Lec.

2
ENDEMIC MYCOSIS

Histoplasma
Part 1

‫محمود الوتار ام د وفاق‬

 DIMORPHIC FUNGI
(Endemic Mycoses)

COMMON CHARACTERISTICS

• LIMITED GEOGRAPHIC AREA

• SPECIFIC ECOLOGICAL NICHE
• SYSTEMIC INFECTIONS
• MORPHOLOGICALLY DISTINCT
 DIMORPHIC FUNGI
(Endemic Mycoses)

COMMON CHARACTERISTICS

• LIMITED GEOGRAPHIC AREA

• SPECIFIC ECOLOGICAL NICHE
• SYSTEMIC INFECTIONS
• MORPHOLOGICALLY DISTINCT
Histoplasmosis
• Intracellular infection of the RES caused by Histoplasma
capsulatum.
• Called caves disease
• Also called Darling’s disease; 1st described by Samuel Darling.
• First it affect the lung.
• Approximately 95% of cases of histoplasmosis are in apparent,
subclinical or benign. The person usually complain flue like
illness.
• 5% of the cases have disseminated infection. Those patients
are immunologicly compromised.
Histoplasma capsulatum
• Member of the phylum Ascomycota
• Worldwide distribution
• Naturally found in fecal-contaminated soils
• Birds and bats appear to be reservoirs
• Etiologic agent of histoplasmosis
• “histio” within histiocytes
• “plasma” resembled plasmodium.
Dimorphic fungus
Sexual multi-cellular saprophytic mycelia. This form is most commonly found in the
environment at 25 c°. The hyaline septate hyphae produce microconidia (2-5 µm)
and large spherical thick walled macroconidia with peripheral projections of cell
wall material (8-16 µm) called tuberculate microconidia.
Asexual single-celled parasitic yeastfound in enriched media or tissue at body
temprature 37c°.these are small oval yeasts in media which are seen inside the the
macrophages in the infected tissues.
pathogenesis
• Infection begins with inhalation of microconidia or hyphal
fragments
• Mycelial form transforms into yeast form Triggered by elevated
temperatures and increased cysteine levels
• Yeast cells are phagocytized by host immune system
• Yeasts is able to survive phagocytosis
• Apoptosis of infected macrophages allow M. capsulatum to spread
2 major forms of histoplasmosis
 Pulmonary and
 Disseminated

Pulmonary histoplasmosis occurs when microconidia or

mycelial fragments are inhaled
Form lesions in the hilar and/or mediastinal nodes
Many types of pulmonary histoplasmosis
• Asymptomatic pulmonary histoplasmosis
• Acute pulmonary histoplasmosis
• Mediastinal granuloma
• Fibrosing mediastinitis
• Chronic cavitary pulmonary histoplasmosis
Disseminated histoplasmosis
• Disseminated histoplasmosis is diagnosed frequently in patients
with AIDS
• It is often the initial manifestation of immunodeficiency.
• In these cases, the organism spreads via blood from the lung to
involve bone marrow, liver, spleen, or skin and CNS.
• Spread can also be associated with underlying lung disease
(e.g., emphysema).
• The disseminated form of disease is usually fatal
Diagnosis
Specimen
sputum, urine, BM, LNs, scrapings from lesions, biopsy &
peripheral blood
Direct Examination
• Blood film with Giemsa or Wright stains, BM slide and biopsy
specimens stained by silver or PAS stain.
• small, oval yeast like cells, 2-4µ within mononuclear or
polymorphonuclear cells, narrow neck budding.
• Fluorescent Ab technique.
Culture
SDA , BHI, glucose cystein blood agar at 25° & 37°C.
Culture must be incubated for at least 4 weeks
Culture of Histoplasma capsulatum on Sabouraud's dextrose agar
showing a white suede-like colony with a pale yellow-brown reverse
Histoplasmin skin test –
Intradermal inj with 0.1 ml histoplasmin Ag – DTH response. skin test
prefered not to be used for diagnosis because they can interfere with other
tests.

Serological tests
CFT: become posative within 2-3 weeks , the titer rise during progressive
disease and then decline to very low level when the disease is inactive. +ve
titer usually 1:32. cross reactivity occure.

Immunodiffusion test (ID): precipitines to two H capsulatum specific Ag.s are

detected
 H Ag signifies active disease
 M Ag signifies past exposure or repeated skin tested

RIA or EIA: for detection of circulating Ag.s

 Nearly all patients with disseminated disease have a positive test
 It is more sensitive despite cross reaction .
Exoantigen immunodiffusion plate showing positive identification of
Histoplasma capsulatum. Note H and M bands of identification; EX = culture
filtrate; H = Histoplasma antibody and antigen, C = Coccidioides antibody and
antigen; B = Blastomyces antibody and antigen.
Treatment:
Oral Itraconazole used for mild to moderate disease

Amphotericin B – disseminated & other severe forms.

Endemic mycosis

Part 2
 Coccidioidomycosis
Coccidioides posadasii and C immitis are phenotypically
indistinguishable soil molds that cause
coccidioidomycosis. The infection is endemic in well-
circumscribed semiarid regions of the south-western
United States, Central America, and South America.
Infection is usually self-limited; dissemination is rare but
always serious, and it may be fatal.
 Morphology & Identification
 On most laboratory media, C immitis produces a white to
tan cottony colony
 The hyphae form chains of arthroconidia (arthrospores),
which often develop in alternate cells of a hyphae. These
chains fragment into individual arthroconidia
These small arthroconidia remain viable for years and are
highly infectious. Following their inhalation, the arthroconidia
become spherical and enlarge, forming spherules that contain
endospores
In histologic sections of tissue, sputum, or other specimens,
the spherules are diagnostic of C immitis. At maturity, the
spherules have a thick, doubly retractile wall and may attain a
size of 80 µm in diameter.
These small arthroconidia remain viable for years and are
highly infectious. Following their inhalation, the arthroconidia
become spherical and enlarge, forming spherules that contain
endospores
In histologic sections of tissue, sputum, or other specimens,
the spherules are diagnostic of C immitis. At maturity, the
spherules have a thick, doubly retractile wall and may attain a
size of 80 µm in diameter.
 Specimens
 Specimens for culture include sputum, exudate from cutaneous
lesions, spinal fluid, blood, urine, and tissue biopsies.
 Microscopic Examination
 Materials should be examined fresh (after centrifuging, if necessary)
for typical spherules. KOH or calcofluor white stain will facilitate
finding the spherules and endospores. These structures are often found
in histologic preparations.
Cultures
 Cultures on inhibitory mold agar, Sabouraud's agar, or
blood agar slants can be incubated at room temperature
or at 37°C.
Serology
 latex agglutination test
 immunodiffusion (ID)
 complement fixation (CF) test
Skin Test
 A symptomatic primary infection is self-limited and requires only
supportive treatment, although itraconazole may reduce the
symptoms.

 However, patients who have severe disease require treatment

with amphotericin B, which is administered intravenously.
Blastomyces dermatitidis
A CHRONIC SUPPURATIVE AND GRANULOMATOUS DISEASE
OF ANY TISSUE WITH A PREDILECTION FOR LUNGS, SKIN,
PROSTATE AND BONE.
More common in black , ,north Americans
 PORTAL OF ENTRY

INHALATION

INOCULATION
(rare)
 WET MOUNT THICK WALLED DOUBLE CELLS 37C
ORGANS OF LESIONS LUNGS SKIN, PROCTATES ,BONES
SC TISSUES.
DRUGS OF CHOICE

•ITRACONAZOLE
•AMPHOTERICIN B
•VORICONAZOLE
PARACOCCIDIOMYCOSIS

• SOUTH AMERICAN
• SKIN LESION
• MOSTLY SELF LIMITED
• AFFECT MUCOUSE MEMBRANE OF THE MOUTH AND FACIAL SKIN
• SOME TIME IN THE LEG DUE TO TRAUMA or lungs
• TREAT BY SURGERY AND ANTIFUNGALS