Systemic fungal Infections

1. MIC 409
MEDICAL MYCOLOGY

2. SYSTEMIC
MYCOSES

3. Introduction
 Systemic fungal infections constitute public health and economic
problems.
 The diseases are endemic in tropic countries
 Most systemic fungal infections are caused by opportunistic fungal
pathogens in immunocompromised hosts.
 However, invasive disease can occur in immunocompetent
individuals if the exposure dose is high or with primary (dimorphic)
fungal pathogens (causes of endemic
mycoses include Blastomyces, Coccidioides, Histoplasma, Paracoccid
ioides and Talaromyces spp.).
 Systemic fungal infections usually originate either in the lungs
(Aspergillus, Cryptococcus, Mucorales spp., as a result of inhalation) or
from endogenous flora (Candida spp. as a result of infected lines or
leakage from the gastrointestinal tract), and may spread to many other
organs.

4. Introduction cont…
 Systemic mycoses are caused by primary pathogenic and opportunistic fungal
pathogens.
 The primary pathogenic fungi are able to establish infection in a normal host;
whereas, opportunistic pathogens require a compromised host in order to
establish infection (e.g., cancer, organ transplantation, surgery, and AIDS).
 The primary deep pathogens usually gain access to the host via the
respiratory tract. Opportunistic fungi causing deep mycosis invade via the
respiratory tract, alimentary tract, or intravascular devices.
 The primary systemic fungal pathogens include Coccidioides immitis,
Histoplasma capsulatum, Blastomyces dermatitidis, and Paracoccidioides
brasiliensis.
 The opportunistic fungal pathogens include Cryptococcus neoformans,
Candida spp., Aspergillus spp., Penicillium marneffei, the
Zygomycetes, Trichosporon beigelii, and Fusarium spp.

5. Dimorphism in the Pathogenic Fungi
 Fungal dimorphism is the morphological and physiological conversion of
certain fungi from one phenotype to another when such fungi change from
one environment to another. Dimorphic fungi include C immitis, H
capsulatum, B dermatitidis, P brasiliensis, P marneffei, and S schenckii,
and certain opportunistic fungi such as Candida albicans and Penicillium
marneffei.
 Various environmental host factors control fungal dimorphism. These
include amino acids, temperature, carbohydrates, and trace elements (e.g.
zinc).
 Among the primary pathogens and S schenckii, the morphological
transformation is from a hyphal form to a yeast-like form (or spherule in the
case of C immitis) in tissue.

6. Dimorphism in the Pathogenic Fungi
 However, the dimorphism of Candida albicans is
somewhat different in that the organism transforms
from a budding yeast-like structures (blastoconidia)
to filamentous structures known as germ tubes.
 Other filamentous structures may later develop as
pseudohyphae and hyphae. Penicillium marneffei is
unique in being the only Penicillium species
pathogenic to humans. It undergoes dimorphic
conversion in vivo to transversely dividing sausage-
shaped cells.

7. Blastomycosis
 Etiologic Agent: Blastomyces dermatitidis.
The organism is spherical, single budding,
broad base with multiple basophilic nuclei in
double walled central body.
Epidemiology
a. Habitat: moist soil and wooded areas
along waterways and undisturbed places
containing organic debris, such as
porches or wood sheds.

8. Epidemiology Cont..
b. Geographic Distribution: endemic in North
America but occurs sporadically in African
countries such as South Africa, Tanzania, and
Zaire, Canada, central and southeastern
United States, India, Israel, and Saudi Arabia.
c. Transmission:. Acquisition is mainly by
inhaling conidia from mycelia growing in soil or
from various articles contaminated by conidia.

9. Blastomycosis: Epidemiology contd..
d. Infection Pattern:
 Infections can occur with all ages.
 Higher incidence among individuals in the age range of 30
to 50.
 no apparent seasonal variation
 no racial or occupational bias
 males are affected more than females
 Incidence among the immunocompromised does not differ
from the general population.

10. Blastomycosis: Pathogenesis and
Clinical Manifestations
Pathogenesis
 conidia into the alveoli, where the conidia undergo
transition to yeasts, the forms that are seen in mammalian
tissue and in cultures at 37°C
Clinical Manifestations
 The spectrum of disease that B. dermatitidis causes
overlaps with those of other fungal pathogens and
malignancy, and the clinical picture may be
indistinguishable from tuberculosis.
 Consequences of B. dermatitidis infection variable and
range from subclinical infection to fatal disseminated
disease.

11. Presentation:
3 clinical forms:
(i) Pulmonary Blastomycosis
(ii) Primary Cutaneous form
(iii) Disseminated Blastomycosis.

12. Blastomycosis: Clinical Manifestations contd…
Clinical Manifestation Distinguishing Features
Pulmonary
blastomycosis
usually begins as a mild respiratory infection which progresses with dry
cough, pleuritic pain, hoarseness, and low grade fever; chest X-ray
examination in early stages shows hilar shadow widening or disease
process suggestive of tuberculosis or carcinoma; disease progresses to
death, if untreated
Signs and Symptoms: as disease progress, sputum becomes purulent and
blood streaked; fever, dyspnea, loss of weight and strength, night sweats
Disseminated
blastomycosis
involves the skin, oronasal mucosa, and subcutanous tissues, and the
respiratory, musculoskeletal, urogenital, and central nervous systems; the
gastrointestinal system is rarely involved;
Signs and Systems: are determined by body system affected; destructive
lesions occur in vertebrae, tibia and femur;
musculoskeletal system - pain and loss of function, takes the form of
osteomyelitis, inflammation of membranes surrounding bones (periostitis)
and septic arthritis;
urogenital system - painful urination, and the presence of blood and pus in
the urine.

13. Blastomycosis: Pathogenesis and Clinical
Manifestations
Clinical Manifestation Distinguishing Features
cutaneous blastomycosis a wide variety of skin lesions may
occur; ulcerated, crusted lesions
appear resulting from an
extension of lesions from
underlying bone and/or
subcutaneous lesions, the
introduction of the pathogen by
direct inoculation of the skin;
these lesions are secondary to
the lung infection;

14. Blastomycosis contd…
Disseminated blastomycosis:
Chronic multifocal
granulomatous pneumonia
Cutaneous blastomycosis
A cutaneous ulcer with
blastomycosis. Note the
heaped-up borders.

15. Specimens for diagnosis of blastomycosis
Infection Specimen(s)
Pneumonia Sputum, bronchial washings,
bronchoalveolar lavage
Cutaneous/subcutaneous Deep tissue biopsy specimen,
scrapings, exudate
Osteoarticular Joint fluid, synovial tissue
biopsy specimen, bone biopsy
specimen
Genitourinary Prostate biopsy specimen,
urine
Meningitis Cerebrospinal fluid
Disseminated disease Bone marrow

16. Blastomycosis: Laboratory Diagnosis
b. Culture:
 the most sensitive method for diagnosis of blastomycosis.
 All specimens should be inoculated into a general-purpose growth
medium: Sabouraud dextrose agar, potato dextrose agar, potato
flake agar, or inhibitory mold agar.
 Colonies initially are white to off-white and glabrous or waxy in
appearance, becoming gray to brown as aerial hyphae develop
with age.
 Microscopically, the mold form of B. dermatitidis is characterized by
delicate, septate hyphae, 1 to 2µm in diameter, and most important
diagnostically, oval or pyriform single-celled conidia, 2 to 4 µm in
diameter, found singly at the tips of short or long conidiophores,
resembling lollipops.

17. Blastomycosis: Laboratory
Diagnosis
Other Methods
 PCR
 Histopathology/Cytopathology:Hematoxylin-
and-eosin-stain
 Antibody Tests using Enzyme Immunoassays
 Antigen Detection tests

18. Blastomycosis:
Treatment
 The drug-of-choice is itraconazole.
 Amphotericin B is used with seriously ill individuals and in
cases of the presence of brain lesions.
Prevention and Control
 avoiding contact with soil contaminated objects possibly
containing conidia and/or mycelial fragments in endemic
areas.
 Disinfection of all contaminated articles is an important
preventative measure.