New anergy guidelines due out this fall
Kinder, gentler recs step back from mandate
After years of debate, a revised set of recommendations for anergy testing is finally due out this fall from the Centers for Disease Control and Prevention (CDC) in Atlanta, says Elsa Villarino, MD, MPH, section chief of the research and evaluation branch of the CDC’s Division for Tuberculosis Elimination.
The new guidelines, now in their second draft, will probably step back a bit from the 1991 guidelines, says Charles Daley, MD, assistant professor of medicine at the University of California, San Francisco (UCSF). He is chief of the chest clinic at San Francisco General Hospital and one of the experts whose testimony on the subject will be incorporated into the new guidelines.
"Based on what I’ve seen, the CDC won’t mandate that it’s wrong to do anergy testing just that it’s OK not to do it," Daley says.
At the April meeting in Atlanta of the CDC’s Advisory Council for the Elimination of Tuberculosis (ACET), the new take on anergy testing was widely in evidence, as TB experts from around the nation took turns energetically bashing the test, or offering, at best, lukewarm testimony on its behalf.
Typical of the tone of the proceedings was a remark by John Bass Jr., MD, director of the division of pulmonary and critical care medicine at the University of South Alabama’s College of Medicine in Mobile. He was a liaison representing the American Thoracic Society at the ACET meeting. "A small subcommittee" biased in favor of the test produced the 1991 set of recommendations, Bass grumbled; otherwise, the 1991 recommendations would surely have never been written as they were.
What test predicts depends on the country
In the United States, a positive anergy test doesn’t portend the same clinical course it does in other countries, some ACET experts present added. In Spain, for example, with its high background rate of TB infection, anergic patients often develop TB, says Ken Castro, MD, director of the CDC’s Division for Tuberculosis Elimination.
But in the United States even in New York or New Jersey, where background rates are relatively high the same course of events doesn’t hold true, Castro added.
Castro’s remarks prompted Wafaa El-Sadr, MD, MPH, director of the infectious disease department at Harlem Hospital Center in New York City, to urge her fellow clinicians not to throw out the baby in this case, isoniazid prophylaxis along with the bathwater. Physicians should still consider giving isoniazid to anergic patients, she says, because some data show anergics’ risk for developing active TB falls approximately midway between that of non-anergics and people who are PPD-positive. Even so, she added, the decrease in active TB among anergics treated with isoniazid wasn’t significant.
In San Francisco, it’s more or less the same story, says Daley. There, a group of anergic patients didn’t get isoniazid prophylaxis but they didn’t develop active TB, either. "According to what the CDC says [in its 1991 recommendations], they should have been expected to do so," he adds.
No standardized method of test reading
The new recommendations are expected to address what many experts see as the test’s biggest problem namely, that it’s not standardized, says Daley. "It’s standardized neither in terms of what antigens are used, nor in terms of what’s considered a positive reaction," he says. Some publications define a positive reaction as greater than a 0 mm induration, some say greater than 2 mm, and some including the CDC in its 1991 recommendations say greater than 5 mm, Daley says.
The situation with antigens is likewise confusing. Only recently have drug companies shown much interest in producing a product that’s consistent from one batch to the next, says Daley. "Within the last year, there’s a new Candida antigen that’s standardized. Tetanus [toxoid], coccidioidin and Candida are starting to get there," he says. "But we need one company and one lot."
Anergy itself may prove so fickle a phenomenon that it’s not even worth assaying, some experts believe.
Despite the fact that most clinicians who use the test do not do retests, a patient who’s anergic today has no guarantee he’ll stay that way, researchers say. (See March 1995 TB Monitor, "Fewer experts enamored of anergy testing. . .")
One multi-center study has shown that anergy waxes and wanes over time, says Daley. After a year, a third of previously anergic patients in a cohort regained their ability to mount a delayed-type hypersensitivity (DTH) response, he says.
Thus, anergy tests in their present form give clinicians nothing of value, Daley says. At UCSF, "we don’t make any clinical decisions based on whether someone is anergic. We don’t provide them with preventive therapy; it doesn’t help us to know they’re anergic."
Theoretically, a standardized test could be useful, he says. But first, antigens must be standardized; how to read the test must be standardized; and the test itself must be tested, says Daley.
"That will all take a very long time," he says. "That means we’re not going to have an answer soon." It also means that for now, at least on the subject of anergy testing, "we’re still confused."
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