Coccidioidomycosis (Valley Fever) in Primary Care

 

Am Fam Physician. 2020 Feb 15;101(4):221-228.

  Patient information: See related handout on valley fever, written by the authors of this article.

Author disclosure: No relevant financial affiliations.

Primary pulmonary coccidioidomycosis (valley fever) is caused by inhaling airborne spores of the fungus Coccidioides immitis or Coccidioides posadasii. Residing in or traveling to areas endemic for Coccidioides is required for the diagnosis; no person-to-person or zoonotic contagion occurs. The incidence of coccidioidomycosis is increasing in endemic areas, and it has been identified as the cause of as many as 17% to 29% of all cases of community-acquired pneumonia in some regions. Obtaining a travel history is recommended when evaluating patients with community-acquired pneumonia. Diagnosis usually relies on enzyme immunoassay with immunodiffusion confirmation, but these tests may not be positive for one to three weeks after disease onset. Antifungal agents are not recommended for treatment unless the patient is at risk of or shows signs of complicated or disseminated infection. When antifungals are used, fluconazole and itraconazole are most commonly recommended, except during pregnancy. Treatment may continue for as long as three to 12 months, although lifetime treatment is indicated for patients with coccidioidal meningitis. Monitoring of complement fixation titers and chest radiography is recommended until patients stabilize and symptoms resolve. In patients who are treated with antifungals, complement fixation titers should be followed for at least two years. (Am Fam Physician. 2020;101(4):221–228. Copyright © 2020 American Academy of Family Physicians.)

Primary pulmonary coccidioidomycosis, also known as valley fever, is an acute pulmonary infection that presents one to three weeks after a person inhales airborne spores of the fungus Coccidioides immitis or Coccidioides posadasii. These fungi normally grow in the soil, but when the soil is mechanically disturbed, airborne spores are released that can be inhaled and begin a parasitic existence in a human or animal host. Person-to-person or zoonotic contagion does not occur, and transplacental infection in humans has never been documented.13 There have been reports, however, of nonrespiratory spread via solid organ transplant or percutaneous transfer of infected fomites, but such cases are rare.47

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComment

Include a travel and residence history when assessing patients presenting with suspected community-acquired pneumonia, and consider primary pulmonary coccidioidomycosis in those who have visited endemic areas in the previous two months.8,9

C

Expert opinion and consensus guideline in the absence of clinical trials

Antifungal agents are not recommended for the treatment of uncomplicated primary pulmonary coccidioidomycosis unless risks for disseminated disease are present.9,29,36,37,50

C

Expert opinion and consensus guideline in the absence of clinical trials

When indicated, antifungals for the treatment of primary pulmonary coccidioidomycosis include oral fluconazole (Diflucan) or itraconazole (Sporanox) for nonpregnant, nonbreastfeeding adults; oral fluconazole for breastfeeding women; oral fluconazole for children; and intravenous amphotericin B for pregnant women.9,29

C

Expert opinion and consensus guideline in the absence of clinical trials

If primary pulmonary coccidioidomycosis is confirmed, monitor complement fixation titers and chest radiography every one to three months for at least one year, and evaluate any symptoms of dissemination, including fungal meningitis.9,30,36

C

Expert opinion and consensus guideline in the absence of clinical trials

Pregnant women with a history of coccidioidomycosis should be monitored with complement fixation titers every six to 12 weeks. Serologic testing should be considered for all women residing in endemic regions at their first antenatal visit.29

C

Expert opinion and consensus guideline in the absence of clinical trials


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComment

Include a travel and residence history when assessing patients presenting with suspected community-acquired pneumonia, and consider primary pulmonary coccidioidomycosis in those who have visited endemic areas in the previous two months.8,9

C

Expert opinion and consensus guideline in the absence of clinical trials

Antifungal agents are not recommended for the treatment of uncomplicated primary pulmonary coccidioidomycosis unless risks for disseminated disease are present.9,29,36,37,50

C

Expert opinion and consensus guideline in the absence of clinical trials

When indicated, antifungals for the treatment of primary pulmonary coccidioidomycosis include oral fluconazole (Diflucan) or itraconazole (Sporanox) for nonpregnant, nonbreastfeeding adults; oral fluconazole for breastfeeding women; oral fluconazole for children; and intravenous amphotericin B for pregnant women.9,29

C

Expert opinion and consensus guideline in the absence of clinical trials

If primary pulmonary coccidioidomycosis is confirmed, monitor complement fixation titers and chest radiography every one to three months for at least one year, and evaluate any symptoms of dissemination, including fungal meningitis.9,30,36

C

Expert opinion and consensus guideline in the absence of clinical trials

Pregnant women with a history of coccidioidomycosis should be monitored with complement fixation titers every six to 12 weeks. Serologic testing should be considered for all women residing in endemic regions at their first antenatal visit.29

C

Expert opinion and consensus guideline in the absence of clinical trials


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

People who have not been in a Coccidioides-endemic region are essentially at no risk of infection. The known endemic range of Coccidioides in the United States is shown in Figure 1.8 Other regions of endemicity include areas in Mexico and parts of Central and South America.

FIGURE 1.

Areas endemic for coccidioidomycosis in the United States, January 2019.

Adapted from Centers for Disease Control and Prevention. Fungal diseases: sources of valley fever (coccidioidomycosis). January 2, 2019. Accessed January 20, 2019. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/causes.html


FIGURE 1.

Areas endemic for coccidioidomycosis in the United States, January 2019.

Adapted from Centers for Disease Control and Prevention. Fungal diseases: sources of valley fever (coccidioidomycosis). January 2, 2019. Accessed January 20, 2019. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/causes.html

Natural History

More than one-half of primary pulmonary Coccidioides infections are subclinical and resolve spontaneously.9 Infections generally impart lifelong immunity to reinfection and confer a positive delayed hypersensitivity skin test.10 Immunocompetent hosts usually overcome the acute infection without treatment but may form pulmonary granulomas containing dormant, noncontagious endospores that can potentially disseminate, particularly if the host later becomes immunocompromised.1113 About 5% to 10% of infected people develop chronic pulmonary sequelae, such as nodules, cavitations, or chronic fibrocavitary pneumonia.14 In about 1% of cases, infection disseminates to bone, joints, or soft tissues within two years.9,14,15 Meningitis is a potential complication and is usually fatal if not treated appropriately.11,16

Epidemiology

The incidence of coccidioidomycosis is increasing. From 1998 to 2011, the age-adjusted incidence in the endemic U.S. region increased by about 700% (from 5.3 to 42.6 cases per 100,000 people) because of factors such as weather, urban development, and changes in reporting methodology.1,17 The annual incidence in California more than tripled between 2014 and 2017 (from 6.0 to 18.8 cases per 100,000 people).18 The endemic range is also increasing and now includes areas in northeastern Utah, northern California, and south-central Washington.1,8 Data suggest that migration of infected wildlife is contributing to this expansion.19,20

Two studies conducted in 2000 to 2004 found that primary pulmonary coccidioidomycosis is a common cause of community-acquired pneumonia, accounting for 17% to 29% of cases in south-central Arizona during that time.21,22 Two-thirds of U.S. coccidioidomycosis cases occur in Arizona, and almost one-third occur in California.17 About 1% of cases present outside these endemic areas when infected travelers return home (Figure 28). Thus, family physicians throughout the country should be familiar with the evaluation and management of coccidioidomycosis.9,11,17,23

FIGURE 2.

Average incidence of reported primary pulmonary coccidioidomycosis per 100,000 people, by patient’s county of residence, 2010 to 2015.

Adapted from Centers for Disease Control and Prevention. Fungal diseases: valley fever maps. January 2, 2019. Accessed January 20, 2019. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/maps.html


FIGURE 2.

Average incidence of reported primary pulmonary coccidioidomycosis per 100,000 people, by patient’s county of residence, 2010 to 2015.

Adapted from Centers for Disease Control and Prevention. Fungal diseases: valley fever maps. January 2, 2019. Accessed January 20, 2019. https://www.cdc.gov/fungal/diseases/coccidioidomycosis/maps.html

Primary pulmonary coccidioidomycosis has a predilection for certain populations. Dusty outdoor activities within endemic areas, such as agriculture, construction, and archaeology, put participants at higher risk of infection. Some California correctional facilities have a disproportionate disease burden, although the reasons for this are not clear.2426 People with deficiencies in cellular immunity are also at risk of disease dissemination, as are people with diabetes mellitus, older adults, blacks, and Filipinos.1,9,27,28 Women are particularly susceptible to complicated disease or dissemination during late pregnancy and in the immediate postpartum period.29

Clinical Presentation

Primary pulmonary coccidioidomycosis often goes unrecognized, and an estimated 60% to 80% of patients are initially treated with antibiotics before they are diagnosed with a fungal infection.8 The diagnosis of coccidioidomycosis should be considered in all patients presenting with community-acquired pneumonia if they live in or have traveled to an endemic area in the previous two months; the diagnosis can essentially be ruled out if the patient has no such travel history.9,30 A history of endemic travel accompanied by prolonged fever, lingering fatigue, weight loss, rash, arthralgias, or eosinophilia should also raise suspicion for coccidioidomycosis, or when usual testing offers no other plausible explanation for the patient’s symptoms.

SYMPTOMS

Primary pulmonary coccidioidomycosis usually presents similarly to community-acquired pneumonia one to three weeks after exposure. It is occasionally associated with rheumatic symptoms. Common presentations are listed in Table 1 and include fatigue, cough, chest pain, headache, and fever, but symptoms are often diverse and nonspecific.8,15,31,32 Erythema nodosum, a manifestation of the patient’s immune response, is a nonspecific finding that indicates a favorable prognosis; its discovery can suggest the diagnosis.15,29,33

 Enlarge     Print

TABLE 1.

Common Presenting Symptoms of Primary Pulmonary Coccidioidomycosis

Constitutional symptomsPulmonary symptoms

Arthralgias Erythema nodosum, erythema multiforme, or a generalized exanthema Fatigue Fever Focal myalgia Headache Night sweats Weight loss

Cough Dyspnea Hemoptysis Pleuritic pain


Information from references 8, 15, 31, and 32.

TABLE 1.

Common Presenting Symptoms of Primary Pulmonary Coccidioidomycosis

Constitutional symptomsPulmonary symptoms

Arthralgias Erythema nodosum, erythema multiforme, or a generalized exanthema Fatigue Fever Focal myalgia Headache Night sweats Weight loss

Cough Dyspnea Hemoptysis Pleuritic pain


Information from references 8, 15, 31, and 32.

Diagnostic Approach

An algorithm for the diagnostic approach to patients with suspected coccidioidomycosis is shown in Figure 3.9,25,34

FIGURE 3.

Diagnostic approach to primary pulmonary coccidioidomycosis.

Information from references 9, 25, and 34.


FIGURE 3.

Diagnostic approach to primary pulmonary coccidioidomycosis.

Information from references 9, 25, and 34.

INITIAL STUDIES

On initial evaluation, the complete blood count is often normal, but eosinophilia greater than 5% should raise suspicion for coccidioidomycosis.25 The erythrocyte sedimentation rate may be mildly elevated.25,31 Chest radiography often appears normal but can show nonspecific findings such as pulmonary infiltrates, mediastinal lymphadenopathy, pleural effusion, pneumothorax, or empyema.32,33  The differential diagnosis is shown in Table 2.9,3537

 Enlarge     Print

TABLE 2.

Differential Diagnosis of Primary Pulmonary Coccidioidomycosis

ConditionDifferentiating characteristics and diagnostic tests

Bacterial

Actinomycosis

Anaerobic culture from deep-needle or biopsy sample (which may require four weeks for growth); elevated CRP level and ESR; sulfur granules on tissue histology

Lung abscess

Blood, pleural fluid, or sputum culture; bronchoscopy with tissue histology; characteristic computed tomography or ultrasound findings

Mycoplasma pneumoniae infection

Cold agglutinin titer > 1:16; enzyme immunoassay; mildly elevated hepatic transaminase levels or ESR; multiplex PCR respiratory panel; normal or mildly elevated white blood cell count; point-of-care serologic testing

Tuberculosis

Chest imaging; exudative pleural fluid showing normal or low glucose level, lymphocytic predominance, and elevated adenosine deaminase level; sputum analyses and culture; tuberculin skin testing or interferon-gamma release assay

Typical community-acquired pneumonia

Blood or sputum culture; chest imaging; multiplex PCR respiratory panel; travel history; urine antigen testing

Fungal

Aspergillosis

Characteristic histology on tissue biopsy; chest imaging; elevated galactomannan level in bronchoalveolar lavage; elevated serum immunoglobulin E level; serology; sputum fungal culture

Blastomycosis

Blood or urine antigen testing; histology; sputum or bronchoscopy culture on specialized media (which may require four weeks for growth); travel history

Cryptococcosis

Association with HIV-infected or other immunocompromised hosts; blood, bronchoscopy, cerebrospinal, sputum, or urine fungal cultures; serologic and antigen testing

Histoplasmosis

Characteristic histopathologic findings on lung tissue or mediastinal lymph node biopsies; enzyme immunoassay on urine, blood, or bronchoalveolar lavage samples; fungal cultures; serologic testing; travel history

Paracoccidioidomycosis

Histology; serology; travel history

Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia

Association with HIV-infected or other immunocompromised hosts; PCR; respiratory histology; serum beta-D glucan assay

Sporotrichosis

Histopathologic findings of pyogenic granuloma; radiographic findings (may mimic tuberculosis); sputum culture

Neoplastic

Lung cancer

Histology on any clinical sample

Lymphoma

Chest imaging; lymph node and/or bone marrow biopsy; peripheral blood analysis

Parasitic

Loeffler syndrome

Larvae in respiratory secretions or gastric aspirate; peripheral eosinophilia

Paragonimiasis

Enzyme-linked immunosorbent assay on serum sample; history of exposure to undercooked seafood; leukocytosis with eosinophilia; trematode ova in bronchoalveolar lavage, 24-hour sputum, stool, fine-needle aspiration, thoracoscopy, or transbronchial biopsy

Viral

Influenza pneumonia

Antigen testing; chest imaging; multiplex PCR respiratory panel; reverse transcriptase–PCR; serology

Other

Collagen-vascular lung disease

Assays for various autoantibodies

Eosinophilic pneumonia

Bronchoalveolar lavage cell count showing > 25% eosinophils; exposure and travel histories; lung biopsy

Granulomatosis with polyangiitis (Wegener granulomatosis)

Abnormal findings on antineutrophil cytoplasmic autoantibody testing, complete blood count, histology, or peripheral blood smear; elevated CRP level and ESR; hematuria

Sarcoidosis

Characteristic findings on pulmonary imaging; histopathology showing noncaseating granulomas Confirmatory tissue diagnosis should be obtained before administering glucocorticoids, which may trigger dissemination of an undiagnosed endemic mycosis


CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; PCR = polymerase chain reaction.

Information from references 9 and 3537.

TABLE 2.

Differential Diagnosis of Primary Pulmonary Coccidioidomycosis

ConditionDifferentiating characteristics and diagnostic tests

Bacterial

Actinomycosis

Anaerobic culture from deep-needle or biopsy sample (which may require four weeks for growth); elevated CRP level and ESR; sulfur granules on tissue histology

Lung abscess

Blood, pleural fluid, or sputum culture; bronchoscopy with tissue histology; characteristic computed tomography or ultrasound findings

Mycoplasma pneumoniae infection

Cold agglutinin titer > 1:16; enzyme immunoassay; mildly elevated hepatic transaminase levels or ESR; multiplex PCR respiratory panel; normal or mildly elevated white blood cell count; point-of-care serologic testing

Tuberculosis

Chest imaging; exudative pleural fluid showing normal or low glucose level, lymphocytic predominance, and elevated adenosine deaminase level; sputum analyses and culture; tuberculin skin testing or interferon-gamma release assay

Typical community-acquired pneumonia

Blood or sputum culture; chest imaging; multiplex PCR respiratory panel; travel history; urine antigen testing

Fungal

Aspergillosis

Characteristic histology on tissue biopsy; chest imaging; elevated galactomannan level in bronchoalveolar lavage; elevated serum immunoglobulin E level; serology; sputum fungal culture

Blastomycosis

Blood or urine antigen testing; histology; sputum or bronchoscopy culture on specialized media (which may require four weeks for growth); travel history

Cryptococcosis

Association with HIV-infected or other immunocompromised hosts; blood, bronchoscopy, cerebrospinal, sputum, or urine fungal cultures; serologic and antigen testing

Histoplasmosis

Characteristic histopathologic findings on lung tissue or mediastinal lymph node biopsies; enzyme immunoassay on urine, blood, or bronchoalveolar lavage samples; fungal cultures; serologic testing; travel history

Paracoccidioidomycosis

Histology; serology; travel history

Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia

Association with HIV-infected or other immunocompromised hosts; PCR; respiratory histology; serum beta-D glucan assay

Sporotrichosis

Histopathologic findings of pyogenic granuloma; radiographic findings (may mimic tuberculosis); sputum culture

Neoplastic

Lung cancer

Histology on any clinical sample

Lymphoma

Chest imaging; lymph node and/or bone marrow biopsy; peripheral blood analysis

Parasitic

Loeffler syndrome

Larvae in respiratory secretions or gastric aspirate; peripheral eosinophilia

Paragonimiasis

Enzyme-linked immunosorbent assay on serum sample; history of exposure to undercooked seafood; leukocytosis with eosinophilia; trematode ova in bronchoalveolar lavage, 24-hour sputum, stool, fine-needle aspiration, thoracoscopy, or transbronchial biopsy

Viral

Influenza pneumonia

Antigen testing; chest imaging; multiplex PCR respiratory panel; reverse transcriptase–PCR; serology

Other

Collagen-vascular lung disease

Assays for various autoantibodies

Eosinophilic pneumonia

Bronchoalveolar lavage cell count showing > 25% eosinophils; exposure and travel histories; lung biopsy

Granulomatosis with polyangiitis (Wegener granulomatosis)

Abnormal findings on antineutrophil cytoplasmic autoantibody testing, complete blood count, histology, or peripheral blood smear; elevated CRP level and ESR; hematuria

Sarcoidosis

Characteristic findings on pulmonary imaging; histopathology showing noncaseating granulomas Confirmatory tissue diagnosis should be obtained before administering glucocorticoids, which may trigger dissemination of an undiagnosed endemic mycosis


CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; PCR = polymerase chain reaction.

Information from references 9 and 3537.

CULTURE AND SEROLOGIC TESTING

Laboratory testing is required for a definitive diagnosis of coccidioidomycosis. The detection of Coccidioides in any clinical specimen by culture or microscopy is the diagnostic standard, but these results are not instantly available, and obtaining samples can be problematic.25 Therefore, the diagnosis is usually made serologically, although serologic results can be falsely negative while the immune response develops or in patients who are immunocompromised.25,38 Serologic results also may take several days to obtain.

Enzyme immunoassay is the most commonly used initial serologic test, and it is usually positive one to three weeks after disease onset.25 Immunodiffusion is also typically performed to confirm the diagnosis and allay concerns about false-positive results. 9,34,39,40 Immunodiffusion is more specific but less sensitive than enzyme immunoassay.9,11,34,41 Negative results may warrant retesting if suspicion for coccidioidomycosis remains.

OTHER TESTS

Polymerase chain reaction (PCR) testing has proved clinically helpful in rapidly detecting elusive pathogens, and multiplex PCR respiratory panels are often used in the emergency department and hospital settings to detect respiratory pathogens. However, their use in coccidioidomycosis has been limited.4246 Several sensitive and specific PCR assays have been developed to detect Coccidioides, and PCR testing is available at reference laboratories as an additional diagnostic option.8,25,4648 Its effectiveness as a rapid initial diagnostic method for primary pulmonary coccidioidomycosis is currently being evaluated by the U.S. Food and Drug Administration.48

Management

The recommended initial management of symptomatic primary pulmonary coccidioidomycosis is shown in Figure 4.9,29,30 Because of a lack of clinical trials, recommendations are almost exclusively based on expert opinion.

FIGURE 4.

Recommended initial management of laboratory-confirmed, symptomatic primary pulmonary coccidioidomycosis.

Information from references 9, 29, and 30.


FIGURE 4.

Recommended initial management of laboratory-confirmed, symptomatic primary pulmonary coccidioidomycosis.

Information from references 9, 29, and 30.

UNCOMPLICATED CASES

No prospective, randomized, double-blind trials have evaluated whether antifungal treatment improves outcomes in uncomplicated cases of coccidioidomycosis. Most untreated infections resolve without sequelae, so antifungal treatment is typically not recommended.9,49 However, patients should receive education and physical therapy as needed, and they should be monitored for chronic pulmonary residua or dissemination, which is clinically evidenced by unresolving respiratory symptoms or new focal symptoms such as skin lesions, joint pain, or unusual headache.9,30

Serial complement fixation titers should be obtained from the same laboratory every one to three months for one year or until they become negative.30,34 As a control, repeated testing of the original serum sample should be performed concurrently, and results should be compared with the newly tested serum. A titer that decreases over time is reassuring, whereas one that increases or is more than 1:32 raises concern for dissemination and a poor prognosis.9,25,32,36 Chest radiography is also typically repeated at intervals of one to three months for at least one year to document radiographic residua or resolution.9,30

ANTIFUNGAL TREATMENT

Antifungals are recommended for symptomatic patients who have clinically significant disease or an elevated risk of dissemination (Table 3).9,2730,36,37,50,51 Nonpregnant, nonbreastfeeding adults are typically treated with oral fluconazole (Diflucan) or itraconazole (Sporanox).9 Children are usually treated with oral fluconazole.9 Pregnant women are normally treated with intravenous amphotericin B, although fluconazole can be considered during the second and third trimesters.9,29,36,37 Fluconazole—but not itraconazole—is recommended for breastfeeding women.9,29

 Enlarge     Print

TABLE 3.

Indications for Antifungal Treatment for Coccidioidomycosis

Manifestations of clinically significant disease

Anti-Coccidioides complement fixation antibody titers > 1:16

Bilateral pulmonary infiltrates

Fever lasting more than one month

Hospitalization

Inability to work

Night sweats lasting longer than three weeks

Pulmonary infiltrates involving more than one-half of one lung

Symptoms lasting longer than two months

Weight loss > 10%

Risk factors for dissemination

Advanced age

Black race or Filipino ethnicity

Certain genetic mutations of immunity

Diabetes mellitus

Hematologic malignancy

High-dose steroid therapy

Immunosuppressive chemotherapy

Inflammatory rheumatic disease

Lymphoma

Pregnancy and peripartum period

Thymectomy

Tumor necrosis factor-alpha inhibitor therapy

Uncontrolled HIV infection


Information from references 9, 2730, 36, 37, 50, and 51.

TABLE 3.

Indications for Antifungal Treatment for Coccidioidomycosis

Manifestations of clinically significant disease

Anti-Coccidioides complement fixation antibody titers > 1:16

Bilateral pulmonary infiltrates

Fever lasting more than one month

Hospitalization

Inability to work

Night sweats lasting longer than three weeks

Pulmonary infiltrates involving more than one-half of one lung

Symptoms lasting longer than two months

Weight loss > 10%

Risk factors for dissemination

Advanced age

Black race or Filipino ethnicity

Certain genetic mutations of immunity

Diabetes mellitus

Hematologic malignancy

High-dose steroid therapy

Immunosuppressive chemotherapy

Inflammatory rheumatic disease

Lymphoma

Pregnancy and peripartum period

Thymectomy

Tumor necrosis factor-alpha inhibitor therapy

Uncontrolled HIV infection


Information from references 9, 2730, 36, 37, 50, and 51.

If antifungals are given, serial complement fixation titers should be monitored for at least two years because antifungal treatment has been associated with delayed dissemination.9,30,49 Antifungal therapy is often discontinued after three to 12 months if complement fixation titers stabilize, chest radiography shows stabilization, and symptoms resolve.9 Normal serologic results are not always required before discontinuing antifungal treatment in lower-risk patients.9

Pregnant women with a history of coccidioidomycosis should have complement fixation titers checked every six to 12 weeks to monitor for any elevation, which would suggest recrudescence.9,29 Serologic screening should be considered for all women in endemic areas at their first antenatal visit.29 Antifungal therapy should be considered if symptoms develop during pregnancy.9,30,36

SPECIAL SITUATIONS

Coccidioidal meningitis is a serious complication that presents insidiously.52 Unusual or frequent headaches, altered mental status, meningismus, nausea, vision changes, or vomiting in a patient with coccidioidomycosis warrants investigation. If coccidioidal meningitis is confirmed, lifelong antifungal therapy is indicated.9,52 Expert recommendations for less common clinical situations are available from the Infectious Diseases Society of America.9

Prevention

Preventive strategies for coccidioidomycosis are being explored. Data suggest that respirator use by construction workers in endemic areas may reduce disease risk.53 Prophylactic use of antifungals, although not generally recommended, is supported in specific clinical situations, such as organ transplant recipients.9,54 Despite a significant and ongoing effort, development of a vaccine for general use has not been successful.55

This article updates previous articles on this topic by Hedges and Miller,11 and by Bayer.23

Data Sources: Essential Evidence Plus and PubMed searches in Clinical Queries were conducted and included combinations of the terms coccidioidomycosis, Coccidioides, valley fever, incidence, therapy, diagnosis, polymerase chain reaction, prognosis, natural history, prevention, and clinical decision rules. The search included prospective studies, statistical analyses, meta-analyses, randomized controlled trials, and reviews. Also searched were websites of the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, UpToDate, and Medscape. Further sources were drawn from the bibliographies of these articles. Search dates: October 2018 through August 2019.

The authors thank Jacinta Leyden, MD; McShirley Tran, PA-C; and Ngoc-Tuyen Tran, PA-C, for editorial assistance with the preparation of the manuscript.

The Authors

show all author info

KEVIN R. HERRICK, MD, PhD, is director of education and research at the Foothill Community Health Center, San Jose, Calif.; an assistant clinical professor of family medicine at Loma Linda (Calif.) University School of Medicine; and an adjunct clinical instructor at Stanford University School of Medicine, Palo Alto, Calif....

MADISON E. TRONDLE, DVM, is an associate veterinarian at Banfield Pet Hospital, Upland, Calif.

TAYNET T. FEBLES, MD, is an infectious disease attending physician at Hazel Hawkins Memorial Hospital, Hollister, Calif.

Address correspondence to Kevin R. Herrick, MD, PhD, Foothill Community Health Center, 5504 Monterey Hwy., San Jose, CA 95138. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Brown J, Benedict K, Park BJ, et al. Coccidioidomycosis: epidemiology. Clin Epidemiol. 2013;5:185–197....

2. Spark RP. Does transplacental spread of coccidioidomycosis occur? Report of a neonatal fatality and review of the literature. Arch Pathol Lab Med. 1981;105(7):347–350.

3. McCaffree MA, Altshuler G, Benirschke K. Placental coccidioidomycosis without fetal disease. Arch Pathol Lab Med. 1978;102(10):512–514.

4. Nel JS, Bartelt LA, van Duin D, et al. Endemic mycoses in solid organ transplant recipients. Infect Dis Clin North Am. 2018;32(3):667–685.

5. Dierberg KL, Marr KA, Subramanian A, et al. Donor-derived organ transplant transmission of coccidioidomycosis. Transpl Infect Dis. 2012;14(3):300–304.

6. Gaidici A, Saubolle MA. Transmission of coccidioidomycosis to a human via a cat bite. J Clin Microbiol. 2009;47(2):505–506.

7. Stagliano D, Epstein J, Hickey P. Fomite-transmitted coccidioidomycosis in an immunocompromised child. Pediatr Infect Dis J. 2007;26(5):454–456.

8. Centers for Disease Control and Prevention. Fungal diseases: valley fever (coccidioidomycosis). January 2, 2019. Accessed January 20, 2019. https://www.cdc.gov/fungal/diseases/coccidioidomycosis

9. Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis. Clin Infect Dis. 2016;63(6):e112–e146.

10. Wack EE, Ampel NM, Sunenshine RH, et al. The return of delayed-type hypersensitivity skin testing for coccidioidomycosis. Clin Infect Dis. 2015;61(5):787–791.

11. Hedges E, Miller S. Coccidioidomycosis: office diagnosis and treatment. [published correction appears in Am Fam Physician. 1990;42(1):44]. Am Fam Physician. 1990;41(5):1499–1506.

12. Galgiani JN. Coccidioidomycosis. West J Med. 1993;159(2):153–171.

13. Forseth J, Rohwedder JJ, Levine BE, et al. Experience with needle biopsy for coccidioidal lung nodules. Arch Intern Med. 1986;146(2):319–320.

14. Thompson GR III. Pulmonary coccidioidomycosis. Semin Respir Crit Care Med. 2011;32(6):754–763.

15. Garcia Garcia SC, Salas Alanis JC, Flores MG, et al. Coccidioidomycosis and the skin: a comprehensive review. An Bras Dermatol. 2015;90(5):610–619.

16. Mischel PS, Vinters HV. Coccidioidomycosis of the central nervous system: neuropathological and vasculopathic manifestations and clinical correlates. Clin Infect Dis. 1995;20(2):400–405.

17. Centers for Disease Control and Prevention (CDC).. Increase in reported coccidioidomycosis—United States, 1998–2011. MMWR Morb Mortal Wkly Rep. 2013;62(12):217–221.

18. California Department of Public Health. Epidemiologic summary of coccidioidomycosis in California, 2017. Accessed January 22, 2019. http://bit.ly/2KdMlTd

19. Del Rocío Reyes-Montes M, Pérez-Huitrón MA, Ocaña-Monroy JL, et al. The habitat of Coccidioides spp. and the role of animals as reservoirs and disseminators in nature. BMC Infect Dis. 2016;16(1):550.

20. Sharpton TJ, Stajich JE, Rounsley SD, et al. Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives. Genome Res. 2009;19(10):1722–1731.

21. Valdivia L, Nix D, Wright M, et al. Coccidioidomycosis as a common cause of community-acquired pneumonia [published correction appears in Emerg Infect Dis. 2006;12(8):1307]. Emerg Infect Dis. 2006; 12(6):958–962.

22. Kim MM, Blair JE, Carey EJ, et al. Coccidioidal pneumonia, Phoenix, Arizona, USA, 2000–2004. Emerg Infect Dis. 2009;15(3):397–401.

23. Bayer AS. Recognizing coccidioidomycosis. Am Fam Physician. 1980;22(3):133–141.

24. Lee LA, Yuan J, Vugia D, et al. Increased coccidioidomycosis among inmates at a California prison: initial investigation in 2005 to 2006. J Correct Health Care. 2017;23(3):347–352.

25. Saubolle MA, McKellar PP, Sussland D. Epidemiologic, clinical, and diagnostic aspects of coccidioidomycosis. JClin Microbiol. 2007;45(1):26–30.

26. Pappagianis D; Coccidioidomycosis Serology Laboratory. Coccidioidomycosis in California state correctional institutions. Ann N Y Acad Sci. 2007;1111:103–111.

27. Blair JE, Logan JL. Coccidioidomycosis in solid organ transplantation. Clin Infect Dis. 2001;33(9):1536–1544.

28. Ruddy BE, Mayer AP, Ko MG, et al. Coccidioidomycosis in African Americans. Mayo Clin Proc. 2011;86(1):63–69.

29. Bercovitch RS, Catanzaro A, Schwartz BS, et al. Coccidioidomycosis during pregnancy: a review and recommendations for management. Clin Infect Dis. 2011;53(4):363–368.

30. Kauffman CA. Primary coccidioidal infection. UpToDate. 2019. Accessed October 30, 2018. https://www.uptodate.com/contents/primary-coccidioidal-infection

31. Yozwiak ML, Lundergan LL, Kerrick SS, et al. Symptoms and routine laboratory abnormalities associated with coccidioidomycosis. West J Med. 1988;149(4):419–421.

32. McCarty JM, Demetral LC, Dabrowski L, et al. Pediatric coccidioidomycosis in central California: a retrospective case series. Clin Infect Dis. 2013;56(11):1579–1585.

33. Stockamp NW, Thompson GR III. Coccidioidomycosis. Infect Dis Clin North Am. 2016;30(1):229–246.

34. Blair JE, Ampel NM. Coccidioidomycosis: laboratory diagnosis and screening. UpToDate. 2019. Accessed October 30, 2018. https://www.uptodate.com/contents/coccidioidomycosis-laboratory-diagnosis-and-screening

35. Kikano GE, Fabien A, Schilz R. Evaluation of the solitary pulmonary nodule. Am Fam Physician. 2015;92(12):1084–1091. Accessed July 28, 2019. https://www.aafp.org/afp/2015/1215/p1084.html

36. Hospenthal DR, Thompson GR III, Oppenheimer AP, et al. Coccidioidomycosis and valley fever. September 20, 2018. Accessed January 30, 2019. https://emedicine.medscape.com/article/215978-overview

37. Ampel NM. Coccidioidomycosis in compromised hosts. UpToDate. 2019. Accessed October 30, 2018. https://www.uptodate.com/contents/coccidioidomycosis-in-compromised-hosts

38. Blair JE, Coakley B, Santelli AC, et al. Serologic testing for symptomatic coccidioidomycosis in immunocompetent and immunosuppressed hosts. Mycopathologia. 2006;162(5):317–324.

39. Blair JE, Currier JT. Significance of isolated positive IgM serologic results by enzyme immunoassay for coccidioidomycosis. Mycopathologia. 2008;166(2):77–82.

40. Kuberski T, Herrig J, Pappagianis D. False-positive IgM serology in coccidioidomycosis. JClin Microbiol. 2010;48(6):2047–2049.

41. Kaufman L, Sekhon AS, Moledina N, et al. Comparative evaluation of commercial Premier EIA and microimmunodiffusion and complement fixation tests for Coccidioides immitis antibodies. J Clin Microbiol. 1995;33(3):618–619.

42. Nascimento ER, Yamamoto R, Herrick KR, et al. Polymerase chain reaction for detection of Mycoplasma gallisepticum. Avian Dis. 1991;35(1):62–69.

43. Sachse K, Frey J, eds. PCR Detection of Microbial Pathogens. Humana Press; 2003:216.

44. Binnicker MJ, Buckwalter SP, Eisberner JJ, et al. Detection of Coccidioides species in clinical specimens by real-time PCR. J Clin Microbiol. 2007;45(1):173–178.

45. Vucicevic D, Blair JE, Binnicker MJ, et al. The utility of Coccidioides polymerase chain reaction testing in the clinical setting. Mycopathologia. 2010;170(5):345–351.

46. Mitchell M, Dizon D, Libke R, et al. Development of a real-time PCR assay for identification of Coccidioides immitis by use of the BD Max system. J Clin Microbiol. 2015;53(3):926–929.

47. Dizon D, Mitchell M, Dizon B, et al. The utility of real-time polymerase chain reaction in detecting Coccidioides immitis among clinical specimens in the Central California San Joaquin Valley. Med Mycol. 2019;57(6):688–693.

48. Saubolle MA, Wojack BR, Wertheimer AM, et al. Multicenter clinical validation of a cartridge-based real-time PCR system for detection of Coccidioides spp. in lower respiratory specimens. J Clin Microbiol. 2018;56(2):e01277–17.

49. Ampel NM, Giblin A, Mourani JP, et al. Factors and outcomes associated with the decision to treat primary pulmonary coccidioidomycosis. Clin Infect Dis. 2009;48(2):172–178.

50. Twarog M, Thompson GR III. Coccidioidomycosis: recent updates. Semin Respir Crit Care Med. 2015;36(5):746–755.

51. Santelli AC, Blair JE, Roust LR. Coccidioidomycosis in patients with diabetes mellitus. Am J Med. 2006;119(11):964–969.

52. Johnson RH, Einstein HE. Coccidioidal meningitis. Clin Infect Dis. 2006;42(1):103–107.

53. Sondermeyer Cooksey GL, Wilken JA, McNary J, et al. Dust exposure and coccidioidomycosis prevention among solar power farm construction workers in California. Am J Public Health. 2017;107(8):1296–1303.

54. Trinh SA, Echenique IA, Penugonda S, et al. Safety and efficacy of chronic suppressive azole therapy for endemic fungal infections in solid organ transplant recipients. Transpl Infect Dis. 2018;20(5):e12963.

55. Cole GT, Hurtgen BJ, Hung CY. Progress toward a human vaccine against coccidioidomycosis. Curr Fungal Infect Rep. 2012;6(4):235–244.

 

 

Copyright © 2020 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


More in AFP


Editor's Collections


Related Content


More in Pubmed

MOST RECENT ISSUE


Apr 15, 2021

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article