CDC: Anergy tests should no longer be routine

New guidelines provide specific situations for use

After years of debate and confusion over the usefulness of anergy testing for HIV-positive patients who are suspected to have tuberculosis, the Centers for Disease Control and Prevention is no longer recommending the test except in limited situations. Even in those cases, the new guidelines recommend that clinicians should consider cost, feasibility, and expertise before making a decision.

The recommendations, published in the Morbidity and Mortality Weekly Report, update the CDC’s 1991 recommendations on anergy testing in HIV-positive patients, whose ability to react to PPD-tuberculin skin testing may be compromised.

The CDC changed its position after accumulated data showed the limited usefulness of anergy testing. Those limiting factors include:

• problems with standardizing anergy tests, which commonly use mumps and Candida antigens to assess cell-mediated immunity;

• the low risk of TB associated with the diagnosis of anergy;

• the lack of proven benefit of providing preventive therapy to anergic HIV-positive patients.

As a result of these limitations, the CDC no longer recommends routine anergy testing in conjunction with PPD testing for TB screening programs among HIV-positive people.

In making its decision, the CDC noted that "lack of standardization and lack of outcome data based on uniform antigens and tests are among the greatest obstacles to evaluating the effectiveness of anergy testing and making decisions concerning TB preventive therapy."

The agency also notes that no definitive association has been drawn between anergy and the risk for active TB in HIV-positive people. For unknown reasons, the magnitude of risk for TB among anergic patients has varied from zero to greater than 12 per 100,000 person-years.

Finally, the CDC points out that even if anergic HIV-positive patients were at high risk for active TB and were given isoniazid preventive therapy, the effectiveness of the intervention is not known for this population.

When to consider using anergy testing

Because some studies have shown a relationship between anergy and the risk for TB, clinicians may find value in anergy test results in limited situations for estimating the risk of TB in individual patients. A decision to test should be made in conjunction with information concerning the patient’s risk of exposure and infection. Clinicians also should weigh the cost of testing and the availability of expertise needed to perform and read the tests, the CDC notes.

"The expertise of the heath care provider and a clear understanding of the limitations of anergy testing are critical to appropriate use," the CDC states.

The results of anergy testing may be useful in high-risk settings, such as prisons, for deciding who should be offered prolonged preventive therapy. Settings that may warrant anergy testing include situations where exposure is likely but PPD conversion has not occurred, and where the consideration of primary prophylaxis may arise. The most vulnerable persons in immunologic terms may have high priority for preventive therapy, the guidelines state.

The MMWR article also reiterates the CDC’s recommendations for TB preventive therapy for HIV-positive, PPD-positive and HIV-negative, PPD-negative patients, as follows:

HIV-positive, PPD-positive: Those persons who have positive reactions to PPD tuberculin (greater than or equal to 5 mm), who have not already been treated for TB infection, and whose test results exclude active TB should be considered for 12 months of isoniazid preventive therapy. Therapy is indicated even if the date of the PPD skin-test conversion cannot be determined.

HIV-negative, PPD-negative: When assessing HIV-infected persons who have negative PPD skin-test results or who are known to be anergic, there are two factors to consider when deciding on preventive therapy — the likelihood of exposure to transmissible active TB and the likelihood of latent TB infection. The CDC notes that preventive therapy should be considered for HIV-positive persons who do not have a documented positive PPD skin test response, but who have had recent contact with patients who have infectious pulmonary TB.

In some cases, isoniazid preventive therapy should be considered for persons who are not PPD-positive. Such therapy may be beneficial for children who are born to HIV-positive mothers and are in close contact of a person who has infectious TB. It may also be beneficial for HIV-positive adults who reside or work in institutions and are frequently exposed to infectious TB.


1. Centers for Disease Control and Prevention. Anergy skin testing and preventive therapy for HIV-infected persons: Revised recommendations. MMWR 1997; 46:No.RR-15.