The Distribution of Henipaviruses in Southeast Asia and Australasia: Is Wallace's Line a Barrier to Nipah Virus?

Nipah virus (NiV) (Genus Henipavirus) is a recently emerged zoonotic virus that causes severe disease in humans and has been found in bats of the genus Pteropus. Whilst NiV has not been detected in Australia, evidence for NiV-infection has been found in pteropid bats in some of Australia's closest neighbours. The aim of this study was to determine the occurrence of henipaviruses in fruit bat (Family Pteropodidae) populations to the north of Australia. In particular we tested the hypothesis that Nipah virus is restricted to west of Wallace's Line. Fruit bats from Australia, Papua New Guinea, East Timor and Indonesia were tested for the presence of antibodies to Hendra virus (HeV) and Nipah virus, and tested for the presence of HeV, NiV or henipavirus RNA by PCR. Evidence was found for the presence of Nipah virus in both Pteropus vampyrus and Rousettus amplexicaudatus populations from East Timor. Serology and PCR also suggested the presence of a henipavirus that was neither HeV nor NiV in Pteropus alecto and Acerodon celebensis. The results demonstrate the presence of NiV in the fruit bat populations on the eastern side of Wallace's Line and within 500 km of Australia. They indicate the presence of non-NiV, non-HeV henipaviruses in fruit bat populations of Sulawesi and Sumba and possibly in Papua New Guinea. It appears that NiV is present where P. vampyrus occurs, such as in the fruit bat populations of Timor, but where this bat species is absent other henipaviruses may be present, as on Sulawesi and Sumba. Evidence was obtained for the presence henipaviruses in the non-Pteropid species R. amplexicaudatus and in A. celebensis. The findings of this work fill some gaps in knowledge in geographical and species distribution of henipaviruses in Australasia which will contribute to planning of risk management and surveillance activities.

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 NiV's 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 Nino 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.

Nipah Virus in the Fruit Bat Pteropus vampyrus in Sumatera, Indonesia

Nipah virus causes periodic livestock and human disease with high case fatality rate, and consequent major economic, social and psychological impacts. Fruit bats of the genus Pteropus are the natural reservoir. In this study, we used real time PCR to screen the saliva and urine of P. vampyrus from North Sumatera for Nipah virus genome. A conventional reverse transcriptase (RT-PCR) assay was used on provisionally positive samples to corroborate findings. This is the first report of Nipah virus detection in P. vampyrus in Sumatera, Indonesia.

Ecological dynamics of emerging bat virus spillover

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.

Ecological dynamics of emerging bat virus spillover

Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.

A systematic review of community-based interventions for emerging zoonotic diseases in Southeast Asia

Background Southeast Asia has been at the epicentre of recent epidemics of emerging and re-emerging zoonotic diseases. Community-based surveillance and control interventions have been heavily promoted but the most effective interventions have not been identified. Objectives This review evaluated evidence for the effectiveness of community-based surveillance interventions at monitoring and identifying emerging infectious disease; the effectiveness of community-based control interventions at reducing rates of emerging infectious disease; and contextual factors that influence intervention effectiveness. Inclusion criteria Participants Communities in Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. Types of intervention(s) Non-pharmaceutical, non-vaccine, and community-based surveillance or prevention and control interventions targeting rabies, Nipah virus , dengue, SARS or avian influenza. Types of outcomes Primary outcomes: measures: of infection or disease; secondary outcomes: measures of intervention function. Types of studies Original quantitative studies published in English. Search strategy Databases searched (1980 to 2011): PubMed, CINAHL, ProQuest, EBSCOhost, Web of Science, Science Direct, Cochrane database of systematic reviews, WHOLIS, British Development Library, LILACS, World Bank (East Asia), Asian Development Bank. Methodological quality Two independent reviewers critically appraised studies using standard Joanna Briggs Institute instruments. Disagreements were resolved through discussion. Data extraction A customised tool was used to extract quantitative data on intervention(s), populations, study methods, and primary and secondary outcomes; and qualitative contextual information or narrative evidence about interventions. Data synthesis Data was synthesised in a narrative summary with the aid of tables. Meta-analysis was used to statistically pool quantitative results. Results Fifty-seven studies were included. Vector control interventions using copepods, environmental cleanup and education are effective and sustainable at reducing dengue in rural and urban communities, whilst insecticide spraying is effective in urban outbreak situations. Community-based surveillance interventions can effectively identify avian influenza in backyard flocks, but have not been broadly applied. Outbreak control interventions for Nipah virus and SARS are effective but may not be suitable for ongoing control. Canine vaccination and education is more acceptable than culling, but still fails to reach coverage levels required to effectively control rabies. Contextual factors were identified that influence community engagement with, and ultimately effectiveness of, interventions. Conclusion Despite investment in community-based disease control and surveillance in Southeast Asia, published evidence evaluating interventions is limited in quantity and quality. Nonetheless this review identified a number of effective interventions, and several contextual factors influencing effectiveness. Identification of the best programs will require comparative evidence of effectiveness acceptability, cost-effectiveness and sustainability.

Emerging henipaviruses and flying foxes - Conservation and management perspectives

Wildlife populations are affected by a series of emerging diseases, some of which pose a significant threat to their conservation. They can also be reservoirs of pathogens that threaten domestic animal and human health. In this paper, we review the ecology of two viruses that have caused significant disease in domestic animals and humans and are carried by wild fruit bats in Asia and Australia. The first, Hendra virus, has caused disease in horses and/or humans in Australia every five years since it first emerged in 1994. Nipah virus has caused a major outbreak of disease in pigs and humans in Malaysia in the late 1990s and has also caused human mortalities in Bangladesh annually since 2001. Increased knowledge of fruit bat population dynamics and disease ecology will help improve our understanding of processes driving the emergence of diseases from bats. For this, a transdisciplinary approach is required to develop appropriate host management strategies that both maximise the conservation of bat populations as well as minimise the risk of disease outbreaks in domestic animals and humans.

Henipaviruses: Emerging Paramyxoviruses Associated with Fruit Bats

Two related, novel, zoonotic paramyxoviruses have been described recently. Hendra virus was first reported in horses and thence humans in Australia in 1994; Nipah virus was first reported in pigs and thence humans in Malaysia in 1998. Human cases of Nipah virus infection, apparently unassociated with infection in livestock, have been reported in Bangladesh since 2001. Species of fruit bats (genus Pteropus ) have been identified as natural hosts of both agents. Anthropogenic changes (habitat loss, hunting) that have impacted the population dynamics of Pteropus species across much of their range are hypothesised to have facilitated emergence. Current strategies for the management of henipaviruses are directed at minimising contact with the natural hosts, monitoring identified intermediate hosts, improving biosecurity on farms, and better disease recognition and diagnosis. Investigation of the emergence and ecology of henipaviruses warrants a broad, cross-disciplinary ecosystem health approach that recognises the critical linkages between human activity, ecological change, and livestock and human health.

Emerging Viruses: Coming in on a Wrinkled Wing and a Prayer

The role that bats have played in the emergence of several new infectious diseases has been under review. Bats have been identified as the reservoir hosts of newly emergent viruses such as Nipah virus, Hendra virus, and severe acute respiratory syndrome–like coronaviruses. This article expands on recent findings about bats and viruses and their relevance to human infections. It briefly reviews the history of chiropteran viruses and discusses their emergence in the context of geography, phylogeny, and ecology. The public health and trade impacts of several outbreaks are also discussed. Finally, we attempt to predict where, when, and why we may see the emergence of new chiropteran viruses.

Henipavirus in Pteropus vampyrus Bats, Indonesia

The emergence of Nipah virus (NiV) in Malaysia in 1999 resulted in 265 known human infections (105 fatal), widespread infection in pigs (with >1 million culled to control the outbreak), and the collapse of the Malaysian pig export market. As with the closely related Hendra virus (HeV) that emerged in Australia in 1994 and caused fatal disease in horses and humans, bats of the genus Pteropus (commonly known as flying foxes) were identified as the major reservoir of Nipah virus in Malaysia. This report describes a serologic survey of Pteropus vampyrus in neighboring Indonesia.

Bats and Emerging Zoonoses: Henipaviruses and SARS.

Nearly 75% of all emerging infectious diseases (EIDs) that impact or threaten human health are zoonotic. The majority have spilled from wildlife reservoirs, either directly to humans or via domestic animals. The emergence of many can be attributed to predisposing factors such as global travel, trade, agricultural expansion, deforestation habitat fragmentation, and urbanization; such factors increase the interface and or the rate of contact between human, domestic animal, and wildlife populations, thereby creating increased opportunities for spillover events to occur. Infectious disease emergence can be regarded as primarily an ecological process. The epidemiological investigation of EIDs associated with wildlife requires a trans-disciplinary approach that includes an understanding of the ecology of the wildlife species, and an understanding of human behaviours that increase risk of exposure. Investigations of the emergence of Nipah virus in Malaysia in 1999 and severe acute respiratory syndrome (SARS) in China in 2003 provide useful case studies. The emergence of Nipah virus was associated with the increased size and density of commercial pig farms and their encroachment into forested areas. The movement of pigs for sale and slaughter in turn led to the rapid spread of infection to southern peninsular Malaysia, where the high-density, largely urban pig populations facilitated transmission to humans. Identifying the factors associated with the emergence of SARS in southern China requires an understanding of the ecology of infection both in the natural reservoir and in secondary market reservoir species. A necessary extension of understanding the ecology of the reservoir is an understanding of the trade, and of the social and cultural context of wildlife consumption. Emerging infectious diseases originating from wildlife populations will continue to threaten public health. Mitigating and managing the risk requires an appreciation of the connectedness between human, livestock and wildlife health, and of the factors and processes that disrupt the balance.

Henipaviruses - unanswered questions of lethal zoonoses.

The highly lethal Hendra and Nipah viruses have been described for little more than a decade, yet within that time have been aetiologically associated with major livestock and human health impacts, albeit on a limited scale. Do these emerging pathogens pose a broader threat, or are they inconsequential 'viral chatter'. Given their lethality, and the evident multi-generational human-to-human transmission associated with Nipah virus in Bangladesh, it seems prudent to apply the precautionary principle. While much is known of their clinical, pathogenic and epidemiologic features in livestock species and humans, a number of fundamental questions regarding the relationship between the viruses, their natural fruit-bat host and the environment remain unanswered. In this paper, we pose and probe these questions in context, and offer perspectives based primarily on our experience with Hendra virus in Australia, augmented with Nipah virus parallels.

All Hands on Deck: Transdisciplinary Approaches to Emerging Infectious Disease

The increasing burden of emerging infectious diseases worldwide confronts us with numerous challenges, including the imperative to design research and responses that are commensurate to understanding the complex social and ecological contexts in which infectious diseases occur. A diverse group of scientists met in Hawaii in March 2005 to discuss the linked social and ecological contexts in which infectious diseases emerge. A subset of the meeting was a group that focused on ‘‘transdisciplinary approaches’’ to integrating knowledge across and beyond academic disciplines in order to improve prevention and control of emerging infections. This article is based on the discussions of that group. Here, we outline the epidemiological legacy that has dominated infectious disease research and control up until now, and introduce the role of new, transdisciplinary and systems-based approaches to emerging infectious diseases.Wedescribe four cases of transboundary health issues and use them to discuss the potential benefits, as well as the inherent difficulties, in understanding the social–ecological contexts in which infectious diseases occur and of using transdisciplinary approaches to deal with them.

Ecosystems and human well-being : health synthesis

This report synthesizes the findings from the Millennium Ecosystem Assessment's (MA) global and sub-global assessments of how ecosystem changes do, or could, affect human health and well-being. Main topics covered are: Food, fresh water, timber, fibre, and fuel, nutrient and waste management, pollution, processing and detoxification, cultural, spiritual and recreational services, climate regulation, and extreme weather events.

N-(3-Cyanophenyl)-2-phenylacetamide, an effective inhibitor of morbillivirus-induced membrane fusion with low cytotoxicity

Based on the structural similarity of viral fusion proteins within the family Paramyxoviridae, we tested recently described and newly synthesized acetanilide derivatives for their capacity to inhibit measles virus (MV)-, canine distemper virus (CDV)- and Nipah virus (NiV)-induced membrane fusion. We found that N-(3-cyanophenyl)-2-phenylacetamide (compound 1) has a high capacity to inhibit MV- and CDV-induced (IC(50) muM), but not NiV-induced, membrane fusion. This compound is of outstanding interest because it can be easily synthesized and its cytotoxicity is low [50 % cytotoxic concentration (CC(50)) >/= 300 muM], leading to a CC(50)/IC(50) ratio of approximately 100. In addition, primary human peripheral blood lymphocytes and primary dog brain cell cultures (DBC) also tolerate high concentrations of compound 1. Infection of human PBMC with recombinant wild-type MV is inhibited by an IC(50) of approximately 20 muM. The cell-to-cell spread of recombinant wild-type CDV in persistently infected DBC can be nearly completely inhibited by compound 1 at 50 muM, indicating that the virus spread between brain cells is dependent on the activity of the viral fusion protein. Our findings demonstrate that this compound is a most applicable inhibitor of morbillivirus-induced membrane fusion in tissue culture experiments including highly sensitive primary cells.