Addendum to our submission of 7th Dec: Terms of Reference

I would like to address the following Terms of Reference of the Committee:

• Strategic approach to managing the species at a regional level.

The public health issues outlined hereunder suggest that both Federal and State authorities need to co-ordinate a strategic national approach to species management as a matter of priority.

Risks to Public health and Agriculture:

We currently have flying-fox roosts in some 56 regional centres and city suburbs spread over 3,000km of the East coast, that have given their local council cause to get permits to carry out management activity. Some of these roosts are seasonal, some permanent. We tolerate the existence of these bio-concentrations on the basis that flying-fox populations are ‘critical’ to the health of our rain forests and native bush. They may very well be important, perhaps critical, but in either case it is evident that the health and survival of the species and benefit to our bush, is NOT dependent on camps or roosts being located and tolerated in residential or suburban areas.

As a community we would quite reasonably prohibit the establishment of a poultry farm with say 20,000 birds in the middle of a regional CBD or a Sydney suburb, citing noise, smell, disease risk etc. However recently a bio-concentration of around 300,000 animals was allowed to build up in a small regional town, Batemans Bay, before effective dispersal action was taken.

These animals are known disease carriers and in recent years have caused human fatalities in from both ABLV (Australian Bat Lyssavirus) and Hendra. Anecdotal evidence from Batemans Bay suggests a markedly higher incidence of lung related to the recent invasion of GHFF, particularly amongst the elderly.

Known diseases carried by flying-fox populations:

• Hendra • Australian Bat Lyssavirus (ABLV) • Menangle virus • (with a high incidence in Cairns corresponding to a high FF concentration) •

If these animals (in conjunction with mosquitoes as happens with ) were to become a for any other contagious disease (think Avian flu or Zika), then the bulk of our East coast population and possibly our agricultural industry would be at increased, and I submit, unacceptable risk.

(Attachment: Journal of Applied Microbiology 2003, 94, 59S–69S Managing emerging diseases borne by fruit bats (flying foxes), with particular reference to and Australian bat lyssavirus.)

Journal of Applied Microbiology 2003, 94, 59S–69S

Managing emerging diseases borne by fruit bats (flying foxes), with particular reference to henipaviruses and Australian bat lyssavirus

J.S. Mackenzie1, H.E. Field2 and K.J. Guyatt1 1Department of Microbiology and Parasitology, School of Molecular and Microbial Sciences, University of and 2Department of Primary Industries, Animal Research Institute, Moorooka, , Queensland, Australia

1. Summary, 59S 5. Other associated with fruit bats, 63S 2. Introduction, 59S 6. Management strategies, 63S 3. Emergence of three new viruses in Australia, 60S 6.1 Current strategies, 64S 3.1 , 60S 6.1.1 Hendra and Nipah viruses, 64S 3.2 Australian Bat Lyssavirus (ABLV), 61S 6.1.2 Menangle virus, 64S 3.3 Menangle virus, 61S 6.1.3 Australian bat lyssavirus, 64S 4. The emergence of similar viruses in Southeast Asia, 62S 6.2 Future strategies, 65S 4.1 , 62S 6.2.1 Can a vaccination strategy be developed to 4.2 Tioman virus, 63S control emerging viral diseases in flying 4.3 Australian bat lyssavirus, 63S foxes? 65S 4.4 Comments on the possible emergence of other 7. Acknowledgements, 66S related viruses, 63S 8. References, 66S

to flying foxes, and better disease recognition and diagnosis, 1. SUMMARY and for ABLV specifically, the use of vaccine for pre- Since 1994, a number of novel viruses have been described and post-exposure prophylaxis. Finally, an intriguing and from bats in Australia and Malaysia, particularly from fruit long-term strategy is that of wildlife immunization through bats belonging to the (flying foxes), and it is plant-derived vaccination. probable that related viruses will be found in other countries across the geographical range of other members of the 2. INTRODUCTION genus. These viruses include Hendra and Nipah viruses, members of a new genus, Henipaviruses, within the family The role of bats in the maintenance and spread of various ; Menangle and Tioman viruses, new viral diseases is well established (Sulkin and Allen 1974; members of the Rubulavirus genus within the Paramyxov- Ghatak et al. 2000; McColl et al. 2000), including members iridae; and Australian bat lyssavirus (ABLV), a member of of the , flaviviruses, rhabdoviruses and arenavi- the Lyssavirus genus in the family . All but ruses. However, much of the information has been gathered Tioman virus are known to be associated with human and/ from members of the suborder Microchiroptera (insectivor- or livestock diseases. The isolation, disease associations and ous and vampire bats), and relatively little information is biological properties of the viruses are described, and are available for the members of the suborder Megachiroptera used as the basis for developing management strategies (fruit bats and flying foxes). Lyssaviruses, particularly for disease prevention or control. These strategies are rabies, have been identified in six genera of fruit bats directed largely at disease minimization through good farm (McColl et al. 2000; Van der Poel et al. 2000), but most management practices, reducing the potential for exposure other reports have been concerned with various flaviviruses, including West Nile (Paul et al. 1970) and Kyasanur Forest Correspondence to: John S. Mackenzie, Department of Microbiology and Parasitology, University of Queensland, Brisbane, Queensland 4072, Australia (Pavri and Singh 1968), and with two unidentified para- (e-mail: [email protected]). myxoviruses (Pavri et al. 1971; Henderson et al. 1995). Of

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the two paramyxoviruses, one was isolated from a Rousette the horses, and subsequently from kidney tissue from the fruit bat (Rousettus leschenaulti) in (Pavri et al. 1971) fatal human case. The virus was named equine morbillivirus and was later identified as a new animal subtype of on the basis of a weak one-way cross-reaction with rinderpest parainfluenza virus (PIV) type 2, and the other, Mapuera virus, but was subsequently renamed Hendra virus (after the virus, a member of the genus Rubulavirus, was isolated from Brisbane suburb where the outbreak occurred). a Yellow-shouldered bat (Sturnira lilium) captured in the A second small outbreak in Mackay, about 1000 km north tropical rain forest of Brazil in 1979 (Henderson et al. 1995). of Brisbane, came to light about 12 months later, although it Experimentally, fruit bats have been shown to be susceptible actually pre-dated the Hendra outbreak by over a month. to with Japanese encephalitis (Banerjee et al. 1979, Two horses died of unknown cause and the farmer, who had 1984) and (Swanepoel et al. 1996) viruses, the former assisted at necropsy, had a mild meningitic illness, but inducing a sufficient viraemia for onward transmission by recovered. Thirteen months later, however, the farmer mosquitoes (Banerjee et al. 1984) and the latter also became ill and died of a severe encephalitis which was shown producing a viraemia with a high virus titre. However, to be caused by Hendra virus (O’Sullivan et al. 1997). considerable interest has recently been engendered by the Subsequent investigations demonstrated that the horses had emergence of novel viruses from fruit bats in Australia and died of Hendra virus infection (Hooper et al. 1996; Rogers Southeast Asia. This paper describes these viruses and the et al. 1996), and the farmer had been infected at that time, problems in their management. but the virus had presumably remained latent and reacti- vated 13 months later (O’Sullivan et al. 1997). A third incident of equine infection with Hendra virus occurred in 3. EMERGENCE OF THREE NEW VIRUSES January 1999 (Field et al. 2000; Hooper et al. 2000), but IN AUSTRALIA only affecting a single animal. Between 1994 and 1997, three novel zoonotic viruses were An extensive seroepidemiological investigation of wild discovered in Australia associated with fruit bats of the and domestic animals was initiated to find the source of the genus Pteropus (flying foxes); Hendra virus in 1994, ABLV virus (Rogers et al. 1996; Ward et al. 1996; Young et al. in 1996, and Menangle virus in 1997. Their emergence was 1996). The only seropositive animals to be found were unprecedented; no similar multi-emergence of three novel flying foxes (Young et al. 1996, 1997). Indeed to viruses belonging to two virus families and three genera, and Hendra virus were detected in all four species of flying all isolated from a single host genus, had been reported foxes found in Australia. These are the spectacled flying previously over such a short time frame. fox (Pteropus conspicillatus), which occurs in northern and eastern parts of Queensland; the black flying fox (P. alecto), which has a wide distribution across northern Australia, 3.1 Hendra virus the little red flying fox (P. scapulatus), which is found The first of the three viruses to appear was Hendra virus, across northern and eastern Australia, and the grey-headed previously called equine morbillivirus. A number of recent flying fox (P. poliocephalus), which occurs in eastern and reviews have described the isolation, ecology, epidemiology, south-eastern Australia (Field et al. 2001a,b). Approxi- molecular biology, virion structure and laboratory diagnosis mately 47% of flying foxes sampled over their full of Hendra virus (Daniels et al. 2001, Field et al. 2001a,b; geographical range have been found to have antibodies to Hyatt et al. 2001; Mackenzie and Field 2001; Wang et al. Hendra virus (Field et al. 2001b), although differences in 2001). Thus the discovery and biological characteristics are seropositivity have been observed between different species described briefly here. The initial outbreak of an acute (Field et al. 2001a). Three virus isolates were obtained respiratory syndrome in 21 thoroughbred horses occurred in from uterine fluid and a pool of foetal lung and liver from 1994, of which 14 died (Murray et al. 1995a). The other one grey-headed flying fox and from foetal lung of a black seven horses had a subclinical infection and were later killed. flying fox (Halpin et al. 2000). These isolates were In addition, two humans were also infected, one of whom indistinguishable from the isolates of horses and the died (Selvey et al. 1995). The clinical features of the affected human isolate. horses were consistent with an interstitial pneumonia. The Hendra virus is the first isolate in a new genus within the detailed clinical features, together with autopsy and histo- subfamily Paramyxovirinae of the family Paramyxoviridae. It logical findings, have been reported elsewhere (Murray et al. differs significantly from members of the other genera within 1995a, 1995b; and reviewed by Mackenzie and Field 2001). A the subfamily in a number of molecular and biological similar picture of interstitial pneumonia was seen in the fatal properties. The complete genome of Hendra virus has been human case, and at autopsy, findings were consistent with sequenced (Gould 1996; Wang et al. 1998; Yu et al. 1998a,b; viral infection. A previously undescribed virus of the family Halpin 2000; Wang et al. 2000); the gene arrangement is very Paramyxoviridae was isolated from lung tissues taken from similar to the Respirovirus and Morbillivirus genera, but the

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genome size (18.2 kb) is much larger, due in part to a larger P 3.2 Australian bat lyssavirus gene and in part to longer untranslated regions at the 3¢ ends of the six transcription units. The biological properties include a Australia has historically been considered free of rabies and much wider in vitro host range, a relatively diverse in vivo host the rabies-like viruses. Rhabdoviruses from the genus range, and a predilection for endothelial cells. The virus has an Ephemerovirus were known to occur (bovine ephemoral unusual double fringe comprising 15 and 8-nm projections fever, Adelaide River virus, Berrimah virus), but none from (Hyatt and Selleck 1996; Hyatt et al. 2001) not found in other the genus Lyssavirus had been described. St George (1989), members of the Paramyxoviridae family. There appears to be postulating the origins of Adelaide River virus, had sugges- an epidemiological link with pregnancy that has yet to be fully ted the possibility of an undiscovered rabies-like virus in understood, with pregnant horses as the index case in the three Australian bats in 1989. St George went further, suggesting outbreaks, the temporal association of the outbreaks with the that the typically low prevalences of the rabies-related birthing period of species of flying foxes, and the first bat viruses in bats meant that an ABLV might not become isolates being from foetal tissues (Halpin et al. 2000; Field evident unless active surveillance of bats was undertaken, or et al. 2001a). Indeed the virus has been shown experimentally unless man or a domestic animal was infected by a bat. to cross the placenta in bats and guinea-pigs (Williamson et al. Interestingly, the increased surveillance for Hendra virus in 2000). bats was indeed the catalyst for the discovery of ABLV. With respect to public health issues and management, it is Thus ABLV was first recognized in a Black flying-fox interesting to note that the three human infections have (P. alecto) from northern New South Wales which was arisen from contact with infected horses and not from flying displaying neurological signs (Fraser et al. 1996). It has now foxes. Indeed, no evidence of prior infection was found been found to occur in all four species of flying fox (black among bat carers, most of whom have a close relationship flying fox, grey-headed flying fox, little red flying fox, and with many flying foxes each year and therefore ample spectacled flying fox) throughout their Australian range, and opportunity for exposure (Selvey et al. 1996), nor among in several species of insectivorous bat (H.E. Field, unpub- people who had variable levels of exposure to infected horses lished data), including the yellow-bellied sheath-tailed bat (such as veterinarians with necropsy contact) and humans (Saccolaimus flaviventris) (Hooper et al. 1997). The preval- (McCormack et al. 1999). In addition, no cases of Hendra ence of ABLV detected by fluorescent test in 366 virus infection were detected in archival tissue specimens sick, injured, or orphaned bats in southern Queensland was (C. Allan, L.A. Selvey and J.S. Mackenzie, unpublished 6% (McCall et al. 2000). The virus was found to be data). Thus these data suggest that the virus is not antigenically similar to classical (RV) and particularly contagious and transmission to humans is a therefore a member of lyssavirus serotype 1, but was very rare event. The mechanism and route of transmission distinguishable on genetic sequence and was therefore from bats to horses is not known; however, experimental ascribed to a new genotype 7 (Gould et al. 1998). Results infections in a range of species, and investigations of natural from the Centers for Disease Control and Prevention (CDC) infections in flying foxes and in horses, have suggested have indicated that rabies vaccine may elicit a protective possible modes of transmission (Mackenzie and Field 2001; immune response to ABLV (Lyssavirus Expert Group Field et al. 2001b). Virus has been isolated from the kidney, 1996a; Hooper et al. 1997). urine and (less so) oral cavity of horses, and the kidney and The ABLV has been responsible for two fatal infections in urine of cats experimentally infected with Hendra virus. bat carers. The first occurred in a 39-year-old animal Horses have been infected experimentally by the naso-oral handler who had been scratched and possibly bitten 5 weeks route, and cat-to-cat transmission and suspected cat- earlier by a yellow-bellied sheath-tailed bat (Allworth et al. to-horse transmission have been reported (Westbury et al. 1996), and the second occurred in a 27-year-old woman who 1996; Williamson et al. 1998). These latter transmissions are had been bitten by a flying fox more than 2 years previously believed to have most probably resulted from exposure to (Hanna et al. 2000). In both instances the clinical signs were infected urine. Respiratory spread has not been demonstra- consistent with classical rabies infection and included a ted experimentally. Horses excrete virus in urine and saliva, diffuse, non-suppurative encephalitis. but transmission between horses has not been observed experimentally, although it probably occurred in the field 3.3 Menangle virus during the second incident at Mackay. Virus has not yet been demonstrated in the urine of flying foxes. Menangle virus emerged in 1997 as the aetiological agent of a The lack of respiratory spread of Hendra virus may be severe reproductive disease that occurred in a large intensive due to the cell tropism in vascular endothelial cells, resulting piggery in New South Wales, causing a reduced farrowing in vascular leakage and pulmonary oedema (Hyatt et al. rate and stillbirths with deformities and mummified foetuses 2001). (Philbey et al. 1998; Love et al. 2001). The virus was isolated

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from lung, brain and heart tissues of infected piglets, and P. capistratus, P. hypomelanus and P. admiralitatum) from shown to be morphologically similar to viruses in the family Port Moresby and New Britain (H. Field, S. Hamilton, Paramyxoviridae. Molecular characterization of the virus has L. Hall, F. Bornacosso, K. Halpin and P.L. Young, shown it to be a new member of the genus Rubulavirus, unpublished data), were found to have antibodies to a although the structural proteins shared less than 50% Hendra-like virus (Mackenzie 1999; Field et al. 2001a). A sequence homology with other members of the genus year after these studies were undertaken, a new Hendra- (Bowden et al. 2001). Two farm workers are believed to like virus, Nipah virus, was isolated from pigs and humans have been infected by the virus, with an illness characterized in Malaysia. The relative antibody titres in the PNG bats by influenza-like symptoms (Chant et al. 1998), but the mode are consistent with Hendra virus infection. of transmission from pigs to farm workers is not known. A large breeding colony of grey-headed and little red flying 4.1 Nipah virus foxes roosted within 200 m of the affected piggery. Neutral- izing antibodies to Menangle virus were found in 42 of 125 A major outbreak of disease in pigs and humans occurred serum samples collected from these animals. In addition, in Peninsular Malaysia between September 1998 and April antibodies were found in flying fox sera collected in 1996 1999 resulting in 265 human cases of which 105 were (prior to the outbreak in pigs), and from flying foxes in north fatal, and the eventual culling of about 1.1 million pigs Queensland, more than 2000 km from the piggery (H.E. (Chua et al. 2000). The disease in pigs was highly Field, unpublished data). It is therefore believed that flying contagious, and characterized by acute fever with respi- foxes are a reservoir host of Menangle virus, and were the ratory involvement with or without neurological signs in source of the outbreak infection in pigs. The method of spread all age classes. The predominant clinical syndrome in from bats to pigs has not been determined. Epidemiological humans was encephalitic rather than respiratory, with studies have suggested that the virus spread between the clinical signs including fever, headache, , drowsi- breeding farm and two associated growing farms by the ness, and disorientation sometimes proceeding to coma movement of piglets. Segregation of the older pigs from young within 48 h (Chua et al. 1999; Goh et al. 2000). A weaners for a prolonged period resulted in the successful Hendra-like virus, subsequently named Nipah virus, was eradication of the virus from the farms (Kirkland et al. 2001). isolated in cell culture (Chua et al. 1999). Retrospective investigations suggest the virus has been responsible for disease in pigs in Peninsular Malaysia since late 1996. 4. THE EMERGENCE OF SIMILAR The majority of human cases were pig farmers, or people VIRUSES IN SOUTH-EAST ASIA closely associated with pig farming. Transmission was In an evolutionary context, flying foxes are believed to believed to be by the respiratory route on the farms. originate from Sulawesi and Papua . Austra- Molecular characterization of Nipah virus has shown lian species represent the southernmost limit of their ultrastructural, antigenic, serological and molecular similar- distribution. Thus, the discovery of three novel viruses ities to the Hendra virus (Chua et al. 2000; Harcourt et al. from flying foxes in Australia suggested that similar viruses 2000; Chan et al. 2001; Hyatt et al. 2001; Wang et al. 2001), may occur in flying fox species elsewhere. There are about although there are also significant differences in ultrastruc- 60 species of bats in the genus Pteropus. Their limited ture and cell tropisms (Hyatt et al. 2001). This latter finding global distribution extends from the west Indian Ocean is important for our understanding of transmissibility. As islands of Mauritius, Madagascar, Pemba, and Comoro, outlined above, Hendra virus replicates in equine pulmonary along the sub-Himalayan region of Pakistan and India, vascular endothelia, resulting in vascular leakage and through South-east Asia, Philippines, Indonesia, New pulmonary oedema, whereas Nipah virus replicates in Guinea, southwest Pacific Islands as far east as the Cook porcine respiratory epithelia allowing release into porcine Islands, and Australia. They are not found on mainland airways. Thus Nipah virus is readily transmissible by the Africa, Europe, or North and South America. It is respiratory route between pigs and probably from pigs to noteworthy that the overlapping distributions of only three humans. However, although Nipah virus has been shown to species of flying foxes are needed to form a continuous link occur in respiratory secretions and urine of human patients, between the east coast of Australia and Pakistan. there is no epidemiological evidence of transmission from Initial surveillance studies focused on Papua New human to human (Chua et al. 2001a). The results demon- Guinea (PNG). Fruit bats belonging to two species strate that although the two viruses are closely related, and (Dobsonia moluccense and P. neohibernicus) from Madang members of a new proposed genus, , within the on the north coast of PNG (K. Halpin, H. Field, J.S. family Paramyxoviridae (Wang et al. 2000, 2001), they also Mackenzie, M. Bockarie, P.L. Young and P.W. Selleck, differ in a number of important features, one of which is unpublished data), and four more species (D. andersoni, transmissibility.

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Surveillance of wildlife species for evidence of the origin Pteropus species, and indeed in other genera of fruit bats of Nipah virus was an integral part of the outbreak sharing the same or similar habitats. The various differences investigation, and knowledge of the similarities between is spillover hosts and transmissibility observed between Nipah virus and Hendra virus focused wildlife surveillance Hendra and Nipah viruses should not be regarded as on bats. Serological sampling of various bat species found 21 probable indicators of the properties of other related viruses. bats from five species (four species of fruit bat, including the Thus, the spillover host may be any species, or indeed flying fox species Pteropus hypomelanus and P. vampyrus) humans may themselves be spillover hosts; and similarly, with neutralizing antibodies to Nipah virus (Field et al. related viruses may display different degrees of transmissi- 2001b). Subsequently, Nipah virus was isolated from the bility, and may even be transmissible between humans. The urine of an Island flying fox, P. hypomelanus, and from a only certainty would seem to be that related viruses exist and partially eaten fruit swab (Chua et al. 2002). will emerge or be uncovered from their specific niches somewhere in their geographical range on members of the genus Pteropus. 4.2 Tioman virus During the search for the natural host of Nipah virus, 5. OTHER VIRUSES ASSOCIATED another previously unknown virus was isolated from the WITH FRUIT BATS urine of Island flying foxes (P. hypomelanus) collected on Tioman Island. This new virus, which is closely related to In Australia, some -transmitted viruses may Menangle virus, was named after the island, Tioman (Chua potentially use flying foxes as a vertebrate host. The viruses et al. 2001b). Although closely related to Menangle virus, of interest are the Alphaviruses, Ross River and Barmah and a member of the Rubulavirus genus, Tioman virus has Forest, and the Flavivirus, Japanese encephalitis. The not yet been associated with any disease in humans or evidence for an involvement of flying foxes in the ecology of animals. However, it is a further example of the expectation was initially based on haemagglutination- that other as yet unrecognized viruses exist in discrete niches inhibition titres found in flying foxes in the Nelson Bay area of across the geographical range of Pteropus species. Indeed New South Wales (Gard et al. 1973). Subsequently, trans- other paramyxovirus-like viruses have been isolated from mission of Ross River virus was demonstrated between grey- bats in Australia and Malaysia and await characterization (K. headed flying foxes (P. poliocephalus) and Aedes funereus Halpin, unpublished observations; K.B. Chua and S.K. mosquitoes (Ryan et al. 1997). Most recently, Harley et al. Lam, unpublished observations). (2000) found a much higher incidence of Ross River virus- infected mosquitoes near a flying fox camp than in areas well away from the camp. Thus, there is growing, albeit circum- 4.3 Australian bat lyssavirus stantial, evidence that flying foxes may play a role in the While two pairs of related paramyxoviruses have been ecology of Ross River virus. There is as yet no evidence that described in flying foxes in Australia and Malaysia, with flying foxes are involved in the ecology of Barmah Forest serological reactivity to one pair (Hendra/Nipah) in Papua virus, but as the two alphaviruses share various vertebrate New Guinea (PNG), ABLV has not been detected in PNG hosts and vectors, it must be considered a possibility. Japanese or Malaysian bat samples to date (H. Field, unpublished encephalitis virus has been shown to be transmitted to and observations). This apparent anomaly is more likely a from two species of fruit bat in India, Rousettus leschenaulti reflection of limited sampling intensity and test sensitivity (Banerjee et al. 1979) and Cynopterus sphinx (Banerjee et al. than evidence of absence of infection in these bat popula- 1984), and with the spread of Japanese encephalitis virus to the tions. However, serological evidence of a virus related to Torres Strait of northern Australia (Mackenzie et al. 2002), ABLV has been reported recently from six different bat there is increasing concern that flying foxes could become species in the Philippines (Arguin et al. 2002), four of which vertebrate hosts in an urban setting. were species in the Microchiroptera (Taphozous melanopogan, Miniopterus schreibersi, Philetor brachyopterus and Scotophilus 6. MANAGEMENT STRATEGIES kuhlii) and two in the Megachiroptera (Pteropus hypomelanus and Rousettus amplexicaudatus). The effective management of a novel or emergent is most often a complex and multi-faceted paradigm. The central issues include a knowledge of the disease 4.4 Comments on the possible emergence ecology (the natural host, modes of transmission and of other related viruses maintenance, and risk factors for spillover), advanced The above observations suggest that other related viruses laboratory and diagnostic capabilities, an understanding of might be expected to emerge throughout the range of the public health and animal health impacts, and the

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potential economic and ecological costs. The discussion here should be strictly applied (Daniels et al. 2000). Cost- will be directed first at current management prospects and effective risk management measures to minimize spillover practices, and then at a possible future direction of wildlife from flying foxes to pigs are also possible in intensive pig- vaccination as a strategy for control. breeding situations with a little forethought. Screening open-sided sheds with wire netting is a simple and effective biosecurity measure. The probability of pig-flying fox 6.1 Current strategies contact can be further reduced by avoiding the cultivation 6.1.1 Hendra and Nipah viruses. For Hendra virus and of favoured flying fox food trees in the vicinity of pig sheds. (to a lesser extent) Nipah virus, knowledge of the mode of It is also important that a rapid laboratory diagnostic transmission in the , from the natural capability is available with experienced veterinarians to reservoir to spillover hosts, and from spillover hosts to interpret test results and, where necessary, respond to and humans, is incomplete. The transmission mechanism from conduct outbreak investigations. natural hosts to spillover hosts can only be surmised and a number of possible mechanisms have been suggested (Field 6.1.2 Menangle virus. Aspects of Menangle virus man- et al. 2001b). Interestingly, the two viruses differ markedly agement are similar to those for Hendra and Nipah viruses. in their transmissibility between and from spillover hosts, Thus it is important to try to avoid any bat–pig contact which is almost certainly a reflection of their cell tropisms through keeping fruit and flowering trees away from pig (Hyatt et al. 2001). Significantly, for both viruses, there is breeding and weaning areas, and that piggeries are not built no evidence supporting direct bat–human transmission close to flying fox camps. Management within the piggery to (Chua et al. 2001a; Field et al. 2001b; Mackenzie and Field exclude Menangle virus infection has been achieved through 2001). segregation of pigs into discrete age groups (Kirkland et al. Strategies to avoid Hendra virus infection in horses 2001). include minimizing exposure, quarantine and movement controls. Minimizing exposure to flying foxes can be 6.1.3 Australian bat lyssavirus. Australian bat lyssavirus achieved by stabling horses at night and by excluding management differs significantly from the other novel bat favoured flying fox food trees from horse paddocks. Specific viruses. Direct transmission has been recognized twice knowledge of the mode of flying fox-to-horse transmission between bats and humans, resulting in fatal encephalitic and of risk factors for spillover will allow refinement of this infections similar to classical rabies; a vaccine is available risk management approach to infection in horses. It should which offers protection from infection with ABLV, and the be noted that only those horses whose geographical location virus has been found in both flying foxes and insectivorous overlaps with the occurrence of flying foxes are regarded as bat species. Unlike the other viruses, there are no interme- at-risk. Quarantine and movement controls have proved diate spillover hosts, with human infection directly attrib- effective where infection has occurred in horses, assisted by utable to at-risk exposure to infected bats. Thus, the low infectivity of Hendra virus in horses (Baldock et al. management of the public health issue has emphasized 1996). Additional management measures should include a public education to avoid handling bats. This strategy is high level of awareness and preparedness by veterinarians supported by vaccination. The finding from murine vaccine and other horse handlers where horses present with severe protection studies that rabies vaccine offers protection respiratory disease. Until Hendra virus is excluded, care against infection with ABLV (Lyssavirus Expert Group should be exercised as nasal secretions and saliva, as well as 1996a,b; Hooper et al. 1997) had major positive public urine, could be infectious. Rapid laboratory testing capabil- health implications. However, a negative aspect has been the ity is also an important aspect in disease control and public perception that bats are unclean and a threat to management. innocent populations of adults and children alike (Scott The Malaysian outbreak showed that Nipah virus in pigs 2000). Pre-exposure vaccination with rabies vaccine is was highly infectious, and the primary mode of on-farm recommended for high risk occupations such as wildlife transmission was respiratory (Daniels et al. 2000). The workers and veterinarians. Postexposure treatment of primary mode of transmission between farms was the vaccine and rabies immune globulin is offered to anyone movement of pigs. Hence, a number of important strategies exposed to bats through bites or scratches unless ABLV can be readily introduced to minimize the potential for an infection can be ruled out in the bat. In a study of outbreak of Nipah virus infection. The central strategy is the occupations resulting in potential exposure in southern implementation of sound farm management practices such Queensland, voluntary animal handlers accounted for 39% as monitoring herd health and early recognition of disease of potential exposures, their family members for 12%, syndromes. In addition, the principles of farm-gate biose- professional animal handlers for 14%, community members curity encompassing the quarantine of new introductions who intentionally handled bats for 31% and community

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members with contacts initiated by bats for 4% (McCall et al. 1999). Trap vaccination release (TVR) programmes et al. 2000). Indeed the incidence of postexposure prophy- employing parenteral vaccination have also been used for laxis has escalated enormously, and has become a significant rabies control in areas of human habitation (Hanlon et al. public health burden, even in those states where ABLV had 1999), although administration of vaccines to large animal not been detected (Torvaldsen and Watson 1998). Thus the populations using TVR is cost-prohibitive, as well as importance of educating bat handlers and the public about logistically impossible for nonterrestrial species. Currently, the risks involved in handling bats cannot be overempha- mass vaccination campaigns using either live attenuated RV sized, and may reduce the requirement for expensive vaccine strains (i.e. Street Alabama Dufferin (SAD) strains postexposure prophylaxis (McCall et al. 2000). and derivatives) or vaccinia virus recombinants expressing The evidence suggests that ABLV only cycles in bats. the RV glycoprotein (V-RG) have been the most successful Retrospective and progressive case investigation and passive means to prevent RV infection in wildlife. These vaccines surveillance have found no evidence of ABLV infection in are administered orally within edible baits made attractive to domestic animal species (McColl et al. 2000) or targeted the targeted species (Brochier et al. 1996), allowing the wildlife mammalian species (H.E. Field unpublished data). vaccines to be readily distributed to large numbers of wild However, limited susceptibility studies to date have animals via bait drops or bait stations, with individuals revealed that dogs and cats experimentally infected with ingesting the vaccine which is hidden inside the food ABLV do seroconvert and, in some cases, show transient reward. clinical signs of disease (K.A. McColl personal communi- Since their introduction, oral wildlife rabies vaccines have cation). brought about a dramatic reduction in the incidence and spread of rabies in coyotes, foxes, skunks and raccoons in large areas of Europe and North America (Brochier et al. 6.2 Future strategies 1996; Hanlon et al. 1998; Pastoret and Brochier 1998). Only 6.2.1 Can a vaccination strategy be developed to one study has been conducted to determine the efficacy of control emerging viral diseases in flying foxes? While the V-RG vaccine for rabies control in vampire bats, and it populations of both captive and free-ranging flying foxes showed that protective immune responses can be generated demonstrate serological evidence of infection with Nipah, in the bats following oral vaccine delivery (Setien et al. Hendra and ABLV (Mackenzie et al. 2001), there are 1998). This suggests that an oral vaccination approach may currently no active vaccination programmes in place to be appropriate for chiropteran species. It should be noted, prevent circulation and spread of these viruses within however, that while vaccination with oral RV vaccines chiropteran species. Given the many difficulties and unique effectively controls the spread of RV in wildlife populations, challenges posed by the management of viral zoonoses in these vaccines have the major drawback of being infectious wildlife populations, this is perhaps not surprising. The and able to replicate in non-target species. This represents a development of successful disease control programmes public health risk, especially when bait distribution occurs requires careful consideration of the management methods close to human habitation, as accidental exposure to available and an understanding of both the agent and the disseminating vaccine viruses through direct contact with target speciesÕ behaviour and ecology. This is well illustrated baits or recently vaccinated animals can result in human by the rabies virus (RV) experience. Following introduction infection (McGuill et al. 1998; Rupprecht et al. 2001). of domestic pet and livestock vaccination against rabies in Furthermore, it is possible for baits using live attenuated RV the latter half of the twentieth century, rabies epizootics in strains to reacquire virulence and cause vaccineinduced wildlife populations have become the major source of RV rabies. Therefore, oral subunit vaccines delivered via responsible for human infection (Krebs et al. 2001). This is transgenic plants may be a feasible alternative to replica- especially the case for bat RV variants in the United States, ting/disseminating animal virus vectors for control of which have caused 24 of the 32 human rabies deaths zoonoses in flying foxes. recorded between 1990 and 2000 (Krebs et al. 2001). As The use of oral subunit vaccines to prevent both human such, several different methods have been applied to the and animal disease has garnered much interest over the last problem of rabies control in wildlife with varying degrees of 10 years. Compared with the more traditional vaccine success. Historically, population reduction was used for formulations, oral subunit vaccines are inexpensive, stable management of sylvatic rabies (especially in vampire bats in (antigens are protected by plant storage tissues), easy to Latin America). However, this control strategy is generally administer and incapable of causing infection in non-target considered undesirable and inappropriate, as the culling species (Tacket and Mason, 1999; Walmsley and Arntzen methods used are expensive, ineffective or inhumane, and 2000; Koprowski and Yusibov 2001). Like other oral some of the targeted animal species have become endangered vaccines, oral subunit vaccines target the mucosal immune in their natural environment (Arellano-Sota, 1988; Hanlon system (MIS) which involves the mucosal linings of the

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gastrointestinal, respiratory and urinoreproductive tracts, delivery of appropriate vaccine to flying foxes, this the sites at which many pathogens first have contact with the approach may be applied to vaccination of other chirop- host. On presentation of foreign antigens at the host mucosa, teran or terrestrial wildlife species to prevent the spread of the MIS can be induced to produce both a systemic and zoonotic disease. humoral immune response (as reviewed in Tacket and Mason 1999), such that antibodies can be detected both in 7. ACKNOWLEDGEMENTS serum and mucosal secretions. Recent studies have shown that RV, hepatitis , canine parvovirus, respiratory We would like to thank Dr Ken McColl for allowing us to syncytial virus, Norwalk-like virus and foot and mouth quote his unpublished work, and Dr John Scott and Dr disease virus antigens produced in transgenic plants, and Russell Rogers for their helpful comments. delivered orally, have been able to stimulate the MIS in mice (Mason et al. 1996; Modelska et al. 1998; Wigdorovitz et al., 8. REFERENCES 1999; Sandhu et al. 2000; Gil et al. 2001; Kong et al. 2001). Additionally, piglets fed transgenic corn expressing the spike Allworth, A., Murray, K. and Morgan, J. (1996) A case of encephalitis protein of swine transmissible gastroenteritis virus (TGEV) due to a lyssavirus recently identified in fruit bats. Communicable were better protected from TGEV infection than those Diseases Intelligence 20, 504. animals vaccinated with a commercial live TGEV vaccine Arellano-Sota, C. (1988) Biology, ecology, and control of the vampire (Streatfield et al. 2001). bat. Reviews of Infectious Diseases 10 (Suppl 4), S615–S619. Arguin, P.M., Murray-Lillibridge, K., Miranda, M.E.G., Smith, J.S., To use a similar vaccination approach for flying foxes, it Calaor, A.B. and Rupprecht, C.E. (2002) Serologic evidence of needs to be determined whether oral delivery of foreign Lyssavirus infections among bats, the Philippines. Emerging Infectious antigens is able to initiate a mucosal immune response, and Diseases 8, 258–262. if so whether that immune response is generated from the Baldock, F.C., Douglas, I.C., Halpin, K., Field, H., Young, P.L. and oropharynx or gut mucosa. Additionally, the food prefer- Black, P.F. (1996) Epidemiological investigations into the 1994 ences and eating habits of flying foxes require investigation equine morbillivirus outbreaks in Queensland, Australia. Singapore to enable design of suitable bait formulations that are Veterinary Journal 20, 57–61. attractive to flying foxes but of little interest to non-target Banerjee, K., Ilkal, M.A., Bhat, H.R. and Sreenivasan, M.A. (1979) species. Indeed, it has been found that flying foxes Experimental viraemia with Japanese encephalitis virus in certain are particularly partial to commercial banana flavouring domestic and peridomestic vertebrates. Indian Journal of Medical (P. Young, personal communication); an observation which Research 70, 364–368. Banerjee, K., Ilkal, M.A. and Deshmukh, P.K. (1984) Susceptibility of may prove useful in developing a successful baiting strategy. Cynopterus sphinx (frugiorous bat) and Suncus murinus (house shrew) It is also important to note that antibodies to Nipah virus, to Japanese encephalitis virus. 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