Measles virus has been among the most important infectious agents in the history of mankind. Prior to the isolation of the virus and development of the first vaccines in the early 1960' s, measles killed between 0.1 - lO% of each birth cohort in the world. Although live-attenuated measles vaccines have significantly reduced mortality by more than 99% in developed countries, - 1 million deaths still occur annually in the developing world, and many questions remain regarding measles immunopathogenesis, the correlates of immunity and the vaccines themselves. The excess mortality associated with the promising high titer (HT) measles vaccines, developed and introduced in the late 1980's, refocused attention on these questions and forms the framework for this thesis.[...] / Le virus de la rougeole a été parmi les agents infectieux le plus important dans l'histoire de l'humanité. Avant l'isolation du virus et l'introduction d'un vaccin attenué au début des années 1960, la rougeole a tué entre 0,1 à 10% de chaque groupe de naissance à travers le monde. Bien que les vaccins contre la rougeole ont réduit la mortalité de plus de 99% dans les pays développés, plusieurs questions telles que l'immunopathogénèse de ce microbe, la corrélation entre l'immunité et les vaccins restent à élucider. L'excès inattendu de mortalité associée aux vaccins contre la rougeole à titres élevés (TE), développés et introduits à la fin des années 1980, ont de nouveau attiré l'attention à ces questions et forment les objectifs de cette thèse.[...]

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A dissertation submitted to the faculty of Medicine of the University of the Witwatersrand in partial fulfillment of the requirements for the Master of Medicine (Community Health) Johannesburg, October 1991. / This dissertation reviews the international literature and South African literature and data on the epidemiology of Measles. The main purpose is to contribute to an understanding of the local epidemiology of the disease that will further the development of more targeted efforts for its control. [Abbreviated Abstract. Open document to view full version] / MT2018

Measles is a vaccine-preventable disease. Implementation of global vaccination programmes has resulted in a dramatic decrease in measles-related deaths, from 2.6 million in 1980 to 164 000 in 2008. To support the global measles elimination goal, laboratories provide case-based surveillance which includes both serological diagnosis and viral characterisation using molecular platforms. In this study, conventional hemi-nested amplification methods were developed to detect the nucleoprotein- and haemagglutinin-genes of measles virus, in specimens collected for rashsurveillance programmes in Africa. Viral characterisation involved amplicon sequencing and phylogenetic analyses of 1402 PCR-positive specimens (2655 specimens tested, 52.8% PCR-positive) with sequence submission to global databases. Only imported strains of genotypes B2, B3, D2, D4 and D8, have been detected in South Africa since 2002, demonstrating the successful interruption of transmission of endemic strains. Genotypic analyses of specimens from African countries provided information relating to strain origins, as well as temporal and spatial data relevant to the molecular epidemiology of measles in Southern Africa.

A thesis submitted to the Faculty of Health Sciences University of the Witwatersrand, Johannesburg for the degree of Doctor of Philosophy / Andrew Chakane 2018

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