Assessment of the utility of repeat tuberculin testing: a prospective study of adolescents in a high tuberculosis prevalence setting in South India
Abstract
Background -Under-nutrition is associated with sub-optimal or false -negative tuberculin responses, while BCG vaccination may produce false-positive reactions. The two-step tuberculin test may be of value in populations where under - nutrition is highly prevalent in young children as in India, to help identify individuals who could potentially boost their immune response to the second test, thus preventing them from undergoing further serial testing and preventing their misclassification as converters. We studied the factors that were associated with a sub-optimal response to the initial tuberculin skin test (TST) as well as an enhanced response following two-step testing in a cohort of adolescents. Materials and Methods - Adolescent subjects aged 11-18 years who attended high-schools and junior colleges in Palamaner Taluk, South India were recruited. Baseline demographic, clinical and anthropometric data were collected. A tuberculin test using 2 TU of RT23 was administered. Those who developed a sub-optimal response (less than 5mm) to this test were subjected to a second test 1-4 weeks following the initial test. Chi-square test and multiple logistic regression were used to test the association between the various categorical variables-demographic, socio-economic and clinical with sub-optimal and enhanced responses following two-step testing. Results- A total of 6643 participants were recruited, of whom 6608 underwent initial TST screening. Nearly 30% were under-nourished, and only about 62.3% had a BCG scar. 1257 (19%) developed a sub-optimal response to the initial TST (less than 5mm). Younger age {AOR 1.96 (1.31- 2.93)}, under-nutrition {AOR 1.22 (1.06-1.39)}, presence of BCG scar {AOR 0.74(0.65-0.85)} and higher socio-economic class {AOR 0.77(0.66-0.89)} were associated with a sub-optimal response. With repeat testing within 1-4 weeks of the first test ( N=1098), an enhanced response ( greater than or equal to 10mm, with an increment of 6mm or more over initial test) was seen in 47(4.3%) of the participants. With the sole criterion of greater than or equal to 6mm used to define an enhanced response, 145 (13.2%) developed such a response. A history of exposure was linked to an enhanced response at this cut-off {AOR 5.86 (1.15-29.76)}. A history of exposure was associated with development of an enhanced response; both at initial as well as at repeat testing {unadjusted OR 2.56 (1.15-5.54)}. Conclusion- The two-step tuberculin test may be useful in undernourished populations, to identify potential boosters and prevent their misclassification as converters during further tuberculin testing.