Clinical Characteristics of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in North Indian Population of HIV/AIDS Patients Receiving HAART

Background & Objective. IRIS is an important complication that occurs during management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous studies have reported variable incidence of IRIS. The present study was undertaken to describe the pattern of TB-associated IRIS using recently proposed consensus case-definitions for TB-IRIS for its use in resource-limited settings. Methods. A prospective analysis of ART-naïve adults started on HAART from November, 2008 to May, 2010 was done in a tertiary care hospital in north India. A total 224 patients divided into two groups, one with HIV-TB and the other with HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB was categorised as ‘‘definitive” and ‘‘probable”. Results. Out of a total of 224 patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%) HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A reduction in plasma viral load was significantly (P = .016) associated with paradoxical TB-IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Conclusion. The consensus case-definitions are useful tools in the diagnosis of TB-associated IRIS. High index of clinical suspicion is required for an early diagnosis

Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis.

BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health

Influence of genetic variability in toll-like receptors (TLR 2, TLR 4, and TLR 9) on human immunodeficiency virus-1 disease progression

Background: It has been demonstrated that toll-like receptors (TLR2), TLR4, and TLR9 which were initially known for recognizing bacterial products are involved in the detection of viral components. It was planned to undertake a prospective longitudinal study among ethnically homogeneous antiretroviral treatment and antitubercular treatment naïve human immunodeficiency virus (HIV)-positive patients representing the north Indian population. The aim of the study was to investigate the influence of TLR2, TLR4, and TLR9 polymorphism in HIV disease progression. Methods: The present study was designed to investigate genetic polymorphism in TLRs (TLR2, TLR4, and TLR9) among HIV-infected patients with and without TB coinfection. The study population consisted of two groups: (i) HIV-positive patients without TB infection and disease (n = 223, HIV-positive patients); (ii) HIV-positive patients with latent tuberculosis infection (LTBI) (n = 150, HIV-positive LTBI patients). These participants were of either gender between 18 and 60 years of age and treatment naïve for both TB and HIV. HIV-positive and HIV-positive LTBI patients were longitudinally followed up for t2 years to study HIV disease progression. Results: On comparing TLR2 and TLR4 allelic and genotypic frequencies between 306 HIV-positive patients (no TB/AIDS) and 47 HIV-positive patients progressed to active TB/AIDS, no significant difference was observed between the two groups. The frequency of “A” allele in TLR9 was found to be significantly increased in 47 HIV-positive patients who progressed to active TB/AIDS (61.7%) as compared to 42.16% in 306 HIV-positive patients (no TB/AIDS), (P < 0.001). Furthermore, a significantly increased frequency of “AA” genotype in TLR9 was observed in 47 HIV-positive patients progressed to active TB/AIDS (55.32%) as compared to 20.26% in HIV-positive patients (no TB/AIDS). Conclusion: Findings of the present study revealed that genetic variability in TLR9 may influence HIV disease progression. The AA genotype in TLR9 may be associated with progression to TB/AIDS for 2 years in HIV-positive patients

Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting.

There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings.1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases.Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72-1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97-2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients.Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings

Baseline characteristics of the household contacts of pulmonary TB patients.

<p>Baseline characteristics of the household contacts of pulmonary TB patients.</p

Incidence of active TB among subjects with LTBI stratified by age and TST and QFT-GIT assay results (n = 1511).

<p>Incidence of active TB among subjects with LTBI stratified by age and TST and QFT-GIT assay results (n = 1511).</p

Predictors of TB development among household contacts of pulmonary TB patients (n = 1511).

<p>Predictors of TB development among household contacts of pulmonary TB patients (n = 1511).</p

Agreement of TST and QFT-GIT assay with BCG in household contacts of pulmonary TB.

<p>Agreement of TST and QFT-GIT assay with BCG in household contacts of pulmonary TB.</p