CDC Update

British Columbia, Canada, and the Pacific Northwest of the UnitedStates. Appl Environ Microbiol. 2007;73:1433-1443.

7. Upton A, Fraser JA, Kidd SE, et al. First contemporary case ofhuman infection with Cryptococcus gattii in Puget Sound: evidencefor spread of the Vancouver Island outbreak. J Clin Microbiol.2007;45:3086-3088.

8. Sorrell TC. Cryptococcus neoformans variety gattii. Med Mycol.2001;39:155-168.

9. Fyfe M, MacDougall L, Romney M, et al. Cryptococcus gattiiinfections on Vancouver Island, British Columbia, Canada:emergence of a tropical fungus in a temperate environment. CanCommun Dis Rep. 2008;34:1-12.

COMMENTARY

[Ann Emerg Med. 2011;57:62-63.]

Emergency physicians are the front-line providers fordiagnosis and initial empiric treatment of meningoencephalitis.The diagnosis of subacute central nervous system infections isoften difficult, and additional consideration of these infections isgiven to patients with impaired immune function. For example,meningitis caused by C neoformans would be a consideration inan HIV-infected patient with a new or unusual headache. Theemergence of C gattii in the Pacific Northwest represents aconcerning challenge to this approach because C gattii primarilyaffects nonimmunocompromised individuals and is associatedwith serious morbidity and mortality.1

Cryptococcus gattii is an encapsulated yeast that has beencultured from eucalyptus trees exported from Australia toCalifornia and the Pacific Northwest.2 Fungal spores arereleased into the environment and come into direct contact withthe human nasal passageway through contaminated soil and air.Cryptococcus gattii infections in humans typically begin asprimary pulmonary infection from spore inhalation, leading topneumonia and pulmonary cryptococcomas. The primaryinfection disseminates in the blood to other organs, includingthe central nervous system (CNS) and causesmeningoencephalitis or brain cryptococcomas.3

Cryptococcomas represent infectious granulomas of denselyconcentrated cryptococcal organisms. They are commonly seenin the lung, brain, and soft tissues. Because C gattii primarilyaffects immunocompetent individuals, it is believed that thesehealthy hosts are able to contain the foci of infection intogranulomas by immune response. Cryptococcus gattii–infectedhealthy hosts thus have higher prevalence rates ofcryptococcomas, particularly in the lung and CNS. Theselesions have significant effect on patient symptoms andsubsequent management because they are more indolent andless responsive to therapy. Cryptococcomas represent space-occupying lesions and can lead to localized pneumonia orabscesses in the lung and obstructing hydrocephalus or abscessesin the brain.

The clinical course of C gattii infection resembles Cneoformans infection. Patients present with a vague constellationof symptoms related to constitutional, pulmonary, central

nervous, and gastrointestinal systems during weeks to months.

62 Annals of Emergency Medicine

The most common symptoms in this report were cough,headache, dyspnea, nausea, and fever. In British Columbia,90.8% of C gattii–infected persons sought treatment for arespiratory syndrome with or without neurologic findings.3 Incontrast, an Australian study showed that 85% of Cgattii–infected patients had meningitis, and 59% of patientspresented with headache.4 The most common clinical findingsin this report were pneumonia, meningitis, lungcryptococcomas, brain cryptococcomas, and encephalitis,consistent with those of other studies.1,3,4 Thus, the emergencyphysician should suspect a C gattii infection in patients whohave had exposure to an endemic area and a slow indolentcourse of symptoms with pulmonary and CNS findings. Correctdiagnosis is important, as evidenced by the extremely highmortality rate observed in this study; 20% (1 of 5 patients) dieddirectly from C gattii infection, and 13% (1 of 8 patients) diedas a result of other complicating factors. Taken together, 33%(1 of 3 patients) died in this study directly or indirectly becauseof C gattii. In previous studies, abnormal mental status atpatient presentation is a poor prognostic indicator of mortality.5

Radiologic imaging can be extremely helpful to theemergency physician for the diagnosis of C gattii lung and brainmanifestations. Chest radiography or contrast computedtomography (CT) can show single or multiple pulmonarynodules, segmental or lobar consolidation, or a reticulonodularpattern of opacities. Furthermore, pulmonary cavitations,lymphadenopathy, or pleural effusions may also be present.6

Contrast CT scan or magnetic resonance imaging (MRI) of thebrain can show hydrocephalus, abscess, or ring-enhancinglesions representing brain cryptococcomas.7 Diagnosis ofpulmonary and brain cryptococcomas will have implications forantifungal medications and medical versus surgical treatment.

For the emergency physician, initial management andtreatment for C gattii will be similar to that of treatment for Cneoformans, with special attention to sepsis care if the patientclinically meets criteria. Historical questions should includetravel history to endemic areas and clinical symptoms previouslymentioned. Laboratory investigations should include bloodculture and cerebrospinal fluid analysis. India ink staining of thecerebrospinal fluid can quickly identify the presence of thecryptococcal polysaccharide capsule, which appears as a haloaround the organism. Cryptococcal antigen tests of blood andcerebrospinal fluid are more sensitive than India ink staining,but results may not be immediately available. The cryptococcalantigen test will not differentiate C gattii from C neoformans butwill be helpful to support the diagnosis. Initial diagnosticimaging should include chest radiography and CT of the brain.

The Infectious Diseases Society of America has justpublished its 2010 updated clinical practice guidelines for themanagement of cryptococcal disease.7 It specifically highlightsnew recommendations for management and treatment of Cgattii. For the emergency physician, the following are relevantclinical recommendations: (1) for CNS and disseminated

disease caused by C gattii, induction treatment is the same as for

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CDC Update

C neoformans; (2) more diagnostic focus by radiology andfollow-up examinations are needed forcryptococcomas/hydrocephalus caused by C gattii than thatcaused by C neoformans, but the management principles are thesame; (3) for pulmonary cryptococcosis, single, smallcryptococcoma can be treated with fluconazole (400 mg/dayorally); for very large or multiple cryptococcomas, consider acombination of amphotericin B and flucytosine therapy withpossible surgery; (4) consider surgery if there is compression ofvital structures or clinical treatment failure; (5) multiplecryptococcomas require prolonged therapy, with or withoutcorticosteroids; and (6) hydrocephalus requires placement of aventriculoperitoneal shunt, combined with antifungal therapy.7

Because C gattii infection is transmitted through the air,spread of this disease to other regions of the country seemshighly plausible. In 2007, North Carolina reported its firstconfirmed case of C gattii. The patient was an otherwisehealthy, non-HIV infected man found to have a thighcryptococcoma. He had the lesion surgically removed andreceived long-term, high-dose fluconazole therapy. The patientdeveloped seizures 3 months later and presented to theemergency department, where MRI revealed 2 large CNScryptococcomas. On review, previous chest CT imagingrevealed small lung nodules that were thought to be the primarysite of pulmonary cryptococcomas that disseminated to thethigh and CNS. A history of travel to San Francisco, CA,combined with molecular analysis of the C gattii speciesphenotype, revealed a link from an imported AustralianEucalyptus tree.8 This case report further supports the newInfectious Diseases Society of America recommendations forfurther diagnostic imaging once C gattii infection has beendiscovered.

The emergence of C gattii is cause for vigilance in newlyaffected areas. Early recognition and treatment may improvemorbidity and mortality. Emergency physicians should

recognize that this subacute infection often occurs among

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nonimmunocompromised individuals and be aware ofgeographic risk factors, pulmonary and neurologic clinicalpresentations, radiologic findings, and treatmentrecommendations by the Infectious Diseases Society of America.Cryptococcus gattii infections should be reported to the localhealth department to promote continued surveillance andpublic health safety.

Section editors: David A. Talan, MD; Gregory J. Moran, MD;Robert Pinner, MD

REFERENCES1. Byrnes EJ III, Li W, Lewit Y, et al. Emergence and pathogenicity of

highly virulent Cryptococcus gattii genotypes in the northwestUnited States. PLoS Pathogens. 2010;6:1-16.

2. Pfeiffer T, Ellis D. Environmental isolation of Cryptococcus gattiifrom California. J Infect Dis.1991;163:929-930.

3. Galanis E, MacDougall L. Epidemiology of Cryptococcus gattii,British Columbia, Canada 1999-2007. Emerg Infect Dis. 2010;16:251-257.

4. Speed B, Dunt D. Clinical and host differences between infectionswith the two varieties of Cryptococcus neoformans. Clin Infect Dis.1995;21:28-34.

5. Mitchell DH, Sorrell TC, Allworth AM, et al. Cryptococcal disease ofthe CNS in immunocompetent hosts: influence of cryptococcalvariety on clinical manifestations and outcome. Clin Infect Dis.1995;20:611-616.

6. Fox D, Muller N. Pulmonary cryptococcosis in immunocompetentpatients: CT findings in 12 patients. AJR Am J Roentgenol. 2005;185:622-626.

7. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practiceguidelines for the management of cryptococcal disease: 2010update by the Infectious Diseases Society of America. Clin InfectDis. 2010;50:291-322.

8. Byrnes EJ III, Li W, Lewit Y, et al. Cryptococcus gattii in thesoutheastern USA: implications for travel-associated acquisition ofan emerging pathogen. PLoS One. 2009;4:1-12.

doi:10.1016/j.annemergmed.2010.11.003

Annals of Emergency Medicine 63