Recurrent invasive pneumococcal disease in children: A retrospective cohort study, England, 2006/07-2017/18.

BACKGROUND

Recurrent invasive pneumococcal disease (IPD) is rare in children and usually associated with underlying comorbidities. We aimed to assess the risk and describe the characteristics of children with recurrent IPD over a 12-year period covering the introduction of the 7-valent (PCV7), followed by the 13-valent (PCV13) pneumococcal conjugate vaccine (PCV) in the national childhood immunisation programme in England.

METHODS

We used enhanced national surveillance data for England and included all laboratory-confirmed IPD cases in children (<15 years) during 2006/07-2017/18. We assessed the risk and rate of recurrent IPD, the serotypes responsible and the demographics, comorbidity status and prevalence, vaccination status, clinical presentation and outcomes in children with recurrent IPD compared to those with a single IPD episode.

FINDINGS: There were 5158 IPD episodes reported in 5033 children over 12 years and 2.2% (105/4814) of those surviving their first IPD had at least one recurrence. Recurrence risk decreased with increasing age and over time. During 2015/16-2017/18, five years after PCV13 replaced PCV7, IPD recurrence rate was 229.0 (95% CI 154.8-339.0) per 100,000 person-years, with all recurrent cases caused by non-PCV13 serotypes. Where serotype information was available, recurrence was due to the same serotype in 25 cases, with a shorter median (IQR) interval of 88 (57-177) days between recurrent episodes, and in 60 cases due to different serotypes, with a median (IQR) interval of 223 (125-574) days (p=0.001). Compared to healthy children (103.0; 95%CI 63.1-168.1), recurrence rate per 100,000 person-years was 10 times higher in children with any comorbidity (1061.0; 95% CI 827.2-1360.9; 62/78 [79.5%] with available information had comorbidities), and almost 30 times higher in immunosuppressed children (2788.5; 95%CI 2029.0-3832.2; 38/78 [48.7%] were immunosuppressed). The 30-day case-fatality rate after recurrent IPD was 2.9% (3/105) compared to 4.4% (219/4928; p=0.63) after single-episode IPD.

INTERPRETATION: Recurrent IPD is rare in children and occurs mainly in children with comorbidities, especially immunosuppression. Higher-valent PCVs have the potential to further reduce the risk of recurrent IPD in children.