Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes
severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where
outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap.
Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the
“Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present
throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic
spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead
to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in
eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in
circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure
studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and
hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims:
1) To compare NiV exposure and its behavioral determinants among human populations inside and
outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in
Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex
Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if
Nipah exposure has occurred and how behavioral risk varies by locality.
2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the
Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern),
characterize local bat demography, measure changes in seroprevalence over time; determine viral
shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4
lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected
and shed virus. This will answer a critical question about transmission dynamics and allow us to test the
hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats,
which may influence zoonotic transmission.
3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and
outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different
clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern
Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV
strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.