Needed: New and Better Tools to Combat Latent Tuberculosis Infection

Treatment of latent tuberculosis infection (LTBI) is a major strategy for tuberculosis control in the United States, Canada, and selected resource-intensive countries (1, 2). Given the decline in tuberculosis cases in the United States since 1992, interest in treating patients with LTBI is renewed in order to eliminate the large reservoir of individuals at risk for progression to tuberculosis (1, 3). The Centers for Disease Control and Prevention, such professional organizations as the American Thoracic Society and the Infectious Diseases Society of America, and others (1–3) recommend targeted testing of persons at increased risk for tuberculosis and provision of therapy for LTBI after active tuberculosis disease has been excluded. Persons at greatest risk for progression to active tuberculosis disease after infection with Mycobacterium tuberculosis include those with HIV infection (the greatest single risk factor for progression) or recent tuberculosis infection, immigrants with LTBI from high endemic areas (especially within their first year in the United States), and those with LTBI and selected underlying illnesses (for example, silicosis, diabetes mellitus, chronic renal failure, some malignant conditions, and immunosuppressive medications) (1, 3).

A major limitation to this strategy is poor acceptance and adherence to treatment regimens for LTBI (typically <50%) (4). Poor adherence is not surprising because treatment is arduous (9 months of isoniazid therapy is the preferred regimen [1]) and patients have no symptoms of infection. There was initial excitement about a 2-month, short-course regimen of rifampin and pyrazinamide for the treatment of LTBI, which was as efficacious as isoniazid in a narrowly defined HIV-infected study sample and had better adherence (5). However, when applied to the general population of patients with LTBI, rifampin–pyrazinamide led to an unacceptably high rate of severe hepatotoxicity and death (the estimated mortality rate was 1 in 1000 uses), and …