Article: Antifungal Drug Helps Kids with Immune Disorder Avoid Hospitalization

The antifungal medication itraconazole is well tolerated and effectively prevents fungal infections in children who have chronic granulomatous disease (CGD), report scientists from the National Institute of Allergy and Infectious Diseases (NIAID). About 25,000 people worldwide have CGD, an inherited disorder that leaves individuals prone to frequent, severe bacterial and fungal infections. "The addition of prophylactic antifungals to the standard regimen of antibiotics should markedly reduce a significant cause of death from this rare disease," says John I. Gallin, M.D., a researcher at NIAID and lead author of the paper published in this week's edition of The New England Journal of Medicine.

This ten-year-long study is the latest contribution by NIAID researchers to a better understanding of CGD. Forty years ago, Dr. Gallin notes, children with CGD rarely lived past adolescence. In the early 1980s, doctors began administering prophylactic antibiotics to prevent bacterial infections, and the number of annual hospitalizations for the average CGD patient dropped greatly.

Then, in 1991, Dr. Gallin and his colleagues in NIAID's Laboratory of Host Defenses published clinical trial results showing that an immune-boosting substance called interferon gamma reduced serious bacterial infections in CGD patients by 70 percent. Prophylactic interferon gamma was soon added to the treatment regimen for children with CGD, and the quality of their lives improved further, notes Dr. Gallin. "Now people with this disease are living long enough to marry and start families of their own. In fact, I'll soon be attending the wedding of a patient whom I've followed for 30 years."

The latest clinical trial was designed to evaluate the effectiveness of antifungal prophylaxis. The 39 CGD patients enrolled between 1991 and 2001 received a daily dose of either the antifungal drug itraconazole or an inactive look-alike, or placebo. Following the initial random assignment, participants alternated between itraconazole and the placebo annually. The entire study was double-blind, meaning neither the researchers nor the volunteers knew which drug was being administered at any given time. If any participant developed a fungal infection, he or she was withdrawn from the study pool and treated as necessary. Trial participants completed 61 courses of itraconazole and 63 courses of placebo.

Over the term of the study, the investigators recorded 12 cases of fungal infection, seven severe and five superficial. When the study was "unblinded," researchers saw that 11 cases occurred in patients who were receiving placebo when the infection arose. One case of severe fungal infection occurred during itraconazole treatment; however, that patient was probably not taking the drug daily, says Dr. Gallin. Including 12 cases of fungal infection in their data analysis, the scientists found that patients on itraconazole had a statistically significant reduction of fungal infection risk. "We suggest that itraconazole prophylaxis should be added to the treatment regimens for all patients over five years of age who have chronic granulomatous disease," conclude the paper's authors.

NIAID Director Anthony S. Fauci, M.D., says, "In their laboratory and clinical research, Dr. Gallin and his colleagues combine excellence in basic science and medicine. The dedication and skill of these researchers led directly to healthier lives for the children they treat."

Researchers from the National Cancer Institute and the Warren G. Magnuson Clinical Center, both components of the National Institutes of Health, also contributed to this research.

NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

The International Chronic Granulomatous Disease Cooperative Study Group. The New England Journal of Medicine 324:509-16 (1991).