Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis.

BACKGROUND: Tuberculosis remains a global health concern, and half of cured patients have permanent lung injury. N-acetylcysteine (NAC) has shown beneficial antimicrobial, antioxidant, and immunomodulatory effects in preclinical tuberculosis models. We examined its effects on tuberculosis treatment outcomes. METHODS: This prospective, randomized, controlled trial nested within the TB SEQUEL cohort study enrolled 140 adults with moderate or far-advanced tuberculosis. Participants were randomly assigned 1:1 to standard therapy with or without 1200 mg of oral NAC twice daily for days 1 to 112. Clinical evaluations, sputum culture, and spirometry were performed at specified intervals through day 168, after which participants returned to the TB SEQUEL cohort. The primary outcome was culture conversion. Secondary outcomes included whole-blood glutathione levels and lung function. RESULTS: Participants were predominantly young, male, and human immunodeficiency virus 1-negative and had heavy sputum Mycobacterium tuberculosis (MTB) infection burdens. NAC increased glutathione levels (NAC × day interaction, 8.48; 95% confidence interval [CI], 1.93 to 15.02) but did not increase stable culture conversion (hazard ratio, 0.84; 95% CI, 0.59 to 1.20; P=0.33). NAC treatment was associated with improved recovery of lung function (NAC × month, 0.49 [95% CI, 0.02 to 0.95] and 0.42 [95% CI, -0.06 to 0.91] for forced vital capacity and forced expiratory volume in the first second, respectively, as percentages of predicted values). The effects of NAC on lung function were greatest in participants with severe baseline lung impairment and appeared to persist beyond the period of NAC administration. Rates of serious or grade 3 to 4 nonserious adverse events did not differ between the groups. CONCLUSIONS: Despite increasing whole-blood glutathione levels, NAC did not affect eradication of MTB infection in adults with pulmonary tuberculosis that was moderate to far advanced. Secondary outcomes of lung function showed changes that merit further investigation. (Funded by TB SEQUEL grant 01KA1613 of the German Ministry for Education and Research, the Health Africa Project, and the German Center for Infection Research; ClinicalTrials.gov number, NCT03702738.).

Impact of N-Acetyl Cysteine (NAC) on Tuberculosis (TB) Patients-A Systematic Review.

Sustained TB infection overproduces reactive oxygen species (ROS) as a host defense mechanism. Research shows ROS is destructive to lung tissue. Glutathione (GSH) neutralizes ROS, although it is consumed. NAC is a precursor of GSH synthesis, and administering an appropriate dose of NAC to patients with respiratory conditions may enhance lung recovery and replenish GSH. The present review searched for articles reporting on the effects of NAC in TB treatment from 1960 to 31 May 2022. The PICO search strategy was used in Google Scholar, PubMed, SciFinder, and Wiley online library databases. The COVIDENCE tool was used to delete inappropriate content. We eventually discovered five clinical trials, one case report, seven reviews, in vitro research, and four experimental animal studies from the twenty-four accepted articles. The use of NAC resulted in increased GSH levels, decreased treatment time, and was safe with minimal adverse events. However, the evidence is currently insufficient to estimate the overall effects of NAC, thus the study warrants more NAC clinical trials to demonstrate its effects in TB treatment.

Treatment outcomes of multi-drug resistant tuberculosis patients with or without human immunodeficiency virus co-infection in Africa and Asia: Systematic review and meta-analysis.

Background: Treatment outcomes of multidrug resistant tuberculosis (MDRTB) is a challenge, especially in resource limited settings. The aim of this study was to compare whether Human Immune Virus (HIV) has influence on the treatment outcomes of MDRTB among patients in Africa and Asia. Methods: Studies were searched from PubMed, Google scholar, African Journals online, EBSCOhost and CENTRAL from year 2000 until January 2021. The participants in the studies were reported of using MDRTB treatment regimen and also included those with HIV. Studies published before 2000 were excluded. Quality of the review was assessed by AMSTEL 2 criteria. The Mantel- Haenszel random effects method was used for the analysis, with risk ratio (RR) as an effect estimate, with 95% confidence interval and using Stata 14 software. Results: Nine studies were included in the meta-analysis. Treatment success was low in HIV negative participants (RR 0.62, 95% CI 0.58-0.67). However, death was higher in the HIV co-infected participants. (RR 1.35, 95% CI 1.25-1.45). There was no significant difference in treatment failure among patients with or without HIV. (RR 1.08, 95% CI 0.97-1.20). Consistently, no significant difference was found in lost to follow up (LTF) between the two groups (RR 1.07, 95% CI 0.93-1.20). Conclusion: Treatment success was lower for the MDRTB and HIV co-infections. No significant difference has been found on other outcomes like failure and lost to follow up between patients with HIV co-infected and HIV negative group. The study limitations are that we had only 2 studies representing Asia, and this could have affected the outcome of results. There is need for interventions to improve treatment success in the HIV co-infected group. Other: The protocol was registered in International prospective register of systematic reviews (PROSPERO), ID: CRD42021247883. There was no funding for the review.

Linkage into care among newly diagnosed HIV-positive individuals tested through outreach and facility-based HIV testing models in Mbeya, Tanzania: a prospective mixed-method cohort study.

OBJECTIVE: Linkage to care is the bridge between HIV testing and HIV treatment, care and support. In Tanzania, mobile testing aims to address historically low testing rates. Linkage to care was reported at 14% in 2009 and 28% in 2014. The study compares linkage to care of HIV-positive individuals tested at mobile/outreach versus public health facility-based services within the first 6 months of HIV diagnosis. SETTING: Rural communities in four districts of Mbeya Region, Tanzania. PARTICIPANTS: A total of 1012 newly diagnosed HIV-positive adults from 16 testing facilities were enrolled into a two-armed cohort and followed for 6 months between August 2014 and July 2015. 840 (83%) participants completed the study. MAIN OUTCOME MEASURES: We compared the ratios and time variance in linkage to care using the Kaplan-Meier estimator and Log rank tests. Cox proportional hazards regression models to evaluate factors associated with time variance in linkage. RESULTS: At the end of 6 months, 78% of all respondents had linked into care, with differences across testing models. 84% (CI 81% to 87%, n=512) of individuals tested at facility-based site were linked to care compared to 69% (CI 65% to 74%, n=281) of individuals tested at mobile/outreach. The median time to linkage was 1 day (IQR: 1-7.5) for facility-based site and 6 days (IQR: 3-11) for mobile/outreach sites. Participants tested at facility-based site were 78% more likely to link than those tested at mobile/outreach when other variables were controlled (AHR=1.78; 95% CI 1.52 to 2.07). HIV status disclosure to family/relatives was significantly associated with linkage to care (AHR=2.64; 95% CI 2.05 to 3.39). CONCLUSIONS: Linkage to care after testing HIV positive in rural Tanzania has increased markedly since 2014, across testing models. Individuals tested at facility-based sites linked in significantly higher proportion and modestly sooner than mobile/outreach tested individuals. Mobile/outreach testing models bring HIV testing services closer to people. Strategies to improve linkage from mobile/outreach models are needed.