Hume E. Field

Bats: Important Reservoir Hosts of Emerging Viruses

SUMMARY Bats (order Chiroptera, suborders Megachiroptera [“flying foxes”] and Microchiroptera) are abundant, diverse, and geographically widespread. These mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. Some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roosting behaviors, ability to echolocate, virus susceptibility) make them exquisitely suitable hosts of viruses and other disease agents. Bats of certain species are well recognized as being capable of transmitting rabies virus, but recent observations of outbreaks and epidemics of newly recognized human and livestock diseases caused by viruses transmitted by various megachiropteran and microchiropteran bats have drawn attention anew to these remarkable mammals. This paper summarizes information regarding chiropteran characteristics and information regarding 66 viruses that have been isolated from bats. From these summaries, it is clear that we do not know enough about bat biology; we are doing too little in terms of bat conservation; and there remain a multitude of questions regarding the role of bats in disease emergence.

Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra virus.

Since it was first described in Australia in 1994, Hendra virus (HeV) has caused two outbreaks of fatal disease in horses and humans, and an isolated fatal horse case. Our preliminary studies revealed a high prevalence of neutralizing antibodies to HeV in bats of the genus PTEROPUS:, but it was unclear whether this was due to infection with HeV or a related virus. We developed the hypothesis that HeV excretion from bats might be related to the birthing process and we targeted the reproductive tract for virus isolation. Three virus isolates were obtained from the uterine fluid and a pool of foetal lung and liver from one grey-headed flying-fox (Pteropus poliocephalus), and from the foetal lung of one black flying-fox (P. alecto). Antigenically, these isolates appeared to be closely related to HeV, returning positive results on immunofluorescent antibody staining and constant-serum varying-virus neutralization tests. Using an HeV-specific oligonucleotide primer pair, genomic sequences of the isolates were amplified. Sequencing of 200 nucleotides in the matrix gene identified that these three isolates were identical to HeV. Isolations were confirmed after RNA extracted from original material was positive for HeV RNA when screened on an HeV Taqman assay. The isolation of HeV from pteropid bats corroborates our earlier serological and epidemiological evidence that they are a natural reservoir host of the virus.

The natural history of Hendra and Nipah viruses

Pteropid bats (flying foxes), species of which are the probable natural host of both Hendra and Nipah viruses, occur in overlapping populations from India to Australia. Ecological changes associated with land use and with animal husbandry practices appear most likely to be associated with the emergence of these two agents.

Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission.

Bats of the genus Pteropus have been identified as the reservoir hosts for the henipaviruses Hendra virus (HeV) and Nipah virus (NiV). The aim of these studies was to assess likely mechanisms for henipaviruses transmission from bats. In a series of experiments, Pteropus bats from Malaysia and Australia were inoculated with NiV and HeV, respectively, by natural routes of infection. Despite an intensive sampling strategy, no NiV was recovered from the Malaysian bats and HeV was reisolated from only one Australian bat; no disease was seen. These experiments suggest that opportunities for henipavirus transmission may be limited; therefore, the probability of a spillover event is low. For spillover to occur, a range of conditions and events must coincide. An alternate assessment framework is required if we are to fully understand how this reservoir host maintains and transmits not only these but all viruses with which it has been associated.

Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiVs wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.

Human Hendra Virus Encephalitis Associated with Equine Outbreak, Australia, 2008

Emergence of this virus is a serious medical, veterinary, and public health challenge.

Epidemiologic Clues to SARS Origin in China

An epidemic of severe acute respiratory syndrome (SARS) began in Foshan municipality, Guangdong Province, China, in November 2002. We studied SARS case reports through April 30, 2003, including data from case investigations and a case series analysis of index cases. A total of 1,454 clinically confirmed cases (and 55 deaths) occurred; the epidemic peak was in the first week of February 2003. Healthcare workers accounted for 24% of cases. Clinical signs and symptoms differed between children (<18 years) and older persons (>65 years). Several observations support the hypothesis of a wild animal origin for SARS. Cases apparently occurred independently in at least five different municipalities; early case-patients were more likely than later patients to report living near a produce market (odds ratio undefined; lower 95% confidence interval 2.39) but not near a farm; and 9 (39%) of 23 early patients, including 6 who lived or worked in Foshan, were food handlers with probable animal contact.

Henipavirus Infection in Fruit Bats (Pteropus giganteus), India

We tested 41 bats for antibodies against Nipah and Hendra viruses to determine whether henipaviruses circulate in pteropid fruit bats (Pteropus giganteus) in northern India. Twenty bats were seropositive for Nipah virus, which suggests circulation in this species, thereby extending the known distribution of henipaviruses in Asia westward by >1,000 km.

A framework for the study of zoonotic disease emergence and its drivers: spillover of bat pathogens as a case study

Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.

Nipah virus: impact, origins, and causes of emergence.

Nipah virus is an emerging zoonotic pathogen that causes severe febrile encephalitis resulting in death in 40% to 75% of human cases. Nipah virus is considered a biosafety level-4 pathogen and is listed as a select agent with high risk for public health and security due to its high mortality rate in people and the lack of effective vaccines or therapies. The natural reservoir for Nipah virus and related members of the genus Henipavirus are fruit bats of the genus Pteropus. Nipah virus emerged in Malaysia in 1998 as a porcine neurologic and respiratory disease that spread to humans who had contact with live, infected pigs. Research reviewed in this paper suggests that anthropogenic factors, including agricultural expansion and intensification, were the underlying causes of its emergence. Nipah virus has caused five subsequent outbreaks between 2001 and 2005 in Bangladesh. Here, it appears to have spilled over directly from bats to humans, and person-to-person transmission is evident suggesting a heightened public health risk.