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.

Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID₅₀ within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody. Nipah virus and Hendra virus are closely related and highly pathogenic zoonoses whose primary natural reservoirs are several species of Pteropus fruit bats. Both Nipah and Hendra viruses can cause severe and often fatal disease in a variety of mammalian hosts, including humans. The henipaviruses are categorized as biosafety level 4 (BSL-4) agents, which has limited the development of animal models and the testing of potential therapeutics and vaccine countermeasures. We show here a new ferret model of Nipah virus pathogenesis in which the underlying pathology closely mirrors the illness seen in Nipah virus-infected humans, including both respiratory and neurological disease. We also show that m102.4, a cross-reactive neutralizing human monoclonal antibody that targets the viral attachment glycoprotein, completely protected ferrets from disease when given ten hours after a lethal Nipah virus challenge. This study is the first successful and viable post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.

In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra virus (HeV), a zoonotic paramyxovirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease. <!-- link to audio presentation here --> <!--[if!IE]><!--> Download MP3 <!--><![endif]--><!--[if IE]> Download MP3 <![endif]--> Length: 1:13

Rabies is a fatal neurological pathogen that is a persistent problem throughout the developing world where it is spread primarily by domestic dogs. Although the disease has been extensively studied in wildlife populations in Europe and North America, the dynamics of rabies in domestic dog populations has been almost entirely neglected. Here, we demonstrate that rabies epidemics in southern and eastern Africa cycle with a period of 3–6 years and show significant synchrony across the region. The observed period is shorter than predictions based on epidemiological parameters for rabies in domestic dogs. We find evidence that rabies prevention measures, including vaccination, are affected by disease prevalence and show that a simple model with intervention responses can capture observed disease periodicity and host dynamics. We suggest that movement of infectious or latent animals combined with coordinated control responses may be important in coupling populations and generating synchrony at the continental scale. These findings have important implications for rabies prediction and control: large-scale synchrony and the importance of intervention responses suggest that control of canine rabies in Africa will require sustained efforts coordinated across political boundaries.

Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID ₅₀ ) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID ₅₀ of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.

Dogs are Zimbabwe's primary vector for rabies, and the majority live in communal lands (traditional agropastoralist rural areas). In 1994, a household questionnaire survey was conducted to provide baseline data on the demography and dog‐human relationships of the dogs in the communal lands. The survey showed that all the dogs were owned, and there was no evidence of a feral population. They were unrestricted and semi.dependent on people. The numbers of dogs per capita varied little in each communal land, resulting in higher dog densities in communal lands with higher human densities, and indicating that people were not intolerant of dogs at higher densities. The population turnover was rapid: the life expectancy of the dogs was 1.1 years, the mean age 2.0 years, and 71.8 per cent died in their first year. The population was heavily skewed towards juveniles, with 40.8 per cent aged less than 12 months. Despite the high juvenile mortality, the population was growing by 6.52 per cent per annum. It was estimated that in 1994 there were 1.36 million dogs in communal lands.