Coccidioidomycosis

Coccidioidomycosis
Classification and external resources
Histopathological changes in a case of coccidioidomycosis of the lung showing a large fibrocaseous nodule.
ICD-10	B38
ICD-9	114
MedlinePlus	001322
eMedicine	med/103 ped/423
MeSH	D003047

Coccidioidomycosis (pron.: /kɒkˌsɪdiɔɪdoʊmaɪˈkoʊsɪs/, (kok-sid-e-oy-doh-my-KOH-sis), commonly known as "Valley fever", as well as "California fever", "Desert rheumatism", and "San Joaquin Valley fever") is a fungal disease caused by Coccidioides immitis or C. posadasii. It is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah and northern Mexico.

C. immitis resides in the soil in certain parts of the southwestern United States, northern Mexico, and parts of Central and South America. It is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when the rains come. The spores, known as arthroconidia, are swept into the air by disruption of the soil, such as during construction, farming, or an earthquake.

Infection is caused by inhalation of the particles. The disease is not transmitted from person to person. The infection ordinarily resolves leaving the patient with a specific immunity to re-infection.C. immitis is a dimorphic saprophytic organism that grows as a mycelium in the soil and produces a spherule form in the host organism.

Epidemiology

It is confined to the western hemisphere between 40° N and 40° S. Dry soil, especially in the Lower Sonaran Life Zone, is supportive of the organism's growth. In harmony with organism's life history, incidence increases with periods of dryness after a rainy season; this phenomenon, termed "grow and blow", refers to growth of the fungus in wet weather, producing spores which are spread by the wind during succeeding dry weather.

Besides humans, dogs, and cats, the fungus can be shown to infect most mammals, even if they do not get sick from it very often. Species in which Valley Fever has been found include livestock such as cattle and horses; llamas; marine mammals, including sea otter; zoo animals such as monkeys and apes, kangaroos, tigers, etc; and wildlife endemic to the geographic area such as cougar, skunk, and javelina.

The geographic distribution of coccidioidomycosis.

Incidence (North America)

California state prisons, as far back as 1919, have been particularly affected by Coccidioidomycosis. In 2005 and 2006, the Pleasant Valley State Prison near Coalinga and Avenal State Prison near Avenal on the western side of the San Joaquin Valley had the highest incidence in 2005, of at least 3,000 per 100,000. The receiver appointed in Plata v. Schwarzenegger issued an order in May 2013 requiring relocation of vulnerable populations in those prisons.

Incidence varies widely across the west and southwest. In Arizona, for instance, in 2007, there were 3,450 cases in Maricopa County, which in 2007 had an estimated population of 3,880,181 for an incidence of approximately 1 in 1,125. In contrast, though southern New Mexico is considered an endemic region, there were 35 cases in the entire state in 2008, and 23 in 2007, in a region that had an estimated 2008 population of 1,984,356 for an incidence of approximately 1 in 56,695.

There was an outbreak in the summer of 2001 in Colorado, away from where the endemic is persistent. A group of archeologists visited Dinosaur National Monument, and eight members of the crew, along with two National Park Service workers were diagnosed with valley fever.

Infection rates vary greatly by county, and although population density is important, so are other factors that have not been proven yet. Greater construction activity may disturb spores in the soil. In addition, the effect of altitude on fungi growth and morphology has not been studied, and altitude can range from sea level to 10,000 feet or higher across California, Arizona, Texas and New Mexico.

In California from 2000 to 2007, there were 16,970 reported cases (5.9 per 100,000 people) and 752 deaths (0.26 per 100,000 people) with the highest incidence in the San Joaquin Valley (44.1 per 100,000). Following the Northridge Earthquake, there was a sudden increase of cases in the areas affected by the quake, at a pace of over 10 times baseline.^{[citation needed]}

Pathogenesis

Life cycle of coccidioides

In soil (and also in agar media), coccidioides exists in filament form. It forms hyphae in both horizontal and vertical directions. With time, cells within hyphae degenerate to form alternating barrel-shaped cells (arthroconidia). Arthroconidia are light-weight and carried by air currents. They can be easily inhaled without the person knowing. On arriving in alveoli, they enlarge in size and internal septations are developed. This structure is called a spherule. Septations develop to form endospores. Rupture of spherules release these endospores, which in turn repeat the cycle and spread the infection locally. Nodules can form in lungs surrounding these spherules. When these rupture, they release their contents into bronchi, forming thin-walled cavities. These cavities can result in symptoms like characteristic chest pain, hemoptysis and persistent cough. In immunocompromised individuals, infection spreads through blood.

Presentation

Symptomatic infection (40% of cases) usually presents as an influenza-like illness with fever, cough, headaches, rash, myalgia (muscle pain), and arthralgia (joint pain). The rash is maculopapular. Erythema nodosum on lower extremities, and erythema multiforme in necklace-like fashion can occur predominantly in women.

Some patients fail to recover and develop chronic pulmonary infection or widespread disseminated infection (affecting meninges, soft tissues, joints, and bone). Severe pulmonary disease may develop in HIV-infected persons.

In order of decreasing risk, people of Filipino, African, Native American, Hispanic, and Asian descent are susceptible to the disseminated form of the disease. Immunocompromised individuals are more susceptible to the disease.

Types

Coccidioidomycosis may be divided into the following types:

• Primary pulmonary coccidioidomycosis
• Disseminated coccidioidomycosis
• Primary cutaneous coccidioidomycosis

Diagnosis

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 Gomori's methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.

With specific nucleotide primers C.immitis DNA can be amplified by PCR. 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 be achieved also by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin (TP) assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in CSF. TP antibody is specific and is used as confirmatory test, while ELISA is sensitive and thus used for screening.

Chest X-Ray usually shows nodules in upper lobes of the lung, usually less than 4 cm in diameter. They rarely calcify.

If meninges are affected, CSF will show hypoglycorrhachia (abnormally low glucose levels in CSF) , decreased proteins and lymphatic pleocytosis. Rarely, CSF eosinophilia is present.

The disease is commonly misdiagnosed as community acquired pneumonia and sometimes as cancer.

Treatment

There are no published prospective studies that examine optimal antifungal therapy for coccidioidomycosis. Mild cases often do not require treatment. Oral Fluconazole and intravenous Amphotericin B are used in progressive or disseminated disease, or in which patients are immunocompromised. Alternatively, itraconazole or ketoconazole may be used. Fluconazole is preferred drug for coccidioidal meningitis, due to its penetration into CSF. Intrathecal or intraventricular Amphotericin B therapy is used if infection persists after fluconazole treatment. Itraconazole is used for infection involving bones and joints.

Posaconazole and voriconazole have also been used. There is currently no practical preventative measures available for people who live or travel through Valley Fever endemic areas. It is recommended to avoid airborne dust or dirt, though this is not a guaranteed manner of prevention. People in certain occupations may be advised to wear face masks.

Complications

Serious complications include severe pneumonia, lung nodules, and disseminated disease, where the fungus spreads throughout the body. The disseminated form of valley fever can devastate the body, causing skin ulcers, abscesses, bone lesions, severe joint pain, heart inflammation, urinary tract problems, meningitis, and often death.

Biological warfare

C. immitis was investigated by the United States during the 1950s and 1960s as a potential biological weapon.^{[citation needed]} The Cash strain received the military symbol OC, and original hopes were for its use as an incapacitant. As medical epidemiology later made clear, OC would have lethal effects on several segments of the population, so it was later considered a lethal agent. It was never standardized, and beyond a few field trials, it was never weaponized. Most military work on OC was on vaccines by the mid-1960s. It is still on the CDC's list of select agents, however.

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See also

• Medical geology
• List of cutaneous conditions
• Thunderhead, a 1998 novel by Douglas Preston and Lincoln Child which uses the fungus and illness as a central plot point.

External links

• U.S. Centers for Disease Control and Prevention page on Coccidioidomycosis
• Medline Plus Entry for Coccidioidomycosis