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.

Latent tuberculosis among household contacts of pulmonary tuberculosis cases in Nairobi, Kenya

“…A hallmark of the natural history of tuberculosis is the diverse outcome of infection. There are three possible outcomes of exposure to an infectious TB case: the infection may be cleared by sterilizing immunity [ 3 ] as evidenced by immunological assays [ 4 ]; development of active TB and development of latent tuberculosis infection (LTBI). Studies have shown that 10% of LTB infected individuals develop active TB and because of the underlying immune deficiency, HIV-infected individuals with LTBI are at 26-fold higher risk for TB reactivation [ 5 ].…”

Tuberculosis preventive treatment should be considered for all household contacts of pulmonary tuberculosis patients in India

“…Our analyses of HHC at baseline, included additional data that was not available for earlier C-TRIUMPH publications [ 29 , 30 ]. After excluding HHC found to have active TBD at initial screening, baseline characteristics, including characteristics of the TB index patients and households, of the asymptomatic HHC with and without TBD were compared.…”

Phenotype Definition for “Resisters” to Mycobacterium tuberculosis Infection in the Literature—A Review and Recommendations

“…This score is composed of a number of questions that provides a good understanding of the extent of exposure (i.e. whether the HHC share the same room or bed as the index case, whether the index case is actively coughing, whether the index case has a smear-positive sputum, whether the index case see the HHC every day) ( 11 , 12 , 15 ). The score can be used in both adult and pediatric populations.…”

“…Mave et al. recruited a total of 799 children, adolescents and adults who had been living in the same household of an adult pulmonary TB index case from two different sites in India ( 15 ). Follow-up included three QFT tests and three TSTs (5 TU, PPD, SPAN/Arkray, India) at baseline, at 4 months and at 12 months.…”