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Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting
Anna M Mandalakas1, H Lester Kirchner, Gerhard Walzl
11 Section on Retrovirology and Global Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Insights
Improved interferon-gamma release assays (IGRAs) show promise for detecting tuberculosis (TB) infection in young children, especially those with HIV. These tests may offer advantages over the tuberculin skin test for targeted preventive therapy.
Area of Science:
- Pediatric infectious diseases
- Global health
- Diagnostic test evaluation
Background:
- Children, particularly those who are young, malnourished, and HIV-infected, face a high risk of tuberculosis (TB) morbidity and mortality.
- Accurate detection of TB infection in children is challenging due to limited pediatric data and diagnostic limitations.
Purpose of the Study:
- To identify improved diagnostic tests for detecting pediatric TB infection.
- To compare the performance of the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) in children.
Main Methods:
- A prospective, community-based study involved 1,343 children aged 6 months to 15 years in TB-HIV high-burden settings.
- Assessed the tuberculin skin test (TST) and two IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB.
- Analyzed associations between test results and child characteristics, including HIV status and nutritional status.
Main Results:
- Contact tracing identified TB in 8% of child contacts within 3 months.
- IGRAs showed higher positivity than TST in children without documented TB contact.
- Nearly 8% of children exhibited discordance between IGRA and TST results.
- IGRAs correlated better with TB contact than TST (P=0.0011).
- Indeterminate QFT-GIT results were more frequent in HIV-infected children (4.7%) compared to uninfected children (1.9%).
- T-SPOT.TB showed rare indeterminate results (0.2%) unaffected by HIV status.
- Test correlation with TB contact decreased with worsening malnutrition in HIV-infected children.
Conclusions:
- Interferon-gamma release assays may offer advantages over the tuberculin skin test for identifying TB infection in young children, especially those recently exposed and HIV-infected.
- IGRAs can improve targeted, cost-effective delivery of preventive TB therapy in high-burden settings.
- Development of affordable TB infection tests holds significant potential for global TB control efforts.
Rationale:
Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data.
Objectives:
Identify improved testing to detect pediatric TB infection.
Methods:
This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured.
Measurements And Main Results:
Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened.
Conclusions:
Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.
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