National Institute of Research in Tuberculosis

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    Ethambutol-induced optic neuropathy: should we mandate ophthalmic examination in TB treatment?

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    India’s National Tuberculosis Elimination Programme (NTEP)1 and the WHO have recommended ethambutol (EMB) for use in the continuation phase of TB treatment due to the higher prevalence of isoniazid resistance in the patient community. This leaves only a single drug in the continuation phase that might adversely affect treatment outcomes.2 While reporting adverse drug reactions (ADRs), we found that EMB often induced optic neuropathy during anti-TB therapy (ATT) for drugsusceptible TB (DS-TB). In the study presented here, we define these ADRs and recommend adopting safety precautions when treating DS-TB patients

    Role for Linezolid in drug sensitive tuberculosis

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    Tuberculosis (TB) continues to be a global challenge. Reducing the duration of TB treatment for drugsensitive TB (DSTB) has direct and distinct advantages. We ventured into the aspect of utilizing linezolid as a pivotal drug in shortening therapy in DSTB. Linezolid has gained prominence as it is faring well in resistant TB management. Only a few studies use the strategy of Linezolid in DS-TB but it seems a lucrative approach, the bactericidal effects have been reported favourably in the studies. There have been concerns about the potential adverse drug effects of Linezolid reported but clinical trials have demonstrated safety and tolerability when administered for shorter periods. If the safety and efficacy of giving Linezolid for a shorter period along with standard drugs for DSTB is established it could lead to newer avenues using Linezolid for shortening the duration of treatment for DSTB as an alternative to treat DSTB

    Economic aspects of shortening the duration of tuberculosis treatment

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    With the currently recommended 6-month antituberculosis therapy (ATT), 85% of people with drugsensitive tuberculosis could be cured.1 However, this regimen still requires four medications and a minimum of 6 months of therapy. Long duration of treatment and drug-related toxicity leads to drug fatigue and non-compliance. Recurrence, community transmission, and acquired drug-resistance are all risks associated with premature treatment discontinuation, especially for drug-resistant tuberculosis, which requires more intensive treatment and longer duration.2 The prevailing cost of treatment constrains available resources in lowincome and middle-income countries, and thus shorter regimens for both drug-susceptible and drug-resistant tuberculosis are vital

    Virulence and Replicative Fitness of HIV-1 Transmitted/Founder (T/F) Viruses Harbouring Drug Resistance-Associated Mutation

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    The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants. All the clones were characterized genotypically through whole genome sequencing and phenotypically for infectivity, replication kinetics, co-receptor usage, as well as their susceptibility to neutralizing antibodies and entry inhibitors using standard virological assays. Genotypic analysis revealed that all the T/F clones were of non-recombinant subtype C, but some of them harboured the Y181C drug resistance mutation associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretroviral drugs. In vitro studies showed that while all the IMCs were capable of replicating in PBMCs and utilized the CCR5 co�receptor for cellular entry, the drug-resistant variants had significantly lower replicative capacity and per particle infectivity than the drug-sensitive viruses. Both exhibited similar sensitivities to a standard panel of broadly neutralizing monoclonal antibodies and viral entry inhibitors. These findings suggest that despite their diminished replicative fitness, the drug-resistant T/F variants retain transmission fitness and remain susceptible to neutralizing antibody-based interventions and viral entry inhibitor

    POPULATION ATTRIBUTABLE FRACTION FOR UNDER NUTRITION IN TB, IN THE SELECTED DISTRICTS OF TAMIL NADU; THE STATE TB SURVEY

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    A population based state wide TB survey was conducted in 2021-2022 in Tamil Nadu, India, among the participants aged 15 and above, to identify the microbiologically confirmed pulmonary TB cases. Population attributable fraction (PAF) was calculated for the state and the districts. In total 130,932 participants were screened across the state and 244 participants were diagnosed with microbiologically confirmed pulmonary TB. PAF for the risk factors for TB with under nutrition (BMI60 years was 27(20-34). Krishnagiri 78(23 - 97), Pudukkottai 72(14 -96) and Vellore 71(37–90) districts were having higher PAF values for under nutrition. Wide range was observed due to low sample size. Population attributable risk factors for TB in Tamil Nadu state was higher for under nutrition. Public health interventions could be planned to address this issue accordingly, during TB elimination activities

    Association of CYP27B1 gene polymorphisms with pulmonary tuberculosis and vitamin D levels

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    Background and Objectives: Genetic factors are reported to be connected with tuberculosis (TB) infection. Studies have shown that genetic variations in genes involved in the vitamin D pathway influence the levels of vitamin D found in the bloodstream (serum). Cyp27b1 (1α-hydroxylase) is an enzyme that activates the synthesis of bioactive vitamin D3 by hydroxylation of 25(OH)D3. The in vitro studies reported rare gene variants of Cyp27b1 such as rs118204011 and rs118204012, associated with loss of Cyp27b1 function and lower serum vitamin D levels. Globally, a critical gap exists in understanding the link between these gene variants with TB and vitamin D levels. Hence, the study objective is to comprehend the association of Cyp27b1 rs118204009 (G/A), rs118204011 (C/T), and rs118204012 (A/G) with tuberculosis susceptibility/protection and to assess the influence of gene variants on vitamin D levels in both healthy controls (HCs) and those with pulmonary tuberculosis (PTB) in South India

    Distinct TB-antigen stimulated cytokine profiles as redictive biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis

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    The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertai

    Biomolecular InteractionofCarnosineandAnti-TBDrug: PreparationofFunctionalBiopeptide-BasedNanocompositesand CharacterizationthroughInVitroandInSilicoInvestigations

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    The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants. All the clones were characterized genotypically through whole genome sequencing and phenotypically for infectivity, replication kinetics, co-receptor usage, as well as their susceptibility to neutralizing antibodies and entry inhibitors using standard virological assays. Genotypic analysis revealed that all the T/F clones were of non-recombinant subtype C, but some of them harboured the Y181C drug resistance mutation associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of antiretroviral drugs. In vitro studies showed that while all the IMCs were capable of replicating in PBMCs and utilized the CCR5 co-receptor for cellular entry, the drug-resistant variants had significantly lower replicative capacity and per particle infectivity than the drug-sensitive viruses. Both exhibited similar sensitivities to a standard panel of broadly neutralizing monoclonal antibodies and viral entry inhibitors. These findings suggest that despite their diminished replicative fitness, the drug-resistant T/F variants retain transmission fitness and remain susceptible to neutralizing antibody-based interventions and viral entry inhibitors

    Diagnostic accuracy of truenat MTB plus for the detection of pulmonary and extrapulmonary tuberculosis

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    The diagnosis of Tuberculosis (TB) has been a challenge till the advent of rapid molecular diagnostic tests. The traditional diagnostic tests have its own limitations with regard to its performance or the turnaround time. Truenat MTB Plus assay, a battery-operated molecular assay developed in India has been introduced for its use in pulmonary TB (PTB). However, the diagnostic accuracy of the assay is not well studied in comparison with Mycobacterial culture, especially for extrapulmonary TB (EPTB)

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