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Home  >  Medical Research Archives  >  Issue 149  > 4 Origin Scenarios if a Nipah Virus outbreak occurs outside South/SE Asia
Published in the Medical Research Archives
Jun 2023 Issue

4 Origin Scenarios if a Nipah Virus outbreak occurs outside South/SE Asia

Published on Jun 26, 2023




Nipah virus is a bat-borne zoonotic RNA virus discovered in Malaysia during an 1998-1999 outbreak that involved pigs, fruit bats, and humans in Malaysia (1). Clinical manifestations are primarily encephalitis and pneumonia. The case fatality rate of symptomatic cases is 40%-70%. Survivors can have severe neurologic sequelae (2-5). There are no licensed vaccines, antiviral drugs, monoclonal antibodies, or point-of-care rapid diagnostic tests, although extensive work on vaccines and monoclonal antibodies is underway (6). Person-to-person transmission, including a small number of superspreading events, has occurred in Bangladesh and India (7-9).


From 1998-2023 all reported outbreaks have been in either southeast (SE) Asia (Malaysia, Singapore, the Philippines), or south Asia (Bangladesh, India) (2, 7-10). It is likely that a future Nipah outbreak, and possibly widespread epidemic, will occur outside south/SE Asia, whether elsewhere in Asia such as China, or on another continent. When it does, then as with the COVID-19 pandemic, multiple questions will be raised regarding the origin of the epidemic. Each of the following four (4) main scenarios could be anticipated to account for the origin of such a geographically-unprecedented Nipah epidemic during analysis on Day 1 of the event by national and international organizations.

Author info

Daniel Lucey

Scenario 1: Accidental Infection in a Nipah virus Field Researcher or a Traveler
In September 2022 the World Health Organization (WHO) published a landmark document11 titled, “Global guidance framework for the responsible use of the life sciences: mitigating biorisks and governing dual use research. Annex 2 offers three Case studies for responsible life sciences research on high-consequence pathogens. Along with chemical synthesis of poliovirus cDNA and 1918 pandemic influenza reconstruction is a case study11 titled, Environmental surveillance for Nipah virus.
Two types of environmental surveillance for Nipah virus from Pteropus species fruit bats are listed. These are: (1) spreading tarpaulins on the ground beneath trees where the fruit bat species (pteropus) that can be infected with Nipah virus roost, and then pooling the collected samples from the tarpaulins before testing for Nipah virus; (2) capturing and then testing individual bats for Nipah virus e.g., via blood, throat, and urine specimens. The WHO case study specifies the pandemic risk of such work below (boldtype added for emphasis):

Criticism of environmental surveillance research tends to focus on the risk posed to society if a field researcher is infected with a pathogen with pandemic potential. The risk of viral exposure is most prevalent when collecting samples directly from living wild  animals. These risks can include needle  sticks while  taking  blood  samples,  exposure  of  animal excreta to open wounds, and bites or scratches from improperly anaesthetized animals. The first environmental surveillance collection method limits the risks posed by needle sticks and bites or scratches, but the data quality is sacrificed as a result. Lower data quality may reduce the impact the study results can have on preventing or mitigating Nipah virus spillover events. The second environmental surveillance collection method produces high-quality and specific data, but the risk to field researchers is considerably increased. The UNINTEntional infection of a researcher with Nipah viRUS has the potential to resULt in a global pandemic if proper pRECAUTIOns are not followed. 11

In the hypothetical Day 1 outbreak analysis,  this  scenario  could  be  initiated  by  the accidental infection of one or more field researchers and  potential person-to-person spread of Nipah virus in at least two ways. The first is if the field researcher is working in a location in south/SE Asia and  then  that individual, or someone infected by them, travels to a location elsewhere in Asia such as China, or somewhere  outside  Asia  altogether.  A second   scenario that can be envisioned and anticipated is if the infected field researcher is working in a location where Nipah-infected bats exist outside south/SE Asia.

Scenario 2: Animals Known or Unknown to Infect Humans
Another scenario hypothesizes that the infection occurred from an animal to a human. For example, in the first-recognized Nipah outbreak of 1998-1999 in Malaysia pigs on large commercial pig farms constructed in rural areas were infected by fruit bats carrying the virus. Persons in contact with the pig farms, or abattoirs, became infected. Infected pigs transferred to different places in Malaysia, and Singapore, also resulted in more pig and human infections1.
In 2014 the first and still only reported Nipah outbreak occurred in the Philippines on the southern island of Mindanao. Filipino public health officials reported in 2015 that horses were infected in two villages in Ninoy Aquino province and then horse-to-horse and horse-human infections occurred10. It was suggested that humans might have been infected through consumption of undercooked horse meat 10. Until this outbreak it was not clear that humans could be infected by Nipah-infected horses. Thus, additional still- unrecognized animal species might exist that can transmit the virus to humans (see also next scenario). Unlike rabies virus, direct infection of humans by bats has not been established.

Scenario 3: Food or Drink
A third scenario hypothesizes that Nipah virus-infected food would be the source of an outbreak. This scenario could include direct consumption and infection of humans via the food. Implicated Nipah-infected food to date includes mango (in the Malaysia 1998-1999 outbreak, but not implicated to date anywhere outside Malaysia), and date palm sap in Bangladesh, including a liquor (tari) made from fermented date palm sap 12.
Alternatively, it could involve consumption of the virus-infected food by an animal e.g., pigs or horses or other susceptible animals, or even an unrecognized susceptible animal species in a part of the world outside of south/SE Asia.
An example of the latter occurred with a different virus in 2003 in the USA. Prairie dogs were infected for the first time with mpox (then called  monkeypox) in pet dealerships in the USA following importation of mpox-infected exotic pets (e.g., African giant pouched rats, dormice, and rope squirrels) from Ghana 13.

Food-borne transmission of Nipah virus in Syrian hamsters was reported in 2014 by US researchers 14. Important caveats, however, include that the food was a laboratory-prepared artificial date palm sap to which the virus was added in a laboratory setting. Of note, some hamster-to-hamster transmission was observed after this food-borne infections.

Scenario 4: Laboratory-Related
It must be emphasized that currently there are no reports or published studies on Nipah virus and any type of research variously referred to as gain-of-function (GoF), dual use research of concern (DURC), or “enhanced potential pandemic pathogens (ePPP). Moreover, there are no reports of serial passage of Nipah virus in any susceptible animal species e.g., ferrets, Syrian hamsters, or African Green Monkeys.
Nevertheless, such research could occur in one or more laboratories worldwide. This hypothetical concern was acknowledged briefly in a 1,028-page document15 discussing a wide spectrum of GoF research and policy issues that was published online in the US in 2016 by Gryphon Scientific:

Similar techniques to those used in GoF experiments could be leveraged for other pathogens to create a highly transmissible strain of an already deadly virus (like the Hendra and Nipah viruses)… page 217 of 1028.

Examples of concern regarding potential use of a Nipah virus with genetically-enhanced transmissibility occurred in two hypothetical simulation exercises in the USA in 2016 and 2018. The first scenario imagined a bioterrorism attack on Washington, DC and four states16

…during our Independence Day celebrations. Many of our own colleagues and staff fell ill and died. Thousands more were killed in coordinated attacks in allied nations in the days that followed. The attack here in Washington, D.C. used aerosol delivery devices we could see, but did not know contained dangerous organisms. We discovered later that other attacks had already begun elsewhere in the Nation, using methods we have yet to identify that spread the disease among livestock in rural communities. Delays in recognition – because most veterinarians and physicians had never seen Nipah virus – meant animals and people were sick for more than a week before we realized what had happened. And now we are being told that the virus, which in nature does not spread easily among people, was genetically modified to increase its ability to spread from animal to animal, animal to person, and person to person.16.

The second hypothetical scenario was a tabletop exercise held on May 2018 in Washington, DC called Clade X. In this scenario, on another continent certain genes from Nipah virus were inserted into a known respiratory-transmitted highly contagious virus. This hybrid virus was termed clade X. In this extreme-case scenario the resulting pandemic began in Europe and South America and eventually resulted in 150 million deaths 17.
The potential for accidental infection with Nipah virus of humans and/or animals associated in any way with a laboratory is of perhaps enhanced concern given the ongoing three-year controversy 18 regarding the origin of SARS-CoV-2/COVID-19, given its first report in Wuhan, China. The World Health Organization Scientific Advisory Group on Origins of Novel pathogens (WHO SAGO) has addressed this issue18 and continues to do so as of 2023.

This hypothetical Day 1 outbreak scenario analysis might be considered by the WHO SAGO of international experts if an unusual Nipah virus epidemic occurred. Their involvement would be especially likely if the earliest-recognized location of the outbreak was outside of south/SE Asia, and particularly if it was in Wuhan or elsewhere in Hubei province, China. Importantly however, given the growing number of BSL-4 laboratories worldwide that might work on Nipah virus, including ones in the USA, Europe, Asia and likely elsewhere, then high vigilance for optimal biosafety is essential everywhere worldwide and not only in China.

At the large international Nipah virus conference held in Singapore December 9-10, 2019 researchers from around the world gave presentations on what had been learned, and what still needed to be learned, over the 20 years since the discovery of Nipah virus.19 Abstracts of the presentations are still available in a 67-page online document. One of the final abstracts (on page 65 of 67) was by the renowned virologist at the Wuhan Institute of Virology and Editor-in-Chief of the journal Virologica Sinica, Dr. Zhengli Shi19. This abstract included the following statements: Nipah represents a priority pathogen for the Wuhan facility, due to 1) its ability to infect animals and humans; 2) its high mortality in humans; and 3) the prevalence of henipaviruses and henipa-like viruses in countries of Southeast Asia, including China. Work on Nipah is divided into six work packages: 1) NiV pathogenesis; 2) Epidemiology; 3) Development of a DC-based prophylactic mucosal vaccine; 4) Therapeutics development; 5) Diagnostics development; 6) Biostatistics analyses.19

Although there have not been any reported human or animal cases of Nipah virus infection in China, a review article on Nipah20 published in 2018 in Virologica Sinica by five authors from the Wuhan Institute of Virology stated that NiV is also distributed in China…. However, the reference cited21 did not report Nipah virus itself, but only antibody to Nipah or a related virus in bats in China.
Nevertheless, if a first-ever Nipah outbreak occurred in China and particularly near Wuhan, whether in humans or animals (e.g., pigs in the city of Ezhou, approximately 40km from Wuhan where large numbers of pigs are raised in 26-storey buildings22), then on the first day of the recognition of the outbreak all four scenarios discussed above could prove relevant.

This paper serves as an anticipatory guide to four origin scenarios on a future day 1 of the first-ever Nipah virus outbreak anywhere in the world e.g., China, Europe, the Americas, or Africa, that is outside of past outbreaks in south/SE Asia. As has occurred with the ongoing origin controversy of SARS-CoV-2/COVID-19 since at least January 25-26, 202023 , each of the potential natural and laboratory-related Nipah virus origin scenarios discussed in this paper should be rapidly considered in order to control and stop the outbreak. A part of such a rapid investigation should also include searching retrospectively for unrecognized cases of Nipah, as illustrated by retrospectively identifying the earliest known cases of another coronavirus, the Middle East Respiratory Syndrome (MERS), in Zarqa, Jordan in April 201224.

1.    Chua K.B., Bellini W.J., Rota P., Harcourt B., Tamin A., Lam S. Nipah virus: a recently emergent deadly paramyxovirus. Science 2000;288:1432–1435.
2.    Donaldson H, Lucey D. Enhancing preparation for large Nipah outbreaks beyond Bangladesh: Preventing a tragedy like Ebola in West Africa. Int J Infect Dis. 2018 Jul;72:69-72. doi: 10.1016/j.ijid.2018.05.015.
3.    Gurley ES, Spiropoulou CF, de Wit E. Twenty Years of Nipah Virus Research: Where Do We Go From Here?, The Journal of Infectious Diseases, Volume 221, Issue Supplement_4, 1 May 2020, Pages S359–S362,
4.    Chadha M.S., Comer J.A., Lowe L., Rota P.A., Rollin P.E., Bellini W.J. Nipah virus-associated encephalitis outbreak, Siliguri, India. Emerg Infect Dis. 2006;12(February (2)):235–240.
5.    Bangladesh Ministry of Health and Family Welfare. National Guideline for Management, Prevention and Control of Nipah virus infection including encephalitis. Nipah.pdf
6.    Roman RG, Tornieporth N, Cherian NG et al. Medical countermeasures against henipaviruses: a review and public health perspective. Lancet Infect Dis 2022; 22:e13-27.
7.    Nikolay B, Salje H, Hossain MJ, Khan AKMD, Sazzad HMS, Rahman M, Daszak P, Ströher U, Pulliam JRC et al. Transmission of Nipah Virus - 14 Years of Investigations in Bangladesh. N Engl J Med. 2019;380(19):1804-1814. doi: 10.1056/NEJMoa1805376.    PMID:    31067370; PMCID: PMC6547369.
8.    Epstein, J., Anthony S, Islam A, et al.. Nipah virus dynamics in bats and implications for spillover to humans. Proceedings of the National Academy of Sciences 2020; 117(46), 29190–29201.
9.    Arunkumar G., Chandni R., Mourya D.T., Singh S.K., Sadanandan R., Sudan P., Bhargava B., Nipah Investigators P., Health Study G. Outbreak Investigation of Nipah Virus Disease in Kerala, India, 2018. J. Infect. Dis. 2019;219:1867–1878.
10.    Ching PK, de los Reyes VC, Sucaldito MN et al. Outbreak of Henipavirus Infection, Philippines, 2014. Emerg Infect Dis 2015; 21 (2). 1433_article
11.    WHO. Global guidance framework for the responsible use of the life sciences: mitigating biorisks and governing dual use research. 2022 (Sept); 0056107
12.    Islam MS, Sazzad HMS, Satter SM, et al. Nipah Virus Transmission from Bats to Humans Associated with Drinking Traditional Liquor Made from Date Palm Sap, Bangladesh, 2011–2014. Emerg Infect Dis 2016; 22(4). April. 1747_article
13.    Reynolds M, Davidson W, Currus A, et al. Spectrum of infection and risk factor for human monkeypox, United States, 2003. Emerg Infect Dis 2007;13 (9) 0175_article
14.    de Wit E, Prescott J, Falzarano D, Bushmaker T, Scott D, et al. Foodborne Transmission of Nipah Virus in Syrian Hamsters. PLoS Pathog 2014; 10(3): e1004001. doi:10.1371/journal.ppat.1004001
15.    Gryphon Scientific. “Risk and Benefit Analysis of
Gain of Function Research Final ReportApril 2016.” content/uploads/2018/12/Risk-and-Benefit- Analysis-of-Gain-of-Function-Research-Final- Report-1.pdf
16.    Lieberman J, Ridge T. A national blueprint for biodefense. Bipartisan report of the Blue Ribbon study    panel    on    biodefense.    2015    October. content/uploads/2016/03/A-National-Blueprint- for-Biodefense-October-2015.pdf.
17.    Watson C, Toner E, Shearer M, et al. Clade X: a    Pandemic    Exercise.    Health    Secur    2019 Sep/Oct;17(5):410-417. doi: 10.1089/hs.2019.0097.
18.    WHO. Presentation: report of the Scientific Advisory Group for the Origins of Novel Pathogens to WHO Member States - March 30, 2023. ation--report-of-sago-to-member-states---march- 2023
19.    Nipah at 20. Nipah virus international conference. December 9-10, 2019 Singapore. 2019-Nipah-Conference-Proceedings.pdf
20.    Sun B, Jia L, Liang B, Chen Q, Liu D. Phylogeography, transmission, and viral proteins. Virologica Sinica 2018;33(5) online October 11.
21.    Yan L, Wang J, Hickey AC, Zhang Y, Li Y, Yi W, Zhang H, Yuan J, Han Z, Jennifer ME (2008) Antibodies to Nipah or Nipah-like viruses in bats, China. Emerg Infect Dis 14:1974–1976.
22.    Wakabayashi D, Fu C. China’s hulking towers of pigs. New York Times 2023; February 10. Page B1-B5.

23.    Cohen J. The seafood market may not have been the source of the novel virus spreading globally. Science 2020 (January 26) seafood-market-may-not-be-source-novel-virus- spreading-globally. (accessed May 3, 2023). Doi:10.1126/science.abb0611.

24.    Lucey D. Editorial commentary: Still learning from the earliest known MERS outbreak, Zarqa, Jordan, April 2012. Clin Infect Dis 2014; 59 (9): 1234-46. Doi:10.1093/cid/ciu638.

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