Coccidioidomycosis

Coccidioidomycosis is a mammalian fungal disease caused by Coccidioides immitis or Coccidioides posadasii. It is commonly known as cocci, Valley fever, or San Joaquin Valley fever. Coccidioidomycosis is endemic in certain parts of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico.

Description

Classification

After Coccidioides infection, coccidioidomycosis begins with Valley fever, its initial acute form. Valley fever may progress to the chronic form and then to disseminated coccidioidomycosis. Therefore, coccidioidomycosis may be divided into the following types:

Acute coccidioidomycosis, sometimes described in the literature as primary pulmonary coccidioidomycosis
Chronic coccidioidomycosis
Disseminated coccidioidomycosis, which includes primary cutaneous coccidioidomycosis

Valley fever is not a contagious disease. In some cases, the infection may recur or become chronic.

Signs and symptoms

An estimated 60% of people infected with the fungi responsible for coccidioidomycosis have minimal to no symptoms, while 40% will have a range of possible clinical symptoms. Of those who do develop symptoms, the primary infection is most often respiratory, with symptoms resembling bronchitis or pneumonia that resolve over a matter of a few weeks. In endemic regions, coccidioidomycosis is responsible for 20% of cases of community-acquired pneumonia. Notable coccidioidomycosis signs and symptoms include a profound feeling of tiredness, loss of smell and taste, fever, cough, headaches, rash, muscle pain, and joint pain. Fatigue can persist for many months after initial infection. The classic triad of coccidioidomycosis known as "desert rheumatism" includes the combination of fever, joint pains, and erythema nodosum.
A minority of infected individuals do not recover from the initial acute infection and develop a chronic infection. This can take the form of chronic lung infection or widespread disseminated infection. Chronic infection is responsible for most of the morbidity and mortality. Chronic fibrocavitary disease is manifested by cough, fevers, night sweats, and weight loss. Osteomyelitis, including involvement of the spine, and meningitis may occur months to years after initial infection. Severe lung disease may develop in HIV-infected persons.

Complications

Serious complications may occur in patients who have weakened immune systems, including severe pneumonia with respiratory failure and bronchopleural fistulas requiring resection, lung nodules, and a possible disseminated form, where the infection spreads throughout the body. The disseminated form of coccidioidomycosis can devastate the body, causing skin ulcers, abscesses, bone lesions, swollen joints with severe pain, heart inflammation, urinary tract problems, and inflammation of the brain's lining, which can lead to death. Coccidioidomycosis is a common cause of community-acquired pneumonia in the endemic areas of the United States. Infections usually occur due to inhalation of the arthroconidial spores after soil disruption.
A particularly severe case of meningitis caused by Valley fever in 2012 initially received several incorrect diagnoses, such as sinus infections and cluster headaches. The patient could not work during the diagnosis and the original search for treatments. Eventually, the right treatment was found—albeit with severe side effects—requiring four pills a day and medication administered directly into the brain every 16 weeks.

Cause

C. immitis is a dimorphic saprophytic fungus that grows as a mycelium in the soil and produces a spherule form in the host organism. It resides in the soil in certain parts of the southwestern United States, most notably in California and Arizona. It is also commonly found in northern Mexico, and parts of Central and South America. C. immitis is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when it rains. The spores, known as arthroconidia, are swept into the air by disruption of the soil, such as during construction, farming, low-wind or singular dust events, or an earthquake. Windstorms may also cause epidemics far from endemic areas. In December 1977, a windstorm in an endemic area around Arvin, California led to several hundred cases, including deaths, in non-endemic areas hundreds of miles away.
Rain starts the cycle of initial growth of the fungus in the soil. In soil, Coccidioides exist in filament form. It forms hyphae in both horizontal and vertical directions. Over a prolonged dry period, cells within hyphae degenerate to form alternating barrel-shaped cells which are light in weight and carried by air currents. This happens when the soil is disturbed, often by clearing trees, construction, or farming. As the population grows, so do all these activities, causing a potential cascade effect. The more land that is cleared and the more arid the soil, the riper the environment for Coccidioides. These spores can be easily inhaled unknowingly. On reaching alveoli, they enlarge in size to become spherules, and internal septations develop. This division of cells is made possible by the optimal temperature inside the body. Septations develop and form endospores within the spherule. The rupture of spherules releases these endospores, which in turn repeat the cycle and spread the infection to adjacent tissues within the infected individual's body. Nodules can form in the lungs surrounding these spherules. When they rupture, they release their contents into the bronchi, forming thin-walled cavities. These cavities can cause symptoms including characteristic chest pain, coughing up blood, and persistent cough. In individuals with a weakened immune system, the infection can spread through the blood. The fungus can also, rarely, enter the body through a break in the skin and cause infection.

Diagnosis

Coccidioidomycosis diagnosis relies on a combination of an infected person's signs and symptoms, findings on radiographic imaging, and laboratory results.
The disease is commonly misdiagnosed as bacterial community-acquired pneumonia. The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy tissue by methods of Papanicolaou or Grocott's methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.
With specific nucleotide primers, C. immitis DNA can be amplified by polymerase chain reaction. It can also be detected in culture by morphological identification or by using molecular probes that hybridize with C. immitis RNA. C. immitis and C. posadasii cannot be distinguished on cytology or by symptoms, but only by DNA PCR.
An indirect demonstration of fungal infection can also be achieved by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in cerebrospinal fluid. TP antibody is specific and is used as a confirmatory test, whereas ELISA is sensitive and thus used for initial testing.
If the meninges are affected, CSF will show abnormally low glucose levels, an increased level of protein, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present.

Imaging

rarely demonstrate lung nodules or cavities. These images commonly demonstrate lung opacification, pleural effusions, or enlargement of lymph nodes associated with the lungs. Computed tomography scans of the chest are more sensitive than chest X-rays to detect these changes.

Prevention

Preventing coccidioidomycosis is challenging because it is difficult to avoid breathing in the fungus should it be present; however, the public health effects of the disease are essential to understand in areas where the fungus is endemic. Enhancing surveillance of coccidioidomycosis is key to preparedness in the medical field and improving diagnostics for early infections. No completely effective preventive measures are available for people who live or travel through Valley fever-endemic areas. Recommended preventive measures include avoiding airborne dust or dirt, but this does not guarantee protection against infection. People in certain occupations may be advised to wear face masks. The use of air filtration indoors is also helpful, in addition to keeping skin injuries clean and covered to avoid skin infection.
From 1998 to 2011, there were 111,117 U.S. cases of coccidioidomycosis logged in the National Notifiable Diseases Surveillance System. Since many U.S. states do not require reporting of coccidioidomycosis, the actual numbers may be higher. The United States' Centers for Disease Control and Prevention called the disease a "silent epidemic" and acknowledged that there is no proven anticoccidioidal vaccine available. A 2001 cost-effectiveness analysis indicated that a potential vaccine could improve health as well as reducing total health care expenditures among infants, teens, and immigrant adults, and more modestly improve health but increase total health care expenditures in older age groups.
Raising surveillance and disease awareness while medical researchers develop a human vaccine can positively contribute to prevention efforts. Research demonstrates that patients from endemic areas who are aware of the disease are most likely to request diagnostic testing for coccidioidomycosis. Presently, Meridian Bioscience manufactures the so-called EIA test to diagnose the Valley fever, which however is known for producing a fair quantity of false positives. Recommended prevention measures can include type-of-exposure-based respirator protection for persons engaged in agriculture, construction, and others working outdoors in endemic areas. Dust control measures such as planting grass and wetting the soil, and also limiting exposure to dust storms are advisable for residential areas in endemic regions.