TY - JOUR
T1 - 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
AU - Chandrasekaran, Padmapriyadarsini
AU - Mave, Vidya
AU - Thiruvengadam, Kannan
AU - Gupte, Nikhil
AU - Yogendra Shivakumar, Shri Vijay Bala
AU - Hanna, Luke Elizabeth
AU - Kulkarni, Vandana
AU - Kadam, Dileep
AU - Dhanasekaran, Kavitha
AU - Paradkar, Mandar
AU - Thomas, Beena
AU - Kohli, Rewa
AU - Dolla, Chandrakumar
AU - Bharadwaj, Renu
AU - Sivaramakrishnan, Gomathi Narayan
AU - Pradhan, Neeta
AU - Gupte, Akshay
AU - Murali, Lakshmi
AU - Valvi, Chhaya
AU - Swaminathan, Soumya
AU - Gupta, Amita
N1 - Funding Information:
Funding:Datainthismanuscriptwerecollectedas partoftheRegionalProspectiveObservational ResearchforTuberculosis(RePORT)India Consortium.Thisprojecthasbeenfundedby DepartmentofBiotechnology(DBT)andtheIndian CouncilofMedicalResearch(ICMR),Government ofIndiaandtheUnitedStatesNationalInstitutesof Health(NIH),NationalInstituteofAllergyand InfectiousDiseases(NIAID),OfficeofAIDS Research(OAR),anddistributedinpartbyCivilian ResearchDevelopmentFoundation(CRDF)Global. Researchreportedinthispublicationwasalso supportedbytheNIH/NIAIDJohnsHopkins Baltimore-Washington-IndiaClinicalTrialsUnit (BWICTU)(UM1AI069465),andtheFogarty InternationalCenter,NIHD43TW009574.The contentsofthispublicationaresolelythe responsibilityoftheauthorsanddonotrepresent theofficialviewsoftheDBT,theICMR,theNIH, JHUorCRDFGlobal.Anymentionoftradenames, commercialprojectsororganizationsdoesnot implyendorsementbyanyofthesponsoring organizations.Thesponsorshadnoroleinthe studydesignandwritingofthisreport.We acknowledgesupportfromPersistentSystems. Thefundershadnoroleinthestudydesign,data collectionandanalysis,decisiontopublish,or preparationofthemanuscript.
Publisher Copyright:
© 2018 Chandrasekaran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/8
Y1 - 2018/8
N2 - Background World 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 methods A 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. Results Of 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. Conclusion Prevalence 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.
AB - Background World 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 methods A 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. Results Of 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. Conclusion Prevalence 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.
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U2 - 10.1371/journal.pone.0199360
DO - 10.1371/journal.pone.0199360
M3 - Article
C2 - 30067752
AN - SCOPUS:85050980157
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 8
M1 - e0199360
ER -