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Opportunistic Mycoses Infections due to fungi of low virulence in patients who are immunologically compromised www.freelivedoctor.com

Opportunistic Mycoses

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Page 1: Opportunistic Mycoses

Opportunistic Mycoses

Infections due to fungi of low virulence in patients who are immunologically compromised

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Medical Mycology Iceberg

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PATHOGENIC FUNGI

• NORMAL HOST

• Systemic pathogens - 25 species• Cutaneous pathogens - 33 species• Subcutaneous pathogens - 10 species

• IMMUNOCOMPROMISED HOSTOpportunistic fungi - 300 species

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HOST-PATHOGEN EQUILIBRIUM

NUMBER OF ORGANISMS X VIRULENCE =DISEASE

HOST RESISTANCE

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Opportunistic Fungi

1. Saprophytic - from the environment

2. Endogenous – a commensal organism

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Opportunistic Fungi

Include many species from:

A (Aspergillus)

To

Z (Zygomyces)

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MOST SERIOUS OPPORTUNISTIC INFECTIONS

• CANDIDA SPECIES

• ASPERGILLUS SPECIES

• MUCOR SPECIES (ZYGOMYCES)

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Upward Trend InOpportunistic Mycoses

1. Increased clinical awareness

2. Improved clinical diagnostic tools

3. Improved laboratory diagnostic technics

4. An increase in susceptible hosts.

5. More invasive diagnostic and therapeutic procedures

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Must distinguish between

1. Transient fungemia

2. Colonization

3. Infection

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Transient fungemia

The fortuitous isolation of a commensal or environmental organism

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EYE

SKIN

UROGENITAL TRACT

ANUS

MOUTHRESPIRATORY

TRACT

COLONIZATION

Multiplication of an organism at a given site without harm to the host

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EYE

SKIN

UROGENITAL TRACT

ANUS

MOUTHRESPIRATORY

TRACT

INFECTION

Invasion and multiplication of organisms in body tissue resulting in local cellular injury..

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Predisposing Factors

Malignancies

• Leukemias

• Lymphomas

• Hodgkins Disease

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Predisposing Factors

Drug therapies

• Anti-neoplastics

• Steroids

• Immunosuppressive drugs

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Predisposing Factors

Antibiotics

Over-use or inappropriate use of antibiotics alter the normal flora allowing fungal overgrowth

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Predisposing Factors

Therapeutic procedures

• Solid organ or bone marrow transplant

• Open heart surgery

• Indwelling catheters

• Artificial heart valves

• Radiation therapy

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Predisposing Factors

Other Factors

• Severe burns

• Diabetes

• Tuberculosis

• IV Drug use

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Predisposing Factors

AIDS

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Human Immunodeficiency Virus(HIV)

HIV destroys the CD4 helper T cells

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CD4 helper T cells are the basis of cell mediated immunity and play a role in host defenses against fungal diseases

ERGO

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Virtually all AIDS patients will have a fungal infection sometime during the course of their illness

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BIOFILMS

A POLYSACCHARIDE SLIME WHICH IS A MICROCOLONY OF

ORGANISMS CONTAINING CHANNELS TO BRING IN

NUTRIENTS AND CARRY OFF WASTE

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Diagnosis of opportunistic infections requires a

high index of suspicion

1. Atypical signs or symptoms

2. Unusual organ affinity

3. Outside the endemic area

4. Unusual Histopathology

5. Etiologic agent may be a saprophyte

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CLINICAL PRESENTATION

1. Atypical Signs and Symptoms

2. Unusual Organ Affinity

3. Outside Endemic Area

4. Unusual histopathology

5. Unusual Pathogenswww.freelivedoctor.com

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NORMAL PATIENT

Malasezzia furfur

Tinea versicolor

(mild disease)

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COMPROMISED PATIENTS

Malasezzia furfur can cause disseminated infection--------Particularly in patients receiving hyperalimentation.

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COMPROMISED IMMUNE SYSTEMMalasezzia furfur

NUMBER OF ORGANISMS x LOW VIRULENCE= DISEASE HOST RESISTANCE

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CLINICAL PRESENTATION

1. Atypical Signs and Symptoms

2. Unusual Organ Affinity

3. Outside Endemic Area

4. Unusual histopathology

5. Unusual Pathogenswww.freelivedoctor.com

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Candida species

Endogenous

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Normal Flora

The population of microorganisms that may be found residing in or on the human body without causing disease.

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COMPETENT IMMUNE SYSTEMCandida albicans

NUMBER OF ORGANISMS x VIRULENCE= NO DISEASE HOST RESISTANCE

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COMPROMISED IMMUNE SYSTEMCandida albicans

NUMBER OF ORGANISMS = DISEASE HOST RESISTANCE

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IMMUNOCOMPROMISED PATIENTS

CAN DEVELOP HEPATIC CANDIDIASIS

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Candida species

In the previous lecture I only mentioned Candida albicans. There are several Candida species that infect the compromised host.

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Candida species

• C. glabrata

• C. krusei

• C. torulopsis

• C. parapsilosis

• C. lusitaniae

• C. dubliniensiswww.freelivedoctor.com

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Cryptococcosis

A sub-acute or chronic infection which may affect the lungs or skin but most commonly manifests as a meningitis

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Ecological Niche

Cryptococcus neoformans

• pigeon droppings

• Chicken droppings

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Cryptococcus neoformansPORTAL OF ENTRY

•INHALATION

•INOCULATION

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Cryptococcus neoformans

LOW NUMBER X HIGH VIRULENCE = NO DISEASENORMAL HOST

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Cryptococcus neoformans

LOW NUMBER X HIGH VIRULENCE = INFECTION

COMPROMISED HOST

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Cryptococcosis

In the Compromised patient:

• Amphotericin B

• 5 FC

Then Fluconazole the remainder of their life.

Fluconazole penetrates the CSFwww.freelivedoctor.com

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SPOROTRICHOSIS

Primarily a disease of the cutaneous tissue and lymph nodes. Recently, pulmonary disease.

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PORTALS OF ENTRY

• Inhalation

• Inoculation

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ECOLOGICAL ASSOCIATIONS

• Rose thorns

• Sphagnum moss

• Timbers

• Soil

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SPOROTRICHOSIS

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Blastomycosis in AIDS patients

• One report

• 16 Patients

• 10 localized disease– 7-lung, 2-skin, 1 CNS

• 6 Disseminated– 5/6 – CNS

All did poorly

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Aspergillus species

HIGH NUMBER X LOW VIRULENCE = NO DISEASENORMAL HOST

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Aspergillus species

LOW NUMBER X LOW VIRULENCE = INFECTION

COMPROMISED HOST

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CLINICAL PRESENTATION

1. Atypical Signs and Symptoms

2. Unusual Organ Affinity

3. Outside Endemic Area

4. Unusual histopathology

5. Unusual Pathogens

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AIDS Patient

• Pneumocystis pneumonia

• Disseminated coccidioidomycosis

(not pulmonary)

• Mycelial forms in abscesses

(not spherules)

• Outside the endemic area

(St. Louis, MO)www.freelivedoctor.com

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Spherules

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HISTOPLASMOSIS IN AIDS PATIENTS

• ALL CASES ARE DISSEMINATED

• RELAPSES ARE GREATER THAN 50 %

• RAPIDLY FATAL IN 10 %

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AIDS Patients

• Disseminated histoplasmosis

(not pulmonary disease)

• New York City

(outside the endemic region)

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CLINICAL PRESENTATION

1. Atypical Signs and Symptoms

2. Unusual Organ Affinity

3. Outside Endemic Area

4. Unusual Histopathology

5. Unusual Pathogenswww.freelivedoctor.com

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INFLAMMATORY REACTION

• NORMAL HOST– PYOGENIC– GRANULOMATOUS

• IMMUNODEFICIENT HOST– NECROTIC

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CLINICAL PRESENTATION

1. Atypical Signs and Symptoms

2. Unusual Organ Affinity

3. Outside Endemic Area

4. Unusual histopathology

5. Unusual Pathogenswww.freelivedoctor.com

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Opportunistic Fungi

Include many species from:

A (Aspergillus)

To

Z (Zygomyces)

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Penicillium marneffei

1. Usually not a pathogen

2. The only dimorphic penicillium

3. Produces a red pigment

4. Endemic in the Far Eastwww.freelivedoctor.com

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Pneumocystis jiroveci

Recently confirmed as a member of Kingdom Fungi. Formerly thought to be a protozoan.

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Cryptococcus neoformans

• Diabetes mellitus

• Tuberculosis

• Lymphoma

• Hodgkin’s disease

• Corticosteroid therapy

• Immunosuppression

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Candida albicans

• Prolonged antibiotic therapy

• Prolonged intravenous therapy

• Prolonged urinary catheters

• Corticosteroid therapy

• Diabetes mellitus

• Hyperalimentation

• Immunosuppressionwww.freelivedoctor.com

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Torulopsis (Candida) glabrata

• Cytotoxic drugs

• Immunosuppression

• Diabetes mellitus

• Hyperalimentation

• Intravenous catheters

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Mucormycetes

• Diabetes mellitus

• Leukemias

• Corticosteroid therapy

• Intravenous therapy

• Severe burns

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Aspergillus species

• Leukemias

• Corticosteroid therapy

• Tuberculosis

• Immunosuppression

• Intravenous drug abuse

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IMPROVING TREATMENT

1. New Drugs

2. New therapeutic regimen

3. Aggressive therapy

4. Conjunctive therapy

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IMPROVING TREATMENT

New Drugs

Lipid Amphotericin B

Third generation azoles

(Posaconazole, Voriconazole)

New classes of antifungal agents

(Echinocandins)www.freelivedoctor.com

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IMPROVING TREATMENT

New Therapeutic Regimen

Combination Therapy

1. Simultaneously administering two drugs

2. Sequential Tx with two or more drugs

3. Alternate Administration of two or more

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IMPROVING TREATMENT

AGGRESSIVE THERAPY

FOR IMMUNOCOMPROMISED PATIENTS

1. Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy.

2. Posaconazole now approved.

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IMPROVING TREATMENT

AGGRESSIVE THERAPY

FOR IMMUNOCOMPROMISED PATIENTS

2. Empirical – Start therapy when patient at risk, i.e., fever and/or infiltrate without response to anti-bacterials.

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IMPROVING TREATMENT

AGGRESSIVE THERAPY

FOR IMMUNOCOMPROMISED PATIENTS

3. Pre-emptive –When there is some additional evidence of fungal infection (serology, isolate, etc.)

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IMPROVING TREATMENT

CONJUNJUNCTIVE THERAPY

Antifungal agent plus a recombinant monoclonal antibody.

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IMPROVING TREATMENT

CONJUNJUNCTIVE THERAPY

FOR IMMUNOCOMPROMISED PATIENTS

The use of anti-fungal agents with immunotherapy.

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Immunotherapy

• Interferons

• Colony stimulating factors

• Interleukins

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