Mycoses

Opportunistic Mycoses

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

Medical Mycology Iceberg

PATHOGENIC FUNGI
NORMAL HOST Systemic pathogens - 25 species Cutaneous pathogens - 33 species Subcutaneous pathogens - 10 species IMMUNOCOMPROMISED HOST Opportunistic fungi - 300 species

HOST-PATHOGEN EQUILIBRIUM

NUMBER OF ORGANISMS X VIRULENCE = DISEASE HOST RESISTANCE

Opportunistic Fungi

1. Saprophytic - from the environment2. Endogenous – a commensal organism


Opportunistic Fungi
Include many species from: A (Aspergillus) To Z (Zygomyces)

MOST SERIOUS OPPORTUNISTIC INFECTIONS

CANDIDA SPECIES ASPERGILLUS SPECIES MUCOR SPECIES (ZYGOMYCES)

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

Must distinguish between

Transient fungemia Colonization Infection

Transient fungemia

The fortuitous isolation of a commensal or environmental organism


EYE
SKIN
UROGENITAL TRACT
ANUS
MOUTH
RESPIRATORY TRACT
COLONIZATION
Multiplication of an organism at a given site without harm to the host


EYE
SKIN
UROGENITAL TRACT
ANUS
MOUTH
RESPIRATORY TRACT
INFECTION
Invasion and multiplication of organisms in body tissue resulting in local cellular injury.

Predisposing Factors

Malignancies Leukemias Lymphomas Hodgkins Disease

Predisposing Factors

Drug therapies Anti-neoplastics Steroids Immunosuppressive drugs

Predisposing Factors

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

Predisposing Factors

Therapeutic procedures Solid organ or bone marrow transplant Open heart surgery Indwelling catheters Artificial heart valves Radiation therapy


Predisposing Factors
Other Factors Severe burns Diabetes Tuberculosis IV Drug use

Predisposing Factors

AIDS

Human Immunodeficiency Virus(HIV)

HIV destroys the CD4 helper T cells


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

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

BIOFILMS

A POLYSACCHARIDE SLIME WHICH IS A MICROCOLONY OF ORGANISMS CONTAINING CHANNELS TO BRING IN NUTRIENTS AND CARRY OFF WASTE

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

CLINICAL PRESENTATION

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

NORMAL PATIENT

Malasezzia furfur Tinea versicolor (mild disease)

COMPROMISED PATIENTS

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

COMPROMISED IMMUNE SYSTEMMalasezzia furfur

NUMBER OF ORGANISMS x LOW VIRULENCE= DISEASE HOST RESISTANCE



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

Candida species

Endogenous

Normal Flora

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

COMPETENT IMMUNE SYSTEMCandida albicans

NUMBER OF ORGANISMS x VIRULENCE= NO DISEASE HOST RESISTANCE

COMPROMISED IMMUNE SYSTEMCandida albicans

NUMBER OF ORGANISMS = DISEASE HOST RESISTANCE

IMMUNOCOMPROMISED PATIENTS

CAN DEVELOP HEPATIC CANDIDIASIS

Candida species

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

Candida species

C. glabrata C. krusei C. torulopsis C. parapsilosis C. lusitaniae C. dubliniensis

Cryptococcosis

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

Ecological Niche

Cryptococcus neoformans
pigeon droppings Chicken droppings

Cryptococcus neoformansPORTAL OF ENTRY

INHALATION INOCULATION

Cryptococcus neoformans

LOW NUMBER X HIGH VIRULENCE = NO DISEASE NORMAL HOST

Cryptococcus neoformans

LOW NUMBER X HIGH VIRULENCE = INFECTION COMPROMISED HOST

Cryptococcosis

In the Compromised patient: Amphotericin B 5 FC Then Fluconazole the remainder of their life. Fluconazole penetrates the CSF

SPOROTRICHOSIS

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

PORTALS OF ENTRY

Inhalation Inoculation

ECOLOGICAL ASSOCIATIONS

Rose thorns Sphagnum moss Timbers Soil


SPOROTRICHOSIS

Blastomycosis in AIDS patients

One report16 Patients10 localized disease7-lung, 2-skin, 1 CNS6 Disseminated5/6 – CNSAll did poorly

Aspergillus species

HIGH NUMBER X LOW VIRULENCE = NO DISEASE NORMAL HOST

Aspergillus species

LOW NUMBER X LOW VIRULENCE = INFECTION COMPROMISED HOST

CLINICAL PRESENTATION

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

AIDS Patient

Pneumocystis pneumonia Disseminated coccidioidomycosis (not pulmonary) Mycelial forms in abscesses (not spherules) Outside the endemic area (St. Louis, MO)

Spherules

HISTOPLASMOSIS IN AIDS PATIENTS

ALL CASES ARE DISSEMINATED RELAPSES ARE GREATER THAN 50 % RAPIDLY FATAL IN 10 %

AIDS Patients

Disseminated histoplasmosis (not pulmonary disease) New York City (outside the endemic region)

CLINICAL PRESENTATION

Atypical Signs and Symptoms Unusual Organ Affinity Outside Endemic Area Unusual Histopathology Unusual Pathogens

INFLAMMATORY REACTION

NORMAL HOST PYOGENIC GRANULOMATOUS IMMUNODEFICIENT HOST NECROTIC

CLINICAL PRESENTATION

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

Opportunistic Fungi

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


Penicillium marneffei
Usually not a pathogen The only dimorphic penicillium Produces a red pigment Endemic in the Far East

Pneumocystis jiroveci

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

Cryptococcus neoformans

Diabetes mellitusTuberculosisLymphomaHodgkin’s diseaseCorticosteroid therapyImmunosuppression

Candida albicans

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

Torulopsis (Candida) glabrata

Cytotoxic drugs Immunosuppression Diabetes mellitus Hyperalimentation Intravenous catheters

Mucormycetes

Diabetes mellitus Leukemias Corticosteroid therapy Intravenous therapy Severe burns

Aspergillus species

Leukemias Corticosteroid therapy Tuberculosis Immunosuppression Intravenous drug abuse

IMPROVING TREATMENT

New Drugs New therapeutic regimen Aggressive therapy Conjunctive therapy

IMPROVING TREATMENT

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

IMPROVING TREATMENT

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

IMPROVING TREATMENT

AGGRESSIVE THERAPYFOR IMMUNOCOMPROMISED PATIENTSProphylactic – Anti-fungal agents at, or near, the time of chemotherapy.Posaconazole now approved.

IMPROVING TREATMENT

AGGRESSIVE THERAPYFOR IMMUNOCOMPROMISED PATIENTS2. Empirical – Start therapy when patient at risk, i.e., fever and/or infiltrate without response to anti-bacterials.

IMPROVING TREATMENT

AGGRESSIVE THERAPYFOR IMMUNOCOMPROMISED PATIENTS3. Pre-emptive –When there is some additional evidence of fungal infection (serology, isolate, etc.)


IMPROVING TREATMENT
CONJUNJUNCTIVE THERAPY Antifungal agent plus a recombinant monoclonal antibody.

IMPROVING TREATMENT

CONJUNJUNCTIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS The use of anti-fungal agents with immunotherapy.

Immunotherapy

Interferons Colony stimulating factors Interleukins


“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.
“In the field of observation, chance only favors those who are prepared.” Louis Pasteur -1854

“Only the prepared mind can help the impaired host”Libero Ajello, Chief Mycology Division, CDC 1972

MYCOLGISTS have more

FUNGI