Veterinary Science - Theses

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    Nipah viruses from Malaysia and Bangladesh: comparisons of viral shedding and pathogenesis, and investigations of transmission in the ferret model for infection
    Clayton, Bronwyn Anne ( 2014)
    Nipah virus (NiV) has caused human disease with a high fatality rate in Malaysia, Singapore, India, and Bangladesh. Isolates from Malaysia (NiV-MY) and Bangladesh (NiV-BD) are associated with markedly different patterns of transmission in people. In Malaysia, symptomatic human infection was attributed to pig-to-human transmission. In Bangladesh, where outbreaks continue to occur on almost an annual basis, human-to-human transmission is a regularly identified pathway for infection. Despite observed epidemiological differences, no comparisons of NiV transmission have been reported in a mammalian infection model under controlled conditions. This project compared infections of NiV-MY and NiV-BD in ferrets (a human surrogate) with respect to tissue tropism, shedding and transmission. Following oronasal exposure to NiV-MY or NiV-BD, increased viral loads were observed in oropharyngeal secretions from NiV-BD-infected ferrets sampled over the course of infection, consistent with enhanced replication of NiV-BD at sites relevant to transmission via respiratory secretions. In a comparative time-course study, NiV in respiratory secretions was demonstrated to originate primarily from the lower respiratory tract at early time points following infection, and significantly higher viral loads were detected in respiratory tissues from NiV-BD-infected ferrets, compared to those of NiV-MY-infected ferrets. A transmission study was carried out to investigate whether these findings were reflective of increased transmissibility of NiV-BD, and to document the nature of contact required to achieve NiV transmission in ferrets. For both viral isolates, ferrets inoculated with respiratory secretions from infected donor ferrets were more likely to acquire infection than animals whose exposure was limited to cohabitation. Critically, exposure of ferrets to secretions from NiV-MY-infected donors resulted in similar outcomes of infection to those exposed to secretions of NiV-BD-infected donors. Findings from these studies suggest that, although NiV-BD appears to replicate to higher levels in respiratory tissues of infected ferrets, differences observed in natural NiV outbreaks are likely to be driven by environmental and/or host factors, rather than differences between viral strains.