Includes abstract.Includes bibliographical references.Rheumatic Heart Disease (RHD) is a post-infectious immune disease ascribed to an interaction between a rheumatogenic strain of group A streptococcus, a susceptible host who lives in poor social conditions with limited access to medical facilities. The disease process begins with repeated group A streptococcal (GAS) infections, which, subsequently result in acute rheumatic fever (ARF). In the absence of intervention, repeated bouts of ARF in turn, may result in progression to RHD, particularly in those ARF patients with cardiac involvement. The prevalence of ARF and RHD in developed countries has shown considerable decline during the last century, largely attributed to improved living conditions and access to healthcare. Epidemiological data from developing countries, while scant, indicate a continued high prevalence of GAS-positive pharyngitis and RHD. Furthermore, while much is known about the social factors and the microbial agent that predispose individuals to ARF, little progress has been made in elucidating genetic susceptibility factors that are reproducible in different populations. This thesis aimed to establish determinants of RHD as well as to document the prevalence of RHD in South African school children. The specific objectives of each study component were as follows: To derive quantitative estimates of the size of the genetic contribution to the risk of developing ARF/RHD. To determine the prevalence of GAS carriage and emm strains of GAS isolates among asymptomatic children enrolled in primary and secondary school. To describe the epidemiology of GAS among 3- to 15-year old children with pharyngitis attending primary health care facilities. To develop a clinical prediction rule for diagnosis of GAS throat infection that is valid for children aged 5-15 years in the primary care setting within the South African context. To determine the prevalence of echocardiographically-proven rheumatic heart disease in school children
