Risk of Invasive Pneumococcal Disease in Children with Sickle Cell Disease in the Era of Conjugate Vaccines: a Systematic Review of the Literature

Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing invasive pneumococcal diseases (IPD) in children, including those with sickle cell disease (SCD). A systematic review of the English literature published between 2000 and 2017 was undertaken to evaluate the serotype distribution, clinical presentation and outcomes of IPD in children with SCD in PCV programmes. We identified 475 potential studies and included 16 publications, involving 9438 children up to 22 years of age with SCD and 182 IPD episodes (prevalence, 1·9%. 95% confidence interval [CI], 1·7-2·2%). Septicaemia was the most prevalent clinical presentation (84/137; 61%) followed by lower respiratory tract infection (39/137; 29%) and meningitis (12/137, 9%). More than half the serotypes associated with IPD (88/148; 59·5%) were not included in the 13-valent PCV; of these, 54% (44/82) were due to serogroup 15. The crude case fatality rate was 11·5% (21/182 cases; 95% CI, 7·3-17·1%). Most cases of IPD in children with SCD were due to serotypes that are not included in any of the licensed PCVs. IPD in children with SCD remains associated with high morbidity and mortality, highlighting the importance of strict adherence to daily penicillin prophylaxis. Until a serotype-independent pneumococcal vaccine becomes available, higher-valent PCVs should include serogroup 15 to protect this highly vulnerable group of children.