Aids Alert International-Rare disease strikes AIDS patients in SE Asia
Aids Alert International-Rare disease strikes AIDS patients in SE Asia
U.S. researchers find life-saving treatment
Thousands of HIV-infected people in northern Thailand have been devastated in recent years by an opportunistic infection that had infected only one to three people a year there prior to the AIDS epidemic.
Penicillium marneffei first was discovered in 1956 as a fungus that infected the internal organs of bamboo rats of central Vietnam. In fact, the first known human case was the result of a 1959 needle stick injury to researcher Gabriel Segretain, an investigator from the Pasteur Institute in Paris.1
The organism is the only dimorphic species of penicillium, meaning it can exist in two different forms, and it can kill both animals and humans.2
Since Thailand's HIV epidemic escalated in the 1990s, the fungus has infected and killed thousands of AIDS patients. The organism has infected people living throughout Southeast Asia and is endemic to Burma, Cambodia, southern China, Indonesia, Laos, Malaysia, Thailand, and Vietnam.1
"Untreated in AIDS patients, it's close to 100% fatal, like cryptococcus in AIDS patients," says Kenrad E. Nelson, MD, professor of epidemiology at the Johns Hopkins School of Public Health in Baltimore.
Fewer than 50 people had contracted the disease prior to the AIDS epidemic, which created a unique opportunity for the fungus to grow and kill.
"When the AIDS epidemic hit Thailand and Southeast Asia, for whatever reasons, this disease hit with a fury," says Chester R. Cooper, PhD, assistant professor in the Center for Tropical Diseases in the department of pathology at the University of Texas Medical Branch in Galveston.
Symptoms of the disease include fever, chronic coughing, generalized lymphadenopathy, septicemia, anemia, hepatomegaly, splenomegaly, weight loss, diarrhea, and skin lesions, which are similar to skin lesions associated with tuberculosis, cryptococcosis, and other diseases.1
Nelson and other researchers have developed a treatment for the disease that has been surprisingly effective and inexpensive. They found that patients infected with P. marneffei respond well to an antifungal drug called amphotericin B, when the drug is given intravenously. The drug was successful in 75% of the patients, whereas more than 60% of the patients treated with an alternative treatment with fluconazole failed therapy.
The regimen includes giving patients amphotericin for eight to 10 weeks, or they're given amphotericin for two weeks, followed by 10 weeks of oral itraconazole in two doses per day. The medications are fairly inexpensive, at a cost of about 50 cents to $1 per dose, he says.
"We studied the regimen, and the mortality was 10% to 15%, but most patients responded well," Nelson says. "But we found that after they'd been treated, unless they received a prophylaxis, they tended to relapse."
Researchers conducted a clinical trial, giving patients one tablet per day of itraconazole after the treatment with amphotericin ended. The study included a placebo arm, and patients were randomized to each. Half of the patients who received the placebo had a relapse, but none of the patients given itraconazole relapsed.
Patients in developing nations, such as Thailand, will have to take the prophylaxis indefinitely because they don't have access to antiretroviral therapies that could help improve their immune function, Nelson notes.
Fungus grows like yeast cell in human body
P. marneffei probably grows in the soil of Southeast Asia. Only people with severely compromised immune systems become infected. The fungus can invade a person's body and grow like a yeast cell, shifting its shape to adapt, Chester says.
"You can reproduce this change in a lab by shifting the fungus to body temperature, where it will eventually become this yeast-like cell," Cooper says.
The disease has infected HIV patients who have traveled to Thailand from the United States and other western countries. And at least one case, in which a Pasteur Institute student was exposed to it without having ever directly worked with the fungus, suggests the organism can easily spread through the air.1
References
1. Cooper CR. From bamboo rats to humans: The odyssey of Penicillium marneffei. ASM News 1998; 64:390-396.
2. Nelson KE, Kaufman L, Cooper CR, Merz WG. Penicillium marneffei: An AIDS-related illness from Southeast Asia. Infections in Medicine 1999; 2:118-128.
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