Serial IGRA testing of Tanzanian adolescents to detect TB in household contacts

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PROJECT SUMMARY Tanzania has one of the highest burdens of tuberculosis (TB) in the world. Achieving global TB elimination under the 2035 End TB Strategy will require an expanded focus on active TB case finding. A key component of the current case finding strategy is testing household contacts (HCs) of new cases of remotely-acquired but recently diagnosed TB disease (index case) to find HCs who may also have TB disease. Only 2-4% of households are typically found to have a previously undetected case of TB disease. This is because TB disease typically requires 2-5 years to develop after exposure and infection, suggesting that if transmission occurred in the household the source HC may have already been treated, recovered or died from TB. We hypothesize that testing HCs of recently acquired (incident) cases of TB infection is likely to result in detection of a significantly higher proportion of HCs who were the source of the adolescent infection and still have undiagnosed active TB disease. In a recently completed 3-year prospective study in Tanzania we developed methods for school-based serial testing of adolescents to detect newly acquired TB infection. The trial used the T spot interferon gamma assay (IGRA) assay to detect new infection, and determined that the annual rate of new infection was 2.9%. In the proposed 2-year study we will screen 800 adolescent schoolchildren and follow the estimated 680 IGRA- negative participants for 1.5 years to detect >25 new incident TB infections. We hypothesize that the proportion of their 25 households (and their 100 HCs) with a previously undetected case of TB will be as high as 14%, and will therefore identify a new and more robust global strategy for active case finding. Control households will include those of 25 adolescents with prevalent TB infection (100 HCs) and households of 25 adolescents with no TB infection (100 HCs). The trial will be conducted under 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). This innovative study has the potential to identify a game-changing strategy for more effective active TB case finding.