10.3.1 Rhabdoviruses Rabies virus (RABV) is the longest and best-known member of the genus Lyssavirus (family Rhabdoviridae) and still one of the most significant zoonoses known from bats (recent reviews include: Banyard et al. 2011 2014 2014 10.1 2009 2014 Geographical distribution Lyssavirus species Phylogroup Bat species most commonly associated with lyssavirus infection Common name Known human cases The Americas Rabies virus (RABV) I Eptesicus fuscus Big brown bat Yes Tadarida brasiliensis Mexican/Brazilian free-tail bat Lasionycteris noctivagens Silver-haired bat Perimyotis subflavus Tri-coloured bat Desmodus rotundus Vampire bat Eurasia European bat lyssavirus type 1 (EBLV-1) I Eptesicus serotinus Serotine bat Yes European bat lyssavirus type 2 (EBLV-2) I Myotis daubentonii Daubenton’s bat Yes Bokeloh bat lyssavirus (BBLV) I Myotis nattereri Natterer’s bat No Aravan virus (ARAV) I Myotis blythi Lesser mouse-eared bat No Irkut virus (IRKV) I Murina leucogaster Greater tube-nosed bat Yes Khujand virus (KHUV) I Myotis mystacinus Whiskered bat No West Caucasian bat virus (WCBV) NAa Miniopterus schreibersii Common bent-wing bat No Lleida bat lyssavirus (LLEBV) NAa Miniopterus schreibersii Common bent-wing bat No Africa Duvenhage virus (DUVV) I Miniopterus sp? Undefined Yes Nycteris thebaica Egyptian slit-faced bat Lagos bat virus (LBV) II Eidolon helvum Straw-coloured fruit bat No Rousettus aegyptiacus Egyptian fruit bat Epomorphorus wahlbergi Wahlberg’s epauletted fruit bat Mokola virus (MOKV) II not detected Yes Shimoni bat virus (SHIBV) II Hipposideros commersoni Commerson’s leaf-nosed bat No Ikoma virus (IKOV) NAa not detected No Australasia Australian bat lyssavirus (ABLV) I Pteropus scapulatus b Little red flying fox Yes Saccolaimus flaviventris Yellow-bellied sheath-tailed bat Pteropus alecto Black flying fox (RABV) is the longest and best-known member of the genus Lyssavirus (family Rhabdoviridae) and still one of the most significant zoonoses known from bats (recent reviews include: Banyard et al.; Banyard et al.and Kuzmin). The genus is rapidly expanding, with 14 of the currently recognised species (plus another known from genetic material only), and all but two (Mokola and Ikoma viruses) having been isolated from bats (Table). Lyssaviruses spill over directly from bats to domestic animals, other wildlife and humans, or indirectly to humans via these other species. All lyssaviruses are potentially neurotropic, meaning that the virus infects nerve cells and replicates in the brain, resulting in clinical signs consistent with classical rabies (Schnell et al.). Although isolated from a variety of tissues and body fluids in the late stages of infection, the predominant route of transmission is via saliva (mostly via biting; Kuzmin). Lyssaviruses can be divided into two distinct “phylogroups” (Badrane et al. 2001, Table 10.1), reflecting biological and genetic differences, and they are distributed globally in bats. Classical rabies virus occurs in bats across North, Central and South America (Messenger et al. 2003; Banyard et al. 2011) and was first associated with vampire bats following an outbreak in cattle in South America in 1911 (Carini 1911). It is reported most frequently in the common vampire bat ( Desmodus rotundus ; Kuzmin et al. 2011a), which has a wide distribution across Mexico, Central America, and South America. Bites from this species appear to be responsible for the majority of human and domestic animal rabies infections of bat origin in South and Central America, with increased prey availability via expansion of livestock into new areas across the region hypothesised to be contributing to increasing incidences (Schneider et al. 2009; Ruiz and Chávez 2010). In Canada and the USA, 51 cases of human rabies transmitted by non-haematophagous bats were recognised or inferred between 1951 and 2006 (mostly silver-haired bats ( Lasionycteris noctivagans ), eastern pipistrelle bats ( Perimyotis subflavus ) and Brazilian/Mexican free-tailed bats ( Tadarida brasiliensis )) (Constantine and Blehert 2009; Banyard et al. 2011). However, across the Americas, only 15 % of human rabies cases between 1993 and 2002 were reported as resulting from encounters with bats (Belotto et al. 2005). Reported antibody prevalences against RABV in D. rotundus include 3–28 % in Peru (Streicker et al. 2012) and 12 % in Brazil (Almeida et al. 2011). Depending on the year, location and species, prevalence in other bats varies from relatively low 2 % in T. brasiliensis in New Mexico (Steece and Altenbach 1989) and 2.5 % in the little brown bats ( Myotis lucifugus ) in New York (Trimarchi and Debbie 1977), to 58 % in Seba’s short-tailed bat ( Carollia perspicillata ) in Peru (Salmón-Mulanovich et al. 2009) and 67 % in T. brasiliensis in Texas (Baer and Smith 1991). As with other lyssaviruses discussed below, the potential for high antibody prevalences in bat populations and infrequent reports of mortality suggest that many individuals exposed to the virus survive, contrary to the overwhelmingly lethal nature of lyssavirus infections in other mammalian species (reviewed in Banyard et al. 2011). The mechanisms for this remain unclear. Seven bat lyssaviruses have been isolated in Eurasia (Table 10.1). European bat lyssavirus type 1 and type 2 (EBLV-1 and EBLV-2; Bourhy et al. 1992) are the most widely recognised and studied. Five fatal cases of human infections with EBLV have so far been reported, three from EBLV-1 (Roine et al. 1988; Selimov et al. 1989; Botvinkin et al. 2005) and two from EBLV-2 (Lumio et al. 1986; Fooks et al. 2003; Nathwani et al. 2003). Spillover of EBLV-1 into other mammals has also been observed, but rarely, with examples including zoo bats (Rønsholt et al. 1998), sheep (Tjørnehøj et al. 2006), domestic cats (Dacheux et al. 2009) and a stone marten (Müller et al. 2004). While EBLV-1 and EBLV-2 have been detected in a range of bat species (reviewed in Schatz et al. 2013), they are most frequently associated with serotine bats ( Eptesicus serotinus ) and Daubenton’s bat ( Myotis daubentonii ), respectively. The dynamics of EBLV infections in their natural hosts is poorly understood, but banding and recapture data and the frequent capture of apparently healthy bats with antibodies against EBLV suggest that many bats survive infection (Serra-Cobo et al. 2002; Amengual et al. 2007; Schatz et al. 2013). In cases where bats develop clinical symptoms of EBLV infection, the affected individuals are often unable to fly, are generally weak and show abnormal behaviour, including attempts to bite (Banyard et al. 2011). Experimental studies suggest that variable development of clinical signs may be related to inoculation route and dose (reviewed in Banyard et al. 2011). Comparatively, little is known about the remaining Eurasian bat lyssaviruses, which have each been isolated from bats only once: West Caucasian bat virus (WCBV, Botvinkin et al. 2003), Bokeloh bat lyssavirus (BBLV, Freuling et al. 2011), Aravan virus (ARAV, Kuzmin et al. 1991), Irkut virus (IRKV, Botvinkin et al. 2003) and Khujand virus (KHUV, Kuzmin et al. 2001), or is only known from partial genetic sequence data (Lleida virus, Ceballos et al. 2013, Table 10.1). Of these, only IRKV has been detected in other mammals (a human who developed rabies after a bat bite, Leonova et al. 2009). WCBV appears to have a large geographical range. It was isolated from Miniopterus schreibersii in Russia, but cross-reactive antibodies have also been detected in Miniopterus bats in Kenya (Kuzmin et al. 2008a). The relatively wide distribution and migratory behaviour of Miniopterus spp. may facilitate cross-continental transmission of this virus. Alternatively, given the close relationship between WCBV and Ikoma virus (IKOV), which was recently isolated in neighbouring Tanzania, the serological findings from Kenya could in fact indicate exposure to IKOV or another related lyssavirus rather than WCBV (Marston et al. 2012; Horton et al. 2014). Similarly, serological surveys have detected antibodies against ARAV virus and KHUV virus in Indian flying foxes ( Pteropus giganteus ) from Bangladesh (Kuzmin et al. 2006), and ARAV, KHUV, IRKV or Australian bat lyssavirus in Lyle’s flying foxes (P. lylei ) and dawn bats ( Eonycteris spelaea ) from Thailand (Lumlertdacha et al. 2005). Yet, given the limited lyssavirus surveillance in bats performed to date in this region and that individuals in these studies tested positive to multiple viruses, these results likely represent cross-reactivity of serological assays to unknown lyssaviruses. Africa also hosts significant lyssavirus diversity, with five species identified, though only three of these isolated from bats to date (Table 10.1). Duvenhage virus (DUVV, Meredith et al. 1971) is the only phylogroup I lyssavirus in Africa and is more closely related to RABV, ABLV and the majority of the European species than other known African lyssaviruses. Since it was first isolated from a human in 1970, two more fatal human infections of DUVV have been reported, one in South Africa in 2006 (Paweska et al. 2006) and one from the Netherlands in 2007 after obtaining the infection in Kenya (van Thiel et al. 2008). DUVV has been isolated from bats twice, once from a presumed M. schreibersii bat in South Africa and once from an Egyptian slit-faced bat ( Nycteris thebaica ) in Zimbabwe (Schneider et al. 1985; Foggin 1988; Paweska et al. 2006). No further information is so far available on this apparently rare African lyssavirus. In contrast, Lagos bat virus (LBV) is the most widely detected lyssavirus in Africa (Banyard et al. 2011). In 1956, this virus was first isolated from a straw-coloured fruit bat ( Eidolon helvum ; Boulger and Porterfield 1958). Since then, the virus has been isolated and neutralising antibodies detected in a variety of fruit bat species, one insectivorous bat species, domestic cats, domestic dogs and a water mongoose, but not in humans (reviewed in Banyard et al. 2011). E. helvum and Rousettus aegyptiacus are likely primary reservoir hosts for LBV, with seroprevalences ranging from 6 to 80 % and 29 to 46 %, respectively, depending on the region (Hayman et al. 2008, 2012; Kuzmin et al. 2008b; Dzikwi et al. 2010; Peel et al. 2013). LBV has been isolated from healthy, rabid and dead bats (reviewed in Banyard et al. 2011), but longitudinal studies in Ghana (Hayman et al. 2012) and surveys across continental Africa (Peel et al. 2010, 2013) suggest widespread exposure, no difference in survival between seropositive and seronegative E. helvum, and viral persistence in very small, isolated island populations. Early infection experiments with LBV suggested that LBV and other phylogroup II viruses were less pathogenic than other lyssaviruses (Boulger and Porterfield 1958; Badrane et al. 2001). However, recent experimental infections indicated the potential for comparable mortality between LBV and RABV and indicated that significant differences might instead exist between different LBV isolates (Kuzmin et al. 2010; Markotter et al. 2009). Of the other African lyssaviruses, only Shimoni bat virus (SHIBV) has been detected in bats (Commerson’s leaf-nosed bat ( Hipposideros commersoni ) in Kenya; Kuzmin et al. 2010) and only Mokola virus (MOKV) has been detected in humans (on two occasions in Nigeria, Familusi and Moore 1972; Familusi et al. 1972). MOKV has also been isolated from cats and small wild mammals, however, the natural reservoir host is unknown (Nel 2001). Ikoma virus was isolated from a rabid African civet ( Civettictis civetta ), but it is believed that the civet was a spillover host and the true reservoir host is yet to be identified (Horton et al. 2014). The only lyssavirus detected in Australia to date— Australian bat lyssavirus (ABLV)—has two known lineages, one circulating in flying foxes and one in an insectivorous bat (Fraser et al. 1996; Gould et al. 2002; Warrilow 2005). In 1996, shortly after ABLV was first isolated from a black flying fox (P. alecto ) that was unable to fly (Fraser et al. 1996), a 39-year-old woman died of clinical rabies after being bitten by a yellow-bellied sheath-tail bat ( Saccolaimus flaviventris ; Gould et al. 2002). Two subsequent human cases have been identified, a woman who died in 1998, 27 months after being bitten by a flying fox (Hanna et al. 2000), and a child who died in 2014 after being scratched by a flying fox (Francis et al. 2014). Experimental infection of grey-headed flying foxes (P. poliocephalus ) with ABLV resulted in clinical signs of weakness, trembling and limb paralysis in three out of ten individuals (McColl et al. 2002). As with other bat lyssaviruses, a small proportion of ABLV-positive bats succumb to encephalitis-like symptoms (Hooper et al. 1997), yet serological tests show a high prevalence of antibodies in populations of surviving bats (McColl et al. 2000).

10.3.2 Paramyxoviruses The most notable viruses from the Paramyxoviridae family in bats are those of the genus Henipavirus , which are the subject of many reviews (e.g. Halpin and Rota 2015; Smith and Wang 2013, Luby and Gurley 2012; Clayton et al. 2013; Middleton and Weingartl 2012; Field and Kung 2011). The first recognised henipavirus, Hendra virus (HeV), was first detected during an outbreak of infectious respiratory disease in horses and then humans in Hendra, Australia, in 1994 (Murray et al. 1995). Ultimately, 13 of 20 infected horses died or were euthanised, and of two humans working closely with horses who became infected, one died from acute pneumonia (Murray et al. 1995; Plowright et al. 2015). This spillover was preceded a month earlier by another involving two horses and one human over 800 km away in Mackay, but which went unrecognised until 1995 (Rogers et al. 1996; O’Sullivan et al. 1997). An initial serological survey of 46 wildlife species (excluding bats) failed to identify a reservoir host; however, serological evidence of HeV infection was later identified in all four species of flying foxes native to Australia (Young et al. 1996). Virus isolation (Halpin et al. 2000) and experimental studies (Halpin et al. 2011) have confirmed pteropodid bats as reservoir hosts for henipaviruses (with a lack of clinical signs), with evidence that black (P. alecto ) and spectacled flying foxes (P. conspicillatus ) are the main reservoir species for HeV (Smith et al. 2014; Goldspink et al. 2015). Because HeV is frequently detected in the urine of wild flying foxes (Smith et al. 2014), the predominant transmission route to horses is likely via material recently contaminated with bat urine (e.g. pastures) or via direct transmission (Martin et al. 2015). Recognised spillover events from bats to horses occurred sporadically from 1994 to 2004 and annually since 2006, with five spillover events resulting in ongoing transmission to humans in close contact with horses (a total of seven human cases and four deaths; Field et al. 2010). Spillover events are spatiotemporally clustered, occurring year-round in the northern tropics, but seasonally clustered in winter with a peak in July in subtropical regions (Plowright et al. 2015). The relative importance of various hypothesised drivers of HeV dynamics in bats and subsequent spillover to horses is still unclear (Plowright et al. 2015). Nipah virus (NiV), the second henipavirus to be recognised, was first isolated in 1999 from pigs and encephalitic pig workers in Malaysia (Center of Disease Control and Prevention 1999). NiV spillover has not been observed since this time in Malaysia; however, annual seasonal outbreaks with high case fatality (average 73 %) have occurred in people in Bangladesh since 2001 (Hsu et al. 2004; Luby et al. 2009; Luby and Gurley 2012), with occasional spillover also occurring in neighbouring India (Chadha et al. 2006; Harit et al. 2006). Due to the close relatedness of HeV and NiV, fruit bats were targeted, and serological evidence quickly identified them to be the natural reservoir of NiV (Enserink 2000; Yob et al. 2001). This was subsequently supported by isolation of NiV from the urine of P. hypomelanus (Chua et al. 2002a), P. vampyrus (Rahman et al. 2010) and P. lylei (Reynes et al. 2005), and seroconversion in the absence of clinical signs following experimental infections in P. vampyrus (Halpin et al. 2011). Antibodies against NiV and NiV-related viruses have now been detected in a variety of bat species (including non-pteropid bats) across a wide geographical area (summarised in Breed et al. 2013). NiV transmission to humans appears to occur via a wider variety of routes compared with HeV. Infection of domestic animal intermediate hosts (via consumption of saliva- or urine- contaminated partially eaten fruits or raw date palm sap) has been implicated as a source of human infections in both Malaysia and Bangladesh (Chua et al. 2002b; Chowdhury et al. 2014). In Malaysia, human infections resulted from direct contacts with infected pigs (Chua et al. 1999; Paton et al. 1999; Parashar et al. 2000), whereas in Bangladesh, transmission to humans regularly occurs via consumption of contaminated date palm sap (Luby et al. 2006; Rahman et al. 2012) or directly from human to human (e.g. via nursing sick individuals or preparation for burial; Hughes et al. 2009). The risk of direct human infection with NiV from bats is considered to be lower than horizontal transmission once the virus enters the human population (Gurley et al. 2007; Luby et al. 2009; Chong et al. 2003). A third henipavirus, Cedar Virus (Marsh et al. 2012), has been isolated from urine collected under a mixed P. alecto /P. scapulatus roost in Australia. In contrast to HeV and NiV, however, it appears to be of low pathogenicity and failed to induce clinical signs in experimentally infected laboratory animal species (Marsh et al. 2012). Serological evidence from South-East Asia and Australasia (Breed et al. 2013) and the wide diversity of paramyxovirus sequences detected in Australia (Vidgen et al. 2015) suggest more henipaviruses are yet to be found. Additionally, although henipaviruses were long thought to be restricted to Asia and Australia, antibodies cross-reactive to HeV and NiV were detected in Madagascar in 2007, suggesting a potentially wider geographical distribution of henipa-related paramyxoviruses (Iehlé et al. 2007). This was supported by serological findings and molecular detection of henipa- or henipa-like viruses in mainland Africa and its offshore islands (Hayman et al. 2008, 2012; Peel et al. 2010, 2013; Drexler et al. 2012). Indeed, a recent serological study indicates that these viruses are also occasionally transmitted to humans in Africa (Pernet et al. 2014), though no African henipavirus has been isolated to date. Viruses from the paramyxovirus genus Rubulavirus (a genus which includes the human mumps virus) have also been frequently detected in bats (Barr et al. 2015). Menangle virus was isolated from pigs following the birth of unusually high numbers of stillborn and deformed piglets in Australia (Philbey et al. 1998). Two piggery personnel had neutralising antibodies against Menangle virus after having recovered from an unexplained febrile illness (Philbey et al. 1998). Flying fox colonies roosting in close proximity to the piggeries were a suspected source of infection for pigs, with subsequent transmission to humans (Philbey et al. 1998). This was supported by serological evidence from P. poliocephalus , P. alecto and P. conspicillatus , and recent virus isolation from P. alecto (Barr et al. 2012). Other isolated bat rubulaviruses with unknown or limited understanding of their zoonotic potential include Tioman virus from Malaysia (Chua et al. 2001), Tuhokovirus 1, 2 and 3 from China (Lau et al. 2010), Achimota virus 1 and 2 from Ghana (Baker et al. 2013c) and Hervey, Grove, Teviot and Yeppoon paramyxoviruses from Australia (Barr et al. 2015). Neutralising antibodies to Tioman virus and Achimota viruses have been detected in humans, suggesting previous exposure and infection with the virus (Yaiw et al. 2007; Baker et al. 2013c). Pigs experimentally infected with Tioman virus produced neutralising antibodies and excreted virus in saliva, but were either asymptomatic or developed only a fever (Yaiw et al. 2008). Undetected infection in pigs could therefore facilitate transmission to humans. Finally, viral fragments related to rubulaviruses and the proposed genus Jeilongvirus have also been detected outside the range of fruit bats, in European insectivorous bat species (Kurth et al. 2012). However, nothing is yet known about the relevance of these viruses as potentially zoonotic threats to humans.

10.3.3 Coronaviruses Bat coronaviruses were first identified from species of the genus Miniopterus (Poon et al. 2005), however, with unknown zoonotic potential. The most prominent coronavirus, the one causing severe acute respiratory syndrome ( SARS ), was followed by a pandemic spread in humans after the first outbreak in China in 2002 (Rota et al. 2003). Soon after the outbreak, the virus was detected in masked palm civet ( Paguma larvata ) and raccoon dogs (Nyctereutes procyonoides) in a market in Guangdong Province, where SARS was first reported (Guan et al. 2003). A survey of common wildlife species in the area identified bats to be the natural reservoir of SARS coronavirus, with viruses from bats showing greater genetic diversity than the ones isolated from other species, including humans (Li et al. 2005). Bats can regularly be found in markets in China, which makes direct transmission of the virus from bats to humans likely (Li et al. 2005). The followed pandemic spread with 8096 confirmed cases of which 774 were fatal can be accounted to rapid interindividual transmission of the virus once it entered the human population (World Health Organization 2003). Outside Asia, SARS-like coronaviruses have been detected in the lesser horseshoe bat ( Rhinolophus hipposideros) from Europe (Rihtarič et al. 2010), in Chaerephon sp. from Kenya (Tong et al. 2009) and in Hipposideros commersoni from Nigeria (Quan et al. 2010). Antibodies against SARS coronavirus are present in various African bat species (Müller et al. 2007). As with many newly detected viruses, their potential threat as a zoonotic disease is yet unclear. Since the outbreak of SARS in Asia has been traced to bats as natural hosts of the virus, the same was suspected to be the case for Middle East respiratory syndrome ( MERS ), an infection that has been occasionally spreading among humans of the Arabian peninsula since 2012 (Zaki et al. 2012). Most human infections have been traced down to close contacts with dromedary camels ( Camelus dromedarius ), which carry a virus with a similar genome organisation as human MERS (Hemida et al. 2014). There is at least one report of direct transmission of the virus from camels to humans via contact with infected animals (Memish et al. 2014). However, a small fragment of a coronavirus PCRed from an Egyptian tomb bat ( Taphozous perforatus ) showed 100 % nucleotide identity to virus from the human index case-patient of MERS, suggesting that this species may be one of the putative natural reservoirs of the virus (Memish et al. 2013). Bat-derived MERS virus has been shown to be able to use human receptors and thus could potentially infect human cells (Yang et al. 2014). However, given the generally low prevalence of MERS virus in bat populations, a direct spillover from bats to humans is unlikely, and transmission probably happens mainly via camels as intermediate hosts (Memish et al. 2013). In fact, no other bat has yet been found to carry MERS virus since the one reported by Memish and colleagues in 2013. The intensified search for viruses in bats worldwide has led to the detection of coronaviruses other than SARS and MERS, whose potential to be or become zoonotic has yet to be investigated (Woo et al. 2006; Tang et al. 2006; Dominguez et al. 2007; Carrington et al. 2008; Brandão et al. 2008; Misra et al. 2009; Pfefferle et al. 2009; Donaldson et al. 2010; Watanabe et al. 2010; Drexler et al. 2010; Falcón et al. 2011; Annan et al. 2013; Ge et al. 2013; Anthony et al. 2013; Ithete et al. 2013). No clinical symptoms associated with infections with SARS-like and other coronaviruses have yet been described for bats.