Research Topics
Human Exposure to Cryptococcus gattii
Environmental Distribution of Cryptococcus gattii in BC
Genetic Diversity among Cryptococcus gattii in BC
Ecological niche modeling of Cryptococcus gattii in BC
Evaluating Human Exposure to Cryptococcus gattii in BC
Andrea Griffiths has been developing tools to identify biomarkers of exposure of individuals to Cryptococcus gattii, in order to determine the extent to which residents of BC have been exposed to the fungus. A test was developed to identify cytoplasmic antigens of Cryptococcus gattii which have been recognised by the antibodies in human serum (a component of blood) . Using this test, Andrea has found that approximately 80% of serum samples (77 samples) collected from residents of Vancouver Island who have not had cryptococcosis, contain antibodies to Cryptococcus gattii. This suggests that a significant proportion of Vancouver Island residents have been exposed to the fungus, but have not necessarily become ill with cryptococcosis. Further research is underway to determine the identity of the Cryptococcus gattii antigens that were most commonly recognised by the immune systems of the tested individuals, since these could be useful targets for anti-fungal drugs in the future.
Griffiths, Andrea (2006). "Antibodies to Cryptococcus gattii among Vancouver Island Residents." Presented at the UBC/ UW 18th Annual Occupational and Environmental Health Conference. Semiahmoo, WA: January 5 2006. Download PDF file.
Adrian Hingston has been investigating occupational exposure to Cryptococcus gattii, particularly among arborists and watershed workers. In addition, Adrian has evaluated the environmental and weather conditions that may affect occupational exposure to Cryptococcus gattii. To assess exposure to Cryptococcus gattii, air sampling was performed in the breathing zone of workers carrying out woodland tasks, such as chainsawing, limbing, and chipping. Adrian also recorded measurements of temperature, relative humidity and wind velocity. He found that the highest concentrations of airborne Cryptococcus gattii occurred under working conditions - during tasks such as chain-sawing and chipping, Cryptococcus gattii can become increasingly aerosolised, leading to high concentrations of very small Cryptococcus gattii cells or spores that could potentially be inhaled by workers or other people in the area and cause infection.
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Felling a tree |
Chipping branches |
Environmental Distribution of Cryptococcus gattii in BC
Karen Bartlett and her research group have been investigating the distribution of Cryptococcus gattii on Vancouver Island and other parts of BC, including the Lower Mainland and the Gulf Islands. This is the largest environmental study of Cryptococcus gattii to date. By developing an understanding of the conditions that support colonisation and growth of Cryptococcus gattii populations, it may be possible to better assess exposure of residents and outdoor workers to the fungus, and determine whether previously unaffected areas are likely to become contaminated with Cryptococcus gattii. Since 2002 more than 3000 different trees in BC have been tested for Cryptococcus gattii, and approximately 240 have tested positive. The trees that have tested positive to Cryptococcus gattii belong to more than 10 different species, including Douglas-fir, arbutus, red cedar, red alder, Garry oak, and maple, and are located in many different areas of Vancouver Island and BC. In addition we have identified Cryptococcus gattii in soil, air and water samples from many different parts of BC.
Click here for a sampling map of the Cryptococcus gattii distribution in BC.
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| Air sampling under arbutus tree using Andersen 6-stage sampler | Swabbing inside a hollow in a Garry Oak tree | A group of samplers |
Other goals of the environmental study are to investigate mechanisms of Cryptococcus gattii spread from one area to another, and how small differences in conditions can affect the survival or colonisation of Cryptococcus gattii in a new area. For example, pH (acidity), relative humidity, temperature, salt concentration, and the presence of other microorganisms in the area.
Bartlett, Karen, et al. (2004). "Cryptococcus gattii: A tropical pathogen emerging in a temperate climate zone". Presented at the 16th Biometeorology and Aerobiology Conference. Vancouver, BC. August 26 2004. Download PDF File. Watch the recorded presentation.
Kidd, Sarah (2006). "Mobilisation and Transmission of Cryptococcus gattii in the Pacific Northwest." Presented at the UBC/ UW 18th Annual Occupational and Environmental Health Conference. Semiahmoo, WA, USA: January 5 2006. Download PDF file.
Genetic Diversity among Cryptococcus gattii in BC
Sarah Kidd has been using a variety of genetic fingerprinting methods (PCR-fingerprinting, Restriction Fragment Length Polymorphism Analysis, and Multilocus Sequence Typing) to assess the extent of genetic variation among Cryptococcus gattii isolates that caused infections in humans and animals, as well as those isolates recovered from trees, soil, air and water in BC. It has been determined that the majority of clinical and environmental isolates belong to a genotype known as "VGII", which is relatively rare in other parts of the world where Cryptococcus gattii is found. Among these VGII isolates from BC, two subtypes have been identified and designated "VGIIa" and "VGIIb". Approximately 90 % of the VGII isolates belong to the VGIIa subtype, while only 10 % belong to the VGIIb subtype. Other VGII subtypes also exist outside of BC. In addition, a small proportion (less than 5 %) of clinical and environmental isolates belong to a molecular type known as "VGI". Interestingly, while VGI is relatively rare in BC, it is very common in other areas of the world where Cryptococcus gattii is found (e.g. Australia). The reason for differences in the prevalence of different genotypes are not well understood, but our research continues to search for clues.
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| PCR-fingerprint using the M13 minisatellite-specific primer. Copyright. | RFLP of the URA5 gene. Copyright. |
Genetic comparisons between clinical isolates and those from the environment have demonstrated that all of the strains that cause infection in humans and animals of BC can be found in the environment in BC. Therefore it is highly likely that the majority of Cryptococcus gattii infections occurring in BC residents or animals were actually acquired in BC. Sarah is also investigating patterns of molecular variation among Cryptococcus gattii isolates from BC in the context of those from other areas of the world, as well as the population structure of Cryptococcus gattii in BC using a comparative gene genealogy approach. The results suggest a predominantly clonal population structure among BC isolates, while there is evidence for sexual recombination between different molecular types on a global scale. There appears to be no geographic pattern of strain relationships, and DNA sequence comparisons indicate that genotypes among isolates from BC are also present in other areas of the world, indicating extensive strain dispersal.
Epidemiology of Human Cases
Laura MacDougall is investigating the epidemiological aspects of human Cryptococcus gattii infection. Since Cryptococcus gattii has only recently emerged as the cause of infection on Vancouver Island, a well-defined focal area, it was possible to use this to advantage to estimate the incubation time between exposure to the fungus and the onset of symptoms. Several human cases that lived on the BC mainland reported short periods of travel to Vancouver Island, presumably where they were exposed to Cryptococcus gattii. By interviewing the cases and reviewing medical charts, the dates of travel and of symptom onset were determined. From this, the median incubation period of Cryptococcus gattii was estimated to be 6 - 7 months, with a range of 2 - 11 months. This incubation period is much shorter than the estimated 110 months incubation or dormancy of infection caused by the ly related pathogen, Cryptococcus neoformans (reference).
Veterinary Aspects
Colleen Duncan completed her Masters research in 2005, investigating the veterinary aspects of the emergence of Cryptococcus gattii in BC. After reviewing records from veterinary and human diagnostic laboratories throughout BC, Colleen found that there was a continual increase in the annual number of animal cases but not human cases diagnosed. There were 75 % more animal cases than human cases, even though animal cases were more likely than human cases to go undiagnosed or unreported. Animal cases were identified before the 1999 emergence of human cases, suggesting that Cryptococcus gattii may have existed in BC prior to 1999, and that animal cases represent a good indicator for human infection.
Colleen found that there were 50 % more Cryptococcus gattii infections in cats compared to dogs. Cat and dog cases were characterised most commonly by respiratory infection, followed by central nervous system (CNS) infection. However, a higher proportion of dogs had CNS infection relative to cats. Neurological symptoms were found to be the only significant indicator of mortality - animals with CNS symptoms were four times more likely to die than those animals that never exhibited CNS symptoms. Host and environmental risk factors for infection were identified through a case-control study, that suggested the risk of infection in an individual animal increased when it resided within 10 km of a large-scale environmental disturbance (e.g. construction, logging), or when it had increased opportunity for exposure to Cryptcoccus gattii through travel or activity. Cryptococcus gattii was found to colonise the nasal passages of squirrels, horses, dogs and cats from BC. Serum testing found that a small number of dogs and cats had been exposed to the fungus but had not developed symptoms of infection at the time of testing. Over a 14 month follow-up period, these asymptomatic animals went on to either develop clinical infection, remain asymptomatic, or clear the fungus.
Duncan, Colleen. (2005). The emergence of Cryptococcus gattii in British Columbia: Veterinary Aspects. MSc Thesis. Department of Large Animal Clinical Studies, University of Saskatchewan, SK, Canada.
Ecological niche modeling of Cryptococcus gattii in BC
Sunny Mak has been mapping and modeling the geographic distribution of Cryptococcus gattii in BC. He used a landscape epidemiology approach, which is based on the relationship between the ecology and epidemiology of infectious diseases, to identify and forecast geographical areas where Cryptococcus gattii disease transmission occurs.
Optimal ecological niche areas for Cryptococcus gattii were identified along the central and south eastern coast of Vancouver Island, the Gulf Islands, Sunshine Coast and Vancouver Lower Mainland. Small, isolated geographical areas on the Queen Charlotte Islands, BC central coast, west coast of Vancouver Island and southern BC interior have environmental conditions that could potentially support the establishment of Cryptococcus gattii in these areas. The results of these analyses are visualized in GIS, and shared with public health to prioritize environmental sampling and increase public and physician awareness of cryptococcal disease in BC.
Mak, Sunny. 2007. Ecological niche modeling of Cryptococcus gattii in British Columbia, Canada. MSc Thesis. Department of Geography, University of British Columbia, Vancouver, Canada.
List of Publications
Datta, K. Bartlett, K, Baer, R, Byrnes, E, Galanis, E, Heitman, J, Hoang, L, Leslie, M, MacDougall, L, Magill, S, Morshed, M, Marr, K. Spread of Cryptococcus gattii
into Pacific Northwest Region of the United States. Emerging Infectious Diseases. 2009; 15(8):1185-1191.
Galanis E, Hoang L, Kibsey P, Morshed M, Phillips P. Clinical presentation, diagnosis and management of Cryptococcus gattii cases: Lessons learned from British Columbia. Can J Infect Dis Med Micro. 2009;20(1):23-28.
Datta, K., Bartlett, KH, Marr, KA. 2009. Cryptococcus gattii emergence in Western North America: Exploitation of a novel ecological niche. Interdisciplinary Perspectives on Infectious Diseases v. 2009, Article ID 176532, 8 pages. doi:10.1155/2009/176532.
Bartlett, KH, Kidd, SE, Kronstad, J. 2008. The emergence of Cryptococcus gattii in British Columbia and the Pacific Northwest. Current Infectious Disease Reports, 10(1): 58-65.
Nicol, A-M, Hurrell, C, McDowall, W, Bartlett, K, Elmieh, N. 2008. Communicating the risks of a new, emerging pathogen: the case of Cryptococcus gattii. Journal of Risk Analysis 28(2): 373-386 doi:10.1111/j.1539-6924.2008.01024.x.
Bartlett, KH, Kidd, SE, Kronstad, J. 2007. The emergence of Cryptococcus gattii in British Columbia and the Pacific Northwest. Current Fungal Infection Reports, 1:108 - 115
Upton, A, Fraser, JA, Kidd, SE, Bretz, C, Heitman, J, Bartlett, KH, Raverty, S. Marr, KA. 2007. First Contemporary Case of Human Infection with Cryptococcus gattii in Puget Sound: Evidence for Spread of the Vancouver Island Outbreak. Journal of Clinical Microbiology, 45(9):3086-8.
Fyfe M, MacDougall L, Romney M, Starr M, Pearce M, Mak S, Mithani S, Kibsey P. (2008) Cryptococcus gattii Infections on Vancouver Island, British Columbia, Canada: Emergence of a Tropical Fungus in a Temperate Environment. Canada Communicable Disease Report. 34(06).
BC Centre for Disease Control. (2007) BC Cryptococcus gattii Surveillance Summary, 1999-2006. Available from: http://www.bccdc.org/topic.php?item=109
BC Centre for Disease Control. (2007) 2006 Epidemiology Report: 2006 British Columbia Annual Summary of Reportable Diseases. July 2007. (note: see page 103 for information on C. gattii)
Upton A, Fraser JA, Kidd SE, Bretz C, Bartlett K, Heitman J, Marr K. (2007). First Contemporary Case of Human Infection with Cryptococcus gattii in Puget Sound: Evidence for Spread of the Vancouver Island Outbreak. Journal of Clinical Microbiology. 45(9): 3089-3088, June 2007.
Galanis E, Waters S, Li M, Hoang L, MacDougall L, Phillips P. (2007). Cryptococcus gattii in BC: Update on an emerging disease. BC Medical Journal. 49(4), May 2007.
Kidd S.E., Chow Y., Mak S., Bach P.J., Chen H., Hingston A.O., Kronstad J.W. and Bartlett KH. (2007). Characterization of Environmental Sources of the Human and Animal Pathogen Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the United States. Applied Environmental Microbiology. 73(5):1433-43.
Kidd SE, Bach PJ, Hingston AO, Mak S, Chow Y, MacDougall L, et al. Cryptococcus gattii dispersal mechanisms, British Columbia, Canada. Emerg Infect Dis.
MacDougall L, Kidd SE, Galanis E, Mak S, Leslie MJ, Cieslak PR, et al. Spread of Cryptococcus gattii in British Columbia, Canada, and detection in the Pacific Northwest, USA. Emerg Infect Dis.
MacDougall L. and Fyfe M. (2006). Emergence of Cryptococcus gattii in a novel
environment provides clues to its incubation period. Journal of Clinical Microbiology. 44(5):1851-1852.
Duncan C., Schwantje H., Stephen C., Campbell J., and Bartlett K. (2006). Cryptococcus gattii in wildlife of Vancouver Island, British Columbia, Canada.
Journal of Wildlife Disease. 42(1):175-8.
Duncan C.G., Stephen C., and Campbell J. (2006). Evaluation of risk factors for Cryptococcus gattii infection in dogs and cats. Journal of the American Veterinary Medicine Association. 228(3):377-82.
Bartlett K.H., Davies H.W, Fyfe M, Hingston A. (2006). Investigation of occupational exposures to forestry workers from environmental Cryptococcus neoformans var. gattii. Report.
Duncan C., Stephen C., Lester S., and Bartlett K.H. (2005). Follow-up study of dogs and cats with asymptomatic Cryptococcus gattii infection or nasal colonization. Medical Mycology. 43(7):663-6.
Duncan C., Stephen C., Lester S., and Bartlett K.H. (2005). Sub-clinical infection and asymptomatic carriage of Cryptococcus gattii in dogs and cats during an outbreak of cryptococcosis. Medical Mycology. 43(6):511-6.
Kidd S.E., Guo H., Bartlett K.H., Xu J., and Kronstad J.W. (2005). Comparative gene genealogies indicate that two clonal lineages of Cryptococcus gattii in British Columbia resemble strains from other geographical areas. Eukaryotic Cell. 4(10):1629-38.
Hoang LM, Maguire JA, Doyle P, Fyfe M, Roscoe DL. Cryptococcus neoformans infections at Vancouver Hospital and Health Sciences Centre (1997-2002): epidemiology, microbiology and histopathology. J Med Microbiol. 2004 Sep;53(Pt 9):935-40
Kidd, S.E., Hagen F. , Tscharke R.L., Huynh M., Bartlett K.H., Fyfe M., MacDougall L. , Boekhout T., Kwon-Chung K.J., and Meyer W. (2004). A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proceedings of the National Academy of Sciences of the USA. 101(49):17258-63.
Stephen C., Lester S., Black W., Fyfe M., and Raverty S. (2002). Multispecies outbreak of cryptococcosis on southern Vancouver Island, British Columbia. Canadian Veterinary Journal. 43(10):792-4.
