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Recent progress in henipavirus research

Halpin K, Mungall BA

Comp Immunol Microbiol Infect Dis, 2007 Sep;30(5-6):287-307.
PMID: 17629946

Following the discovery of two new paramyxoviruses in the 1990s, much effort has been placed on rapidly finding the reservoir hosts, characterising the genomes, identifying the viral receptors and formulating potential vaccines and therapeutic options for these viruses, Hendra and Nipah viruses caused zoonotic disease on a scale not seen before with other paramyxoviruses. Nipah virus particularly caused high morbidity and mortality in humans and high morbidity in pig populations in the first outbreak in Malaysia. Both viruses continue to pose a threat with sporadic outbreaks continuing into the 21st century. Experimental and surveillance studies identified that pteropus bats are the reservoir hosts. Research continues in an attempt to understand events that precipitated spillover of these viruses. Discovered on the cusp of the molecular technology revolution, much progress has been made in understanding these new viruses. This review endeavours to capture the depth and breadth of these recent advances.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Mapping risk of Nipah virus transmission across Asia and across Bangladesh

Peterson AT

Asia Pac J Public Health, 2015 Mar;27(2):NP824-32.
PMID: 23343646 DOI: 10.1177/1010539512471965

Nipah virus is a highly pathogenic but poorly known paramyxovirus from South and Southeast Asia. In spite of the risks that it poses to human health, the geography and ecology of its occurrence remain little understood-the virus is basically known from Bangladesh and peninsular Malaysia, and little in between. In this contribution, I use documented occurrences of the virus to develop ecological niche-based maps summarizing its likely broader occurrence-although rangewide maps could not be developed that had significant predictive abilities, reflecting minimal sample sizes available, maps within Bangladesh were quite successful in identifying areas in which the virus is predictably present and likely transmitted.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Fulltext Emerging epidemic viral encephalitides with a special focus on henipaviruses

Wong KT

Acta Neuropathol, 2010 Sep;120(3):317-25.
PMID: 20652579 DOI: 10.1007/s00401-010-0720-z

In the last few decades, there is an increasing emergence and re-emergence of viruses, such as West Nile virus, Enterovirus 71 and henipaviruses that cause epidemic viral encephalitis and other central nervous system (CNS) manifestations. The mortality and morbidity associated with these outbreaks are significant and frequently severe. While aspects of epidemiology, basic virology, etc., may be known, the pathology and pathogenesis are often less so, partly due to a lack of interest among pathologists or because many of these infections are considered "third world" diseases. In the study of epidemic viral encephalitis, the pathologist's role in unravelling the pathology and pathogenesis is critical. The novel henipavirus infection is a good example. The newly created genus Henipavirus within the family Paramyxoviridae consists of two viruses, viz., Hendra virus and Nipah virus. These two viruses emerged in Australia and Asia, respectively, to cause severe encephalitides in humans and animals. Studies show that the pathological features of the acute encephalitis caused by henipaviruses are similar and a unique dual pathogenetic mechanism of vasculitis-induced microinfarction and parenchymal cell infection in the CNS (mainly neurons) and other organs causes severe tissue damage. Both viruses can cause relapsing encephalitis months and years after the acute infection due to a true recurrent infection as evidenced by the presence of virus in infected cells. Future emerging viral encephalitides will no doubt continue to pose considerable challenges to the neuropathologist, and as the West Nile virus outbreak demonstrates, even economically advanced nations are not spared.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Fulltext Evidence for Nipah virus recrudescence and serological patterns of captive Pteropus vampyrus

Sohayati AR, Hassan L, Sharifah SH, Lazarus K, Zaini CM, Epstein JH, et al.

Epidemiol Infect, 2011 Oct;139(10):1570-9.
PMID: 21524339 DOI: 10.1017/S0950268811000550

This study aimed to describe the transmission dynamics, the serological and virus excretion patterns of Nipah virus (NiV) in Pteropus vampyrus bats. Bats in captivity were sampled every 7-21 days over a 1-year period. The data revealed five NiV serological patterns categorized as high and low positives, waning, decreasing and increasing, and negative in these individuals. The findings strongly suggest that NiV circulates in wild bat populations and that antibody could be maintained for long periods. The study also found that pup and juvenile bats from seropositive dams tested seropositive, indicating that maternal antibodies against NiV are transmitted passively, and in this study population may last up to 14 months. NiV was isolated from the urine of one bat, and within a few weeks, two other seronegative bats seroconverted. Based on the temporal cluster of seroconversion, we strongly believe that the NiV isolated was recrudesced and then transmitted horizontally between bats during the study period.

Matched MeSH terms: Henipavirus Infections/epidemiology
Fulltext Emerging paramyxoviruses: molecular mechanisms and antiviral strategies

Aguilar HC, Lee B

Expert Rev Mol Med, 2011;13:e6.
PMID: 21345285 DOI: 10.1017/S1462399410001754

In recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. Hendra and Nipah viruses (henipaviruses within this family) were first identified in the 1990s in Australia, Malaysia and Singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. Other paramyxoviruses, such as Menangle virus, Tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.

Matched MeSH terms: Henipavirus Infections/epidemiology
Fulltext Transmission of human infection with Nipah virus

Luby SP, Gurley ES, Hossain MJ

Clin Infect Dis, 2009 Dec 1;49(11):1743-8.
PMID: 19886791 DOI: 10.1086/647951

Nipah virus (NiV) is a paramyxovirus whose reservoir host is fruit bats of the genus Pteropus. Occasionally the virus is introduced into human populations and causes severe illness characterized by encephalitis or respiratory disease. The first outbreak of NiV was recognized in Malaysia, but 8 outbreaks have been reported from Bangladesh since 2001. The primary pathways of transmission from bats to people in Bangladesh are through contamination of raw date palm sap by bats with subsequent consumption by humans and through infection of domestic animals (cattle, pigs, and goats), presumably from consumption of food contaminated with bat saliva or urine with subsequent transmission to people. Approximately one-half of recognized Nipah case patients in Bangladesh developed their disease following person-to-person transmission of the virus. Efforts to prevent transmission should focus on decreasing bat access to date palm sap and reducing family members' and friends' exposure to infected patients' saliva.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Fulltext Lessons from the Nipah virus outbreak in Malaysia

Looi LM, Chua KB

Malays J Pathol, 2007 Dec;29(2):63-7.
PMID: 19108397 MyJurnal

The Nipah virus outbreak in Malaysia (September 1998 to May 1999) resulted in 265 cases of acute encephalitis with 105 deaths, and near collapse of the billion-dollar pig-farming industry. Because it was initially attributed to Japanese encephalitis, early control measures were ineffective, and the outbreak spread to other parts of Malaysia and nearby Singapore. The isolation of the novel aetiological agent, the Nipah virus (NiV), from the cerebrospinal fluid of an outbreak victim was the turning point which led to outbreak control 2 months later. Together with the Hendra virus, NiV is now recognised as a new genus, Henipavirus (Hendra + Nipah), in the Paramyxoviridae family. Efforts of the local and international scientific community have since elucidated the epidemiology, clinico-pathophysiology and pathogenesis of this new disease. Humans contracted the infection from close contact with infected pigs, and formed the basis for pig-culling that eventually stopped the outbreak. NiV targeted medium-sized and small blood vessels resulting in endothelial multinucleated syncytia and fibrinoid necrosis. Autopsies revealed disseminated cerebral microinfarctions resulting from vasculitis-induced thrombosis and direct neuronal involvement. The discovery of NiV in the urine and saliva of Malaysian Island flying foxes (Pteropus hypomelanus and Petropus vampyrus) implicated these as natural reservoir hosts of NiV. It is probable that initial transmission of NiV from bats to pigs occurred in late 1997/early 1998 through contamination of pig swill by bat excretions, as a result of migration of these forest fruitbats to cultivated orchards and pig-farms, driven by fruiting failure of forest trees during the El Nino-related drought and anthropogenic fires in Indonesia in 1997-1998. This outbreak emphasizes the need for sharing information of any unusual illnesses in animals and humans, an open-minded approach and close collaboration and co-ordination between the medical profession, veterinarians and wildlife specialists in the investigation of such illnesses. Environmental mismanagement (such as deforestation and haze) has far-reaching effects, including encroachment of wildlife into human habitats and the introduction of zoonotic infections into domestic animals and humans.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Fulltext Role of electron microscopy in Nipah virus outbreak investigation and control

Chua KB, Wong EM, Cropp BC, Hyatt AD

Med J Malaysia, 2007 Jun;62(2):139-42.
PMID: 18705447 MyJurnal

In 1998, a novel paramyxovirus (order Mononegavirales, family Paramyxoviridae, subfamily Paramyxovirinae, genus Henipavirus) emerged in peninsular Malaysia causing fatal encephalitis in humans and severe respiratory illness with encephalitis in pigs. The virus was successfully isolated in cultured mammalian cells. Transmission electron microscopy of infected tissue culture cells played a crucial role in the early preliminary identification of the causative agent of the outbreak. This in turn was pivotal to determine the correct direction of control measures that subsequently brought the epidemic under control. In light of this investigation, and indeed identification of infectious agents associated with other disease episodes, electron microscopy will remain an important frontline method for rapid diagnostic virology and investigation of any future outbreak of new and unusual cases of illness suspected of an infectious aetiology.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Henipaviruses: a new family of emerging Paramyxoviruses

Wild TF

Pathol. Biol., 2009 Mar;57(2):188-96.
PMID: 18511217 DOI: 10.1016/j.patbio.2008.04.006

Paramyxoviruses have been implicated in both animal and human infections. Some viruses, such as Morbilliviruses are responsible for large-scale epidemics. However, there are limited observations of these viruses crossing the host species barrier in nature. In 1994, in Australia a fatal infection in horses and humans was identified to be caused by a new Paramyxovirus, Hendra virus (HeV), and in 1998 in Malaysia, a closely related virus, Nipah virus (NiV) was responsible for fatal infections in pigs and humans. These two viruses were sufficiently different from previously described Paramyxoviruses to create a new genus, Henipaviruses. The natural reservoir of these viruses was the fruit bat (Pteropus), which is found in regions extending from the western Pacific to the eastern coast of Africa. Serological studies have established that as many as half the fruit bats in colonies throughout these regions may have antibodies against this family of viruses. The availability of diagnostic reagents for Nipah virus in humans have identified infections in several countries including, Bangladesh, India and Indonesia. In some of these epidemics, mortality in humans exceeds 75%. Deforestation is probably responsible for fruit bats leaving their ecological niches and approaching farms and villages. The infection of humans and animals may occur via contaminated foods or in certain cases by animals to man. At present, only within close families has human-to-human transmission been proposed. Henipavirus infections are probably more widespread than it is at presently known and so it is important to have an intense monitoring for these diseases, especially in countries where large-scale deforestation is happening.

Matched MeSH terms: Henipavirus Infections/epidemiology*
The emergence of Nipah virus, a highly pathogenic paramyxovirus

Lo MK, Rota PA

J Clin Virol, 2008 Dec;43(4):396-400.
PMID: 18835214 DOI: 10.1016/j.jcv.2008.08.007

Nipah virus first emerged in Malaysia and Singapore between 1998 and 1999, causing severe febrile encephalitis in humans with a mortality rate of close to 40%. In addition, a significant portion of those recovering from acute infection had relapse encephalitis and long-term neurological defects. Since its initial outbreak, there have been numerous outbreaks in Bangladesh and India, in which the mortality rate rose to approximately 70%. These subsequent outbreaks were distinct from the initial outbreak, both in their epidemiology and in their clinical presentations. Recent developments in diagnostics may expedite disease diagnosis and outbreak containment, while progress in understanding the molecular biology of Nipah virus could lead to novel therapeutics and vaccines for this deadly pathogen.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Henipaviruses: emerging paramyxoviruses associated with fruit bats

Field HE, Mackenzie JS, Daszak P

Curr. Top. Microbiol. Immunol., 2007;315:133-59.
PMID: 17848064

Two related, novel, zoonotic paramyxoviruses have been described recently. Hendra virus was first reported in horses and thence humans in Australia in 1994; Nipah virus was first reported in pigs and thence humans in Malaysia in 1998. Human cases of Nipah virus infection, apparently unassociated with infection in livestock, have been reported in Bangladesh since 2001. Species of fruit bats (genus Pteropus) have been identified as natural hosts of both agents. Anthropogenic changes (habitat loss, hunting) that have impacted the population dynamics of Pteropus species across much of their range are hypothesised to have facilitated emergence. Current strategies for the management of henipaviruses are directed at minimising contact with the natural hosts, monitoring identified intermediate hosts, improving biosecurity on farms, and better disease recognition and diagnosis. Investigation of the emergence and ecology of henipaviruses warrants a broad, cross-disciplinary ecosystem health approach that recognises the critical linkages between human activity, ecological change, and livestock and human health.

Matched MeSH terms: Henipavirus Infections/epidemiology
Nipah's return. The lethal "flying fox" virus may spread between people

Choi C

Sci. Am., 2004 Sep;291(3):21A, 22.
PMID: 15376742
Matched MeSH terms: Henipavirus Infections/epidemiology
Fatal fruit bat virus sparks epidemics in southern Asia

Butler D

Nature, 2004 May 6;429(6987):7.
PMID: 15129247
Matched MeSH terms: Henipavirus Infections/epidemiology*
Fulltext Nipah outbreak in North Kerala - What worked? Insights for future response and recovery based on examination of various existing frameworks

Rahim AA, Chacko TV

Indian J Public Health, 2019 9 26;63(3):261-264.
PMID: 31552860 DOI: 10.4103/ijph.IJPH_117_19

Asia Pacific region has been witnessing numerous public health emergencies in recent years with the Nipah outbreak in North Kerala (2018), India, needs special mention. Threats posed and experiences gained have compelled health systems to draft frameworks nationally and internationally for preparedness, outbreak response, and recovery. Our failure to obtain comprehensive guiding frameworks for application in the Indian context for Ebola, Severe Acute Respiratory Syndrome, Influenza A (H1N1), and Nipah outbreaks led us to the search outside India for frameworks that have worked in the past. A thorough review of the WHO, Centers for Disease Control and Prevention, and Malaysian framework was done to identify explicit components and replicable objectives to the national context. In the absence of a specific framework, Nipah recovery and response experience that worked in Kerala outbreak (2018) was compared against novel H1N1 (2015) guidelines at national level. This article provides the groundwork and insights as a value addition toward an India-specific framework of action for response and recovery for Nipah outbreaks in future.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Fulltext Genetic diversity of Nipah virus in Bangladesh

Rahman MZ, Islam MM, Hossain ME, Rahman MM, Islam A, Siddika A, et al.

Int J Infect Dis, 2021 Jan;102:144-151.
PMID: 33129964 DOI: 10.1016/j.ijid.2020.10.041

BACKGROUND: Nipah virus (NiV) infection, often fatal in humans, is primarily transmitted in Bangladesh through the consumption of date palm sap contaminated by Pteropus bats. Person-to-person transmission is also common and increases the concern of large outbreaks. This study aimed to characterize the molecular epidemiology, phylogenetic relationship, and the evolution of the nucleocapsid gene (N gene) of NiV.
METHODS: We conducted molecular detection, genetic characterization, and Bayesian time-scale evolution analyses of NiV using pooled Pteropid bat roost urine samples from an outbreak area in 2012 and archived RNA samples from NiV case patients identified during 2012-2018 in Bangladesh.
RESULTS: NiV-RNA was detected in 19% (38/456) of bat roost urine samples and among them; nine N gene sequences were recovered. We also retrieved sequences from 53% (21 out of 39) of archived RNA samples from patients. Phylogenetic analysis revealed that all Bangladeshi strains belonged to NiV-BD genotype and had an evolutionary rate of 4.64 × 10-4 substitutions/site/year. The analyses suggested that the strains of NiV-BD genotype diverged during 1995 and formed two sublineages.
CONCLUSION: This analysis provides further evidence that the NiV strains of the Malaysian and Bangladesh genotypes diverged recently and continue to evolve. More extensive surveillance of NiV in bats and human will be helpful to explore strain diversity and virulence potential to infect humans through direct or person-to-person virus transmission.

Matched MeSH terms: Henipavirus Infections/epidemiology
Fulltext A 'what-if' scenario: Nipah virus attacks pig trade chains in Thailand

Wongnak P, Thanapongtharm W, Kusakunniran W, Karnjanapreechakorn S, Sutassananon K, Kalpravidh W, et al.

BMC Vet Res, 2020 Aug 24;16(1):300.
PMID: 32838786 DOI: 10.1186/s12917-020-02502-4

BACKGROUND: Nipah virus (NiV) is a fatal zoonotic agent that was first identified amongst pig farmers in Malaysia in 1998, in an outbreak that resulted in 105 fatal human cases. That epidemic arose from a chain of infection, initiating from bats to pigs, and which then spilled over from pigs to humans. In Thailand, bat-pig-human communities can be observed across the country, particularly in the central plain. The present study therefore aimed to identify high-risk areas for potential NiV outbreaks and to model how the virus is likely to spread. Multi-criteria decision analysis (MCDA) and weighted linear combination (WLC) were employed to produce the NiV risk map. The map was then overlaid with the nationwide pig movement network to identify the index subdistricts in which NiV may emerge. Subsequently, susceptible-exposed-infectious-removed (SEIR) modeling was used to simulate NiV spread within each subdistrict, and network modeling was used to illustrate how the virus disperses across subdistricts.
RESULTS: Based on the MCDA and pig movement data, 14 index subdistricts with a high-risk of NiV emergence were identified. We found in our infectious network modeling that the infected subdistricts clustered in, or close to the central plain, within a range of 171 km from the source subdistricts. However, the virus may travel as far as 528.5 km (R0 = 5).
CONCLUSIONS: In conclusion, the risk of NiV dissemination through pig movement networks in Thailand is low but not negligible. The risk areas identified in our study can help the veterinary authority to allocate financial and human resources to where preventive strategies, such as pig farm regionalization, are required and to contain outbreaks in a timely fashion once they occur.

Matched MeSH terms: Henipavirus Infections/epidemiology
A longitudinal study of the prevalence of Nipah virus in Pteropus lylei bats in Thailand: evidence for seasonal preference in disease transmission

Wacharapluesadee S, Boongird K, Wanghongsa S, Ratanasetyuth N, Supavonwong P, Saengsen D, et al.

Vector Borne Zoonotic Dis, 2010 Mar;10(2):183-90.
PMID: 19402762 DOI: 10.1089/vbz.2008.0105

After 12 serial Nipah virus outbreaks in humans since 1998, it has been noted that all except the initial event in Malaysia occurred during the first 5 months of the year. Increasingly higher morbidity and mortality have been observed in subsequent outbreaks in India and Bangladesh. This may have been related to different virus strains and transmission capability from bat to human without the need for an amplifying host and direct human-to-human transmission. A survey of virus strains in Pteropus lylei and seasonal preference for spillover of these viruses was completed in seven provinces of Central Thailand between May 2005 and June 2007. Nipah virus RNA sequences, which belonged to those of the Malaysian and Bangladesh strains, were detected in the urine of these bats, with the Bangladesh strain being dominant. Highest recovery of Nipah virus RNA was observed in May. Of two provincial sites where monthly surveys were done, the Bangladesh strain was almost exclusively detected during April to June. The Malaysian strain was found dispersed during December to June. Although direct contact during breeding (in December to April) was believed to be an important transmission factor, our results may not entirely support the role of breeding activities in spillage of virus. Greater virus shedding over extended periods in the case of the Malaysian strain and the highest peak of virus detection in May in the case of the Bangladesh strain when offspring started to separate may suggest that there may be responsible mechanisms other than direct contact during breeding in the same roost. Knowledge of seasonal preferences of Nipah virus shedding in P. lylei will help us to better understand the dynamics of Nipah virus transmission and have implications for disease management.

Matched MeSH terms: Henipavirus Infections/epidemiology
Henipaviruses at the Interface Between Bats, Livestock and Human Population in Africa

Mbu'u CM, Mbacham WF, Gontao P, Sado Kamdem SL, Nlôga AMN, Groschup MH, et al.

Vector Borne Zoonotic Dis, 2019 07;19(7):455-465.
PMID: 30985268 DOI: 10.1089/vbz.2018.2365

Nipah virus (NiV) and Hendra virus (HeV) are closely related members within the genus Henipavirus, family Paramyxoviridae, for which fruit bats serve as the reservoir. The initial emergence of NiV infections in pigs and humans in Malaysia, and HeV infections in horses and humans in Australia, posed severe impacts on human and animal health, and continues threatening lives of humans and livestock within Southeast Asia and Australia. Recently, henipavirus-specific antibodies have also been detected in fruit bats in a number of sub-Saharan African countries and in Brazil, thereby considerably increasing the known geographic distribution of henipaviruses. Africa is progressively being recognized as a new high prevalence zone for henipaviruses, as deduced from serological and molecular evidence of past infections in Madagascar, Ghana, Republic of Congo, Gulf of Guinea, Zambia, Tanzania, Cameroon, and Nigeria lately. Serological data suggest henipavirus spillover from bats to livestock and human populations in Africa without reported clinical disease in any of these species. All virus isolation attempts have been abortive, highlighting the need for further investigations. The genome of the Ghanaian bat henipavirus designated Ghana virus (GhV), which was detected in a pteropid Eidolon helvum bat, is the only African henipavirus that has been completely sequenced limiting our current knowledge on the genetic diversity and pathogenesis of African henipaviruses. In this review, we summarize the available data on the circulation of henipaviruses in Africa, discuss potential sources for virus spillover, and highlight existing research gaps.

Matched MeSH terms: Henipavirus Infections/epidemiology*
Nipah virus: transmission of a zoonotic paramyxovirus

Clayton BA

Curr Opin Virol, 2017 Feb;22:97-104.
PMID: 28088124 DOI: 10.1016/j.coviro.2016.12.003

Nipah virus is a recently-recognised, zoonotic paramyxovirus that causes severe disease and high fatality rates in people. Outbreaks have occurred in Malaysia, Singapore, India and Bangladesh, and a putative Nipah virus was also recently associated with human disease in the Philippines. Worryingly, human-to-human transmission is common in Bangladesh, where outbreaks occur with near-annual frequency. Onward human transmission of Nipah virus in Bangladesh is associated with close contact with clinically-unwell patients or their infectious secretions. While Nipah virus isolates associated with outbreaks of human infection have not resulted in sustained transmission to date, specific exposures carry a high risk of person-to-person transmission, an observation which is supported by recent findings in animal models. Novel paramyxoviruses continue to emerge from wildlife hosts, and represent an ongoing threat to human health globally.

Matched MeSH terms: Henipavirus Infections/epidemiology
Fulltext The Main Risk Factors of Nipah Disease and Its Risk Analysis in China

Yu J, Lv X, Yang Z, Gao S, Li C, Cai Y, et al.

Viruses, 2018 10 19;10(10).
PMID: 30347642 DOI: 10.3390/v10100572

Nipah disease is a highly fatal zoonosis which is caused by the Nipah virus. The Nipah virus is a BSL-4 virus with fruit bats being its natural host. It is mainly prevalent in Southeast Asia. The virus was first discovered in 1997 in Negeri Sembilan, Malaysia. Currently, it is mainly harmful to pigs and humans with a high mortality rate. This study describes the route of transmission of the Nipah virus in different countries and analyzes the possibility of the primary disease being in China and the method of its transmission to China. The risk factors are analyzed for different susceptible populations to Nipah disease. The aim is to improve people's risk awareness and prevention and control of the disease and reduce its risk of occurring and spreading in China.

Matched MeSH terms: Henipavirus Infections/epidemiology*

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