A critical component of the 2035 End TB Strategy is development of improved
methods for Active Case Finding (ACF) of previously undiagnosed TB disease. Most
ACF conducted by national tuberculosis control programs is based on testing
household contacts (HCs) of remotely-acquired but newly-diagnosed cases of TB
disease. This approach typically detects previously undiagnosed TB disease in 2-4%
We propose to test an entirely new method of ACF based on testing HCs of
adolescents with recently-acquired and newly-diagnosed TB infection. This innovative
method of ACF has the advantage that, since infections were recently acquired, the
source cases are likely still among the close contacts of the new IGRA convertor. For
this reason, we hypothesize that a source case will be found for as many as 50% of
these new convertors.
This approach is based on results of our recent 3-year study of serial testing for
TB infection among 650 adolescent schoolchildren in Tanzania. The study was based
on annual testing for TB infection using an interferon gamma release assay (IGRA).
We showed that such testing was feasible and detected a 2.9% annual rate of
In the proposed new 5-year study we will perform baseline IGRA testing on
1200 Tanzanian adolescents followed by Q4 month IGRA testing x4 on the estimated
1020 who are IGRA negative at baseline. We anticipate detecting new TB infection
(IGRA conversion to positive) in 50 participants. We will then test 200 of their
household and other close contacts (collectively, their close contacts, CC) and predict
that we will identify a source case of previously undiagnosed TB in a minimum of 25 or
50% of these 50 new adolescent infections. The predicted rate of new TB disease
detection among CCs is therefore 25/200 or 12.5%, which is 3-6 times higher than the
current approach for testing HCs of patients with TB disease. Cost-effectiveness will be
analyzed and compared to the current approach used by the National Program on
Tuberculosis and Leprosy.
Successful completion of the proposed study with the hypothesized outcomes
has the potential for a major impact on global tuberculosis outcomes. It is expected
that the numerous new point-of-care IGRA tests under development will make serial
testing feasible and economical at a programmatic level in low income countries.
The research study will be conducted with the comprehensive DarDar
Research Program, a 20-year research collaboration between Muhimbili University of
Health and Allied Sciences (MUHAS, Tanzania) and the Geisel School of Medicine at
Dartmouth (USA) and will include two consultant epidemiologists with extensive
experience in evaluating TB control programs (Horsburgh, Whalen).