Coccidioides Immitis

1
Coccidioides Immitis

• cause of the fungal disease coccidioidomycosis,
  aka Valley Fever, San Joaquin Valley Fever, or
  desert bumps

2
Intro

• Fungus, eukaryotic
• Taxonomic Classification
• Kingdom FungiPhylum AscomycotaClass
  EuascomycetesOrder OnygenalesFamily
  OnygenaceaeGenus Coccidioides
• First discovered in 1891 in a hospital in Buenos
  Aires, Argentina.
• These fungi are endemic to certain regions of
  North and South America. The endemic areas in the
  United States include Arizona, south central
  California (San Joaquin Valley), Nevada, New
  Mexico, and the western half of Texas.
• This intracellular pathogen causes a nasty fungal
  disease know as Coccidioidomycosis
• Most virulent of all pathogenic fungi

3
Structure and Features

• The Coccidioides immitis organism is dimorphic,
  meaning it assumes 2 different forms, depending
  on the environment. This feature adds to its
  virulence.
• Form 1mycelial arthrospore phase It grows in
  the mycelial form in the arid soil . As the
  mycelial structure matures, alternating hyphal
  cells expand into barrel-shaped structures called
  arthroconidia. The arthroconidia are the
  infectious particles of coccidioidomycosis. These
  conidia require little nutrition and can
  withstand extreme heat, desiccation, and changes
  in soil salinity for months to years.
• Form 2 spherule endospore phase
• When the soil is disrupted, the arthroconidia
  become airborne. If inhaled by a host, produce
  infection. The arthrospore sheds its outer
  coating and becomes a round structure called a
  spherule. The spherule, the parasitic stage of
  the organism, reproduces by a process known as
  endosporulation. When the spherule ruptures, the
  endospores are released, each of which matures
  into spherules, repeating the cycle. If the
  organism is cultured, it reenters the mycelial
  phase, with hyphal cell formation (hence
  dimorphic)

4
1. At 25CHyphae and are produced, which are
hyaline and thin. Arthroconidia are thick-walled,
barrel-shaped, and 2-4 x 3-6 µm in size.
2. At 37CLarge, round, thick-walled spherules
(10-80 µm in diameter) filled with endospores
(2-5 µm in diameter) are observed.
5
Growth and Development

• Optimal nutritional conditions for growth and
  arthrospore formation 7 days incubation in a
  synthetic medium consisting of glucose, ammonium
  lactate, and inorganic salts. Production of
  spherules in vitro requires an incubation
  temperature of 37-40C and presence of CO2 at a
  concentration as high as 20.

6
Virulence and Pathogenicity

• Virulence factor C. immitis changes from the
  room-temperature hyphal form to the
  body-temperature spherule form containing
  endospores. These endospores can be transported
  by the bloodstream to other parts of the body,
  particularly to the brain and central nervous
  system, where they can germinate and grow to
  cause even more severe disease. The dimorphism
  helps the fungus to evade the immune system by
  the changing of the surface antigens of the
  fungus. During an in-vitro assay (using mice), it
  was observed that the polypeptide surface of the
  antigen was bound to mamillian extracellular
  matrix proteins.  In other words, this suggests
  that the parasitic cell surface glycoproteins act
  as adhesion molecules.
• Virulence factor Inhaled airborne arthroconidia
  are deposited into the terminal bronchiole and
  transform into spherules, causing an acute
  inflammatory reaction. Spherules react with
  complement and promote chemotaxis of neutrophils
  and eosinophils. The spherules reproduce by a
  process known as endosporulation, rupture, and
  release endospores. Some of the endospores are
  engulfed by macrophages, initiating inflamation.
  If the infection is not cleared during this
  process, a new set of lymphocytes travel to site
  of infection, leading to granuloma formation with
  the presence of giant cells. If this takes place,
  its known as chronic inflammation.

7
Diagnosis and Immune Response

• One way to diagnose and assess of the severity of
  an coccidioidal infection is to gauge the immune
  response.
• Immunoglobin M (IgM) is detected in 50 of
  primary coccidioidal infections within the first
  week and in 90 of infections by the third week.
• Immunoglobulin G (IgG) is used to gauge the
  intensity of the immune response and provides
  information on the host control of the infection
  and risk for disseminated (extrathoracic)
  disease.
• IgG may not be detected for several months, but
  it can persist for years.
• Also, a diagnostic test is easily done by
  microscopic examination of a tissue biopsy that
  show spherules and endospores

8
Diagnosis and Immune Response cont

• Immunity mediated by T cells is critical to
  controlling the infection. The innate cellular
  response (neutrophils, macrophages, NK cells)
  contributes to host defense also. T-cell
  activation and cytokine formation stimulate
  inflammatory cells and facilitate killing of the
  organism. T-helper cytokines promote macrophage
  killing of endospores. People who get the disease
  usually develop immunity.

9
Epidemiology

• Who gets coccidioidomycosis?
• Children, pregnant women, and HIV patients are
  most susceptible.
• C. immitis grows in arid areas of the Western
  Hemisphere, which include California to southern
  Texas. There are recent cases documented in
  Australia all of which traveled to endemic
  areas.
• Most prevalent in areas that receive rainfall all
  in one season
• The exact incidence of coccidioidal infections
  can only be estimated because about 60 of those
  infected are asymptomatic and never seek to
  medical attention.
• An estimated 150,000 infections occur annually in
  the United States. Based on skin test data, 80
  or more of residents living in endemic areas for
  5 years or longer will have a positive skin test
  result.

10
Symptoms Signs

• Symptoms and Signs
• 60 of patients infected with C. immitis are
  asymptomatic and the infection resolves
  naturally.
• Those who become symptomatic show signs of a
  respiratory syndrome 1-3 weeks following
  inhalation of arthrospores. The symptoms are
  identical to other respiratory illnesses
• fever
• sore throat
• cough
• headache
• fatigue
• chest pain.
• It is resolved in several weeks, and 95 or more
  of patients recover. If not resolved, it
  progresses to disseminated coccidioidomycosis,
  which manifest into lesions on every part of the
  body (lining of the brain, bones, joints, and
  subcutaneous and cutaneous tissues. If it
  progresses to a chronic pulmonary condition, TB-
  like lesions develop on the lungs and the
  patientscoughs up blood.

Abscesses, known as desert bumps are common
when the infection progresses to the systemic
form.
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Treatment and Prevention

• Treatment
• ketoconazole (Nizoral)
• amphotericin B (Fungizone).(which is a powerful
  fungistatic drug with potentially toxic side
  effects. As a result, hospitalization is required
  in order to monitor patients. The patient may
  also receive other drugs to minimize the side
  effects of the amphotericin B.)
• Fungal diseases are difficult to treat because
  both fungi and humans are eukaryotic. It is
  difficult to find drugs that kill the fungus
  without killing the human or animal host.
•   There is neither a vaccine, nor cure for
  Coccidioidomycosis. Maintaining general good
  health and by eating a diet low in dairy
  products, sugars, including honey and fruit
  juice, and foods like beer that contain yeast can
  help prevent infection.
•  
• Prevention
• stay indoors during dusty days, stay away from
  construction and even wear a face mask, moisten
  soil with oil or water

12
References

• Hung, Chiung-Yu, Yu, Jieh-Juen, Seshan, Kalpathi
  R., Reichard, Utz, Cole, Garry T. (2002).
• A Parasitic Phase-Specific Adhesin of
  Coccidioides immitis Contributes to the Virulence
  of This Respiratory Fungal Pathogen Electronic
  Version. American Society for Microbiology,
  Vol. 70, No. 7, 3443-3456.
• Coccidioides immitis. (2010). Encyclopædia
  Britannica. 9 November 2010. Encyclopædia
• Britannica Online lthttp//www.britannica.com/EBc
  hecked/topic/123470/Coccidioides-immitisgt
• Maza, Luis M. de la, M.D., Ph.D. (1993).
  Coccidioides immitis Electronic Version. The
  New
• England Journal of Medicine. 23 December 1993,
  3291935.
• Shields, Thomas W. Online book of General
  Thoracic Surgery. 2009.
• lthttp//books.google.com/books?idbVEEHmpU-1wCpr
  intsecfrontcoverv onepageqffalsegt
• The University of Adelaide Mycology Online. 9
  November 2010. lt http//www.mycology.
• adelaide.edu.au/Fungal_Descriptions/Dimorphic_Path
  ogens/Coccidioides/gt
• Utah Department of Health Division of Disease
  Control and Prevention. 5 August 2010.
• lt http//health.utah.gov/epi/fact_sheets/cocci.ht
  mlgt
• Volk, T. Tom Volks Fungi. Department of Biology
  University of Wisconsin-La Crosse. Web.