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TRANSCRIBED GEN CAMATO

OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

Opportunistic Mycosis

1.
2.
3.
4.
5.
6.
7.

Generally harmless
Can become pathogenic in a host who is:

Seriously debilitated/traumatized,

Under treatment w/ broad spectrum antibiotic

Under treatment w/immunosuppressive drugs

Suffering from chronic disease such as diabetes


mellitus
Candidiasis
Cryptococcosis
Aspergillosis
Zygomycosis
Pneumocystosis
Penicillosis marneffei
Others

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


candidiasis is commonly seen

Vaginal Candidiasis 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
Prominent
Infections with Candida

Oral Thrush produced by Candida albicans

1) Candidiasis

Candidiasis also called as Moniliasis,


mycotic infection caused by members of the genus
Candida

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 Diabetes 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


Macroscopic and Microscopic
spp.
appearance of Candida spp

Pseudohypal structures in Candida

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OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

(Continuation Candidiasis)

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

Isolation of Candida from various specimens


confers diagnosis

Serology

Molecular Methods

Corn meal agar with tween 80


[ Used to identify Candica albicans
through its production of
chlamydospores

Germ tube test


[ Identifies C.albicans from other Candida
species.
[ Production of germ tubes by C. albicans
in serum or plasma after 2-3 hours
O
incubation at 37 C.
[ Majority of Diagnostic laboratories
depend on this test.

Emerging Methods for detection of Candida


infections
[ Molecular Methods
[ PCR

Treatment/Management for Candidiasis in:


Immunocompetent patients
[ Correct the underlying conditions that
[ Allow Candida to colonise the skin or
mucosa ie
[ To restore the normal epithelial barrier
function.
[ Cutaneous candidiasis:

Control excessive moisture, heat


and friction which cause local
skin

Treat with a topical imidazole


compound
[ Vaginal candidiasis
[ Azole suppositories and creams
Immunosuppressed patients
[ Oropharyngeal candidiasis in AIDS
patients

Oral Fluconazole [100-400


mg/day for 1-2 weeks]
[ Neutropenic patients with invasive
candidiasis

High dose Amphotericin B


treatment [1.0 mg/kg/day] in
combination with 5- Flucytosine
[150 mg/kg/day].

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
9 A semiquative estimations are essential
Colony forming units essential in attributing
infections

CHROM agar
allows the detection of mixed species of Candida
[ C. albicans (greencolonies)
[ C. tropicalis (blue colonies)
[ C. parapsilosis (white)
[ C. glabrata (pink)

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OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

2) Cryptococcosis

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.neoformans, birds do not get infected.

Pigeons and Red river gum tress harbors the Cryptococcus in


Pigeons and Red river gum tress
nature
harbors the Cryptococcus in nature

Life cycle of C.neoformans

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.

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.

Can manifest with involvement of Skin,


mucosa,organs,Bones,and as Disseminated form.

Can mimic Tuberculosis

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


0
incubated at 37 c for up to to 3 weeks
[ Cultures appear as Creamy, white,
yellow Brown colored
[ Simple urease test helps in confirming
the isolate C. neoformans Urease +

Pathogenesis

Can manifest with


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

Birdseed/Nigerseed/Staibs medium (with niger seed


and thistle seed)
[ Production of phenoloxidase by C. neoformans
result to the production of melanin, resulting in
brown pigments

Can mimic
Tuberculosis
X-ray showing pulmonary cryptococcal
infection [right upper lobe]

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OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

(ContinuationC.neoformans)

Laboratory Diagnosis

CSF Microscopic observation under India Ink


preparation

Direct microscopy - Gram staining

Cultures on Sabouraud dextrose agar

Urease test

L-DOPA ferric citrate test

Serological tests for detection of Capsular antigen

CSF findings mimic like Tuberculosis

CSF - latex test for detection of Antigen

Blood cultures

ELISA

Laboratory Diagnosis.

A positive cryptococcal antigen latex test. It should be noted that the detection
of cryptococcal capsular polysaccharide antigen in spinal fluid is now the
method of choice for diagnosing patients with cryptococcal meningitis

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.

Control: Avoid contact with Birds

3) Aspergillosis

In nature >100 species of Aspergillosis exist, Few are


important as human pathogens
[ A.fumigatus
[ A.niger
[ A.flavus
[ A.terreus
[ 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

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

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.

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

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OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

4) Zygomycosis

Also called as Mucor Mycosis or Phycomycosis


Saprophytic mould fungi
Causative agents:
[ Rhizopus
Microscopy

Shows non septate hyphae

Sporangiophores in groups

They are above the Rhizoids

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

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.

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 IV Amphotericin B

Surgical interventions

Control of Diabetes a basic requirement for better


clinical outcome

Mucor

Microscopy

Non septate hyphae

Having branched
sporangiophores

With sporangium at terminal


ends

Absidia

Patients may manifest with Rhinocerbral zygomycosis


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

Important Clinical Manifestations

Rhino cerebral Zygomycosis associate with


Diabetus mellitus, leukemia, or lymphomas

Causes extensive Cellulitis, and tissue


destruction.

Mucormycosis

Cellulitis causes extensive tissue destruction.

Spread from Nasal mucosa to turbinate bone,


paranasal sinuses, orbit, and Brain

Rapidly fatal if untreated

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OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

5) Pneumocytosis

Identified as most Important opportunistic fungal infection in


the Era of AIDS
Pneumocystis jiroveci
9 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 carinii found in rats
[ Pneumocystis jiroveciin 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,


Lymph nodes, 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

Immunity Pneumocytosis

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 TrimethoprimSulphamehoxazole

Pentamidine, Isothionate are very effective


compounds

Prophylaxis

Treating with TMP-SMZ

Aerolized Pentamidine is effective and locally


reaches higher concentration in the lungs.

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
[ Toludine blue
[ Methenamine silver
[ Calcofluor white
[ X ray of Chest supports the 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.

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OPPORTUNISTIC MYCOSES

M YCOLOGY AND VIROLOGY | LECTURE

6) Pencilliosis marneffi

7) Other Oppotunistic Mycoses

Causes serious disseminated infection


Papular skin lesions in AIDS
Common in South east Asia
Morphology

A dimorphic fungi

Mould at 25c

Yeast at 37c

Intracellular yeast like appearance as in


Histoplasmosis

The fungi are associated with Bamboo rat

Disease
Hyalohyphomycosis

Phaeohyphomycosis

Typical microscopic appearance of P. marneffi

Causative
organisms
Penicillium
Paecilomyces
Beauveria
Fusarium
Scopulariopsis etc.
Cladosporium
Exophiala
Wangiella
Bipolaris
Exserohilum
Curvularia

Incidence

Rare

Rare

References:

Lecture slides of T.V.Rao MD


th

Murray, P eat al. Medical Microbiology 6 Ed.

Dimorphic chaterization of Pencillum marneffi

Pathology and Pathogenesis

Inhalation of Conidia

Primary site of infection RES

Present with Chills, Fever Malaise


Hepatosplenomegaly

Probably AIDS defining infection

Laboratory Diagnosis

Microscopy

Tissues, skin Lymph node bone marrow

Use of special stains

Culturing on Sabouraud dextrose agar

Immunoblot methods

PCR

Treatment

Some times Amphotericin B may be considered.

Major Antifungal treatments are speculative

What shall we then say to these things?


If God be for us, who can be against us?
- Romans 8:31
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