Introduction: Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. Methods: We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005–2008) and post-PCV introduction (2012–2013) in children aged 0–59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. Results: In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000–140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000–50,000) severe pneumococcal disease cases were estimated in 2012–2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000–6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000–2500) in 2012–2013, a mortality rate difference of 61 per 100,000 child-years. Conclusions: While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0–59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.
