New guidelines on the testing and treatment of persons with latent tuberculosis infection (LTBI) issued this month by the American Thoracic Society and the Centers for Disease Control and Prevention recommend several important changes from previously recommended practices, based on available evidence. The guidelines stress the importance of these activities for the elimination of TB in the United States.
The guidelines, developed by a panel of 47 experts from three continents, endorse targeted testing of at-risk populations, rather than widespread screening. In addition, the statement recommends nine months of daily treatment with isoniazid for adults with LTBI, regardless of whether the patient is coinfected with HIV. This departure from the previously recommended regimens of isoniazid for 12 months for HIV-infected patients and for six months for HIV-negative patients is based on further analyses of earlier clinical trials.
The statement strongly discourages widespread screening or testing of persons at low risk of TB, and recommends targeted tuberculin testing for LTBI to identify individuals at high risk of TB who, if found to be infected, would benefit from treatment of LTBI. According to the statement, persons at highest risk include those with recent TB infection and those with clinical conditions that are associated with an increased risk for progression to active TB. The guidelines provide criteria for tuberculin positivity by risk group and recommends targeted testing for those at risk.
Although isoniazid has been the mainstay of treatment for LTBI for more than 30 years, its application has been limited because of poor adherence and because of concerns about toxicity, according to the statement. Recent clinical trials in HIV-infected persons have evaluated shorter, rifampin-based regimens for LTBI treatment. Based on these studies, the guidelines recommend a two-month regimen of rifampin and pyrazinamide for use in both HIV-positive and HIV-negative adults.
However, the experts state that more data will be needed to determine the acceptability of this regimen and the settings in which it will be most useful. They also note potential drug interaction problems, particularly in HIV patients receiving anti-retroviral therapy.
The guidelines also eliminate routine baseline and follow-up laboratory monitoring, except for patients with HIV infection, pregnant and post-partum women, and patients with a history or risk of liver disease. The experts emphasize the importance of monthly clinical monitoring for signs of adverse drug effects. Children should be screened, usually with a questionnaire, for risk factors for TB infection. Those at risk may be candidates for a tuberculin skin tests, which generally can be interpreted the same as tests on adults except that 10 mm should be considered positive in children younger than 4-years-old. The only recommended regimen for treatment for TB infection in infants, children and adolescents is nine months of isoniazid taken daily (self-supervision) or twice weekly (directly observed therapy). There are no available data to support the use of the other adult regimens in children, according to the statement.
The ATS/CDC statement is endorsed by the Infectious Diseases Society of America, and the American Academy of Pediatrics endorses sections of the statement relating to infants and children. It is published as a supplement to the April issue of the ATS¹s American Journal of Respiratory and Critical Care Medicine, and will be reprinted next month in CDC's Morbidity and Mortality Weekly Report. The April issue of the American Journal of Respiratory and Critical Care Medicine also contains the revised ATS/CDC statement "Diagnostic Standards and Classification of Tuberculosis in Adults and Children."
The ATS/CDC statements will be posted on the ATS Website, http://www.thoracic.org/statementframe.html, and can be ordered by E-mailing Jeremy Dardick at the ATS, jdardick@thoracic.org. The statement will also be posted on the CDC MMWR Website, http://www.cdc.gov/mmwr/, where Continuing Education credits are available. Following the MMWR printing, the document may also be ordered from CDC through the Division of TB Elimination on-line ordering system at http://www.cdc.gov/nchstp/tb/ or from an a touch-tone telephone by calling CDC's Voice and FAX Information System (recording) toll free at 888-232-3228, then pressing options 2, 5, 1, 2.
Contact: ATS/CDC Statement Committee Co-chair David L. Cohn, M.D., Denver Public Health, Denver, Colorado. Phone: 303-436-7204; Fax: 303-436-7194; E-mail: dcohn@dhha.org.
Contact: ATS/CDC Statement Committee Co-chair Richard J. O'Brien, M.D., Division of TB Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia. Phone: 404-639-8123; fax: 404-639-8961; E-mail: rjo1@cdc.gov.
The American Thoracic Society, founded in 1905, is an independently incorporated, international educational and scientific society, which focuses on respiratory and critical care medicine. Today, the Society has approximately 13,500 members, 25 percent of whom are from outside the U.S. The Society's members help prevent and fight respiratory disease around the globe, through research, education, patient care and advocacy. The Society's long-range goal is to decrease morbidity and mortality from respiratory disorders and life-threatening acute illnesses.