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Nipah Virus Outbreaks: New Reasons Why the West Needs to Start Caring

Flying Pipistrelle bat (Pipistrellus pipistrellus) action shot of hunting animal on wooden attic of city church. This species is know for roosting and living in urban areas in Europe and Asia.
Image: Flying Pipistrelle bat (Pipistrellus pipistrellus) in the wooden attic of a city church. This species is known for roosting and living in urban areas in Europe and Asia.

 

written by Chandana Balasubramanian

Nipah virus (NiV) has been detected in several species of bats. While the Pteropus genus of bats has been the reservoir for NiV, new research from Gokhale et al. identified potential NiV infection in Rousettus leschenaultii and Pipistrellus pipistrellus bats in India [1].

Why is this significant?

In the past, the bat-borne Nipah virus has not raised much concern in the West –  since its discovery in the late nineties, outbreaks have been limited to Southeast Asia. However, NiV mutations, zoonotic spillovers, the effects of deforestation, and other factors signify a growing potential for NiV to spread. 

People think of these bat-borne viruses as exotic diseases that are far away. The COVID-19 pandemic illustrates, however, that local spillover of novel viruses can affect the whole world. 

– Stanford epidemiologist Stephen Luby, MD

Additionally, while NiV transmission was previously assumed to be annual or seasonal (primarily winter), a multi-disciplinary study based on six years of data indicates otherwise. Researchers from Stanford, Columbia, Johns Hopkins, and other global partners suggest that bat immunity levels drive NiV infections and that infected bats can shed the virus at any time of year [2].  This article was published in PNAS (Proceedings of the National Academy of Sciences of the United States) and edited by Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases.

This growing body of Nipah virus research is a bat signal urging the world to pay attention.

The World Health Organization (WHO) prioritized the Nipah virus on their list of epidemic threats that require urgent action. The US National Institutes of Allergy and Infectious Diseases categorizes Nipah at Category C:  “emerging pathogens that could be mass engineered for mass dissemination in the future.” Some governments consider the Nipah virus as a potential agent of bioterrorism and strictly regulate laboratory testing. Several other studies suggest that the NIV virus is a potential pandemic agent [3].

We must track Nipah like a parent that monitors an eight-year-old child in a playground. We do not have to divert all attention and resources urgently, but our eyes and ears need to “stay wide open” for potential issues.

Although NiV is a paramyxovirus – agents primarily responsible for acute respiratory diseases –  transmission from human to human is currently low. The R0 (the number of cases that result from an infected patient) is only 0.48. In comparison, the R0 for SARS-CoV-2 Delta Variant is 5-8, SARS-CoV-2 is 2.5-5.7, SARS-CoV is 2.4, and MERS is 1. Reported case mortality is high at 40 – 70% and is the reason why NiV has not caused mass transmission in a population:  many die before they transmit the disease. Another factor preventing larger outbreaks is that the virus has been detected in villages with a relatively low population density.

But changes are brewing, and we need to track the Nipah virus more closely than before. 

Reasons to Track Nipah Virus (NiV)

1. New Nipah virus mutations

With Nipah, there is no cause for panic just yet. Currently, only a small percentage of infected people transmit NiV. But super-spreaders can infect their loved ones, caregivers, healthcare workers, and others in their community. The incubation period is 5-to-14 days, but in a severe case, it has been reported to extend up to 45 days – sufficient time for an infected person to transmit the virus.

Nipah virus has been confined mainly to Southeast Asian countries with outbreaks in Bangladesh, India, the Philippines, and Malaysia. Still, as new strains continue to be detected, the threat level that NIV poses can potentially escalate. More research is needed in this field, but two distinct strains have been detected – Bangladeshi and Malaysian [2].

 

Nipah virus outbreaks map, 1998 - 2019
Image: Nipah virus global outbreaks map, 1998 – 2019. Copyright © GIDEON Informatics, Inc.

 

Consider another bat-borne disease: COVID-19. Since the start of the pandemic, SARS-CoV-2 has mutated quite rapidly. As you read this, variants such as ‘Delta’ (B.1.617.2) continue to wreak global havoc. WHO now categorizes these “mutants” as ‘Variants of Concern’ (VOC) and ‘Variants of Interest’ (VOI).

One concern is that the NIV receptor in humans is ephrin – found in all tissues. As such, infection by a more potent mutant could affect every organ in our body, including our blood and the central nervous system.

 

2. Potential Zoonotic Spillover: COVID-19 Pandemic Precedent?

As we saw with COVID-19, the spread from a bat to a pangolin and between humans happened extremely rapidly.

NiV was first discovered in pigs but is widely found in bats (Pteropus genus). There is also spillover to horses and other domestic animals. Nikolay et al. report that multiple Nipah spillover events from bats to humans occur in Bangladesh when humans consume raw fermented date palm sap contaminated by infected fruit bats [4]. Another reason for concern is that the Pteropus group of bats is found all over Asia and Australia. If more spillovers continue to occur, the world’s Nipah virus problem may increase quickly [2]. And as discovered in India (and always suspected by NiV experts), more bat species may be infected with NiV [1].

Stanford epidemiologist Stephen Luby MD stated about the Nipah virus, “People think of these bat-borne viruses as exotic diseases that are far away. The COVID-19 pandemic illustrates, however, that local spillover of novel viruses can affect the whole world.”

NiV and SARS-CoV-2 have similarities: both are bat-borne RNA viruses, demonstrate zoonotic spillovers, and cause acute respiratory distress – and without proper medical intervention, can be fatal. Differences include a slower rate of transmission for Nipah versus COVID-19 and its variants, for now. 

Nipah virus and COVID-19 comparison
Image: Comparison between Nipah virus and COVID-19. Copyright © GIDEON Informatics, Inc.

 

3. Nipah Virus can be transmitted continually

One of the most valuable insights from the Epstein et al. PNAS study was that bats do not transmit NiV annually or seasonally. Instead, there are multi-year cycles of transmission across bat species, which can increase the risk to humans.

Additionally, the study found that the Nipah virus in bats can recrudesce or reinfect the same bat. If an infected bat has high levels of immunity against NIV, it may not shed or transmit the virus. But when immunity levels are low, the same bat may start shedding the virus – even after years! If the immunity of a group of bats drops, an infected bat that immigrates to the flock could reinfect the group. Also, if one bat is persistently infected through recrudescence, NiV may be reintroduced into the bat colony [2].  

4. Ecological Changes Driving Closer Bat-Human Interactions

Generally, most animals prefer to stay away from humans. This is true unless their survival is linked to living closer to humans. In the case of Nipah, the Pteropus medius bat (the predominant host) travels short distances and likes to stay close to home. They pick their homes based on the availability of food in high human population density areas. In Bangladesh, they prefer to live close to humans because of more farmland and the greater availability of silver date palm trees. In Malaysia, fruit trees were planted close to piggeries, which, in turn, are within the range of human habitation. The United Nations projects that by 2050, 60% of the world’s population (4.9 billion people) will live in urban areas, increasing the risk of zoonotic spillovers. Most of this urbanization will occur in Asia and Africa.

Bat feces, called guano, is used as fertilizer in Thailand and Cambodia, and selling it is lucrative. Some people in these areas often encourage fruit bats to live close by for easier access to the droppings.

Deforestation is another strong influencer. Some research suggests that bats shed more virus under stress [6]. Bat populations undergo stressful environmental events such as human encroachment, deforestation, and fires that cause them to flee their natural habitats, searching for new ones. Many of them choose to “cut out the middleman” and roost directly on fruit trees, often planted close to humans and other domesticated or farm animals. 

Two men cutting a tree
Image: Deforestation. Photo by Souro Souvik on Unsplash

 

Additionally, bats, including Pteropus medius, are gregarious and social animals. Living in a large roost also offers them greater protection from other predators. Pteropus Medius bats prefer to create large roosts in tall trees. But with deforestation on the rise, these bats have been forced to form smaller populations in other locations [7].

Image: Nipah virus infection summary of disease from GIDEON Informatics (Global Infectious Diseases and Epidemiology Network) database.
Image: Nipah virus infection summary. Copyright © GIDEON Informatics, Inc.

 

Nipah infections are characterized by encephalitis and acute respiratory distress, which are incredibly difficult to treat [5]. The mortality rate is at 40-70%. Since it is found in rural areas with limited lab testing resources and awareness, early detection is often not possible. There are no licensed treatments for Nipah virus infection though some monoclonal antibody therapies are being evaluated. Additionally, there is no vaccine against this virus. According to GAVI, the global vaccine alliance, phase 1 clinical trials are underway.

With COVID-19 being a global public health crisis, investments in vaccine R&D and production have been high from the get-go. But the same mRNA vaccine technology may also be useful in preventing NiV infections.

Conclusion

Nipah virus has been around for 20 years and persists without a vaccine or licensed drug treatment. Though transmission rates are low, mortality rates are high.

The virus has much in common with SARS-COV-2. In particular, both are bat-borne, RNA-based viruses that have spilled over to other animals and humans. The virus of COVID-19, mutating much more often, has spread to every corner of our globe in a full-blown pandemic.

Variant strains of the Nipah virus have been detected. New research also identified more species of bats infected with the NiV virus. Preventing the next pandemic involves equipping researchers and clinicians on the frontlines of emerging disease prevention with the right epidemiological, diagnostic, therapeutic, and preventive tools, right off the bat. 

 

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References

[1] M. D. Gokhale, M. Sreelekshmy, A. B. Sudeep, A. Shete, R. Jain, P. D. Yadav, B. Mathapati and D. T. Mourya, “Detection of possible Nipah virus infection in Rousettus leschenaultii and Pipistrellus Pipistrellus bats in Maharashtra, India,” Journal of Infection and Public Health, vol. 14, no. 8, pp. 1010-1012, 2021.
[2] J. H. Epstein, S. J. Anthony, A. Islam, A. M. Kilpatrick, S. Ali Khan, M. D. Balkey, N. Ross, I. Smith, C. Zambrana-Torrelio, Y. Tao, A. Islam, P. Lan Quan, K. J. Olival, M. S. U. Khan, E. S. Gurley, M. J. Hossein, H. E. Field, M. D. Fielder, T. Briese, M. Rahman, C. C. Broder, G. Crameri, L.-F. Wang, S. P. Luby, I. W. Lipkin and P. Daszak, “Nipah virus dynamics in bats and implications for spillover to humans,” PNAS (Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 46, pp. 29190-29201, 2020.
[3] P. Devnath and H. M. A. A. Masud, “Nipah virus: a potential pandemic agent in the context of the current severe acute respiratory syndrome coronavirus 2 pandemic,” New Microbes and New Infections, vol. 41, 2021.
[4] B. Nikolay, H. Salje, J. M. Hossain, A. M. Dawlat Khan, H. M. S. Sazzad, M. Rahman, P. Daszak, U. Ströher, J. R. C. Pulliam, A. M. Kilpatrick, S. T. Nichol, J. D. Klena, S. Sultana, S. Afroj, S. P. Luby, S. Cauchemez and E. S. Gurley, “Transmission of Nipah Virus – 14 Years of Investigations in Bangladesh.,” New England Journal of Medicine, vol. 380, no. 19, pp. 1804-1814, 2019.
[5] E. S. Gurley, C. F. Spiropoulou and E. d. Wit, “Twenty years of nipah virus research: Where do we go from here?” J. Infect. Dis., vol. 221, No Supplement_4, p. S359–S362, 2020.
[6] C. M. Davy, M. E. Donaldson, S. Subudhi, N. Rapin, L. Warnecke, J. M. Turner, T. K. Bollinger, C. J. Kyle, N. A. S.-Y. Dorville, E. L. Kunkel, K. J. O. Norquay, Y. A. Dzal, C. K. R. Willis and V. Misra, “White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats,” Scientific Reports, vol. 8, no. 15508, 2018.
[7] C. D. McKee, A. Islam, S. P. Luby, H. Salje, P. J. Hudson, R. K. Plowright and E. S. Gurley, “The ecology of Nipah virus in Bangladesh: a nexus of land use change and opportunistic feeding behavior in bats,” Viruses, vol. 13, no. 169, 2021.

 

 

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