Abstract

Since 2001, outbreaks of Nipah virus have occurred almost every year in Bangladesh with high case-fatality rates. Epidemiological data suggest that in Bangladesh, Nipah virus is transmitted from the natural reservoir, fruit bats, to humans via consumption of date palm sap contaminated by bats, with subsequent human-to-human transmission. To experimentally investigate this epidemiological association between drinking of date palm sap and human cases of Nipah virus infection, we determined the viability of Nipah virus (strain Bangladesh/200401066) in artificial palm sap. At 22°C virus titers remained stable for at least 7 days, thus potentially allowing food-borne transmission. Next, we modeled food-borne Nipah virus infection by supplying Syrian hamsters with artificial palm sap containing Nipah virus. Drinking of 5×108 TCID50 of Nipah virus resulted in neurological disease in 5 out of 8 hamsters, indicating that food-borne transmission of Nipah virus can indeed occur. In comparison, intranasal (i.n.) inoculation with the same dose of Nipah virus resulted in lethal respiratory disease in all animals. In animals infected with Nipah virus via drinking, virus was detected in respiratory tissues rather than in the intestinal tract. Using fluorescently labeled Nipah virus particles, we showed that during drinking, a substantial amount of virus is deposited in the lungs, explaining the replication of Nipah virus in the respiratory tract of these hamsters. Besides the ability of Nipah virus to infect hamsters via the drinking route, Syrian hamsters infected via that route transmitted the virus through direct contact with naïve hamsters in 2 out of 24 transmission pairs. Although these findings do not directly prove that date palm sap contaminated with Nipah virus by bats is the origin of Nipah virus outbreaks in Bangladesh, they provide the first experimental support for this hypothesis. Understanding the Nipah virus transmission cycle is essential for preventing and mitigating future outbreaks.

Highlights

  • Nipah virus first emerged in 1998 during a large outbreak of encephalitis and respiratory disease in Malaysia and Singapore, causing 276 cases of encephalitis with 106 fatalities [1]

  • The recurrent outbreaks of Nipah virus in Bangladesh have been epidemiologically associated with the consumption of date palm sap, which has led to the hypothesis that Nipah virus zoonosis is a result of drinking date palm sap contaminated by infected fruit bats [4,5]

  • Based on epidemiological data Nipah virus is thought to be transmitted from fruit bats to humans via drinking of date palm sap contaminated by bats that drink from the sap stream or collection vessel during collection

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Summary

Introduction

Nipah virus first emerged in 1998 during a large outbreak of encephalitis and respiratory disease in Malaysia and Singapore, causing 276 cases of encephalitis with 106 fatalities [1]. Since 2001, outbreaks of Nipah virus have occurred almost every year in Bangladesh with a strikingly high case-fatality rate of up to 90% [2], with 24 cases of Nipah virus occurring to date in 2013 [3]. The recurrent outbreaks of Nipah virus in Bangladesh have been epidemiologically associated with the consumption of date palm sap, which has led to the hypothesis that Nipah virus zoonosis is a result of drinking date palm sap contaminated by infected fruit bats [4,5]. To our knowledge Nipah virus has so far not been detected in date palm sap, human observation and analysis by infrared camera has shown that bats frequently drink from date palm sap during collection [7,8]. Since bats can shed Nipah virus in their urine and saliva [9,10,11,12], it is thought that bats contaminate the date palm sap while drinking from the sap stream or date palm sap collection vessel

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