Blastomyces Dermatitidis Exposure Protocol

Organism or Agent:

Blastomyces dermatitidis

Exposure Risk:

Blastomycosis  

UCSF Occupation Health:

415-885-7580 (work hours, 8am to 5pm)

Exposure Hotline: 415-353-7842 (24 hours)
Environment, Health & Safety:

415-476-1300 (work hours)

UCSF Police Department;

415-476-1414 or 9-911 (In case of emergency, 24 hours)

EH&S Public Health Officer:
415-514-3531  (work hours)
Campus Bio-Safety Officer 415-514-2824
California Poison Control: 800-222-1222

SFDPH Emergency Number

415-554-2830

CDC Emergency Operation

770-488-7100

Occ Hlth Proto Button

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In the event of an accidental exposure or injury, the protocol is as follows:

1. Modes of Transmission:

  1. Skin puncture or injection
  2. Ingestion
  3. Contact with mucous membranes (eyes, nose, mouth)
  4. Contact with non-intact skin
  5. Exposure to aerosols
  6. Respiratory exposure involving inhalation of the mold form

2. First Aid:

  1. Skin Exposure, immediately go to the sink and thoroughly wash the skin with soap and water. Decontaminate any exposed skin surfaces with an antiseptic scrub solution.
  2. Skin Wound, immediately go to the sink, wash thoroughly the wound with soap and water, pat dry
  3. Splash to Eye(s), Nose or Mouth, immediately flush the area with running water for at least 5-10 minutes.
  4. Splash Affecting Garments, remove garments that may have become soiled or contaminated and place them in a double red plastic bag.

3. Treatment:

  1. In the event of an acute injury resulting from a laboratory incident which requires immediate medical care, the injured employee/student should report to the emergency department for medical treatment. The injured individual must take a copy of this entire exposure protocol document to the Emergency Department, including information regarding the specific strain associated with exposure.
  2. In the event of exposure, with or without an injury requiring immediate medical care, call the Exposure Hotline in order to get access to medical care specific to the exposure. The hotline responder will provide guidance to the injured individual on necessary medical treatment and post exposure follow-up. 

4. Follow up is needed in the event of any Laboratory Exposure:

  1. After first aid has been administered, immediately inform your supervisor of the exposure.
  2. In the event of a large spill, contact the emergency response team (9-911) for clean-up.
  3. Contact Occupational Health Services, after first aid is complete, for follow-up care.
  4. Contact the Biosafety Officer at 415/514-2824 to report the injury or exposure.

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Roles and responsibilities after an accidental exposure:

1.  WORKER’S RESPONSIBILITIES (Employee/Student Initial Self-Care)

  1. First Aid: Perform the recommended first aid and decontamination according to the posted instructions.
  2. Treatment: i) In the event of an acute injury resulting from a laboratory incident which requires immediate medical care, the injured individual should report to the Emergency Department for acute medical treatment. ii) In the event of an exposure, with or without such an injury, call the Exposure Hotline in order to get access to medical care for the exposure and evaluation for possible post exposure prophylaxis.
  3. Access to the Exposure Hotline:
     Call the Exposure Hotline in order to get access to medical care for the exposure. Dial 415 /353-7842, and provide your name and contact information to the operator. If there is no call back in 15 minutes, call again.  If there is no call back the second time, proceed to the nearest Emergency Department with a copy of this protocol.
  4. Reporting: Inform your laboratory supervisor / principal investigator of the exposure. Complete an Employee Incident Report Form (http://ucsfhr.ucsf.edu/files/EIR.pdf). 
  5. Secure the laboratory: Identify the equipment involved in the exposure and the mechanism of exposure. Make sure that the laboratory area has been secured and that notification of contamination has been posted to prevent other individuals from entering the area. 
  6. Follow up: Students and workers should contact Occupational Health Services (OHS) at 415 / 885-7580 for any needed follow up care.

2. SUPERVISOR’S/PI’S RESPONSIBILITIES 

  1. First Aid and Decontamination: Verify that the worker has washed and decontaminated himself/herself. Ensure that appropriate medical treatment has been received.
  2. Secure the laboratory: Confirm that the laboratory area has been secured and that notification of contamination has been posted to prevent other individuals from entering the area.
  3. Laboratory clean-up (as needed): Contact the Office of Environmental Health & Safety (OEH&S) through the UC Police Department Emergency Dispatch (from a campus telephone 9-911, from a non-campus phone 415/476-1414).
  4. Report the exposure: Call the Biosafety Officer at 415/514-2824 during regular hours to discuss the exposure. A report summarizing any suspected Blastomyces exposure needs to be submitted to the Biosafety Committee by the Principal Investigator (PI). The report must include the following
  • A brief description of the exposure event, a description of the area involved, and the extent of employee exposure
  • If applicable, specification of the amount of infectious material released, time involved, and explanation of procedures used to determine the amount involved
  • Corrective action taken to prevent the re-occurrence of the incident
  • Blastomyces decontamination procedures

e. Follow Up: Confirm that the worker has called for an appointment at the UCSF Occupational Health Clinic.
f. Report the Injury: Within 24 hours, report the injury to the UCSF Human Resources Disability Management Services (HR DMS) Office on the Supervisor’s Report of Injury (SRI) form, available here:

http://www.cdc.gov/biosafety/publications/bmbl5/index.htm

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Infectious Substance Data Sheet  Blastomyces dermatitidis

SECTION I – Infectious Agent

Organism or Agent: Blastomyces dermatitidis

Synonym or Cross Reference: Blastomycosis

Characteristics: Dimorphic fungus, mold form in soil, yeast form in animals and human hosts

SECTION II – Recommended Precautions

  • Containment Requirements: Biosafety level 2 practices, safety equipment and facilities for specimens or cultures known or suspected to contain the yeast form. Biosafety level 3 practices, safety equipment and facilities for specimens known or suspected to contain the mold form. ABSL-2 practices, containment equipment and facilities for activities involving animals experimentally infected with the yeast form. ABSL-3 practices, containment equipment and facilities for activities involving animals experimentally infected with the mold form.
  • UCSF Required Personal Protective Equipment: BSL2 practices for work with the yeast form. BSL 3 procedures for work involving the mold form. Use personal protective equipment standards as detailed in the Biosafety Use Authorization (BUA).

SECTION III – Handling Information

  • Spills: Allow aerosols to settle; wearing protective clothing, gently cover spill with paper towel and apply 10% bleach (0.5% sodium hypochlorite) solution, starting at perimeter and working towards the center; allow sufficient contact time (30 min) before clean up.
  • Disposal: Decontaminate waste contaminated with known or suspected B. dermatitidis in the mold form before disposal. Dispose as biohazardous waste.
  • Storage: Store in sealed containers that are appropriately labeled.

SECTION IV – Health Hazards

  • Pathogenicity: Symptomatic infection usually presents as a flu-like illness with fever, chills, productive cough, myalgia, arthralgia and pleuritic chest pain. Some patients fail to recover and develop chronic pulmonary infection or widespread disseminated infection (affecting the skin, bones and genitourinary tract in particular). Blastomycosis can also occasionally affect the central nervous system, resulting in meningitis.
  • Epidemiology: Blastomyces dermatitidis is found in parts of the south-central, south-eastern and mid-western United States. Microfoci are also found in Central and South America and parts of Africa. The fungus can be found in moist soil enriched with decomposing organic debris.
  • Host Range: Humans and canines are most commonly affected, but other animals, such as cats, horses, tigers, snow leopards, lions, and sea lions may also develop the disease.
  • Infectious Dose: Unknown.
  • Modes of Transmission: Inhalation of airborne conidia; small size of infective conidia (< 5 µm) is conducive to airborne dispersal and intrapulmonary retention. The spores of B. dermtitidis are of a respirable size.
  • Incubation Period: Symptoms may appear between 3 and 15 weeks after exposure.
  • Communicability: Not transmitted from person-to-person.

SECTION V – Viability

  • Drug Susceptibility: Susceptible to itraconazole, voriconazole, amphotericin B, and amphotericin B deoxycholate.
  • Susceptibility to Disinfectants: Susceptible to sodium hypochlorite, peracetic acid, phenolic compounds, quaternary ammonium compounds, hydrogen peroxide vapor (for at lest 30 min), formaldehyde, formalin, and iodophors.
  • Physical Inactivation: Inactivated by moist heat (121° C for at least 15 min).

FOR THE USE OF THE EXPOSURE HOTLINE

SECTION VI – Medical

  • Surveillance: Monitor for symptoms. Diagnosis can be made by microscopic visualization and culture of the organism. Thick-walled, figure-of-eight shaped, broad-based, single-budding yeast forms may be seen in sputum, tracheal aspirates, cerebrospinal fluid, urine, or material from lesions processed with 10% potassium hydroxide or a silver stain. An enzyme immunoassay (EIA) is available for detection of B. dermatitidis antigen in urine, blood, and other body fluids. EIA measures cell wall-derived antigen in serum or urine with good sensitivity, particularly in the setting of severe or disseminated disease, but cross-reactions may occur with other endemic fungal infections.
  • First Aid/Treatment: Itraconazole is the preferred drug for prophylaxis.
  • Immunization: None.
  • Prophylaxis: Evaluate all exposures for prophylaxis. Prophylaxis should be started the day of exposure, but can be started up to 3 weeks after acute exposure. The rationale for this is that most severe cases would likely produce symptoms within 3 weeks.
  • Prophylaxis Recommended For:
  1. Significant inhalational exposure to spores/conidia.
  2. Percutaneous injury with Blastomyces, or materials contaminated by Blastomyces.
  3. Mucous membrane exposure with Blastomyces.
  • Prophylaxis Considered For:
  1. Potential inhalational exposures to spores/conidia in individuals with risk factors for development of systemic disease.
  2. Potential mucous membrane exposure to either form of Blastomyces.
  • Prophylaxis Not Recommended For:
  1. Intact skin exposure associated with the yeast form of Blastomyces, where there is no inhalation or percutaneous or mucous membrane exposure.

Medication: Itraconazole – load with 200 mg TID for three days, then treat with 200 mg once daily, given with food, for 30 days. Provide one week supply of medication. This drug may have significant side effects and multiple drug interactions. Itraconazole is contraindicated in pregnancy. If there is any question regarding early pregnancy, a pregnancy test should be performed before starting prophylaxis.

The person who was exposed will need close follow up in UCSF Occupational Health Services. 

Reporting: All laboratory exposures must be reported to the Biosafety Officer. Any known cases of blastomycosis exposure must be reported to the Public Health Officer. Reporting to the San Francisco Department of Public Health is not required.

SECTION VII – Laboratory Hazards

  • Laboratory-Acquired Infections: At least 11 reported laboratory-acquired infections with two deaths. Blastomycosis has been acquired in the laboratory as a result of transcutaneous inoculation of the yeast form and from inhalation of conidia. Human infection acquired from tissue of infected animals has been reported.
  • Sources/Specimen: Sputum, tracheal aspirates, cerebrospinal fluid, urine, blood, material from lesions, and tissues of infected animals.
  • Primary Hazards: Yeast forms may be present in the tissues of infected animals and in clinical specimens; parenteral inoculation of these materials may cause granulomas. Inhalation of infectious mold conidia in aerosols can also be an infection hazard.
  • Special Hazards: Mold form cultures of B. dermatitidis or soil containing infectious conidia may pose a hazard of aerosol exposure.

FOR THE USE OF THE EMERGENCY DEPARTMENT

SECTION VIII – Emergency Medical Treatment

Treatment Indications: Emergency department treatment will be required for injuries that require immediate medical care. The treatment needs to consist of the following: 1) decontaminate and debride wound, 2) repair wound, 3) consult with infectious disease specialist for high risk exposure, 4) contact the Exposure Hotline to discuss the need to start post exposure prophylaxis, if indicated (see section VI above), and 4) have patient follow up with UCSF-OHS. For significant exposures, baseline labs should be drawn. Serum samples for fungal titers should be submitted. Repeat serology should be performed in two weeks to identify possible conversions. See Appendix II: Diagnostic Tests.

Exposure Indications: In the event of an exposure, with or without an injury, the Exposure Hotline must be called. 

SECTION IX – References

http://www.cdc.gov/fungal/diseases/blastomycosis/

http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/blastomyces-dermatitidis-eng.php

Appendix I. 

CDC/NIH Recommendations for Laboratory Exposure to Blastomyces

OCCUPATIONAL INFECTIONS

Three groups are at greatest risk of laboratory-acquired infection: microbiologists, veterinarians and pathologists. Laboratory-associated local infections have been reported following accidental parenteral inoculation with infected tissues or cultures containing yeast forms of B. dermatitidis. Pulmonary infections have occurred following the presumed inhalation of conidia from mold-form cultures; two persons developed pneumonia and one had an osteolytic lesion from which B. dermatitidis was cultured. Presumably, pulmonary infections are associated only with sporulating mold forms.

NATURAL MODES OF INFECTION

The fungus has been reported from multiple geographically separated countries, but is best known as a fungus endemic to North America and in association with plant material in the environment. Infections are not communicable, but require common exposure from a point source. Although presumed to dwell within the soil of endemic areas, B. dermatitidis is extremely difficult to isolate from soil. Outbreaks associated with the exposure of people to decaying wood have been reported.

LABORATORY SAFETY AND CONTAINMENT RECOMMENDATIONS

Yeast forms may be present in the tissues of infected animals and in clinical specimens. Parenteral (subcutaneous) inoculation of these materials may cause local skin infection and granulomas. Mold form cultures of B. dermatitidis containing infectious conidia, and processing of soil or other environmental samples, may pose a hazard of aerosol exposure.

BSL-2 and ABSL-2 practices, containment equipment, and facilities are recommended for activities with clinical materials, animal tissues, yeast-form cultures, and infected animals. BSL-3 practices, containment equipment, and facilities are required for handling sporulating mold-form cultures already identified as B. dermatitidis and soil or other environmental samples known or likely to contain infectious conidia.

SPECIAL ISSUES: TRANSFER OF AGENT

Importation of this agent may require CDC and/or USDA importation permits. Domestic transport of this agent may require a permit from USDA/APHIS/VS. A DoC permit may be required for the export of this agent to another country.

Taken directly from:

http://www.cdc.gov/biosafety/publications/bmbl5/index.htm

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 Blastomyces Dermatitidis Exposure Protocol for use of Occupational Health Services

APPENDIX II

I. Risks in Laboratory Workers/clinical summary

A. Overview

Blastomyces dermatitidis is a thermally dimorphic fungus. It grows both as a yeast phase and a mold phase that undergoes sporulation. Blastomycosis is acquired by inhalation of the spores of the organism. Some of the spores (also called conidia) are less than 5 microns in size, and may form an infective airborne aerosol when culture material or contaminated soil is disturbed. All work with the mold phase is performed in a BSL 3-level lab. The yeast form requires BSL 2-level protection and exposure to the yeast form may produce local infection. However, the potential for severe infection exists in the event of a BSL 3 laboratory accident. Workers in the lab will be aware when such an event occurs, and will present at the Emergency Department for evaluation.

Host defenses are overwhelmed by exposure to high concentrations of the organism. Those individuals with any form of immune system compromise are especially susceptible to severe infections. Any exposed employee with defective cell mediated immunity is at greatly increased risk of disseminated disease. Severity of disease is determined both by the number of organisms inhaled and immune status.

B.  Diagnostic Tests

See Bariola et al., Diagnostic Microbiology and Infectious Disease 69 (2011) 187–191. In the event of an exposure or suspicious symptoms, it is important to draw serum samples for fungal antigen titers. Additionally, an assay for detection of B. dermatitidis antigen in urine is commercially available (MiraVista Diagnostics, Indianopolis, IN). This assay has recently been modified to allow quantitative measurement of detectable antigen. However, there is still a high degree of cross-reactivity with Histoplasma capsulatum.

C. Prophylaxis 

With known airborne exposures in the BSL 3 lab, itraconazole prophylaxis is recommended. Prophylaxis is especially important in the event of exposure to high titers of organisms, which is more likely to result in symptomatic disease. The regimen for post exposure prophylaxis with itraconazole is 200 mg TID for three days as a loading dose, then 200 mg once daily, with food, for 30 days. The medication is sometimes given with Classic Coke. Low pH aids solubilization of the capsule, and improves absorption. Patients should avoid medications that increase pH. If the suspension is used, it should be taken on an empty stomach and does not require low pH. This is based on a paper by McKinsey DS, Wheat LJ et al –PMID: 10452633. Even a short course of itraconazole of 2 weeks would likely provide substantial benefit, if side effects are tolerated. The most common side effect is GI upset. 

Significant warnings exist for patients with a history of cardiac disease and hepatic insufficiency according to Mosby’s Drug Consult. Itraconazole should not be given to pregnant women or women who plan to become pregnant while taking the medication. In addition, there is a list of contraindications, warnings, and drug interactions that should be reviewed. 

D. Risk Factors

Any decrease in cell-mediated immunity puts individuals at risk for severe sequelae of Blastomyces infection.

II. Discharge Instructions for the Patient Exposed to Blastomyces dermatitidis

A.  Background Information

Blastomyces dermatitidis is a fungus. It grows both as a yeast and a mold that can become airborne as spores. The disease of Blastomycosis can be acquired by inhalation of the spores produced by the mold form. The disease can also be produced in animals by direct injection or mucous membrane exposure to either the yeast or mold forms. If you have worked in the BSL 2 lab, you have had contact with the yeast form, which could result in a local infection if you have had an accident. If you have worked in a BSL 3 lab, you have had contact with the mold form, and the potential for severe infection exists in the event of a BSL 3 laboratory accident. Therefore, the physician recommendation is that you take anti-fungal medication for a month following an exposure to prevent severe infection. 

Those individuals with any form of immune system compromise are especially susceptible to severe infections. Most disease is self-limited and the time of onset of symptoms varies with the severity of exposure. 

B. Medication

With known airborne exposures in the BSL 3 lab, the medication itraconazole is recommended. Prophylaxis is especially important in the event of exposure to a high volume of organisms because this is more likely to result in symptomatic disease. 

You will be given anti-fungal medication itraconazole 3 times a day for 3 days, then once a day for 30 days. If you develop symptoms of the disease, you may have to take the medication for 3 months, and for severe disease, for up to a year. The medication is sometimes given with food and Classic Coke. This helps absorption.

Preventive medication should be started the day of exposure, but can be started up to 3 weeks after acute exposure. The rationale for this is that most severe cases would likely produce symptoms within 3 weeks. You should not take the medication if you are pregnant or are planning to become pregnant.

C. Side Effects

The most common side effects include: skin rash and digestive system problems (such as nausea, bloating, and diarrhea). It is important that you report this to your provider. If you develop tingling or numbness in your hands or feet, call your provider right away. If you become unusually tired, lose your appetite, or develop nausea, vomiting, a yellow color to your skin or eyes, dark colored urine, or pale stools, call your provider. In rare cases, this medication may cause serious liver problems and these could be the warning signs. (Taken from Janssen Pharmaceutical products, Patient Information) 

Stop the medication and call your provider right away if you develop shortness of breath, have unusual swelling of the feet, ankles or legs, suddenly gain weight, are unusually tired, cough up white or pink phlegm, or have unusual fast heartbeats. In rare cases, patients taking this medication could develop serious heart problems, and these could be warning signs of heart failure. 

D.  Follow Up 

It is important that you report as soon as possible to Occupational Health Services (415/885-7580) for follow up and workers’ compensation evaluation. For patients receiving medication, follow up will be conducted at 1, 3-6, and 8-12 weeks after exposure in the Occupational Health clinic at Mount Zion. This will include symptom review, assessment of your medical status, and repeat blood tests at 3-6 weeks after initial exposure and at 3 months after exposure. In case of development of flu-like symptoms, patients should return immediately for reevaluation. In the event that you think you may be pregnant, stop taking itraconazole and go to the Occupational Health Clinic at Mount Zion.