Invasive Pneumococcal Disease in Kids Suggests Underlying Immunodeficiency

By Will Boggs MD

October 03, 2019

NEW YORK (Reuters Health) - Invasive pneumococcal disease (IPD) in children without known risk factors could be a marker of underlying primary immunodeficiency (PID), according to a systematic review.

Introduction of pneumococcal vaccines was followed by substantial reductions in IPD in vaccine-eligible children, but IPD still accounts for about 11% of all deaths in children under 5, amounting to 826,000 deaths annually worldwide.

Dr. Coen Butters of The Royal Children's Hospital, in Melbourne, Australia, and colleagues evaluated the incidence of PID in children presenting with IPD without another predisposing condition in their review of 12 studies that included children with primary IPD and five studies that included children with recurrent IPD.

Vaccination rates in the included studies of primary IPD ranged widely, from 8% to 75%.

Across studies, the frequency of PID in children presenting with IPD without another predisposing condition ranged from 1.3% to 26.4%, the researchers report in JAMA Pediatrics, online September 30.

The overall frequency of PID in children younger than 16 years presenting with primary IPD was 10.4% and was higher among children younger than 2 years (26%) than among older children (3%).

Three studies that systematically screened for immunodeficiency in children with recurrent IPD reported PID rates from 10.5% to 66.7%.

"This review's findings suggest that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of S. pneumoniae meningitis, pneumonia, or recurrent IPD," the researchers conclude. "Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia."

"Further studies, beginning with prospective cohort studies, are required to further delineate the predisposing factors for IPD in the era of pneumococcal vaccine," they add. "This should also include assessment of the public health economics of immune evaluation in all children with IPD balanced against the potential for preventing the significant complications and mortality associated with PID."

"Although PID remains uncommon among children with IPD, children with recurrent episodes and those older than 5 years (and in some studies those older than 2 years) with disease due to nonvaccine serotypes are more likely to have comorbid illness," write Dr. Stephen I. Pelton of Boston University School of Medicine and colleagues in a linked editorial.

"In those children, in whom no other comorbid illness is present, evaluation for PID-antibody deficiency, complement deficiency, toll-like receptor signaling defects, and asplenia or hyposplenia uncovers immune defects in a greater proportion of children than in either children with vaccine failure or children younger than 2 years with initial episodes of IPD," they add.

"Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with PID," the editorialists conclude.

Dr. Ricardo U. Sorensen of Louisiana State University, in New Orleans, and the University of La Frontera, in Temuco, Chile, who recently reviewed antibody-mediated immunity to S. pneumoniae, told Reuters Health by email, "When IPDs occur, the predisposing factors making it possible need to be considered."

"We do not know if the IPD was a vaccine failure because the child did not develop appropriate immunity to a vaccine serotype, or that the serotype causing the infections was not included in the vaccine used," he said. "Even considering this problem, all patients immunized in the first year of life with 2 or more doses of vaccine who develop an IPD should be evaluated for a possible immunodeficiency. This should be done in addition to the recommendation made by the authors to evaluate all patients who developed an IPD after 2 years of age or a meningitis or severe pneumonia form of IPD."

Dr. Godelieve J. de Bree of the University of Amsterdam, who recently reviewed the incidence of IPD in immunocompromised patients, told Reuters Health by email, "The prevalence of primary immune deficiency in infants of two years and older that they observe is so high that it, in my opinion, would justify screening for primary immune deficiency in every infant that presents with one episode of IPD (without other comorbidity that is associated with increased susceptibility)."

"There are (to my knowledge) no guidelines available that indicate when to test for PID, but this study hopefully will move that forward," she added.

Dr. Butters did not respond to a request for comments.


JAMA Pediatr 2019.