Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000-17: a prospective national observational cohort study

Background Pneumococcal conjugate vaccines (PCVs) have substantially reduced the incidence of invasive pneumococcal disease caused by vaccine serotypes; however, replacement disease with non-PCV serotypes remains a concern. We describe the population effect of the seven-valent and 13-valent PCVs (PCV7 and PCV13) on invasive pneumococcal disease in England and Wales. Methods Using national invasive pneumococcal disease surveillance data for 2016/17, we compared incidence rate ratios (IRRs) against pre-PCV13 (2008/092009/10) and pre-PCV7 (2000/012005/06) baselines. We also estimated the number of invasive pneumococcal disease cases prevented since the introduction of PCVs. Findings In 2016/17, overall invasive pneumococcal disease incidence (9.87 cases per 100 000; 5450 cases) across all age groups was 37% lower (IRR 0.63, 95% CI 0.600.65) than pre-PCV7 incidence (14.79 per 100 000; 8167 cases) and 7% lower (0.93; 0.890.97) than pre-PCV13 incidence (10.13 per 100 000; 5595 cases). By 2016/17, PCV7-type invasive pneumococcal disease incidence across all age groups had decreased by 97% (0.24 per 100 000; 0.03, 0.020.04) compared with the pre-PCV7 period, whereas additional PCV13-type invasive pneumococcal disease decreased by 64% (1.66 per 100 000; 0.36, 0.320.40) since the introduction of PCV13. Invasive pneumococcal disease incidence due to non-PCV13 serotypes doubled (7.97 per 100 000; 1.97, 1.862.09) since the introduction of PCV7, and accelerated since 2013/14especially serotypes 8, 12F, and 9N, which were responsible for more than 40% of invasive pneumococcal disease cases by 2016/17. Invasive pneumococcal disease incidence in children younger than 5 years remained stable since 2013/14, with nearly all replacement disease occurring in adults. We estimated 38 366 invasive pneumococcal disease cases were prevented in the 11 years since the introduction of PCV7. Interpretation Both PCV7 and PCV13 have had a major effect in reducing the burden of invasive pneumococcal disease in England and Wales; however, rapid increases in some non-PCV13 serotypes are compromising the benefits of the programme.