Diagnosis of pediatric tuberculosis (TB) in resource-limited settings with high rates of HIV and TB is severely limited by methods that are slow, inefficient, and costly, which leads to increased morbidity and mortality. Our research team has made significant progress in the development of new TB diagnostic tools that demonstrate significant advantages over the gold standard diagnostics in adults. We propose to evaluate the potential of these new tools as well as others for the detection and direct susceptibility testing of Mycobacterium tuberculosis (Mtb) in children from 0-5 years of age. This project will be set in Ethiopia, where pediatric TB and HIV co- infection are major problems. We hypothesize that, compared to current standard techniques, the diagnosis of active TB in children and the recovery of Mtb isolates from these children can be done more quickly, efficiently, and cost-effectively using alternative clinical specimens in combination with more rapid diagnostic methods for both confirmation of TB and detection of drug resistance. If our hypothesis is correct, use of these methods will allow clinicians to institute rapid treatment directed specifically against the bacterial isolate from the infected child, improving the speed and outcome of anti-tuberculous therapy. To evaluate the potential utility of these techniques, we propose two studies. In the first study, we will evaluate the testing of various clinical specimens using innovative, inexpensive tests that may greatly facilitate the diagnosis of pediatric TB in developing countries with high rates of TB and HIV co-infection. The second study will include children with confirmed TB (identified in the first study) and healthy age-matched children. We will evaluate three immunologically-based techniques for their sensitivity and specificity in the diagnosis of TB disease. We believe the results in known TB cases can be extrapolated to assess the potential utility of these tests in the diagnosis of the large population of children with TB who are not able to have disease microbiologically confirmed.

Diagnosis of pediatric tuberculosis (TB), particularly among young children and those who are infected with HIV is severely limited by methods that are slow, inefficient, and costly. Our research team has developed new TB diagnostic tools and ways of collecting specimens and we are proposing to evaluate them in young children in Ethiopia where pediatric TB and HIV co infection are major problems. If these methods work well, they could allow clinicians to institute rapid treatment directed specifically against the child''s particular infection, improving the speed and outcome of TB therapy.