1-Sep-2011-2009 - DURHAM, NC - Most AIDS patients, when diagnosed with a fungal infection known simply as
cryptococcosis, are assumed to have an infection with Cryptococcus neoformans, but a recent study from Duke University Medical
Center suggests that a sibling species, Cryptococcus gattii, is a more common cause than was previously known.
The difference between these strains could make a difference in treatment, clinical course, and outcome,
said Joseph Heitman, M.D., Ph.D., senior author of the study and chair of the Duke Department of Molecular Genetics and Microbiology.
The study was published Sept. 1 in PLoS Pathogens.
The study emphasizes that health professionals need more careful recording of the cryptococcal species
to understand different clinical courses and possibly to change treatment strategies.
Researchers at Duke University Medical Center discovered that in the Los Angeles area, over 12 percent of AIDS patients diagnosed with
Crypotococcus were infected with C. gattii, much higher than earlier studies, suggesting only about 1 percent have C. gattii. The
researchers based these figures on molecular testing of fungal DNA barcodes.
This discovery comes at the same time as a C. gattii outbreak is expanding in the Pacific Northwest, spreading southward from
Vancouver, British Columbia, through Washington, Oregon, and into northern California. Molecular testing is helping both
health officials and scientists gain a picture of how a formerly tropical fungus could find new territory, in temperate
climates, for infection.
"Importantly, we found that isolates causing the outbreak and those infecting AIDS patients are completely different
(VGII vs. VGIII)," said co-lead author Edmond Byrnes, Ph.D., a recently graduated student in the Heitman laboratory.
Wenjun Li, Ph.D., also a co-lead author and researcher in the Heitman laboratory, noted that, based on the fungal
isolate samples taken from patients, those with C. gattii may experience resistance to the commonly used "azole" drugs that
combat fungal infections, and clinicians might be better aware of potential treatment problems if they knew the species.
Because cryptococcal strains are responsible for over 620,000 deaths annually and responsible for one-third of all
AIDS deaths, this species distinction may be of public health importance.
"There may be an unrecognized health burden in AIDS patients attributable to C. gattii rather than C.
neoformans," Heitman said.
He said that while a simple test is all that is needed to distinguish the two strains, "few clinical microbiology
labs or hospitals, even in developed countries, are equipped to distinguish C. neoformans from C. gattii."
Heitman said that he doesn't believe that there is any human-to-human transmission of C. gattii, but rather, patients
are being exposed in the environment. For example, one AIDS patient from San Diego had an isolate that was traced back to a type of
tree, which is a common place to find C. gattii, in Australia and elsewhere.
"This study clearly illustrates that AIDS patients in certain areas of the world might be infected by two different
cryptococcal species," said John R. Perfect, M.D., professor of medicine at Duke University Medical Center. "Although the outcome
of infection in comparison between the two species remains uncertain, this study shows that we need to carefully control for
potential differences and study them further."
Medical management might be more complicated for C. gattii compared to C. neoformans, including the possibility of
azole drug resistance and the formation of cryptococcomas in the central nervous system that can be difficult to treat and that
cause abscesses. "Based on the prevalence we found, it makes sense to pursue further clinical studies, not just to find out
the species, but also the molecular type, so we can learn all we can about how this pathogen is travelling and
evolving," Heitman said.
Other authors include co-lead author Yonathan Lewit of Duke Molecular Genetics and Microbiology and Fred S. Dietrich
of Duke Molecular Genetics and Microbiology, as well as the Duke Institute for Genome Sciences and Policy; co-lead author
Ping Ren, Sudha Chatuverdi and Vishnu Chatuverdi of the Mycology Laboratory at Wadsworth Center in Albany, N.Y.; Kerstin
Voelz and Robin C. May of the of the Department of Molecular Pathobiology in the School of Biosciences at the University
of Birmingham in the United Kingdom (UK); and James A. Fraser of the Department of Molecular and Microbial Sciences at
the University of Queensland, Brisbane, Australia.
The work was supported by the National Institutes of Health, the National Institute for Allergies and Infectious Disease, the
Medical Research Council (UK), and funds from the Wadsworth Center Clinical Laboratory Reference System.
Contact: Mary Jane Gore
Duke University Medical Center