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 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

• Increased clinical awareness
• Improved clinical diagnostic tools
• Improved laboratory diagnostic technics
• An increase in susceptible hosts.
• 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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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

• Atypical Signs and Symptoms
• Unusual Organ Affinity
• Outside Endemic Area
• Unusual histopathology
• Unusual Pathogens
• 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

• Atypical Signs and Symptoms
• Unusual Organ Affinity
• Outside Endemic Area
• Unusual histopathology
• Unusual Pathogens
• 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

• Atypical Signs and Symptoms
• Unusual Organ Affinity
• Outside Endemic Area
• Unusual histopathology
• Unusual Pathogens
• 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

• Atypical Signs and Symptoms
• Unusual Organ Affinity
• Outside Endemic Area
• Unusual Histopathology
• Unusual Pathogens
• Depressed serological response

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INFLAMMATORY REACTION

• NORMAL HOST
• PYOGENIC
• GRANULOMATOUS
• IMMUNODEFICIENT HOST
• NECROTIC

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CLINICAL PRESENTATION

• Atypical Signs and Symptoms
• Unusual Organ Affinity
• Outside Endemic Area
• Unusual histopathology
• Unusual Pathogens
• Depressed serological response

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Opportunistic Fungi

• Include many species from
• A (Aspergillus)
• To
• Z (Zygomyces)

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Penicillium marneffei

• Usually not a pathogen
• The only dimorphic penicillium
• Produces a red pigment
• 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