Opportunistic Mycoses

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Opportunistic Mycoses

• Ordinary fungi causing extraordinary disease

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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 HOST
• Opportunistic 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

• Transient fungemia
• Colonization
• Infection

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Transient fungemia

• The fortuitous isolation of a commensal or
  environmental organism

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COLONIZATION
MOUTH
RESPIRATORY TRACT
EYE
Multiplication of an organism at a given site
without harm to the host
SKIN
UROGENITAL TRACT
ANUS
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INFECTION
MOUTH
RESPIRATORY TRACT
EYE
Invasion and multiplication of organisms in body
tissue resulting in local cellular injury.
SKIN
UROGENITAL TRACT
ANUS
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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

• Atypical signs or symptoms
• Unusual organ affinity
• Outside the endemic area
• Unusual Histopathology
• Etiologic agent may be a saprophyte
• Serological response may be suppressed

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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
6. Depressed serological response

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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 Pathogens
6. Depressed serological response

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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. dubliniensis

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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 DISEASE
• NORMAL 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 CSF

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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 DISEASE
• NORMAL 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
6. Depressed serological response

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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)

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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 Pathogens
6. Depressed serological response

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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 Pathogens
6. Depressed serological response

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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 East

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Pneumocystis jiroveci(P. carinii)

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

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Cryptococcus neoformans

• Diabetes mellitus
• Tuberculosis
• Lymphoma
• Hodgkins disease
• Corticosteroid therapy
• Immunosuppression

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Candida albicans

• Prolonged antibiotic therapy
• Prolonged intravenous therapy
• Prolonged urinary catheters
• Corticosteroid therapy
• Diabetes mellitus
• Hyperalimentation
• Immunosuppression

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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

• New Drugs
• New therapeutic regimen
• Aggressive therapy
• Conjunctive therapy

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IMPROVING TREATMENT

• New Drugs
• Lipid Amphotericin B
• Third generation azoles
• (Posaconazole, Voriconazole)
• New classes of antifungal agents
• (Echinocandins)

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IMPROVING TREATMENT

• New Therapeutic Regimen
• Combination Therapy
• Simultaneously administering two drugs
• Sequential Tx with two or more drugs
• Alternate Administration of two or more

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IMPROVING TREATMENT

• AGGRESSIVE THERAPY
• FOR IMMUNOCOMPROMISED PATIENTS
• Prophylactic Anti-fungal agents at, or near,
  the time of chemotherapy.
• 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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In the field of observation, chance only favors
those who are prepared.
Louis
Pasteur - 1854
In the field of observation, chance only favors
those who are prepared.
Louis Pasteur -1854

• From
• Inaugural Address as Professor of Chemistry and
  Dean of Faculty of Science, Lillie, France.

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Only the prepared mind can help the impaired
host Libero Ajello, Chief Mycology Division, CDC
1972
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MYCOLGISTS have more

• FUNGI