Rare Yeast in African AIDS Patients Surprises Researchers
DURHAM, N.C. -- Duke University Medical Center researchers have discovered that a surprising number of meningitis cases among AIDS patients in sub-Saharan Africa were caused by an extremely rare subspecies of the infectious yeast Cryptococcus.
The finding represents the largest cluster of Cryptococcus gattii serotype C cases ever recognized, and is unusual because C. gattii typically only infects people with healthy immune systems. Cryptococcus strains such as serotype C are distinguished by characteristic sugar polymers (polysaccharides) surrounding the cell wall and designated by letters of the alphabet.
Understanding the prevalence of different serotypes is an important step in combating this devastating infection because even closely related Cryptococcus strains can vary tremendously in virulence, the researchers said. Studies report that in sub-Saharan Africa, between 15 and 45 percent of patients with advanced HIV infection will die of cryptococcal infections.
"C. gattii is clearly more abundant in Africa than had been previously thought," said Anastasia Litvintseva, Ph.D., a postdoctoral researcher in Duke's Medical Mycology Research Laboratory. "We have now discovered two unusual populations of Cryptococcus in sub-Saharan Africa, which has the largest global population of HIV-positive individuals, who are great risk for infection with these yeasts. There is the newly discovered population of C. gattii serotype C, which is the rarest type of Cryptococcus. And in 2003, we discovered an atypical population of C. neoformans in Botswana capable of undergoing sexual recombination, which is producing genetically unique strains we have never seen before."
The results were published in the Sept. 1, 2005, issue of The Journal of Infectious Diseases. The study was funded by the National Institutes of Health.
The incidence of Cryptococcus infections in sub-Saharan Africa has risen sharply since the 1980s, paralleling the increase in HIV/AIDS patients. Meningitis and meningoencephalitis (infection of the brain and central nervous system) caused by Cryptococcus can be fatal within weeks without early diagnosis and treatment.
C. gattii is closely related to another infectious yeast, Cryptococcus neoformans. While C. neoformans is the most common cause of fungal meningitis in patients with AIDS and compromised immune systems, C. gattii typically only infects people with normal immune systems. The yeast cells of Cryptococcus first infect the lungs when a person inhales the airborne spores or yeast cells. In nature, C. neoformans is associated with birds and bird droppings, and another serotype of C. gattii can be found on the bark and debris of several species of tropical trees. However, C. gattii serotype C has rarely been isolated from the environment, and little is known about its ecology or natural habitat.
Cryptococcal infection is generally harmless in healthy people because the normal immune system combats the yeasts. But in people with suppressed immunity, such as transplant patients, those who receive cancer chemotherapy and people with HIV/AIDS, Cryptococcus can evade the immune system and infect organs such as the lungs and the brain. Even so, more than 99 percent of HIV-positive patients who develop cryptococcal meningitis are infected with C. neoformans, not C. gattii. Its prevalence in patients with AIDS in Botswana and Malawi was a surprise, Litvintseva said.
The Duke team examined strains of Cryptococcus isolated from spinal fluid from 161 patients in Botswana and blood from 15 patients in Malawi, all of whom had AIDS and meningitis. The Botswana samples were collected and first identified as C. gattii by Rameshwari Thakur, Ph.D., of the National Health Laboratory in Botswana.
The Duke researchers analyzed the fungal DNA and cataloged the genetic makeup of the different strains of Cryptococcus in a process called genotyping. About 86 percent (139) of the Botswana group and 87 percent (12) of the Malawi group were the common C. neoformans variety grubii serotype A. One of the isolates from Malawi was a hybrid Cryptococcus strain.
The remaining samples – 22 from Botswana and two from Malawi, which represent about13 percent of each group – were the rare C. gattii serotype C. Infections caused by this species tend to be more serious than those resulting from C. neoformans, Litvintseva said. Patients develop more nodules in their lungs and brains, and the infection is more aggressive and resistant to treatment.
Although the environmental source of C. gattii serotype C is unknown in Africa, Litvintseva said it would be surprising if the strain was not found in other sub-Saharan countries as well. "This may explain, in part, the serious impact of cryptococcal meningitis in sub-Saharan Africa."
Co-authors include Rameshwari Thakur of the National Health Laboratory, Ministry of Health, Gaborone, Botswana; and L. Barth Reller, M.D., and Thomas G. Mitchell, Ph.D., of Duke University Medical Center.