High Mortality Due to Pneumococcal Meningitis in Children With Sickle Cell Disease: A French Multicenter Observational Study From 2001 to 2021.

Background: Sickle cell disease (SCD) predisposes children to bacterial infections, particularly invasive pneumococcal disease. Pneumococcal immunization associated with antibiotic prophylaxis reduced the incidence of invasive pneumococcal disease in these patients. However, the risk remains higher than in the general population. Our main objective was to describe the features of pneumococcal meningitis and estimate the case-fatality rate in children with SCD. The secondary objective was to assess serotype distribution and resistance patterns and the proportion of cases related to vaccine failure.

Methods: This nationwide multicenter observational study was conducted in France between 2001 and 2021. All cases of pneumococcal meningitis in children with SCD < 18 years old from the French National Registry of Pediatric Pneumococcal Meningitis were included.

Results: Of 2145 pneumococcal meningitis, 25 cases (1.2%, 95% CI: 0.8-1.7) occurred in children with SCD [mean age = 4.6 years (±4)], with a high case-fatality rate (28%, n = 7, 95% CI: 10.4-45.6). Nonvaccine serotypes were predominant (n = 15, 65%, 95% CI: 45.8-84.7) over vaccine serotypes (n = 8, 35%, 95% CI: 15.3-54.3). One case of vaccine failure (4%, n = 1/23) and 2 breakthrough cases (n = 2/23, 9%) were observed. Penicillin-non-susceptible Streptococcus pneumoniae strains were identified in 39% (n = 7).

Conclusions: The occurrence of pneumococcal meningitis in children with SCD during the pneumococcal conjugate vaccines era was associated with a high case-fatality rate and a predominance of nonvaccine serotypes. The implementation of new serotype-expanded PCV may have a potentially positive impact on this vulnerable population.