Blastomyces dermatitidis- An Overview

Blastomyces dermatitidis is a fungus that causes blastomycosis, a potentially serious infection that affects the lungs, skin, bones and other organs. This fungus is found in the environment, especially in soil and organic materials such as animal feces, plant fragments, insect remains and dust. It prefers moist, dark places that contain organic debris and have a pH of 6.0.

Blastomyces dermatitidis is a dimorphic fungus that can grow in two different forms depending on the temperature and the environment.

At room temperature (25 °C) or lower

Blastomyces dermatitidis grows as a mold that produces hyphae and spores. The hyphae are branched and septate, and they bear conidia (asexual spores) at the tips or along the sides of the conidiophores (specialized hyphal branches). The conidia are spherical, ovoid, or pear-shaped, and measure 3–5 μm in diameter.

Some strains of Blastomyces dermatitidis can also produce large, thick-walled spores called chlamydospores, which are resistant to adverse environmental conditions. The chlamydospores are usually found at the ends of the hyphae or in clusters, and they measure 7–18 μm in diameter.

Blastomyces dermatitidis can grow on various culture media, such as Sabouraud dextrose agar (SDA), potato dextrose agar (PDA), or brain heart infusion agar (BHI). The mold colonies are white or tan in color, with a cottony or woolly texture. They may turn brownish or grayish with age. The growth rate is slow, and it may take up to four weeks for the colonies to reach a diameter of 1 cm.

At body temperature (37 °C) or higher

Blastomyces dermatitidis grows as a yeast that produces buds. The yeast cells are spherical, oval, or elongated, and measure 8–15 μm in diameter. They have thick cell walls and multiple nuclei. They form single buds that are attached to the parent cells by a broad base. The buds may grow to the same size as the parent cells before they separate.

Blastomyces dermatitidis can grow as a yeast in host tissues or in certain culture media that mimic the host environment, such as blood agar, serum agar, or brain heart infusion broth (BHI). The yeast colonies are cream-colored, moist, and wrinkled. They have a waxy or mucoid appearance. They grow faster than the mold colonies, and they may reach a diameter of 1 cm within one week.

The pathogenesis of blastomycosis involves the inhalation of spores or conidia of the fungus into the lungs, where they can convert into the pathogenic yeast form and cause infection. The spores are light and thick-walled, allowing them to be easily carried by air and adhere to the host tissues. The conversion from the mold to the yeast form is triggered by temperature, pH, and host factors.

The yeast form of Blastomyces dermatitidis is very resistant to phagocytosis and killing by the host immune cells, as it possesses a thick capsule that protects it from oxidative damage and complement-mediated lysis. The yeast cells can proliferate in the alveoli and cause inflammation, necrosis, and granuloma formation. The granulomas are composed of neutrophils, macrophages, lymphocytes, and giant cells that attempt to contain the infection.

If the natural defenses in the lungs fail to control the infection, the yeast cells can disseminate through the bloodstream or lymphatic system to other organs, such as the skin, bones, genitourinary tract, and central nervous system. The dissemination can occur within weeks or months after the initial exposure, or remain latent for years before reactivation. The signs and symptoms of disseminated blastomycosis vary depending on the site and extent of involvement, but they generally include fever, weight loss, night sweats, and organ-specific manifestations.

The host immune response plays a crucial role in the outcome of blastomycosis. Cell-mediated immunity, mediated by T cells and cytokines, is essential for preventing the progression and dissemination of the infection. Humoral immunity, mediated by antibodies and complement, does not play a significant role in host defense against Blastomyces dermatitidis. However, some antigens produced by the fungus, such as blastomycin and antigen A, can be detected by immunological tests and used for diagnosis.

Blastomyces dermatitidis has several virulence factors that enable it to infect and survive in the host tissues. Some of these factors are:

• Thermal dimorphism: The ability to switch from mold to yeast form in response to temperature is essential for the pathogenicity of Blastomyces dermatitidis. The mold form produces conidia that are easily inhaled and reach the lungs, where they convert to yeast form at 37°C. The yeast form is more resistant to phagocytosis and can disseminate to other organs through the bloodstream or lymphatics.
• BAD1: This is a cell surface protein that is selectively expressed in the yeast phase of Blastomyces dermatitidis. It has multiple functions that contribute to the virulence of the fungus, such as:
  • Adhesion: BAD1 binds to host cells, such as macrophages, epithelial cells, and fibroblasts, and facilitates the invasion and colonization of the fungus.
  • Immune evasion: BAD1 inhibits the production of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-12, by macrophages and dendritic cells. It also impairs the antigen presentation and T cell activation by these cells. Furthermore, it induces the production of anti-inflammatory cytokines, such as IL-10 and TGF-beta, that suppress the immune response.
  • Protection: BAD1 shields the yeast cell from complement-mediated lysis and oxidative damage by neutrophils. It also confers resistance to antifungal drugs, such as amphotericin B.
• DPPIVA: This is a secreted serine protease that degrades cytokines, such as IL-2, IL-4, IL-10, and GM-CSF, that are involved in the activation and proliferation of T cells and macrophages. By reducing the levels of these cytokines, DPPIVA impairs the immune response and allows the fungus to persist in the host tissues.
• Zinc scavenging: Blastomyces dermatitidis expresses genes that encode for zinc transporters and metallothioneins that enable it to acquire zinc from the host environment. Zinc is an essential micronutrient for fungal growth and survival, as well as for the expression of virulence factors, such as BAD1 and DPPIVA.

These virulence factors enable Blastomyces dermatitidis to cause a chronic and invasive infection that can affect various organs and systems in humans and animals.

The main route of transmission of Blastomyces dermatitidis is by inhalation of the fungal spores from contaminated soil and organic materials. The spores are small, light, and thick-walled, which allows them to be easily carried by air currents and to adhere to the respiratory mucosa. Spore exposure is more likely to occur during activities that disturb the soil or generate dust, such as excavation, construction, digging, or wood clearing. The spores can also be transported by wind over long distances.

Very rarely, the fungus can infect an open skin wound and cause infection in just that area of the body. This can happen when the wound comes into contact with contaminated soil or debris. There have been a few reported cases of cutaneous blastomycosis following animal bites or scratches.

Blastomycosis is not spread from person to person or animal to person. There is no evidence of human-to-human transmission through respiratory droplets or body fluids. Likewise, perinatal transmission of the fungus from mother to child is exceedingly uncommon. Animal-to-human transmission is also very unlikely, although some animals, such as dogs, cats, horses, and cattle, can be infected by Blastomyces dermatitidis and develop blastomycosis. However, there is no need to isolate or treat infected animals unless they have severe or disseminated disease.

Blastomycosis is a systemic fungal infection that can affect various organs and tissues in the body. The clinical features of blastomycosis depend on the site and extent of involvement, the immune status of the host, and the duration of the infection. Blastomycosis can be classified into three main forms: pulmonary, cutaneous, and disseminated.

Pulmonary blastomycosis

Pulmonary blastomycosis is the most common form of the disease, as it results from the inhalation of the fungal spores from the environment. The spores germinate in the lungs and transform into yeast cells that cause inflammation and tissue damage. Pulmonary blastomycosis can present with a wide spectrum of symptoms, ranging from asymptomatic infection to acute respiratory distress syndrome and death. The most common clinical manifestations of pulmonary blastomycosis are:

• A self-limited flu-like illness with fever, chills, headache, non-productive cough, and myalgia. This usually occurs within 3 to 21 days after exposure and resolves spontaneously within 2 to 6 weeks.
• An acute illness resembling bacterial pneumonia, with high fever, chills, productive cough, chest pain, and dyspnea. The sputum may be mucopurulent or purulent and may contain blood. Chest radiographs may show patchy or lobar infiltrates, cavities, nodules, or pleural effusions.
• A chronic illness resembling tuberculosis or lung cancer, with low-grade fever, weight loss, night sweats, hemoptysis, and fatigue. Chest radiographs may show fibrosis, calcification, or mass lesions. This form usually occurs in patients with underlying lung diseases or immunosuppression.
• A fast, progressive, severe illness resembling acute respiratory distress syndrome (ARDS), with high fever, hypoxia, respiratory failure, and shock. This form is rare but life-threatening and may occur in patients with a heavy inoculum or impaired immunity.

Cutaneous blastomycosis

Cutaneous blastomycosis is the second most common form of the disease, accounting for about 20 to 40% of cases. It results from hematogenous dissemination of the fungus from the lungs to the skin or from direct inoculation through skin trauma. Cutaneous blastomycosis can present with various types of skin lesions that may evolve over time. The most common clinical manifestations of cutaneous blastomycosis are:

• Papules or pustules that develop at the site of inoculation or dissemination. These lesions may enlarge and ulcerate over time, forming verrucous granulomas with raised borders and central scarring. The lesions may be single or multiple and may involve any part of the body.
• Subcutaneous nodules or abscesses that form along the lymphatic drainage of the primary lesion. These lesions may rupture and drain purulent material containing yeast cells.
• Chronic ulcers that persist for months or years without healing. These lesions may be painless or painful and may be associated with secondary bacterial infection or squamous cell carcinoma.

Disseminated blastomycosis

Disseminated blastomycosis is the least common but most serious form of the disease, occurring in about 10 to 15% of cases. It results from widespread hematogenous spread of the fungus from the lungs to other organs and tissues. Disseminated blastomycosis can affect any organ system but most commonly involves the bones, genitourinary tract, central nervous system (CNS), liver, spleen, adrenal glands, lymph nodes, and eyes.

Blastomyces dermatitidis is a fungus that lives in moist soil and organic materials in certain areas of the world, especially in North America. People can get infected by inhaling the fungal spores from the air, which can cause a disease called blastomycosis. Blastomycosis can affect the lungs, skin, bones, and other organs, and can be mild or severe depending on the person`s immune system and the extent of the infection.

There are no specific measures to prevent or control blastomycosis, as it is not possible to completely avoid exposure to the fungus in areas where it is endemic. However, some general recommendations are:

• There is no vaccine to prevent blastomycosis.
• There is no prophylaxis (preventive treatment) recommended for blastomycosis.
• People who have weakened immune systems may want to consider avoiding activities that involve disrupting soil (such as digging, excavation, construction, or wood clearing) in areas where Blastomyces lives in the environment.
• People who work in occupations that expose them to soil or dust (such as forestry workers, farmers, landscapers, or construction workers) should wear protective clothing and respiratory masks when possible.
• People who work in laboratories or veterinary clinics that handle Blastomyces cultures or infected animals should follow biosafety guidelines and wear gloves, gowns, and eye protection. They should also report any needlestick injuries, bites, or other exposures to their occupational health department or local health authority.
• People who have pets, especially dogs, that may be infected with blastomycosis should take them to a veterinarian for diagnosis and treatment. They should also avoid contact with their pet`s saliva or lesions.
• People who develop symptoms of blastomycosis (such as fever, cough, chest pain, skin lesions, bone pain, or weight loss) should seek medical attention as soon as possible. Blastomycosis is treatable with antifungal medications, but early diagnosis and treatment are important to prevent complications and improve outcomes.

References:

: Treatment for Blastomycosis | Blastomycosis | Fungal Disease | CDC

: Treatment of blastomycosis - UpToDate

: Blastomycosis - Infectious Diseases - Merck Manuals Professional Edition

: Chapman SW et al. Practice Guidelines for the Management of Patients with Blastomycosis. Clin Infect Dis 2008; 46:1801–1812.

: Medical Microbiology by Jawerts, 23rd Edition

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