Cryptococcus gattii Spreading in North America

The Centers for Disease Control reported late last year that Cryptococcus gattii fungal infections were diagnosed in Alabama (1), California (13), Florida (1), Georgia (5), Hawaii (1), Michigan (1), Montana (1), and New Mexico (2) since 2009.  This is surprising because the fungus only first emerged in North America in British Columbia in 2009.  Shortly after, it spread to the Pacific Northwest, and it has now reached the North American East Coast.

C. gattii infections are contracted by inhalation of fungal spores after encountering areas of decaying forest matter or areas near pigeon droppings, which support the growth of the fungus2.  The resulting cryptococcosis infection can lead to pulmonary irritation/infection and potential pneumonia or, more seriously, central nervous system infection1.  Animals present symptoms similar to humans, and the wide array of species that have been affected includes cats, dogs, birds, ferrets, llamas, alpacas, goats, sheep, horses, and porpoises.2

Fungal infections have been known to generally threaten only immunocompromised humans and animals, and infections of this type have usually been associated with the opportunistic pathogen Cryptococcus neoformans rather than C. gattii.  These recent North American infections have been reported in otherwise clinically healthy people and animals, and the C. gattii infections have been more difficult treat than C. neoformans3.  According to microbiologists such as Joseph Heitman, Director for Center for Microbial Pathogenesis at Duke University Medical Center,4 these developments and the changes in geographic spread could be due to C. gattii participating in sexual reproduction and forming previously unseen and more virulent strains.  Additionally, global climate changes could be playing a role in providing new ideal environments for the fungus.  This is thought to be the case in British Columbia, where Douglas fir trees were discovered to be hosting the organism after several years during which the average temperature in the area was consistently one degree higher than normal3. The new North American cases were not always connected with travel to places in which the fungus is endemic within the expected incubation period of 2-13 months1.  Such instances could suggest that the C. gattii strains arrived years earlier from endemic regions, but are just now causing illnesses as the climates in their new habitats have become more favorable3.  

Authored by Paige Meier

References:

1. Harris JR, SR Lockhart, G Sondermeyer, DJ Vugia, MB Crist, MT D’Angelo, et al. 2013. “Cryptococcus gattii infections in multiple states outside the US Pacific Northwest.” Emerg Infect Dis [Internet]. 19.10 (Oct 2013). Accessed 20 Jan 2014. http://wwwnc.cdc.gov/eid/article/19/10/13-0441_article.htm 
2. Nielsen K, AL De Obaldia, J Heitman. 2007. “Cryptococcus neoformans mates on pigeon guano: implications for the realized ecological niche and globalization.” Eukaryot Cell. 6.6 (Jun 2007): 949-59. Accessed 20 Jan 2014. http://www.ncbi.nlm.nih.gov/pubmed/17449657
3. Frazer, J. 2013. “Fungi on the March.” Scientific American. 309(Nov 2013): 50-57. Accessed 20 Jan 2014. http://www.nature.com/scientificamerican/journal/v309/n6/full/scientificamerican1213-50.html.
4. Heitman, J. 2013. “Sexual reproduction and the emergence and evolution of microbial pathogens.” Duke University Medical Center for Microbial Pathogenesis. Accessed 20 Jan 2014. http://mgm.duke.edu/microbial/mycology/heitman/.
5.  Naureen I, EE DeBess, R Wohrle, B Sun, RJ nett, AM Ahlquist, T Chiller, SR Lockhart. 2009. “Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii strains from the Pacific Northwest of the United States.” J. Clin. Micorobiol. 48.2 (Dec 2009): 539. Accessed 20 Jan 2014. http://jcm.asm.org/content/48/2/539.full.pdf+html.
6. Duncan CG, C Stephen, J Campbell. 2006. “Evaluation of risk factors for Cryptococcus gattii infection in dogs and cats.” J Am Vet Med Assoc. 228.3 (Feb 2006): 377-82. Accessed 20 Jan 2014. http://avmajournals.avma.org/doi/abs/10.2460/javma.228.3.377?prevSearch=allfield%253A%2528c.%2Bgatti%2529&searchHistoryKey.

A Multidisciplinary Approach to Parasitic Diseases: Tuesday, January 21st

Armando E. Gonzalez, PhD, is the head of the Veterinary Epidemiology and Economics Laboratory at the San Marcos School of Veterinary Medicine in Peru.  He obtained a Master degree in microbiology from San Marcos and his PhD in veterinary epidemiology and economics at the University of Reading.  He holds an Associate Appointment at the Bloomberg School of Public Health (Johns Hopkins University), and is currently the president of the Peruvian Academy of Veterinary Sciences.  Dr. Gonzalez devotes his time to the study of the control and transmission of cysticerosis, and the tapeworm Taenia solium.  Specifically, his research examines the transmission of zoonotic cestodes and the role that invertebrates play in T. solium egg dispersion.  His talk at the North Carolina One Health Intellectual Exchange centered on the epidemiology of T. solium, as well as, intervention and control techniques used in multidisciplinary approaches to parasitic diseases. 

Dr. Gonzalez began his talk with a brief explanation of the zoonotic cestode parasite T. solium’s life cycle.  T. solium infection, and the resulting disease cysticerosis, is prevalent in less developed regions throughout the world including Latin America, Asia, and sub-Saharan Africa.  High transmission rates are associated with poor sanitation and hygiene, poverty, low living standards, poor waste disposal, and primitive pig husbandry sites.  Pigs become infected when they consume gravid proglottids (T. solium eggs), that are contained in the human feces.  These pigs act as the intermediate host and develop porcine cysticerosis.  Humans, the definitive host, then ingest viable cysts when eating undercooked meat and develop Taeniasis.  Human intestinal cysticerosis is generally asymptomatic; however, when humans acquire the larval stage through the ingestion of eggs, neurological problems develop. 

Dr. Gonzalez argued that continual porcine infection reflects the poor development state of endemic areas, and that the only long-term sustainable solution and control strategy to eradicate this infection is to improve development.  Dr. Gonzalez supports this argument by stating the failure of the World Health Organization’s strategy: slaughterhouse control, which lacks sustainability and only removes 3% of cases.  Other tested control strategies included mass human chemotherapy, which decreased prevalence but lacked sustainability; health education; and immunotherapy.  Other alternatives included pig treatment, pig corralling, pig vaccination, pig re-population, and refinement of how meat is processed.  Examples of Peruvian methods involved killing the tapeworm and treating infected pigs, a solution that included both medical doctors and veterinarians, yet still showed no success.  Nonetheless, this collaboration between professionals was later key to the elimination of T. solium.  

However, research results noted a matched interval incidence pattern that occurred for both control and intervention areas, suggesting an unknown variable or mechanism of transmission.  A simulation model was developed, and it was concluded that the control methods mentioned above are not sustainable because T. solium returns to endemic stability after only two years following control interventions.    

Dr. Gonzalez aimed to develop and evaluate a new control strategy based on serologic identification, mass targeted chemotherapy, and evaluation of efficacy.  His research, and work with the board of the Cysticerosis Working Group in Peru, is responsible for transmission interruption of T. solium in an area with 100,000 inhabitants.  This control strategy involved the collaboration of veterinarians and medical doctors and provides an ideal example of a successful One Health type approach.  The team eliminated cysticerosis using 4 rounds of Oxfendazole on pigs and two rounds of human chemotherapy with 142 days between human interventions. 

GIS technology was used to further examine two rural Peruvian villages.  The data revealed that 35% of pigs were infected with Spiruroid nemotodes (Ascarops strongylina), a pig parasite which utilizes dung beetles as an intermediate host.  The odds of the pigs having viable cysts increased nearly four times in pigs with Ascarops strongylina compared to those without.  Additional evidence for dung beetles as a potential source of the infection came from the discovery that T. solium eggs were found to remain viable in the dung beetle’s intestine for at least one week following ingestion.  Dr. Gonzalez noted that T. solium proglottids do not move and are very sticky; therefore this discovery is crucial to understanding the dispersion and transmission of cysticerosis.  Additionally, only a small number of alpha male pigs consume human feces, which indicates that another dispersion route in addition to pigs consumption was involved.

If this is true and invertebrates are involved, Dr. Gonzalez argued that control and elimination activities will not change.  However, this knowledge will be taken into account for more intensive veterinary inspection, corralling, diagnostic inspections, and tongue examinations. Dr. Gonzalez concluded his talk by arguing the importance of a multidisciplinary approach that involves medical doctors, veterinarians, biologists, mathematicians, entomologists, sociologists, and environmentalists to solve not only parasitic diseases, such as cysticerosis, but many health problems that plague the world.

Blog Post authored by: Emma Seagle (UNC)

From 2/3 to One Health: an MD’s Perspective. Tuesday January 14th

The One Health Discussion series continued this year with Peter Rabinowitz, MD, MPH who is an Associate Professor in the Department of Environmental and Occupational Health Science and the Department of Global Health at the University of Washington, where he directs the Human Animal Medicine Project. http://deohs.washington.edu/hamp/  He completed a Family Medicine residency at UC San Francisco and a fellowship in General Preventive Medicine/Occupational and Environmental Medicine at the Yale School of Medicine. 

The Human Animal Medicine Project explores the linkages between human, animal, and environmental health including zoonotic infectious disease at the human-animal interface, animals as ‘sentinels’ of environmental health hazards, and clinical collaboration between human health care providers and veterinarians in a species-spanning approach. A goal of the Project is to serve as an incubator and organizer of research, training, and clinical activities at the University of Washington related to the human-animal-ecosystem interface.

Dr. Rabinowitz began the discussion by providing a working definition: “One Health (formerly called One Medicine) is dedicated to improving the lives of all species—human and animal—through the integration of human medicine, veterinary medicine and environmental science.”  He provided a history of One Health through examples from Virchow, Osler, and Schwabe.

Dr. Rabinowitz emphasized the emerging and reemerging infections from vector-borne or zoonotic means.  He explained the intensification of agriculture, resulting in large farms of pigs and chickens, with chickens reaching numbers into the 20 billion. He also noted how deforestation and changing water resources are changing the global environment. He emphasized how 50% of US households have pets, with most pets being in households with children.

It was noted how the concept of ‘One Health’ has gained endorsements from the WHO, CDC, USDA, OIE, FAO, AMA, AVMA, CPHA, NCCID, and the Gates Foundation.  It spans the concepts of individual health, population health, and ecosystem health encompassing Zoonotic infections along with Comparative Medicine/Translational Medicine.

He endorsed the book “Zoobiquity: The Astonishing Connection Between Human and Animal Health” by Barbara Natterson-Horowitz and Kathryn Bowers.

Dr. Rabinowitz noted the disparity of One Health Programs, which are more prevalent in Veterinary schools than Medical schools.

Several case presentations were made.  The first involved a dog with a mass in his spinal column and its owner with non-specific gastrointestinal symptoms that progressed to altered mental status and fever of unknown origin.  A discussion ensued from all fields as to the differential and appropriate course of care.  Quite quickly, a differential of Rocky Mountain Spotted Fever was offered and a review of the pathophysiology was covered.  In the case example, the Veterinarian received the diagnosis from the CDC through pathology and conveyed the information to the Physician resulting in the corrected treatment and resolution of symptoms. A discussion followed as to how the case could have been handled more efficiently and effectively.  Most discussion focused on developing a better monitoring infrastructure and communication network.

A second case was presented involving a pregnant woman with cats exhibiting anorexia, dehydration, ataxia, tremor, and hypersalivation for 3 weeks which was ineffectively treated with an H2 blocker for reflux. The cats where admitted to a veterinary hospital where they were found to be anemic with lead levels that was lethal to one of the cats even after chelation therapy.  The pregnant woman was instructed to follow-up with her own doctor and was found to have a lead level of 40mcg/dL. It turned out that she was stripping old paint with a blowtorch while preparing her house for the baby.  A discussion ensued as to how animals can act as sentinels and how the case could have been handled differently.  The conversation focused on better avenues of communication.

There was an emphasis on barriers to One Health including the following:  Professional Segregation, ‘Us vs Them’ attitude, need for evidence, training structure, time needed for paradigm shifts, and location.   There should be a shift from an ‘Us vs Them’ mentality to a ‘Shared Risk’ viewpoint.

The cases were reviewed with this vantage point with a postulated shared electronic medical record that would be able to alert an MD for a possible differential prompting a quicker diagnosis and treatment with cost savings.

New Competencies for Human Health were suggested including:

• Understanding of shared environmental risks
• Including veterinarians in health care
• Ability to interpret comparative medical information
• Awareness of the role of zoonotic infection in both acute and chronic disease; including smoldering infection
• Awareness of the relevance of a shared microbiome

There was emphasis on developing evidence for clinical relevance of animal disease events to humans through retrospective review of veterinary medical charts.  The example of feline asthma was given as sentinels of air quality.

The session concluded with reference back to the Human Animal Medicine Project and the Zoobiquity conference in Seattle. http://zoobiquity.com/events/upcoming-events/

Post authored by Johann Hsu, MD