Role for Linezolid in drug sensitive tuberculosis

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

Safety profile of BCG revaccination for COVID prevention among elderly individuals in India

BCG vaccination is known to be safe in infants and a part of immunization schedule in high tuberculosis (TB)burden countries. In the conquest to bring down the severity of the COVID 19 pandemic, many drugs were repurposed in research mode including BCG vaccination/revaccination in various populations. We did a study among the elderly population (>60 years of age) to assess the role of BCG revaccination in preventing the severity of COVID 19 disease. Live attenuated BCG vaccine was given to the willing participants and were followed up for 6 months to estimate COVID19 incidence, understand severity and immunogenicity profile. A total of 48 serious adverse events (SAE) were reported among 1566 elders, none of them had more than one SAE. None of the SAEs were related to the BCG revaccination. Among the 372 adverse events reported, 96% were local reactions at the vaccine site and resolved on its own. BCG revaccination appeared to be safe and could be explored further if repurposing studies were planned for other diseases

Current trends and intricacies in the management of HIV-associated pulmonary tuberculosis

Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy. Liquid culture methods and nucleic acid amplification tests for TB confirmation have replaced conventional solid media, enabling quicker and simultaneous detection of mycobacterium and its drug sensitivity profile Unique problems posed by the syndemic include Acquired rifampicin resistance, drug–drug interactions, malabsorption of drugs and immune reconstitution inflammatory syndrome or paradoxical reaction that complicate dual and concomitant therapy. While the antiretroviral therapy armamentarium is constantly reinforced by discovery of newer and safer drugs every year, only a few drugs for anti tuberculosis treatment have successfully emerged. These include bedaquiline, delamanid and pretomanid which have entered phase III B trials and are also available through conditional access national programmes. The current guidelines by WHO to start Antiretroviral therapy irrespective of CD4+ cell count based on benefits cited by recent trials could go a long way in preventing various complications caused by the deadly duo. This review provides a consolidated gist of the advancements, concepts and updates that have emerged in the management of HIV-associated pulmonary TB for maximizing efficacy, offering latest solutions for tackling drug–drug interactions and remedial measures for immune reconstitution inflammatory syndrome

A national-level analysis of life expectancy associated with the COVID-19 pandemic in India.

BACKGROUND From a demographic perspective, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on life expectancy is not clear. Hence, there is a need to study the number of years of life lost concerning the existing average life expectancy due to COVID-19 in India. OBJECTIVE This study aimed to estimate the impact of life expectancy due to the COVID-19 pandemic in India. METHODOLOGY We considered day-wise age-specific mortality due to COVID-19 which was extracted from the COVID-19 data repository from March 11, 2020, to June 30, 2021, in India. All-cause mortality was collected from the United Nations population estimates. An abridged life table technique was utilized for calculating life expectancies based on all-cause mortality and mortality due to COVID-19. MortPak software was used to calculate the life expectancy with and without the COVID-19 pandemic. Life expectancy at birth in different age groups was estimated with respect to with and without COVID-19. RESULTS A total of 399,459 deaths due to COVID-19 were distributed age wise, and their corresponding life expectancy was calculated. The general mortality was compared with COVID-19 mortality for the various age groups, and it was observed that mortality due to COVID-19 was significantly higher among the elderly age group [i.e., 45 to 60 years (36%) and > 60 years (51%)] when compared with < 25 years (1%) and 26-44 years (11%) (trend Chi-square 7.59; = 0.001). The life expectancy without and with COVID-19 was 69.28 years and 69.16 years, respectively. CONCLUSION Overall, it was estimated that COVID-19 has an impact on life expectancy by 0.12 years during the study period. Even though mortality due to COVID-19 was high, factors such as lockdown, vaccination, and accidents also had an influence on mortality. Thus, there is a need to assess the impact of COVID-19 on life expectancy in future

Long-term Survival of Treated Tuberculosis Patients in Comparison to a General Population In South India: A Matched Cohort Study

Objectives: This study aimed to measure the mortality rate, potential years of life lost, and excess general mortality among individuals treated for pulmonary tuberculosis (TB) in a TB endemic country. Methods: A retrospective analysis was conducted on a population-based cohort study of 4022 TB patients and 12,243 gender-matched and age-matched controls from prevalence surveys conducted between 2000 and 2004 in the Thiruvallur district of Tamil Nadu, South India. Results: The mortality rate among TB patients was 59/1000 person-years. The excess standardized mortality ratio was 2.3 (95% CI: 1.7–3.1). The rate of potential years of life lost was 6.15/1000 (95% CI: 5.97–6.33) in the TB cohort compared to the general population of 1.52/1000 (95% CI: 1.46–1.60). Individuals aged >50 years, those underweight (<40 kg), with treatment failures, or lost to follow-up had higher mortality rates when compared with the rest of the TB cohort. The risk of death was significantly higher in the TB cohort until the end of the fourth year when compared with later years. Conclusion: Mortality in the TB cohort was 2.3 times higher than in the age-matched general population. Most deaths occurred in the first year after completing treatment. Post-treatment follow-ups and interventions for reducing comorbid conditions are necessary to prevent deaths

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized &gt;90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT &gt; 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine

Randomised trial to evaluate the effectiveness and safety of varying doses of linezolid with bedaquiline and pretomanid in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary tuberculosis: study protocol.

INTRODUCTION Drug-resistant tuberculosis (DR-TB) is a global public health problem. Patients suffer for months if undiagnosed or treated inadequately, transmitting DR-TB in the community before succumbing to the disease. Early diagnosis, prompt treatment initiation and completion play a significant role in treatment success. However, extended regimens with injectable result in poor treatment adherence and outcomes. Our objective is to evaluate the effectiveness, safety and tolerability of various doses and duration of linezolid (LZD) in combination with bedaquiline (BDQ) and pretomanid (Pa) after 26 weeks of treatment in adults with pre-extensively drug-resistant or treatment intolerant/non-responsive multidrug-resistant pulmonary TB. METHODS AND ANALYSIS A multicentric, randomised pragmatic clinical trial in India will enrol participants in one of the three arms-control arm (arm 1): BDQ, Pa and LZD 600 mg daily for 26 weeks or intervention arms (arm 2): BDQ, Pa and LZD 600 mg for 9 weeks followed by 300 mg for 17 weeks or arm 3: BDQ, Pa and LZD 600 mg for 13 weeks followed by 300 mg for 13 weeks. The primary endpoint is the proportion of patients with favourable outcomes as sustained cure and treatment completion. The secondary endpoint is unfavourable outcomes, including deaths, treatment failure, toxicity/adverse events and lost to follow-up till 48 weeks post-treatment. ETHICS AND DISSEMINATION The study has been approved by the ethics committees of participating institutes and the National Institute for Research in TB. The trial results will help establish evidence towards a safe and effective dose of LZD that can be used in a fully, all-oral short course regimen for highly DR-TB patients. The results of this study will be shared with the National TB Elimination Programme of the country and the WHO guidelines development group through publications and dissemination meetings. TRIAL REGISTRATION NUMBER NCT05040126