opportunistic mycoses
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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
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
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
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
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
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
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
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
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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