Latent tuberculosis: revised treatment guidelines.

ing to 1999 estimates, 1.86 billion people — one third of the world’s population — are infected with tuberculosis. Most people with primary tuberculosis (TB) do not have signs or symptoms and may not know that they are infected. Their immune systems contain the tubercle bacilli in oxygen-deprived small granulomas, where the bacilli lie dormant for years. Following primary infection, the lifetime cumulative risk for active TB is estimated to be 10%. Certain factors increase the risk of reactivation because of diminished local or systemic immunity; these include HIV infection, transplantation, silicosis, chronic renal failure, cancer, recent TB infection (within 2 years), diabetes mellitus, malnutrition and low age (less than 5 years) when first infected. Identifying and treating latent TB is a key component of global efforts to eliminate TB. A number of therapeutic regimens using courses and combinations of isoniazid (INH), rifampin or pyrazinamide have been presented in the literature. Recently, the American Thoracic Society and the US Centers for Disease Control and Prevention issued revised treatment recommendations for latent TB and indicated that the 2-month regimen of rifampin plus pyrazinamide should generally not be offered because of high rates of severe liver injury. The preferred regimen is INH for 9 months; alternatives are INH for 6 months or rifampin for 4 months. These revised treatment guidelines are based on data collected from cohorts of patients with latent TB in the United States who received pyrazinamide during January 2000–June 2002. The rates of severe liver injury and death were significantly higher among patients given pyrazinamide than among those given INH. These findings echo the results from an earlier randomized controlled trial, in which the incidence of liver injury was higher among people receiving short-course rifampin and pyrazinamide therapy for latent TB than among those receiving INH of standard duration (odds ratio 8.5, 95% confidence interval 1.9–76.5). The recommendation against the use of pyrazinamide for the treatment of latent TB does not apply to the appropriate use of rifampin and pyrazinamide in multidrug regimens for the treatment of active TB. The loss of the 2-month regimen of combined rifampin plus pyrazinamide leaves us with longer-duration treatment regimens for latent TB, which are associated with high rates of noncompliance and may be ineffective in the face of increasing resistance to INH worldwide.