Nipah virus is a bat-borne, zoonoticvirus that causes Nipah virus infection in humans and other animals, a disease with a very high mortality rate (40-75%). Numerous disease outbreaks caused by Nipah virus have occurred in South East Africa and Southeast Asia. Nipah virus belongs to the genus Henipavirus along with the Hendra virus, which has also caused disease outbreaks.[1]
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.[2][3] The enveloped virus particles are variable in shape, and can be filamentous or spherical; they contain a helical nucleocapsid.[2] Six structural proteins are generated: N (nucleocapsid), P (phosphoprotein), M (matrix), F (fusion), G (glycoprotein) and L (RNA polymerase). The Popen reading frame also encodes three nonstructural proteins, C, V and W.
The Nipah virus structural model, constructed at an atomic resolution, depicts a particle with a diameter of 90 nm, adorned with spikes. This model affords a glimpse into the virus's interior. The Nipah virus is known for its high mortality rate and is viewed as a potential candidate for the next pandemic. The construction of this model utilized components from the UCSF Chimera database, sourced from the Protein Data Bank (pdb).
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.[4] 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.[4] 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.[5] The F glycoprotein forms a trimer, which mediates membrane fusion.[2][3]
Tropism
Ephrins B2 and B3 have been identified as the main receptors for Nipah virus.[2][3][6] 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.[7]
Geographic distribution
Pteropus vampyrus (large flying fox), one of the natural reservoirs of Nipah virus
Nipah virus has been isolated from Lyle's flying fox (Pteropus lylei) in Cambodia[8] and viral RNA found in urine and saliva from P. lylei and Horsfield's roundleaf bat (Hipposideros larvatus) in Thailand.[9] Ineffective forms of the virus has also been isolated from environmental samples of bat urine and partially eaten fruit in Malaysia.[10]Antibodies to henipaviruses have also been found in fruit bats in Madagascar (Pteropus rufus, Eidolon dupreanum)[11] and Ghana (Eidolon helvum)[12] indicating a wide geographic distribution of the viruses. No infection of humans or other species have been observed in Cambodia, Thailand or Africa as of May 2018. In September 2023, India reported at least five infections and two deaths.[13]
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.[15][16][17] The virus was isolated the following year in 1999.[1] This outbreak resulted in the culling of one million pigs. In Singapore, 11 cases, including one death, occurred in abattoir 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.[18][19]
The outbreak was originally mistaken for Japanese encephalitis, but physicians in the area noted that persons who had been vaccinated against Japanese encephalitis were not protected in the epidemic, and the number of cases among adults was unusual.[20] 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.[citation needed]
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.[21]
The transmission of 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 close proximity to the piggery, allowing the spillage of urine, faeces and partially eaten fruit onto the pigs.[22] Retrospective studies demonstrate that viral spillover into pigs may have been occurring, undetected, in Malaysia since 1996.[15] During 1998, viral spread was aided by the transfer of infected pigs to other farms, where new outbreaks occurred.[14]
Future threat
The Nipah virus has been classified by the Centers for Disease Control and Prevention as a Category C agent.[23] Nipah virus is one of several viruses identified by 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.[24][25]
Prevention & 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 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.[14]
In January 2024 a candidate vaccine, ChAdOx1 NipahB, commenced Phase I clinical trials after completing laboratory and animal testing.[26][27]
Nipah virus infection outbreaks have been reported in Malaysia, Singapore, Bangladesh and India. The highest mortality due to Nipah virus infection has occurred in Bangladesh, where outbreaks are typically seen in winter.[28] Nipah virus first appeared in 1998, in peninsular Malaysia in pigs and pig farmers. By mid-1999, more than 265 human cases of encephalitis, including 105 deaths, had been reported in Malaysia, and 11 cases of either encephalitis or respiratory illness with one fatality were reported in Singapore.[29] In 2001, Nipah virus was reported from Meherpur District, Bangladesh[30][31] and Siliguri, India.[30] The outbreak again appeared in 2003, 2004 and 2005 in Naogaon District, Manikganj District, Rajbari District, Faridpur District and Tangail District.[31] In Bangladesh there were also outbreaks in subsequent years.[32] In September 2021, Nipah virus resurfaced in Kerala, India claiming the life of a 12-year-old boy.[33] The most recent outbreak of Nipah virus occurred during January and February 2023 in Bangladesh with a total of 11 cases (ten confirmed, one probable) resulting in 8 deaths, a case fatality rate of 73%.[34] This outbreak resulted in the highest number of cases reported since 2015 in Bangladesh, and ten of the 11 cases during the 2023 outbreak had a confirmed history of consuming date palm sap.[34]
Locations of henipavirus outbreaks (red stars–Hendra virus; blue stars–Nipah virus) and distribution of henipavirus flying fox reservoirs (red shading–Hendra virus; blue shading–Nipah virus)
^ abField H, Young P, Yob JM, Mills J, Hall L, MacKenzie J (2001). "The natural history of Hendra and Nipah viruses". Microbes and Infection. 3 (4): 307–14. doi:10.1016/S1286-4579(01)01384-3. PMID11334748.
^Chua KB, Chua BH, Wang CW (2002). "Anthropogenic deforestation, El Niño and the emergence of Nipah virus in Malaysia". The Malaysian Journal of Pathology. 24 (1): 15–21. PMID16329551.
