Cladophialophora bantiana: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Cladophialophora bantiana

Agent type

Fungi

Taxonomy

Family

Herpotrichiellaceae

Genus

Cladophialophora

Species

Cladophialophora bantiana

Synonym or cross-reference

Previously named Torula bantiana, Cladosporium trichoides, Cladosporium trichoides var. chlamydosporum, Cladosporium bantianum, Xylohypha bantiana, Xylohypha emmonsii, and phaeophyphomycosis^{Footnote 1Footnote 2Footnote 3}.

Characteristics

Brief description

C. bantiana is a dematiaceous, neurotropic fungus. Its brown/black appearance is due to dihydroxynaphthalene melanin in its cell wall^Footnote 4. Conidia are oval-shaped, 1-5 μm x 1-2 μm, and form long, sparsely branched chains^{Footnote 5Footnote 6}. The DNA genome is approximately 37 Mbp in length^Footnote 5.

Properties

Production of heat-stress proteins enable survival and growth of C. bantiana at temperatures up to 42 °C^Footnote 7. C. bantiana produces melanin, which provides protection against oxidative stress, and may play a role in crossing the blood-brain barrier^Footnote 8. The C. bantiana genome encodes several enzymes (e.g., superoxide dismutases, catalases) that neutralize reactive oxygen species, protecting the fungus against the host's immune response^Footnote 5.

Section II – Hazard identification

Pathogenicity and toxicity

The majority of C. bantiana infections affect the central nervous system (CNS), usually the brain, causing cerebral phaeophyphomycosis^{Footnote 3Footnote 9}. Clinical characteristics of brain abscess due to C. bantiana include headache (56%-58%), hemiparesis (17%-54%), seizure (29%-32%), nausea and vomiting (22%), and fever (22%)^{Footnote 3Footnote 9}. Infection of the meninges has been found in 12-14% of cases^{Footnote 3Footnote 9}. Treatment for cerebral infection due to C. bantiana is often unsuccessful; the mortality rate is approximately 65%^Footnote 3. Duration of illness can range from 16 days to 7 years^Footnote 9. Recurrence of cerebral infection has been reported 2-6 months post-treatment^Footnote 9.

C. bantiana can also cause cutaneous or subcutaneous infection^{Footnote 9Footnote 10}, pulmonary infection^Footnote 9, sinusitis (1 case)^Footnote 11, septic arthritis (1 case)^Footnote 12, osteomyelitis (1 case)^Footnote 13, and systemic disease affecting multiple organs. In some cases, infection can remain localized without dissemination to the CNS^{Footnote 5Footnote 8}.

Rare instances of C. bantiana infections in animals including horses, cats, and dogs have been reported^Footnote 14. Infections are usually fatal; and often animals are euthanized before they succumb to infection^Footnote 14. C. bantiana has been implicated in equine rhinitis and sinusitis^Footnote 15, and equine endometritis^Footnote 14. Localized infections without CNS involvement, CNS infections, and systemic C. bantiana infections have been described in cats and dogs^Footnote 14.

Epidemiology

C. bantiana is found worldwide. Less than 200 cases of cerebral infection due to C. bantiana have been reported to date in 26 countries, including Canada^{Footnote 3Footnote 9}. Of these, 32% of cases were reported in India and 24% in the United States^Footnote 9. Men are affected more frequently than women^{Footnote 3Footnote 9}.

Fewer than 20 cases have been reported for cats and dogs^Footnote 14. Equine infections due to C. bantiana are rare^{Footnote 14Footnote 15}.

Brain abscess due to C. bantiana affects both immunosuppressed and immunocompetent individuals^Footnote 3. However, the mortality rate is higher for individuals with compromised immune status (e.g., organ transplant recipients, corticosteroid users) (77%) compared to immunocompetent individuals (56%)^Footnote 3.

Host range

Natural host(s)

Humans, horses^Footnote 14, cats^Footnote 14, dogs^Footnote 14, snow leopards^Footnote 16, and alpacas^Footnote 17.

Other host(s)

Mice, rabbits, and guinea pigs have been experimentally infected^{Footnote 9Footnote 18}.

Infectious dose

Unknown.

Incubation period

Approximately 3 to 8 weeks, but can be several years depending on infection route and dose. Shorter incubation periods occur when the infection site is closer to the brain or CNS regions, whereas longer incubation periods occur when infection sites are at a distance from the CNS^{Footnote 9Footnote 19}.

Communicability

C. bantiana can be transmitted via penetrating trauma where the fungus is inoculated directly into tissue^{Footnote 9Footnote 20}. Inhalation of airborne conidia is suspected of being the main route of transmission^{Footnote 9Footnote 18}.

Section III – Dissemination

Reservoir

No animal reservoir has been identified. Environmental sources of C. bantiana are also not well established. C. bantiana has been isolated on rare occasions from soil, tree bark, and brick surfaces^{Footnote 21Footnote 22Footnote 23}.

Zoonosis

While C. bantiana can cause infection in both humans and animals, transmission from animals to humans, or from humans to animals, has not been documented to date.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Amphotericin B; 5-flucytosine; azoles (e.g., voriconazole, fluconazole, itraconazole, isavuconazole, posaconazole, ketoconazole)^{Footnote 5Footnote 13}; and echinocandins (e.g., caspofungin, anidulafungin, micafungin) have been used in the treatment of C. bantiana infection^{Footnote 3Footnote 5}. Other azole agents effective in vitro against C. bantiana include Syn-2869^Footnote 24, SCH56592^Footnote 25, and ravuconazole^Footnote 26. Terbinafine was also effective against C. bantiana in vitro^{Footnote 27Footnote 28}.

Susceptibility to disinfectants

The susceptibility of C. bantiana to disinfectants is unknown. Other dematiaceous fungi are susceptible to chlorine (1%), biguanide (e.g., chlorhexidine) and quaternary ammonium compounds (e.g., benzalkonium chloride, cetrimide)^{Footnote 29Footnote 30}.

Physical inactivation

Filamentous fungi are inactivated by moist heat treatment at 121 °C for 30 minutes^Footnote 31. Other melanized fungi are inactivated by gamma radiation treatment^{Footnote 32Footnote 33}.

Survival outside host

Conidia of filamentous fungi can remain viable for prolonged periods. Other filamentous fungi survived after being stored for 12 months in sand^Footnote 34.

Section V – First aid/medical

Surveillance

Diagnosis is accomplished through the monitoring of clinical symptoms. Magnetic resonance imaging or a computed tomography (CT) scan can be used to visualize lesions on the brain^{Footnote 9Footnote 35}. Clinical specimens can be analysed by microscopy, culture, and molecular methods to detect C. bantiana. C. bantiana can be cultured on nutrient agar (e.g., Sabouraud dextrose agar) at 30 °C^Footnote 5. Colonies appear velvety, with gray or brown pigment on the surface and a black underside^{Footnote 5Footnote 14}. Species-level identification can be achieved by PCR and sequencing the internal transcribed spacer region or 18S rRNA^{Footnote 9Footnote 14Footnote 16}. Use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for identification of fungi is being explored, but databases are currently insufficient to identify many clinical species^Footnote 36.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Treatment of C. bantiana infections may involve administration of one or more antifungal drugs^{Footnote 9Footnote 14}. For brain abscesses, surgical excision of the abscess and treatment with one or a combination of antifungal drugs may be recommended^{Footnote 3Footnote 9}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine is currently available.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

None.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

None have been reported to date^Footnote 14.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Biopsy specimens (e.g., brain, nasal, lung, skin), aspirated abscess contents^{Footnote 9Footnote 14}.

Primary hazards

Primary exposure hazards include autoinoculation with infectious material, inhalation of airborne conidia, and exposure of mucous membranes or wounded skin to infectious material.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

C. bantiana is a Risk Group 3 (RG3) human pathogen and RG3 animal pathogen^{Footnote 37Footnote 38}.

Containment requirements

Containment Level 3 facilities, equipment and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment (PPE) and clothing outlined in the CBS to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of infectious material are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and RG4 pathogens, and SSBA toxins in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with C. bantiana require a Human Pathogens and Toxins Licence , issued by the Public Health Agency of Canada^Footnote 38.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations

Last file update

October, 2019

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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