Hendra virus, first identified in 1994 in Queensland, is an emerging zoonotic pathogen gaining importance in Australia because a growing number of infections are reported in horses and people. The virus, a member of the family Paramyxoviridae (genus Henipavirus), is transmitted to horses by pteropid bats (fruit bats or flying foxes), with human infection a result of direct contact with infected horses. Case-fatality rate is high in both horses and people, and so far, more than 60 horses and four people have died from Hendra virus infection in Australia. Human infection is characterised by an acute encephalitic syndrome or relapsing encephalitis, for which no effective treatment is currently available. Recent identification of Hendra virus infection in a domestic animal outside the laboratory setting, and the large range of pteropid bats in Australia, underpins the potential of this virus to cause greater morbidity and mortality in both rural and urban populations and its importance to both veterinary and human health. Attempts at treatment with ribavirin and chloroquine have been unsuccessful. Education, hygiene, and infection control measures have hitherto been the mainstay of prevention, while access to monoclonal antibody treatment and development of an animal vaccine offer further opportunities for disease prevention and control.

Hendra virus (HeV) and Nipah virus (NiV) are biosafety level 4 zoonotic pathogens causing severe and often fatal neurological and respiratory disease. These agents have been recognized by the World Health Organization as top priority pathogens expected to result in severe future outbreaks. HeV has caused sporadic infections in horses and a small number of human cases in Australia since 1994. The NiV Malaysia genotype (NiV-M) was responsible for the 1998-1999 epizootic outbreak in pigs with spillover to humans in Malaysia and Singapore. Since 2001, the NiV Bangladesh genotype (NiV-B) has been the predominant strain leading to outbreaks almost every year in Bangladesh and India, with hundreds of infections in humans. The natural reservoir hosts of HeV and NiV are fruit bats, which carry the viruses without clinical manifestation. The transmission pathways of henipaviruses from bats to humans remain poorly understood. Transmissions are often bridged by an intermediate animal host, which amplifies and spreads the viruses to humans. Horses and pigs are known intermediate hosts for the HeV outbreaks in Australia and NiV-M epidemic in Malaysia and Singapore, respectively. During the NiV-B outbreaks in Bangladesh, following initial spillover thought to be through the consumption of date palm sap, the spread of infection was largely human-to-human transmission. Spillover of NiV-B in recent outbreaks in India is less understood, with the primary route of transmission from bat reservoir to the initial human infection case(s) unknown and no intermediate host established. This review aims to provide a concise update on the epidemiology of henipaviruses covering their previous and current outbreaks with emphasis on the known and potential role of livestock as intermediate hosts in disease transmission. Also included is an up-to-date summary of newly emerging henipa-like viruses and animal hosts. In these contexts we discuss knowledge gaps and new challenges in the field and propose potential future directions.

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic zoonotic viruses of the genus Henipavirus, family Paramyxoviridae that cause severe disease outbreaks in humans and also can infect and cause lethal disease across a broad range of mammalian species. Another related Henipavirus has been very recently identified in China in febrile patients with pneumonia, the Langya virus (LayV) of probable animal origin in shrews. NiV and HeV were first identified as the causative agents of severe respiratory and encephalitic disease in the 1990s across Australia and Southern Asia with mortality rates reaching up to 90%. They are responsible for rare and sporadic outbreaks with no approved treatment modalities. NiV and HeV have wide cellular tropism that contributes to their high pathogenicity. From their natural hosts bats, different scenarios propitiate their spillover to pigs, horses, and humans. Henipavirus-associated respiratory disease arises from vasculitis and respiratory epithelial cell infection while the neuropathogenesis of Henipavirus infection is still not completely understood but appears to arise from dual mechanisms of vascular disease and direct parenchymal brain infection. This brief review offers an overview of direct and indirect mechanisms of HeV and NiV pathogenicity and their interaction with the human immune system, as well as the main viral strategies to subvert such responses.

Incubation period is ≈5–16 days (and rarely ≤2 months). Both Hendra and Nipah virus infections can cause a severe influenza-like illness with dizziness, headache, fever, and myalgias. The disease can progress to severe encephalitis with confusion, abnormal reflexes, seizures, and coma; respiratory symptoms also might be present. Relapsing or late-onset encephalitis can occur months or years after acute illness. The case-fatality ratio of Hendra virus is 57%; among 7 known human cases, 4 were fatal. Case-fatality ratios for Nipah virus infection are 40%–70% but have been 100% in some human outbreaks.
Most of the 35 known cases of Langya virus infection have reported non-specific clinical symptoms (e.g., anorexia, cough, fatigue, fever, headache, myalgia, nausea, vomiting). No deaths due to Langya virus have yet been identified.

Nipah henipavirus (NiV) and Hendra henipavirus (HeV) are zoonotic emerging paramyxoviruses causing severe disease outbreaks in humans and livestock, mostly in Australia, India, Malaysia, Singapore and Bangladesh. Both are bat-borne viruses and in humans, their mortality rates can reach 60% in the case of HeV and 92% for NiV, thus being two of the deadliest viruses known for humans. Several factors, including a large cellular tropism and a wide zoonotic potential, con-tribute to their high pathogenicity. This review provides an overview of HeV and NiV pathogenicity mechanisms and provides a summary of their interactions with the immune systems of their different host species, including their natural hosts bats, spillover-hosts pigs, horses, and humans, as well as in experimental animal models. A better understanding of the interactions between henipaviruses and their hosts could facilitate the development of new therapeutic strategies and vaccine measures against these re-emerging viruses.

The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.

Hendra virus and Nipah virus are bat-borne paramyxoviruses that are the prototypic members of the genus Henipavirus. The henipaviruses emerged in the 1990s, spilling over from their natural bat hosts and causing serious disease outbreaks in humans and livestock. Hendra virus emerged in Australia and since 1994 there have been 7 human infections with 4 case fatalities. Nipah virus first appeared in Malaysia and subsequent outbreaks have occurred in Bangladesh and India. In total, there have been an estimated 582 human cases of Nipah virus and of these, 54% were fatal. Their broad species tropism and ability to cause fatal respiratory and/or neurologic disease in humans and animals make them important transboundary biological threats. Recent experimental findings in animals have demonstrated that a human monoclonal antibody targeting the viral G glycoprotein is an effective post-exposure treatment against Hendra and Nipah virus infection. In addition, a subunit vaccine based on the G glycoprotein of Hendra virus affords protection against Hendra and Nipah virus challenge. The vaccine has been developed for use in horses in Australia and is the first vaccine against a Biosafety Level-4 (BSL-4) agent to be licensed and commercially deployed. Together, these advances offer viable approaches to address Hendra and Nipah virus infection of livestock and people.

Hendra virus (HeV) and Nipah virus (NiV) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. HeV appeared in Queensland, Australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. NiV emerged a few years later in Malaysia and Singapore in 1998-1999 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. The key pathological elements of HeV and NiV infection in several species of mammals, and also in people, are a severe systemic and often fatal neurologic and/or respiratory disease. In people, both HeV and NiV are also capable of causing relapsed encephalitis following recovery from an acute infection. The known reservoir hosts of HeV and NiV are several species of pteropid fruit bats. Spillovers of HeV into horses continue to occur in Australia and NiV has caused outbreaks in people in Bangladesh and India nearly annually since 2001, making HeV and NiV important transboundary biological threats. NiV in particular possesses several features that underscore its potential as a pandemic threat, including its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals, along with a capacity of limited human-to-human transmission. Several HeV and NiV animal challenge models have been developed which have facilitated an understanding of pathogenesis and allowed for the successful development of both active and passive immunization countermeasures.