HISTOPLASMA CAPSULATUM

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Histoplasma capsulatum

SYNONYM OR CROSS REFERENCE: The teleomorph of Histoplasma capsulatum is known as Ajellomyces capsulatus . Infection by H. capsulatum results in Histoplasmosis^(1,2,3,4). Histoplasma capsulatum has three variants: var. capsulatum, var. duboissii, and var. farciminosum⁽⁵⁾.

CHARACTERISTICS: Histoplasma capsulatum is a dimorphic fungus⁽¹⁾. The filamentous mould form is found in the environment and can be cultured in conditions below 35ºC using general fungal media. When it is present in tissue or grown in cultures, using brain heart infusion agar or brain heart infusion with blood at temperatures greater than 35ºC, it grows to a yeast form, which appear as small oval buds of 2-4 um⁽¹⁾. Macronidia are 8-15 μm and are thick walled with tubercles or projections. The micronidia are 2-4 μm and are smooth walled.

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Infection by Histoplasma capsulatum usually presents as a pulmonary infection that may be transient or chronic. There are a number of clinical forms, including asymptomatic, acute pulmonary, chronic pulmonary, acute disseminated, chronic disseminated, mediastinitis, meningitis, osteomyelitis, and cutaneous infection⁽⁶⁾. Widespread infection (dissemination) throughout the body has resulted in death; however, dissemination usually results in chronic illness^(1,7). Symptoms can appear with in 1 week and include fever, chills, headache, non productive cough, myalgia, chest pain, loss of appetite and fatigue. Infection is usually asymptomatic for low level exposure or mild infections. There is no evidence that mild or asymptomatic infections can induce protective immunity. Interestingly it has been noted that previously controlled infections can become active upon impaired cellular immunity⁽⁸⁾. Higher levels of exposure and more severe infections will result in symptomatic presentations like flu-like symptoms that may persist for several weeks. Visceral infection can lead to the destruction of the adrenal gland. Infection of the CNS will appear as chronic meningitis or focal brain lesions and occurs in 5-20 % of the cases. Var. duboisii causes African histoplasmosis⁽¹⁾. Infection sites are typically the skin and bones and will spread to the liver and spleen if left untreated. Lesion on face and trunk are common. Thirty percent of patients develop osteomyelitis. Arthritis and purulent subcutaneous abscesses can occur when the infection spreads to joints and soft tissue. Var. farciminosum infects horses and mules but not humans⁽⁵⁾. The mechanisms underlying host specificity and tissue tropism remain unknown.

EPIDEMIOLOGY: Histoplasmosis is the most prevalent mycosis in North America and more often reported in the areas surrounding the Mississippi and Ohio rivers⁽¹⁾. Exposure to dust or soil for prolonged periods of time as well as activities which disturb bird and bat guano increase the risk of infection and have also been indicators of localized outbreaks⁽⁹⁾. Approximately 80 % of the general population tested around the Mississippi and Ohio rivers showed hypersensitivity to Histoplasma capsulatum⁽¹⁰⁾. The largest group of affected individuals were young adults⁽¹¹⁾.

Most children presented mild to no symptoms. Immune compromised individuals are at an increased risk of infection, and experience an increased severity of infection and a higher mortality rate⁽¹⁾. Histoplasmosis is also found in Central and South America, Australia, eastern Asia, and the tropical areas of Africa.

HOST RANGE: Histoplasma capsulatum is found in humans and animals, including horses, cattle, sheep, dogs, cats, chickens, rats, skunks and opossum^(1,12,13).

INFECTIOUS DOSE: Under experimental conditions, inhalation of 5 yeast cells resulted in 10 % mice developing infection⁽⁴⁾. Ten spores administered intra-nasally resulted in a 9.2 % mortality rate in mice⁽¹⁴⁾.

MODE OF TRANSMISSION: Infection occurs by inhalation of the micronidia spores^(1,15). Infection can also occur by contact with mucosa or non-intact skin.

INCUBATION PERIOD: Symptoms present 1-3 weeks after initial infection. Upon re- infection, symptoms present in a shorter period of time 4-7 days⁽¹⁾.

COMMUNICABILITY: Not transmitted from person–to-person, except through tissue organ donors and recipient.

SECTION III - DISSEMINATION

RESERVOIR: The primary reservoir for Histoplasmosis is nitrogen rich soils⁽¹⁾. Both bird and bat droppings will increase the levels of nitrogen in soils and are, therefore, often found to be contaminated with Histoplasma capsulatum⁽¹⁶⁾.

ZOONOSIS: Histoplasma capsulatum is not transmitted between animals and humans, although, transfer form soil contaminated with avian or bat guano does occur⁽¹⁷⁾.

VECTORS: None.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Histoplasma capsulatum shows susceptibility to amphotericin B, and the azole group of antifungal drugs, including ketoconazole, itraconazole, and fluconazole⁽¹⁾.

DRUG RESISTANCE: Reduced efficacy has been observed in treatments using deoxycholate, itraconazole, and fluconazole⁽¹⁸⁾.

SUSCEPTIBILITY TO DISINFECTANTS: Histoplasma capsulatum is susceptible to 1 % solutions of sodium hypochlorite, 2 % phenol, 2 % gluteraldehyde, isopropyl alcohol, and formaldehyde⁽¹⁹⁾.

PHYSICAL INACTIVATION: Histoplasma capsulatum spores and yeast cells are inactivated when held at temperatures above 40ºC for extended periods of time⁽²⁰⁾. Growth is inhibited at pH below 5 and above 10. Dry conditions also facilitate the inactivation of spores.

SURVIVAL OUTSIDE HOST: Histoplasma capsulatum is found primarily in nitrogen rich soils with a pH ranging between 5-10⁽¹⁾. Moist soils at temperatures between -18 to 37ºC can support the growth of the fungus. Organisms are known to survive in excess of 10 years in soil.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Identification of Histoplasma capsulatum can be done using Giema and Wrights's stain of blood and bone marrow samples⁽¹⁾. Grocott-Gomori methenamine silver and periodic acid-Schiff stains can be used for tissue samples and pulmonary alveolar lavage fluid. Other tests for identification include the histoplasma polysaccharide antigen test, real time PCR for bone marrow samples, nested PCR for unique proteins, and serological tests.

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

FIRST AID/TREATMENT: For extensive infection due to H. capsulatum, amphotericin B and itraconazole are used^(7,15). Milder infections are treated using itraconazole. The antifungal regime for acute histoplasmosis is IV amphotericin for 1-2 weeks followed by itraconazole for three days⁽²¹⁾. Mild or moderate histoplasmosis does not usually require treatment unless symptoms persist for longer then one month, in which case itraconazole may be indicated for 6-12 weeks. Newer azole antifungals with intravenous formulations (i.e. voriconazole and posaconazole) show great promise for the treatment of histoplasmosis⁽²²⁾.

IMMUNIZATION: None.

PROPHYLAXIS: None.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: There have been 81 reported infections of Histoplasma capsulatum and 1 associated death in humans^(17,23,24). The one reported death occurred to a mycologist who was working with soil samples. He had previously visited both chicken coups and caves. Death in this single case occurred 51 days after the first symptoms appeared.

SOURCES/SPECIMENS: Sources of H. capsulatum in the laboratory include blood, urine, lymph node, bone marrow, sputum, bronchoaveolar lavage fluid⁽¹⁾ and soil⁽¹⁷⁾.

PRIMARY HAZARDS: Inhalation of conidia spores posses the greatest risk^(1,23). Accidental parenteral inoculation may result in cutaneous infection.

SPECIAL HAZARDS: Collecting and processing soil samples may cause pulmonary infections in laboratory workers⁽¹⁷⁾.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3⁽²⁵⁾.

CONTAINMENT REQUIREMENTS: Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and cultures.

PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes⁽²⁶⁾.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings⁽²⁶⁾. Additional precautions should be considered with work involving animals or large scale activities⁽²⁶⁾.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)⁽²⁶⁾.

DISPOSAL: Decontaminate before disposal using steam sterilization, incineration, and/or chemical disinfection⁽²⁶⁾.

STORAGE: Store in sealed containers that are appropriately labelled⁽²⁶⁾.

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: November 2010

PREPARED BY: Pathogen Regulation Directorate, 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, 2010
Canada

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