A One Health approach to fight the future epidemics: the case of Nipah virus in Bangladesh

Deadly epidemics have been threatening humanity since our earliest days. The recent 2013-2016 outbreak of Ebola virus disease (EVD) in West Africa taught us a lesson: epidemics can only be prevented when health systems are prepared for them. [1] At the beginning of the year, this lesson informed the mission of the newly launched Coalition for Epidemic Preparedness Innovations (CEPI). CEPI is a US $540 million project funded by multinational governmental and private foundations; its aim is to develop vaccines for diseases identified by the World Health Organisation (WHO) as having high epidemic potential, yet for which no vaccine or curative options exist. [2,3] Initially, CEPI will concentrate on Middle Eastern Respiratory Syndrome (MERS)-coronavirus, Lassa virus and Nipah virus (NiV). Both the academic [4,5] and non-academic [6,7] press warmly welcomed this initiative: undoubtedly, the availability of an effective vaccine before the onset of the next epidemic could be a useful tool to staunch its spread, a preparedness option that the EVD outbreak notably lacked.

A vaccine-centred approach, however, has its limitations. As highlighted in a recent article in The Lancet Global Health Blog, all diseases on CEPI’s initial vaccine development shortlist are zoonotic (i.e., transmitted from animals to humans), yet no plans have been announced to develop vaccines for use in animals, nor to study the underlying human-animal interface. Beyond benefitting human and animal health, there are huge economic benefits to tackling these diseases at their source and thereby minimising the impact of epidemics on agriculture and food security. [8] A One Health approach, encompassing both technological developments and research into the deeper ecological context of a disease, will be critical to fighting future epidemics.

The One Health initiative is a growing movement to promote collaboration between the fields of medicine, veterinary medicine and environmental sciences to improve the interconnected health of people, animals, and ecosystems. [9] The importance of such an approach is particularly obvious in the field of infectious disease, as 75% of all emerging infectious diseases are zoonotic. [10]

Nipah virus (NiV) exemplifies the need for a One Health approach. The first known outbreak of NiV occurred in Malaysia in 1998, killing 105 people and requiring the culling of over one million pigs. [11] The virus initially causes fever, headaches and vomiting in infected people, which can progress to severe encephalitis (inflammation of the brain), respiratory disease, and often death. [12] Outbreaks of NiV also began to be recorded approximately annually in Bangladesh starting in 2001, with an average fatality rate of 74.5%. [13] The natural reservoir hosts of NiV are large fruit bats known as flying foxes, which are not known to suffer clinical disease when infected. [14]

Interactions between humans, animals, and the environment are key factors behind NiV outbreaks. Deforestation and urbanisation of some areas in Bangladesh have contributed to greater overlap between human and bat habitats. By promoting human-bat interactions, this overlap can increase the risk of ‘spillover’ events, with NiV crossing the species barrier and infecting people. For example, NiV can be shed on fruit discarded by infected bats. Domesticated animals which consume this fruit can become a vector for NiV transmission to people. In isolated cases, cows, pigs, and goats have been implicated in NiV outbreaks in Bangladesh in this manner. [15] However, a more important route through which humans acquire NiV from bats is the consumption of raw date palm sap, a delicacy in Bangladesh. Sap is collected in jars underneath trees, where it can be contaminated by virus-containing secretions from bats. Once infected, people can transmit NiV to each other, which may cause local epidemics.

Vaccines are a potentially powerful tool to directly prevent and limit NiV outbreaks in Bangladesh and beyond, but their role should be evaluated in light of the ecological complexities of NiV transmission, including deforestation, human-bat interactions, and human-to-human transmission. Interventions to reduce the burden of NiV in Bangladesh could target different levels of transmission, including protecting raw date palm sap from bat secretions through skirts/covers on collection pots, boiling sap to kill live virus particles, and improving infection control protocols in Bangladesh’s hospitals. [16] Long-term strategies to limit the environmental patterns likely to contribute to NiV spillover from bats to humans, such as forest fragmentation, should also be considered. [17] These strategies may involve additional cultural and economic hurdles, but could nonetheless effectively complement vaccine development.

With the announcement of CEPI, a human NiV vaccine could be on the horizon. The international community has the responsibility to evaluate its use and, if established, to guide its implementation, with consideration of the human-animal-environment interface and the One Health perspective. In addition, NiV dynamics in bats and other animals need to be further investigated, including the possibility of an animal vaccine. This could both reduce the burden of Nipah virus in Bangladesh and leave the global health community better prepared for a potential outbreak than it was during the recent Ebola crisis. [8]

References:

[1] Team WER. After Ebola in West Africa — Unpredictable Risks, Preventable Epidemics. N Engl J Med 2016;375:587–96. doi:10.1056/NEJMsr1513109.

[2] CEPI, http://www.cepi.net/mission [date accessed 14.04.17]

[3] WHO, WHO publishes list of top emerging diseases likely to cause major epidemics, http://www.who.int/medicines/ebola-treatment/WHO-list-of-top-emerging-diseases/en/ [date accessed 14.04.17]

[4] Cohen J. New vaccine coalition aims to ward off epidemics. Science (80- ) 2016. doi:10.1126/science.aah7263.

[5] Vaccine initiative marks bold resolution. Nature 2017;541:436–436. doi:10.1038/541436a.

[6] Jack A, Partnership of nations set to combat pandemic health threats. Financial Times, https://www.ft.com/content/d42351b2-155b-11e7-b0c1-37e417ee6c76 [date accessed 19.04.17]

[7] Boseley S, $460m pledged for vaccine initiative aimed at preventing global epidemics , The Guardian, https://www.theguardian.com/society/2017/jan/18/460m-pledged-for-vaccine-initiative-to-prevent-global-epidemics-davos-mers-nipah-lassa [date accessed 19.04.17]

[8] Seifman R, Making the Coalition for Epidemic Preparedness Innovations (CEPI) more effective, The Lancet Global Health Blog, http://globalhealth.thelancet.com/2017/03/17/making-coalition-epidemic-preparedness-innovations-cepi-more-effective [date accessed 14.04.17]

[9] One Health Commission, https://www.onehealthcommission.org/ [date accessed 30.04.17]

[10] Vorou RM, Papavassiliou VG, Tsiodras S. Emerging zoonoses and vector-borne infections affecting humans in Europe. Epidemiol Infect 2007;135:1231–47. doi:10.1017/S0950268807008527.

[11] Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, Lam SK, et al. Nipah Virus: A Recently Emergent Deadly Paramyxovirus. Science (80- ) 2000;288.

[12] Looi L-M, Chua K-B. Lessons from the Nipah virus outbreak in Malaysia. Malays J Pathol 2007;29:63–7.

[13] WHO, Nipah virus outbreaks in the WHO South-East Asia Region, http://www.searo.who.int/entity/emerging_diseases/links/nipah_virus_outbreaks_sear/en/ [date accessed 30.04.17]

[14] Mire CE, Satterfield BA, Geisbert JB, Agans KN, Borisevich V, Yan L, et al. Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy. Sci Rep 2016;6:30916. doi:10.1038/srep30916.

[15] Luby SP, Gurley ES, Hossain MJ. Transmission of Human Infection with Nipah Virus. Clin Infect Dis 2009;49:1743–8. doi:10.1086/647951.

[16] Chakraborty A, Sazzad HMS, Hossain MJ, Islam MS, Parveen S, Husain M, et al. Evolving epidemiology of Nipah virus infection in Bangladesh: evidence from outbreaks during 2010–2011. Epidemiol Infect 2016;144:371–80. doi:10.1017/S0950268815001314.

[17] Hahn MB, Gurley ES, Epstein JH, Islam MS, Patz JA, Daszak P, et al. The Role of Landscape Composition and Configuration on Pteropus giganteus Roosting Ecology and Nipah Virus Spillover Risk in Bangladesh. Am J Trop Med Hyg 2014;90:247–55. doi:10.4269/ajtmh.13-0256.

About the authors:

Rebecca Conway-Jones is a second year medical student at the University of Oxford and the Treasurer of Oxford Medical Students’ Society. Prior work at a vaccine clinic piqued an interest in immunology and she is now working on a research project on malaria vaccinology at the Jenner Institute.

Matt Dickinson is a practising veterinary surgeon and DPhil student in Clinical Medicine at Oxford, working on innate HIV-1 immunology in acute infection. He has a particular interest in emerging viral diseases of humans and animals, and comparative medicine.

Emma Glennon is a PhD student in the Department of Veterinary Medicine at the University of Cambridge, where she studies the ecology of bat-borne viruses. She is also secretary of the Cambridge University Science and Policy Exchange and is interested in engagement between scientists, policymakers and their communities.

Cristiana Vagnoni is a Neuroscience DPhil student at the University of Oxford and the chair of the Oxford Branch of the British Science Association. She is interested in promoting the dialogue between science and society, not only through public engagement, but also via policymaking.

Aniruddha Voruganti is a first year undergraduate medical student at the University of Oxford. Having lived in India for nearly all his life, he has founded student-run charity initiatives for education, and is very interested in making a difference to primary healthcare in developing countries.