Coccidioidomycosis

                                  
   Brijesh Singh Yadav
                                E.Mail brijeshbioinfo@gmail.com

Disease Name: Coccidioidomycosis

Common 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 infection
Fig.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 Abscesses
Joints / 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: Fungi
Phylum: Ascomycota
Class: Euascomycetes
Order: Onygenales
Family: 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°C
Hyphae 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°C
Large, 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:
 
Histopathology
The 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.htm
2. http://www.doctorfungus.org/
3. http://www.wrongdiagnosis.com/
4. http://health.allrefer.com/health/blastomycosis-info.html
5. http://www.cureresearch.com/c/coccidioidomycosis/stats.htm
 
 
 
 
 
 
 Fig Refrence
1.    webs.wichita.edu ,www.mycology.adelaide.edu.au, botit.botany.wisc.edu
2.    www.nlm.nif.gov, www.residentandstaff.com
3.    http://www.cureresearch.com/c/coccidioidomycosis/stats.htm