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Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

Background: Adolescents are a prime target group for tuberculosis (TB) vaccine trials that include prevention of infection (POI). The BCG vaccine is given at birth and does not prevent TB infection. TB infection, a critical endpoint for POI vaccine trials would need to be documented to estimate sample sizes in target populations., Methods: Adolescents aged 12-18 years of age were enrolled in an area under continuous demographic surveillance. A tuberculin skin test (TST) survey was conducted as part of a study on TB prevalence and incidence. All adolescents got TSTs at enrolment and returned after 72 h for reading. A TST of ≥10 mm if HIV negative or ≥ 5 mm if HIV positive, was considered positive., Results: Of 4808 adolescents returning for TST readings (96% of those enrolled), mean age was 14.4 (SD 1.9), 4518(94%) were enrolled in school and 21(0.4%) gave a previous history of tuberculosis. Among adolescents with TST reactivity, the mean TST induration was 13.2 mm (SD 5.4). The overall prevalence of latent TB infection was 1544/4808 (32.1, 95% CI 29.2-35.1) with a corresponding annual risk of TB infection (ARTI) of 2.6% (95% CI 2.2-3.1). Risk factors for a positive TST included being male (OR 1.3, 95% CI 1.2,1.5), history of having a household TB contact (OR 1.5, 95% CI 1.2,1.8), having a BCG scar (OR 1.5,95% CI 1.2,1.8), living in a rural area (OR 1.4, 95% CI 1.1,1.9), and being out of school (OR 1.8, 95% CI 1.4,2.3)., Conclusion: We conclude that the high TB transmission rates we found in this study, suggest that adolescents in this region may be an appropriate target group for TB vaccine trials including TB vaccine trials aiming to prevent infection.

Background: Stigma is associated with health conditions that drive disease burden in low- and middle-income countries (LMICs), including HIV, tuberculosis, mental health problems, epilepsy, and substance use disorders. However, the literature discussing the relationship between stigma and health outcomes is largely fragmented within disease-specific siloes, thus limiting the identification of common moderators or mechanisms through which stigma potentiates adverse health outcomes as well as the development of broadly relevant stigma mitigation interventions., Methods: We conducted a scoping review to provide a critical overview of the breadth of research on stigma for each of the five aforementioned conditions in LMICs, including their methodological strengths and limitations., Results: Across the range of diseases and disorders studied, stigma is associated with poor health outcomes, including help- and treatment-seeking behaviors. Common methodological limitations include a lack of prospective studies, non-representative samples resulting in limited generalizability, and a dearth of data on mediators and moderators of the relationship between stigma and health outcomes., Conclusions: Implementing effective stigma mitigation interventions at scale necessitates transdisciplinary longitudinal studies that examine how stigma potentiates the risk for adverse outcomes for high-burden health conditions in community-based samples in LMICs.

Background: Engagement of communities and civil society organizations is a critical part of the Post-2015 End TB Strategy. Since 2007, many models of community referral have been implemented to boost TB case detection in Nigeria. Yet clear insights into the comparative TB yield from particular approaches have been limited., Methods: We compared four models of active case finding in three Nigerian states. Data on presumptive TB case referral by community workers (CWs), TB diagnoses among referred clients, active case finding model characteristics, and CWs compensation details for 2012 were obtained from implementers and CWs via interviews and log book review. Self-reported performance data were triangulated against routine surveillance data to assess concordance. Analysis focused on assessing the predictors of presumptive TB referral., Results: CWs referred 4-22% of presumptive TB clients tested, and 4-24% of the total TB cases detected. The annual median referral per CW ranged widely among the models from 1 to 48 clients, with an overall average of 13.4 referrals per CW. The highest median referrals (48 per CW/yr) and mean TB diagnoses (7.1/yr) per CW (H =70.850, p < 0.001) was obtained by the model with training supervision, and $80/quarterly payments (Comprehensive Quotas-Oriented model). The model with irregularly supervised, trained, and compensated CWs contributed the least to TB case detection with a median of 13 referrals per CW/yr and mean of 0.53 TB diagnoses per CW/yr. Hours spent weekly on presumptive TB referral made the strongest unique contribution (Beta = 0.514, p < 0.001) to explaining presumptive TB referral after controlling for other variables., Conclusion: All community based TB case-finding projects studied referred a relative low number of symptomatic individuals. The study shows that incentivized referral, appropriate selection of CWs, supportive supervision, leveraged treatment support roles, and a responsive TB program to receive clients for testing were the key drivers of community TB case finding.