Monday, November 23, 2015


                        Coccidioides immitis (Etiology of coccididiomycosis)
My name is Olanrewaju ADEYEMI, a graduate student in Biological sciences at Western Illinois University. I developed this blog to make people aware of medical importance Fungi. Coccidioides immitis was used as the subject organism and I hope this blog will increase knowledge about medical mycology.
GENERAL DESCRIPTION
Taxonomic classification:
Kingdom: Fungi
 Phylum: Ascomycota
 Class: Eurotimycetes
 Order: Onygenales
 Family: Onygenaceae
Genus: Coccidioides
 Species: immits. (www.mushroomobserver.org, 2009).

Coccidioides immitis is a dimorphic fungus that has the ability to exist in two distinct forms. It lives primarily in the soil (Davis et al. 1942). C. immitis colonies grow at a very fast rate compared to other medically important fungal at either 25 or 37°C and on Sabouraud Dextrose Agar. The colonies are moist, and grayish at first, later they produce white and cottony aerial mycelium. After a long time, colonies become tan to brown in color (Drutz, D., and M. Huppert, 1896). Coccidiosis immitis belongs to a class of human pathogenic fungi and exist in both saprophytic and parasitic forms. In the saprophytic form, it occurs as a mould with septate hyphae looking like barrel. As a parasite, the arthroconidia (spores) are released from the hyphae and transformed into spherules (Fig1). The spherules grow and also divide intrinsically, forming smaller structures called endospores inside the host (Drutz, and Hupper, 1983).The parasitic form is known to cause a wide spectrum of aliments, varying from a subtle illness to severe pulmonary manifestations or disseminated disease.


Geographic distribution
Commonly found in arid to semiarid regions of the southern San Joaquin Valley, California, which is part of the Lower Sonoran Lifezone (Maddy et al. 1957).  Also found in New Mexico, Nevada, Texas, and Utah; and in Central and South America in Argentina, Brazil, Colombia, Guatemala, Honduras, Mexico, Nicaragua, Paraguay, and Venezuela (Frederick et al. 2013). The geographic range for Coccidioides immitis has been described based on epidemiologic studies of persons infected and diagnosed with coccidioidomycosis. Edwards and Palmer in 1957 used skin testing to map the distribution of Coccidioides in the USA. The results of this and similar studies established that the south-central valley of California and the deserts of southern Arizona, were the most highly endemic for Coccidioides (Beadenkopf et al. 1949) (Fig 2). Presently, it is known that Coccidioides spp. are endemic to specific regions in the Western Hemisphere, primarily those located between the north and south 40° latitudes (Burt A et al. 1997).

(Fig2) Coccidioides in North, Central, and South America. Endemic areas are shown in gray
Habitat and life cycle
Research has shown that factors like physical, chemical and biological, affect the growth of Coccidioides (Fiese 1958, Sorensen 1964). Important factors include: amount and timing of rainfall and moisture, soil humidity, soil temperature, soil texture, alkalinity, salinity, organic content of soils, amount of sunlight and ultraviolet light.
Approximately 100,000 primary coccidioidal infections occur in humans per year in the areas of endemicity in the United States (Galgiani et al. 1999). Increment of the disease have been recorded in California and Arizona, which may be partially due to the rapid immigration of previously unexposed persons from states outside the endemic areas (Ampel et al. 1998). Generally, diagnosis in patients who have symptoms is established by serological diagnosis combined with patient history. Coccidioidal skin test antigen was a useful adjunct in the diagnosis decades ago, but it became unavailable in the 1980s (Smith CE et al. 1951).
Life Cycle: (fig 3).The organism follows the saprophytic cycle in the soil and the parasitic cycle in vertebrates. The saprophytic cycle starts in the soil with arthrospores (mould form) that develop into mycelium. The mycelium then matures and forms alternating spores within itself. The arthrospores are then released, and germinate back into mycelia. The parasitic cycle which occur in vertebrates involves the inhalation of the arthrospores by animals which then mature, at maturation, form spherules filled with uninucleated endospores. C. immitis is unique because it produces spherules containing endospores in tissue, and hyphae at 25°C. In addition, since C. immitis is an anaerobic organism, spherules produce rapidly in presence of CO2. Increased temperature and nutrition are also important for the production of sporulating spherules (http://www.ppdictionary.com/mycology/immitis.htm).
(Fig3). Life Cycle of Coccidioides immitis (Illustration: Michael Borjon/The Bakersfield Californian). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC545195/figure/pmed-0020002-g002/

Clinical manifestations and diagnosis
About 60% of infections by this fungus results in asymptomatic infections (Smith et al. 1946).  Symptoms in the 40% remaining can be a primary, a benign, a pulmonary infection (commonly known as “Valley Fever”) to a progressive pulmonary or extra pulmonary disease involving different parts of the body including central nervous system. Most patients with primary disease are self-limiting and retain lifelong immunity to future exogenous infection. Chronic and disseminated disease is known to occur in up to 5% of infected individuals, with comparatively more cases occurring in older individuals and in males (Ampel et al.1998). The most dangerous form of the disease is in the central nervous system, which occur in about 0.15%–0.75% of extrapulmonary coccidioidomycosis cases and requires treatment throughout lifetime (Cortez et al. 2003). In a tuberculosis endemic area, both diseases may occur at the same time. Coccidioidomycosis can be misdiagnosed for tuberculosis because both disease share common epidemiological, clinical, radiographic, and even histopathological features (Castañeda-Godoy; et al. 2002).

CASE STUDY 1
A 72-year-old man in the outpatient unit of a hospital presented with a four-month history of progressive dyspnea, hemoptysis and weight loss. The patient was a resident of southwestern Ontario and had been travelling to Arizona annually for six years. He had a significant smoking history. Three years before, he had a left upper lobe cavityof the lung lesion diagnosed as a poorly differentiated bronchogenic carcinoma with coexistent blastomycosis. For treatment, a left upper lobectomy was performed and itraconazole was given for six months.
The patient’s most recent chest x-ray showed left pleural thickening, unchanged from three years previously. A presumptive diagnosis of recurrent bronchogenic carcinoma and/or blastomycosis was made, and the patient underwent investigation with fibre optic bronchoscopy (Lee et al. 2008).
On bronchoscopy, abnormal tissue was found invading the left lower lobe. Bronchoalveolar lavage (BAL), along with brushings and a biopsy, was performed. The bronchial washing smear showed atypical cells, interpreted as a poorly differentiated nonsmall cell carcinoma along with occasional organisms identified as Blastomyces species. The biopsy specimen showed atypical squamous epithelium and fungal organisms compatible with Blastomyces species, but no malignant cells were detected. Direct microscopy of the tissue biopsy, which was performed in the hospital microbiology laboratory using a calcofluor white preparation, showed the presence of a few spherules, suggestive of C. immitis. A culture of the specimen grew C. immitis. Molecular technique was further used to confirm that the isolate was C. immitis (Lee et al. 2008).

CASE STUDY 2
A 51-year-old man presented with right-sided pleuritic chest pain and cough. He just returned from a camping trip to the Grand Canyon (Arizona, USA). He was misdiagnosed and treated with an oral antibiotic for community-acquired pneumonia, based on his symptoms and an infiltrate on chest radiography. At follow-up, he complained of cough (only occasionally productive of clear sputum) and had no episodes of hemoptysis. He experienced intermittent fevers and chills, but no other systemic complaints or weight loss. He was previously well and on no regular medications. Baseline blood work including complete blood counts, electrolytes, creatinine and liver enzymes were normal (Lee et al. 2008).
A repeat chest radiography and high-resolution CT scan (computed tomography) of the chest showed an opacity in the periphery of the right upper lobe. There were no calcifications or cavitations within the lesion. He underwent bronchoscopy, with BAL, mediastinoscopy and biopsy. The organisms seen on the BAL smear were interpreted by a pathologist to be consistent with Blastomyces species and a culture of the specimen grew C. immitis (Lee et al. 2008).





REFERENCES
1   Davis, B. L., Jr., Smith, R. T. &Smith, C. E. An epidemic of coccidioidal infection (coccidioidomycosis). J. Am. Med. Assoc. 118:1182–1186. (1942)
   Drutz, D. J., and M. Huppert. Coccidioidomycosis: factors affecting the host-parasite interaction. J. Infect. Dis. 147: 372-390 (1983)
3  Edwards PQ, Palmer CE. Prevalence of sensitivity to coccidioidin, with special reference to specific and nonspecific reactions to coccidioidin and to histoplasmin. Dis Chest. 1957;31(1):35–60.
4 Beadenkopf WG, Loosli CG, et al. Tuberculin, coccidioidin, and histoplasmin sensitivity in relation to pulmonary calcifications; a survey among 6,000 students at the University of Chicago. Public Health Rep. 1949;64(1):17–32. [PubMed]
    Burt A, Dechairo BM, Koenig GL, Carter DA, White TJ, Taylor JW. Molecular markers reveal differentiation among isolates of Coccidioides immitis from California, Arizona and Texas. Mol Ecol. 1997;6(8):781–786
6   Drutz, D. J., and M. Huppert. Coccidioidomycosis: factors affecting the host-parasite interaction. (http://www.ncbi.nlm.nih.gov/sites /entrez?cmd=Retrieve&db=PubMed&list_uids=6300253& dopt=AbstractPlus) J. Infect. Dis. 147: 372-390 (1983).
7   Maddy K. 1957. Ecological factors of the geographic distribution of Coccidioides
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8   Frederick S. Fisher, Mark W. Bultman, Suzanne M.Johnson, Demosthenes Pappagianis, and Erik Zaborsky Coccidioides Niches and Habitat Parameters in the Southwestern United StatesAnn. N.Y. Acad. Sci. 1111: 47–72 (2007).
       Fiese, M.J. 1958. Coccidioidomycosis. Charles C Thomas. Springfield, IL.

1Sorensen, R.H. 1964. Survival characteristics of mycelia and spherules of Coccidioides immitis in a simulated natural environment. Am. J. HyG. 80: 275–285.
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1  Castañeda-Godoy R, Laniado-Laborín R. Coexistencia de tuberculosis y coccidioidomicosis. Presentación de dos casos clínicos. Rev Inst Nal Enf Resp Mex. 2002;15:98–101.
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    Lee, C. H., Wilcox, L., Chorneyko, K., & McIvor, A. (2008). Coccidioides Immitis: Two Cases of Misidentified Mycosis. Canadian Respiratory Journal : Journal of the Canadian Thoracic Society, 15(7), 377–379.