Systemic fungal infections are uncommon
Natural immunity is high; physiologic barriers include:
1. Skin and mucus membranes
2. Tissue temperature - fungi grow better at less than
3. Redox potential - in vivo conditions too reducing for
Infection requires a large inoculum and is affected
by the resistance of the host
• infection often occurs in endemic areas
• most infections are asymptomatic or self-limiting
• in immune-compromised hosts, infections are more
often fatal (distinction between infection and disease)
Systemic fungal disease is most often
associated with four organisms
1. Coccidioides immitis
2. Histoplasma capsulatum
3. Blastomyces dermatitidis
4. Paracoccidioides brasiliensis
• Coccidioides immitis is considered to be
the most virulent of fungal pathogens.
• Restricted to hot, semi-arid areas of SW
USA and Mexico.
• Grows in the soil, but inhalation of a
single spore can initiate infection.
In infected tissues, C. immitis
appears as a mixture of hyphae and
Coccidioidomycosis: Normally a benign, sub-
clinical upper respiratory infection
In a small percentage of cases, organism disseminates
from the lungs to a variety of organs, particularly the
CNS, meanings, skin, soft tissues, and bone.
In infected tissues, organism is seen as a mixture of
spherules and endospores.
• This is primarily an infection of the lungs caused by
Coccidioides immitis and C. posadasii, two closely related
dimorphic fungi found in the soil of semi-arid regions
• In culture and in soil Coccidioides grows as a mould,
producing large numbers of barrel-shaped arthroconidia,
which are easily dispersed in wind currents.
• In the lungs the arthroconidia form spherules which contain
numerous endospores. Endospores are released by rupture
of the spherule wall and develop to form new spherules in
adjacent tissue or elsewhere in the body.
• In culture the mould colonies are initially moist and white but
change within 5–12 days to become floccose and pale grey
Epidemiology of COCCIDIOIDOMYCOSIS
• Infection is acquired by inhalation; the incubation
period is 1–3 weeks. The major risk factor for infection is
• Outbreaks have been associated with ground-disturbing
activities, such as building construction and
archaeological excavation, as well as with natural
events that result in the generation of dust clouds, such
as earthquakes and dust storms.
1. Race: Filipinos > African American> Caucasian
2. Age: Extremes more susceptible
3. Sex: Males more susceptible
Risk factors for disseminated
Microscopical appearance of
Coccidioides arthroconidia(4 × 6
Microscopical appearance of Coccidioides
spherules in tissue (up to 120 μm in
Clinical features of COCCIDIOIDOMYCOSIS
• Coccidioides causes a wide spectrum of disease, ranging
from a transient pulmonary infection that resolves without
treatment, to chronic pulmonary infection, or to more
widespread disseminated disease.
• About 40% of newly infected persons develop an acute
symptomatic and often severe influenza-like illness.
• most otherwise healthy persons recover without treatment,
their symptoms disappearing in a few weeks. In some cases
primary infection may result in chronic pulmonary disease.
• Fewer than 1% of infected individuals develop disseminated
coccidioidomycosis. This is a progressive disease that
usually develops within 3–12 months of the initial infection,
although it can occur much later following reactivation of a
quiescent infection in an immunosuppressed individual.
• One or more sites may be involved, but the skin, soft
tissue, bones, joints and the central nervous system are
most commonly affected.
• Meningitis is the most serious complication of
coccidioidomycosis, occurring in 30–50% of patients with
disseminated disease. Without therapy, it is almost always
1. Suppurative or granulatomas inflammation
2. Microscopical examination of sputum, pus and
biopsy material (Spherule or endospores seen on
3. Culture of microorganisms
4. Complement fixation assay (in cerebrospinal fluid)
5. Serological tests
• Microscopical examination of sputum, pus and biopsy material is helpful
as the relatively large size and numbers of mature spherules present
makes their detection and identification comparatively straightforward.
• Material for culture should be inoculated on to screw-capped slopes
of Sabouraud agar and incubated at 25–30°C for 1–2 weeks. The
fungus can be identified by its colonial morphology and the presence
of numerous thick-walled arthroconidia formed in chains from
alternate cells of the septate hyphae.
• The arthroconidia are highly infectious and are a serious danger to
laboratory staff. Consequently, Petri dishes should never be used for
isolation of the organism and all procedures should be carried out in a
biological safety cabinet under Category 3 containment.
• Preparations for microscopy should be made only after wetting the
colony to reduce spore dispersal.
• Serological tests play an important part in diagnosis.
• The immunodiffusion test is most useful for detection of early
primary infection or exacerbation of existing disease; antibodies
appear 1–3 weeks after infection but are seldom detectable
after 2–6 months, or in patients with disseminated
• The latex agglutination test gives similar results to the
immunodiffusion test, but is less specific. Complement fixing
antibodies appear 1–3 months after infection and persist for
long periods in individuals with chronic or disseminated disease.
• In most cases the titre is proportional to the extent of infection;
failure of the titre to fall during treatment of disseminated
coccidioidomycosis is an ominous sign.
• The historical standard of treatment is intravenous
amphotericin B, but oral fluconazole is now used to treat
many patients with skin, soft tissue, bone or joint
infections. Itraconazole is also effective, but less well
tolerated. Because oral fluconazole is so much more
benign than intrathecal amphotericin B, it is now the drug
of choice for coccidioidal meningitis.
Amphotericin B, Fluconazole
(also called cave disease)
Caused by the dimorphic fungus Histoplasma capsulatum
Tuberculated macroconidia,grown at 25C Intracellular yeast at 37°C
Histoplasmosis is characterized by intracellular growth of the
pathogen in macrophages and a granulomatous reaction in
tissue. These granulomatous foci may reactivate and cause
dissemination of fungi to other tissues.
Microscopical appearance of Histoplasma
capsulatum microconidia and macroconidia
Microscopical appearance of Histoplasma
capsulatum yeast cells in tissue.
1.Usually, acute benign
2.Rarely, progressive, chronic
or disseminated disease
3.Endemic area in U.S. -Atlantic
Ocean to N. Dakota (500,000
cases/year in U.S.), except
New England & Florida. Most
cases in Ohio and Mississippi
• Other endemic regions
include parts of Africa,
Australia, India and Malaysia.
H. capsulatum grows in soil.