Coccidioidomycosis                                      Brijesh Singh Yadav                                E.Mail brijeshbioinfo@gmail.com

Disease Name: CoccidioidomycosisCommon Name: San Joaquin Valley fever, California valley fever, desert fever,Disease Category: Fungal Disease

Description: Coccidioidomycosis is the infection caused by the dimorphic fungus Coccidioides immitis. The disease is endemic only in regions of the Western Hemisphere. In the United States, the endemic areas include southern Arizona, central California, Southern New Mexico, and west Texas. The endemic region extends southward into Central and South America. An arid climate, alkaline soils, hot summers, few freezings, and yearly rainfalls ranging between 5 to 20 inches characterize this area. Outbreaks occur following dust storms, earthquakes, and earth excavation where dispersion for arthroconidia is favored. Coccidioidomycosis is acquired from inhalation of the spores (arthroconidia). Once in the lungs, the arthroconidia transform into spherical cells called "spherules". An acute respiratory infection occurs 7 to 21 days after exposure and typically resolves rapidly. However, the infection may alternatively result in a chronic pulmonary condition or disseminate to the meninges, bones, joints, and subcutaneous and cutaneous tissues. About 25% of the patients with disseminated disease have meningitis . 

                          The face of Biologicalwarfare       Chronic cutaneous                    Leg infectionFig.1.Showing different from of coccidiomycosis                                                                                               Types of the disease:

Asymptomatic: Occurs in about 50% of patients

Acute Symptomatic:

o Pulmonary syndrome that combines cough, chest pain, shortness of  breath, fever, and fatigue.

o Diffuse pneumonia affects immunosuppressed individuals o Skin manifestations include fine papular rash, erythema nodosum, and

Erythema multiforme Occasional migratory arthralgias and fever

Chronic Pulmonary: Affects between 5 to 10% of infected individuals

     Usually presents as pulmonary nodules or peripheral thin-walled cavities 

Extrapulmonary/Disseminated Varieties:

Chronic skin disease:             Keratotic and verrucose ulcers or subcutaneous fluctuant AbscessesJoints / Bones:

             Severe synovitis and effusion that may affect knees, wrists, feet, ankles,                           And/or pelvis              Lytic lesions commonly affecting the axial skeleton

 Meningeal Disease:

     The most feared complication      Presenting with classic meningeal symptoms and signs        Hydrocephalus is a frequent complication

Others:  May affect virtually any organ, including thyroid, GI tract, adrenal glands, genitourinary tract, pericardium, peritoneum

 Host organism: It has been known to infect humans, dogs, cattle, livestock, llamas, apes, monkeys, kangaroos, wallabies, tigers, bears, badgers, otters and marine mammals.   

Causal Organism: Coccidioides immitis/posadasii Pathogen Description: Coccidioides immitis and C. posadasii are thermally dimorphic fungi found in soil particularly at warm and dry areas with low rain fall, high summer temperatures, and low altitude. The two species are morphologically identical but genetically and epidemiologically distinct. C. immitis is geographically limited to California's San Joaquin valley region, whereas C. posadasii is found in the desert southwest of the United States, Mexico, and South America. The two species appear to co-exist in the desert southwest and Mexico.

Although it was recognized for some years that C. immitis contained two genetic subgroups, their description as separate species did not occur until 2002 . Prior to this, the two groups were simply known as the California and non-California variants of C. immitis. Thus, essentially all prior literature treats them as a single species. As the two species can be distinguished only by genetic analysis and different rates of growth in the presence of high salt concentrations (C. posadasii grows more slowly), little is known as yet about differences in pathogenicity. Thus, the remainder of this discussion will simply refer to the pair of species as C. immitis/posadasii.C. immitis/posadasii specifically inhabits alkaline soil. It is isolated in rodent burrows at desert-like areas of southwest United States. It has no known teleomorph.Coccidioides immitis/posadasii is a pathogenic fungus and is among the causative agents of true

systemic (endemic) mycoses. It is endemic at southwest United States, Northern Mexico, and certain areas in Central and South America. Imported cases may be observed following travel to endemic areas.  Taxonomic Classification:

 

Kingdom: FungiPhylum: AscomycotaClass: EuascomycetesOrder: OnygenalesFamily: Onygenaceae                 Genus: Coccidioides

       Coccidioides immitis/posadasii Other Species:Coccidioides immitis and C. posadasii are the only species included in the genus Coccidioides. Macroscopic Features:Coccidioides immitis/posadasii colonies grow rapidly. The macroscopic morphology may be very variable. At 25 or 37°C and on Sabouraud dextrose agar, the colonies are moist, glabrous, membranous, and grayish initially, later producing white and cottony aerial mycelium. With age, colonies become tan to brown in color.

Microscopic Features:

Microscopic appearance of the fungus depends on the temperature of isolation.

1. At 25°CHyphae and arthroconidia are produced. Hyphae are hyaline, septate and thin. Racquet hyphae may occasionally be observed on slides prepared from young cultures. Arthroconidia are thick-walled, barrel-shaped, and 2-4 x 3-6 µm in size.Typically these arthroconidia alternate with empty disjuncture cells. On the released arthroconidia, annular frills that are the remnants of the disjuncture cells are observed.2. At 37°CLarge, round, thick-walled spherules (10-80 µm in diameter) filled with endospores (2-5 µm in diameter) are observed. Production of spherules in vitro requires inoculation into a special synthetic medium, such as converse liquid medium, an incubation temperature of 37-40°C and presence of CO2 at a concentration as high as 20%.

Coccidioides immitis/posadasii continues to grow as a mould and does not produce spherules at any temperature unless special growth medium is provided in vitro. This finding indicates that temperature is not the only variable that controls the spherule formation. Thus, some authorities prefer not to classify this fungus as thermally dimorphic. Nevertheless, Coccidioides immitis/posadasii is commonly classified among the thermally dimorphic fungi.

The definitive identification of an isolated Coccidioides immitis/posadasii strain requires demonstration of spherule production in vitro, use of DNA probes, application of exoantigen tests, or demonstration of spherule production in vivo by animal experiments. Molecular typing studies have also been initiated and appear useful in identification.

Disease Transmission:

Coccidioides immitis/posadasii is the causative agent of coccidioidomycosis in humans. Coccidioidomycosis is one of the true systemic (endemic) mycoses. It is acquired by inhalation and initially presents with a pulmonary infection which may later disseminate to other organs and systems. Airway coccidioidomycosis involving the endotracheal and endobronchial tissues may develop. Inhalation of the dry arthroconidia of Coccidioides immitis/posadasii, which are carried by dust storms, initiates the infection. Afterwards, hematogenous spread of the organism results in infection of skin, bones, joints, lymph nodes, adrenal glands, and central nervous system .The clinical picture has a remarkably wide spectrum. The infection remains as an acute and self-limited respiratory infection in most exposed hosts, but it progresses to a chronic and sometimes fatal disease in others. Spontaneous healing is observed in as high as 95% of the otherwise healthy hosts. Dissemination may occur particularly during pregnany and carries a high risk of mortality.Although coccidioidomycosis basically effects otherwise healthy immunocompetent hosts due to the true pathogenic nature of the fungus, it may also develop in immunocompromised patients, such as patients with AIDS and organ transplant recipients. Activities and professions related to tillage of the soil, such as agricultural work, telephone post digging, archeology, or simply playing with soil appear to be associated with development of coccidioidomycosis .Coccidioidomycosis has also been described in warm-blooded water animals such as bottlenose dolphins and horses.

Histopathologic Features

Spherules containing endospores are the typical structures formed in infected tissues. The transition form of C. immitis/posadasii producing septate hyphae that develop into arthroconidia may be observed in necrotic nodules and misdiagnosed as one of the fungi in hyphomycetes group, particularly if the spherules are not yet evident. Hyphal forms may also be observed in brain tissue or cerebrospinal fluid in the presence of plastic devices. These devices presumably trigger the morphological reversion to the saprophytic form. Diagnosis of disease: HistopathologyThe tissue reaction is one of acute suppurative and granulomatous inflammation. Acute suppuration is usually present around the arthroconidia and after a spherule ruptures.

Granulomatous inflammation usually occurs around developing spherules. Hyphae may be present in pulmonary cavities and meningeal lesions without arthroconidia, which can lead to confusion with the hyphae of an Aspergillus spp.Laboratory

 Direct examination:Direct examination of clinical specimens, such as fluids, sputa, and tissue in 10% KOH may show spherules 30-60 um in diameter with a thick wall (up to 2 um) and endospores 2-5 um in diameter characteristic of Coccidioides immitis. Endospores are released when the wall of the spherule ruptures. Endospores that are no longer in a spherule may remain close to each other, resulting in potential confusion with the yeast cells of Blastomyces dermatitidis. This is especially true if the spherule wall is no longer visible and the clinical specimen has been homogenized.

Isolation:Isolation involves inoculating the clinical material onto IMA agar, BHI agar with 10% sheep blood and a medium containing cycloheximide and incubating at 30°C. Cultures should be kept 4 weeks before discarding as negative. The fungus is fast growing and readily produces barrel-shaped arthroconidia 2.5-4 x 3-6 um with a disjunctor cell between each arthroconidium. Coccidioides immitis is a dangerous fungus and should be handled at all times with due respect in a Class II or III biological safety cabinet. It is classified as a BSL-3 agent. Laboratory confirmation of C. immitis is required because other fungi, such as members of the Gymnoascaceae, may develop an anamorph similar to Coccidioides. Useful in vitro identification procedures include special conversion media, exoantigen tests, and DNA probes. Slide cultures should not be set up when Coccidioides immitis is suspected due to its dangerous nature.Susceptibility testing

Standardized testing procedures are not available. Microbiological resistance has not been demonstrated.    

                                                    chest X-ray                    Disseminated                                Fig2. diagnosis of coccidioidomycosis.   Prognosis and therapy:Coccidioidomycosis includes a variety of illnesses many of which do not require therapy. Ninety-five percent of acute episodes resolve spontaneously. Nevertheless, follow up for 1 to 2 years is recommended for early identification of chronic pulmonary and extrapulmonary forms. Treatment should be given to patients with, or at high risk for, the more severe forms of the disease. 

Amphotericin B has often been used as initial therapy, but is increasingly being supplanted by therapy with an oral azole . Ketoconazole, fluconazole and itraconazole have all been used. However, because of the toxicity profiles, the last two are preferred. Length of therapy should be at least 1 year. Even after such a prolonged course of therapy, relapses are frequent. Intrathecal amphotericin B has long been the standard therapy for meningeal disease,but fluconazole is increasingly found to be an effective and better tolerated option . Surgical management could be of help in the treatment of pulmonary and extrapulmonary lesions. Geographical Distribution:   Natural habitat:Alkaline soil of the Lower Sonoran Life Zone in North, Central, and South America. 

Fig3.   Geographic distribution of coccidioidomycosis 

 

 Statistical Information:

 Prevalence and incidence statistics for coccidioidomycosis:

California state prisons have been particularly affected by Coccidioidomycosis, as far back as 1919. In 2005 and 2006, the Pleasant 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

                                                                           Incidence (annual) of Coccidioidomycosis: 15 cases per 100,000 population in Arizona in 1995 (DBMD)   Incidence Rate: approx 1 in 6,666 or 0.01% or 40,800 people in USA [about data]   Prevalance of Coccidioidomycosis: Incidence was 15 cases per 100,000 population   in Arizona in 1995. Of persons living in areas with endemic disease, 10-50% are skin-test positive.

Society statistics for Coccidioidomycosis :  Hospitalization statistics for Coccidioidomycosis: The following are statistics from various sources about hospitalizations and Coccidioidomycosis:

               0% (6) of hospital consultant episodes were for coccidioidomycosis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               67% of hospital consultant episodes for coccidioidomycosis required hospital admission in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               33% of hospital consultant episodes for coccidioidomycosis were for men in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               67% of hospital consultant episodes for coccidioidomycosis were for women in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               75% of hospital consultant episodes for coccidioidomycosis required emergency hospital admission in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               49.7 days was the mean length of stay in hospitals for coccidioidomycosis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               6 days was the median length of stay in hospitals for coccidioidomycosis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               54 was the mean age of patients hospitalised for coccidioidomycosis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               33% of hospital consultant episodes for coccidioidomycosis occurred in 15-59 year olds in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               17% of hospital consultant episodes for coccidioidomycosis occurred in people over 75 in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               17% of hospital consultant episodes for coccidioidomycosis were single day episodes in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03)

               0.003% (152) of hospital bed days were for coccidioidomycosis in England 2002-03 (Hospital Episode Statistics, Department of Health, England, 2002-03

   Source-1.http://dhs.wisconsin.gov/communicable/FactSheets/Blastomycosis_42030_0504.htm2. http://www.doctorfungus.org/3. http://www.wrongdiagnosis.com/4. http://health.allrefer.com/health/blastomycosis-info.html5. http://www.cureresearch.com/c/coccidioidomycosis/stats.htm       Fig Refrence

1.    webs.wichita.edu ,www.mycology.adelaide.edu.au, botit.botany.wisc.edu2.    www.nlm.nif.gov, www.residentandstaff.com3.    http://www.cureresearch.com/c/coccidioidomycosis/stats.htm