Coccidioides
Coccidioides is a genus of pathogenic fungi primarily found in the southwestern United States, northern Mexico, and parts of South America, thriving in warm, sandy, alkaline soils. The two main species, C. immitis and C. posadasii, cause coccidioidomycosis, commonly known as valley fever, which presents a spectrum of health impacts ranging from asymptomatic cases to severe, potentially life-threatening infections. Infection typically occurs through inhalation of arthroconidia, leading to pulmonary symptoms that can include fever, cough, and fatigue, though many individuals experience no symptoms at all.
While the majority of cases resolve spontaneously, a minority of patients may develop chronic or disseminated disease, affecting various organs, particularly in individuals with weakened immune systems or certain ethnic backgrounds, such as Asians and Hispanics. Treatment for more serious cases often involves antifungal medications, notably amphotericin B and azoles like fluconazole, with some patients requiring surgical intervention. Despite advancements, relapse can occur, necessitating prolonged or indefinite treatment for individuals with severe manifestations of the disease. Understanding Coccidioides and its impact is crucial for those living in or traveling to endemic regions, as awareness can lead to prompt diagnosis and treatment.
Coccidioides
- TRANSMISSION ROUTE: Blood, inhalation
Definition
Pathogenic fungi from the genus Coccidioides are soil-based organisms found in particular parts of the southwestern United States, northern Mexico, and several other areas of the Western Hemisphere. These fungi cause coccidioidomycosis, a systemic fungal infection that encompasses a broad spectrum of illnesses, including asymptomatic, acute, and chronic pneumonia and potentially fatal disseminated disease. The infection can involve any organ in the body.
Natural Habitat and Features
Members of the genus Coccidioides (C. immitis and C. posadasii) are soilborne fungi that grow in sandy, warm, alkaline soils in low-altitude areas with high summer temperatures and low annual rainfall (five to fifteen inches per year). Although these two fungal species are morphologically indistinguishable, they are genetically distinct and occupy different geographical areas. C. posadasii exists in the deserts of the southwestern United States, Mexico, and South America, and C. immitis is geographically limited to California’s San Joaquin Valley.
Both C. immitis and C. posadasii (C. immitis/posadasii) are thermally dimorphic fungi, which means that they vary their growth mode in response to temperature changes. At 77° Fahrenheit (25° Celsius), they grow as extended filaments called hyphae that possess occasional cross-walls (septae). At their tips, some hyphae form barrel-shaped, desiccation-resistant, resting cells called arthroconidia that alternate with empty cells called disjunctor cells.
Arthroconidia (2 to 4 by 3 to 6 micrometers [m] in size) break apart easily and are readily disseminated by air currents. At 98.6° F (37° C), these fungi grow as large, round, thick-walled structures called spherules. Spherules (20 to 80 m in diameter) divide by internally partitioning themselves into smaller cells called endospores (2 to 5 m in diameter) that eventually mature and then rupture the spherule. The liberated endospores then grow into new spherules.
In the laboratory, in addition to a growth temperature of 98.6° to 104° F (37 to 40° C), spherule formation also requires a liquid medium and elevated carbon dioxide levels (up to 20 percent). This has led some researchers to question if C. immitis/posadasii are thermally dimorphic fungi because more than just temperature is necessary to induce an alternative growth mode. Nevertheless, mycologists continue to classify C. immitis/posadasii with the other thermally dimorphic fungi.
Pathogenicity and Clinical Significance
C. immitis/posadasii cause the systemic fungal infection coccidioidomycosis, which is also known as San Joaquin Valley fever, valley fever, and desert rheumatism. Primary pulmonary coccidioidomycosis begins with the inhalation of arthroconidia. Upon deposition into the lower respiratory system, the arthroconidia transform into spherules and elicit an acute inflammation response in the lungs.
More than 60 percent of infected persons will experience no symptoms (asymptomatic). However, in other cases, one to four weeks after the initial infection, infected persons will have any one or a combination of the following symptoms: fever, chills, cough, chest pain, fatigue, shortness of breath, weight loss, muscle and joint soreness, headache, and night sweats. Some persons (25 percent) may also develop rashes. In the vast majority of people, the disease resolves without intervention.
Between 5 and 8 percent of infected persons develop chronic coccidioidomycosis, in which cavities form in the lungs, but 50 percent of these cases self-resolve within two years. Progressive pulmonary disease occurs in those whose chronic disease does not self-resolve, and in this case the lungs undergo increased and progressive inflammation and scarring, with decreased respiratory capacity.
Less than one percent of all infected persons experience disseminated disease, in which the fungus travels from the lungs, through the bloodstream, and to other organs in the body. Even though disseminated disease can involve any organ in the body, C. immitis/posadasii have a predilection for the skin, bone, joints, lymph nodes, adrenal glands, and central nervous system.
People from certain ethnic groups, in particular, Asians, Filipinos, Hispanics, and African Americans, show an increased risk of developing disseminated coccidioidomycosis, as do pregnant women. Likewise at risk are persons with subfunctional immune systems, which includes solid organ transplant recipients undergoing therapies that suppress the immune system and persons with acquired immune deficiency syndrome (AIDS), cancer, or inherited deficiencies of the immune system.
Drug Susceptibility
People with self-resolving or localized pulmonary infections do not require treatment. However, those with unresolved pulmonary disease, severe pneumonia just after infection, chronic pneumonia, or disseminated disease require antifungal treatment. Specific antifungals for treatment of coccidioidomycosis include amphotericin B and several members of the azole antifungal group, including ketoconazole, itraconazole, and fluconazole.
Newer azole antifungal drugs, such as voriconazole, have shown efficacy in specific infected persons with coccidioidomycosis. Posaconazole was shown to be effective in a small clinical trial and has been approved by the European Commission for the treatment of refractory coccidioidomycosis. However, as of 2022, ketoconazole was the only azole antifungal drug approved by the Food and Drug Administration (FDA) to treat coccidioidomycosis. The echinocandin antifungal drug caspofungin has been used with varying success, but it appears mainly to work well in combination with other antifungal drugs.
Because of its superior ability to penetrate the blood-brain barrier, fluconazole is the preferred treatment for coccidioidal meningitis. Even if the infected person improves, relapse is common, so indefinite treatment is necessary. For refractory cases, amphotericin B is given as an intrathecal drug, which means that the drug is introduced into the central nervous system by means of a needle inserted into the subarachnoid space of the spinal cord to bypass the blood-brain barrier.
Experimental drugs that have shown promise in tested animals include nikkomycins. For persons with pulmonary, bone, or joint involvement, surgical interventions in combination with antifungal drug therapy are often required.
Bibliography
Dismukes, William E., Peter G. Pappas, and Jack D. Sobel, eds. Clinical Mycology. New York: Oxford University Press, 2003.
Galgiani, John, et al. “Coccidioidomycosis.” Clinical Infectious Diseases 41 (2005): 1217-1223.
Lim, James, et al. "Clinical Characteristics and Mortality Risks Among Patients With Culture-Proven Coccidioidomycosis Who Are Critically Ill: A Multicenter Study in an Endemic Region." Open Forum Infectious Diseases, vol. 11, no. 8, 7 Aug. 2024, doi.org/10.1093/ofid/ofae454. Accessed 2 Feb. 2025.
Wright, Patty W., et al. “Donor-Related Coccidioidomycosis in Organ Transplant Recipients.” Clinical Infectious Diseases 37 (2003): 1265-1269.