IN THIS ISSUE:

• Once weekly treatment with rifapentine
• QuantiFERON update

 ONCE WEEKLY TREATMENT WITH RIFAPENTINE

New data released by the Tuberculosis Trials Consortium (TBTC) confirms that a once-weekly TB regimen, initiated after the first eight weeks of therapy, is a viable option for selected patients being treated for active TB disease. TBTC is a network of 23 clinical research facilities, which included Maricopa County Public Health Department.

In this TBTC study, published in the August 17^th edition of The Lancet, we evaluated a regimen of once-weekly isoniazid and rifapentine given during the continuation phase of therapy, as an alternative to the standard twice-weekly regimen of isoniazid and rifampin in a group of HIV-negative TB patients. We found the once-weekly regimen to be safe and effective for HIV-negative patients without signs of advanced tuberculosis (i.e. those with no lung cavities identifiable on chest x-ray). Rifapentine is the first new TB-specific drug approved by the Food and Drug Administration in 30 years.

More than 1,000 HIV-negative patients with active TB disease were randomly assigned to one of two groups. All completed eight weeks of intensive TB therapy with the four frontline TB drugs – isoniazid, rifampin, pyrazinamide and ethambutol. In the 16-week continuation phase, one group received isoniazid and rifapentine once a week; the other group received the standard therapy of twice-weekly isoniazid and rifampin.

Both groups of patients were then followed for two years. Nine percent (46 patients) of those who took the once-a-week regimen either relapsed or experienced treatment failure. Six percent (28 patients) who took the twice-weekly regimen relapsed or had a treatment failure. However, among those without lung cavities, the relapse rates were comparable (about three percent in both treatment arms).

Since the once-weekly isoniazid and rifapentine regimen is administered less frequently than the standard regimen, adherence may be improved, helping to cure more HIV-negative TB patients and prevent further TB transmission. The once-weekly regimen is not recommended for HIV-infected TB patients or HIV-negative patients with cavitary disease.

We also noted that higher relapse rates were seen in patients who remained culture-positive at two months of treatment in both treatment groups. This finding has lead to a new recommendation that treatment with standard therapy should be extended to 9 months total in patients with positive sputum cultures at two months. This and other revised treatment recommendations will be released jointly by the Centers for Disease Control and the American Thoracic Society in January 2003. Watch for a special edition of this newsletter when those guidelines are released.

(adapted from a press release from the Centers for Disease Control)

QuantiFERON-TB UPDATE

As previously reported (ADHS TB newsletter #1, March 2002. Posted on our website www.azdhs.gov/phs/oids/tuberculosis/index.htm), QuantiFERON-TB (QFT) is a new whole blood assay for latent TB infection which was approved by the FDA in November 2001. The Centers for Disease Control has just released its guidelines for use of this test. For those on our email list, I am attaching the full text as a .pdf file. It is also available on the MMWR website at http://www.cdc.gov/mmwr/. Here are the highlights:

• Patient lab results will be reported as one of four categories (based on complex calculations given in the full test):
• "Positive" means that M. tuberculosis infection is likely
• "Conditionally positive" means that M. tuberculosis infection is likely IF the patient has a defined risk factor for tuberculosis; otherwise interpreted as negative
• "Negative" means that M. tuberculosis infection is unlikely
• "Indeterminate" means that the patient specimen did not show an immunologic reaction to the positive control. (This may be due to impaired immune response in the patient, mishandling of the specimen en route to the lab, or other factors.)
• As with the TB skin test (TST), testing of low risk persons is discouraged. If a positive QFT result is obtained on a low risk person, confirmation with a TST is recommended prior to initiation of treatment of latent TB infection. Chest x-ray should be done to rule out active disease regardless of TST results.
• If positive QFT results are obtained on a person with risk factors for tuberculosis, confirmation with TST is optional. Again, chest x-ray should be done to rule out active disease.
• QFT may be used for routine periodic screening such as hospital or correctional employees
• QFT is not recommended for evaluation of persons suspected of having active TB
• QFT is not recommended for TB contact investigation (not yet anyway—clinical trials are ongoing)
• QFT is not recommended for children < 17 years old, pregnant women, or those with HIV infection or other conditions that would increase risk of progression to active disease

Pilot projects using QFT to screen for latent tuberculosis in two high risk groups (the homeless and jail inmates) are soon to begin in Maricopa County. We will report on these projects in future issues of this newsletter.

Please direct any comments, questions, or items you would like to submit for the newsletter to: 
Cheryl McRill, M.D., M.P.H. 
State TB Control Officer Arizona Department of Health Services 
150 N. 18th Ave, Suite 140
Phoenix, AZ 85007
cmcrill@azdhs.gov  
602-364-3856