Screening for Immunodeficiencies in Children With Invasive Pneumococcal Disease: Six-year Experience From a UK Children's Hospital

Background: A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting. Methods: We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Immunological investigations included complement C3 and C4 levels, classical and alternative pathway complement function, IgG, IgA and IgM levels, specific IgG levels (H. influenza B, tetanus and pneumococcal serotypes), peripheral blood film, lymphocyte subsets, and CD62L-shedding upon activation with Toll-like receptor-agonists in selected cases. Results: We identified a total of 68 children with IPD, with a mortality of 6%. Immunological investigations were performed in 51 children. Four children (8%) had abnormal findings that were deemed of clinical significance. Two children had complement deficiencies (Factor I and C2 deficiency), one child had specific antibody deficiency, and another child had low IgM, low NK-cells and poor persistence of serotype-specific anti-pneumococcal IgG concentrations. Of the 17 children with IPD who were not tested for immunodeficiencies, 4 died and four had possible explanations for the infection. Conclusions: We identified clinically relevant abnormal immunological findings in 4/51 (8%) of children with IPD. Our results support the recommendation to perform immunological investigations in children with IPD, since this might reveal underlying immunodeficiencies, allowing for necessary preventive measures and close follow-up.