Risk of invasive meningococcal disease in people with sickle cell disease: A systematic review

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BACKGROUND: Asplenia and splenic dysfunction is associated with an increased risk of severe and fatal infections, especially due to encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae serotype b (Hib) and Neisseria meningitidis. People with sickle cell disease (SCD) develop recurrent splenic infarcts rendering them functionally asplenic. Consequently, additional vaccination against these three pathogens is recommended. There is robust evidence of an increased risk for invasive pneumococcal (IPD) and Hib disease, in people with SCD, but for not invasive meningococcal disease (IMD). METHODS: We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) recommendations. Studies published in any language before June 2024 and including people with SCD of all ages and from all geographical locations were included. Studies were included if they documented bacterial culture and/or PCR in patients with SCD with suspected infection. The primary outcome was to estimate IMD risk in people with SCD. Secondary outcomes included estimating the risk of IMD and Hib disease in people with SCD. FINDINGS: We identified 3804 publications and included 86 in the final analyses. Among 74 cohort studies published during 1971-2023, there were three IMD cases among 26,404 persons with SCD compared with 570 IPD and 113 Hib cases. Eight case-control studies published during 1983-2022 reported one IMD case among 932 people with SCD (0.1%) compared to 118 IMD cases among 7143 people without SCD (1.65%). In contrast, there were 126 IPD cases (126/932, 13.5%) in people with SCD compared to 588 (588/7143, 8.2%) in those without SCD. For Hib, the rates were 32/932 (3.4%) and 316/7143 (4.4%), respectively. After including all published studies, we identified five IMD cases in people with SCD across studies published worldwide during 1965-1995 and all five survived their infection. INTERPRETATION: We found no evidence of any increased risk of IMD in people with SCD. This has important implications for policymakers in countries and organisations that currently recommend meningococcal vaccination for people with SCD.

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