Introduction We evaluated pneumococcal conjugate vaccine (PCV) effectiveness against hospitalisation for presumed bacterial pneumonia (PBP) in HIV-uninfected South African children. 7-valent PCV was introduced in April 2009 using a 2+1 schedule (doses at age 6, 14 and 39 weeks), superseded with 13-valent PCV in May 2011.

Methods A matched case–control study was conducted at three public hospitals (Soweto, Cape Town and KwaZulu-Natal) between April 2009 and August 2012. PBP cases had either WHO defined radiographically confirmed pneumonia or ‘other infiltrate’ on chest radiograph with C-reactive protein ≥40 mg/L. Hospitalised controls were children admitted with a disease unlikely to be pneumococcal and matched for case age, site and HIV infection status. Age-matched community controls were enrolled from Soweto. Adjusted vaccine effectiveness (aVE) was estimated using conditional logistic regression.

Results Of 1444 HIV-uninfected enrolled PBP cases, 1326 had ≥1 hospital controls (n=2075). Overall, aVE of an up-to-date PCV schedule was 20.1% (95% CI −9.3% to 41.6%) in children aged ≥8 weeks and 39.2% (95% CI 8.46% to 59.6%) among children 16–103 weeks of age. There were 889 PBP cases in Soweto with hospital controls and ≥1 community control (n=2628). The aVE using community controls was similar compared with hospital controls in Soweto, including 32.1% (95% CI 4.6% to 51.6%) and 38.4% (95% CI 7.7% to 58.8%), respectively, in age group ≥8 weeks and 52.7% (95% CI 25.7% to 69.9%) and 53.8% (95% CI 19.5% to 73.5%), respectively, in age group 16–103 weeks.

Conclusions PCV implemented using a 2+1 schedule in the routine infant immunisation programme was effective at preventing PBP in HIV-uninfected children. Effectiveness estimates were similar to efficacy measured by earlier randomised controlled trials using different vaccination schedules.