CDC Issues Recommendations on Use of New Treatment Option for Latent TB Infection

New regimen will make treatment simpler and easier

Health care providers in the United States have a new way to treat latent tuberculosis infection, according to recommendations released today by the Centers for Disease Control and Prevention. The new recommendations, published today in CDC’s Morbidity and Mortality Weekly Report, provide guidance on how to administer a new 12-dose regimen for TB preventive therapy that will significantly shorten and simplify the course of treatment from about nine months to 12 weeks. The recommendations are based on the results of three clinical trials, as well as expert opinion.

The recommendations follow results from the largest of those clinical trials, first announced in May 2011 and published this week in the New England Journal of Medicine. That multi-national clinical trial conducted by CDC’s TB Trials Consortium found that a once-weekly regimen of the anti-TB drugs rifapentine and isoniazid taken as directly observed therapy over a period of three months was as effective in preventing TB disease as the standard self-administered nine-month daily regimen of isoniazid alone, and was completed by more patients. The new regimen has a significant benefit over the previous standard of treatment by cutting the doses required from 270 daily doses to 12 once-weekly doses.

“This regimen has the potential to be a game-changer in the United States when it comes to fighting TB,” said CDC Director Thomas R. Frieden, M.D., M.P.H. “It gives us a new, effective option that will reduce by two-thirds – from nine months to three months — the length of time someone needs to take medicine to prevent latent TB infection from progressing to active TB disease.”

Latent TB infection occurs when a person has TB bacteria but does not have symptoms and cannot transmit the bacteria to others. If the bacteria become active, the person will develop TB disease, become sick, and may spread the disease to others. Although not everyone with latent TB infection will develop TB disease, some people, such as those with weakened immune systems, are at higher risk of progression to TB disease. Many of those at high risk of developing TB disease never even begin the cumbersome nine-month course of standard treatment, and among those who do, many do not complete it.

In the United States, the number of persons with TB disease is at an all-time low (11,182 total cases were reported in 2010); however, approximately 4 percent of the U.S. population, or 11 million people, are infected with the TB bacterium. TB continues to disproportionately affect people of color and foreign-born persons in this country.

“If we are going to achieve our goal of TB elimination in the United States, we must ensure that those with latent TB infection receive appropriate evaluation and treatment to prevent their infection from progressing to TB disease and possibly spreading to others,” said Kevin Fenton, M.D., director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. “It is critical that we accelerate progress against TB in the United States in order to avoid a resurgence of the disease.”

Highlights of the recommendations

The new 12-dose regimen adds another effective treatment option to the prevention toolkit for TB, and is not meant to replace other preventative treatment regimens for all patients where the new regimen is not the best option. Major components of the recommendations for this regimen include:

• Provision of 12 once-weekly doses via directly observed therapy:The new regimen consists of 12 once-weekly doses of rifapentine and isoniazid. Doses should be taken under the supervision of a health care worker to ensure completion of doses and to allow for monitoring of safety among patients. Clinicians should rule out TB disease among all patients before beginning the two-drug regimen.
• Regimen is recommended for otherwise healthy people aged 12 and older who are at high risk for developing TB disease: This includes anyone who has had recent exposure to contagious TB, conversion from negative to positive on a test for TB infection, or a chest X-ray indicating prior TB disease. Persons living with HIV who are otherwise healthy and not taking anti-HIV medications (antiretrovirals) may also use this regimen if TB preventive treatment is indicated.Public health officials may also consider use of this regimen among populations that are unlikely to complete nine months of daily therapy (e.g., in correctional settings, clinics for recent immigrants, homeless shelters). Use should be considered on a case-by-case basis among children between the ages of 2 and 11, and patients with underlying conditions associated with TB.
• Regimen is not recommended for certain groups: Because the safety of the regimen for some patients is unknown, it is not recommended for use among children under the age of 2, women who are pregnant or planning to become pregnant, and HIV-infected persons taking antiretrovirals. Patients whose TB infection is presumed to be the result of exposure to a person with TB disease that is resistant to one of the two drugs should not receive this regimen.
• Monitoring for adverse events is critical: Health care workers supervising patients who are taking the drugs should educate patients and monitor for possible adverse effects, and report any problems to a clinician. Patients should undergo a clinical assessment at least monthly.

CDC is increasing awareness of the new treatment option among clinicians and public health professionals. Efforts under way by CDC’s Division of Tuberculosis Elimination include developing educational materials on the proper use of the new treatment regimen, outreach to multiple networks of clinicians and physicians, and collaborating with the four CDC-funded Regional Training and Medical Consultation Centers to further educate TB programs about the guidelines.

CDC is also assessing whether self-administered use of the 12-dose regimen is feasible and will result in similar levels of adherence. Additionally, CDC is working with the American Thoracic Society and the Infectious Diseases Society of America to update full public health guidelines for finding and treating latent TB infection.

CDC officials note that these recommendations are only for the United States. Countries with a high incidence of TB, especially those with high HIV prevalence and where the risk of TB re-infection is greater, will likely require additional studies before considering whether to recommend this regimen.

For more information, please visit www.cdc.gov/tb.

CDC works 24/7 saving lives, protecting people from health threats, and saving money through prevention. Whether these threats are global or domestic, chronic or acute, curable or preventable, natural disaster or deliberate attack, CDC is the nation’s health protection agency.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES