Long-Term Impact of Pneumococcal Conjugate Vaccines from National, Active, Laboratory-Based Surveillance of Invasive Pneumococcal Disease, South Africa, 2005-2019

Background: We evaluated the ongoing effects (direct and indirect) of prevention of 13-valent pneumococcal conjugate vaccine (PCV13) serotypes, replacement disease, and effects on antimicrobial resistance, eight years after the introduction of PCV13 in 2011 and before the COVID-19 pandemic. Methods: In South Africa, PCV7 was introduced in 2009, and PCV13 in 2011, in a two plus one schedule. We conducted national, active, laboratory-based surveillance for invasive pneumococcal disease (IPD), including isolate serotyping and susceptibility testing. We compared incidence of IPD prior to any PCV use (2005 through 2008) to the final year of surveillance (2019). Findings: During 2005 through 2019, surveillance identified 52,957 IPD cases: 9,398/50,705 (18.5%) and 2,854/50,705 (5.6%) occurred in children aged <2 and 2–4 years, respectively. Compared to pre-PCV baseline, overall IPD rates among children aged <2 years declined 76.8% (percentage change 95%CI:-73.9%,-79.5%) by 2019; notably, PCV7 and additional PCV13-serotype IPD rates declined 94.2% (95%CI: -92.2%, -95.8%) and 93.2% (95%CI:-89.6%,-95.7%), respectively. Non-vaccine serotypes (NVT) did not increase in this age group. Similar changes were seen in age groups 2-4, 5-14 and 15-24 years. Among adults aged 25 to 44 years, PCV7 and additional PCV13-serotype IPD rates declined 83.3% (95%CI: -80.1%, -86.2%) and 80.3% (95%CI:-77.0%,-83.2%), respectively. Older individuals also benefited from declines in IPD, but in those >64 years of age, declines were negated by significant increases of NVTs. Interpretation: We documented sustained reductions in vaccine-serotype IPD in children directly benefiting from vaccination, eight years after PCV13 introduction. Indirect benefits from PCV were also documented.Funding: National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa) and US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.Declaration of Interest: SAM has received grant funds from Pfizer, Minervax, GSK, the Gates Foundation, and the South African Medical Research Council, and honoraria from GSK, related to this work. Other authors declare no conflicts of interest related to this work.Ethical Approval: Ethics approval was obtained for GERMS-SA surveillance (M081117 and M1809107) from the Human Research Ethics Committee (Medical), University of the Witwatersrand, Johannesburg, South Africa. GERMS-SA surveillance study protocols were also approved by local hospital and provincial ethics committees, as required.