Abstract
BackgroundDue to immunologic immaturity, IFN-γ-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-γ responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-γ production in response to mycobacterial antigens between children and adults in Uganda.Methodology/Principal FindingsWe studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-γ production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (≥15 years old, n = 528). We evaluated the relationship between IFN-γ responses and the tuberculin skin test (TST), and between IFN-γ responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-γ responses. Young household contacts demonstrated robust IFN-γ responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-γ response.Conclusions/SignificanceYoung children in a TB endemic setting can mount robust IFN-γ responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection.
Highlights
Pediatric tuberculosis represents a major cause of childhood morbidity and mortality worldwide, affecting more than 800,000 children each year, and comprising approximately 10% of all cases of TB [1]
In the murine TB model, IFN-c is necessary for control of Mycobacterium tuberculosis (Mtb) [3] and rare humans with mutations in the IFN-c receptor are prone to mycobacterial infection [4]
The two study populations were similar with regard to demographic factors, and prevalence of TB at enrollment, latent TB infection (LTBI), and HIV-infected individuals
Summary
Pediatric tuberculosis represents a major cause of childhood morbidity and mortality worldwide, affecting more than 800,000 children each year, and comprising approximately 10% of all cases of TB [1]. We hypothesized that IFN-c production in response to mycobacterial infection would be deficient compared to those observed in older children and adults. To address this hypothesis, we analyzed whole blood IFN-c responses to Mtb antigens among household contacts of different ages in a setting of high level Mtb transmission. IFN-c-producing T cell responses may be decreased in young children compared to adults, we hypothesized that IFN-c responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults.
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