Coccidioidomycosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or C. posadasii. It can be caused by breathing coccidioides spores in the air, especially after a soil disturbance. As per CDC [3] about 30-60 % people living in endemic areas are exposed to the infection sometimes in their lives.^[1]

Coccidioidomycosis was first discovered in 1892 by, Alejandro Posadas (a medical student) along with his mentor. They grouped coccidioidomycosis under parasitic family. Emmet Rixford and T. Caspar Gilchrist coined the term coccidioidomycosis (resembling coccidia) in 1896. William Ophüls and Herbert C. Moffitt described its dimorphic nature and defined it as a fungal etiology in 1900. C. immitis was investigated by the United States during the 1950s and 1960s as a potential biological weapon. It was never standardized, around beyond a few field trials, it was never weaponized.

Coccidioidomycosis is a fungal infection, that is acquired through inhalation of the spores from the environment. Following inhalation, the spores gets deposited into terminal bronchioles and enlarge, become rounded and develop internal septations to form what are known as the spherules. It then disseminates through the lymphatics and blood stream to gain access to any organ of the body.^[2][3][4][5]

Coccidioidomycosis is caused by an infection with Coccidioides immitis or Coccidioides posadasii

California state prisons have been particularly affected by Coccidioidomycosis, as far back as 1919. 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 rate in 2005, of at least 3,000 per 100,000. It is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah and northwestern Mexico.

Coccidioidomycosis presents as a mild flu-like illness that needs to be differentiated from a number of other fungal/bacterial disorders. These disorders have overlapping signs & symptoms such as fever, muscle pain along with rash that often needs detailed history, physical examination, and serological tests to pinpoint the diagnosis. Blastomycosis, Histoplasmosis, Aspergillosis, Pneumocystis pneumonia, Sporotrichosis.

On occasion, those particularly susceptible, including pregnant women, people with weakened immune systems, and those of Asian, Hispanic and African descent, may develop a serious or even fatal illness from valley fever.

Symptomatic infection (40% of cases) usually presents as an influenza-like illness with fever, cough, headaches, rash, and myalgia. 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.^[6][7]

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 and abscesses to bone lesions, severe joint pain, pericarditis, prostatitis,urinary tract infection, meningitis, and death.

The prognosis of Coccidioidomycosis is good in immunocompetent patients. It is self-limited in most of the patients and recovery is without any complications. The mortality rate is currently <0.07%. Approximately less than 1 % of patients develop disseminated coccidioidomycosis.

A positive history of fever, arthralgia and erythema nodosum are suggestive of coccidioidomycosis. The most common symptoms of coccidioidomycosis include fever with chills, cough, and pleuritic chest pain.

The physical manifestations of the disease depends on the organ of involvement. In the order of incidence the most commonly involved organs are lungs, skin, bones, genitourinary system, central nervous system and other organs.

The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy-tissue. 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. An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host antibody produced against the fungus.

Every patient suspected of coccidioides infection needs a chest X-ray. The findings can be variable ranging from infiltrates, nodules, cavities to mediastinal adenopathy and pleural effusions. Nodules in the upper part of the lung is a usual finding, they are rarely calcified if at all. The nodules are better visualized on CT scan and after contrast enhancement

Antifungals are the mainstay of treatment. The drug therapy is guided by the severity of symptoms and the immune status of the patient. Since most patients are asymptomatic or mildly affected, no treatment or a single drug azole therapy (fluconazole or itraconazole) may be sufficient in these cases. More recently resistant cases are being treated with voriconazole or posaconazole.[1]. However, patients with HIV, immunocompromised, those on steroids or pregnant females need much more aggressive approach. More severe cases may require intravenous amphotericin B, with or without simultaneous oral azole therapy. Meningitis or vasculitis often need initial in-patient treatment with oral azoles plus intravenous amphotericin B with or without intrathecal amphotericin B. Untreated cases may sometimes be fatal.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Coccidioidomycosis was first discovered for the time in 1892 by Alejandro Posadas (a medical student) along with his mentor and they grouped coccidioidomycosis under parasitic family. Emmet Rixford and T. Caspar Gilchrist coined the term coccidioidomycosis (resembling Coccidia) in 1896. William Ophüls and Herbert C. Moffitt described its dimorphic nature and defined it as a fungal etiology in 1900. C.immitis was investigated by the United States during the 1950s and 1960s as a potential biological weapon. It was never standardized, around beyond a few field trials, it was never weaponized.

• In 1892, Alejandro Posadas (a medical student) along with his mentor, Robert Wernicke discovered coccidioidomycosis.^{[1] [2]}

• In 1896, Emmet Rixford and T. Caspar Gilchrist coined the term coccidioidomycosis (resembling Coccidia), they grouped coccidioidomycosis under parasitic family.
• In 1900, William Ophüls and Herbert C. Moffitt described its dimorphic nature and defined it as a fungal etiology.
• In 1914, Cooke discovered coccidioidin skin test using precipitin reaction for the first time in diagnosing coccidioidomycosis.
• In 1929, Ernest Dickson described coccidioidomycosis as a lethal fungal disease.
• In 1936, Ernest Dickson along with his student Myrnie Gifford discovered that coccidioidomycosis is the same “San Joaquin fever,” “Desert fever,” or “Valley fever” which was considered as a separate entity until then.
• C. immitis was investigated by the United States during the 1950s and 1960s as a potential biological weapon. It was never standardized, around beyond a few field trials, it was never weaponized.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Vidit Bhargava, M.B.B.S [2]; Aditya Ganti M.B.B.S. [3]

Coccidioidomycosis is a fungal infection, that is acquired through inhalation of the spores that is present in the environment. Following transmission, coccidioidomycosis are deposited into terminal bronchioles and enlarge, become rounded and develop internal septations to form what are known as the spherules. It then disseminates to the lymphatics and blood stream to gain access to any organ of the body.^[1][2][3][4]

The pathogenesis of coccidioidomycosis can be described in following steps.^[1][2][3][4]

• Coccidioiodomycosis exist as mycelia in the soil with septations.
• During hot climate or dry environment, they proliferate asexually, transforming into spores, known as arthroconidia.
• Infection is caused by inhalation of these arthroconidia.
• The disease is not transmitted from person to person.

• Incubation period of coccidioidomycosis varies from one to three weeks.

• Following inhalation, arthroconidia reach terminal bronchioles.
• Then they are ingested by pulmonary macrophages.
• Inside macrophages these arthroconidia enlarge, become rounded and develop internal septations to form what are known as the spherules.
• It then disseminates to the lymphatics and blood stream to gain access to any organ of the body.

• Spherules contain uni-nuclear cells called as endospores which may propagate the infection further as they have the capability to develop into spherules.
• This conversion of arthroconidia into spherules initiates an inflammatory reaction and leads to a chemotaxic response (peptides derived from activation of the complement pathway, leukotrienes ) which attracts neutrophils and eosinophils to the site of inflammation.
• Cell mediated immunity keeps the infection in check and keeps them limited to the organ of origin by forming granulomas.

Coccidioidomycosis elicits cell-mediated immune responses.

• Delayed type hypersensitivity to coccidioidal antigens is common after acute infection has resolved.
• Dissemination usually occurs via the lymphatics and is more common in immune suppressed in whom the primary infection is not contained.

There is no known genetic association to coccidioidomycosis.

It is a dimorphic fungus and on microscopy, the following can be seen

• Spherule with endospores
• Rarely as hyphae in lung biopsy

• 
  Methenamine silver stain reveals reveals spherules of Coccidioides immitis in brain tissue. From Public Health Image Library (PHIL). ^[5]
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  PAS-stained photomicrograph of an unknown tissue specimen revealed the presence of three Coccidioides immitis spherules. From Public Health Image Library (PHIL). ^[5]
• 
  PAS-stained photomicrograph of an unknown tissue specimen revealed the presence of three Coccidioides immitis spherules. From Public Health Image Library (PHIL). ^[5]
• 
  Photomicrograph of of pus from a Guinea pig, Cavia porcellus, reveals presence of numbers of Coccidioides sp. fungal sporangia. From Public Health Image Library (PHIL). ^[5]
• 
  Photomicrograph of of pus from a Guinea pig, Cavia porcellus, reveals presence of numbers of Coccidioides sp. fungal sporangia. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathologic characteristics found within a pus specimen, prepared using potassium hudroxide (KOH). Specimen harvested from a skin lesion in a case of cutaneous coccidioidomycosis. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathologic characteristics found within a pus specimen, prepared using periodic acid-Schiff (PAS). Specimen harvested from a skin lesion in a case of cutaneous coccidioidomycosis. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathologic characteristics found within a pus specimen, prepared using periodic acid-Schiff (PAS). Specimen harvested from a skin lesion in a case of cutaneous coccidioidomycosis. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathology of coccidioidomycosis, lung. Methenamine silver stain. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathology of coccidioidomycosis, retroperitoneal area. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathologic changes due to coccidioidomycosis of the lung caused by Coccidioides immitis. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathologic changes in a case of coccidioidomycosis of the lung showing a large fibrocaseous nodule. From Public Health Image Library (PHIL). ^[5]
• 
  Histopathology of coccidioidomycosis of lung. From Public Health Image Library (PHIL). ^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Vidit Bhargava, M.B.B.S [2]

Coccidioidomycosis presents as a mild flu-like illness that needs to be differentiated from a number of other fungal/bacterial disorders. These disorders have overlapping signs & symptoms that often need detailed History, Physical examination, and serological tests to pinpoint the diagnosis.

• Blastomycosis
• Histoplasmosis
• Aspergillosis
• Pneumocystis pneumonia
• Sporotrichosis

• Anthrax
• Legionella
• Listeriosis
• Brucellosis
• Tuberculosis
• Scrub typhus
• Leptospirosis
• Cat scratch fever

• Chickenpox
• Herpes(Prodrome)
• Influenza
• Parainfluenza
• HIV -1/-2
• Coxsackie B virus
• Hepatits
• Cytomegalovirus
• Eastern equine encephalitis virus
• Venezuelan equine encephalitis
• Coronavirus
• California Encephalitis virus

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Vidit Bhargava, M.B.B.S [2] Aditya Ganti M.B.B.S. [3]

The annual incidence of coccidioidomycosis in United states is variable but overall is increasing, from a rate of 5.3 per 100,000 in 1998 to a rate of 42.6 in 2011.The case fatality rate of coccidioidomycosis is approximately 0.59 per million person if left untreated. 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 rate in 2005, of at least 3,000 per 100,000. It is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah and northwestern Mexico.^[1]

Epidemiology and Demographics of Coccidioidomycosis include:^[2][3][4][5]

• The annual incidence of coccidioidomycosis in United states is variable but overall is increasing, from a rate of 5.3 per 100,000 in 1998 to a rate of 42.6 in 2011.
• Arizona has the highest incidence of coccidioidomycosis of any state, with a yearly rate of approximately 248 cases per 100,000 population in 2011.
• 95% of all coccidioidomycosis cases in the USA occur in Arizona and California, with 70 % being in Arizona and rest from California.
• As per CDC [4] in 2010 there were over 16,000 reported cases of coccidioidomycosis most of which were localized to Arizona and California.

• The case fatality rate of coccidioidomycosis is approximately 0.59 per million person if left untreated.^[6]

• Coccidioidomycosis affects all age groups.
• The higher incidence rates have been documented among adults >65 years.

• Men are more commonly affected with coccidioidomycosis than women.

• Racial predilection for Filipino or African American patients has been reported to have higher rates of infection and dissemination, ranging from 10 to 175 times higher than other ethnicities.

• Coccidioidomycosis is found only in the Western hemisphere. It is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah and northwestern Mexico.
• It has been made a mandatory reportable disease in 15 US states, which includes Arizona, California, Delaware, Louisiana, Maryland, Michigan, Minnesota, Missouri, Nevada, New Hampshire, New Mexico, Ohio, Rhode Island, Utah, and Wyoming

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Coccidioidomycosis is a fungal infection most commonly seen in the desert regions of the southwestern United States, and in Central and South America. Common risk factors include traveling to an area where the fungus is commonly seen raises your risk for this infection, native American, African or Philippine descent, and having a weakened immune systems due to AIDS, diabetes, or medications that suppress the immune system.^{[1] [2][3]}

• Dust exposure in endemic areas, due to occupational activities agricultural or construction workers
• Military personnel training in endemic areas
• Construction work, and model airplane competitions
• Natural disasters such as earthquakes and windstorms

• HIV/AIDS
• Organ transplantation
• Use of immunosuppressive medications
• Older age >65
• Diabetes mellitus
• Late-stage pregnancy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Vidit Bhargava, M.B.B.S [2]; Aditya Ganti M.B.B.S. [3]

It is important to screen for Coccidioidomycosis in all cases of community acquired pneumonia in endemic areas.

Coccidioidomycosis is often mistaken for community acquired pneumonia(CAP) and this grossly underestimates the actual cases in the community. It is therefore important to screen for Coccidioidomycosis in all cases of community acquired pneumonia in endemic areas.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Vidit Bhargava, M.B.B.S [2]

Coccidioidomycosis is usually a self-limited mild clinical illness. A large proportion of individuals are clinically infected without any manifestations and are thus completely asymptomatic. The remaining develop a mild pulmonary illness which in most cases is self-limited requiring no treatment, and even those cases which do require treatment have an excellent prognosis. The mortality rate is currently <0.07%. If left untreated in patients with weakened immune systems, the infection spreads throughout the body. The clinical picture may be complicated due to widespread dissemination of the organism leading to a number of complications pleural effusion, relapse, pyopneumothorax, hemoptysis, and pleuritic chest pain, synovitis and osteomyelitis.

• Coccidioidomycosis is usually a self-limited mild clinical illness.
• A large proportion of individuals are clinically infected without any manifestations and are thus completely asymptomatic.
• The remaining develop a mild pulmonary illness which in most cases is self-limited requiring no treatment, and even those cases which do require treatment have an excellent prognosis.
• It is often misdiagnosed as community-acquired pneumonia. There are several cutaneous manifestations such as erythema multiforme and erythema nodosum, it may even cause arthritis and arthralgias.
• If left untreated in patients with weakened immune systems, 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, pericarditis, prostatitis,urinary tract infection, and meningitis, which can lead to death.^[1]

Complications of coccidioidomycosis include:^[2][3]

• Pleural effusion
• Return of the infection (relapse)
• Meningitis
• Pulmonary cavities, that may rupture leading to pyopneumothroax, otherwise causing persistent cough, hemoptysis, and pleuritic chest pain
• Synovitis and osteomyelitis

The prognosis of Coccidioidomycosis is good in immunocompetent patients. It is self-limited in most of the patients and recovery is without any complications. The mortality rate is currently <0.07%. Approximately less than 1 % of patients develop disseminated coccidioidomycosis.

Factors associated with poor prognosis:

• HIV disease,with low CD4 count (<250)
• Late stage Pregnancy( third trimester)
• Organ transplantation
• Immunosuppressant therapy ^[4]

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