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Cryptococcal Infection Has Taken a New Twist
Abstract & Commentary
By Joseph H. John, MD, Associate Chief of Staff for Education, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, is Associate Editor for Infectious Disease Alert.
Dr. John reports no financial relationships relevant to this field of study.
Source: Okamoto K, et al. Cryptococcus gattii genotype VGIIa infection in man, Japan, 2007. Emerg Infect Dis. 2010;16:1155-1157
Cryptococcal infection has taken another new twist. For years before the HIV epidemic, infection with C. neoformans mostly occurred in immunosuppressed individuals who also had some defined zoonotic exposure, often to birds or pigeons. Then along came the AIDS epidemic and a pre-HAART proliferation of cryptococcal infection with a tropism for the leptomeninges. Cryptococcal meningitis became a scourge of the early HIV epidemic. With the advance of HAART, there has been a significant decrease in cryptococcal infection, certainly in HIV-positive individuals. Historically only one species, C. neoformans, has been associated with human infection.
About eight years ago, the Vancouver Island outbreak of C. gattii began and has spread throughout the northwest of the United States and British Columbia. Cases have been documented in humans and other animals. Now, the infection appears in Japan, in 2007, with the same genotype of C. gattii that caused the Vancouver outbreak.
The Japanese patient was 44 years old at the time, and presented at the University of Tokyo Hospital with headache and loss of right-sided vision in both eyes (homonymous hemianopsia). He was an ex-smoker but taking no immunosuppressive medications. The only overseas travel had been to Guam and Saipan in the 1990s. He worked near constructions sites in urban areas but had no major wildlife exposures. He was afebrile when admitted and, upon physical examination, had agraphia, anarithmia, and the homonymous hemianopsia. His serum glucose was 367 mg/dL. His HIV testing was negative. On T1-weighted images, he had an enhancing mass in the occipital lobe. The mass was resected and showed growth for Cryptococcus spp, which was later speciated by rRNA gene-sequence analysis. Multilocus sequence typing using 11 alleles showed the Vancouver Island genotype R265 (VGIIa). The isolate was susceptible to amphotericin B, flucytosine, fluconazole, and itraconazole, respectively.
There have been few to no cases of C. gattii in Japan. Because we are just getting experience with the organism outside of North America, many issues arise, including the natural habitat and the question of contagion. The first cases in the United States were not seen until 2006 (J Clin Microb. 2007;45:3086-3088). Now, the infection has been recognized in Japan and, most curiously, with the same serotype as the Vancouver outbreak. Other isolates of C. gatti, for example from South America and Europe, have not been the Vancouver serotype. Other Cryptococcus spp., such as albidus, luteolus, or terrus, may rarely cause human infection in debilitated individuals. Thus, the upswing in C. gattii infections in the northwest, and this report in Japan, suggests it may be spreading. One of the problems in identifying the latter pathogen is that many laboratories, including ones in Japan, may not test further for non-neoformans species.
There has been a rapid upbeat of studies of C. gattii in an attempt to understand its emergence. One such study in mice using the Vancouver strain showed that C. gattii induced a much less protective inflammatory response, including a decline in neutrophile migration to infected sites. Virulence of the strain tested, however, was equal to the C. neoformans isolated and tested in mice.
There also has been further genetic analysis of the neoformans and gattii strains, particularly with regard to their MLST types; more information is available at http://www.mlst.net.
Clearly, we are eagerly awaiting any information on further dissemination of gattii clones, as well as peculiarities of the Vancouver outbreak. Many authorities have warned about the continued emergence in the modern age of viral pathogens, particularly zoonotic ones, but here we have the specter of a new emergent fungal pathogen.