Prevalence of Immunodeficiency in Children With Invasive Pneumococcal Disease in the Pneumococcal Vaccine Era

Abstract

IMPORTANCE Despite increasing access to vaccination, invasive pneumococcal disease (IPD) is responsible for approximately 826 000 deaths worldwide in children younger than 5 years each year. To allow early identification and prevention, an improved understanding of risk factors for IPD is needed.OBJECTIVES To review the literature on the prevalence of primary immunodeficiency (PID) in children younger than 18 years presenting with IPD without another predisposing condition and to inform guidelines for immunologic evaluation after the first episode of IPD based on published evidence.EVIDENCE REVIEW A literature search of PubMed, Embase (inception [1974] to February 28, 2019), and MEDLINE (inception [1946] to February 28, 2019) was conducted using the terms Streptococcus pneumonia, Streptococcus pneumoniae, pneumococcal infection, Streptococcus infection, pneumococcal meningitis, immunodeficiency, immune response, immunocompromised, susceptib*, precursor, predispose*, recurren*, newborn, neonat*, infan*, toddler, child, preschooler, adolescen*, and pediatric. Publications reporting original data on immunodeficiency in children with microbiologically confirmed primary or recurrent IPD were included. Strength of clinical data was graded according to the 5-point scale of the Oxford Centre for Evidence-Based Medicine.FINDINGS In 6022 unique children with primary IPD, 5 of 393 (1.3%) to 17 of 162 (10.5%) of all children and 14 of 53 (26.4%) of those older than 2 years had a PID identified. Higher rates of PID, up to 10 of 15 (66.7%), were found in children with recurrent IPD. Antibody deficiency was the most common immunodeficiency, followed by complement deficiency, asplenia, and rarer defects in T-cell signaling. The site of infection was a key indicator for the risk of underlying PID, with the greatest risk of PID in children with meningitis or complicated pneumonia. CONCLUSIONS AND RELEVANCEResults of this study suggest that invasive pneumococcal disease, and particularly recurrent IPD, is an important marker of underlying PID in children without other risk factors. The findings also suggest that children older than 2 years with pneumococcal meningitis or complicated pneumonia and all children with recurrent IPD should be referred for an immune evaluation.

Lessons Learned From the Clinical Presentation of Common Variable Immunodeficiency Disorders: A Systematic Review and Meta-Analysis

“…Other alerts to potential PID that are in line with the JMF warning signs that may be more discriminatory include severe bacterial infections (osteomyelitis in 4%, meningitis in 6%, septicemia in 8%, mastoiditis in 8%), which are clearly more frequent than lifetime prevalence in the general population. Recent studies already demonstrated a high incidence of antibody deficiency in patients with pneumococcal meningitis (86)(87)(88), confirming our finding of a high frequency of infectious meningitis in CVID, but we also show a high incidence of bloodstream infections, mastoiditis and to a somewhat lesser extent osteomyelitis in CVID patients. This suggests that the incidence of CVID may also be increased in patients with bloodstream infections, mastoiditis and osteomyelitis without other clear predispositions and suggest screening for CVID could be useful in these patients.…”

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network

“…5 Primary immunodeficiency has been shown to be more prevalent in pediatric rIPD cases than all pediatric IPD cases (66.7% vs. 1.3-10.5% in a 2019 systematic review). 16 With respect to primary IPD, children over the age of 2 years are more likely to have a primary immunodeficiency. 16 Recurrent IPD, particularly in vaccinated children, has been suggested to be used as an indication for immunodeficiency screening.…”

Emergence of Meningitis Caused by Nonvaccine Serotypes of Pneumococcus in Rural United States

“…Studies have observed that IPD due to nonvaccine serotypes and/or those with presumed low invasive disease capacity such as 35B and 11A was more prevalent among children with comorbidities [ 8 , 12 ]. In studies of children over 2 years without a predisposing condition, IPD may be a manifestation of an underlying primary immunodeficiency and warrant immune evaluation [ 13 ]. Our patients presented under 2 years of age and had abnormalities detected on immunologic evaluation.…”