Transcript Opportunistic Fungal Infections.

Opportunistic Fungi
&
Pneumocystis
Doç.Dr.Hrisi BAHAR
Opportunistic organisms
Opportunistic organisms are normal resident
flora that become pathogenic only when the
host's immune defense reduses.
 In immunosuppressive therapy,
 In a chronic disease such as diabetes mellitus,
 During steroid or antibacterial therapy that
upsets the balance of bacterial flora in the body.
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Opportunistic Mycosis
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Opportunistic mycosis is a fungal or
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Candidiasis
Aspergillosis
Cryptococcosis
fungus-like disease occurring in an animal
or human’s with a compromised immune
system.
 Opportunistic fungal infections are:
CANDIDA SP
Candidia can infect
skin, mucosa, or
internal organs
 It is as Yeast Like
fungus
 It is an important
cause of opportunistic
fungal infection.
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Candida
► Candida is found in normal flora,exist in mouth,
gastrointestinal tract, vagina, skin in 20 % of normal
individuals.
►Colonization increases with age,in pregnancy,
hospitalization…..
►Candida is an important etiological agent presenting as
opportunistic infection in Diabetes and HIV patients.
Morphology and Culturing
The shape is ovoid or spherical budding cells
and produces pseudo mycelium
 Routine cultures are done on Sabouraud's
dextrose 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.
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Macroscopic and Microscopic
appearance of Candida spp
Pseudohypal structures in Candida
Candida as Pathogenic fungi
Systemic Candidosis
Occurs in Patients who carry more yeasts in mouth,
and gastrointestinal system,
 Predisposed with individuals
1. On antibiotic or/and steroid therapy
2. Immunosupressed
3. Recipients with organ transplantation
4. Infancy – Old age – Pregnancy
5. Diabetes mellitus
7. Zink and iron deficiencies
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Pathogenesis and Pathology
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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,
In pregnancy in advanced stage,
Majority experience one episode in a life time
Important species of Candida
in human infections
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C.albicans
C.tropicalis
C.glabrata
C.krusei
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,
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Observations
Microscopic observation after Gram staining.
Presence of Gram + yeast cells.
Laboratory Diagnosis
Isolation of Candida
from various
specimens
 Easier to culture on
Sabouraud's dextrose
agar
 Serology, molecular
methods,PCR
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CRYPTOCOCCUS
NEOFORMANS
A capsulated yeast –
A true yeast..
 A sporadic disease in
the past.
 Most common
infection in AIDS
patients.
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Structure of C.neoformans
Morphology
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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.
C.neoformans 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.
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Cryptococcus neoformans
Serotypes
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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.
Life cycle of C.neoformans
Pathogenesis
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Enters through lungs by inhalation of “basidiospores” of
C.neoformans
Enters deep into lungs, pulmonary infections can occur.
 Men acquires more infections, and women less infected.
 Self limiting in most cases,
 Present as discrete nodules - Cryptococcoma.
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Pathogenesis
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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.
Clinical manifestation
1.Pulmonary Cryptococcosis
 2.Central Nervous System Cryptococcosis
 3.Cutaneous Cryptococcosis
 4.Cryptococcosis of bone
 5.Ocular Cryptococcosis
 6.Other forms (Cryptococcus neoformans is often isolated from urine of
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patients with disseminated infection. Occasionally, signs of pyelonephritis or prostatitis
may be observed. Other rare forms of cryptococcosis include adrenal cortical lesions,
endocarditis, hepatitis, sinusitis, and localized oesophageal lesions) .
Laboratory Diagnosis.
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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
Fluconazole,Itraconazole
Immune Deficient
Amphotericin B,Flucytosine
AIDS patients are not totally cured , Relapses are
frequent with fatal outcome.
Rapid resistance develops with Fluconazole.
Avoid contact with Birds
ASPERGILLUS SP
In nature > 100 species of Aspergillus
exist, Few are important as human
pathogens
 1 A.fumigatus
 2 A.niger
 3 A.flavus
 4 A.terreus
 5 A.nidulans
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Fungal spores enters through
respiratory tract
Morphology
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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
Clinical presentations
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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
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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
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occurs in immunocompromised host
with underlying disease
Neutropenia is the most common
predisposing factor
A.fumigatus is the most common
infecting species
In bone marrow recipients leads to
high mortality
Fungus invades blood vessels, causes
thrombosis septic emboli
Can spread to Kidney and heart.
ZYGOMYCETES
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The ilness is called Zygomycosis,also called as
Mucor Mycosis or Phycomycosis
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Saprophytic mould fungi
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Major Causative agents of Zygomycosis
Rhizopus
Mucor
Absidia
Morphology
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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
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Rhizopus
Microscopy
► Shows non septate
hyphae
► Sporangiophores in
groups are above the
Rhizoids
Important Clinical
Manifestations
Rhino cerebral
Zygomycosis
associate with
Diabetus mellitus,
leukemia, or
lymphomas
 Causes extensive
Cellulitis, and tissue
destruction.
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Mucormycosis
Cellulitis causes
extensive tissue
destruction.
 Spread from nasal
mucosa to turbinate
bone,paranasal
sinuses ,orbit, and
brain
 Rapdily fatal if
untreated
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Laboratory Diagnosis
Histopathology
more reliable than
culturing
Pathology and Pathogenesis
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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 Diabetes a basic requirement
for better clinical outcome
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PNEUMOCYSTIS
Identified as the most
Important opportunistic
fungal infection in persons
with impaired immune
systems & AIDS
Pneumocystis
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Pneumocystis is a genus of unicellular fungi
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The organism was first described in 1909 by
Chagas and then a few years later by Delanöes,
who ultimately named the organism in honor of
Dr. Carini after isolating it from infected rats.
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The name was Pneumocystis carinii
found in the respiratory tracts of many
mammals and humans.
Pneumocystis
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Years later, Dr. Otto Jirovec and his group
isolated the organism from humans, and
the organism responsible for P.carinii
pneumonia (PCP) was renamed after him
and P.carinii change to Pneumocystis
jiroveci
Pneumocystis
The taxonomic classification of the Pneumocystis
genus was debated for some time
 It was a trypanasome then a protozoan and
today it is accepted as a fungus.
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The organism is found in 3 distinct morphologic
stages, as follows:
The trophozoite (trophic form), The sporozoite
(precystic form)and the cyst, which contains
several intracystic bodies
Life cycle of P.Jiroveci
Pathogenesis
Pneumocystis jiroveci pneumonitis (PCP) is a
common opportunistic disease that occurs
almost exclusively in persons who have
profound immunodeficiency.
PCP was and still is the most common lifethreatening opportunistic infection occurring in
patients with HIV disease.
Pathogenesis
►The portal of entry for P carinii has not been firmly
established; however, because the organism has
been found only in the lung, inhalation is a likely
mode of transmission.
►In most individuals, the organism is dormant and
sparsely dispersed in the lung, with no apparent
host response (latent infection).
►In susceptible (immunocompromised) hosts, the
organism occurs in massive numbers.
Clinical manifestation
► Tachypnea and fever are consistent features of
the pneumonitis, and diffuse bilateral alveolar
disease can be observed by radiography.
► Diagnosis requires the identification of P carinii
in pulmonary tissue or lower airway fluids.
► Such specimens may be obtained by lung
biopsy, inducement of sputum, bronchoalveolar
lavage, or needle aspiration of the lung.
► The Gomori, Giemsa, fluorescence-labelled
antibody, or toluidine blue stains may be used to
identify the organism.
http://www.doctorfungus.org
Pneumocystis carinii
• Genus/Species:
• Image Type:
• Legend:
Pneumocystis carinii
Microscopic Morphology
• Title:
• Disease(s):
An electron micrograph of P. carinii cyst from rat lung tissue.
EM Image of Pneumocystis carinii
Pneumocystis pneumonia
http://www.doctorfungus.org
Pneumocystis carinii
• Genus/Species:
• Image Type:
Pneumocystis carinii
Microscopic Morphology
• Title:
• Disease(s):
Pneumocystis carinii-infected
Rat Lung Tissue
Pneumocystis pneumonia
• Legend:
An H&E stain of a rat lung infected with P. carinii. It does not show any organisms, but shows the
proteinaceous exudate which results from Pneumocystis infection, and ultimately causes reduced gas exchange.
http://www.doctorfungus.org
Pneumocystis carinii
• Genus/Species:
• Image Type:
• Legend:
Pneumocystis carinii
Microscopic Morphology
• Title:
Disease(s):
Pneumocystis carinii Silver Stain
Pneumocystis pneumonia
A silver stain of P. carinii cysts from rat lung tissue showing the typical 'deflated ball' shape.
http://www.doctorfungus.org
Pneumocystis carinii
• Genus/Species:
• Image Type:
• Legend:
Pneumocystis carinii
Microscopic Morphology
• Title:
Disease(s):
EM Image of Pneumocystis carinii
Pneumocystis pneumonia
An electron micrograph of a P. carinii troph from rat lung tissue, showing its binding
to a type I pneumocyte.
Treatment
Four drugs currently available for therapy of
P carinii pneumonitis are:
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pentamidine isethionate
 trimethoprim-sulfamethoxazole
 atovaquone
 trimetrevate
Trimethoprim-sulfamethoxazole is
preferred because of its low toxicity
and greater efficacy.
Pencillium
marneffi
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
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Typical microscopic
appearance of P.marneffi
Pathology and Pathogenesis
Inhalation of Conidia
 Primary site of infection RES
 Present with Chills, Fever Malaise Hepato
splenomegaly
 Probably AIDS defining infection
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Laboratory Diagnosis
Microscopy
 Tissues, skin Lymph node bone marrow
 Use of special stains
 Culturing on Sabouraud dextrose agar
 Immunoblot methods
 PCR
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Treatment
Some times Amphotericin B may be
considered.
 Major Antifungal treatments are
speculative
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