Diagnostics

Diagnosis is the entry point to TB care, yet the largest gap in the tuberculosis care cascade is in identifying individuals with TB disease. Some 4 million TB cases per year go undiagnosed, and thus untreated—leaving people with TB sick and at risk of death and allowing more opportunity for the disease to spread. Challenges with current diagnostic tests contribute to this gap. The best currently available molecular tests are not suitable for many settings where people seek care, and rely on sputum, which is challenging for children and people living with HIV to produce.

SMART4TB is focused on bringing accurate TB tests to the points where people seek care, through two main activities: technology scouting to identify promising technologies for co-development and clinical evaluation, and a trial platform to assess the accuracy of diagnostics ready for evaluation.

Adithya Cattamanchi
University of California, Irvine

 

Yuka Manabe
Johns Hopkins University

Claudia Denkinger
Heidelberg University

Maunank Shah
Johns Hopkins University

Kristin Kremer
KNCV Tuberculosis Foundation

Devan Jaganath
University of California, San Francisco

Nilesh Bhatt
Elizabeth Glaser Pediatric AIDS Foundation

Activities

    • Tech scouting: The goal of this activity is to identify and review novel promising point-of-care TB diagnostics for development support. SMART4TB launched the first stage of partner selection in 2023, leading to the announcement of five awardees in 2024. These partners have been granted funding and technical assistance to advance the development of oral swab-based TB assays compatible with their existing POC molecular platforms. Tests that meet the benchmarking and feasibility criteria at the end of this stage may be eligible for future funding and assistance to support iterative development towards clinical evaluation and eventual design lock.

      In parallel, we are actively seeking new partners through technical scouting for in-kind support through the large-scale, multi-center clinical evaluation of the accuracy of design-locked TB diagnostics in the ADAPT and ADAPT for Kids trials.

    • Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT): Promising existing technologies and those developed via SMART4TB’s tech scouting process need clinical evaluation to assess their suitability for diagnosing TB in the field. The Assessing Diagnostics At Point-of-care for Tuberculosis (ADAPT) trial serves as a platform to evaluate the diagnostic accuracy, yield, and acceptability of novel point-of-care TB diagnostics through a standardized protocol for TB diagnostic accuracy. ADAPT will first rigorously evaluate the performance of using tongue swab samples on Xpert MTB/RIF Ultra, a rapid molecular test endorsed by WHO for detecting TB via sputum, and Truenat MTB Ultima, to determine whether they are an effective alternative method for diagnosing TB. Read more about the ADAPT trial in our press release, study overview, and on ClinicalTrials.gov.

    • ADAPT for Kids: Ensuring the inclusion of children, often neglected in diagnostics research and especially in need of non-sputum based tests given the difficulty for children of producing sputum, SMART4TB is also evaluating a novel, oral swab point-of-care TB tests in children with presumptive TB. The study began enrollment in Mozambique in late 2023, with plans for a second site in Uganda in 2024. Read more in our press release, study overview, and on Clinicaltrials.gov

Partners & Collaboration

SMART4TB’s leverages partnerships with the U.S. National Institute of Allergy and Infectious Diseases-funded Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network), Feasibility of Novel Diagnostics for TB (FEND-TB), and the Unitaid-funded DriveDx4TB project.

For the ADAPT trial, SMART4TB is partnering with the Zankli Research Centre at Bingham University in Nigeria, De La Salle Medical and Health Sciences Institute in the Philippines and Centre for Infectious Disease Research in Zambia.

For the ADAPT for Kids trial, SMART4TB is partnering with Instituto Nacional de Saúde in Mozambique and Mulago National Referral Hospital in Uganda.

Diagnostic tech partners include Boditech Med, Co-Diagnostics, Molbio Diagnostics, Nuclein and Sherlock Biosciences.

Input from USAID, USAID country missions, the SMART4TB Regional Collaboratives, and our investigator network is also essential to optimizing SMART4TB’s diagnostic research.