] . Other bunyaviruses that have been detected in bats but with uncertain clinical significance are listed in Supplementary Table. The coronaviruses have become the focus of research since the 2003 global epidemic of SARS caused by the SARS-CoV. Coronaviruses are known to have diverse animal hosts ranging from mammalian to avian species. Human coronavirus infections prior to the SARS outbreak were caused by human coronaviruses 229E and OC43 which commonly result in the common cold. The first cases of SARS occurred in late 2002 in the southern Chinese province of Guangdong. The first confirmed case of SARS was a chef working in a local restaurant and he had had contacts with wild game animals prior to the onset of disease [28] . The emergence of a novel viral infection, together with the occupational history of contact with wild animals among four index patients in the Guangdong outbreak, prompted the search for an animal reservoir of SARS-CoV. The live animal retail markets in the city of Shenzhen, Guangdong, was investigated and evidence of infection was found in the Himalayan palm civet (Paguma larvata) and to a lesser extent, Chinese ferret badgers (Melogale moschata) and raccoon dogs (Nyctereutes procyonoides) [29] . Further evidence for zoonotic transmission of SARS-CoV came from studies which showed that wild animal traders and slaughterers had a significantly higher seroprevalence (20 to 45%) against SARS-CoV than vegetable traders and control populations (0 to 5%) [30] . Review of seroprevalence studies showed that persons with an occupational history of contact with wild animals had a substantially higher prevalence of antibodies as compared to healthy blood donors, household contact or health care workers caring for SARS patients (12.99 to 16.69% vs. 0 to 2.92%, respectively) [31] . A recent study showed that contact with game animals could result in asymptomatic infection with the SARS-CoV but that the individual could still have detectable coronavirus antigenaemia and seroconversion [32] . Restrictions on the sale and consumption of game animals therefore became important control measures during the SARS epidemic in China. In contrast to other zoonotic pathogens that crossed the species barrier to humans, the SARS-CoV is notable in that it spreads readily from person-to-person and therefore outbreaks within health care facilities was a prominent feature during the SARS epidemic with a fifth of all global cases being health care workers [33] . It is also unique amongst coronaviruses in that a wide host range is observed, with the virus being able to infect (with or without the development of illness) humans, Chinese ferret badgers (Melogale moschata) and raccoon dogs (Nyctereutes procyonoides), cynomolgus macaques (Macaca fascicularis), African green monkeys (Cercopithecus atheiops, Chlorocebus sabeus), rhesus monkeys (Macaca mulata), ferrets (Mustela furo), domestic cats (Felis domesticus), mice, golden Syrian hamsters (Mesocricetus auratus), common marmosets (Callithrix jacchus), pigs, and chickens [34, 35, 36, 37, 38] . The sudden emergence of the SARS-CoV was initially linked to the palm civet and related animals which were found to carry the SARS-CoV asymptomatically. The palm civet was consumed as a game animal in southern China and sold in the wet markets. Subsequent studies however did not show a significant amount of SARS-CoV in wild or farmed palm civets. This suggested that the caged palm civets in the markets may not be a primary reservoir host of SARS-CoV in nature, but merely a secondary amplifying host that increases the viral burden and provides ample contact with humans, thereby facilitating animal to human transmission, a situation that is similar to the Henipavirus discussed below. The search for the primary reservoir host of SARS-CoV led to the finding of novel coronaviruses among bats in Hong Kong. One of these was detected in Chinese horseshoe bats (Rhinolophus sinicus (R. rouxii)) in Hong Kong which is currently named bat SARS-CoV (bat-SARS-CoV) [39] . The bat-SARS-CoV was initially found by RT-PCR in 39% of R. sinicus tested but seropositivity of bats ranged from 67 to 84% when the sera were tested by western blot and enzyme immunoassay respectively. It is postulated that the bats might serve as the natural reservoir of the SARS-CoV (or a related virus) and the palm civets acquired the virus from the bats before passing it on to humans. Another new coronavirus was detected in the lesser bent-winged bats (Miniopterus pusillus), large bent-winged bats (Miniopterus magnater), and Japanese long-winged bats (Miniopterus schreibersii) [40] . This virus belongs to group 1 coronaviruses, which also includes the human pathogens human coronaviruses 229E and NL63. The virus was detected in 3 of 25 (12%) Miniopterus pusillus bats in a subsequent survey in Hong Kong which also revealed a great diversity of coronaviruses among the bat population [41] . Coronaviruses were detected by RT-PCR of the anal swabs in 37 of 309 bats (12%) with the bat-SARS-CoV being detected in 21 of 118 (17.8%) R. sinicus. Six other coronaviruses were also discovered in different bat species: bat-CoV-HKU2 from 2 of 118 R. sinicus; bat-CoV-HKU4 from 4 of 21 (19%) lesser bamboo bats (Tylonycteris pachypus); bat-CoV-HKU5 from 4 of 14 (28.6%) Japanese pipistrelle bats (Pipistrellus abramus); bat-CoV-HKU6 from 1 of 23 (4.3%) Rickett's big-footed bat (Myotis ricketti); bat-CoV-HKU7 from 1 of 51 (1.9%) Miniopterus magnater, and bat-CoV-HKU8 from 1 of 25 (4%) Miniopterus pusillus. Bat-CoV-HKU2, HKU6, HKU7, and HKU8 all belong to group 1 coronaviruses, while bat-CoV-HKU4, HKU5 belong to group 2 coronaviruses, the latter also includes human coronaviruses OC43, HKU1 and the SARS-CoV. The association of coronaviruses with bats is also confirmed in another study by Li et al. who documented the presence of SARS-like coronavirus infection of bats in Guangxi and Hubei, two provinces in southern and central China respectively [42] . Notably, with the exception of two positive samples which came from Rousettus leschenaulti (Family Pteropodidae), the majority of bats carrying SARS-like coronaviruses in China were Rhinolophus spp., members of which were also found to be infected with SARS coronavirus-like virus in Hong Kong. Figure 2 shows the phylogenetic relationship between the known human and bat-associated coronaviruses. These findings suggest that bats could represent a hitherto undiscovered reservoir of the coronaviruses, many of which might have important clinical or veterinary significance. Filoviruses known to cause human infection belong of two genera: Marburgvirus and Ebolavirus, the latter containing four species, viz Sudan, Zaire, Reston and Ivory Coast. Both Marburg and Ebola viruses are endemic in Africa, except the Ebola Reston virus which was acquired from primates imported from the Philippines. Human infections due to filoviruses typically occur in outbreaks due to interpersonal and nosocomial transmission, and mortality rates in outbreaks reach a staggering 50-80%. The most recent outbreak of Marburg virus occurred in Angola in 2005, involving 374 cases and 329 deaths (88% case-fatality rate) [43] ; the Ebola virus outbreak which occurred in 2005 in the Republic of Congo involved 12 cases and 9 deaths (75% case-fatality rate) [44] . Primary human infections in most cases resulted from contact with non-human primates which are generally sick or dead as a result of filovirus infection. The primates, however, are not believed to be important reservoirs of filoviruses in nature since they regularly die from the infections. Epidemiological and virological studies suggested that the regular outbreaks of filovirus infection in primates probably did not occur as a result of interspecies transmission between primates, but due to introduction to a hitherto unknown animal or environmental source [45] . The nature of such natural reservoirs remains elusive despite extensive surveys until a recent study which discovered the presence of Ebola virus (by serology and 76 76 S. Wong S. Wong et al. et al. Gabon and the Republic of Congo. These include Hypsignathus monstrousus (4 of 17 animals, 23.5%), Epomops fraqueti (8 of 117 animals, 6.8%), and Myonycteris torquata (4 of 58 animals, 6.9%), all belonging to the Pteropodidae family of flying foxes [46] . If the bats are indeed the natural reservoir of the Ebola virus, two factors have been suggested to facilitate their transmission to primates [46] . The scarcity of food during the dry season is thought to affect the immune system of bats, thereby facilitating viral replication. At the same time, primates and bats could come into closer contact in search for food so cross species transmission of the virus from bats to primates could become easier. These findings have important implications in future studies of the ecology and epidemiology of Ebola virus. The natural reservoir hosts of Marburg virus have not been identified, though bats would now be an obvious and important group of animals to investigate. Direct transmission of either of the filoviruses from bats to humans has not been confirmed. However, it is interesting to note that in some of the previous outbreaks of filoviruses in Africa not involving contact with primates, bats were sighted in caves or buildings which the index cases had visited or worked in [45] . With the present knowledge in the epidemiology of the filoviruses, it appears that direct bat-to-human transmission of [47] . Recent surveillance studies in the USA also showed occasional infection of bats by the West Nile virus [48, 49, 50] . In a series of experiments by Sulkin et al., bats (Tadarida brasiliensis mexicana, Myotis lucifugus lucifugus, Eptescius fuscus fuscus) were shown to be susceptible to infection by Japanese encephalitis and St. Louis encephalitis viruses by either the subcutaneous and intracerebral route [51] . The susceptibility of bats to infection and the level of viral replication varied with different viral strains and the species of bats tested. Of particular interest is that bats developed relatively long periods of viraemia (upto 30 days) after infection and developed no clinicopathological sequelae following inoculation, even though there was significant viral multiplication in the brain fol-lowing intracerebral inoculation. Importantly, infections due to these neurotropic viruses produced significant viral loads not only in the blood but also in the interscapular brown fat, in contrast to brains and kidneys which were less frequently found positive for viruses. Sulkin et al. also demonstrated that infection at low temperatures (from 8 C to 24 C) was associated with prolonged viraemia of over 100 days and persistence of viruses in the brown fat [52] . Transplacental infection of Japanese encephalitis virus also occurred readily in Tadarida brasiliensis mexicana, again without any clinicopathological sequelae to the fetuses [53] . Similar experiments also showed that the big brown bat (Eptesicus fuscus) can maintain St. Louis encephalitis during hibernation [54] . Isolation of Japanese encephalitis virus in naturally infected bats in Japan and Taiwan, and serological evidence of St. Louis encephalitis infection in Ohio and Trinidad have been reported [16, 23, 54, 55] . These data suggested that bats could easily serve as a suitable host for the persistence of these viruses in nature, perhaps with special significance to overwintering of viruses. Similarly, natural infection of bats by dengue virus was suggested by a serological study in Costa Rica and Ecuador, and more convincingly by positive RT-PCR of the brains of Rousettus leschenaulti bats in southern China [56, 57] . Kyasanur Forest disease is a flaviviral haemorrhagic fever mainly seen in western India. The virus is mainly transmitted between rodents and insectivores via ixodid ticks. Isolation of the virus from bats (Rhinolophus rouxii and Cynopterus sphinx) had been reported on two occasions from India. The role of bats in the ecology of these medically important flaviviruses is unknown [58, 59] . Antibody against the yellow fever virus was described in a bat in one study, though primates are still believed to be the most important reservoir of sylvatic yellow fever [23] . A virus named Montana Myotis leukoencephalitis (MML) virus was initially isolated in the 1960s from Myotis lucifugus [60] . Subsequent genome analysis placed it into the family Flaviviridae [61] . No arthropod vectors have been identified for this virus and the virus can be transmitted directly to mice from bat bites. The Rio Bravo virus was isolated from the salivary glands of Brazilian free-tailed bats (Tadarida brasiliensis) in the USA and Mexico and also from Molossus ater in Trinidad [62, 63] . It has no known arthropod vectors and is 78 78 S. It is evident that bats can be infected by numerous flaviviruses in nature. It is also biologically plausible that they have the potential to serve as reservoir hosts in certain situations, such as overwintering of viruses. However, as pointed out by Scott, evidence of viral infection in a vertebrate host does not equate to a significant role for them in the natural ecology of the viruses [66] . Virological profiles of infected animals, density of vectors, feeding habits of vectors and their vectorial capacity are all essential factors to be considered in this regard. Isolation of influenza virus A/H3N2 from Nyctalus noctula bats in Kazakhstan was reported in the 1970s in the Russian literature [67] . Subsequently, serological evidence of influenza A/H2N2 and A/ H3N2 infections of various bat species was found in India [68] . Although bats are likely to be susceptible to influenza virus infection, current epidemiological studies do not consider them a significant reservoir of the viruses in nature. Paramyxoviruses are common pathogens of humans. Important human pathogens include Respirovirus (human parainfluenza viruses 1 and 3), Rubulavirus (human parainfluenza viruses 2 and 4, mumps virus), Morbillivirus (measles virus), and Metapneumovirus. The first finding of a paramyxovirus in bats was described in 1966 [69, 70] . A parainfluenza virus type 2 was isolated from the frugivorus bat Rousettus leschenaulti in India. The Mapuera virus was the second paramyxovirus isolated from the yellow-shouldered bat (Sturnira lilium) in Brazil in 1979 [71] . Both have not been found to cause human infections. The significance of paramyxoviruses in bats, however, became evident in the 1990s with the occurrence of two outbreaks in humans and animals. The new genus Henipavirus was proposed to encompass two of the three zoonotic paramyxoviruses that are pathogenic to humans, namely Hendra and Nipah viruses. Whether the Indian type 2 parainfluenza virus is related to the newly described paramyxoviruses is unknown. In 1994, an outbreak of fatal hyperacute respiratory illness occurred in horses in Queensland, Australia. Two human contacts of the index horse were infected and developed an influenza-like illness. One of them died of pneumonitis, respiratory failure, and renal failure and a virus was isolated from both the fatal patient and the horses [72] . The virus was initially called equine morbillivirus and later named Hendra virus. In the 1995 outbreak in Queensland, another patient died of encephalitis after Hendra virus infection [73] . Following the initial outbreaks of Hendra virus infection, a serological survey in Australia involving 5264 sera from 46 terrestrial animal species failed to show any evidence of infection by this new virus. However, seropositivity was detected in the spectacled fruit bat (Pteropus conspicillatus), black fruit bat (P. alecto), little red (P. scapulatus), and grey-headed bat (P. poliocephalus) [74] . Subsequently, Hendra virus was isolated from the viscera and fetuses of P. policephalus and P. alecto [75] . Retrospective analysis of bat sera showed that the virus was present in Australian flying foxes as early as 1982 and in some surveys, seroprevalence as high as 47% had been documented [76] . As is the case for many other bat-associated infections, Hendra virus does not cause disease or pathology in bats, and transplacental transmission to the fetus is possible. The route of transmission from flying foxes to horses has not been directly documented, though exposure to infected urine has been considered possible [76] . In addtion to horses, cats and guinea pigs are also susceptible to Hendra virus infection and these animals can shed the virus in urine [77] . Humans acquired the infection solely from horses to date and not from flying foxes. The route of transmission to humans probably occur through contact with the respiratory secretions of the infected horses. From September 1998 to June 1999, an outbreak of encephalitis occurred amongst pig-farmers in Malaysia. The aetiology of the disease is a novel paramyxovirus name Nipah virus isolated from [79, 80] . The outbreak in humans was preceded by sudden and massive deaths of the pigs due to acute respiratory distress syndrome and encephalitis, and close contacts with pigs was confirmed to be the major risk factor for acquisition of the infection in a case-control study [80] . The presence of the virus in the respiratory secretions and urine of infected pigs suggested that contact with these secretions is the likely route of transmission. About 8% of the patients did not have a contact history with sick pigs; dogs were suspected to be another possible vector for transmission as they can also be infected by Nipah virus. Culling of over 1 million pigs was needed to terminate the outbreak. Singapore was concurrently hit by an outbreak of Nipah encephalitis in March 1999 which affected 11 abbatoir workers who handled pigs imported from Malaysia [81] . Contact with live pigs was again confirmed to be a major risk factor for infection [82] . No interpersonal or nosocomial transmission of Nipah virus infection was noted in these two outbreaks [83] . A search for the reservoir hosts of Nipah virus found that in addition to pigs, wild boars (Sus scrofa), domestic dogs (Canis lupus) and rodents (Rattus rattus) could be secondarily infected. But the main natural reservoir of the virus appears to be flying foxes. Serological studies showed that, in Malaysia, a number of bat species are seropositive, with the majority of the animals belonging to the Megachiroptera [84] . The highest seroprevalence was found in Pteropus hypomelanus (31% seropositive), followed by Pteropus vampyrus (17%), Eonycteris spelaea (5%), Cynopterus brachyotis (4%), and the Microchiropteran Scotophilus kuhlii (3%). Subsequently, Nipah virus was cultured from the urine of the flying fox P. hypomelanus [85] . It was postulated that the combination of anthropogenic deforestation and drought caused by the El Niñ o Southern Oscillation drove the frugivorous flying foxes from their natural habitats into orchard plantations. The close proximity between the bats and pigs thus created, resulted in the cross-species infection of the pigs and subsequently humans [86] . There was no epidemiological evidence to suggest that Nipah virus was transmitted from flying foxes to humans directly and no person-to-person transmission of the infection has been confirmed in the outbreaks in Malaysia and Singapore. Nevertheless, the presence of the virus in the respiratory secretions and urine of infected humans has been documented, suggesting that the risk of interpersonal spread may not be zero [87] . Although the number of cases that has been studied was small, it appeared that the presence of Nipah virus in respiratory secretions and urine is confined to the first week of illness before the appearance of IgM antibodies. In 2001 and 2003, outbreaks of a febrile neurological disease occurred in Bangladesh. Retrospective studies showed that the outbreak was again caused by Nipah virus infection [88, 89] . The Bangladeshi outbreaks are notable in two aspects. Firstly, pig populations were very small in Bangladesh and there were no reports of massive animal deaths in the vicinity of the affected villages. Direct bat-to-human transmission through accidental exposures to bats or bat secretions was suspected. Secondly, there were familial clusters of cases suggesting the possibility of interpersonal spread through contact with the patients' secretions. Nipah virus antibodies were found in two flying foxes (Pteropus giganteus) in Bangladesh. A similar outbreak of encephalitis occurred in the northeastern part of India in 2001 and retrospective studies again confirmed Nipah virus as the cause of encephalitis [90] . Animal studies were not performed in the Indian outbreak but nosocomial spread of the infection was observed. In Cambodia, Pteropus lylei has a 11.5-12.3% seroprevalence for Nipah virus but only 0.26% of the urine samples were culture positive, suggesting a transient infection of the flying foxes by the virus [91, 92] . In Thailand, seroprevalence among Pteropus hypomelanus, P. lylei, P. vampyrus, and Hipposideros larvatus ranged from 1.3% to 15.4%, and the virus was detectable by RT-PCR in P. lylei (saliva and urine) and H. larvatus (saliva) bats [93] . Recently, serological evidence of infection by Henipavirus was also reported among Pteropus vampyrus in Indonesia [94] . Phylogenetic analysis of the nucleocapsid gene sequence suggested that there are three lineages of Nipah virus, with Nipah-Bangladesh and Nipah-India being closer to each other than Nipah-Malaysia and Nipah-Cambodia [88, 90] . From April to September in 1997, sows in New South Wales, Australia, were found to have 80 80 S. Wong S. Wong et al. et al. decreased pregnancy rate and litter size. There was an increase in mummified, stillborn, and deformed piglets. The affected stillborn piglets were found to have severe degeneration of the central nervous system and some had myocarditis. Subsequently a new virus-later named the Menangle virus-was isolated from the infected piglets [95] . Among 251 persons with contact with the pigs in the piggeries, 2 were seropositive for the virus [96] . Both of the patients developed a febrile illness with headache, malaise, myalgia, and skin rashes with no long term sequelae. The flying foxes Pteropus policephalus and P. alecto were seropositive for the Menangle virus [95] . The route of transmission of menangle virus from flying foxes to pigs, amongst pigs, and from pigs to human is unknown. The complete genome of the Menangle was reported which confirmed its position in the family Paramyxoviridae [97] . As a result of enhanced surveillance for batassociated viruses in Southeast Asia, the Tioman virus was discovered. Tioman virus is a novel paramyxovirus isolated from the urine of the flying fox Pteropus hypomelanus in Malaysia and the genome of the virus has been published. It was placed under the genus Rubulavirus by genomic analysis [98, 99] . Human infections due to Tioman virus have not been described. Two reoviruses have been isolated from bats. They include the Nelson Bay virus and Pulau virus [100, 101] . The transmissibility and pathogenicity of these viruses to humans are unknown. By searching through the mouse (Mus musculus) and rat (Rattus norvegicus) genomes, genetic elements belonging to betaretroviruses were discovered in these rodents. In the same study, sequences similar to the env gene of an endogenous retrovirus CpERV-5_AC138156 was found in the genome of the Seba's short-tail bat (Carrollia perspicillata) [102] . The Rhabdoviridae contains six genera, Vesiculovirus, Lyssavirus, Ephemerovirus, Novirhabdovirus, Cytorhabdovirus, Nucleorhabdovirus, the last two being plant viruses. Vesicular stomatitis (Vesiculo-virus) occurs in horses, cattle, and pigs in the Western Hemisphere. It produces a disease in livestock similar to foot-and-mouth disease. Seroprevalence amongst humans can be high in enzootic areas but human infection is generally mild or asymptomatic. Bats have been implicated, but not proven, as a possible carrier for vesicular stomatitis virus [103] . In contrast, the Chandipura virus, another Vesiculovirus, causes a much more severe encephalitis, sometimes in large outbreaks, in India [104] . Sandflies were believed to be the vector of Chandipura virus but it has not been found in association with bats. Mount Elgon bat virus was another rhabdovirus isolated from Rhinolophus hildebrandtii eloquens and described in 1969 [105] . It has not been associated with human infections. The lyssaviruses are arguably the most important of all bat-associated viruses. The Lyssavirus species include rabies virus, (genotype 1), Lagos bat virus (genotype 2), Mokola virus (genotype 3), Duvenhage virus (genotype 4), European bat lyssaviruses 1 and 2 (genotypes 5 and 6, respectively), Australian bat lyssavirus (genotype 7), and four newly described genotypes found in Eurasia, Aravan (isolated in 1991), Khujand (isolated in 2001), Irkut (isolated in 2002), and West Caucasian bat viruses (isolated in 2002) [106, 107, 108] . These four Eurasian genotypes and the Lagos bat virus have not been shown to cause human infections to date [109] . There had only been one reported case of human infections caused by the Duvenhage virus to date which occurred in South Africa in 1970 [110, 111] . Miniopterus schreibersii was considered to be the host associated with the infection and the virus was isolated once from a Nycteris thebaica bat [111] . The lyssaviruses differ from each other not only in their genotypes (based on nucleoprotein gene sequences), but also in their pathogenicity in animals and cross-neutralisation by antibodies. Based on the transmembrane glycoprotein sequence, these seven lyssavirus genotypes were further divided into two phylogroups [112] . Phylogroup I consists of genotypes 1, 4, 5, 6 and 7 while phylogroup II consists of genotypes 2 and 3. Phylogenetic analyses of the four Eurasian lyssaviruses using the glycoprotein, nucleocapsid and phosphoprotein gene sequences has also been published [113] . Aravan, Irkut, Khujand and West Caucasian bat viruses are considered to be separate genotypes according to nucleoprotein gene viruses, and these six viruses are believed to represent a phylogroup of Old World bat lyssaviruses. The West Caucasian bat virus is the most divergent of all known lyssaviruses. All the above lyssaviruses have been isolated from bats except Mokola virus which is mainly isolated from cats and occasionally from rodents and shrews. For the bat-associated lyssaviruses, only rabies virus is also associated with other terrestrial animals (especially carnivores); all the others have bats as the sole natural reservoir hosts. Rabies virus has a worldwide distribution while the other lyssaviruses are relatively restricted geographically. A large number of animals are susceptible to infection by the classical rabies virus. However, only mammals of the orders Chiroptera and Carnivora transmit the virus efficiently in nature. In countries which are free from canine rabies, bats are the most important source for human rabies. The evolution of rabies virus has been studied in detail. Phylogenetic studies showed that the different genotypes of lyssaviruses are clearly distinct from each other and that, within genotype 1, distinct lineages with respect to the reservoir host range can be recognised [114] . The chiropteran rabies viruses are likely to be older than the carnivoran viruses, and the current rabies viruses amongst carnivores probably arose as a result of two cross-species spillover events from bats to carnivores. One of the events resulted in the North American raccoon and skunk rabies virus lineage while the other resulted in the carnivore rabies lineage in the rest of the world. Cross-species transmission of rabies virus still occurs today but all these incidents are the result of bat-to-terrestrial animals spillover not the reverse [115] . Phylogenetic division of bat rabies viruses was clearly shown to be associated with clustering of specific bat species in two studies, suggesting that some rabies viruses co-segregate with their bat hosts [116, 117] . In Canada, for example colonial and non-migratory Myotis bats are associated with rabies virus clades that are distinct from those assicated with solitary, tree-dwelling and migratory Lasiurus bats [117] . The vast majority of human rabies in the world is acquired from canine sources. In some countries, however, bats carrying variants of the genotype 1 rabies virus are equally, if not more important, causes of human infections. From 1958 to 2000, bat rabies accounted for 32 of the 35 indigenous cases of rabies in the USA [118] . In 26 of the patients, there was no history of bat bites. Nineteen of these 26 'cryptic' rabies were associated with two species, Lasionycteris noctivagans and Pipistrellus subflavus. Similarly in Latin America, bat rabies is as important as canine rabies in causing disease in humans and livestocks. In Brazil, analysis showed that canine-and bat-related rabies viruses reside in distinct groups, reinforcing the hypothesis that different rabies virus strains are preferentially related to different mammalian hosts [119, 120] . Bat rabies viruses are associated with a large number of bat species, both frugivorous, insectivorous, and sanguivorous. In the Latin America, Desmodus rotundus, Artibeus lituratus, Artibeus planirostris, Tadarida brasiliensis, Nyctinomops laticaudatus, Eumops auripendulus, Eptesicus furinalis, Lasiurus borealis, Molossus spp. are often encountered [119, 120, 121, 122] . In North America, Eptesicus fuscus, is one of the commonest rabid bat species, followed by Myostis spp. (e.g. M. lucifugus), Lasionycteris noctivagans, Lasiurus spp. (e.g. L. cinereus, L. borealis, L. intermedius, L. seminolus), Tadarida brasiliensis and Pipistrellus subflavus [117, 118, 123, 124] . Pteropus bats have been found to be infected by rabies virus in India [125] . Rabid bats may become sick, though most of the animals will remain healthy and asymptomatic. Transmission of rabies virus among bats likely occurs orally and through biting. Although aerosolisation of bat rabies virus in saliva or excreta has been postulated as a possible means of transmission, humans are mainly infected via percutaneous or mucosal contacts with infected bats. European bat lyssaviruses 1 and 2 are found in a number of European countries including Denmark, Finland, France, Germany, Hungary, Lithuania, the Netherlands, Poland, the Russian Federation, Slovakia, Spain, Switzerland, Ukraine and the United Kingdom [126] . European bat lyssaviruses are generally restricted to bats. They only rarely infect other mammalian species including one stone marten (Martes foina), two sheep, and three human beings [127] . One of the three human infections was due to European bat lyssavirus 1 (1985, Ukraine) and two due to European bat lyssavirus 2 (1985, diagnosed [126] . A fouth case occurred in 1977 in Ukraine and the isolate was believed to be European bat lyssavirus 1, but the strain was not genetically typed [128] . European bat lyssavirus 1 is the commoner of the two types and is mainly associated with Eptesicus serotinus [19, 129, 130, 131] . Asymptomatic infection of a zoo bat Rousettus aegyptiacus has been reported [132] . The sole reservoirs of European bat lyssavirus 2 to date are the Myotis bats (M. daubentonii and M. dasycneme) [128, 130, 133, 134] . Australian bat lyssavirus was first recovered from Pteropus alecto in New South Wales, Australia, and later also found in other bat species [135] . Two fatal human infections in Australia have been reported, both had sustained bat-related injuries prior to onset of disease [136, 137] . Post-exposure prophylaxis with rabies vaccine and immunoglobulin were given in subsequent potential exposures to Australian bat lyssavirus and no human cases have ever been described [138, 139] . In contrast to other bat-associated pathogens, Australian bat lyssavirus can cause encephalitis in infected bats [138, 139] . Surveillance using immunofluorescent staining of bat brains showed that healthy flying foxes have a lower positive rate than sick and injured animals ( < 1% vs. 6.5%, respectively) [139] . Bat-associated lyssaviruses have also been increasingly recognised in Asian countries. In India, the flying fox Pteropus policephalus was found to be infected by rabies virus using direct immunofluorescent staining of brain tissue [125] . In the Philippines, no lyssaviruses were detected in the brains of 821 bats, but 9.5% of the bats in six species possessed neutralising antibodies against Australian bat lyssavirus, especially among Miniopterus schreibersi [140] . In Cambodia, neutralising antibodies were detected against a number of lyssaviruses, including rabies virus, European bat lyssavirus 1, Australian bat lyssavirus, and Lagos bat virus [141] . A similar picture was seen in Thailand in which serological evidence of infection by Aravan, Khujand, Irkit and Australian bat lyssavirus was found in 3.8% (all from Pteropus lylei and Hipposideros armiger) of the bat samples [142] . Neutralising antibodies against Aravan and Khujand viruses were detected in three Pteropus giganteus samples in Bangladesh [143] . In these latter four Asian surveys, no lyssaviruses were detected in the brains of the bats by direct immunofluorescence and/or mouse inoculation. Although serological assays per se may be complicated by cross-reactions between different lyssaviruses, the studies do raise the possibility that these lyssavirus species may have a broader geographical distribution than previously described. In addition to the natural route of zoonotic transmission of rabies virus to humans, organ transplantation has in recent years been recognised as an iatrogenic route of transmission. The first report of such transmission occurred in Texas in 2004 when four recipients received organs from a donor who died of subarachnoid haemorrhage. The organs transplanted included iliac artery, liver and two kidneys. All four recipients subsequently developed rabies encephalitis within 30 days of infection and all succumbed to the infection. In retrospect, the donor was found to have been bitten by a bat before his death [18] . In 2005, a similar incident occurred in Germany. A 26-year old woman visited India in October in 2004 and died in Germany in late 2004. Three recipients received lungs, combined kidney/pancreas and kidney, and all of them died of rabies. Subsequent examination of the donor's brain showed typical pathological features of rabies including Negri bodies and positive immunohistochemical staining [144] . The three recipients of liver and cornea remained asymptomatic as of February 2005. Such incidents highlight the importance of excluding rare and exotic diseases in potential organ donors and the novel iatrogenic routes of transmitting batassociated pathogens. The prognosis of human rabies after the onset of symptoms is extremely poor with almost 100% mortality. The only useful specific post-exposure management, apart from local wound cleansing, is the use of rabies vaccine and immunoglobulin (local infiltration and systemic injection). Although no useful antiviral agent is available to date, one recent report showed that a potent anti-excitotoxic therapy led to the survival of a patient. A 15-year old girl who sustained a laceration from a bat developed clinical rabies without post-exposure prophylaxis. A regimen of high doses of midazolam, barbiturates, diazepam and ketamine, together with ribavirin and amantadine, appeared to tide over the acute phase of infection before the development of immunity, and the patient eventually regained consciousness, albeit with some neurological deficits [145] . The currently available [148] . The urban cycle of chikungunya is maintained by human-to-human transmission via mosquitoes (mainly Aedes aegypti but also Aedes albopictus), while a rural cycle is maintained between non-human primates. Bats have occasionally been found to be infected by chikungunya virus, though the potential of the bat for further transmission requires confirmation [149] . The reservoir of eastern equine encephalitis virus is primarily birds, but other animals such as rodents, marsupials, and bats are often infected in Latin America. Serological evidence for bat infection by eastern equine encephalitis virus was documented in Trinidad and Guatemala [23, 150] . Venezualan equine encephalitis virus has a broad host range including rodents, bats, horses, sheep, dogs and birds, but the main sylvatic reservoir is believed to be rodents. Horses are efficient amplifying hosts and human infections and outbreaks mostly resulted from equine infections [151] . Several species of bats have serological evidence of infection by the Venezualan equine encephalitis virus in Guatemala and positive viral cultures have been obtained from Carollia perspicillata, Desmodus rotundus and Uroderma bilobatum [152, 153, 154] . Bats might have been infected through mosquito bites, ingesting infected mosquitoes, or feeding on the blood of viraemic animals in the case of vampire bats. They may play a role in geographical dispersal of the virus and as an alternative reservoir for the virus [151, 152] . The flying foxes (Pteropus poliocephalus and Pteropus pscapulatus) are considered to be unimportant reservoirs of Ross River virus in one study [155] . To prevent transmission of bat-associated zoonoses to humans, the key is to gain a better understanding of the ecology of bats and the range of infectious agents associated with them. Surveillance of bat-associated viruses is based on passive surveillance in many countries of the world, in part because of the conservation status of bats. Passive surveillance usually targets towards sick, injured or dead animals, which may bias the results. To better understand the prevalence of old and new pathogens, active surveillance is obviously preferable. The primary preventive measure against batassociated infections is conservation of the natural habitats of bats. pig population and subsequently to humans serves as the most recent example. In Latin America, outbreaks of human rabies from vampire bats almost always followed the destruction of the bats' habitats, forcing the animals to feed on humans and livestock. In situations where exposure to bats is unavoidable, measures to reduce contact between bats and humans may be considered, such as bat-proofing of houses in the endemic areas and the use of personal protective equipment for workers and scientists in frequent contact with bats. In Latin America, application of anticoagulants to bats and cattle have been utilised to control the vampire bat population. This approach, however, has not achieved much success and may have adverse effects on the ecology of bats or other fauna and flora. With the excellent results from the use of oral rabies vaccine to control rabies in wildlife in Europe and North America, oral vaccines against bat rabies were being tested in vampire bats with satisfactory experimental results [156, 157] . Pre-and post-exposure prophylaxis using rabies vaccines appears to be effective against genotypes of lyssavirus that are known to cause human infections despite the antigenic differences from classical rabies virus. Pre-exposure vaccination is especially important for persons with constant exposure to bats such as bat biologists. The value of vaccines against other bat-associated viruses remains unknown mainly because of the lack of effective vaccines (e.g. against Henipavirus) or the uncertain role of bats in the transmission of infections (e.g. Japanese encephalitis virus). As depicted in the Supplementary Table, the known and potential viral pathogens are distributed in numerous families of bats. However, one thing that stands out from the table is that most of the important pathogens are often associated with four families: Pteropodidae, Molossidae, Phyllostomidae and Vespertilionidae. This could be due to a greater biodiversity of these species, better known biological features, or indeed, a co-evolution of the main pathogens with specific bat species. The understanding of the association between viruses and bat families could also be useful to predict the likelihood of transmission or dissemination to humans. For example, many of the flying foxes (Pteropodidae) are relatively large animals and, being strong flyers, they could reach relatively long distances from their roosting sites. Being frugivorous bats, Pteropus spp. often encroach onto fruit plantations and hence may bring them into closer contacts with humans. The big brown bat (Eptesicus fuscus, Vespertilionidae), an insectivorous species, likewise is relatively close to humans in that it often roosts in buildings and man-made structures in cities or rural areas. The serotine bat (Eptesicus serotinus) is equally at home in buildings. The carriage of lyssaviruses by these bats is an obvious concern to man. Although bats are currently not considered the most dominant group of mammals giving rise to emerging or re-emerging infections in humans, this could reflect a relative paucity of studies on this important group of mammals [2] . In the last decade, a number of new infections have caused outbreaks in different parts of the world. Some of these causative agents, such as the henipavirus and SARS coronavirus, have been found to have a reservoir in bats. Bats have also been proven to be a natural host for enigmatic viruses such as the Ebola virus and their significance in the natural ecology of filoviruses remains to be uncovered. It is interesting to note that many of the bat-associated pathogens do not cause any clinicopathological damage to the bats, and coupling with the longevity and migratory habits of the bats, make this animal a potentially important reservoir for emerging and re-emerging infections. It can be seen from the above checklist of viruses that very often the geographical distribution and host range of many bat-associated infections broadens as more surveillance was performed in different parts of the world and when more bat species were studied. Examples include coronaviruses, Henipavirus and lyssaviruses. In lyssaviruses, for example surveys of South and Southeast Asian bats showed that Australian bat lyssavirus and the Eurasian lyssaviruses may indeed have a broader distribution than previously known. Many of the new viruses were discovered in bats following recent human or animal outbreaks of infectious diseases and enhanced surveillance in wild animals. A variety of coronaviruses were discovered in southern China after the SARS epidemic in diverse bat species. The outbreak of Nipah encephalitis in Malaysia and the association of the virus with flying foxes prompted enhanced surveillance of bats. This led to the discovery of the new Tioman and Pulau viruses. The finding of these new viruses is the result of a systematic and targeted surveillance of bats, which underscores the importance of such an approach in the future study of zoonotic agents. It is therefore hardly surprising to predict that more viruses will be discovered in bats in the future. However, one should not forget that the mere isolation of a virus from bats does not necessarily implicate an active role of bats in the natural ecology of the microbe. Whether bats are incidental and dead-end hosts or actively support the maintenance of the viruses need to be investigated in more vigorous studies. Anthropogenic and natural changes in the environment due to deforestation, alteration of habitats of bats, alterations in animal diversity, and climatic events may shift the ecology of bats and expose humans to new pathogens. 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type 2 from a Daubenton's bat in the United Kingdom Encephalitis caused by a Lyssavirus in fruit bats in Australia A human case of encephalitis due to a lyssavirus recently identified in fruit bats Emerging viral diseases: an Australian perspective Potential exposure to Australian bat lyssavirus Defining the risk of human exposure to Australian bat lyssavirus through potential non-bat animal infection Serologic evidence of Lyssavirus infections among bats, the Philippines Serologic evidence of lyssavirus infection in bats Survey for bat lyssaviruses Lyssavirus surveillance in bats E-alert 18 February: cases of rabies in Germany following organ transplantation Survival after treatment of rabies with induction of coma Rabies human diploid cell vaccine elicits cross-neutralising and cross-protecting immune responses against European and Australian bat lyssaviruses Efficacy of rabies biologics against new lyssaviruses from Eurasia Chikungunya and Dengue in the south west Indian Ocean Vectors of Chikungunya virus in Senegal: current data and transmission cycles Serologic survey of neotropical bats in Guatemala for virus antibodies Venezuelan equine encephalitis Venezuelan encephalitis virus infection in neotropical bats. I. Natural infection in a Guatemalan enzootic focus Epidemic strain of Venezuelan equine encephalomyelitis virus from a vampire bat captured in Oaxaca Identification of a new Venezuelan equine encephalitis virus from Brazil Investigation of gray-headed flying foxes (Pteropus poliocephalus) (Megachiroptera: Pteropodidae) and mosquitoes in the ecology of Ross River virus in Australia Indirect oral immunization of captive vampires, Desmodus rotundus Experimental rabies infection and oral vaccination in vampire bats (Desmodus rotundus) Ultrastructural, antigenic and physicochemical characterization of the Mojuí dos Campos (Bunyavirus) isolated from bat in the Brazilian Amazon region