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Infection free "resisters" among household contacts of adult pulmonary tuberculosis.

ABSTRACT: Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GIT), underwent follow-up testing at 4-6 and/or 12 months. We defined persons with persistently negative LTBI tests at both baseline and followup as pLTBI- and resisters as those who had a high exposure to TB using a published score and remained pLTBI-. We calculated the proportion of resisters overall and resisters with complete absence of response to LTBI tests (0mm TST and/or QFT-GIT <0.01 IU/ml). Using random effects Poisson regression, we assessed factors associated with pLTBI-. Of 799 HHCs in 355 households, 67 (8%) were pLTBI- at 12 months; 52 (6.5%) pLTBI- in 39 households were resisters. Complete absence of response to LTBI tests was found in 27 (53%) resisters. No epidemiological characteristics were associated with the pLTBI- phenotype. LTBI free resisters among HHC exist but are uncommon and are without distinguishing epidemiologic characteristics. Assessing the genetic and immunologic features of such resister individuals is likely to elucidate mechanisms of protective immunity to TB.

SUBMITTER: Mave V

PROVIDER: S-EPMC6638997 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Infection free "resisters" among household contacts of adult pulmonary tuberculosis.

Mave Vidya V Chandrasekaran Padmapriyadarshini P Chavan Amol A Shivakumar Shri Vijay Bala Yogendra SVBY Danasekaran Kavitha K Paradkar Mandar M Thiruvengadam Kannan K Kinikar Aarti A Murali Lakshmi L Gaikwad Sanjay S Hanna Luke Elizabeth LE Kulkarni Vandana V Pattabiraman Sathyamoorthy S Suryavanshi Nishi N Thomas Beena B Kohli Rewa R Sivaramakrishnan Gomathi Narayan GN Pradhan Neeta N Bhanu Brindha B Kagal Anju A Golub Jonathan J Gandhi Neel N Gupte Akshay A Gupte Nikhil N Swaminathan Soumya S Gupta Amita A

PloS one 20190718 7

Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GI ...[more]

PMID: 31318864

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Project description:BackgroundMumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known.MethodsWe conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB® Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease.ResultsAmong 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT.ConclusionA test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation.

Project description:The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Project description:BackgroundThe risk of tuberculosis transmission is higher among household contacts than the general population. However, there is a paucity of information that explains the risk of experiencing active tuberculosis among household contacts in countries with a high burden of tuberculosis.ObjectiveThis study aimed to assess the prevalence of tuberculosis infection and associated factors among adult household contacts of smear-positive pulmonary tuberculosis patients in the Kembata-Tembaro zone, southern Ethiopia.MethodsA cross-sectional study design was conducted in the Kembata-Tembaro zone, southern Ethiopia, from August to September 2022. Data were collected from 336 adult household contacts using a pretested questionnaire, and sputum examinations were done using fluorescence microscopy. Binary logistic regression models were used to identify factors associated with tuberculosis infection among adult household contacts.ResultsThe prevalence of active tuberculosis among adult household contacts of smear-positive pulmonary tuberculosis patients was 6.9% (95% CI 4% to 10%). Nearly half, 47.8%, of them belonged to economically productive adults aged 30-44 years. Smoking cigarettes (adjusted OR (AOR) 6.5, 95% CI (1.04 to 40.17)), sharing a bed with the index tuberculosis case (AOR 6.0, 95% CI (1.97 to 18.28)), poor housing ventilation (AOR 4.2, 95% CI (2.85 to 17.16)) and overcrowded housing (AOR 4.6, 95% CI (1.42 to 14.58)) were associated with tuberculosis infection among household contacts of patients with smear-positive pulmonary tuberculosis.ConclusionsThis study has revealed that the prevalence of active tuberculosis among adult household contacts of smear-positive pulmonary tuberculosis patients was detected to be similar to other reports from Ethiopia. Additionally, interventions to prevent tuberculosis transmission among household contacts should focus on providing behaviour change education, improving housing conditions, early detection and isolation of index cases, contact tracing, isoniazid chemoprophylaxis of household contacts with weakened immunity and covering the mouth and nose when coughing or sneezing.

Dataset Information

Infection free "resisters" among household contacts of adult pulmonary tuberculosis.

Publications

Infection free "resisters" among household contacts of adult pulmonary tuberculosis.

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