Risk of invasive pneumococcal disease in children with sickle cell disease in the era of conjugate vaccines: a systematic review of the literature

Abstract

Summary 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.

Evaluation of Outcomes and Quality of Care in Children with Sickle Cell Disease Diagnosed by Newborn Screening: A Real-World Nation-Wide Study in France

“…Likewise, severe infections (including pneumococcal) still accounted for the main cause of death. Although severe pneumococcal infections most often occurred in patients fully vaccinated with PVC as previously reported, [17] further improvement can be achieved by increasing P23 vaccination coverage. One striking and recurrent result was the somewhat counter intuitive finding of decreased TCD and vaccination coverage in smaller centers, along with higher rates of patients lost to follow-up.…”

“…Likewise, probability of severe infection (meningitis or septicemia) was low (1.6%), despite a known persistent increased risk of invasive pneumococcal infection with a high mortality rate in SCA patients [15,16]. This low rate probably reflects the effectiveness of pneumococcal vaccination and penicillin prophylaxis, as reported consistently in other settings [17]. Indeed, vaccination coverage regarding conjugated vaccine was 87% during first year of life, although this percentage fell to 47.4% by age three regarding full pneumococcal vaccination including P23 at two years, mainly because P23 was generally administered later i.e., during the fourth or fifth year of life.…”

Mortality in children with sickle cell disease in mainland France from 2000 to 2015

“…Pneumococcal invasive infection per se represented 15,1% of SCD-related causes in this study further underlying the ongoing pneumococcal burden in younger children. 10 , 11 Acute splenic sequestration was the second cause of death, a distressing finding given that these children were diagnosed with SCD and urgent blood transfusion is a readily available life-saving treatment. Of note, two of these children had a S-b + -thalassemia genotype, less commonly associated with this complication, although the severity of the mutation was unknown.…”

Reevaluating immunization delays after red blood cell transfusion

“…Finally, due to the small number of research subjects, the discrepancies between observed and theoretical seroconversion rates might be due to chance alone. Although scant, there is some published evidence suggesting that patients with sickle cell disease seem to have an adequate response to some vaccines such as the conjugated pneumococcal and influenza vaccines . However, vaccine responses to live attenuated vaccines in sickle cell disease patients compared to a healthy population have not been published.…”