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WHO-validated serological assay improved CAP diagnosis in children
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A standardized enzyme-linked immunosorbent assay recently validated by WHO may help shed light on what is causing a patient’s community-acquired pneumonia, according to study results published online ahead of print.
David Tuerlinckx, MD, of the department of pediatrics at the Université Catholique Louvain, University Hospital Mont-Godinne in Belgium, and colleagues performed a multicenter study of children aged younger than 15 years who had been hospitalized for community-acquired pneumonia (CAP) between Sept. 1, 2008, and Dec. 31, 2009.
The researchers took blood samples of 163 children with clinically confirmed CAP; the first sample was taken at admission, and a second sample was taken 3 to 4 weeks later. Pneumococcal (P)-CAP was determined by the presence of a positive blood or pleural fluid culture. Quellung reaction was used to serotype Streptococcus pneumoniae isolates.
Of the 35 cases with proven P-CAP and 128 with non-proven P-CAP, the study reported that the assay successfully detected pneumococci in 82.8% of patients with proven P-CAP.
“The serotypes identified were the same as with the Quellung reaction in 82% and 59% of cases by IgG enzyme-linked immunosorbent assay (ELISA) and IgA ELISA,” the researchers wrote. “ELISA identified a pneumococcal aetiology in 55% of patients with non-proven P-CAP. Serotypes 1 (51.6%), 7F (19%) and 5 (15.7%) were the most frequent, according to IgG ELISA.”
Researchers noted some limitations to the test; specifically, that it is unhelpful in acute daily clinical work because two samples spread weeks apart are needed, and the test is less sensitive for children aged younger than 2 years because of their “low ability to produce anti-polysaccharide antibodies.”
Despite these limitations, the researchers said, “This assay should improve the diagnosis of P-CAP in children and could be a useful tool for future epidemiological studies on childhood CAP etiology, especially for children above 2 years of age.”
Disclosure: Tuerlinckx reports financial ties to GlaxoSmithKline and Pfizer. Pfizer supported this study.
Perspective
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John S. Bradley, MD
The need to accurately diagnose pneumococcal pneumonia exists for several reasons: 1) acute diagnosis of invasive pneumococcal infection at the time a child presents in a clinic, ED or hospital; 2) diagnosis of serotype-specific infection in a child previously immunized with a conjugate pneumococcal vaccine, to provide insight into possible immune deficiency or vaccine failure; and 3) to collect information on the epidemiology of invasive strains to assess efficacy of vaccines and the potential need for newer vaccines for infection caused by serotypes not present in our current vaccines.
For practicing clinicians, having a rapid test at the time of clinical presentation of pneumonia (complete with antibiotic susceptibility data) would be spectacular! The WHO-validated serology showcased by these authors, with blood drawn at the time of infection and 3 to 4 weeks later, is not likely to help in the management of any particular child with acute onset of cough and fever.
However, this study presents very useful epidemiologic data by investigators from Belgium using an advanced ELISA serologic test (used currently to assess immunologic responses to pneumococcal vaccines) for diagnosis of serotype-specific pneumococcal pneumonia after the introduction of Prevnar (Pfizer), but before the introduction of Prevnar13 (Pfizer). Of note, most of the serotypes diagnosed by culture or serology in this study were not those present in Prevnar7, but fortunately are present in Prevnar13.
Realizing that children aged younger than 2 years, in general, are less capable of responding immunologically to pneumococcal polysaccharides, it is logical that only half of those younger than 2 years had a serologic response to the infecting strain, but almost 90% of those older than 2 years seroconverted!
When the test was applied to children having complicated pneumonia with pleural effusion, but with negative cultures, about 54% of children older than 2 years had seroconverted to one of the nine serotypes included in the ELISA assays used in this study.
The authors also point out that for children with positive cultures, 25% of those infected by serotype 1, and 40% of those infected by serotype 5 (both included now in Prevnar13) were documented to have pre-existing levels of serotype-specific antibody to the infecting strain that were actually above the level felt to be protective following immunization, suggesting that we may need to revise what levels we consider protective in future vaccine trials.
While this WHO-validated ELISA test for diagnosis of pneumococcal pneumonia may not serve us for acute diagnosis, it is valuable in advancing our understanding the epidemiology of the serotypes involved in invasive pneumococcal disease and potential correlates of protection.
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