coccidioidomycosis coccidioidomycosis coccidioidomycosis (/kɒkˌsɪdiɔɪdoʊmaɪˈkoʊsɪs/, kok-sid-ee-oy-doh-my-koh-sis), commonly known as cocci, valley fever, as well as california fever, desert rheumatism, or san joaquin valley fever, is a mammalian fungal disease caused by coccidioides immitis or coccidioides posadasii. coccidioidomycosis is endemic in certain parts of the united states in arizona, california, nevada, new mexico, texas, utah, and northern mexico. coccidioidomycosishistopathological changes in a case of coccidioidomycosis of the lung showing a large fibrocaseous nodule.specialtyinfectious diseasetypesacute, chroniccausescoccidioidestreatmentantifungal medicationmedicationamphotericin b, itraconazole, fluconazole 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. 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 become chronic. it was reported in 2022 that valley fever had been increasing in california's central valley for years (1,000 cases in kern county in 2014, 3,000 in 2021); experts said that cases could rise across the american west as the climate makes the landscape drier and hotter. classification after coccidioides infection, coccidioidomycosis begins with valley fever, which is 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 literature as primary pulmonary coccidioidomycosis chronic coccidioidomycosis disseminated coccidioidomycosis, which includes primary cutaneous coccidioidomycosis valley fever is not a contagious disease. signs and symptoms a skin lesion due to coccidioides infection 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 (3–5%) 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 (affecting the tissues lining the brain, soft tissues, joints, and bone). chronic infection is responsible for most of the morbidity and mortality. chronic fibrocavitary disease is manifested by cough (sometimes productive of mucus), 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 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. 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 became unable to work during diagnosis and 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 life cycle of coccidioides both coccidioides species share the same asexual life cycle, switching between saprobic (on left) and parasitic (on right) life stages. rain starts the cycle of initial growth of the fungus in the soil. in soil (and in agar media), 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 (arthroconidia) 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. rupture of spherules release these endospores, which in turn repeat the cycle and spread the infection to adjacent tissues within the body of the infected individual. nodules can form in lungs surrounding these spherules. when they rupture, they release their contents into 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 a case of pulmonary fibrosis caused by coccidioidomycosis 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 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. pas stain of a coccidioidomycosis spherule. 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 more sensitive than chest x-rays to detect these changes. prevention preventing valley fever is challenging because it is difficult to avoid breathing in the fungus should it be present; however, the public health effect of the disease is essential to understand in areas where the fungus is endemic. enhancing surveillance of coccidioidomycosis is key to preparedness in the medical field in addition to improving diagnostics for early infections. 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. the use of air filtration indoors is also helpful, in addition to keeping skin injuries clean and covered to avoid skin infection. 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 may 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. 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 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 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. treatment significant disease develops in fewer 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 benefit from antifungal therapy, which requires 3–6 months or more of treatment depending on the response to the treatment. there is a lack of prospective studies that examine optimal antifungal therapy for coccidioidomycosis. on the whole, oral fluconazole and intravenous amphotericin b are used in progressive or disseminated disease, or in immunocompromised individuals. amphotericin b was originally the only available treatment, but alternatives, including itraconazole and ketoconazole, became available 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. because the symptoms of coccidioidomycosis are similar to the common flu, pneumonia, and other respiratory diseases, it is important for public health professionals to be aware of the rise of coccidioidomycosis and the specifics of diagnosis. greyhound dogs often get coccidioidomycosis; their treatment regimen involves 6–12 months of ketoconazole taken with food. toxicity conventional amphotericin b desoxycholate (amb: used since the 1950s as a primary agent) is known to be associated with increased drug-induced nephrotoxicity impairing kidney function. other formulations have been developed such as lipid-soluble formulations to mitigate side-effects such as direct proximal and distal tubular cytotoxicity. these include liposomal amphotericin b, amphotericin b lipid complex such as abelcet (brand) amphotericin b phospholipid complex also as ambisome intravenous, or amphotec intravenous (generic; amphotericin b cholesteryl sul), and amphotericin b colloidal dispersion, all shown to exhibit a decrease in nephrotoxicity. the latter was not as effective in one study as amphotericin b desoxycholate which had a 50% murine (rat and mouse) morbidity rate versus zero for the amb colloidal dispersion. the cost of the nephrotoxic amb deoxycholate, in 2015, for a patient of 70 kilograms (150 lb) at 1 mg/kg/day dosage, was approximately us$63.80, compared to $1318.80 for 5 mg/kg/day of the less toxic liposomal amb. epidemiology coccidioidomycosis is endemic to the western hemisphere between 40°n and 40°s. the ecological niches are characterized by hot summers and mild winters with an annual rainfall of 10–50 cm. the species are found in alkaline sandy soil, typically 10–30 cm below the surface. in harmony with the mycelium life cycle, incidence increases with periods of