Abstract
Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.
Highlights
Preventing and controlling emerging zoonoses require identification of the processes that drive cross-species pathogen transmission [1]
The marked decline in both end-of-year standing pig population (SPP) and annual mango production between 1998 and 1999 indicates that this correlation may reflect widespread dual use of agricultural land to produce both pigs and mangoes, with the decline in commercial mango harvest reflecting the widespread abandonment and culling of infected pig farms that occurred in the first half of 1999
We found that flying foxes are consistently present throughout Perak State, including near the index farm, where we located two seasonal P. vampyrus roosts: one in Lenggong, Perak,50 km from the index farm, where we observed a maximum population of approximately 2500 bats, and another near Tambun, Perak, within 2 km of the index farm, which had been previously reported in 1999 [32] and where we observed bats in 2003 – 2005 [33]
Summary
Preventing and controlling emerging zoonoses require identification of the processes that drive cross-species pathogen transmission [1]. Between September 1998 and April 1999, NiV caused 246 reported cases of febrile encephalitis in humans in peninsular Malaysia and Singapore [7,8] and an epidemic of respiratory and neurological disease in commercially farmed pigs [9,15]. Initial human cases were seen in Tambun village and surrounding areas in Perak State, followed by a large epidemic in the southern states of Negeri Sembilan and Selangor and several cases in Singapore (figure 1a). The majority of these cases occurred in pig farmers and abattoir workers [17]. Six of the nine cases are considered confirmed cases on the basis of serological tests performed in 1999 [16]; the remaining three are probable cases
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