Opportunistic

Fungal Infections

Opportunistic Mycosis

Opportunistic mycosis a fungal or fungus-like

disease occurring in an animal / humans
with a compromised immune system.
Opportunistic organisms are normal resident
flora that become pathogenic only when the
host's immune defenses are altered, as in
immunosuppressive therapy, in a chronic
disease, such as diabetes mellitus, or during
steroid or antibacterial therapy that upsets
the balance of bacterial flora in the body.
T.V.Rao M.D

Common Opportunistic
Fungus
We

find the highest frequency of

opportunistic fungal infections come
in the following order:

1.Candidiasis
2.Aspergillosis
3.Cryptococcosis

Candida as
Opportunistic
Infection

Candidosis

Candidiasis also
called as Monoliasis,
Can infect Skin,
Mucosa, or Internal
Organs
Called as Yeast Like
fungus
Currently important
cause of opportunistic
fungal infection.

What are Candida

Normal flora
Exist in Mouth, Gastrointestinal tract.
Vagina, skin in 20 % of normal
Individuals.
Colonization increases with age,in pregnancy
Hospitalization
Immunity Depends on T lymphocytes, and effective
Immunity
Important etiological agent presenting as
opportunistic infection in Diabetus and HIV
patients

Morphology and
Culturing
Ovoid shape or spherical budding cells
and produces pseudo mycelium
Routine cultures are done on
Sabouraud's Glucose agar,
Grow predominantly in yeast phase
A mixture of yeast cells and pseudo
mycelium and true mycelium are seen
in Vivo and Nutritionally poor media.

Macroscopic and
Microscopic appearance of
Candida spp

Pseudohypal structures in
Candida

Normal Flora to
Pathogenic fungi
As

Candida is present in practically

all humans, it has many
opportunities to cause endogenous
infections in compromised host - so,
Candida infections continues to most
frequent opportunistic fungal
infection.

Systemic Candidosis

Occurs in Patients who carry more yeasts in Mouth,

Gastrointestinal system,
Predisposed with Individuals with
1 On antibiotic or/and Steroid Therapy
2 Immunosupressed
3 Recipients with organ transplantation
4 Infancy Old age Pregnancy
On Antibiotic therapy
5 Indisposed with trauma Occluding lesions,
6 Immuno Supression, Major event in AIDS patients
7 Diabetus mellitis.
8 Zink and iron deficiencies

Pathogenesis and
Pathology

Mucosal infections occur superficially Discrete

white patches on mucosal surface.
Can affect tongue
Infants and old persons are affected
In Immune compromised /AIDS. Oral candidois
is commonly seen
Vaginal Candidosis causes itching soreness
white discharge, White colored lesions,
Pregnancy in advanced stage,
Majority experience one episode in a life time
T.V.Rao MD

Predisposition after
Surgery and Therapeutic
Approaches

Post operative
Immuno Supression
Use of IV catheters
Use of cytotoxinc
drugs and
cortosteriods
Use of Urinary
Catheters

Important species of
Candida in Human
infections

C.albicans
C.tropicalis
C.glabrata
C.Krusei

Prominent Infections
with Candida

Oral Thrush produced by

Candia albicans

Many cases of AIDS are

suspected by observation of
Oral Cavity

Laboratory Diagnosis
Skin

scrapings,
Mucosal scrapping,
Vaginal secretions
Culturing Blood and other body
fluids,
Observations
Microscopic observation after Gram
staining. Gram + yeast cells.

Laboratory Diagnosis

Isolation of
Candida from
various specimens
confers diagnosis
Serology
Molecular Methods

Microscopy

Gram staining A
rapid method
KoH preparation
Methylamine silver
staining

Culturing

Easier to culture on
Sabouraud's dextrose
agar
Culturing in routine
Blood culture Media
Culturing urine - A
semiquative estimations
are essential Colony
forming units essential
in attributing infections
T.V.Rao MD

Easier Identification of
species as C.albicans

Germ tube test

identifies C.albicans
from other Candida
species.
Majority of
Diagnostic
laboratories depend
on this test.

Emerging Methods for

detection of Candida
Infections

Molecular Methods
PCR

Cryptococcosis.

Cryptococcus
neoformans

A Capsulated yeast
A true yeast..
A sporadic disease
in the past.
Most common
infection in AIDS
patients.

Structure of
C.neoformans

Morphology

A true yeast
Round 4 10 microns
Surrounded by Mucopolysaccharide capsule.
Thick in vivo
Negative staining with India Ink and Nigrosin
60% of the infected prove positive by India Ink
preparation on examination of CSF
KoH preparations in Sputum and other tissues,
PAS and Mucicaramine staining helps
confirmation.

As Seen in India Ink

preparation

Culturing

CSF -Culturing on
Sabouraud's agar,
and incubated at 370
c for upto to 3 weeks
Cultures appear as
Creamy, white,
yellow
Brown colored
Simple urease test
helps in confirming
the isolate.

Cryptococcus neoformans
Serotypes
A true yeast
4 serotypes - A,B,C,D
A and D - C.neofromans var neoformans
B and C - C.neoformans var gatti.
Many infections are caused by
C.neofromans var neoformans.
Found in wild/Domesticated birds.
Pigeons carry C.neofromans,
Birds do not get infected.

Pigeons and Red river gum

tress harbors the
Cryptococcus in nature

Life cycle of
C.neofromans

Pathogenesis

Enters through lungs - inhalation of

Basidiospores of C neoformans
Enters deep into lungs, Men acquires more
infections, and women less infected.
Self limiting in most cases,
Pulmonary infections can occur.
Present as discrete nodules - Cryptococcoma.
T.V.Rao MD

Pathogenesis

Can infect normal humans

Abnormalities of T lymphocyte function
aggravates, the clinical manifestations.
In AIDS 3- 20% develop Cryptococcosis.
Present with Chronic meningitis , Meningo
encephalitis
Manifest with head ache low grade fever,
Visual abnormalities ,Coma fatal
Treatment reduces the morbidity and cure
in non immuno supressed expected.

Pathogenesis
Can

manifest with involvement of

,Skin,
mucosa,organs,Bones,and as
Disseminated form.

Can mimic like

Tuberculosis,

Laboratory Diagnosis.

CSF Microscopic observation under India

Ink preparation
Direct microscopy - Gram staining
Cultures on Sabouraud dextrose agar,
Serological tests for detection of Capsular
antigen
CSF findings mimic like Tuberculosis
IN CSF - latex test for detection of Antigen
Blood cultures,
ELISA

Treatment
Immune competent Fuconazole,Itraconazole
Immune Deficient Amphotericin B
Flu cytosine
AIDS patients are not totally
cured , Relapses are frequent
with fatal outcome.
Rapid resistance with Fluconazole.
Avoid contact with Birds

ASPERGILLOSIS

Aspergillosis
In

nature > 100 species of

Aspergillosis exist, Few are important
as human pathogens
1 A.fumigatus
2 A.niger
3 A.flavus
4 A.terreus
5 A.nidulans

Fungal spores enters

through respiratory tract

Morphology

Cultured as Mycelial
fungus
Separate hyphae with
distinctive sporing
structures
Spore bearing hyphae
Conidiophores
terminates in a swollen
cell vesicle surrounded
by one or two rows of
cell ( Streigmata ) from
which chains of
asexual conidia are
produced

Pathogenesis - varied
clinical presentations

Allergic Aspergillosis Atopic individuals,

with elevated IgE levels
10-20% of Asthmatics react to A.fumigatus
Allergic alveoitis follows particularly heavy
and repeated exposure to larger number of
spores
Maltsters Lung causes allergic alveolitis,
who handle barley on which A.claveus has
sporulated during malting process
T.V.Rao MD

Pathogenesis

Aspergilloma A
fungal ball, fungus
colonize Preexisting
(Tuberculosis ) cavities
in the lung and form
compact ball of
Mycelium which is later
surrounded by dense
fibrous wall presents
with cough, sputum
production
Haemoptysis occurs
due to invasion of blood
vessels

Pathogenesis

Invasive Aspergillosis
occurs in
immunocompromised with
underlying disease
Neutropenia Most
common predisposing
factor
A.fumigatus is the most
common infecting species

In Bone marrow recipients leads

to high mortality
Lung sole site in 70 % of
patients
Fungus invades blood vessels,
causes thrombosis septic emboli
Can spread to Kidney and heart.

Pathogenesis

Endocarditis A rare

complication
Open heart surgeries are
risk factors
Poor prognosis

Paranasal granulomas
Caused by

A.flavus,A,fumigtus
may invade paranasal
sinuses spread to bone to
orbit of the eye, and Brain

T.V.Rao MD

Zygomycosis

Zygomycosis
Also called as Mucor Mycosis or
Phycomycosis
Saprophytic mould fungi
Major Causative agents
Rhizopus,
Mucor,
Absidia.
Patents may manifest with Rhinocerbral
Zygomycosis

T.V.Rao MD

Morphology

Majority are with

Broad aseptate
mycelium with
many number of
asexual spores
inside a
sporangium which
develops at the
end of the aerial
hyphae

Mucor

Microscopy
Non septate
hyphae
Having branched
sporangiophores
with sporangium
at terminal ends
T.V.Rao MD

Rhizopus

Microscopy
Shows non
septate hyphae
Sporangiophores in
groups
they are above
the Rhizoids

Important Clinical
Manifestations

Rhino cerebral
Zygomycosis
associate with
Diabetus mellitus,
leukemia, or
lymphomas
Causes extensive
Cellulitis, and tissue
destruction.
T.V.Rao MD

Mucormycosis

Cellulitis causes
extensive tissue
destruction.
Spread from Nasal
mucosa to turbinate
bone,paranasal
sinuses ,orbit, and
Brain
Rapdily fatal if
untreated

Other Manifestations
Severe

immuno compromised may

manifest as primary cutaneous
lesions
Rarely infects Burns patients
But lesions can be less severe than
Brain lesions

Laboratory Diagnosis
Histopathology

more reliable than

culturing
A certain Diagnosis
needs Biopsy
Nasal discharges
Sputum, rarely
contain many
fungal elements

Histological sections

Contain non septate

hyphae in
thromboses vessels
or sinuses
surrounded by
leukocytes or giant
cells

T.V.Rao MD

Microscopy

In Koh preparation
shows broad
aseptate branching
mycelium, and
distorted hyphae
But staining with
Methenamine silver
is more sensitive.
Staining with PAS
not helpful

Culturing

Always depend on
clinical history and
presentation for
certain diagnosis
Cultured on
Sabouraud's
dextrose agar.
T.V.Rao MD

Pathology and
Pathogenesis

Spread from nasal mucosa

Spread to turbinate bones Para nasal
sinuses , orbit, brain
Associated with uncontrolled diabetes
mellitus
In leukemia patients , Lymphoma patients,
Leads to fatal outcome,
Improved with Anti fungal treatment.
Spread to lungs disseminated infection,.

Treatment
Early

Diagnosis highly essential for

effective cure
High doses of I V Amphotericin B
Surgical interventions
Control of Diabetus a basic
requirement for better clinical
outcome

PNEUMOCYSTOSIS
Identified as most
Important opportunistic
fungal infection in the
Era of AIDS

Pneumocystosis

Pneumocystis jiroveci causes pneumonia

in immunocompromised
In the past considered as Protozoan
Now Molecular biologic studies prove as
Fungus Related to Ascomycetes
Many Animals harbor in lungs in Rats,
Ferrets, Rabbits,
Causes the diseases in human if
immunocompromised

Species

Pneumocystis
carnii found in rats
Pneumocystis
jiroveci in human
species

Predisposing factors

Corticosteroid therapy
Transplant recipients
Antineoplastic therapy
Transplant recipients
When retroviral treatment is not
started,a major cause of death in
AIDS patients.
Infections of the other organs is on raise,
Spleen,Lymphnodes, Bone marrow,

Morphology
Spherical, Elliptical
4- 6 microns, contains 4
to 8 nuclei
Stained with
Silver stain, toludine
blue, Calcoflour white
Trophozites present in a
tight mass
P.Jiroveci is an extracellular
pathogen

T.V.Rao MD

Life cycle of P.Jiroveci

Pathogenesis
P.Jiroveci is extracellular pathogen,
In AIDS patients infiltration of
alveolar spaces with plasma cell leads
to interstitial plasma cell pneumonias
Plasma cells are absent in AIDS
related Pneumocystis pneumonia
Blockade of oxygen exchange
interface, results in Cyanosis

Diagnosis

Ideal specimens

1 Bronchoalveloar lavage
2 Lung biopsy
3 Induced sputum
Stains preferred
1.Giemsa
2 Toludine blue
3 Methenamine silver
4 Calcofluor white

X ray of Chest supports

the Diagnosis
T.V.Rao MD

Diagnosis
Culturing

yet not possible

Direct Fluorescent method with
Monoclonal's a rapid and
emerging method
Serology For epidemiological
purpose only to establish prevalence
of Infection.

Immunity Pneumoctistis
In the absence of immuno Supression
P.Jiroveci does not cause disease.
Cell Mediated immunity plays a
dominant role in resitance to Infection.
Infection not seen until CD4 counts
drop to
<400/microliters.

Treatment
Acute

cases are treated with

Trimethoprim-Sulphamehoxazole
Pentamidine, Isothionate are very
effective compounds

Prophylaxis
Treating

with TMP-SMZ
Aerolized Pentamidine is effective
and locally reaches higher
concentration in the lungs.

Pencillium
marnef
Causes serious disseminated
infection, Papular skin lesions
in AIDS
Common in South east Asia

Morphology
A

dimorphic fungi
Mould at 250 c
Yeast at 370c
Intracellular yeast like appearance as
in Histoplasmosis
The fungi are associated with
Bamboo rat

Typical microscopic
appearance of P.marnef

Dimorphic chaterization
of Pencillum marnef

Pathology and
Pathogenesis
Inhalation

of Conidia
Primary site of infection RES
Present with Chills, Fever Malaise
Hepato splenomegaly
Probably AIDS defining infection

T.V.Rao MD

Laboratory Diagnosis
Microscopy
Tissues,

skin Lymph node bone marrow

Use of special stains
Culturing on Sabouraud dextrose agar
Immunoblot methods
PCR
T.V.Rao MD

Treatment
Some

times Amphotericin B may be

considered.
Major Antifungal treatments are
speculative

Other Opportunistic
Fungus

Advances in Medicine have resulted in

increase in fungal infections
Devastating systemic infections have been
caused by species of
1. Fusarium
2 Paecilomyces
3 Bipolaris
4 Curvilaria
5 Alternaria