For children in France with sickle cell disease (SCD), the rate of death caused by pneumococcal meningitis remains high despite pneumococcal conjugate immunization, according to a retrospective study presented at the European Hematology Association 2025 Congress. The study discovered predominant non-vaccine serotypes and a low vaccine failure rate but an often incomplete immunization schedule.
In children with SCD, “infections are the leading cause of mortality, even in high-income countries such as France,” said presenting author, Inès Fafi, MD, pediatrician and PhD candidate at Jean Verdier Hospital in Paris. Despite preventive strategies, including early pneumococcal immunization, daily penicillin prophylaxis, and neonatal screening for early diagnosis of SCD, children with SCD remain at higher risk of invasive pneumococcal disease (IPD) and of dying from IPD, “with meningitis being the deadliest IPD.”
Dr. Ines said because there are limited data on pneumococcal meningitis in children with SCD, the researchers completed a multicenter observational study. It included all cases of pneumococcal meningitis in children with SCD recorded in the French National Registry of Pediatric Bacterial Meningitis between 2001 and 2021. The researchers sought to describe the features of pneumococcal meningitis and to estimate the case fatality rate in children with SCD. They also assessed the serotype distribution and the proportion of antibiotic-resistance strains.
Of 2,145 cases of pneumococcal meningitis, 25 (1.2%) from 20 hospitals occurred in children (mean age = 4.6 years) with SCD, all presenting with the SS genotype. At the time of diagnosis, daily penicillin prophylaxis was prescribed in 20 of the 25 cases (80%) and hydroxycarbamide in four (16%) cases. Nonspecific initial symptoms were frequently reported.
The researchers reported a high case-fatality rate, with seven children (28%) dying from pneumococcal meningitis, including five (20%) cataclysmic clinical presentations that led to a postmortem diagnosis without antibiotic initiation. Streptococcus pneumoniae isolates were obtained from blood culture in 20 cases (83%, data not available [NA] = 1) and cerebrospinal fluid culture in 15 cases (60%). Aseptic meningitis with positive blood cultures occurred in seven cases (28%). Penicillin-non-susceptible Streptococcus pneumoniae accounted for seven cases (39%, NA = 7).
For the 23 cases (92%) that underwent serotyping, non-vaccine serotypes were predominant, occurring in 15 cases (65%) versus eight cases (35%) with vaccine serotypes. The pneumococcal conjugate immunization schedule of four doses appeared complete for eight patients (35%), while nine patients (39%) received three doses, and at least one dose had been administered in 11 patients (50%). Among 23 vaccine cases, the researchers observed one case (4%) of vaccine failure and two breakthrough cases (9%).
“We have reported a very high case-fatality rate in children with SCD for cases of pneumococcal meningitis,” Dr. Fafi said. “These cases were frequently due to non-vaccine serotypes, which underlines the importance of serotype replacement, like in the general pediatric population.”
“Non-vaccine serotypes could be targeted by new conjugate vaccines, but this impact has to be confirmed by further studies,” Dr. Fafi added. “However, we have to remain vigilant with the emergence of non-vaccine serotypes and the emergence of resistant strains.”
Conflicts of interest from the authors were not published in the original abstract.
Reference
Fafi I, Cohen R, Levy C, et al. High mortality due to pneumococcal meningitis in children with sickle cell disease: a French multicenter observational study from 2001 to 2021. Abstract S286. Presented at the European Hematology Association (EHA) 2025 Congress; June 14, 2025; Milan, Italy.
