SYSTEMIC MYCOSES

DR JOHN EGBAGBA.
Contents
Introduction- Brief overview of fungi
What are systemic mycoses?
Classification
What are the implicated organisms?
The general characteristics of systemic fungal
organisms?
Pathogenesis
Clinical Features
Laboratory diagnosis
Specific Infections
Introduction: What are Fungi?
A diverse, heterogenous group of eucaryotes
Few cause disease in humans
Have a nucleus bound by membrane; ER and
mitochondrion
Generally have two phases of growth- vegetative and
reproductive
Vegetative- cells are haploid and divide mitotically
Introduction
Most fungi exist as molds with hyphae but some fungi
exist as unicellular yeast cells
Some change their morphology- DIMORPHIC e.g.
Candida- Yeast (370c) and mold (250c)
The reproductive phase can either asexual or sexual
Asexual- generation of spores (fungi imperfecti)
Sexual- requires specific cellular structures (perfect
fungi)
Introduction
Fungal membranes contain ergosterol rather than
cholesterol and this provides a target for
chemotherapy
They are chemotropic (equipped with a rich enzyme
system and are thus able to degrade a wide variety of
organic substrates into soluble nutrients)
Pathogenic fungi are exogenous with water, soil and
organic debris as natural habitat.
SYSTEMIC MYCOSES
a.k.a. Deep mycoses
Fungal infections affecting various organs
Caused by thermally dimorphic fungi (i.e. can exist as
molds or yeast)
 Classification
•Primary systemic mycoses:
Fungal infections of the body caused by fungal
pathogens which can overcome the physiological and
cellular defenses of the normal human host by
changing their morphological form.
• are often asymptomatic but when disseminated the
prognosis becomes poor
 Dimorphic systemic mycosis
DISEASE CAUSATIVE ORGANISMS

Histoplasmosis Histoplasma capsulatum (American

Histo)
Histoplasma dubosii (African Histo)
Coccidioidomycosis Coccidioides immitis

Blastomycosis Blastomyces dermatitidis

(North American Blastomycosis;
Gilchrist’s disease)
Paracoccidioidomycosis Paracoccidioides brasiliensis
(South American blastomycosis/ Lutz-
Splendore-Almeida disease)
Sporotrichosis Sporothrix schenkii

Penicilliosis marneffei Penicillium marneffei

Classification
• Opportunistic systemic mycoses:
occur almost exclusively in debilitated patients whose
normal defense mechanisms are impaired;
The increasing incidence can be paralleled with;
Emergence of AIDS
More aggressive Cancer
Post transplantation chemotherapy
Use of antibiotics, cytotoxics, immunosuppressives,
corticosteroids etc
Opportunistic systemic mycosis
DISEASE Causative organism
Candidiasis Candida albicans and
related species
Cryptococcosis Cryptococcus
neoformans
Aspergillosis Aspergillus fumigatus
Pseudallescheriasis Pseudallescheria boydii
Zygomycosis Rhizopus, Mucor,
(Mucormycosis) Rhizomucor, Absidia etc
Hyalohyphomycosis Penicillium,
Paecilomyces, Beauveria
Phaeohyphomycosis Cladosporium,
Exophiala, Wangiella,
Bipolaris, Exserohilum,
Curvularia
Penicillosis marneffei Penicillium marneffei
Pathogenesis
Spores in natural habitat - soil

Spores inhaled with dust by

humans

Progression may
produce pulmonary
In the human lungs; symptoms (primary
Phagocytosis by macrophages pulmonary
mycosis) or
Spread to other organs by ulcerative lesions
hematogenous or lymphogenous
route

Host responses produce formation of

syncytia, fibrous tissue, granulomas
and calcified lesions
Pathogenesis
Host defenses against the fungi include nonspecific
and specific factors:
 Nonspecific defenses include:
skin (lipids, fatty acids, normal flora)
internal factors (mucous membranes, ciliated cells,
macrophages),
blood components, temperature, genetic and
hormonal factors.
Pathogenesis
In other words, both physical and chemical factors
and phagocytic defenses play major roles in prevention
and control of mycotic disease.
Pathogenesis
Specific defenses include both humoral and cell-
mediated.
some antibodies may be protective
cell-mediated defenses are probably more important.
Acquired resistance is usually T-cell mediated and
persons with compromised cell-mediated defenses
generally show more disseminated disease.
Clinical Features
Asymptomatic/mild respiratory illness (goes
unreported)
Pneumonia---fever, cough ;
---CXR infilterates like TB (granulomas with
calcification can follow resolution of the pneumonia);
---small % progress to severe pneumonia
---smaller % progress to chronic cavitatory pneumonia
(like chronic TB pneumonia with weight loss, night
sweats, low grade fever etc)
Clinical Presentation
Disseminated infection
---Rare,
---follows haematogenous spread
---complications include meningitis; Bone lytic
granulomas; Skin granulomas( breaks down to ulcers
and other organ lesions)
---Common in immunocompromised hosts
Clinical features
low grade fever with chills
night sweats
Malaise
appetite loss.
Similarities between systemic mycoses and
tuberculosis
Transmission by inhalation
Local infection in the lung
Cell mediated immunity involved in both
Asymptomatic, mild, severe or chronic lung infections
Lung granulomas, calcification and or calcifications
 Similarities between systemic mycoses and
tuberculosis
•Like PPD in tuberculosis, there is coccidioidin and
histoplasmin ( swelling in 24-48hours)
•Can disseminate via hematogenous route to distant sites

•DIFFERENCES
•No person to person transmission
•Fungi has spores while tuberculosis has acid fast bacteria
Clinical diagnosis
Epidemiology
History
Symptoms and signs
Skin testing for a delayed hypersensitivity response is
useful for epidemiological purposes but not often for
diagnosis
Laboratory

diagnosis
Clinical materials
Skin scrapings,
 sputum and bronchial washings,
cerebrospinal fluid, pleural fluid and blood,
bone marrow, urine and tissue biopsies from various
visceral organs.
Laboratory Diagnosis
2) Direct Microscopy:
(a) Skin scrapings should be examined using 10% KOH
and Parker ink or calcofluor white mounts;
(b) Exudates and body fluids should be centrifuged and
the sediment examined using either 10% KOH and
Parker ink or calcofluor white mounts,
Laboratory Diagnosis
c) Tissue sections should be stained using PAS digest,
Grocott's methenamine silver (GMS) or Gram stain.
(difficult to observe with in H &E preparations)
Histopathology is especially useful and is one of the
most important ways of alerting the laboratory that
they may be dealing with a potential pathogen.
Laboratory Diagnosis
3. Culture
Grow at 250C on saboraud dextrose agar
Grow at 370C on blood agar
 Organisms
•Histoplasma capsulatum
•Blastomyces dermatitidis
•Paracoccidioides braziliensis
•Coccidioides immitis
•Cryptococcus neoformans
•Penicilliosis marneffei
•Candida albicans
BLASTOMYCOSIS
BLASTOMYCOSIS
Endemic in Ohio and Mississippi Rivers valleys,
important veterinary problem
Cases recently diagnosed in Africa, Asia and Europe
Dimorphic fungi (mycelial forms with spores at 25C
and Yeast forms at 37C)
IP: 3-15weeks
Indolent onset
Blastomycosis
Asymtomatic (rare)
Pneumonia (lesions rarely calcify)
Disseminated is the most common-weight loss, night
sweats and lung involvement
Cutaneous ulcer (face, upper limbs, neck and scalp)
SLOGAN says: bLAST to get, No BLAST to have( rarest
systemic fungal infection but it is rarely asymptomatic
or mild i.e. hardest to get and hardest to have)
Blastomycosis
Biopsy of affected tissue: lung, skin etc
Silver stain specimen
Culture on saboraud agar
Serology
Skin tests

Tissue morphology:
Large broad based unipolar budding yeast cells(8-10um)
Blastomycosis
Treatment
Itraconazole
Ketoconazole
Amphotericin B
Blastomyces
Tissue sections showing large , broad-base, unipolar
budding yeast-like cells, 8-15um in diameter
Ulcerated granuloma due to B.dermatitidis
Cutaneous blastomycosis
COCCIDIOIDOMYCOSIS
COCCIDIOIDOMYCOSIS
Endemic in Southwestern United States and Northern
Mexico
Dimorphic
Respiratory transmission
Asymptomatic in most persons
Pneumonia
Disseminated affecting lungs, skin, bones and meninges
A small % of individuals develop painful erythematous
nodular lesions called erythema nodosum
COCCIDIOIDOMYCOSIS
Biopsy
Tissue morphology: Spherules(10-80um) with
endospores (2-5um)
Serology
Skin tests
TREATMENT
Amphotericin B
Itraconazole
Fluconazole
Chronic cutaneous coccidioidomycosis showing
granulomatous lesions of the face, neck and chin
Extension of pulmonary coccidioidomycosis
showing a large superficial, ulcerated plaque
COCCIDIOIDOMYCOSIS
Direct microscopy of skin scrapings
from a cutaneous lesion mounted in Tissue section showing typical
10% KOH and parker ink solution andosporulating spherules of
showing endosporulating spherules C.immitis
of C. immitis
Culture of Coccidioides immitis showing a suede-like to
downy, greyish white colony with a tan to brown reverse
HISTOPLASMOSIS
Histoplasmosis
Endemic in Ohio and Mississippi Rivers valleys, most
infections are asymptomatic.
Present in bird and bat droppings
Dimorphic (It has no capsule despite its name)
Respiratory transmission; can survive intracellularly
within macrophages
All stages of this disease may mimic tuberculosis
Histoplasmosis
Asymptomatic in most persons
Pneumonia: Lesions calcify which can be seen on
chest x-ray(may look similar to TB)
Disseminated : can occur in almost any organ
especially the lung, spleen or liver
Histoplasmosis
Diagnosis
Lung biopsy
Silver stain specimen
Culture
Serology
Immunodiffusion +/- complement fixation tests for the
detection of antibody
Small narrow base budding yeast cells (1-5um; 2-5um
in var. duboisii)
Histoplasmosis
TREATMENT
Itraconazole
Amphotericin B in immunocompromised patients
Histoplasmosis of the lower gum
showing ulcer around base of the teeth
Tissue morphology of H. capsulatum var. capsulatum (left)
showing numerous small narrow base budding yeast cells (1-5um
diam) inside macrophages and H. capsulatum var. duboisii (right)
showing larger sized budding yeast cells (5-12 um in diameter).
Paracoccidioidomycosis
Paracoccidioidomycosis
Endemic in Central and South America, primarily
Brazil

Large narrow base, multi-budding yeast cells (20-

60um)
Paracoccidioidomycosis
Phase contrast of cells from a
culture (left).
Multiple, narrow base, budding yeast
cells "steering wheels" of P.
brasiliensis. GMS stained lung section
(right)
Mucocutaneous paracoccidioidomycosis showing facial
destruction on the left and ulceration of the pharyngeal mucosa
on the right
Cryptococcosis
Cryptococcosis
Worldwide distribution. Most common clinical
presentation is meningitis.
Found in pigeon droppings
Respiratory transmission
Has a polyssacharide capsule
Not dimorphic, exist as yeast form only
Most cases occur in immunocompromised patients
Cryptococcosis
Diagnosis
India stain of CSF: observe encapsulated yeast
Cryptococcal antigen stain of CSF: detects
polysaccharide antigens
Fungal culture
Cryptococcosis
Subacute or chronic meningitis (headache, fever ,
vomiting, neurologic or mental status change)
Pneumonia usually self limiting
Acne like skin lesions

TREATMENT
Amphotericin B and Flucytosine (is superior
amphotericin B alone)
Fluconazole
Sporotrichosis
Sporotrichosis
Chronic mycotic infection of the cutaneous or
subcutaneous tissues and adjacent lymphatics
Characterised by nodular lesions which may
suppurate and ulcerate
Infection is by traumatic implantation of the fungus
into the skin or very rarely by inhalation into the lungs
Small narrow base budding yeast cells (2-5um)
Sporotrichosis
20 spread to the articular surfaces, bone and muscle
is common
Occasionally involves the CNS, lungs or GIT
Fixed Cutaneous Sporotrichosis
Primary lesions develop at the site of
implantation of the fungus, usually at more
exposed sites mainly the limbs, hands and
fingers.

Painless nodular
which soon become
palpable

These lesions become

localised and does not
Nodular lesion
spread along lymphatic
ulcerates to
channels
discharge a serous
or purulent fluid
 Lymphocutaneous sporotrichosis
Sporotrichosis
Fixed cutaneous sporotrichosis
showing typical elevated subcutaneous
nodules developing along the regional
showing an ulcerating lesion on the lymphatics of the forearm.
leg.
Lymphocutaneous Sporotrichosis
Primary lesions develop at the site of implantation of
the fungus

Painless nodule which later ulcerates

secondary lesions appear along

the lymphangitic channels
Sporothricosis
Lymphocutaneous sporotrichosis
showing more advanced, ulcerating
lesions developing along the lymph
system of the forearm.
Section from a fixed cutaneous
lesion showing round Periodic Acid-
Schiff (PAS) positive budding yeast-
like cells. Sporothrix schenckii is a
dimorphic fungus and this is the
typical yeast-like form seen in tissue.
P. Marneffei infection
P. Marneffei infection
It has now become a major opportunistic pathogen
in HIV positive patients in Indochina.
Also common seen in Northern Thailand; Vietnam,
Hong Kong, Taiwan and Southern China
Other predisposing factors include
lymphoproliferative disorders; bronchiectasis; and
tuberculosis; Autoimmune diseases and corticosteroid
therapy
P. marneffei
Focal or disseminated
In HIV patients, this infection is disseminated at the time
of diagnosis
Skin, RES, lung and gut are infected
Fungaemia is present in majority of cases and other
organs are infected; kidney, bone, joints and pericardium
Non specific symptoms like fever, weight loss and anemia
Skin lesions: papules with central umbilication similar to
those seen in molluscum contagiosum are seen on the
face, trunk and extremities
P. marneffei
Little is known about its habitat but the following
sources have been implicated
Traumatic implantation
Enteric route (Eating of bamboo rats )
Inhalation of spores with dust or specific host plant
Diagnosis
Direct microscopy
Culture of infected tissues
P.marneffei
Molluscum contagiosum
lesions caused by P. marneffei
on the neck of an HIV+
patient.
Typical papules often with
a central necrotic
umbilication due to P.
marneffei.
P. Marneffei infections
Molluscum contagiosum"
lesions caused by P. marneffei
in the buccal cavity.
Molluscum contagiosum"
lesions caused by P. marneffei
below the eye and on the
cornea.
P. marneffei
GMS stained tissue section showing
typical septate yeast like cells of P.
marneffei.
Giemsa stained touch smear
Resembles those seen in
histoplasmosis
Penicilliosis
marneffei
Culture showing a
common green
saprophytic
Penicillinium sp and
the typical yellow-
pink colony with
distinctive red
diffusible pigment
of Penicillin
marneffei
Candidiasis
Candidiasis
Not found in blood
Normal inhabitant of the skin, mouth and GIT
Exist as pseudohyphae and yeast
In the normal host : oral thrush, vulvovaginal
candidiasis, cutaneous (diaper rash, skin fold rash)
In the immunocompromised host, it causes:
---Esophageal candidiasis (retrosternal chest pain,
dysphagia and fever)
Disseminated candidiasis: in sick hospitalised patients
leading to multiorgan failure
Chronic mucocutaneous candidiasis
Candidiasis
Diagnosis
KOH stain of specimen
Silver stain fo specimen
Blood culture

TREATMENT
Amphotericin B
Fluconazole
Aspergillosis
Aspergillosis
Inhalation of spores
Ubiquitous, present in peanuts, grain and cereals
Some people develop a type 1 hypersensitivity reation
(IgE mediated allergic reaction
Bronchspasm
Increase IgE antibodies and blood eosinophilia
Also manifest a type 4 reaction and lung infilterates
Individuals who have had a lung cavitation from TB or
malignancy can develop an ASPERGILLOMA
Aspergillosis
Invasive pneumonias and disseminated disease in
immunocompromised patients
Allergic bronchopulmonary aspergillosis (bronchial is
colonized)
AIDS patients with CD4 count less than 50cells/mm3
are predisposed to aspergillosis
Produces toxins (aflatoxin) that cause liver damage
and liver cancer
Aspergillosis
Microscopic examination
Culture
Serology: The ID test for precipitins to A. fumigatus is
positive in over 80% of patients with aspergilloma or
allergic forms of aspergillosis.
TREATMENT
Itraconazole
Amphotericin B
Thank you