Tuberculin skin test and QuantiFERON-Gold In Tube assay for diagnosis of latent TB infection among household contacts of pulmonary TB patients in high TB burden setting

Abstract

BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15–40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Cough-aerosol cultures of Mycobacterium tuberculosis in the prediction of outcomes after exposure. A household contact study in Brazil

“…Although BCG is known to produce false positive TST results, the effect is minimal after 10 years of age [ 26 ]. Further, 75% of HHCs had TST ≥ 10 mm compared with 53% of IGRA ≥ 0.35 UI/ml which is consistent with other household contact studies in developing countries whereas TST often yields more positive results compared with IGRA [ 27 – 28 ].…”

Undiagnosed diabetes mellitus and tuberculosis infection: A population‐based, observational study from eastern China

“…In high‐burden settings and areas in which BCG vaccination is ubiquitous, the accuracy of the tuberculin skin test for the diagnosis of tuberculosis infection is controversial . TST and QFT test concordance test was poor, which was same as other regions with highest TB burden, where BCG are administered . In addition, our project site (Danyang county of Jiangsu province) is located close to the sea where nontuberculous Mycobacterium is highly prevalent.…”

“…21,28 TST and QFT test concordance test was poor, which was same as other regions with highest TB burden, where BCG are administered. [29][30][31][32][33][34] In addition, our project site (Danyang county of Jiangsu province) is located close to the sea where nontuberculous Mycobacterium is highly prevalent. In prior work from our province, we have shown that the prevalence of nontuberculous Mycobacterium is high.…”

The Growing Importance of Tuberculosis Preventive Therapy and How Research and Innovation Can Enhance Its Implementation on the Ground

“…The two main tests in use (TST and IGRAs) both measure the immunological response to MTB antigens. TST is inexpensive but logistically challenging for patients and health care staff, different results may be obtained depending on which purified protein derivative products are used [37] and there continue to be widespread shortages of quality-assured tuberculin in many low-and middle-income countries [38]. IGRAs are more specific than TST and only one clinic visit is required by the patient for a venous blood sample.…”