Coccidioidomycosis (/kÉ'kËŒsɪdiÉ"ɪdoÊŠmaɪˈkoÊŠsɪs/, kok-sid-ee-oy-doh-my-KOH-sis), commonly known as cocci, "valley fever", as well as "California fever", "desert rheumatism", and "San Joaquin Valley fever", is a mammalian fungal disease caused by Coccidioides immitis or Coccidioides posadasii. It is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico.
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, or an earthquake.
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. The disease is not contagious. In some cases the infection may recur or be permanent.
Signs and symptoms
Most people infected with the fungi responsible for coccidioidomycosis have minimal to no symptoms. Of those who do develop symptoms, nearly all develop symptoms resembling bronchitis or pneumonia that resolve over a matter of a few weeks. Notable coccidioidomycosis signs and symptoms include a profound feeling of tiredness, fever, cough, headaches, rash, muscle pain, and joint pain. The classic triad of coccidioidomycosis known as "desert rheumatism" includes the combination of fever, joint pains, and erythema nodosum.
Some people do not recover from the initial acute infection and develop a chronic lung infection or widespread disseminated infection (affecting the tissues lining the brain, soft tissues, joints, and bone). Severe lung disease may develop in HIV-infected persons.
Types
After Coccidioides infection, Coccidioidomycosis begins with Valley fever, which is its initial acute form. If left untreated, it can progress to the chronic form and then to disseminated Coccidioidomycosis. Therefore, Coccidioidomycosis may be divided into the following types:
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- Acute coccidioidomycosis, sometimes described in literature as primary pulmonary coccidioidomycosis
- Chronic coccidioidomycosis
- Disseminated Coccidioidomycosis, which includes primary cutaneous coccidioidomycosis
Complications
Serious complications may occur in patients with weakened immune systems, including severe pneumonia, lung nodules, and 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.
Cause
In soil (and 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 and 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 they rupture, they release their contents into bronchi, forming thin-walled cavities. These cavities can result in symptoms like characteristic chest pain, coughing up blood, and persistent cough. In individuals with a weakened immune system, the infection can spread through the blood.
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 (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 cerebrospinal fluid (CSF). TP antibody is specific and is used as confirmatory test, while ELISA is sensitive and thus used for screening.
If the meninges are affected, CSF will show abnormally low glucose levels in CSF, a decreased level of protein in the CSF, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present.
Imaging
Chest x-rays rarely demonstrate nodules or cavities in the lungs but these images commonly demonstrate lung opacification, pleural effusions, or enlargement of lymph nodes associated with the lungs. Computed tomography scans of the chest are better able to detect these changes than chest x-rays.
Treatment
Significant disease develops in less than 5% of those infected and typically occurs in those with a weakened immune system. Mild asymptomatic cases often do not require any treatment. Those with severe symptoms may warrant anti-fungal therapy. There is a lack of prospective studies that examine optimal anti-fungal therapy for coccidioidomycosis.
On the whole, oral fluconazole and intravenous amphotericin B are used in progressive or disseminated disease, or in immunocompromised individuals. Alternatively, itraconazole or ketoconazole may be used for milder disease. Fluconazole is the preferred medication 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 cases that involve treatment of infected person's bones and joints. The antifungal medications posaconazole and voriconazole have also been used to treat coccidioidomycosis.
Prevention
Currently there are no completely effective preventive measures 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.
In 1998-2011, there were 111,117 cases of coccidioidomycosis in the U.S. that were logged into the National Notifiable Diseases Surveillance System (NNDSS). Since many U.S. states do not require reporting of coccidioidomycosis, the actual numbers can be higher. The United States' Centers for Disease Control and Prevention (CDC) called the disease a "silent epidemic" and acknowledged that there is no proven anticoccidioidal vaccine available.
Raising both surveillance and awareness of the disease while medical researchers are developing a human vaccine can positively contribute towards 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. Currently, recommended prevention measures can include type-of-exposure-based respirator protection for persons engaged in agriculture, construction and others working outdoors in the 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.
Epidemiology
Coccidioidomycosis is confined to the western hemisphere between 40° N and 40° S. Dry soil, especially in the Lower Sonoran Life Zone, is supportive of the pathogenic fungi growth. In harmony with the mycelium life cycle, 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.
In order of decreasing risk, people of Filipino, African, Native American, Hispanic, and Asian descent are more susceptible to the disseminated form of the disease than other ethnic backgrounds. Individuals with a weakened immune system are also more susceptible to the disease.
Aside from humans, dogs, and cats, the fungus can infect other 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 cougars, skunks, and javelina.
North America
California state prisons, beginning in 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 disease was considered endemic. 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 1994 Northridge earthquake, there was a sudden increase of cases in the areas affected by the quake, at a pace of over 10 times baseline.
Coccidioidomycosis cases have been on the rise in the United States in the last decade. The incidence of coccidioidomycosis in the United States in 2011 (42.6 per 100,000) was almost ten times higher than the incidence reported in 1998 (5.3 per 100,000).
History
The first case of what was later named Coccidioidomycosis was described in 1892 in Buenos Aires by Alejandro Posadas, a medical intern at the Hospital de ClÃnicas "José de San MartÃn". Posados established an infectious character of the disease after being able to transfer it in laboratory conditions to lab animals. In the U.S., E. Rixford, a physician from a San Francisco hospital, and T. C. Gilchrist, a pathologist at Johns Hopkins Medical School, became early pioneers of clinical studies of the infection. They decided that the causative organism was a Coccidia-type protozoan and named it Coccidioides immitis (resembling Coccidia, not mild).
During the next several decades it became clear that the etiological agent of the disease that was at first called Coccidioides infection and later Coccidioidomycosis was a fungal pathogen, and Coccidioidomycosis was also distinguished from Histoplasmosis and Blastomycosis. Further, C. immitis was identified as the culprit of respiratory disorders previously called San Joaquin fever, Desert fever, and Valley fever, and a serum precipitin test was developed by Charles E. Smith that was able to detect an acute form of the infection. In retrospect, Smith played a major role in both medical research and raising awareness about Coccidioidomycosis, especially when he became dean of the School of Public Health at the University of California at Berkeley in 1951.
C. immitis was considered by the United States during the 1950s and 1960s as a potential biological weapon. The explored strain was designated with the military symbol OC, and initial expectations were for its employment as a human incapacitant. Medical research suggested that OC might have had some lethal effects on the populace, and C. immitis started to be classified by the authorities as a threat to public health. However, C. immitis was never weaponized, and most of the military research in the mid-1960s was concentrated on developing a human vaccine. Currently, it is not on the U.S. Department of Health and Human Services' (HHS) or Centers for Disease Control and Prevention's list of select agents and toxins.
In 2002, Coccidioides posadasii was identified as genetically distinct from C. immitis despite their morphologic similarities and can also cause coccidioidomycosis.
Additional images
See also
- Coccidioides
- Coccidioides immitis
- Coccidioides posadasii
- Zygomycosis
- 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.
References
External links
- U.S. Centers for Disease Control and Prevention page on Coccidioidomycosis
- Medline Plus Entry for Coccidioidomycosis
- Radiology of Lesions in Valley Fever
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