AFROStrep (SA): a surveillance system for group A streptococcal infection in South Africa

Doctoral Thesis


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University of Cape Town

BACKGROUND AND AIMS OF THE THESIS: Group A β-haemolytic Streptococcus (GAS) also known as Streptococcus pyogenes, is responsible for a wide range of invasive and non-invasive GAS diseases. Prevalence and incidence data on GAS from developing countries are largely lacking when compared with industrialised nations. This thesis sought to (1) establish the South African arm of the AFROStrep biorepository and clinical database for patients with invasive and non-invasive GAS infection, (2) identify and summarize all published studies of laboratory-confirmed GAS infection in Africa, (3) describe, from national laboratory data, the incidence of invasive and non-invasive GAS in South Africa and, (4) conduct a prospective, surveillance study in order to determine the molecular epidemiology of GAS in Cape Town, South Africa over a 12-month period. METHODS: A systematic review was conducted on population-based studies reporting on the prevalence of laboratory-confirmed GAS infection among patients living in Africa (Study 1). A retrospective study of the incidence of GAS infection was conducted on data obtained from the National Health Laboratory Service between 2003 – 2015 (Study 2). The AFROStrep registry and biorepository (based in Cape Town) was established and through passive surveillance, laboratory confirmed invasive and non-invasive GAS cases were collected over a 12-month period. The molecular analysis of invasive and non-invasive infection was determined using emm type sequencing to provide insight into vaccine development (Study 3). RESULTS AND DISCUSSION: The pooled prevalence of GAS pharyngitis in Africa was determined to be 21% (95% CI, 17% to 26%). The incidence rates of laboratory-confirmed non-invasive GAS infection in the South African public sector appears to have declined over the last 13 years. Given the possibility that the lower incidence of invasive and non-invasive GAS infection found in our study is due to infrequent submission of specimens for microbiological culture by health practitioners, our findings may be an underestimate of the true burden of disease in South Africa. In our prospective surveillance study, 46 different emm types were identified. The most prevalent emm types were M76 (16% of isolates), M81 (10%), M80 (6%), M43 (6%), and M183 (6%) and were almost evenly distributed between invasive and non-invasive GAS isolates. When compared against the putative 30-valent vaccine under development, four of our most prevalent emm types are not included; vaccine coverage (i.e. vaccine type and non-vaccine type-killing) for non-invasive and invasive GAS infection in our setting was 60% and 59% respectively, notably lower than coverage in developed countries. CONCLUSION: This work provides evidence for a significantly high prevalence of GAS pharyngitis in Africa. While GAS surveillance in South Africa indicates a declining incidence of GAS disease in parts of the country over the last thirteen years, the findings may be an underestimate of the true burden of disease, demonstrating the need for accurate and comprehensive surveillance of GAS in South Africa. Finally, this research showed a low potential vaccine coverage in our setting and thus, emphasises the need for a reworking of the potential vaccine formulation to improve coverage in areas where the burden of disease is high.