Coccidioidomycosis- An Overview

Coccidioidomycosis is a systemic infection caused by inhalation of Coccidioides immitis or Coccidioides posadasii spores.

• It affects both humans and animals.
• It is also known as Valley fever or cocci or California fever, or desert rheumatism, or San Joaquin Valley fever.
• The spores of the causative agents are commonly found in soil in endemic areas, where they get distributed into the air.
• It commonly occurs in gardening areas, construction, farming, wind areas.
• Endemic areas affected are the arid areas of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and Northern Mexico.

Figure: Arthroconidia of Coccidioides. Image Source: CDC.

Causative agents of coccidioidomycosis

• Coccidioidomycosis is caused by dimorphic fungi of the Coccidioides.
• Coccidioides are a genus of dimorphic fungi existing as mycelia or as spherules of asexual forms and they lack the sexual form of reproduction and structures.
• The two species within the genus coccidioides are C. immitis and Coccidioides posadasii. 
• They are known to cause Coccidioidomycosis in different regions in the endemic areas.
• The two species of coccidioides are phenotypically identical and can only be identified and differentiated by molecular methods and not clinically.
• The coccidioides produce infective spores known as arthroconidia. The arthroconidia get deposited into the lungs during inhalation. They then germinate and grow into spherules within the lungs and tissues.
• Spherules are filled with tiny endospores of about 2um-5um, which burst into the tissues releasing the endospores which cause severe disease.

Figure: Life Cycle of Coccidioides. Image Source: CDC.

Pathogenesis of Coccidioidomycosis

Risk factors of Coccidioidomycosis infection

• People that are living or traveling into endemic areas where the Coccidioides fungus occurs are at risk of infection.
• Dust storms carrying the fungal spores of contaminated soil such as farms or construction sites increases the risks of exposure and infection.
• People who have compromised immune systems are at increased risk of developing the severe or disseminated disease. These include:
  • HIV/AIDS patients
  • Autoimmune patients and rheumatoid disease patients taking immune-suppressing drugs
  • Organ transplant recipients
  • Diabetic patients
  • Pregnant women

Virulence factors of the causative agents

1. Adherence
   1. During mycelial growth and formation of the septae, processes of autolysis and thinning of the spores leaves some cells which are barred-shaped that have the ability to adhere to epithelial cells and tissues.
   2. The lightweight and loosely chained arthroconidia allow them to easily become airborne and attach to surfaces and be inhaled by hosts.
2. Specialization and remodeling
   • The arthroconidia undergo remodeling when in the host cells shedding off the outer layer of the spore, to form the spherules.
   • The spherules which divide internally through the formation of an internal septae divide the spherules into compartments and each compartment contains several small endospores.
   • A fully impregnated spherule with endospores raptures and releases the endospores into the epithelial cells, alveolar sacs, and alveolar macrophages.
   • The alveolar macrophages pick the endospores which cause an acute inflammatory response due to the accumulation of neutrophils and eosinophils, as a host response to the endospores. The endospores can further multiply within the cells and tissues and spread by causing mycelial growth in the tissues.
3. Antigenic Variation
   • The coccidiodes produce two antigens known as coccidiodin and spherulin. Coccidiodin is extracted from mycelial cultures of the coccidiodes and spherulin antigen are produced from broth cultures.
   • They contribute to the immune responses of the fungi.

Clinical features of coccidioidomycosis

• Clinically, over 60% of the infections are asymptomatic; with most of them resembling bacterial pneumonia infections.
• Symptoms appear at least 21 days after infection with symptoms of fever, cough, shortness of breath, and chest pains. Headaches, weight loss, and rashes are common with the rashes appearing faintly, maculopapular, transient and the commonly occur during early infection.
• A headache, weight loss, and rash are often seen. The rash is faint, maculopapular, transient, and occurs early during disease, but not often to detected.
• In women reddish, painful, tender lumps known as erythema nodosum or erythema multiforme occur on the legs just below the knees.  most commonly located in the front of the legs below the knees, associated with migratory arthralgias, a form of pain the spreads from the joints to other parts of the body. These symptoms are collectively known as desert rheumatism
• Lung cavities are common in children but less common in adults. This is a pulmonary infection of nodules and cavities often in the early stage of infection
• Cavities are solitary, and peripheral with a thin wall, often solitary, and with time develop a distinctive thin wall.

Some of the major clinical manifestations of coccidioidomycosis include:

1. Acute and chronic inflammation which is associated with the production of neutrophils and eosinophils in response to endospore exposure in the alveolar sacs and the lung tissues. Neutrophils and eosinophils get attracted to the site where the spherules rupture and release endospores.
2. Chronic granulomatous infection occurs when mature spherules do not rupture, which is an indication of Coccidiodes’ control.
3. progressive Pulmonary coccidioidomycosis which is normally chronic with multiplication and enlargement of nodules or/and cavities.
4. Disseminated coccidioidomycosis which is debilitating and life-threatening; commonly affecting men than women except for pregnant women. Men most affected are those the elderly, those with underlying conditions, HIV/AIDS patients. Majorly caused by C. immitis which has estrogen-binding proteins, and elevated levels of estradiol and progesterone stimulate its growth.
5. Coccidioides Meningitis which is a disseminated infection commonly affecting the Central Nervous system and brain of AIDS patients.