Nipah virus (Henipavirus nipahense) is a bat-borne, zoonotic virus that causes Nipah virus infection in humans and other animals, a disease with a very high case fatality rate (40–75%). Numerous disease outbreaks caused by the Nipah virus have occurred in India, Malaysia, and Singapore. Nipah virus belongs to the genus Henipavirus along with the Hendra virus, which has also caused disease outbreaks.
Virology Like other henipaviruses, the Nipah virus genome is a single (non-segmented) negative-sense, single-stranded RNA of over 18 kb, which is substantially longer than that of other paramyxoviruses. The enveloped virus particles are variable in shape, and can be filamentous or spherical; they contain a helical nucleocapsid. Six structural proteins are generated: N (nucleocapsid), P (phosphoprotein), M (matrix), F (fusion), G (glycoprotein) and L (RNA polymerase). The P open reading frame also encodes three nonstructural proteins, C, V and W.
There are two envelope glycoproteins. The G glycoprotein ectodomain assembles as a homotetramer to form the viral anti-receptor or attachment protein, which binds to the receptor on the host cell. Each strand in the ectodomain consists of four distinct regions: at the N-terminal and connecting to the viral surface is the helical stalk, followed by the beta-sandwich neck domain, the linker region, and finally, at the C-terminal, four heads which contain host cell receptor binding domains.
Each head consists of a beta-propeller structure with six blades. There are three unique folding patterns of the heads, resulting in a 2-up/2-down configuration where two heads are positioned distal to the virus, and two heads are proximal. Due to the folding patterns and subsequent arrangement of the heads, only one of the four heads is positioned with its binding site accessible to associate with the host B2/B3 receptor.
The G protein head domain is also highly antigenic, inducing head-specific antibodies in primate models. As such, it is a prime target for vaccine development as well as antibody therapy. One head-specific antibody, m102.4, has been used in compassionate use cases and has completed Phase 1 clinical trials. The F glycoprotein forms a trimer, which mediates membrane fusion.
Tropism Ephrins B2 and B3 have been identified as the main receptors for Nipah virus. Ephrin sub-types have a complex distribution of expression throughout the body, where the B3 is noted to have particularly high expression in some forebrain sub-regions.
Geographic distribution
Nipah virus has been isolated from Lyle's flying fox (Pteropus lylei) in Cambodia and its RNA has been detected in urine and saliva from P. lylei and Horsfield's roundleaf bat (Hipposideros larvatus) in Thailand. The virus has also been isolated from environmental samples of bat urine and partially eaten fruit in Malaysia. Antibodies to henipaviruses have also been found in fruit bats in Madagascar (Pteropus rufus, Eidolon dupreanum) and Ghana (Eidolon helvum), indicating a wide geographic distribution of the viruses.
No infection of humans or other species has been observed in Cambodia, Thailand, or Africa as of May 2018. In September 2023, India reported at least five infections and two deaths. In July 2024, a new infection occurred and a 14-year-old boy died as a result of it. In January 2026, two Nipah cases were confirmed in the state of West Bengal in India.
Signs and symptoms
History Emergence The first cases of Nipah virus infection were identified in 1998, when an outbreak of neurological and respiratory disease on pig farms in peninsular Malaysia caused 265 human cases, with 108 deaths. The virus was isolated in the following year of 1999. This outbreak resulted in the culling of one million pigs. In Singapore, 11 cases, including one death, occurred in slaughterhouse workers exposed to pigs imported from the affected Malaysian farms.
The name "Nipah" refers to the place, Sungai Nipah (literally 'nipah river') in Port Dickson, Negeri Sembilan, the source of the human case from which Nipah virus was first isolated.
The outbreak was originally mistaken for Japanese encephalitis, but physicians in the area noted that people who had been vaccinated against Japanese encephalitis were not protected in the epidemic, and the number of cases among adults was unusual.. Archived thread from the Malaysian Doctors Only BBS Although these observations were recorded in the first month of the outbreak, the Ministry of Health failed to take them into account, and launched a nationwide campaign to educate people on the dangers of Japanese encephalitis and its vector, Culex mosquitoes.
Symptoms of infection from the Malaysian outbreak were primarily encephalitic in humans and respiratory in pigs. Later outbreaks have caused respiratory illness in humans, increasing the likelihood of human-to-human transmission and indicating the existence of more dangerous strains of the virus.
During the 1999 outbreak of Nipah virus, which occurred among pig farmers, the majority of human infections stemmed from direct contact with sick pigs and the unprotected handling of secretions from the pigs.
Based on seroprevalence data and virus isolations, the primary reservoir for Nipah virus was identified as pteropid fruit bats, including Pteropus vampyrus (large flying fox), and Pteropus hypomelanus (small flying fox), both found in Malaysia.
The transmission of the Nipah virus from flying foxes to pigs is thought to be due to an increasing overlap between bat habitats and piggeries in peninsular Malaysia. In one outbreak, fruit orchards were in proximity to the piggery, allowing the spillage of urine, feces, and partially eaten fruit onto the pigs. Retrospective studies demonstrate that viral spillover into pigs may have been occurring, undetected, in Malaysia since 1996. During 1998, viral spread was aided by the transfer of infected pigs to other farms, where new outbreaks occurred.
Future threat The Nipah virus has been classified by the Centers for Disease Control and Prevention (CDC) as a Category C agent.Bioterrorism Agents/Diseases. bt.cdc.gov Nipah virus is one of several viruses identified by the World Health Organization (WHO) as a potential cause of future epidemics in a new plan developed after the Ebola epidemic for urgent research and development toward new diagnostic tests, vaccines and medicines. Identifying the factors that lead to outbreaks and conducting studies to understand how the virus spreads between species can help create better prevention strategies and reduce the chances of future outbreaks.
A major future challenge is to develop and maintain a supply of reliable, targeted, and affordable testing tools to enable rapid diagnostics in labs located in regions where the virus is likely to be found in wildlife reservoirs. Active collaboration between institutions and coordination among human and animal virologists are crucial for early outbreak detection and prompt implementation of preventive measures.Prarthana, M. S. (2018). Nipah virus in India: past, present and future. International Journal of Community Medicine and Public Health, 5(9), 3653.
The presence of fruit bats in various tropical countries, including Cambodia, Indonesia, Madagascar, the Philippines, and Thailand, is also recognized as a potential risk factor for future Nipah virus outbreaks.World Health Organization. Nipah virus. Accessed 21 September 2023. https://www.who.int/news-room/fact-sheets/detail/nipah-virus
Global travel and trade increase the risk of the Nipah virus spreading beyond its endemic regions, as undetected cases could cross borders. This calls for strong international surveillance and rapid response systems to monitor and contain potential outbreaks effectively.Gushulak, B. D., & MacPherson, D. W. (2013). Global travel, trade, and the spread of viral infections. Viral Infections and Global Change, 111–131.
The clinical impact of the Nipah virus highlights ongoing global public health risks due to the lack of effective treatments and vaccines. A strong international focus on developing vaccines and treatments is essential to reduce the health effects and future risks of Nipah virus.Khan, S., Akbar, S. M. F., Al Mahtab, M., Uddin, M. N., Rashid, M. M., Yahiro, T., ... & Nishizono, A. (2024). Twenty-five years of Nipah outbreaks in Southeast Asia: A persistent threat to global health. IJID regions, 13, 100434.
Prevention and treatment
Presently, there are no dedicated drugs or vaccines available for the treatment or prevention of Nipah virus infection. The World Health Organization (WHO) has designated the Nipah virus as a priority disease within the WHO Research and Development Blueprint. In cases of severe respiratory and neurological complications resulting from Nipah virus infection, healthcare professionals advise intensive supportive care as the primary treatment approach.
In 2019, the World Health Organization (WHO) released an advanced draft of a research and development roadmap aimed at accelerating the creation of medical countermeasures, including diagnostics, treatments, and vaccines, to support effective and timely responses to Nipah virus outbreaks.Moore, K. A., Mehr, A. J., Ostrowsky, J. T., Ulrich, A. K., Moua, N. M., Fay, P. C., ... & Osterholm, M. T. (2024). Measures to prevent and treat Nipah virus disease: research priorities for 2024–29. The Lancet Infectious Diseases.
In the 1998–99 Nipah virus outbreak in Malaysia, 140 patients received ribavirin, with their outcomes assessed against 54 historical controls who either lacked access to the drug or declined treatment. Results indicated a reduced mortality rate (32% compared to 54%) among those treated, although the use of historical controls could have introduced bias.Chong, H. T., Kamarulzaman, A., Tan, C. T., Goh, K. J., Thayaparan, T., Kunjapan, S. R., ... & Lam, S. K. (2001). Treatment of acute Nipah encephalitis with ribavirin. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 49(6), 810–813. No further clinical studies with ribavirin have been conducted, and research in animal models has not demonstrated its effectiveness against Nipah or Hendra virus infections.Rockx, B., Bossart, K. N., Feldmann, F., Geisbert, J. B., Hickey, A. C., Brining, D., ... & Geisbert, T. W. (2010). A novel model of lethal Hendra virus infection in African green monkeys and the effectiveness of ribavirin treatment. Journal of virology, 84(19), 9831–9839. Studies in animal models have also explored the use of chloroquine, both independently and with ribavirin, but have not demonstrated any therapeutic benefit.Freiberg, A. N., Worthy, M. N., Lee, B., & Holbrook, M. R. (2010). Combined chloroquine and ribavirin treatment does not prevent death in a hamster model of Nipah and Hendra virus infection. Journal of General Virology, 91(3), 765–772.