coccidiodomycosis

1. COCCIDIOIDOMYCOSIS
(Coccidioides immitis)
Sundar Khadka,
Microbiologist
HIV Reference Unit, NPHL

2.  Primarily is an infection of the respiratory system of
human and wide variety of animals
 Caused by inhalation of 2 species belonging to genus
Coccidioides
 C. immitis
 C. posadasii
 Dimorphic fungi
 The coccidia is derived from their tissue parasitic phase
resembled protozoa belonging to the genus coccidia.
 Coccidioides (“resembling Coccidia”) immitis (“not mild”).

4. • The endemic areas for Coccidioides in the United States include
Arizona, south central California (San Joaquin Valley), Nevada, New
Mexico, certain parts of Utah, and the western half of Texas.
• Other endemic areas are the regions of Mexico that border the
western United States.
• The fungi also are endemic to some Central American countries,
including Guatemala, Honduras, and Nicaragua. Certain desert
regions of South America (Brazil, Argentina, Paraguay, Venezuela)
also are endemic.
• It is also call San Joaquin Valley fever or Valley fever because it is
widespread (endemic) to that area.

6.  The spores become airborne when the dust is
disturbed, and they are then inhaled.
 Occupational hazards are in those occupations in
the exposure to soil dust, including agricultural
workers, construction workers, telephone pole
diggers, and archaeological students.
 AIDS cases limited by geography.

7. • Coccidioidomycosis was discovered by
Alejandro Posadas in 1891 in a hospital in
Buenos Aries, Argentina.
• He had a patient named Domingo Ezcurra
who had the disease, and Posadas was able
to study the progression of the disease over
the course of 7 years. His head is now the
showpiece of the medical school museum
and has been exhibited at medical mycology
meetings in South America
• Although the disease was discovered in
Argentina, the second case was not found
until 35 years later, and fewer than 30 cases
were reported there before 1967.

8.  Posadas thought that the patient had the malignant skin
disease, mycosis fungoides, but examination of skin biopsy
specimens revealed organisms resembling the
protozoan Coccidia.
 It was orginally assigned to this organism presuming it to
be protozoan and subsequently same name was endoresed
when its fungal nature was established

9.  The disease was considered rare and uniformly
fatal until 1929, when a Stanford University
medical student, Harold Chope, accidentally
inhaled a culture of Coccidioides and developed a
nonfatal pulmonary illness accompanied by
erythema nodosum
 This case sparked interest that resulted in
researchers uncovering the association between
C.immitis and the clinical condition known as San
Joaquin Valley fever.
 Charles E. Smith and colleagues subsequently
developed coccidioidin skin test and serologic
testing for coccidioidomycosis.

10. • The Coccidioides genus is considered dimorphic.
Dimorphism is characterized by production of
filamentous (mycelial) forms by certain fungi during
their saprophytic phase in the environment or when
incubated at lower temperatures on media.
• Dimorphic fungus
• The favorable zone for growth is characterized by
• low elevations (below 3700 ft),
• scant rainfall (5-20 in/y),
• mild winters (40-54°F) and
• hot summers, and
• sandy alkaline soil with increased salinity

11. • About 60 % of coccidiomycosis infections cause no
symptoms.
“benign, asymptomatic lung infection.”
• In cases where symptoms are present (symptomatic
illness), however, the illness can range from mild to
severe.
• People who are immunocompromised, such as those
with AIDS or systemic cancer, are at greater risk for
having severe, disseminated cases of coccidiomycosis.
• In many cases it may not have been recognized,
diagnosed, or treated at the time of the original
infection.
• A disseminated disease, where the infection has spread
to the bones, liver brain, skin and heart may occur, but
is not common.

12. • In soil, Coccidioides grows as a mold (mycelium) with branching
septate hyphae.
• During the rainy season, the mycelia grow rapidly, but they are
also the least infectious form of the organism.
• As the soil becomes dryer, in late summer and early fall, the
hyphae develop into arthrospores.
• Arthrospores are extremely hardy, withstanding extreme heat,
desiccation and changes in soil salinity and remaining viable in
the soil for months to years.
• When the soil is disturbed by wind or excavation, arthrospores
readily disarticulate into single arthroconidia and become
airborne.The arthroconidia are the infectious particles of
coccidioidomycosis.

13. • Morphology
• C. immitis is a dimorphic fungus.
• Mycelial form:
• Cultured on SDA at 25 ºC it grows as a mold
in 2 to 3 days.
• Characteristically, the mycelia develop
arthroconidia.
• It is a barrel-shaped (smaller at the edges,
wider at the middle) asexual spore.
• Typically, the arthroconidia alternate with
non spore-forming cells in the mycelium.
Mycology

14. • Sperules Form:
• When grown in vitro at 37º C, there is no
yeast form in vivo, (pus or tissue but the
pathogenic or invasive form which is a
spherule.
• spherules (30-60 µ) filled with endospores
which are 3 to 5 microns in diameter.
• A spherule break apart releasing the
endospores.
• They can also be seen in a KOH preparation
of sputum.
• It is pathognomonic for coccidioidomycosis.

16.  C. immitis is a dimorphic fungus with 2 life
cycles.
 The organism follows the SAPROPHYTIC
cycle in the soil and the PARASITIC cycle in
man or animals

17. Saprophytic cycle starts in the soil with spores (arthroconidia) that develop
into mycelium.
The mycelium then matures and forms alternating spores within itself.
The arthroconidia are then released, and germinate back into mycelia.
The parasitic cycle involves the inhalation of the arthroconidia by animals
which then form spherules filled with endospores.
The ambient temperature and availability of oxygen appear to govern the
pathway. The organism can be carried by the wind and therefore spread
hundreds of miles in storms so the distribution is quite wide.
The spores of the organism are readily airborne. The cases that occur are
usually in patients who have visited an endemic area and brought back
pottery, or blankets purchase from a dusty roadside stand, who were exposed
when they were stationed in the endemic area.
The cotton, grown in the desert of the Southwest of USA, was contaminated
with the fungus and the mill workers inhaled the spores while handling the
raw cotton and developed coccidioidomycosis

20. • If inhaled by animals or humans, the arthroconidia can
reach the pulmonary alveoli.
• The size of the arthroconidium allows it to be deposited in
the terminal bronchiole but probably does not allow it to
reach the alveolar space by means of direct inhalation.
• Once in the alveoli, Coccidioides enters the yeast stage of
its life cycle.
• The arthroconidium sheds its outer coating, swells, and
becomes a spherule—a round, thick-walled multinucleate
structure that contains hundreds to thousands of
uninucleated endospores.
• Rupture of the spherule leads to release of the
contained endospores, each of which matures into
spherules, repeating the cycle.

21. • Coccidioidomycosis is initially, a respiratory infection,
resulting from the inhalation of conidia, that typically
resolves rapidly leaving the patient with a strong specific
immunity to re-infection.
• However, in some individuals the disease may progress to a
chronic pulmonary condition or to a systemic disease
involving the meninges, bones, joints and subcutaneous
and cutaneous tissues.

22.  Coccidioides arthroconidia are extremely infectious; a single
C.immitis arthroconidium may be sufficient to produce a
respiratory infection. However, exposure to high spore burdens
increases the likelihood of more severe disease in otherwise
healthy persons
 Most often the disease causes mild flu-like symptoms, but usually
is resolved in the lungs.
 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.

23.  The disseminated form of valley fever can devastate the
body, causing skin ulcers, abscesses, bone lesions, severe
joint pain, heart inflammation, urinary
tract problems, meningitis, and often death.

24.  Fatigue (tiredness)
 Cough
 Fever
 Shortness of breath
 Headache
 Night sweats
 Muscle aches or joint pain
 Rash on upper body or legs

25. 1. Pulmonary coccidioidomycosis
2. Disseminated coccidioidomycosis
3. Chronic coccidioidal meningitis
4. Coccidioidomycosis In AIDS patients

27. Extension of pulmonary coccidioidomycosis showing a large
superficial, ulcerated plaque
(Courtesy of John Rippon, USA).

28. Chronic cutaneous coccidioidomycosis showing granulomatous
lesions of the face, neck and chin

29.  Direct microscopic
 Culture
 Serodiagnosis
 Molecular diagnosis

30.  Skin scrapings,
 Sputum and bronchial washings,
 Cerebrospinal fluid,
 Pleural fluid and
 Blood , bone marrow,
 Urine
 Tissue biopsies from various visceral organs

31.  Since this is the most virulent of the fungal pathogens, it
should never be grown out in culture except under very
controlled conditions, such as using gloved transfer hood
and in screw cap vials.
 The fungus produces its small arthrospores in abundance
in culture. If these escape, they can cause lab infections.
 These arthrospores can pass through a 2 mm filter found
in normal biological safety cabinets/ hoods.
 There have been persistent rumors that it is being
developed for use in biological warfare, but it could
probably not be grown in a large enough quantity to be
used for use in bioterrorism because of the danger it would
pose for the people growing it.

32.  KOH
 CFW
 H& E
 PAS
 GMS
 Doubly refractile thick wallled globular sphereules of
about 20-80 micrometer

36.  Media:
1) SDA
2) Blood agar
3) BHI
 25’c for 3-5 days
 Colonies of C. immitis/posadasii on Sabouraud’s
dextrose agar at 250C are initially moist and
glabrous, but rapidly become suede-like to downy,
greyish white with a tan to brown reverse,
however considerable variation in growth rate and
culture morphology has been noted.
 In culture the extremely small arthroconidia are
produced on medium in 5-10 days.

38. • Microscopy shows typical single-celled, hyaline, rectangular to
barrel-shaped, alternate arthroconidia, 2.5-4 x 3-6 µm in size,
separated from each other by a disjunctor cell.

39.  There is a Coccidioides skin test, very similar to
the tuberculosis skin test.
 The test shows that most people in endemic
areas have come into contact with the organism.
A small fever is usually the only symptom. Most
people don't know they have had it. Thus the
skin test is of limited diagnostic value since most
people in endemic areas will test positive.
 The disease must be diagnosed from tissue
material-- spherules with endospores must be
found for an accurate diagnosis.

40.  By using heat stable and heat labile antigens

41.  Latex particle agglutination
 ELISA

43.  Mice, rats, guinea pigs

44.  Some treatments for systemic coccidioidomycosis
include Amphotericin-B or the azoles ketoconazole or
itraconazole.
 Fungal diseases are notoriously difficult to treat
because it is difficult to find drugs that kill the fungus
without killing the human or animal host.