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In this randomized, controlled trial involving children with household exposure to multidrug-resistant tuberculosis, levofloxacin led to a lower incidence of tuberculosis than placebo, but the difference was not significant.

Presents key activities, promising practices, and lessons learned to date from the World Bank's Tuberculosis (TB) in the Mining Sector Initiative, an innovative multisectoral, multicountry, public-private regional initiative. It examines how a collaborative platform was established to cover 10 southern African countries, and it details the processes through which multiple countries, ministries, sectors, and partners have been brought together to address the varied dimensions of the epidemic. The case studies in this book highlight the significant progress and achievements made since 2010 in the effort to develop a regional platform for addressing TB in the mining sector in southern Africa. The primary focus of the case studies is how these cooperative regional processes-- at both technical and political levels-- have been designed, implemented, managed, and sustained through various partnerships to complement country-level efforts. The case studies provide an evidence base for practitioners working in TB management in the mining sector. Despite the achievements that have been made and their potential to strengthen TB interventions, critical gaps remain in addressing barriers to access, delivery of quality services, and increased uptake of TB services. The case studies explore these key challenges and gaps, and they offer strategies for replicating successes and addressing complex health-service delivery interventions in other regions around the world. Further action is needed, including better compliance with occupational health and safety standards by mining companies; strengthened community health systems and improved coordination of TB care; increased empowerment and participation of women in the mining sector; and improved tracking and tracing of ex-mineworkers across borders. The aim of the book is to provide helpful models, lessons learned, and recommendations that can be used as a starting point for analyzing the risks, opportunities, incentives, and contexts of regional health cooperation that involves multiple sectors and stakeholders.

Epidemiological and interventional studies have been rarely conducted among those with positive interferon-γ release assay (IGRA) results and radiologically inactive tuberculosis (TB) lesions on chest radiograph. This study aimed to estimate the effectiveness and safety of a six-week twice-weekly regimen (rifapentine plus isoniazid) among this key population in rural China. First, chest digital radiography was conducted to screen individuals with inactive TB lesions. Then, the identified participants were further evaluated and eligible participants with IGRA-positive results were included in subsequent randomized controlled trial (RCT). Of 44,500 recruited residents, 2,988 presented with radiographically inactive TB among 43,670 with complete results of chest radiography and questionnaire, and 28.61% (855/2,988) tested IGRA positive. Subsequently, 677 eligible participants were included in this RCT (345 in the preventive treatment group and 332 in the untreated control group). The treatment completion rate was 80.00% (276/345), and 11.88% (41/345) participants reported side-effects including two cases of hepatotoxicity (0.58%, 2/345). In the intention-to-treat analysis, the cumulative incidence rate of microbiologically confirmed active TB during a two-year follow-up was 1.16 (95% confidence interval [CI]: 0.03-2.29) in the preventive treatment group and 1.51 (95% CI: 0.20-2.82) in the control group (p = .485). Subgroup analyses showed that the protective rates were 55.42% (95% CI: 10.33-93.07%) and 80.17% (95% CI: 25.36-97.96%) for participants with fibrosis and for those aged ≥60 years, respectively. The expected treatment effect was not observed for the six-week regimen in this study. Future studies with sufficient sample size are needed to verify our findings.

More than 36 million patients have been successfully treated via the World Health Organization's strategy for tuberculosis (TB) control since 1995. Despite predictions of a decline in global incidence, the number of new cases continues to grow, approaching 10 million in 2010. Here we review the changing relationship between the causative agent, Mycobacterium tuberculosis, and its human host and examine a range of factors that could explain the persistence of TB. Although there are ways to reduce susceptibility to infection and disease, and a high-efficacy vaccine would boost TB prevention, early diagnosis and drug treatment to interrupt transmission remain the top priorities for control. Whatever the technology used, success depends critically on the social, institutional, and epidemiological context in which it is applied.

Background. Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. Methods. We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. Results. We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18–.37), or infants (RR, 0.41; 95% CI, .29–.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35–1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59–1.31 and RR, 0.81; 95% CI, .55–1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01–.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03–.25). Conclusions. Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid–based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multi-drug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required.

Abstract Rationale Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested. Objectives We sought to quantify the efficacy of surgical face masks when worn by patients with multidrug-resistant TB (MDR-TB). Methods Over 3 months, 17 patients with pulmonary MDR-TB occupied an MDR-TB ward in South Africa and wore face masks on alternate days. Ward air was exhausted to two identical chambers, each housing 90 pathogen-free guinea pigs that breathed ward air either when patients wore surgical face masks (intervention group) or when patients did not wear masks (control group). Efficacy was based on differences in guinea pig infections in each chamber. Measurements and Main Results Sixty-nine of 90 control guinea pigs (76.6%; 95% confidence interval [CI], 68–85%) became infected, compared with 36 of 90 intervention guinea pigs (40%; 95% CI, 31–51%), representing a 56% (95% CI, 33–70.5%) decreased risk of TB transmission when patients used masks. Conclusions Surgical face masks on patients with MDR-TB significantly reduced transmission and offer an adjunct measure for reducing TB transmission from infectious patients.

In this phase 2 study, investigators evaluated the potential of two vaccines (H4:IC31 and BCG) to prevent the acquisition of tuberculosis infection and the subsequent development of sustained disease.

AbstractObjectiveTo evaluate the safety and efficacy of VPM1002 and Immuvac in reducing the incidence of microbiologically confirmed tuberculosis (TB; pulmonary TB and extrapulmonary TB), development of latent TB infection, and immunogenicity.DesignPhase 3 randomised clinical trial (PreVenTB trial).Setting18 sites across six states of India.Participants12 717 healthy household contacts (aged ≥6 years) of patients with a smear positive TB test.InterventionsParticipants were randomly assigned in a 1:1:1 ratio (using block randomisation with variable sample size) to receive an intradermal injection of VPM1002, Immuvac, or placebo in both arms. After one month, a second dose was administered in one arm to 11 829 healthy participants.Outcome measuresThe primary outcome was efficacy against confirmed TB (pulmonary TB and extrapulmonary TB) over 38 months of follow-up. Secondary outcomes were development of latent TB infection, adverse and serious adverse events, efficacy in predefined age groups, and immunogenicity. Exploratory outcomes were efficacy when considering tuberculin skin test status, and post hoc analyses of efficacy in participants aged 6-14 and according to body mass index.Results252 and 227 participants developed microbiologically confirmed TB in modified intention-to-treat and per protocol groups, respectively. The per protocol analysis showed 65 (1.68%), 80 (2.09%), and 82 (2.13%) participants developed TB in the VPM1002, Immuvac, and placebo groups, respectively. Of these, 12 (0.31%), 16 (0.42%), and 24 (0.62%) developed extrapulmonary TB in the VPM1002, Immuvac, and placebo groups, respectively. In the per protocol analysis, VPM1002 showed vaccine efficacy of 21.4% (95% confidence interval (CI) −8.9% to 43.2%), 19.5% (−14.6% to 43.4%), and 50.4% (0.8% to 75.2%) against all TB, pulmonary TB, and extrapulmonary TB, respectively. Immuvac showed vaccine efficacy of 33.2% (−25.9% to 64.5%) against extrapulmonary TB. VPM1002 and Immuvac showed vaccine efficacy of 64.9% (−2% to 90.1%) and 66.3% (1.9% to 90.5%) against extrapulmonary TB in participants with tuberculin skin test positivity. Both vaccines were well tolerated with mild local reactions in about a third of participants. VPM1002 and Immuvac induced Mycobacterium tuberculosis specific polyfunctional CD4+ T cells. Post hoc analyses showed vaccine efficacy of 64.6% (95% CI 16.3% to 85.1%) against all forms of TB, 62.1% (3.0% to 85.2%) against pulmonary TB, and 77.6% (−3.7% to 95.2%) against extrapulmonary TB in participants aged 6-14 years in the VPM1002 group.ConclusionsBoth vaccines were safe but did not show any efficacy against all forms of microbiologically confirmed TB or pulmonary TB. VPM1002 showed considerable efficacy against extrapulmonary TB. Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test.Trial registrationClinical Trials Registry India CTRI/2019/01/017026.