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 environment 2. 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 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

Must distinguish between 1.Transient fungemia 2.Colonization 3.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 1.Atypical signs or symptoms 2.Unusual organ affinity 3.Outside the endemic area 4.Unusual Histopathology 5.Etiologic agent may be a saprophyte

CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.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 SYSTEM Malasezzia furfur NUMBER OF ORGANISMS x LOW VIRULENCE = DISEASE HOST RESISTANCE

CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.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 SYSTEM Candida albicans NUMBER OF ORGANISMS x VIRULENCE = NO DISEASE HOST RESISTANCE

COMPROMISED IMMUNE SYSTEM Candida 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 neoformans PORTAL 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 report 16 Patients 10 localized disease –7-lung, 2-skin, 1 CNS 6 Disseminated –5/6 – CNS All 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 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.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 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual Histopathology 5.Unusual Pathogens

INFLAMMATORY REACTION NORMAL HOST –PYOGENIC –GRANULOMATOUS IMMUNODEFICIENT HOST –NECROTIC

CLINICAL PRESENTATION 1.Atypical Signs and Symptoms 2.Unusual Organ Affinity 3.Outside Endemic Area 4.Unusual histopathology 5.Unusual Pathogens

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

Penicillium marneffei 1.Usually not a pathogen 2.The only dimorphic penicillium 3.Produces a red pigment 4.Endemic in the Far East

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

Cryptococcus neoformans Diabetes mellitus Tuberculosis Lymphoma Hodgkin’s disease Corticosteroid therapy Immunosuppression

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 1.New Drugs 2.New therapeutic regimen 3.Aggressive therapy 4.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 1.Simultaneously administering two drugs 2.Sequential Tx with two or more drugs 3.Alternate Administration of two or more

IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS 1.Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy. 2.Posaconazole now approved.

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.

IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS 3. 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 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 FUN GI