Coccidioidomycosis, also known as Valley Fever, is a fungal infection caused by breathing in tiny airborne spores from the fungi Coccidioides immitis and Coccidioides posadasii. These fungi live in dry, sandy soil and are most common in hot desert regions. The spores become airborne when the soil is disturbed by wind, farming, or construction. People and animals can become infected by inhaling the spores, but the disease does not spread from person to person.
The infection mainly affects the lungs. In many people, it causes no symptoms or only a mild illness that resembles the flu and clears on its own. Symptoms can include fever, cough, chest pain, tiredness, shortness of breath, headache, and muscle or joint pain. Some patients may also develop a rash called erythema nodosum, which appears as red, tender bumps on the skin. In more serious cases, the infection can cause long-lasting pneumonia or damage to lung tissue.
In a small number of cases, the fungus spreads from the lungs to other parts of the body through the blood or lymph system. This is called disseminated coccidioidomycosis and may affect the skin, bones, joints, or lymph nodes. Rarely, it reaches the brain and causes meningitis, a life-threatening condition. People with weakened immune systems, pregnant women, and those of African or Filipino ancestry are at higher risk of developing this severe form.
Most infections get better without treatment. However, doctors prescribe antifungal medicines such as fluconazole or itraconazole for people with severe or long-lasting disease. Infections of the brain may require lifelong treatment, and a stronger drug, amphotericin B, is sometimes used for the most serious cases.
The disease is most common in the southwestern United States, especially Arizona and California’s San Joaquin Valley, as well as parts of Mexico, Central America, and South America. Reported cases have increased in recent years, possibly due to population growth in affected regions, climate change, and better disease tracking. Preventive measures focus on limiting exposure to dust in high-risk areas, including wearing protective masks, staying indoors during dust storms, and wetting soil before digging or construction.
Historical Background
Coccidioidomycosis was first described in 1892 by Dr. Alejandro Posadas in Argentina. Initially mistaken for tuberculosis due to similar lung symptoms, it took decades to identify its fungal cause.
The term Valley fever originated from outbreaks in California’s San Joaquin Valley during the 1930s. Advances in medical mycology in the mid-20th century clarified fungal life cycles and environmental sources.
Since then, research has improved diagnostic methods and treatment protocols. The disease remains important for public health in endemic regions.
Causes and Transmission
Coccidioidomycosis arises from exposure to specific fungal organisms that live in certain environmental conditions. The disease is closely linked to the ecology of the fungi, the characteristics of the soil in which they grow, and human activities that disturb the ground.
Causative Organisms
The infection is caused by two closely related fungal species, Coccidioides immitis and Coccidioides posadasii. Both are soil-dwelling fungi that naturally occur in arid and semi-arid environments. They produce microscopic reproductive structures called arthroconidia, a type of spore that can easily break free from fungal filaments and become airborne. These spores are highly resistant to environmental stress, making them capable of surviving in harsh desert soils for long periods.
When inhaled, the arthroconidia transform inside the human body into larger structures called spherules. These spherules mature and release hundreds of smaller particles known as endospores, which spread the infection within tissues and perpetuate the disease process. Unlike many infectious agents, Coccidioides does not require an animal or human host to complete its life cycle. Importantly, coccidioidomycosis is not spread from person to person; transmission occurs exclusively through environmental exposure.
Environmental Factors
The distribution of Coccidioides is strongly influenced by environmental conditions. These fungi thrive in soils that are dry, sandy or silty, alkaline in pH, and often contain moderate levels of salt. Endemic regions typically experience hot summers, mild winters, and limited annual rainfall. Periods of rain encourage fungal growth in the soil, while subsequent dry spells promote fragmentation of fungal filaments into infectious arthroconidia.
Soil disturbance is the main factor that brings the spores into the air. Agricultural activities, construction, military training exercises, and archaeological digs have all been associated with outbreaks. Natural phenomena such as earthquakes, windstorms, and dust storms can also raise large amounts of spores into the atmosphere, increasing the likelihood of inhalation by people and animals. Spores can travel significant distances in the air, meaning that individuals without direct soil contact may still be exposed during dust events.
Changes in land use and climate may further influence fungal activity and disease incidence. Warmer temperatures, droughts followed by rainfall, and increased human settlement in desert regions have all been associated with rising case numbers in endemic areas.
Routes of Infection
The vast majority of infections occur through inhalation of airborne arthroconidia. Once inhaled, the spores reach the alveoli, the tiny air sacs in the lungs, where they initiate infection. The likelihood of developing illness depends on several factors, including the number of spores inhaled, the individual’s immune status, and genetic predisposition.
Although extremely uncommon, coccidioidomycosis can also be acquired through direct inoculation when spores enter the skin through cuts or puncture wounds. This route has been documented in laboratory accidents and rare environmental exposures but is not considered a major pathway of transmission.
Person-to-person spread of the disease does not occur under natural circumstances. The infection cannot be passed through casual contact, respiratory droplets, or blood transfusion. As such, coccidioidomycosis is regarded as an environmentally acquired infection, with prevention strategies focusing on minimizing exposure to contaminated dust and soil in endemic regions.
Risk Factors
Several specific factors influence the likelihood of contracting coccidioidomycosis. These include where a person lives or travels, their workplace environment, and individual characteristics such as age or health status.
Geographic Distribution
Geography is the most significant determinant of exposure. Coccidioidomycosis is endemic to arid and semi-arid regions of the southwestern United States, particularly Arizona where the highest number of cases are reported and California’s San Joaquin Valley. The disease is also found in parts of Nevada, New Mexico, Texas, and Utah, as well as in regions of Mexico, Central America, and South America.
The fungi Coccidioides immitis and Coccidioides posadasii thrive in sandy, alkaline soils typical of desert and semi-desert climates. Periods of rainfall promote fungal growth, while subsequent dry spells increase the fragmentation of fungal filaments into infectious arthroconidia. These spores are readily carried into the air when soil is disturbed, making inhalation the primary route of infection. Seasonal fluctuations are also important: infection risk is higher during dry, dusty seasons and during environmental events such as dust storms or earthquakes, which can spread spores over long distances.
Populations residing in endemic areas have the greatest baseline risk, though travelers can also acquire the disease after brief exposure. Infections have been reported in individuals with no direct soil contact
Occupational Exposure
Certain occupations significantly increase the risk of coccidioidomycosis due to frequent soil disruption. Agricultural workers, construction crews, and road maintenance teams are particularly vulnerable, as their work commonly disturbs contaminated soil. Archaeologists and paleontologists working in desert environments have also been identified as an at-risk group.
Military personnel training in endemic regions represent another well-documented high-risk population, as large-scale exercises may involve digging, crawling, or exposure to dust clouds. Outbreaks among prisoners and correctional staff in endemic areas have also been noted, likely due to prolonged outdoor exposure in dusty environments.
The risk of occupational exposure can be reduced through preventive measures such as dust suppression (for example, wetting soil before digging), limiting outdoor work during high wind conditions, and using respiratory protection in high-exposure settings. Employers in endemic regions often adopt occupational health guidelines to mitigate these risks.
Demographic Vulnerabilities
While most cases of coccidioidomycosis are mild or asymptomatic, certain populations are more likely to develop severe disease or disseminated infection. People of African or Filipino descent have been shown to have a higher risk of dissemination, possibly due to genetic or immunological factors. Pregnant women, especially in the later stages of pregnancy, are also more susceptible, likely due to hormonal and immune system changes.
Immunocompromised individuals face the greatest risk of serious outcomes. Patients with HIV/AIDS, those receiving immunosuppressive therapy (such as chemotherapy or corticosteroids), and organ transplant recipients are more likely to develop widespread infection. Older adults and people with chronic lung diseases such as chronic obstructive pulmonary disease (COPD) or asthma are also at increased risk for complications, as pre-existing respiratory conditions can worsen the effects of pulmonary coccidioidomycosis.
Clinical Manifestations
Coccidioidomycosis primarily affects the respiratory system but can also progress to more severe forms depending on host factors. Symptoms range from mild respiratory illness to chronic lung disease or systemic spread affecting multiple organs.
Acute Pulmonary Coccidioidomycosis
Acute pulmonary infection is the most common initial presentation, typically developing one to three weeks after exposure to airborne Coccidioides spores. Patients frequently report nonspecific symptoms resembling influenza or community-acquired pneumonia. These may include fever, dry cough, chest pain, shortness of breath, chills, night sweats, headache, and marked fatigue. Some patients also experience arthralgia (joint pain) and myalgia (muscle pain).
A notable skin manifestation is erythema nodosum, characterized by painful red nodules, usually on the shins, which represent an immune response to infection rather than direct fungal invasion. Erythema multiforme, another hypersensitivity reaction, may also occur. Laboratory findings can include eosinophilia (increased levels of a type of white blood cell), which is suggestive but not specific to the disease.
Chest radiographs often reveal unilateral or bilateral pulmonary infiltrates, which may appear as patchy or nodular opacities. Hilar or mediastinal lymphadenopathy can also be seen. Because of its clinical overlap with bacterial pneumonia and influenza, acute coccidioidomycosis is frequently underdiagnosed or misdiagnosed. In most otherwise healthy individuals, symptoms resolve within weeks to months without medical intervention, though fatigue and cough may persist for an extended period.
Chronic Pulmonary Disease
A minority of patients, particularly those with pre-existing lung disease or impaired immune defenses, progress to chronic pulmonary coccidioidomycosis. This form typically emerges months to years after the initial infection and may present with prolonged cough, weight loss, chest pain, hemoptysis (coughing up blood), and recurrent low-grade fevers.
Radiologically, chronic disease is characterized by persistent pulmonary infiltrates, cavitary lesions, nodules, or progressive fibrosis. Cavities most often form in the upper lobes and may remain stable, enlarge, or cause complications such as rupture into the pleural space, leading to pneumothorax. Secondary bacterial or fungal infections within these cavities are also possible.
Because the clinical and radiographic features of chronic coccidioidomycosis strongly resemble pulmonary tuberculosis, accurate diagnosis requires fungal culture, histopathology, or serologic testing. Long-term antifungal therapy, often lasting years, is typically required. In refractory cases or when cavities cause significant complications, surgical intervention may be considered.
Disseminated Coccidioidomycosis
Disseminated infection occurs when Coccidioides spreads beyond the lungs via the bloodstream or lymphatic system. Although it represents less than 1% of infections, it is the most severe manifestation of the disease. Dissemination is more common in immunocompromised patients, pregnant women, and certain ethnic groups, including individuals of African and Filipino descent.
The skin is the most frequent site of dissemination outside the lungs. Lesions vary widely in appearance, ranging from papules and pustules to verrucous plaques, ulcers, or nodules that may resemble other chronic skin infections. Bone involvement, particularly in the vertebrae, long bones, and skull, results in osteomyelitis and is associated with localized pain, swelling, and, in advanced cases, deformity. Joint involvement can lead to chronic arthritis with swelling and reduced mobility.
A particularly severe complication is coccidioidal meningitis, which occurs when the fungus invades the central nervous system. Symptoms include persistent headaches, fever, nausea, vomiting, confusion, and neurological deficits such as vision changes or seizures. Cerebrospinal fluid (CSF) analysis typically shows elevated white blood cell counts, high protein levels, and low glucose, with fungal culture or molecular testing confirming the diagnosis.
Disseminated disease requires prolonged antifungal treatment, often with azoles such as fluconazole or itraconazole. In the case of coccidioidal meningitis, lifelong antifungal therapy is usually necessary to prevent relapse. Amphotericin B may be used in severe or refractory cases, though its use is limited by toxicity.
Diagnosis of Coccidioidomycosis
Diagnosis involves thorough clinical assessment supported by laboratory methods. Identifying characteristic symptoms guides testing choices, while specific lab tests confirm the presence of Coccidioides infection.
Clinical Evaluation
The first step in diagnosis is a detailed clinical assessment. Patients often present with fever, cough, chest pain, shortness of breath, or fatigue, typically occurring within one to three weeks after inhalation of Coccidioides arthroconidia. A thorough medical history is essential, particularly regarding travel or residence in endemic areas of the southwestern United States (Arizona, California, New Mexico, Texas, Nevada, Utah) and parts of Mexico or Central and South America.
Exposure history plays a critical role. Occupations such as farming, construction, or military training in dusty environments increase suspicion. In addition, immunosuppressive conditions (e.g., HIV/AIDS, organ transplantation, corticosteroid therapy), pregnancy, and certain ethnic backgrounds (African or Filipino descent) should raise awareness of possible severe or disseminated disease.
Physical examination may reveal nonspecific pulmonary signs such as crackles, decreased breath sounds, or wheezing, though many patients show minimal findings. Extrapulmonary manifestations, including skin lesions or joint involvement, should also be noted, as they may indicate dissemination.
Because the symptoms overlap with common respiratory infections, coccidioidomycosis is frequently misdiagnosed as community-acquired pneumonia or even lung cancer.
Laboratory Testing
Laboratory confirmation is essential, as clinical suspicion alone is insufficient. Several diagnostic methods are available, each with unique advantages and limitations:
1. Serologic Assays
Serologic testing forms the cornerstone of diagnosis. Enzyme immunoassay (EIA) is the most widely used initial screening test, capable of detecting both IgM (acute infection) and IgG (progressive or past infection) antibodies. Positive EIA results are often followed by confirmatory tests such as immunodiffusion (ID) or complement fixation (CF), which provide greater specificity and can assess disease severity. High CF titers are associated with disseminated or severe infections.
2. Culture
Definitive diagnosis can be achieved by culturing Coccidioides from sputum, bronchoalveolar lavage fluid, pleural fluid, or tissue samples. However, culturing poses significant biosafety risks due to the ease with which arthroconidia become airborne, requiring biosafety level 3 (BSL-3) laboratory precautions. Positive cultures provide a clear diagnosis but are less commonly pursued in routine settings due to these hazards.
3. Histopathology
Tissue biopsy specimens may reveal characteristic spherules containing endospores, visible with periodic acid–Schiff (PAS) or Gomori methenamine silver (GMS) staining. Histopathology is especially valuable in cases involving extrapulmonary sites such as bone or skin lesions. However, absence of spherules does not fully exclude the disease, and results must be interpreted alongside clinical and serologic findings.
4. Molecular Testing
Polymerase chain reaction (PCR) and other nucleic acid amplification techniques are under development and increasingly available in some centers. These methods offer faster turnaround times and may detect fungal DNA in blood, respiratory, or tissue samples. Despite their promise, molecular tests are not yet widely standardized or universally available, limiting their routine use.
Imaging Studies
Chest imaging provides supportive evidence but is rarely diagnostic on its own. Chest X-rays or computed tomography (CT) scans may reveal pulmonary infiltrates, nodules, or cavities. These findings can mimic tuberculosis, histoplasmosis, or malignancies, necessitating laboratory confirmation. In disseminated cases, imaging may extend to other organs, such as MRI for suspected coccidioidal meningitis.
Treatment Options
Treatment for coccidioidomycosis primarily involves antifungal medications, with choice and intensity depending on disease severity. The length of treatment varies significantly based on the patient’s response and the specific form of the infection.
Antifungal Therapies
1. Azole Antifungals
Azoles remain the mainstay of therapy for most patients.
- Fluconazole is commonly used due to its excellent oral bioavailability, tolerability, and central nervous system (CNS) penetration, making it the first-line agent for coccidioidal meningitis. Doses range from 400–800 mg daily, but higher doses may be required for severe infections.
- Itraconazole is another effective oral option, often used for bone, joint, or cutaneous involvement. Its absorption depends on gastric acidity, and it requires close monitoring of serum levels to ensure therapeutic efficacy.
- Other azoles, such as voriconazole and posaconazole, may be considered in refractory cases or when patients cannot tolerate fluconazole or itraconazole. These newer azoles offer broader antifungal coverage but are associated with higher costs and potential toxicities.
2. Amphotericin B
Amphotericin B, particularly in its lipid formulations, is reserved for severe, rapidly progressive, or disseminated disease. It is often used in hospitalized patients with life-threatening infections, such as severe pulmonary disease, meningitis unresponsive to azoles, or extensive dissemination. While effective, amphotericin B carries a high risk of nephrotoxicity and electrolyte disturbances, requiring close monitoring of kidney function and serum electrolytes.
In rare and complicated cases, combination therapy with azoles and amphotericin B may be employed, though evidence is limited. Adjunctive surgical intervention, such as debridement of infected bone or resection of cavitary lung lesions, may be necessary in refractory or structurally destructive disease.
Duration of Therapy
The length of treatment varies widely, reflecting the complexity of the disease.
- Uncomplicated Pulmonary Coccidioidomycosis: Many otherwise healthy individuals recover without antifungal therapy, though treatment may be given to reduce symptom duration. When used, azoles are typically prescribed for 3 to 6 months.
- Chronic Pulmonary Disease: Patients with persistent cavities, fibrosis, or nodules may require 12 months or more of continuous therapy. Cavitary lesions often relapse after discontinuation, necessitating extended or repeated courses of antifungals.
- Disseminated Coccidioidomycosis: Involvement of the skin, bones, or joints usually requires prolonged treatment lasting 1 to 3 years, with some patients needing indefinite suppressive therapy to prevent relapse.
- Coccidioidal Meningitis: This is the most severe form of the disease and requires lifelong antifungal therapy, typically with high-dose fluconazole. Stopping treatment almost invariably leads to relapse.
Prevention and Control
Preventing coccidioidomycosis requires minimizing exposure to dust particles that carry the fungal spores.
Personal Protective Measures
At the individual level, minimizing exposure to contaminated dust is the most direct method of prevention. People living in or visiting endemic areas should exercise caution during outdoor activities, especially in rural or construction-heavy environments.
- Respiratory Protection: Wearing well-fitted N95 respirators or other particulate-filtering masks can significantly reduce the risk of inhaling spores. These masks are recommended during dust storms, outdoor labor, or soil-disturbing activities.
- Protective Clothing: Long-sleeved shirts, pants, and closed shoes can help minimize skin contact with dust. Although skin inoculation is rare, protective clothing also reduces irritation from airborne soil particles and allergens.
- Soil Wetting Practices: Wetting soil before digging, farming, or construction activities decreases the amount of airborne dust generated, lowering the chances of spore inhalation.
- Avoidance Strategies: Individuals at higher risk, such as immunocompromised patients, pregnant women, or people with chronic lung disease, should avoid unnecessary travel to highly endemic areas and refrain from dust-generating outdoor activities whenever possible.
Occupational Safety and Risk Reduction
Certain professions, such as farming, military training, construction, and archaeology, carry a higher occupational risk. Employers in endemic regions are encouraged to implement protective measures to safeguard workers.
- Using soil stabilizers, water sprays, or vegetation to reduce dust during construction and agricultural operations helps limit spore dispersal.
- Enclosing soil-disrupting equipment or using air filtration systems in vehicles and workspaces can reduce airborne exposure.
- Occupational safety guidelines recommend equipping workers with respirators and providing training on their correct use.
- Workers should be informed about the risks of coccidioidomycosis and trained in preventive measures, including recognizing early symptoms for timely medical evaluation.
Complications and Prognosis
Coccidioidomycosis can lead to a range of complications depending on the severity and the patient’s immune status. Most individuals experience mild symptoms and recover without lasting effects.
However, in some cases, the infection may disseminate beyond the lungs. This can affect the skin, bones, joints, and central nervous system, causing serious health issues.
Common complications include:
- Pulmonary Nodules: Residual nodules may remain in the lungs after resolution of infection. These are often discovered incidentally on imaging and are usually asymptomatic, but they can be mistaken for malignancy, necessitating further evaluation.
- Pulmonary Cavities: Some patients develop cavitary lesions in the lung tissue. These cavities may persist for years, sometimes enlarging or rupturing, leading to complications such as hemoptysis (coughing up blood) or secondary bacterial and fungal infections.
- Chronic pneumonia (explained in paragraphs above)
The prognosis of coccidioidomycosis is variable and depends on the form of the disease, host characteristics, and timeliness of diagnosis and treatment.
- Uncomplicated Pulmonary Disease: Most patients recover fully within weeks to months, often without requiring antifungal therapy. Some may experience lingering fatigue, but long-term outcomes are favorable.
- Chronic Pulmonary Disease: Patients may experience persistent symptoms and radiographic abnormalities, requiring long-term antifungal therapy and regular monitoring. Prognosis is guarded but manageable with treatment.
- Disseminated Disease: Outcomes are significantly worse, with high morbidity and potential for relapse even under therapy. Lifelong antifungal treatment is often necessary, particularly in cases of meningitis.
- CNS Involvement: Coccidioidal meningitis carries the poorest prognosis. With continuous treatment, survival has improved, but neurological complications may persist.
| Factor | Impact on Prognosis |
| Healthy immune system | Usually favorable recovery |
| Immunosuppression | Increased risk of spread |
| Early diagnosis | Better treatment response |
| Delay in treatment | Higher complication risk |