ATLANTA-- The national decline in the incidence of tuberculosis (TB) has motivated the medical community to attempt to completely eradicate the disease from the United States during the next 35 years. An important part of that initiative is the joint statement on latent TB detection and treatment recently released by the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC).[1]

The strategies recommended in the joint statement are vital because they prevent latent TB infections--of which there are millions in the United States--from becoming active. These recommendations are supported by the Institute of Medicine, which recently released a new TB report, Ending Neglect: The Elimination of Tuberculosis in the United States.

The ATS/CDC joint statement contains some important updates--most notably, new recommendations on isoniazid treatment for latent TB. The statement also provides guidelines for the use of alternative regimens. "In the past, all we had was isoniazid," said David L. Cohn, MD, co-chair of the committee that developed the joint statement. "Now we have choices."

A CHANGE IN TERMINOLOGY

In preparing the statement, the joint committee coined some new terms. For example, it replaced "TB screening" with "targeted tuberculin testing." This reflects a renewed focus on latent TB detection only in high-risk groups. "We used to spend a lot of time testing low-risk groups," stated Dr. Cohn, a professor of medicine in the division of infectious diseases at the University of Colorado Health Sciences Center in Denver.

Persons recently infected with Mycobacterium tuberculosis are considered at high risk. Recent M tuberculosis infection is most likely in those who have emigrated within the past several years from countries with high TB rates or who have recently had close contact with an infectious pulmonary TB patient. Recent infection is also presumed when a tuberculin skin test converts from negative to positive within a two-year period.

Patients with conditions that enhance progression of latent TB to active disease (see Table 1) are also considered to be at high risk. So are intravenous drug users, renal and cardiac transplant recipients, gastrectomy and jejunoileal bypass recipients, and those with radiographic findings suggesting prior TB infection.

The definition of a positive tuberculin skin test varies according to patient type. The test must produce a minimum of 5 mm of induration to be positive in those who have had recent contact with a TB-infected individual; have radiographic findings consistent with prior TB; or are immunosuppressed due to human immunodeficiency virus (HIV) infection, organ transplantation, or other causes.

The test must yield at least 10 mm of induration to be considered positive for intravenous drug users; mycobacterial laboratory personnel; gastrectomy and jejunoileal bypass recipients; and residents and employees of homeless shelters, hospitals, and other high-risk settings. At least 10 mm of induration is also required for a positive result among those with conditions that promote latent TB progression; recent immigrants from countries with high TB rates; children under age 4 years; and infants, children, or teens exposed to high-risk adults.

In individuals with no TB risk factors, a tuberculin skin test is considered positive only if it produces induration of 15 mm or greater. "However, we should not be doing tuberculin testing in those at very low risk," stressed Richard J. O'Brien, MD, the other ATS/CDC joint committee co-chair.

NEW TREATMENT RECOMMENDATIONS

Regarding treatment terminology, the joint committee replaced the phrase "preventive therapy" with "treatment of latent TB infection." The latter term is more appropriate, Dr. Cohn told RESPIRATORY REVIEWS, because the joint statement actually addresses early treatment of TB, not prevention.

In another important change, the ATS/CDC joint statement now recommends nine months of isoniazid treatment for latent TB infection in all patients. The previous recommendations were for a treatment duration of six months in HIV-negative patients and 12 months in HIV-positive patients and those with radiographic evidence of prior TB infection.

The joint committee decided on nine months of treatment because a review of data from earlier clinical trials found it to be as effective as 12 months of treatment. Thus, 12 months of isoniazid provides minimal additional benefit, according to Dr. O'Brien, who is also chief of the TB Research and Evaluation Branch at the CDC.

"Six months of isoniazid is still acceptable, though," said Dr. Cohn. While less effective than nine months, this regimen provides a substantial benefit at a lower cost. Health departments and health care providers may therefore give it preference when cost-effectiveness is a concern.

When isoniazid is unavailable or poorly tolerated, physicians may instead prescribe a two-month rifampin/pyrazinamide combination. This regimen is similar in safety and efficacy to 12 months of isoniazid in HIV-positive patients.[2] It is expected to be equally effective, though perhaps less well tolerated, in HIV-negative patients. Rifabutin may replace rifampin in this regimen when the latter drug is not an option--for example, in HIV-positive patients receiving protease inhibitors.

Four months of rifampin is acceptable for patients with latent TB who cannot tolerate isoniazid or pyrazinamide. This recommendation is based on research showing rifampin's effectiveness relative to placebo in HIV-negative patients.

Baseline laboratory tests prior to treatment are not routinely required in older patients, as had previously been thought. Such tests are usually necessary only in patients who regularly use alcohol, are pregnant or in the immediate postpartum period, have or are at risk for chronic liver disease, or have HIV infection.

Patients with latent TB who receive isoniazid or rifampin alone require follow-up at least once a month during treatment. Those taking rifampin and pyrazinamide need follow-up at two, four, and eight weeks of treatment.

Routine laboratory monitoring during treatment is indicated for patients with abnormal baseline liver function tests or other risk factors for hepatic disease. It may also be necessary to evaluate adverse effects, such as hepatotoxicity and joint pain.

--Timothy Begany

References
1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161(suppl):S221-S247.
2. Gordin F, Chaisson RE, Matts JP, et al. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. JAMA. 2000;283:1445-1450.