The ecology of Nipah virus and the first identification of a bat pegivirus in 'Pteropus medius', Bangladesh

Epstein, Jonathan H. (2017) The ecology of Nipah virus and the first identification of a bat pegivirus in 'Pteropus medius', Bangladesh. (PhD thesis), Kingston University, .


Understanding the drivers of zoonotic disease emergence is critical to mitigating spillover, and part of this comes from understanding the ecology of natural reservoirs. Nipah virus (NiV) is a negative sense single-stranded RNA virus (Family 'Paramyxoviridae', Genus 'Henipavirus') carried by Old World fruit bats of the genus 'Pteropus' (family 'Pteropodidae'). Nipah virus was first recognized in Bangladesh in 2001, and there have been clusters of NiV encephalitis reported there almost annually, with a mean mortality rate of 75%. Nipah virus antibodies were identified in 'Pteropus medius' (formerly 'P. giganteus') in northern India in 2003, and in Bangladesh in 2004, providing evidence that this bat may serve as a natural reservoir for NiV. Outbreaks in Bangladesh have been spatially and temporally clustered, occurring in western Bangladesh and West Bengal, India, between November and April. Nipah virus is of high public health concern in that is causes high mortality rates in people, can spread person-to-person, has no treatment or vaccine, and repeatedly spills over from its bat reservoir to people in a populous and globally connected region. Given enough opportunity, Nipah virus has the potential to evolve into an efficiently transmitted human virus with pandemic potential. The overall aim of this thesis is to characterize NiV host-virus dynamics in its putative reservoir, and test the hypothesis the Nipah virus dynamics in bats influences the timing and location of human cases. A second aim of this thesis is to determine whether unknown, potentially zoonotic viruses exist in 'P. medius' that could potentially be transmitted to people or animals via a similar route of infection as Nipah virus. The studies in theis thesis used a combination of ecological, epidemiological, experimental, and diagnostic methods to characterize 1) the spatial distribution of Nipah virus and 'Pteropus medius' in Bangladesh; 2) the temporal dynamics of Nipah virus in 'P. medius'; 3) the duration of maternal antibodies in 'Pteropus'; and 4) novel viruses in 'P. medius' that may be transmitted to people via similar route of infection as Nipah virus. Nipah virus was found to be widely distributed in 'P. medius' populations across Bangladesh, with spatial variation in seroprevalence, but no significant difference in exposure btween colonies within or outside the Nipah belt. Nipah virus RNA was detected at a prevalence of 1%-3%. Phylogenetic analysis of NiV sequences suggests little variation over time within a single location, but diversity was apparent when location varied. An SIR model of a 6-year longitudinal study of NiV seroprevalence in a single bat population suggests that there are seasonal dynamics driven by juvenile bats that result in spikes in viral circulation around June or July. Metagenomic analysis of a subset of 'P. medius' samples from Faridpur led to the discovery of a previously unrecognized flavivirus, now classified as Bat pegivirus (BtPgV), which appears to be ancestral to Hepatitis C virus and may have zoonotic potential. This study confirms 'Pteropus medius' is the reservoir for Nipah virus in Bangladesh and provides new insights into the natural dynamics and genetic variation of Nipah virus circulating in this host. Based in the culmination of previously reported epidemiological data, date palm sap harvesting most likely accounts for the timing and spatial clustering of human Nipah virus encephalitis cases, but understanding that there are periods, approximately every two years, when bats appear least likely to shed Nipah virus, may explain years when no human cases are reported. Also, NiV can be shed by bats at times other than the human NiV season and likely across the entire homerage of this species, which underscores the importance of strengthening disease surveillance systems across the entire range of related pteropid bats to identify and disrupt high risk interfaces and limit opportunity for Nipah virus to cause a pandemic.

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