PROJECT SUMMARY: ENDx-TB proposal
A central component of WHO’s End TB Strategy is to diagnose approximately 3 million patients annually who
are not diagnosed or treated due to inadequate tests that are not tailored towards specific needs for different
levels or capabilities of health care facilities. Better tests are needed at point-of-care, where triage in low-resource
settings is essential to prioritize those with the highest risk for tuberculosis disease to higher levels of care. On
the other hand, more complex, resource-intensive tests aimed at specific phases of host-pathogen interaction,
like at the end of treatment or during latent infection would complement community-based diagnosis in less-
developed health care systems that have access to central, specialized laboratory facilities. Wide-ranging
diagnostic capacities co-exist in different regions of the same country, for instance in rural vs urban areas and
therefore, a comprehensive battery of diagnostic tests that are appropriate for specific settings are needed.
Meeting the End TB Strategy targets will also require dramatically improved prevention of disease approaches
to block transmission. With 1.7 billion people latently infected, it is not cost-effective to provide prophylaxis to all.
Hence a test that could predict those most at risk of developing disease would enable targeted therapeutic
approaches. Similarly, tests to enable personalized or stratified treatment strategies are urgently needed. The
goal is to conduct a clinical research program across the globe to compare side-by-side the most promising new
tests for a wide range of health care settings in experienced clinical sites in Africa (South Africa, The Gambia),
Southeast Asia (Vietnam) and South America (Peru), and advanced laboratories in the USA and Europe. The
cohorts include adults, children, and people living with HIV and with type 2 diabetes mellitus. The new assays
include: 1) at point-of-care: sputum-free assys, including two triage tests, based on detection of host proteins
and host transcripts, both on fingerstick blood, and a high-sensitivity urinary lipoarabinomannan assay; 2) at
regional laboratories: a modified liquid culture method with TiKa reagent for increased sensitivity and faster
performance, and the cycle threshold value of the Xpert Ultra test as a measure of bacterial load for tuberculosis
treatment monitoring; and 3) at central laboratories: a multiplex qRT-PCR test for mRNA signatures for
progression to tuberculosis, and a host 4-protein biosignature in blood for prediction of poor treatmeht outcome.
The performance of these tests will be evaluated according to internationally established target product profiles
for the respective health care levels. The proposal makes provision for the future inclusion of additional tests in
the pipleline and the inclusion of additional cohorts for specialized diagnostic research questions. Together this
approach will identify the best tests for different health care levels and for different phases of infection and
disease. The multi-disciplinary team of test developers and clinical scientists, and the selection of cohorts are
well suited to identify novel technologies towards meeting the End TB milestones.