Oppurtunistic Pathogen

8/14/2019 Oppurtunistic Pathogen

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Opportunistic Mycoses

Infections due to fungi of lowvirulence 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)

ToZ (Zygomyces)


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MOST SERIOUS

OPPORTUNISTIC INFECTIONS

CANDIDA SPECIES

ASPERGILLUS SPECIES

MUCOR SPECIES (ZYGOMYCES)


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Upward Trend In

Opportunistic 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

MOUTH

RESPIRATORYTRACT

COLONIZATION

Multiplication

of an organismat a given site

without harm

to the host


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EYE

SKIN

UROGENITAL TRACT

ANUS

MOUTH

RESPIRATORYTRACT

INFECTION

Invasion and

multiplicationof organisms

in body tissue

resulting inlocal cellular

injury..


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Predisposing Factors

Malignancies

Leukemias

Lymphomas

Hodgkins Disease


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Drug therapies

Anti-neoplastics

Steroids

Immunosuppressive drugs


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Antibiotics

Over-use or inappropriate use of

antibiotics alter the normal flora

allowing fungal overgrowth


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Therapeutic procedures

Solid organ or bone marrow transplant

Open heart surgery

Indwelling catheters

Artificial heart valves Radiation therapy


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Other Factors

Severe burns

Diabetes

Tuberculosis

IV Drug use


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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 ahigh index of suspicion

1. Atypical signs or symptoms

2. Unusual organ affinity

3. Outside the endemic area4. 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 Area4. Unusual histopathology

5. Unusual Pathogens


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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 IMMUNESYSTEM

Malasezzia furfur

NUMBER OF ORGANISMS x LOW VIRULENCE= DISEASEHOST RESISTANCE


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3. Outside Endemic Area

4. Unusual histopathology



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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 IMMUNESYSTEM

Candida albicans

NUMBER OF ORGANISMS x VIRULENCE= NO DISEASEHOST RESISTANCE


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COMPROMISED IMMUNESYSTEM

Candida albicans

NUMBER OF ORGANISMS = DISEASEHOST 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 severalCandida 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 mostcommonly manifests as a meningitis


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Ecological Niche

Cryptococcus neoformans

pigeon droppings

Chicken droppings


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PORTAL OF ENTRY

INHALATION

INOCULATION


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LOW NUMBER X HIGH VIRULENCE =NO DISEASE

NORMAL HOST


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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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4. Unusual histopathology



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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)

S h l


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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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4. Unusual Histopathology



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INFLAMMATORY REACTION

NORMAL HOST

PYOGENIC

GRANULOMATOUS

IMMUNODEFICIENT HOST

NECROTIC


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3. Outside Endemic Area4. Unusual histopathology



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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 penicillium3. Produces a red pigment

4. Endemic in the Far East


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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


Intravenous therapy

Severe burns


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Aspergillus species

Leukemias


Tuberculosis

Immunosuppression

Intravenous drug abuse


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IMPROVING TREATMENT

1. New Drugs2. 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)


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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


PATIENTS2. 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


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 recombinantmonoclonal antibody.


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IMPROVING TREATMENT

CONJUNJUNCTIVE THERAPY


PATIENTSThe 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


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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.

Only the prepared mind can help the impaired host


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Libero Ajello, Chief Mycology Division, CDC 1972


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Oppurtunistic Pathogen

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