Tuberculosis (TB) is the single biggest infectious cause of death globally, a situation worsened by COVID-19. Revolutionary new TB triage tests are required, including at facilities where people are accessible and efficiently referable to confirmatory testing. The Cough Audio triaGE for TB (CAGE-TB) study was EDCTP2-funded to 1) collect cough sounds at people’s point-of-entry into primary care facilities (South Africa) and derive an audio classifier, 2) validate diagnostic accuracy in independent cohorts (South Africa, Uganda), and 3) deploy mixed methods research (costing, implementation science, medical anthropology) to inform design and implementation so that this classifier, which will report people as “likely TB” or “unlikely TB” for confirmatory testing, is embedded within a user-friendly mHealth app with on-device offline computation. Per the original call’s objective, CAGE-TB’s goal was to deliver an accurate validated mHealth app usable in trials assessing clinical outcomes (necessary for adoption). Uniquely, this pure mHealth innovation mitigates barriers that jeopardise target product profile criteria (e.g., reagents, cold-chain, transport, infrastructure). After CAGE-TB hired personnel, COVID-19 prevented and slowed recruitment (people had limited clinic access, recruitment interrupted by successive COVID-19 waves). Throughout this, CAGE-TB paid personnel and trainees, resulting in severe budget overruns without participant recruitment, and limited trainee progress and site visits. In 4-CAGE-TB we request essential support over two years to accomplish the original scope-of-work, ensure trainees can finish degrees and, due to the longer recruitment period, accommodate critical additional site visits. COVID-19 has only reinforced our premise: it caused TB to increase for the first time in a decade, damaged already weak facility-based triage practices, and accelerated cough classification technologies.

The COVID-19 pandemic had a devastating impact on tuberculosis (TB) control. In 2020, the number of people newly diagnosed with TB decreased by 18% despite a rising global TB burden. Intensified efforts to improve TB case detection are critically needed, especially in populations in whom bacteriological confirmation is suboptimal, such as children and people living with HIV (PLHIV) who have also been disproportionately affected by the pandemic. The need for highly sensitive sputum-free diagnostic tools for TB has never been greater. STool4TB, an EDCTP-2 funded diagnostic trial, began its activities in 2020 shortly after the onset of the COVID-19 pandemic. The study aims to validate a novel quantitative PCR assay utilizing a stool homogenization and DNA isolation method that yields a highly sensitive and specific detection of Mycobacterium tuberculosis. STool4TB is implemented in high TB & HIV burden settings of Mozambique, Eswatini, and Uganda under the hypothesis that it will contribute to narrow the large TB case detection gap by improving TB lab-confirmation rates in children and PLHIV, while proving feasible and acceptable. New evidence suggests that this platform has a higher sensitivity when compared to sputum culture and Xpert Ultra and could have an additive lab-confirmation yield of up to 20%. STool4TB is also evaluating the qPCR platform as a treatment monitoring tool. This assay has the potential to be adapted to a POC diagnostic test which could be easily implemented in decentralized levels of care. Given the impact of the COVID-19 pandemic on TB notifications at the three participating sites and on several STool4TB core activities, we request additional funding to finalize recruitment of participants and achieve the target sample size, ensuring full execution of all project’s objectives. The observed upward trend in global TB burden makes the development of promising diagnostic tools, such as this novel stool-based qPCR, more important than ever.

BACKGROUND: Gains achieved in reducing the burden of malaria and advancing its elimination are now threatened by the independent emergence and local spread of artemisinin-resistant parasites in East Africa. Protecting the efficacy of the current first-line malaria treatments, all of which are artemisinin-based, is now a top public health priority. OBJECTIVE: The Mitigating Antimalarial Resistance Consortium for South-East Africa (MARC SE-Africa) is designed to promote the translation of evidence of artemisinin and partner drug resistance of public health significance into policy and practice. METHODS: MARC SE-Africa brings together clinical researchers with experience in implementation research, experts in malaria chemotherapy and health policy, national malaria programmes and end users. Together we will improve estimates of antimalarial drug resistance and co-design a costed, Regional Detailed Action Plan to respond promptly to emerging antimalarial drug resistance. Dynamically-updated, evidence-based malaria treatment guidelines and graphic evidence summaries using MAGICapp will be developed, disseminated and evaluated. EXPECTED RESULTS: Predictive maps will better define antimalarial drug resistance for all eighteen South-East African malaria-endemic countries. We will expedite evidence sharing on antimalarial drug resistance with policy makers in at least eight countries. We will help at least four countries respond promptly and effectively to these results. We will facilitate the use of evidence on antimalarial resistance to inform better malaria treatment policies and will evaluate their uptake into clinical practice by primary healthcare workers in at least two countries. This will provide an evidence-based, reproducible model to mitigate the threat of antimalarial drug resistance and ensure sustained effective malaria treatment, including for the vulnerable communities that bear a disproportionately high burden of malaria and its sub-optimal treatment.