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Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Salles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite the availability of effective antimicrobials, tuberculosis (TB) is still a serious health threat. Mortality is even higher in people living with HIV who are diagnosed with TB. New therapies are needed to shorten the time required to cure TB and decrease fatality rates in this population. N-acetylcysteine (NAC) is a glutathione precursor and has shown recently in experimental setting to present in vitro and in vivo anti-mycobacterial activity. We test the hypothesis that NAC is safe, well tolerated and secondarily efficacious as adjunctive anti-TB therapy in hospitalized individuals with HIV-associated TB. Patients were enrolled sequentially in a tertiary care center, in the Brazilian Amazon. We performed a randomized, parallel group, single-center, open study trial of two arms, in hospitalized patients over 18 years of age, with microbiologically confirmed pulmonary TB in HIV: one with rifampicin, isoniazid, pyrazinamide and ethambutol at standard doses (Control Group), and a second in which NAC 600 mg bid for eight weeks was added (NAC Group). A total of 21 and 18 patients were enrolled to the Control Group and NAC Group, respectively. Adverse event rates were similar in the two arms. Our findings suggest that in the more critical population of hospitalized patients with HIV-associated TB, the use of NAC was not unsafe, despite the low sample size, and a potential impact on faster negative cultures needs to be further explored in larger studies., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Tuberculosis contacts are candidates for active and latent tuberculosis infection screening and eventual treatment. However, many losses occur in the different steps of the contacts' cascade of care. Reasons for this are poorly understood., Objective: To describe the different steps where losses in the contact cascade occur and to explore knowledge and attitudes regarding tuberculosis transmission/prevention and perceptions about tuberculosis services in order to understand the reasons for losses from the tuberculosis service users' perspective., Design: We collected routine data from the index case and contact registry books and from patients' records to build the cascade of care of contacts in 12 health facilities in three Brazilian cities with high tuberculosis incidence rates. During a knowledge, attitudes and practices (KAP) survey, trained interviewers administered a semi-structured questionnaire to 138 index cases and 98 contacts., Results: Most of the losses in the cascade occurred in the first two steps (contact identification, 43% and tuberculin skin testing placement, 91% of the identified contacts). Among KAP-interviewed contacts, 67% knew how tuberculosis is transmitted, 87% knew its key symptoms and 81% declared they would take preventive therapy if prescribed. Among KAP-interviewed index cases, 67% knew they could spread tuberculosis, 70% feared for the health of their families and 88% would like their family to be evaluated in the same services., Conclusion: Only a small proportion of contacts are evaluated for active and latent tuberculosis, despite their-and their index cases'-reasonable knowledge, positive attitudes towards prevention and satisfaction with tuberculosis services. In these services, education of service users would not be a sufficient solution. Healthcare workers' and managers' perspective, not explored in this study, may bring more light to this subject.

Introduction: The impact on treatment outcomes of XpertMTB/RIF, a molecular-based test that provides rapid diagnosis of tuberculosis (TB) and rifampicin resistance with high accuracy, has not been reported despite its adoption in a few countries. We here report treatment outcomes in a step-wedged cluster randomized trial for patients diagnosed with XpertMTB/RIF compared to patients diagnosed with sputum smear examination in public health facilities in Brazil., Methods: Treatment outcome data were added to the trial database of patients diagnosed from 4 February to 4 October 2012, and crosschecked with data from the national mortality and the drug-resistant TB registers. Treatment outcomes in the intervention (n=2232) and baseline (n=1856) arms were compared using a multilevel regression model., Results: Unfavourable outcomes were frequent in both arms, mainly due to loss to follow-up (16%). Overall unfavourable outcomes were not reduced in the intervention arm (29.6% versus 31.7%, OR=0.93; 95%CI=0.79-1.08). However, the overall TB-attributed death rate was lower in the intervention arm (2.3% vs. 3.8%). Adjusted for HIV status, age group and city, the intervention resulted in a 35% decrease in TB-attributed deaths (OR=0.65, 95%CI=0.44-0.97)., Conclusions: The proportion of patients successfully treated did not increase with Xpert MTB/RIF implementation, with high loss to follow-up rates in both arms. We did observe a 35% reduction in TB-related mortality, which we hypothesize may be explained by less advanced disease among the smear-negative patients diagnosed by Xpert. In conclusion, XpertMTB/RIF introduction did not improve TB treatment outcomes in Brazil., Trial Registration: clinicaltrials.gov NCT01363765.

Background: Abundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints)., Methods and Findings: We conducted a stepped-wedge cluster-randomized trial from 4 February to 4 October 2012 in 14 primary care laboratories in two Brazilian cities. Diagnostic specimens were included for 11,705 baseline (smear microscopy) and 12,522 intervention (Xpert MTB/RIF) patients presumed to have TB. Single-sputum-sample Xpert MTB/RIF replaced two-sputum-sample smear microscopy for routine diagnosis of pulmonary TB. In total, 1,137 (9.7%) tests in the baseline arm and 1,777 (14.2%) in the intervention arm were positive (p<0.001), resulting in an increased bacteriologically confirmed notification rate of 59% (95% CI = 31%, 88%). However, the overall notification rate did not increase (15%, 95% CI =  -6%, 37%), and we observed no change in the notification rate for those without a test result (-3%, 95% CI = -37%, 30%). Median time to treatment decreased from 11.4 d (interquartile range [IQR] = 8.5-14.5) to 8.1 d (IQR = 5.4-9.3) (p = 0.04), although not among confirmed cases (median 7.5 [IQR = 4.9-10.0] versus 7.3 [IQR = 3.4-9.0], p = 0.51). Prevalence of rifampicin resistance detected by Xpert was 3.3% (95% CI = 2.4%, 4.3%) among new patients and 7.4% (95% CI = 4.3%, 11.7%) among retreatment patients, with a 98% (95% CI = 87%, 99%) positive predictive value compared to phenotypic drug susceptibility testing. Missing data in the information systems may have biased our primary endpoints. However, sensitivity analyses assessing the effects of missing data did not affect our results., Conclusions: Replacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment., Trial Registration: ClinicalTrials.gov NCT01363765. Please see later in the article for the Editors' Summary.