What is Coccidioidomycosis?
Coccidioidomycosis is a fungal infection mainly isolated to the lung that arises with inhaling the airborne spores of the Coccidioides fungi. It is also known as valley fever and is a common infection among people who live in endemic areas. Coccidioidomycosis is often asymptomatic and when people living in endemic areas develop the infection, it is usually acute. However, some patients do develop a very severe infection that can be chronic. Coccidioidomycosis is a relatively common cause of death in AIDS patients living in endemic regions, especially if the appropriate treatment is not forthcoming.
What Happens in Coccidioidomycosis?
The Coccidioides fungi thrives in the soil in certain regions of the world. When a portion of the fungus breaks off and becomes an airborne spore known as arthroconidia, it can enter the airways of humans. The arthroconidia transform into spherules within the airways. These spherules produce thousands of spores within itself and then rupture to release the endospores into the respiratory system. If these endospores are not neutralized, it can form new spherules and then more endospores thereby overwhelming the host.
In a person with adequate immune functioning, a type of immune cell known as a macrophage consumes these endospores. In this way the endospore is neutralized but acute inflammation is triggered in the process. However, with a massive inoculation dose and inadequate immune function, endospores and spherules attract other immune cells as well that attempt to wall off the fungus. Macrophages containing the fungus fuse to form giant cells and the entire mass is known as a granuloma. This marks the chronic inflammation phase.
Since coccidioidomycosis requires the action of immune cells to combat the infection, a person with impaired cell-mediated immunity is at greater risk of severe and chronic infections. Naturally, HIV/AIDS increases the risk as the virus destroys certain immune cells. However, severe coccidioidomycosis is not only seen in HIV/AIDS patients. It can affect any person who has a weakened immune system, even if it is just a short term state. The elderly and pregnant women are therefore also high risk groups.
In immunocompromised patients, the infection can become disseminated meaning that it spreads beyond the airways and lungs throughout the body to distant sites. This can occur when the infected macrophage moves through the lymphatics, then enters the bloodstream and the fungus is then spread through the circulation. Other sites that are frequently affected in disseminated coccidioidomycosis includes the skin and the tissue just beneath it (subcutaneous tissue), the bones and meninges.
Signs and Symptoms
Coccidioidomycosis causes symptoms about 14 days after contracting the infection. Some patients may develop symptoms as early as within a few days afterwards while symptoms may appear as late as one month after infection. However, it is important to note that less than 30% of patient who are exposed to the fungi and contract the infection will develop any symptoms. Often the infection goes unnoticed as patients are asymptomatic or the symptoms are so mild and non-specific that no further investigation is conducted.
Primary infection often resembles the flu. Some patients may also experience symptoms indicating acute bronchitis or acute pneumonia. In most cases the infection is self limiting and the symptoms may resolve on its own without any need for specific treatment. The more common symptoms of primary infection includes :
- Chest pain
- Shortness of breath
- Sputum production
- Coughing up of blood (hemoptysis)
- Sore throat
Other symptoms that may also be seen in primary coccidioidomycosis includes :
- Joint pains (arthralgia)
- Pink eye (conjunctivitis)
- Skin rash (erythema nodosum or urticaria)
- Night sweats
- Weight loss
Eye and skin symptoms in the primary infection is usually a result of an immune reaction to the fungi and not due to an infection at these sites. Should the primary infection not resolve, coccidioidomycocis may lead to pneumonia and chronic lung infection.
In progressive coccidioidomycosis, there may be severe and extensive lung involvement. It is marked by granuloma formation and cavitations in the lung. It can arise weeks, months or years after the primary infection resolves. It may initially appear with non-specific symptoms such as weakness, loss of appetite, low-grade fever and weight loss. Progressive coccidioidomycosis involving the lungs may present with severe difficulty in breathing, cyanosis (bluish discoloration of the skin) and bloody sputum.
There is a risk of the disease extending beyond the lungs – extrapulmonary involvement. The skin, bones and meninges are commonly involved sites. Without treatment, disseminated coccidioidomycosis is often fatal. AIDS patients are at the greatest risk of death. Disseminated coccidioidomycosis, beyond the respiratory system, is considered an AIDS-defining condition in HIV-infected patients.
Causes of Valley Fever
Coccidioidomycosis is caused by the Coccioides fungi – C. immitis and C. posadasii. The fungi are endemic in certain regions of the United States, Mexico, Central and South America. The soil-dwelling fungi gains entry into the human body when the airborne spore is inhaled. In very rare cases the spores have been on other inanimate objects (fomites) and infection arose at areas outside of the endemic region. Despite regular exposure to the fungus, majority of the people living in the endemic areas will not develop symptoms.
The single greatest contributing factor for developing coccidioidomycosis is a weakened immune system. Although people who are immunocompetent may also develop the infection, it is usually self-limiting. Immunocompromised people develop a more severe disease, which can progress to chronic lung infection or even disseminated disease once the infection spreads beyond the respiratory symptoms. Another major contributing factor is the inoculation dose although even a single spore may be sufficient to cause an infection in immunocompromised patients.
- Pregnancy (second half)
- Elderly patients
- Long term corticosteroid use
- Anti-rejection drugs for organ transplantation
- Diabetes mellitus
- Pre-existing chronic lung disease
Diagnosis of Coccidioidomycosis
Coccidioidomycosis should be considered as a diagnosis in patients with severe respiratory disease, who live in an endemic region and are immunocompromised. However, further investigations are required to confirm the diagnosis. These investigations include :
- Sputum culture to grow the fungus in the laboratory and confirm its presence. Culture of other secretions and tissues may also be used especially if there is disseminated disease.
- Blood tests to identify antibodies that have formed against the Coccidioides fungi.
- Polymerase chain reaction (PCR) testing to detect the fungal genes in the sputum, blood, urine, CSF or biopsied tissue.
- Skin testing can confirm exposure to Coccidioides fungi but is not useful for people who live in endemic regions.
Other diagnostic investigations may be utilized to evaluate the severity and extent of the infection. This includes chest X-rays, computed tomography (CT) scan and bronchoscopy.
Treatment of Coccidioidomycosis
Coccidioidomycosis may not require specific treatment as the infection often resolves on its own, even when symptomatic. Supportive measures like bed rest, fluid intake and medication for symptomatic relief will suffice. However, more severe and prolonged infections or disseminated disease requires specific medical treatment. Untreated disseminated disease is usually fatal. Antifungal drugs are needed and the two most commonly used agents include :
- Fluconazole for mild to moderate illness. It is less toxic and can therefore be used on long term basis in high risk individuals like AIDS patients. Other azoles that may be considered includes voriconazole and itraconazole.
- Amphotericin B for more severe illness but should be used for short periods due to toxicity. It may then be followed by fluconazole on a long term basis if necessary and if the drug is tolerated by the patient.