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TB Notes 2, 2004


National Surveillance for Severe Adverse Events (Hospitalization or Death) Associated with Treatment of Latent Tuberculosis Infection

Between October 2000 and December 2003, DTBE received reports of 49 patients with severe adverse events associated with the use of the 2-month regimen of rifampin and pyrazinamide (RZ) for the treatment of latent tuberculosis infection (LTBI); 12 (24%) of the 49 patients died. In addition, since January 1, 2004, DTBE has received two reports of serious adverse events for patients started on therapy (RZ=1 and isoniazid=1).

A severe adverse event is defined as hospitalization or death of a person receiving treatment for LTBI.1-4 On the basis of these data, the American Thoracic Society and CDC recommended that RZ should generally not be offered for treatment of persons with LTBI, regardless of HIV status.Rifampin and pyrazinamide should continue to be administered in multidrug regimens for the treatment of persons with active TB disease.5

To better estimate the incidence of severe adverse events (hospitalization or death) associated with any treatment for LTBI in the United States, DTBE is developing a national surveillance system. Surveillance of such events will provide data to support further revisions of guidelines, if deemed necessary, for treatment of persons with LTBI. To facilitate this surveillance system, DTBE requests that health care providers and health departments report any hospitalization or death related to any treatment for LTBI to Lilia Manangan in the Surveillance Team; Surveillance, Epidemiology, and Outbreak Investigations Branch; DTBE, CDC; telephone number: 404-639-8401 or email:

—Reported by Lilia Manangan, RN, MPH
Div of TB Elimination

chart displaying Liver Injury Associated with Rifampin and Pyrazinamide by Treatment Start Date. United States, 1999-2003.

*For latent tuberculosis infection (LTBI).

LTBI guidelines: see reference 6 below.


1. CDC. Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection — New York and Georgia, 2000. MMWR 2001;50(15):289-91.

2. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide for  latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations — United States, 2001. MMWR 2001;50(34).

3. CDC. Update: Fatal and severe liver injuries associated with rifampin and pyrazinamide treatment for latent tuberculosis infection. MMWR 2002; 51(44):998-9.

4. American Thoracic Society/CDC. Update: Adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection — United States, 2003. MMWR 2003;52(31):735-9.

5. American Thoracic Society, CDC, Infectious Diseases Society of America. Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-62.

6. American Thoracic Society, CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-S247).


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination -

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