Pathogen Safety Data Sheets: Infectious Substances – Cryptococcus neoformans

Section I - Infectious Agent

Name

Cryptococcus neoformans

Synonym or Cross Reference

C. neoformans var neoformans, cryptococcosis, cryptococcal infections, cryptococci, torulosis, European blastomycosis ^{Footnote 1-Footnote 3}.

Characteristics

C. neoformans is a spherical yeast, 4-6 µm in diameter, that produces a capsule containing glucoronoxylomannan (GXM), extending the overall diameter to 25 μm or more ^{Footnote 4-Footnote 6}. C. neoformans usually has a single bud that pinched off at the mature stage ^{Footnote 4} . C. neoformans may also exist in pseudohyphal form. C. neoformans var neoformans contains serotypes A and D ^{Footnote 1}. C. neoformans can differentiate into several complicated morphological forms, including yeast, chlamydospores, pseudohyphae and hyphae, and is typically present in the yeast form during infections. Small-sized basidiospores (1.8 to 3.0 μm) can turn into yeast cells, the form preferred at 37°C, or can form dikaryotic hyphae which are favoured at 24°C ^{Footnote 8}. This organism exists as a yeast form in the environment ^{Footnote 9}.

Section II - Hazard Identification

Pathogenicity / Toxicity

C. neoformans causes various diseases in immunocompromised and immunocompetent hosts ^{Footnote 10}. Diseases include meningoencephalitis (77.2%), pulmonary cryptococcosis (mostly in immunocompromised hosts, 8.2%), and several other diseases. Disseminated cryptococcosis is a complication and may occur in 91.8% of cases ^{Footnote 11}. Cryptococcosis may be fatal if untreated. Spores or desiccated yeast cells of C. neoformans enter the host respiratory tract by inhalation ^{Footnote 1Footnote 2}. Pulmonary infection disseminates most commonly to the brain and the skin ^{Footnote 2}. C. neoformans can cause systemic infection, including fatal meningitis (meningoencephalitis) in normal, diabetic, and immunocompromised hosts ^{Footnote 13}. The infection from C. neoformans in the brain can be fatal if untreated ^{Footnote 8}.

CNS infection: Cryptococcosis of the CNS presents mostly in the form of acute, subacute, and chronic meningitis, with symptoms of persistent headache, nausea, dizziness, ataxia, impaired memory and judgment, irritability, somnolence, clumsiness, and confusion ^{Footnote 6, Footnote 10}. Patients may or may not have fever, and most have minimal or no nuchal rigidity. As the disease progresses, seizures may occur. CNS infection may also present as a brain abscess (cryptococcomas), subdural effusion, dementia, isolated cranial nerve lesion, spinal cord lesion, and ischaemic stroke. If cryptococal meningitis occurs, mortality rate is between 10-30% ^{Footnote 14}.

Respiratory infection: Pulmonary cryptococcosis may present as cough, dyspnea, blood-streaked sputum, and a dull ache in the chest ^{Footnote 6}. Other respiratory system infections include pneumonia, cavitation, endobronchial masses, empyema, nodules, sinusitis, mediastinitis, bronchiolitis obliterans, and pneumothorax ^{Footnote 10}.

Cutaneous infection: Skin lesions may be single or multiple and commonly begin as painless lesions of the face or scalp ^{Footnote 6}. Skin lesions may take the form of erythematous or umbilicated papules, pustules, acneiform lesions, indurated plaques, palpable purpura, soft subcutaneous masses, sinus tracts, cellulitis, vesicles, or large ulcers with undetermined edges.

Rarer presentations include lymphadenitis, pancreatitis, hepatitis, peritonitis, oesophagitis, osteomyelitis, septic arthritis, myositis, endophthalmitis, papilloedema, optic nerve atrophy, pyelonephritis, prostatitis, endocarditis, fungaemia, myocarditis, pericaditis, Cushing's syndrome, adrenal insufficiency, adrenal mass lesions, and thyroiditis ^{Footnote 10} .

Epidemiology

There are differences in number of cases in different strains of C. neoformans ^{Footnote 1}. C. neoformans serotypes A and D are distributed worldwide and cause the vast majority of cryptococcal infections, predominately in immunocompromised individuals. Serotype A is responsible for over 95% of cryptococcosis cases worldwide ^{Footnote 1}. C. neoformans serotype A appears to be implicated in 99% of AIDS patients with cryptococcosis worldwide, except in France where serotype A is responsible for around 80% of the infections ^{Footnote 12}. More frequent cases of serotype A and D have been reported in Europe where cryptococcosis is associated with 77% of HIV patients. Cryptococcal meningitis, caused by the fungus C. neoformans, can cause up to 30% mortality in AIDS patients in resource-poor regions such as Southeast Asia ^{Footnote 1}. It is estimated that 6% to 10% of patients with AIDS in the United States, Western Europe, and Australia and 0% to 50% of AIDS patients in sub-Saharan Africa are infected with life-threatening cryptococcal meningitis ^{Footnote 12}. By the 1990s, C. neoformans had become the leading cause of culture-positive meningitis in many regions, including New York City. Cryptococcal meningitis alone kills about 624,000 people each year ^{Footnote 1}.

Host Range

Humans and various domestic and wild animals (e.g., cats, birds) ^{Footnote 1Footnote 7}.

Infectious Dose

Unknown.

Mode of Transmission

Spores are inhaled from the environment as the organism is found in the soil ^{Footnote 1Footnote 15}.

Incubation Period

Unknown, C. neoformans can colonize in the host respiratory tract for months to years without causing any clinical symptoms ^{Footnote 1}.

Communicability

Person-to-person transmission has not been documented other than through transplanted organs ^{Footnote 6}.

Section III - Dissemination

Reservoir

C. neoformans may be found in humans and various domestic and wild animals ^{Footnote 1Footnote 7}. Soil and decaying vegetation is also a reservoir for serotypes A and D ^{Footnote 1}. C. neoformans is associated with various environmental niches, especially avian guano ^{Footnote 1Footnote 9}.

Zoonosis

Although C. neoformans may be encountered in animals, direct transmission from animals to persons has not been proven ^{Footnote 17}.

Vector

None.

Section IV: Stability and Viability

Drug Susceptibility / Resistance

Amphotericin B or itraconazole ^{Footnote 15} with or without flucytosine or flucanazole.

Drug Resistance

C. neoformans can develop resistance to fluocytosine when used alone ^{Footnote 5}.

Suceptibility to Disinfectants

C. neoformans is effectively killed by 70% ethyl alcohol and is susceptible to phenolic compounds, formaldehyde, glutaraldehyde, iodophors, and sodium hypochloride (1%) ^{Footnote 18Footnote 19}.

Physical Inactivation

Photodynamic therapy (PDT), which combines methylene blue (MB) with a low-power red laser can inactivate C. neoformans ^{Footnote 20}. PDT can be performed using 150 μM MB and 100mW red laser with a florescence at 180J/cm2 for 9 min. C. neoformans can be inactivated by UV, microwave, gamma radiation, moist heat (121°C for at least 20 min), and dry heat (165-170°C for 2 h) ^{Footnote 21-Footnote 24}.

Survival Outside Host

Unknown; however, the main reservoir for C. neoformans is the environment, including the soil, bird guano, and trees^{Footnote 1Footnote 9}.

Section V – First Aid / Medical

Surveillance

Monitor for symptoms and confirm by culture and histopathology and serologically. Nested PCR may be used ^{Footnote 4Footnote 5Footnote 15Footnote 25}.

Note: All diagnostic methods are not necessarily available in all countries.

First Aid Treatment

Give appropriate antifungal therapy ^{Footnote 6}.

Immunization

No immunization is currently available^{Footnote 15; however, some vaccines are currently in clinical trials, including GXM conjugated to tetanus toxoid vaccine, which has been shown to be effective in immunocompetent individuals in clinical trialsFootnote 12.}

Prophylaxis

HIV patients may receive antifungal therapy such as fluconazole when no symptoms of infections are present ^{Footnote 9}.

Section VI - Laboratory Hazards

Laboratory Acquired Infections

There is 1 reported case of laboratory exposure to C. neoformans from a laceration by a contaminated scalpel blade ^{Footnote 26}. There are 2 reported cases of eye infections related to surgical procedure from C. neoformans ^{Footnote 9}. Cryptococcosis from a needle puncture to the thumb during blood collection from an AIDS patient with cryptococcal fungemia and two percutaneous cryptococcal inoculations from needlestick have been reported.

Sources / Specimens

C. neoformans may be found in soil, bird guano, blood, urine, and specimens from bone marrow, brain, CSF, eye, respiratory sites, skin, and mucous membranes ^{Footnote 1Footnote 4Footnote 26}.

Primary Hazard

Inhalation of basidiospores and desiccated yeast cells could be infectious for the lab workers and should be regarded as potentially serious airborne hazards ^{Footnote 9}. Accidental parenteral inoculation of infectious materials may also occur ^{Footnote 9Footnote 26}.

Special Hazard

Bites from infected lab mice and manipulation of infectious environmental materials (e.g. pigeon dropping) may be a potential hazard ^{Footnote 26}.

Section VII – Exposure Controls / Personal Protection

Risk Group Classification

Risk Group 2 ^{Footnote 27}.

Containment Requirements

Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures ^{Footnote 28}.

Protective Clothing

Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes ^{Footnote 28}.

Other Precautions

All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities ^{Footnote 28}.

Section VIII – Handling and Storage

Spills

Allow aerosols to settle. Wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at perimeter and working towards the centre; allow sufficient contact time before clean up.

Disposal

Decontaminate all wastes that contain or have come in contact with the infectious organism by autoclave, chemical disinfection, gamma irradiation, or incineration before disposing.

Storage

The infectious agent should be stored in leak-proof containers that are appropriately labelled.

Section IX – Regulatory and Other Information

Regulatory Information

The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

Updated

February 2018

Prepared By

Centre for Biosecurity, Public Health Agency of Canada

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2018
Canada