Coccidioides immitis

Valley Fever (Coccidioidomycosis)

Valley Fever (Coccidioidomycosis)

• Sometimes called "San Joaquin Valley Fever" or "desert rheumatism"
• It is an infection caused by the dimorphic fungi of the genus Coccidioides, which consists of two very similar species:
• Coccidioides immitis - San Joaquin Valley of California
• Coccidioides posadasii - desert areas of the Southwest United States, Mexico, and South America

General Characteristics

• Coccidioides immitis is the causative agent of Valley Fever (Coccidioidomycosis)
• Lives in soil, easily windborne in clouds of dust
• Dimorphic fungi
• Mold phase in the environment: Grows as mycelium in soil and produces asexual spores called arthroconidia
• Macroscopic morphology: rapid growth, white to tan to dark gray; young colonies tenacious, older colonies cottony
• Microscopic morphology: Alternating one-celled, "barrel -shaped" arthroconidia w/ disjunctor cells
• Spherule phase at "body temperature" (35-37°C): each spherule matures and creates endospores via multiple divisions until it ruptures. The endospores are then released into the bloodstream and surrounding tissue and each endospore then forms a new spherule to continue the cycle
• It is NOT contagious

Background

History/Discovery

Background

History/Discovery

• Coccidiodomycosis was first documented in 1892 by Dr. Alejandro Posadas
• An intern at University Hospital Clinics in Buenos Aires, Argentina
• Patient Zero: Domingo Ezcurra
• Dr. Posadas thought that the patient had mycosis fungoides, but examination of skin biopsy specimens revealed organisms resembling the protozoan Coccidia
• Incorrectly classified Coccidioides as protozoan
• In 1894, Emmett Rixford and T.C. Gilchrist published their study of Joas Furtado Silverra, the first reported case of coccidioidal granuloma in North America (and the second overall)
• In 1896, they too concluded that the organism resembled the protozoan Coccidia
• Named the organism after both its morphologic and clinical features: Coccidioides (“resembling Coccidia”) immitis (“not mild”)

Epidemiology

• In 2019, there were 20,003 cases of Valley fever reported to the CDC
• 9004 cases in California (quadrupled since 2014)
• It is estimated that there are ~150,000 coccidioidal infections/year in the U.S.
• Endemic regions include California, Arizona, Nevada, New Mexico, and Utah
• A number of notable cases have occured in California
• In 1978, many cases occured in Sacramento, California (500 miles north of the endemic area) following a severe dust storm in southern California
• In 2005, two state prisons in the San Joaquin Valley were disproportionately affected compared with the general population : 180 cases
• Risk of infection within endemic areas is ~3%/year
• Risk of exposure within endemic regions is seasonal
• Highest during dry periods following a rainy season

Risk Factors

Risk Factors

Entry into Host/Multiplication and Spread

Entry into Host/Multiplcation and Spread

• Entry via inhalation of arthroconidia from the environment
• Once inside the lungs, the arthroconidia will germinate inside the alveoli, changing from "barrel-shaped" cells into spherules
• At maturity, spherules produces endospores via multiple divisions/progressive cleavage
• Rupture of spherule wall releases endospores into the bloodstream and surrounding tissue
• Each endospore then forms a new spherule to continue the cycle

Virulence Factors

• Virulence mechanisms of Coccidioides spp. are largely unknown but there are three mechanisms that help C. immitis survive inside the host
• Production of a dominant spherule outer wall glycoprotein (SOWgp)
• modulates host immune response, resulting in compromised cell-mediated immunity to coccidioidal infection
• Depletion of spherule outer wall glycoprotein (SOWgp) presentation on the surface of endospores
• prevents host recognition of the pathogen when the fungal cells are most vulnerable to phagocytic defenses
• Induction of elevated production of host arginase I and coccidioidal urease
• contribute to tissue damage at sites of infection

Damage Caused to Host

• ~60% of all people infected with Valley fever do not come to medical attention because primary infection is either asymptomatic or minimally symptomatic
• Primary disease symptoms (~7-21 days after exposure)
• Fatigue (tiredness)
• Cough
• Fever
• Shortness of breath
• Headache
• Night sweats*
• Muscle aches or joint pain
• Atypical rash on upper body or legs*
• Patients can also develop localized pneumonia and diffuse pulmonary disease
• Symptoms usually last for a few weeks to a few months

Damage Caused to Host

continued...

• In rare cases, Valley fever can cause severe infections in the lungs or in other parts of the body (disseminated Valley fever)
• ~5-10% of people who get Valley fever will develop serious or long-term problems in their lungs
• In ~1% of people, single or multi-system dissemination follows
• The infection will spread from the lungs to other parts of the body such as the central nervous system (brain and spinal cord), skin, or bones and joints

Damage Caused to Host

Diagnosis

Diagnosis

• Valley Fever is usually diagnosed with a blood test
• Serologic tests using enzyme immunoassay (EIA) for IgM and IgG antibodies are ordered first
• Immunodiffusion tests are generally performed to support diagnosis when an initial EIA is positive

• Imaging Tests like chest X-rays or CT scans of the lung to look for Valley fever pneumonia

• Tissue biopsy: small sample of tissue is taken from the body and examined under a microscope

• Sputum smear or culture: checks for presence of C. immitis

Treatment

• For many people, symptoms of Valley fever will go away within a few months without any treatment
• There are no over-the-counter medications for Valley fever
• Approach to treatment of primary coccidiodomycosis in patients depends upon severity of disease and the patient's risk of developing severe or complicated disease (disseminated Valley fever)
• Treat patients who are immunocompromised, Black or Filipino, pregnant, have severe illness or comorbidities, or have diabetes with 3-6 months of oral fluconazole or another type of antifungal like itraconazole
• Nearly all patients with disseminated Valley fever should be treated with antifungal therapy
• High-dose oral fluconazole
• Intravenous amphotericin B

Prevention

• Wearing protective masks like N95 respirators in endemic areas
• Staying inside during dust storms and keeping windows closed
• Running air filters indoor
• Avoiding activities that involve close contact to soil or dirt
• Avoiding dusty areas outside like construction or evacuation sites

• Currently no vaccine to prevent Valley fever

References

• Stan Deresinski, Laurence F Mirels, Coccidioidomycosis: What a long strange trip it's been, Medical Mycology, Volume 57, Issue Supplement_1, February 2019, Pages S3–S15, https://doi.org/10.1093/mmy/myy123
• Jan V. Hirschmann, The Early History of Coccidioidomycosis: 1892–1945, Clinical Infectious Diseases, Volume 44, Issue 9, 1 May 2007, Pages 1202–1207, https://doi.org/10.1086/513202
• Lewis ER, Bowers JR, Barker BM. Dust devil: the life and times of the fungus that causes valley Fever. PLoS Pathog. 2015 May 14;11(5):e1004762. doi: 10.1371/journal.ppat.1004762. PMID: 25973899; PMCID: PMC4431877.
• https://www.cdc.gov/fungal/diseases/coccidioidomycosis/index.html
• https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/ValleyFeverGroupsAtRisk.aspx
• Hernandez, H., Erives, V.H. & Martinez, L.R. Coccidioidomycosis: Epidemiology, Fungal Pathogenesis, and Therapeutic Development. Curr Trop Med Rep 6, 132–144 (2019). https://doi.org/10.1007/s40475-019-00184-z
• Mahon, C. R., Lehman, D. C., & Manuselis, G. (2019). Textbook of diagnostic microbiology (6th ed.). Saunders.
• Bauman, R. W. (2017). Microbiology with diseases by body system (5th ed.). Pearson.
• Hung, Chiung-Yu & Xue, Jianmin & Cole, Garry. (2007). Virulence Mechanisms of Coccidioides. Annals of the New York Academy of Sciences. 1111. 225-35. 10.1196/annals.1406.020.
• https://phil.cdc.gov/Details.aspx?pid=20828
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