Epidemiology of Sindbis fever in South Africa and development of a real-time pan-alphavirus PCR assay for the detection of Sindbis and other medically important alphaviruses

Abstract

The genus Alphavirus in the family Togaviridae consists of approximately 30 single stranded, positive-sense RNA viruses which cause diseases ranging from mild, febrile illness with rash and arthritis to life-threatening encephalitis. Sindbis virus is the prototype virus for this genus and is the most widely distributed alphavirus globally. Little epidemiological data exists for this virus due to inadequate surveillance efforts in most countries, and it is suspected that Sindbis and other alphavirus infections are largely underreported. Additionally, changing patterns of alphavirus infections are challenging conventional knowledge of these diseases and have created the need for improved diagnostic methods and increased vigilance and disease surveillance around the globe. To date, no real-time PCR assay exists that is able to detect all of the medically important (and other) alphaviruses. This study was therefore aimed at developing and evaluating such an assay in order to improve the diagnostic and surveillance activities of these viruses in South Africa. Additionally, this study was aimed at providing novel information on the molecular and epidemiological characteristics of Sindbis virus in South Africa, and to provide insights in the diversity of this virus compared to elsewhere in the world. This study has revealed that an outbreak of Sindbis fever occurred during 2010, with the Free State and Northern Cape Provinces being most affected. The outbreak coincided with an outbreak of Rift Valley fever. The risk for acquiring a Sindbis virus infection was found to be highest during late summer/early autumn, and was slightly higher among males of increasing age. The phylogenetic results obtained in this study have demonstrated that Sindbis isolates form five separate groups with a considerable amount of genetic variation among these groups. The grouping of the isolates corresponded to the major migratory patterns of birds, suggesting that birds may play a large role in the dispersal of Sindbis viruses between continents. In addition, a real-time reverse transcription PCR assay has been developed which is able to detect Sindbis virus and other medically important alphaviruses with varying sensitivities. This project contributes to the update of epidemiological and phylogenetic data on Sindbis virus in South Africa and delivers potential tools for improved surveillance activities of alphaviruses in future.