Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB. Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided. Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Background: The GeneXpert diagnostic platform from the US based company Cepheid is an automated molecular diagnostic device that performs sample preparation and pathogen detection within a single cartridge-based assay. GeneXpert devices can enable diagnosis at the district level without the need for fully equipped clinical laboratories, are simple to use, and offer rapid results. Due to these characteristics, the platform is now widely used in low- and middle-income countries for diagnosis of diseases such as TB and HIV. Assays for SARS-CoV-2 are also being rolled out. We aimed to quantify public sector investments in the development of the GeneXpert platform and Cepheid’s suite of cartridge-based assays. Methods: Public funding data were collected from the proprietor company’s financial filings, grant databases, review of historical literature concerning key laboratories and researchers, and contacting key public sector entities involved in the technology’s development. The value of research and development (R&D) tax credits was estimated based on financial filings. Results: Total public investments in the development of the GeneXpert technology were estimated to be $252 million, including >$11 million in funding for work in public laboratories leading to the first commercial product, $56 million in grants from the National Institutes of Health, $73 million from other U.S. government departments, $67 million in R&D tax credits, $38 million in funding from non-profit and philanthropic organizations, and $9.6 million in small business ‘springboard’ grants. Conclusion: The public sector has invested over $250 million in the development of both the underlying technologies and the GeneXpert diagnostic platform and assays, and has made additional investments in rolling out the technology in countries with high burdens of TB. The key role played by the public sector in R&D and roll-out stands in contrast to the lack of public sector ability to secure affordable pricing and maintenance agreements.

In this article, we highlight technological pediatric TB research advances across the TB care cascade; discuss recently completed or ongoing work in adults and corresponding significant research gaps for children; and offer recommendations and opportunities to increase investments and accelerate pediatric TB R&D.

Tuberculosis (TB) is an infectious disease closely intertwined with stigma, discrimination, and the social determinants of health. Communities of people affected by TB are experts in their care pathways, but the TB field continues to fall short of meaningfully engaging communities in TB research. This is a missed opportunity to improve the quality, relevance, person-centeredness, positive impact, and sustainability of TB research outputs. We acknowledge the important progress that has been made to date regarding community engagement in TB, but emphasize persisting barriers to meaningful engagement, and the urgent need for updated and comprehensive TB-specific standards for such engagement in research. We highlight that core components of these standards should include the mobilisation of communities affected by TB, bilateral training in community engagement (for researchers and communities), as well as ensuring appropriate remuneration, representation of priority groups, and the use of non-stigmatising language in the engagement process. In addition, to meaningfully incorporate the experiences and expertise of communities affected by TB, their engagement in the research process should occur as early as possible, ideally before research priorities and directions are set, and the scope of the research should encompass questions and outputs relevant to the community. Further, knowledge-sharing between researchers and the community should be ensured, not only of the research outputs but also regarding the engagement process itself, so that lessons learned can be carried forward. Lastly, the sustainability of community engagement processes (whether within institutions or projects) should be ensured, including through adequate funding for such engagement and the training, community mobilisation and relationship-building that this requires.

Affecting both mother and the existing pregnancy, tuberculosis (TB) increases the likelihood of poor birth outcomes. Despite substantial clinical need for TB prevention and treatment, pregnant women remain neglected by research initiatives. As members of 3 community advisory boards that provide input into TB drug trials, we offer a community perspective on the inclusion of pregnant women in TB drug research and discuss (1) our perspective on the risk/benefit tradeoff of including pregnant women in research to address different forms of TB; (2) recent examples of progress in this area; (3) lessons learned from the human immunodeficiency virus research field, where pregnant women have enjoyed better—although imperfect—representation in research; and (4) recommendations for different stakeholders, including researchers, regulatory authorities, ethics committees, and policymakers.