| dc.description.abstract |
Despite significant progress through the DOTS strategy in the 1990s and the STOP TB strategy in 2006, tuberculosis (TB) control, especially in sub-Saharan Africa, remains immensely challenging in the face of the HIV epidemic. A key factor sustaining the TB epidemic is our inability to interrupt the on-going transmission cycle of Mycobacterium tuberculosis (Mtb). Even if current control measures are successful, future control is in jeopardy unless we can dramatically reduce the large reservoir of latent infections in high HIV/TB burden settings. In order to attempt to meet the STOP TB Partnership target of TB eliminationi by 2050, a detailed understanding of Mtb transmission dynamics in HIV-prevalent settings is urgently required to effectively and efficiently implement interventions to reduce transmission and disease. The contribution of different non-household sources to Mtb transmission is unknown. Household contacts of a tuberculosis case are at high risk for Mtb infection and disease, yet most Mtb transmission occurs outside the household in endemic areas. In Karonga, Malawi, the setting for this study, the proportion attributable to household contact was < 20% whether estimated from molecular epidemiology, case-control studies, or skin-testing household contacts. The potentially long latent period of infection with Mtb and the inability to distinguish between recent and historic infection complicates studies examining transmission. However, Mtb infection in young children indicates recent transmission and acts as a sentinel of the presence of infectious adult tuberculosis, as well as young children at risk of active disease. Identifying infection in pre-school children may pinpoint areas where control measures are failing. Ascertainment of infection relies on the tuberculin skin test (TST), one of the oldest diagnostic tests still in use, which measures the host immune response to a extract?? of antigens from killed tubercule bacilli. Despite concerns about lack of specificity due to cross-reactivity with non-tuberculous mycobacteria and BCG, in endemic settings most positive indurations (≥10mm) can be attributed to Mtb infection, and using interferon gamma release assays (IGRA) alone provides few advantages. Young children spend more time near their home and close family than do adults, and are less likely to be already infected with Mtb, thus increasing the chance of being able to pinpoint the source of new infections. In this study we aimed to identify locations and sources of recent transmission in a rural HIV-prevalent community using Mtb infection in a cohort of children aged under-5 years. |
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