Opportunistic Mycoses Batch 17 April 17, 2012 Dr S Gokul Shankar

Opportunistic Mycoses Opportunistic mycoses are fungal infections that do not normally cause disease in healthy people, but do cause disease in people with weakened immune defenses (immuno-compromised people). Infections due to fungi of low virulence

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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

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)

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

Weakened immune function may occur due to inherited immunodeficiency diseases, drugs that suppress the immune system (cancer chemotherapy, corticosteroids, drugs to prevent organ transplant rejection), radiation therapy, infections (e.g., HIV), cancer, diabetes, advanced age and malnutrition.

MOST SERIOUS OPPORTUNISTIC INFECTIONS Candidiasis Aspergillosis Cryptococcosis Zygomycosis Pneumocystis carinii Pneumonia

Candidosis Candidiasis also called as Monoliasis, Can infect Skin, Mucosa, or Internal Organs Called Yeast Like fungus Currently important cause of opportunistic fungal infection.

Macroscopic and Microscopic appearance of Candida spp

Normal Flora to Pathogenic fungi As Candida is present in practically all humans, it has many opportunities to cause endogenous infections in compromised host - so, Candida infections continues to be the most frequent opportunistic fungal infection.

Systemic Candidosis Occurs in Patients who carry more yeasts in Mouth, Gastrointestinal system, Predisposed Individuals with 1 On antibiotic or/and Steroid Therapy 2 Immuno-supressed 3 Recipients with organ transplantation 4 Infancy – Old age – Pregnancy On Antibiotic therapy -5 Indisposed with trauma Occluding lesions, -6 Immuno-comprimised, Major event in AIDS patients -7 Diabetus mellitis. -8 Zinc and iron deficiencies

Pathogenesis and Pathology Mucosal infections occur superficially –Discrete white patches on mucosal surface. Can affect tongue Infants and old persons are affected In Immune compromised /AIDS. Oral candidiasis is commonly seen _- Marker Vaginal candidiasis causes itching soreness white discharge, White colored lesions, Pregnancy in advanced stage, Majority experience one episode in a life time

Predisposition after Surgery and Therapeutic Approaches Post operative Immuno Supression Use of IV catheters Use of cytotoxic drugs and cortosteriods Use of Urinary Catheters

Important species of Candida in Human infections C.albicans C.tropicalis C.glabrata C.krusei

Prominent Infections with Candida

Oral Thrush produced by Candida albicans

Laboratory Diagnosis Samples Skin scrapings, Mucosal scrapping, Vaginal secretions Culturing Blood and other body fluids, Observations Microscopic observation after Gram staining. Gram + yeast cells.

Easier Identification of species as C.albicans Germ tube test identifies C. albicans from other Candida species. Majority of Diagnostic laboratories depend on this test.

Cryptococcus neoformans Primary infection in lungs Cryptococcal meningitis is most common disseminated manifestation Can spread to skin, bone and prostate Organism is ubiquitous and infections occur worldwide C. neoformans recovered in large amounts in pigeon poop Does not cause disease in birds

Other reservoir Birds

Diagnosis Lumbar puncture and microscopic examination of cerebrospinal fluid is diagnostic. (India ink staining) Cyrptococcal antigens in CSF and serum. Immune response Phagocytosis by neutrophils is inhibited by the presence of a capsule. Melanin is another virulence factor

Isolation : Guizotia abyssinicia (Niger seed)/Bird seed agar

Aspergillosis Genus occurs worldwide and contains hundreds of species. These species constitute the most commonly found fungi in any environment Major portal of entry is the respiratory tract. Dissemination can occur from the lungs to the brain, GI tract, and kidney. CNS and nasal-orbital cavities can also occur without lung involvement. Risk factors for invasive disease are neutropenia and high doses of adrenal corticosteroids

Aspergillus Hypha with Conidia

Hyphae of invasive aspergillosis

Aspergillosis Aspergillosis is the most common fatal infection seen in patients with chronic granulomatous disease of childhood. Progressive and disseminated disease can complicate neoplastic diseases, especially acute leukemia, bone marrow and organ transplantation (not necessarily AIDS). ABPA - Aspergillus fumigatus In immunosuppressed hosts: invasive pulmonary infection, usually with fever, cough, and chest pain. May disseminate to other organs, including brain, skin and bone. In immunocompetent hosts: localized pulmonary infection in persons with underlying lung disease. Also causes allergic sinusitis and allergic bronchopulmonary disease. Other Agent: A. flavus.

Pneumocystis carinii I was a protozoan… I am now a fungus Pneumocystis carinii pneumonia (PCP) renamed Pneumocystis jiroveci (yee row vet zee) unicellular fungi found in the respiratory tracts of many mammals and humans P jiroveci is now one of several organisms known to cause life-threatening opportunistic infections in patients with advanced HIV infection worldwide.

Morphology Spherical, Elliptical Trophozites present in a tight mass

© Ranjith’s Pneumocystis on silver stain, DFA, and calcofluor white

Pneumocystis pathogenesis Cysts inhaled - In susceptible patients (e.g. HIV infected patients with CD4 count <250) disease is predominantly pulmonary, with alveolar filling with plasma cells and edema. Pneumocystis pneumonia –acute-to-subacute fever, dry cough, dyspnea Extrapulmonary pneumocystis involving various body sites seen almost exclusively in AIDS patients receiving aerosolized pentamidine prophylaxis

Other opportunistic infections Zygomycosis Rhizopus, Rhizomucor, Absidia, Mucor species, or other members of the class of Zygomycetes, also causes invasive sinopulmonary infections An especially life-threatening form of zygomycosis (also known as mucormycosis) - rhinocerebral syndrome In addition to diabetic ketoacidosis, neutropenia and corticosteroids are other major risk factors for zygomycosis

Rhinocerebral mucormycosis

Zygomycete hyphae in tissue

Phaeohyphomycosis. Phaeohyphomycosis is an infection by brown to black pigmented fungi of the cutaneous, superficial, and deep tissues, especially brain. These infections are uncommon, life-threatening, and occur in various immunocompromised states. Hyalohyphomycosis. Hyalohyphomycosis is an opportunistic fungal infection caused by any of a variety of normally saprophytic fungi with hyaline hyphal elements. For example, Fusarium spp. infect neutropenic patients to cause pneumonia, fungemia, and disseminated infection with cutaneous lesions.

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

IMPROVING TREATMENT New Drugs Lipid Amphotericin B Third generation azoles (Posaconazole, Voriconazole) New classes of antifungal agents (Echinocandins) – inhibit synthesis of glucan

IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS 1.Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy. Posaconazole now approved. 2. Empirical – Start therapy when patient at risk, i.e., fever and/or infiltrate without response to anti-bacterials. 3. Pre-emptive –When there is some additional evidence of fungal infection (serology, isolate, etc.)

IMPROVING TREATMENT CONJUNJUNCTIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS The use of anti-fungal agents with immunotherapy. (Interferons, Colony stimulating factors, Interleukins)

MYCOLGISTS have more FUN GI

The End