Age-specific prevalence of TB infection among household contacts of pulmonary TB: Is it time for TB preventive therapy?

Abstract

Background Household contacts (HHCs) of TB patients are at high risk of developing evidence of latent TB infection (LTBI) and active disease from the index patient. We estimated the age-specific prevalence of LTBI and the force of infection (FI), as a measure of recent transmission, among HHCs of active TB patients. Methods A cross-sectional analysis of HHCs of pulmonary TB patients enrolled in a prospective study, ‘CTRIUMPh’, was conducted at two sites in India. LTBI was defined as either a positive tuberculin skin test (induration ≥5 mm) or QuantiFERON–Gold in tube test (value ≥0.35 IU/ml) and was stratified by age. FI, which is a measure of recent transmission of infection and calculated using changes in age-specific prevalence rates at specific ages, was calculated. Factors associated with LTBI were determined by logistic regression models. Results Of 1020 HHCs of 441 adult pulmonary TB cases, there were 566 (55%) females and 289 (28%) children aged ≤15 y. While screening for the study 3% of HHC were diagnosed with active TB. LTBI prevalence among HHCs of pulmonary TB was 47% at <6 y, 53% between 6–14 y and 78% between 15–45 y. FI increased significantly with age, from 0.4 to 1.15 in the HHCs cohort (p=0.05). Conclusion This study observed an increased prevalence of LTBI and FI among older children and young adults recently exposed to infectious TB in the household. In addition to awareness of coughing etiquette and general hygiene, expanding access to TB preventive therapy to all HHCs, including older children, may be beneficial to achieve TB elimination by 2035.

Implementing contact tracing for tuberculosis in Kyrgyz Republic and risk factors for positivity using QuantiFERON-TB Gold plus

“…However, when stratifying by age, this association completely dissipated for contacts below 15 years of age suggesting that children are also at high risk to be infected by smear negative cases. Particularly for children, living in a densely populated household was a much stronger risk factor for TB infection than the smear status of the index case, as finding that is supported in the literature [3,8,15,19]. Currently, WHO defines only household contacts per se as high risk [14], but our findings suggest that the average household density should be considered as criterion for risk-stratified contact investigation among children in Kyrgyz Republic.…”

“…The Quantiferon-TB Gold plus has been successfully applied in many contact tracing and ACF projects [3,5,15,17]; however, this is the first time it has been used and reported in an ACF program in Central Asia. The logistics of timely collection, storage, and incubation of blood samples from rural areas as far as 400 km from the place of analysis are a few of the challenges that are overcome with close collaboration and communication between the country's public TB sector, local SES and private public partnerships established with laboratories in the region.…”

“…Two additional logistic regressions were also performed with the outcome defined as either "presence of symptoms" or "TST positive result". Stratified analysis was separately conducted for adults (≥15 years) and children (< 15 years) due to an association of Quan-tiFERON positivity with age [15]. Analysis was further stratified by index case smear results [16].…”

Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers

“…In this context, our work represents the first example, in an Indian cohort of TB patients, on how non-invasive serum biomarkers able to distinguish active TB or potential LTB cases can be identified based on the metabolic differences between A-TB patients and HHC-TB individuals. In the last few years, enrolment of HHC-TB individuals in TB studies, specifically focused on the identification of potential LTB cases is gaining importance [3,4]. Thus, with no recommended diagnostics that can ensure M.tb.-exposure, HHC-TB included in this study were surely M.tb.-exposed, irrespective of their TST responses.…”

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

“…The conditional WHO recommendation does not require IGRA testing due to cost and feasibility considerations, since prevalence of IGRA-positivity among close contacts is high (World Health Organizataion [WHO], 2018b). For example, although overall Mtb infection prevalence in the South-East Asia region is estimated at 28% (Cohen et al, 2019), as determined by TST, a study of adult household contacts in India reported 78% prevalence (Dolla et al, 2019). A case could be made for post-exposure vaccination to prevent TB disease among household contacts, but several considerations temper enthusiasm for this approach.…”