Butters C, et al. - Researchers performed this systematic review, wherein they analyzed data from 17 studies with 6,022 unique patients with primary invasive pneumococcal disease (IPD), to determine the prevalence of primary immunodeficiency (PID) in children younger than 18 years having IPD without another predisposing condition. They also utilized the published evidence in order to inform guidelines for immunologic assessment following the first episode of IPD. The included studies were identified from PubMed, Embase (inception [1974] to February 28, 2019), and MEDLINE (inception [1946] to February 28, 2019). Rates of primary immunodeficiency as high as 26% were found in children older than 2 years without a recognized predisposing condition presenting with their first episode of Streptococcus pneumoniae meningitis or pneumonia or recurrent IPD. Children with recurrent IPD exhibited higher rates of PID, up to 10 of 15 (66.7%). The most prevalent immunodeficiency was antibody deficiency, followed by complement deficiency, asplenia, and rarer defects in T-cell signaling. Findings revealed the significance of IPD, and especially recurrent IPD, as a marker of underlying PID in children not carrying other risk factors. A referral for an immune assessment was recommended for children older than 2 years with pneumococcal meningitis or complicated pneumonia and all children with recurrent IPD.