Effect of delamanid on interim outcomes of bacteriological conversion amongst pediatric drug resistant tuberculosis cases in India.

AIM: To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion. METHODS: This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports. Follow-up sputum TB MGIT culture was carried out monthly after DLM initiation for 6 months. Factors associated with sputum bacteriological conversion such as age, gender, pulmonary TB (PTB) versus disseminated TB, unilateral or bilateral lung involvement, type of DR-TB, prior treatment failure, and type of DR-TB regimen were analyzed. RESULTS: Sixty patients received DLM of which two had extrapulmonary TB (EPTB) and sputum conversion could not be assessed. The mean age at presentation was 12.69 ± 3.03 years. Five patients (8.3%) died while on DLM treatment. On follow-up, 8 (13.7%) out of 58 patients had no sputum bacteriological conversion after 6 months of DLM initiation of which three patients were on salvage therapy; 46 (79.3%) had sputum bacteriological conversion within 6 months of DLM initiation. CONCLUSION: Sputum bacteriological conversion rate was almost 80% at the end of 6 months of DLM-based treatment.

Vitamin D receptor genetic polymorphisms in severe and recurrent tuberculosis in children.

AIM: To analyze the genetic polymorphisms of vitamin D receptor FokI, TaqI, ApaI and BsmI gene polymorphisms in children with severe and recurrent tuberculosis (TB). METHODS: A prospective, observational study was conducted in 35 children with severe and recurrent TB referred to our Pediatric TB clinic at a tertiary referral center for children. The blood samples were analysed for genetic polymorphisms of Vitamin D receptor with respect to FokI, TaqI, ApaI and BsmI genotypes and their individual alleles and association of various clinical and laboratory parameters were analysed. RESULT: Ten (28.6%) children had recurrent TB and 26 (74.3%) had severe TB. The severity of TB was not associated with Ff and ff polymorphism of FokI (Odd's ratio 7.88) as compared to no FokI polymorphism. Absence of FokI polymorphism was associated with recurrent lymph node TB (Odds ratio 3.429). Presence of Tt polymorphism of TaqI (p = 0.04) and Fok1 Polymorphism [Odds ratio 7.88] were not associated with recurrent TB. CONCLUSION: Recurrent TB was absent in presence of Tt polymorphism of TaqI. Severe TB was not associated polymorphism of Vitamin D receptor polymorphisms.

Feasibility of a "Salvage Regimen" Using Home-based Intravenous Meropenem Therapy With a Delamanid/Bedaquilline Containing Regimen in the Management of MDR/XDR Pediatric Tuberculosis.

INTRODUCTION: The prevalence of multidrug resistant (MDR) tuberculosis (TB) with additional resistance to fluoroquinolones or second-line injectables (MDRFQ/SLI)/extensively drug-resistant TB (XDR-TB) in children is high in Mumbai. There are limited therapeutic options available in management of such children. Carbapenems, although approved for this indication, requires 2 to 3 daily injections, which are cumbersome. Bedaquilline (Bdq) and Delamanid (Dlm), the new antitubercular drugs still remain inaccessible to this subset of patients caused by conditional approvals. Hence, newer strategies to combat MDRFQ/SLI/XDR-TB needs to be explored. OBJECTIVES: To study feasibility and interim outcomes of a "salvage regimen" using home-based carbapenem therapy through peripherally inserted central catheter as part of a longer (18-20 months) optimized background regimen including Dlm or Bdq or both in pediatric MDRFQ/SLI/XDR-TB patients who failed a standard MDR-TB regimen under the National Tuberculosis Elimination Programme in Mumbai, India. DESIGN AND METHODS: Retrospective descriptive analysis study. National Tuberculosis Elimination Programme medical records of all MDRFQ/SLI/XDR-TB patients enrolled at the pediatric TB clinic at BJ Wadia Hospital for Children, Mumbai who were initiated on such "salvage regimen" during the period between April 2018 and December 2020 were retrospectively studied. Treatment outcomes and adverse events were described. RESULTS: Of the 15 patients enrolled, mean age of the patient population was 12.53 ± 2.47 years and the female:male ratio was 13:2. Seven patients had XDR-TB while 8 patients had MDRFQ/SLI. Most common adverse event noted was dyselectrolytemia (3 patients). Catheter-related complications were reported in 5 patients and included catheter blockage, leak, and thrombosis. Sputum culture conversion was reported in all of the patients. One child mortality was reported and 2 patients were lost to follow up during study period. CONCLUSIONS: Home-based meropenem therapy using peripherally inserted central catheter is feasible with few adverse effects. This can be a promising strategy in the management of MDRFQ/SLI/XDR-TB when an effective oral regimen cannot be otherwise constituted and needs to be explored further.

Discordance between TST and QFT-TBGold Plus for Latent Tuberculosis Screening among Under-Five Children: An Interim Analysis.

AIM: To analyze the agreement between tuberculin skin test (TST) and fourth-generation QuantiFERON (QFT)-TB Gold Plus [interferon gamma (INF-γ) release assays (IGRA)] for latent tuberculosis infection (LTBI) diagnosis among under-five children who are undernourished and/or who have history of contact with active tuberculosis (TB) patients. METHODS: Children from the age group of 6 months to 5 years (undernourished or tuberculosis household contacts) were screened through anganwadis (government playschools) and TB Health posts from Mumbai, India during September 2019 to January 2021. Both TST and QFT-TB Gold Plus test were carried out to diagnose LTBI. RESULTS: Out of the total 299, 35 (11.7%) (95% CI 8.1-15.3%) children tested positive by IGRA (QFT-TB Gold Plus) and 68 (22.7%) (95% CI 18.0-27.4%) by TST, suggestive of moderate concordance (κ = 0.483) between both tests. IGRA and TST showed moderate concordance in children <24 months (κ = 0.478). Moreover, 26 (21.1%) children with TB contact had both TST and IGRA positive with moderate concordance (κ = 0.550). A fair concordance (κ = 0.396) was observed between IGRA and TST in undernourished children. Also, 45 (15.0%) children showed discordance of which 39 (13.0%) had positive TST but negative IGRA and 6 (2.0%) had negative TST but positive IGRA. CONCLUSIONS: The study strongly recommends both TST and QFT-TB Gold Plus test for the diagnosis of LTBI in under-five children. A moderate concordance in children <24 months endorses the reliability of QFT-TB Gold Plus in diagnosing LTBI in this age group. This study highlights the need for screening undernourished children for LTBI to consider repeating IGRA testing for TST positives as per the window period and risk of ongoing exposure.

The current study focuses on discordance and concordance between tuberculin skin test (TST) and fourth-generation QuantiFERON (QFT)-TB Gold Plus [interferon gamma (INF-γ) release assays (IGRA)] for latent tuberculosis infection (LTBI) diagnosis among at-risk under-five children who are underweight and/or who have history of contact with active tuberculosis patients. The IGRA prevalence came out to be 11.7% (95% CI 8.1­15.3%) whereas the TST prevalence turned out to be 22.7% (95% CI 18.0­27.4%). A stronger concordance was observed between IGRA and TST among the age group of 2 to 5 years, and a relatively fair one for children below the age of 1 year. The present study strongly recommends to include both TST and IGRA test for the diagnosis of LTBI with respect to Indian pediatric population. This study also suggests the importance of repetition of IGRA for TST positive patients. Another vital opinion that is showcased in the present study is the inclusion of undernourished pediatric population residing in at-risk areas like urban slums for routine LTBI screening programs.

RepEx: A web server to extract sequence repeats from protein and DNA sequences.

Evolution builds up new genetic material from existing ones, not in random, but in highly ordered and eloquent patterns. Most of these sequence repeats are revelatory of valuable information contributing to areas of disease research and function of macromolecules, to name a few. In the age of next generation genome sequencing, rapid and efficient extraction of all unbiased sequence repeats from macromolecules is the need of the hour. In view of this reckoning, an online web-based computing server, RepEx, has been developed to extract and display all possible repeats for DNA and protein sequences. Apart from exact or identical repeats, the server has been designed adeptly to identify and extract degenerate, inverted, everted and mirror repeats from both DNA and protein sequences. The server has striking output displays, featuring interactive graphs and comprehensive output files. In addition, RepEx has been accoutered with an easy-to-use interface and search filters to facilitate a user-defined query or search and is freely available and accessible via the World Wide Web at http://bioserver2.physics.iisc.ac.in/RepEx/.