Pneumococcal Infections in Children with Sickle Cell Disease Before and After Pneumococcal Conjugate Vaccines.

Children with sickle cell disease (SCD) are at increased risk of invasive pneumococcal infections (IPD). Over 25 years the Georgia Emerging Infections Program/CDC Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (p<0.001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS 0-4 years old, and by 80% in those aged 5-9. However, IPD incidence rate ratios comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD prior to PCV7 licensure. After 2010, all IPD serotypes were not included in the 13-valent pneumococcal conjugate vaccine (PCV13). Within 3 years of vaccination, effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence-interval: 40.8, 99.0, p=0.014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, while PCV15, PCV20 and PCV21/V116 (in development) could cover 16%, 51% and 92% respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.