Opportunistic

Fungal Infections
Dr.T.V.Rao MD
 Opportunistic Mycosis
 Opportunistic mycosis a fungal or
fungus-like disease occurring in an animal
/ human’s 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
 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
 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
 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,
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
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
 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
Monoclonals 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
marneffi
Causes serious
disseminated infection,
Papular skin lesions in
AIDS
Common in South east
 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.marneffi
Dimorphic chaterization of
Pencillum marneffi
 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
Mycoses
 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
Created as Educative
Material for Graduate
Medical Students
Dr.T.V.Rao MD
Email
doctortvrao@gmail.com