1. Cryptococcus gattii Fungal Meningitis
By Cassy Hedberg
BI 234

2. “This disease’s deadliest weapon is the fact you’ve never heard of it” -Kausik Datta, Post-doctoral Fellow at Johns Hopkins Medicine
A deadly fungal infection of the lungs and CNS caused by the Cryptococcus gattii fungus has been spreading throughout the west coast of the United States and Canada. The first case was in Canada in 1999 on Vancouver Island. Over 200 cases have been seen there. New cases were showing up in Washington state in the early 2000’s with people who had not traveled to Canada.
By 2004 the first case showed up in Oregon. Environmental testing on soil and trees showed the genetics of C. gattii in Oregon were unique to Oregon, so evidence showed that it didn’t come here from Canada. Here in the Northwest, the genotype VGII has been identified in our soil. Several different strains of the fungus have been discovered in other areas.
This originally was thought to be a tropical or subtropical disease, first found in Australia and SE Asia. There are several theories of how the fungus ended up in the northwest. Some blame it on global warming and the shifting of climate zones.

3. C.gattii, NOT C. neoformans!
If you google just the word “Cryptococcus”, you will find an abundance of information on C. neoformans. This is a different species than C. gattii. C.gattii is a fairly new disease that infectious disease doctors are still researching and learning about. Not a lot of data is available on the disease, so the treatment is still somewhat trial and error.

4. C. neoformans vs C. gattii
C. neoformans is most commonly seen in patients with a compromised immune system, such as with AIDS.
C. gattii is seen in both immunocompromised and immunocompetent people. Immunocompetent people do not already have a primary disease that is weakening the immune system, allowing for the secondary infection. Healthy people can get C. gattii, whereas they do not generally get C. neoformans.
C. gattii is more difficult to treat, requires longer treatment, and is less responsive to anti-fungal drugs.
C. gattii is more likely to cause cryptococcomas (lesions, usually in the brain or lungs caused by the fungus).

5. An Oregon Case Study
A 68 year old woman in good health began to get headaches in January of The headaches gradually became worse. The patient was taking daily maximum doses of ibuprofen and Tylenol by March At the time, the headaches were blamed on migraines caused by arthritis in the neck.
In March 2011, she began to lose balance periodically. Other symptoms noted by family were personality changes like irritability and difficulty making normal daily decisions.
In April 2011 her tailbone and spine started bothering her, making walking difficult. She blamed it on a bad mattress, and bought a new bed. This didn’t help the pain. It got progressively worse. The pain spread up to her neck.

6. By the end of April, the patient was having excruciating migraines, nausea and vomiting, pain in the spine and neck that was debilitating, and mental disorientation coupled with drastic personality changes and irrationality.
Patient presented to either urgent care or the emergency department three different times, after several previous visits to her primary care physician. The third visit to the ED, patient was not responsive, and blood pressure was very low. The patient went into a semi-coma, where she was in and out of consciousness.
Tests administered were x-ray of the lungs, MRI and CT scan of the brain, blood tests, and lumbar puncture to test the cerebral spinal fluid (CSF).
Case Study Cont.

7. Case Study Cont.
Tests found the Cryptococcus genus of fungus in her CSF, along with cryptococcomas in her brain and lung. Species was still unidentified. Immediately, anti-fungal IV medication, Amphotericin B was started. (It took another 6 weeks to culture, grow and identify the Cryptococcus gattii species, a slow-growing fungus.)
After two weeks in the hospital, she was sent home. However, the story does not stop there. It goes on for another year and a half. The illness relapsed three times, each time needing IV anti-fungals plus oral flucytosine administered during a lengthy hospital stays. The patient spent months in the hospital and in rehab.
Other therapies were regular lumbar punctures to regulate CSF pressure, and steroids (Decadron) to control intracranial pressure.

8. Case Study Cont.
Long-term affects of the disease were moderate hearing loss, peripheral vision loss, imbalanced gate, and avascular necrosis (bone loss/death, due to long-term steroid use to reduce brain swelling) in the hip, requiring a hip replacement. Mental status went back to normal after the intracranial pressure was normalized.
The patient in this case study was not just any patient. She was my mom, and is the reason why I am taking this class. She survived, and has inspired me to help other people survive too.
This is a very rare disease. My mom was one of 62 cases in Oregon since 2004, the first recorded case.

9. Important to know:
It’s important to learn more about this disease because some scientists think we are seeing more of this fungus in the Northwest because of climate change. We could see more of this disease in the future. It’s difficult to diagnose, yet time is of essence since the fungus is deadly if left untreated.
About 33% of patients die from this disease.
Long-term effects of the disease can be minimized with early treatment.

11. Reservoirs
C. gattii is an environmental fungus that has been isolated from native trees, soil, air, and water in the Pacific Northwest. In Australia, C. gattii can be found in certain species of eucalyptus trees.
Cryptococcus gattii in Oregon: C. gattii infection was first diagnosed in Oregon in late 2004, and since then a number of human and animal cases have been reported. Since the exposure period can be long, determining exposure location may be difficult. Environmental sampling has also confirmed the presence of the fungus in Oregon.

12. Electron Scanning Microscope image of C. gattii
Cryptococcus gattii is found in the decaying bark of some Douglas fir and Hemlock trees in the Northwest, as well as the soil and water surrounding. When this area is upset, the fungus becomes airborne.

13. Etiologic agent The Cryptococcus spp. are environmental fungi.
C. gattii was previously known as a fungus that was found in tropical or subtropical climates, but an environmental reservoir has recently been recognized in the Pacific Northwest. Animal and human cases appeared in an outbreak on Vancouver Island, British Columbia (BC), Canada, starting in The fungus has subsequently been found in environmental samples on Vancouver Island, mainland BC, Washington State, and Oregon.
C. gattii has caused illness among people as well as in domestic and wild animals, including dogs, cats, ferrets, horses, llamas, sheep, goats and porpoises.
Cryptococcus spp. are saprophytic, encapsulated yeasts. They are Gram-positive and have a spheroid or ovoid shape. There are many species of Cryptococcus, but C. neoformans (varieties neoformans and grubii) and C. gattii are the primary human pathogens of this genus.

14. C. gattii is not transmitted person-to-person or animal-to-person
Incubation Period
Two to 13 months. Pulmonary disease may precede brain infection by months or years.
Communicability
C. gattii is not transmitted person-to-person or animal-to-person
C. gattii spores thrive in soil and grow on tree bark. The spore becomes airborne and is breathed in and lodged deep into the lung tissue.

15. How do I avoid getting cryptococcal disease?
There are no particular precautions that will prevent cryptococcal disease. The benefits of outdoor recreation and activities far outweigh the risks of acquiring cryptococcal disease.
How do I avoid getting cryptococcal disease?

16. What are the symptoms of cryptococcal disease?
Cough that lasts weeks or months
Sharp chest pain
Unexplained shortness of breath
Severe headache
Confusion
Fever
Night sweats
Unintended weight loss

17. Treatment
Cryptococcus gattii needs to be treated aggressively with antifungal medications.
IV medication, Amphoteracin B (there are a few different varieties of this medication) needs to be administered in the hospital under close supervision because of the possibility of allergic reaction in the patient.
This is usually given with flucytosine, taken orally for 4-6 weeks.
Follow-up medication is usually fluconazole, taken for 6-12 months. Voriconazole can be used if the patient relapses after the above regiment.

18. The treatment for C. gattii is dependent on the patients health before they got sick, how soon the disease was caught (early intervention is very important) before treatment was started, and types of medications used and whether they are tolerated by the patient.
In my mom’s case, the disease was well established when she began treatment, thus was on anti-fungal medications for four years.
Treatment cont.

19. In Oregon, Cryptococcus diseases are now reportable, since 2011.

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Datta, K. (2009, August 1). Spread of Cryptococcus gattii into Pacific Northwest Region of the United States.(SYNOPSIS)(Report). Emerging Infectious Diseases.
Perfect, J., Dismukes, W., Dromer, F., Goldman, D., Graybill, J., Hamill, R., Sorrell, T. (2010). Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases CLIN INFECT DIS,

21. Result Filters. (n. d. ). Retrieved July 15, 2015, from http://www
This disease's deadliest weapon is the fact you've never heard of it. (n.d.). Retrieved July 15, 2015, from