Abstract
BackgroundThe utility of two-step tuberculin skin testing among adolescents in high tuberculosis prevalence settings is not well established.ObjectivesTo determine the proportion and determinants of a 0-4 mm response to an initial standard tuberculin skin test (TST) and evaluating 'boosting' with repeat testing.MethodsAdolescents between 11 and 18 years attending schools/colleges underwent a TST; those with a response of between 0–4 mm had a repeat TST 1-4 weeks later.ResultsInitial TST was done for 6608/6643 participants; 1257 (19%) developed a 0-4 mm response to the initial TST. Younger age and under-nutrition were more likely to be associated with a 0-4 mm response, while the presence of BCG (Bacillus Calmette Guerin) scar and higher socio-economic class were less likely to be associated with a 0-4 mm response. On repeat testing boosting was seen in 13.2% (145/1098; ≥ 6 mm over the initial test) while 4.3% showed boosting using a more conservative cutoff of a repeat TST ≥ 10 mm with an increment of at least 6 mm (47/1098). History of exposure to a tuberculosis (TB) case was associated with enhanced response.ConclusionThe proportion of adolescents who demonstrated boosting on two-step TST testing in our study was relatively low. As a result repeat testing did not greatly alter the prevalence of TST positivity. However, the two-step TST helps identify individuals who can potentially boost their immune response to a second test, and thus, prevents them from being misclassified as those with newly acquired infection, or tuberculin converters. While two-step tuberculin skin testing may have a limited role in population- level TST surveys, it may be useful where serial tuberculin testing needs to be performed to distinguish those who show an enhanced response or boosters from those who indeed have a new infection, or converters.
Highlights
Tuberculosis (TB) accounts for the second highest number of deaths related to an infectious disease, globally, after HIV [1]
While interferon-gamma release assays (IGRAs) have the benefit of increased specificity [7,8,9], the TST continues to be employed throughout the world
In a metaanalysis of T-cell based assays (including TST and Quantiferon (QFT), a type of IGRA based assay) to detect latent TB infection (LTBI) that included studies from low/middle income and high income countries, Pai M et al showed that the pooled sensitivity of the QFT was 78%, while the TST was 77% [10]
Summary
Tuberculosis (TB) accounts for the second highest number of deaths related to an infectious disease, globally, after HIV [1]. In a metaanalysis of T-cell based assays (including TST and Quantiferon (QFT), a type of IGRA based assay) to detect latent TB infection (LTBI) that included studies from low/middle income and high income countries, Pai M et al showed that the pooled sensitivity of the QFT was 78%, while the TST was 77% [10]. None of the specificity studies had data from countries where the BCG vaccine was given during infancy This gives us scope to study two-step tuberculin testing in our setting, which is not routinely done; and in a population who are routinely BCG vaccinated at birth. While two-step tuberculin skin testing may have a limited role in population- level TST surveys, it may be useful where serial tuberculin testing needs to be performed to distinguish those who show an enhanced response or boosters from those who have a new infection, or converters
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