1. Medical Mycology Systemic Mycoses
Hugh B. Fackrell
Filename; fungi_system.ppt

2. Fungal Infections Systemic Mycoses Opportunistic Infections
Superficial fungal infections
Cutaneous Mycoses
Subcutaneous Mycoses
Systemic Mycoses

3. Systemic or Deep Mycoses
Histoplasmosis
Coccidiomycosis
Blastomycosis
Cryptococcosis

4. Histoplasmosis before HIV
Before the appearance of HIV, approximately 95% of the cases reported of histoplasmosis capsulati where inapparent, subclinical, or benign and five percent of them where a chronic progressive lung disease with chronic cutaneous or systemic disease, or an acute fulminating fatal systemic disease.
Histoplamosis capsulati
Synonyms
North American histoplasmosis
Definition
Before the appearance of HIV, approximately 95% of the cases reported of
histoplasmosis capsulati where inapparent, subclinical, or benign and five percent
of them where a chronic progressive lung disease with chronic cutaneous or
systemic disease, or an acute fulminating fatal systemic disease. After the
appearance of HIV the disease is almost always seen in HIV positive patients or
other immunocompromised individuals. All stages of this disease may mimic
tuberculosis. Histoplasmosis may coexist with actinomycosis, other mycoses,
sarcoidosis, or tuberculosis.
Forms of the disease
Disseminated
Pulmonary
Prognosis and therapy
Disseminated, chronic cavitary, mucocutaneous, or systemic disease require
therapy. Amphotericin B is the drug of choice and recovery is typically fast with
essentially no relapse if adequate drug is given and the patient has no underlying
debilitating disease. Itraconazole and voriconazole can be considered.
Fluconazole is used in AIDS patients.
Histopathology
The histopathological picture in acute disseminated histoplasmosis is different
from that seen in the more chronic disease, and in solitary pulmonary nodules
("coin lesion"). In the first entity, Histoplasma capsulatum var. capsulatum is
localized in histiocytes and eticuloendothelial cells. The cells enlarge, but with no
evidence of inflammation. The intracellular budding yeasts are approximately 3
µm in diameter , similar to Leishmania sp., but do not contain a kinetoplast. In
addition, Leishmania does not stain with the special stains use for fungi. Older
lesions are well-developed granulomata and have a central area of caseation
resembling tuberculosis. The solitary pulmonary nodules are well organized and
usually have a circumferential rim of calcification accounting for its visibility on
chest X-ray. Fungi within these nodules are usually dead. Histoplasma
capsulatum cells are found in the center of the lesions.
Laboratory
Direct examination
The direct detection of fungi in clinical material such as bone marrow, sputum,
and tissue is usually difficult. Material stained by the PAS, Giemsa, GMS or
cellufluor methods are superior to KOH preparations.
Isolation
Inoculate the clinical material onto Inhibitory Mould agar and or yeast
extract-phosphate agar and or BHI agar with 10% sheep blood and or a medium
containing cycloheximide. Incubate cultures at 30° and do not discard until 12
weeks.
Laboratory confirmation
Confirmation is necessary to ensure that the fungus is not a species of
Chrysosporium or Sepedonium. This can be accomplished by the mould to yeast
convertion, exoantigen technique or by DNA probes.
Mycology
Histoplasma capsulatum var. capsulatum
Ajellomyces capsulatus (sexual form)

5. Histoplasmosis After HIV
Now the disease is almost always seen in HIV positive patients or other immunocompromised individuals.
All stages of this disease may mimic tuberculosis.
Histoplasmosis may coexist with actinomycosis, other mycoses, sarcoidosis, or tuberculosis.

6. Histoplasmosis
Histoplasma capsulatum
Ohio,Mississippi valleys

8. v

9. Coccidiomycosis SW deserts, San Joaquin Coccidioides immitus
Coccidioidomycosis
Synonyms
San Joaquin Valley fever, Valley fever
Definition
Coccidioidomycosis is a respiratory infection that typically resolves rapidly.
The mycosis can become acute, chronic, severe, or fatal. The disease may
result in a chronic pulmonary condition or disseminate to the meninges, bones,
joints, and subcutaneous and cutaneous tissues. The initial tissue response in
rapidly disseminating disease is suppuration, whereas chronic and advancing
infections are characterized by a granulomatous reaction with some areas
being a mixed-type cellular response. It is believed that recovery results in
immunity to reinfection. Approximately 60% of patients with primary infections
are asymptomatic, 40% have mild to acute pulmonary disease and
approximately 0.5% develop serious disease. About 25% of the patients with
disseminated disease have meningitis.
Forms of the disease
Primary ( Pulmonary , Cutaneous), Secondary ( Pulmonary , Disseminated )
Prognosis and therapy
Primary coccidioidomycosis is treated with bed rest and restricted activity.
Steroids may be used to control allergic reactions. Untreated secondary
disease has a grave prognosis. The drug of choice is amphotericin B.
Meningitis usually requires intrathecal as well as intravenous administration of
amphotericin B. 5-Fluorocytosine has little value in the treatment of
coccidioidomycosis. Itraconazole, fluconazole, ketoconazole and voriconazole
should be considered.
Histopathology
The tissue reaction is acute suppurative and granulomatous inflammation.
Acute suppuration is usually present around the arthroconidia and after a
spherule ruptures. Granulomatous inflammation usually occurs around
developing spherules. Hyphae may be present in pulmonary cavities and
meningeal lesions without arthroconidia, which can lead to confusion wih the
hyphae of an Aspergillus sp.
Laboratory
Direct examination
Directo examination of clinical specimens, such as fluids, sputa, and tissue, in
10% KOH may show spherules um in diameter with a thick wall (up to
2 um) and endospores 2-5 um in diameter characteristic of Coccidioides
immitis. Endospores are released when the wall of the spherule ruptures.
Endospores that are no longer in a spherule may remain closely appressed to
each other, resulting in a potential confusion with the yeast cells of
Blastomyces dermatitidis. This is especially true if the spherule wall is no
longer visible and the clinical specimen has been homogenized.
Isolation
Isolation involves inoculating the clinical material onto IMA agar, BHI agar
with 10% sheep blood and a medium containing cycloheximide and incubate
at 30C. Cultures should be kept 4 weeks before discarding as negative. The
fungus is fast growing and readily produces barrel-shaped arthroconidia 2.5-4
x 3-6 um with a disjunctor cell between each arthroconidium. Coccidioides
immitis is a dangerous fungus and should be handled at all times with due
respect in a Class II or III biological safety cabinet. It is classified as a BSL-3
agent. Laboratory confirmation of C. immitis is required because other fungi,
such as members of the Gymnoascaceae, may develop an anamorph similar to
Coccidioides. In vitro procedures including special conversion media,
exoantigen test or DNA probes. Slide cultures should not be set up when
Coccidioides immitis is suspected due to its dangerous nature.
Mycology
Coccidioides immitis
Natural habitat
Alkaline soil of the Lower Sonoran Life Zone in North, Central, and South
America.

10. Valley Fever

21. Blastomycosis Blastomyces dermatitidi as histo but rarer.
Canada- Manitoba and St.Lawrence river valley
Disease in horses.
Veternarians at risk.
Blastomycosis Synonyms Chicago disease, Gilchrist's disease, North American
Blastomycosis
Definition Blastomycosis may be a benign and self-limiting infection or a
chronic granulomatous and suppurative mycosis in which the
primary infection is initiated in the lungs with frequent, subsequent
dissemination to other body sites, especially the skin and bone. The
disease is most prevalent in males years of age and in
children. Blastomycosis may coexist with bronchogenic carcinoma,
histoplasmosis, severe pulmonary disease, or tuberculosis.
Forms of the disease
Chronic cutaneous and osseous
Primary pulmonary
Systemic
Prognosis and therapy
Therapy is necessary. Amphotericin B is the drug of choice, and at
least 1.5 gm must be given to avoid relapse. Hydroxystilbamidine
has been used with success in treating the cutaneous form of the
disease, but is of limited value in treating other forms of
blastomycosis. Itraconazole and voriconazole should be
considered.
Histopathology
The tissue response is a combination of acute suppurative and
granulomatous inflammation. These may vary proportionately from
one person to another and from one site to another in the same
individual. The lung generally has widespread granulomatous
inflammation with small areas of abscess formation. Fungi are
usually demonstratable at the edge of the abscess. Skin involvement
typically shows pseudoepitheliomatous hyperplasia with focal
microabscesses in the papillary dermis. The yeast cells are globose
to ovoid in shape and approximately 8-15 um in diameter. The
single blastoconidium is attached by a broad base to the parent cell.
In most instances, predominantly single cells without attached
blastoconidia are seen. The cell wall of the yeast is thick and
appears doubly refractile.
Laboratory
Direct examination
Clinical material, such as fluids, prostate fluid, sputa, or tissue, is
examined in 10% KOH . The fungus usually occurs as a thick-walled,
globose yeast that measures 8-15 um in diameter. Some yeast cells
have been reported to be up to 30 um in diameter. The fungus may
also form yeast cells that are less than 8 um in diameter. Each
blastoconidium is attached to the parent cell by a broad base.
Owing to their size, Blastomyces dermatitidis could be confused
with Coccidioides immitis or Cryptococcus neoformans under
some circumstances.
Isolation
Inoculate the clinical material onto Sabouraud glucose agar, brain
heart infusion agar, yeast-extract-phosphate agar, and a medium
with cycloheximide, and then incubate at 30C. The cultures should
be kept 4 weeks before discarding as negative. Blastomyces
dermatitidis grows best on the yeast extract agar or agar containing
yeast extract such as Mould Inhibitory Agar (IMA).
Laboratory confirmation
The mould form to yeast form conversion is necessary to ensure that
the fungus suspected to be B. dermatitidis is not a similar fungus,
such as a species of Chrysosporium or Sepedonium. The mould to
yeast conversion can be readily accomplished by inoculating
Kelley's agar or blood agar supplemented with glutamine and then
incubating the inoculated tubes at 37C. The yeast form will begin to
develop within a few days. The entire colony does not have to be
converted to the yeast form in order to consider the fungus to be B.
dermatitidis. An exoantigen technique and a DNA culture
confirmation kit are available.
Mycology
Blastomyces dermatitidis
Ajellomyces dermatitidis (sexual form)
Natural habitat
Unknown
Sensitivity Testing

27. Cryptococcosis Cryptococcus neoformans Sporadic Pigeons
Meningitis form
fatal
Cryptococcosis
Synonyms
European blastomycosis, torulosis
Definition
Cryptococcosis is a chronic, subacute to acute pulmonary, systemic,
or meningitic disease. The primary infection is in the lungs.
Following inhalation of the fungus, the primary infection may remain
localized or disseminate. On dissemination, the fungus usually
shows a predilection for the central nervous system. Primary
pulmonary infections have no diagnostic symptoms and usually are
asymptomatic. Central nervous system disease is in the form most
frequently diagnosed.
Forms of the disease
Central nervous system
Cutaneous and mucocutaneous
Osseous
Pulmonary
Visceral
Prognosis and therapy
Localized pulmonary lesions in noncompromised patients have a
good prognosis. They usually heal without treatment. Hematogenous
spread to the central nervous system has a grave prognosis unless
treated immediately. Systemic infections are usually fatal, especially
in debilitated patients, whereas primary cutaneous or
mucocutaneous lesions typically resolve spontaneously. Chronic
disease is usually characterized by alternating intervals of remission
and exacerbation, but eventually is fatal. Amphotericin B is the drug
of choice. Chronic pulmonary lesions and osteal lesions may be
managed by surgical excision. Many strains rapidly develop
resistance to 5-fluorocytosine during chemotherapy, hence
susceptibility testing is required. 5-Fluorocytosine and amphotericin
B are used concurrently in the treatment of meningitis. Fluconazole
has use in AIDS for meningitis.
Histopathology
The tissue reaction is initially a myxoid degeneration with the area of
inflammation assuming a gelatinous appearance. Large numbers of
round yeast cells are found in the mucoid matrix. As the lesion
progresses, a granulomatous reaction ensues. Organisms decrease
numerically and are usually found in giant cells and histiocytes. In old
healed granulomata, the yeasts are usually dead with disintegrated
capsules. They may be difficult to see in H & E stained slides. The
yeasts are round, typically encapsulated, and 5-15 um in diameter.
The blastoconidia are attached by a narrow neck. The capsules
stain pink by the mucicarmine technique.
Laboratory
Direct examination
Globose yeast cells are easily seen in most clinical materials, such
as cerebrospinal fluid and pulmonary tissue mounted in 10% KOH or
India ink. A capsule may or may not be present.
Isolation
Inoculate aspirates and tissue (processed in tissue homogenizer)
onto Sabouraud glucose agar, Inhibitory Mould agar and or Brain
heart infusion agar and incubate at 30C. Cryptococcus neoformans
is sensitive to cycloheximide. Growth is usually present in 2-5 days.
Spinal fluid should be processed by a filtration or centrifugation
technique.
Mycology
Cryptococcus norformans
Filobasidiella neoformans (sexual form)
Natural habitat
Fruit, pigeon manure, plants
Sensitivity Testing

31. Click on image for more details
Click on image for more details

32. Systemic Mycoses: Disease Patterns
Subacute respiratory infection
Acute infection
Severe disseminated infection

33. Systemic Mycoses: Subacute Respiratory Infection
Low fever
Non-productive cough
Mild & self limiting

34. Systemic Mycoses: Acute Infections
Productive cough
purulent sputum
pain in chest
Weight loss.
night sweats
X-ray positive
one,many lesions
consolidation
Differential diagnosis: pneumonia, tumour.

35. Systemic Mycoses: Severe Disseminated Infections
Acute Infections +
spread to other organs
chronic
Differential diagnosis t.b.

36. Systemic Mycoses: Diagnosis
X-ray
Immunochemical
skin test
serology
Microscopy
Sputum
biopsy
autopsy

37. Systemic Mycoses: Transmission
Fungal spores inhaled ...pneumonitis..no human to human transmission
Primary source bird and bat droppings and roosts. If roosts disturbed- dust, aerosol .
Chickens, Pigeons,starlings.

38. Systemic Mycoses: Treatment
Amphotericin B
and/or
5-fluorocytosine