Grant: Operating Grant

Tuberculosis (TB) infects about a third of the world's population and is the most important infectious cause of death in adults' worldwide. A cornerstone of TB control is treating TB while it is still dormant or latent, before it causes illness. The current standard treatment of latent TB is isoniazid for 9 months (9INH). This lengthy treatment is burdensome, and can sometimes cause serious side effects, so is often not taken. A potential alternative is 4 months of rifampin (4RIF), which is more rapidly effective than isoniazid - allowing the shorter duration of treatment. A blood test that tested whether treatment of latent TB infection was effective could make it much easier to study new drugs or combinations of drugs to prevent TB, and to indicate when an individual could stop latent TB treatment. The blood tests that are most promising are measures of the immune response to TB. We have begun a randomized trial to compare 9INH with 4RIF for the treatment of latent TB infection in almost 6,000 adults. We propose to measure results of immune response tests before, and at the end of 4RIF and 9INH. We will determine whether reduction in these immune responses is greater in persons who complete the standard treatment (9INH), or complete 4RIF, and if changes occur more rapidly with 4RIF. These results in turn will be compared to the effectiveness of the two drugs for preventing TB. Finally the most promising results will be re-tested in stored samples of blood that were gathered in an independent study of INH treatment of LTBI. This will act to confirm (validate) our results. This proposal is a unique, cost effective opportunity to compare the effect of each of these two drugs on the immune responses to TB. If these results can be correlated with the effectiveness of treatment, it could be used as a measure of treatment effectiveness for future clinical studies, allow them to be conducted more quickly, with fewer patients, and much lower costs.