Nipah virus

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Nipah virus
Nipah virus from an infected VERO cell.jpg
False-color electron micrograph showing a Nipah virus particle (purple) by an infected Vero cell (brown)
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Monjiviricetes
Order: Mononegavirales
Family: Paramyxoviridae
Genus: Henipavirus
Species:
Nipah virus

Nipah virus is a bat-borne, zoonotic virus 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]

Contents

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 P open 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). Nipah 12142023 1 ps.tif
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 Pteropus vampyrus2.jpg
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] In July 2024 a new infection occurred and a 14-year-old boy died as a result of it. [14]

Symptoms

These symptoms can be followed by more serious conditions including:

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. [16] [17] [18] 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. [19] [20]

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. [21] 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. [22]

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. [23] Retrospective studies demonstrate that viral spillover into pigs may have been occurring, undetected, in Malaysia since 1996. [16] During 1998, viral spread was aided by the transfer of infected pigs to other farms, where new outbreaks occurred. [15]

Future threat

The Nipah virus has been classified by the Centers for Disease Control and Prevention as a Category C agent. [24] 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. [25] [26] 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. [27]

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. [28]

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. [29]

Global travel and trade increase the risk of Nipah virus spreading beyond its endemic regions, as undetected cases could cross borders undetected. This calls for strong international surveillance and rapid response systems to monitor and contain potential outbreaks effectively. [30]

The clinical impact of 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. [31]

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 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. [15]

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. [32]

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. [33] 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. [34] Studies in animal models have also explored the use of chloroquine, both independently and with ribavirin, but it has not demonstrated any therapeutic benefit. [35]

A potentially more effective method is the application of monoclonal antibodies (mAbs), which can help neutralize the Nipah virus through passive administration. [36] Treatment with anti-Nipah virus monoclonal antibodies (mAbs) could be beneficial for early intervention and post-exposure prophylaxis in individuals exposed to the virus. The m102.4 antibody has demonstrated protective effects against lethal Nipah virus challenges in animal studies and has been administered under compassionate use to those exposed to either Hendra or Nipah viruses. [37] [38] In 2016, a phase 1 clinical trial for m102.4 was conducted in Australia with 40 participants, demonstrating that the treatment was safe and well-tolerated, with no signs of an immunogenic response. [38] Further research requirements for mAb therapy involve conducting clinical trials in endemic regions to evaluate its safety, tolerability, effectiveness, and pharmacokinetic properties in more detail. [38]

Remdesivir is another potential treatment option for Nipah virus. [39] Favipiravir and fusion inhibitory peptides may also show potential; however, additional studies are required to evaluate their effectiveness. [40] [41]

In January 2024 a candidate vaccine, ChAdOx1 NipahB, commenced Phase I clinical trials after completing laboratory and animal testing. [42] [43] However, the low occurrence of Nipah virus presents a significant challenge for conducting traditional phase 3 vaccine efficacy trials, as achieving a sample size large enough to reliably estimate vaccine effectiveness with sufficient statistical power is difficult. [44]

Outbreaks of disease

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. [45] 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. [46] In 2001, Nipah virus was reported from Meherpur District, Bangladesh [47] [48] and Siliguri, India. [47] The outbreak again appeared in 2003, 2004 and 2005 in Naogaon District, Manikganj District, Rajbari District, Faridpur District and Tangail District. [48] In Bangladesh there were also outbreaks in subsequent years. [49] In September 2021, Nipah virus resurfaced in Kerala, India claiming the life of a 12-year-old boy. [50] An 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%. [51] 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. [51] In July 2024, an outbreak was confirmed in Kerala state in India. A 14-year-old boy died and an additional 60 people were identified as being in the high-risk category of having the disease. [52]

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) Flying fox distribution.png
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)

Factors Contributing to Outbreaks

Population Density

The Nipah virus (NiV) has been detected in several of the world's most densely populated areas, particularly in Southeast Asia (SEAR). This region covers just 5% of the Earth's total land area, yet it is home to 26% of the global population. [53] Bangladesh is home to the world's most densely populated urban area, while Kerala, a state in southern India, ranks among the most densely populated states in India. [54] [27] High population density leads to increased interactions among people and between humans and their environments, which, coupled with the presence of farm animals in densely populated areas, raises the risk of virus spillover. [27]

Deforestation and Climate Change

Deforestation in the Southeast Asia region is occurring at an alarming pace, driven by factors such as grazing, agricultural expansion, industrialization, and urban development. [55] Deforestation has been identified as the key factor in the NiV outbreak in Malaysia during 1998–1999, as it increased human contact with bats infected with the virus. [56] Widespread deforestation and habitat fragmentation drive wildlife, especially fruit bats, the natural reservoirs of the Nipah virus, into closer proximity with human communities and livestock. As bats lose their natural habitats, they increasingly venture into agricultural areas to find food, which raises the likelihood of spillover events. [57]

Severe climatic changes have also been implicated in triggering NiV outbreaks in Bangladesh and India. The northwestern areas of Bangladesh have experienced extreme temperatures along with a rise in drought occurrences. [57] The Nipah virus outbreak in Malaysia occurred following a drought linked to El Niño conditions. The particular weather patterns and changes have been associated with spillover events. [58] In addition to droughts, flooding and rising sea levels have driven bats to migrate further into village areas. [57] Climate change, and extreme weather events negatively impact biodiversity, animal distribution, and microflora, all of which may raise the likelihood of zoonotic agents emerging and infectious disease outbreaks occurring. [59]

Socioeconomic Factors

The economic conditions, poverty levels, and population dynamics significantly influence a nation's overall strength; in areas where healthcare infrastructure is lacking, effectively managing outbreaks and delivering sufficient care to those infected becomes particularly difficult, worsening the consequences of Nipah virus outbreaks. [60] While pig farming has served as a significant source of income for farmers, the Nipah virus outbreak in Malaysia originated from pigs and their enclosures. The extensive culling of pigs due to the outbreak resulted in increased poverty and challenges related to recovery in the affected regions. [61] Limited public awareness about safe eating practices and the dangers linked to wildlife can increase exposure risks. Public health campaigns focused on food safety and avoiding bat habitats are essential for lowering these risks. [62]

In the 2011 movie Contagion the Nipah virus protein model was used in a scene describing the recombination found in a fictional paramyxovirus. [63]

See also

Related Research Articles

A zoonosis or zoonotic disease is an infectious disease of humans caused by a pathogen that can jump from a non-human to a human and vice versa.

<span class="mw-page-title-main">Encephalitis</span> Inflammation of the brain

Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, trouble speaking, memory problems, and problems with hearing.

<span class="mw-page-title-main">Marburg virus disease</span> Human viral disease

Marburg virus disease (MVD), formerly Marburg hemorrhagic fever (MHF) is a viral hemorrhagic fever in human and non-human primates caused by either of the two Marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV). Its clinical symptoms are very similar to those of Ebola virus disease (EVD).

<i>Henipavirus</i> Genus of RNA viruses

Henipavirus is a genus of negative-strand RNA viruses in the family Paramyxoviridae, order Mononegavirales containing six established species, and numerous others still under study. Henipaviruses are naturally harboured by several species of small mammals, notably pteropid fruit bats, microbats of several species, and shrews. Henipaviruses are characterised by long genomes and a wide host range. Their recent emergence as zoonotic pathogens capable of causing illness and death in domestic animals and humans is a cause of concern.

<span class="mw-page-title-main">Japanese encephalitis</span> Infection of the brain caused by the Japanese encephalitis virus

Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include headache, vomiting, fever, confusion and seizures. This occurs about 5 to 15 days after infection.

<span class="mw-page-title-main">Hendra virus</span> Species of virus

Hendra virus is a zoonotic virus found solely in Australia. First isolated in 1994, the virus has since been connected to numerous outbreaks of disease in domestic horses and seven human cases. Hendra virus belongs to the genus Henipavirus, which also contains the zoonotic Nipah virus. The reservoir species of Hendra virus are four species of bat within the genus Pteropus native to Australia.

<span class="mw-page-title-main">Viral hemorrhagic fever</span> Type of illnesses

Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses. VHFs may be caused by five distinct families of RNA viruses: the families Filoviridae, Flaviviridae, Rhabdoviridae, and several member families of the Bunyavirales order such as Arenaviridae, and Hantaviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, while others, such as Ebola virus, can cause severe, life-threatening disease.

Tioman virus is a paramyxovirus first isolated from the urine of island fruit bats on Tioman Island, Malaysia in 2000. The virus was discovered during efforts to identify the natural host of Nipah virus which was responsible for a large outbreak of encephalitic illness in humans and pigs in Malaysia and Singapore in 1998–99.

<i>Australian bat lyssavirus</i> Species of virus

Australian bat lyssavirus (ABLV), originally named Pteropid lyssavirus (PLV), is a enzootic virus closely related to the rabies virus. It was first identified in a 5-month-old juvenile black flying fox collected near Ballina in northern New South Wales, Australia, in January 1995 during a national surveillance program for the recently identified Hendra virus. ABLV is the seventh member of the genus Lyssavirus and the only Lyssavirus member present in Australia. ABLV has been categorized to the Phylogroup I of the Lyssaviruses.

<span class="mw-page-title-main">Emerging infectious disease</span> Infectious disease of emerging pathogen, often novel in its outbreak range or transmission mode

An emerging infectious disease (EID) is an infectious disease whose incidence has increased recently, and could increase in the near future. The minority that are capable of developing efficient transmission between humans can become major public and global concerns as potential causes of epidemics or pandemics. Their many impacts can be economic and societal, as well as clinical. EIDs have been increasing steadily since at least 1940.

<span class="mw-page-title-main">Rabies</span> Deadly viral disease, transmitted through animals

Rabies is a viral disease that causes encephalitis in humans and other mammals. It was historically referred to as hydrophobia because its victims would panic when offered liquids to drink. Early symptoms can include fever and abnormal sensations at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, the result is virtually always death. The time period between contracting the disease and the start of symptoms is usually one to three months but can vary from less than one week to more than one year. The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system.

<span class="mw-page-title-main">Vaccine Research Center</span>

The Vaccine Research Center (VRC), is an intramural division of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), US Department of Health and Human Services (HHS). The mission of the VRC is to discover and develop both vaccines and antibody-based products that target infectious diseases.

<span class="mw-page-title-main">Marburg virus</span> Species of filamentous virus responsible for hemorrhagic fever

Marburg virus (MARV) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. It causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.

Cedar virus, officially Cedar henipavirus, is a henipavirus known to be harboured by Pteropus spp. Infectious virus was isolated from the urine of a mixed Pteropus alecto and P. poliocephalus in Queensland, Australia in 2009. Unlike the Nipah and Hendra virus, Cedar virus infection does not lead to obvious disease in vivo. Infected animals mounted effective immune responses and seroconverted in challenge studies.

<span class="mw-page-title-main">Bat virome</span> Group of viruses associated with bats

The bat virome is the group of viruses associated with bats. Bats host a diverse array of viruses, including all seven types described by the Baltimore classification system: (I) double-stranded DNA viruses; (II) single-stranded DNA viruses; (III) double-stranded RNA viruses; (IV) positive-sense single-stranded RNA viruses; (V) negative-sense single-stranded RNA viruses; (VI) positive-sense single-stranded RNA viruses that replicate through a DNA intermediate; and (VII) double-stranded DNA viruses that replicate through a single-stranded RNA intermediate. The greatest share of bat-associated viruses identified as of 2020 are of type IV, in the family Coronaviridae.

<span class="mw-page-title-main">Nipah virus infection</span> Disease caused by Nipah virus

Nipah virus infection is an infection caused by the Nipah virus. Symptoms from infection vary from none to fever, cough, headache, shortness of breath, and confusion. This may worsen into a coma over a day or two, and 50 to 75% of those infected die. Complications can include inflammation of the brain and seizures following recovery.

<span class="mw-page-title-main">Nipah virus outbreaks in Kerala</span> Nipah virus outbreaks occurring in India

There have been several outbreaks of Nipah virus in Kerala, some of which have been traced to fruit bats. The NIV Pune confirmed the first case of Nipah virus in Kerala in May 2018. A total of 21 Nipah virus infected individuals died between 2018 and 2024.

<span class="mw-page-title-main">1998–1999 Malaysia Nipah virus outbreak</span> Disease outbreak in Malaysia

The 1998–1999 Malaysia Nipah virus outbreak occurred from September 1998 to May 1999 in the states of Perak, Negeri Sembilan and Selangor in Malaysia. A total of 265 cases of acute encephalitis with 105 deaths caused by the virus were reported in the three states throughout the outbreak. At first, the Malaysian health authorities thought that Japanese encephalitis (JE) was the cause of the infection. This misunderstanding hampered the deployment of effective measures to prevent the spread, before the disease was identified by a local virologist from the Faculty of Medicine, University of Malaya as a newly discovered agent. It was named Nipah virus (NiV). The disease was as deadly as the Ebola virus disease (EVD), but attacked the brain system instead of the blood vessels. University of Malaya's Faculty of Medicine and the University of Malaya Medical Centre played a major role in serving as a major referral centre for the outbreak, treating majority of the Nipah patients and was instrumental in isolating the novel virus and researched on its features.

Ghanaian bat henipavirus (also known Kumasi virus belongs to the genus Henipavirus in the family Paramyxoviridae. Human infections are caused by zoonotic events where the virus crosses over from another animal species. Therefore, humans are not the innate host for this virus family but instead become infected by peripheral viral reservoirs such as bats and other carriers of the virus. When these virus are spread to humans through zoonotic events they have been found to be one of the most deadly viruses with the capability to infect humans, with mortality rates between 50 and 100%. Therefore, these viruses have been classified as a biosafety level four virus with regards to its pathogenesis when it infects humans.

<span class="mw-page-title-main">Mòjiāng virus</span> Species of virus

Mòjiāng virus(MojV), officially Mojiang henipavirus, is a virus in the family Paramyxoviridae. Based on phylogenetics, Mòjiāng virus is placed in the genus Henipavirus or described as a henipa-like virus. Antibodies raised against Mòjiāng virus glycoproteins are serologically distinct from other henipaviruses (among which higher cross-reactivity is observed).

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