5.DESCRIPTION, IDENTIFICATION AND CLINICAL IMPORTANCE OF CANDIDA.pptx

DESCRIPTION, IDENTIFICATION AND CLINICAL IMPORTANCE OF CANDIDA ALBICANS, CRYPTOCOCCUS NEOFORMANS, HISTOPLASMA SPP AND MYCETOMA BY DR. RAZAQ MOMOH • Candida albicans • This is a yeast • Causative agent of candidiasis, the MC systemic mycosis • Note: All pathogenic Candida are actually commensals of...

DESCRIPTION, IDENTIFICATION AND CLINICAL IMPORTANCE OF CANDIDA ALBICANS, CRYPTOCOCCUS NEOFORMANS, HISTOPLASMA SPP AND MYCETOMA BY DR. RAZAQ MOMOH • Candida albicans • This is a yeast • Causative agent of candidiasis, the MC systemic mycosis • Note: All pathogenic Candida are actually commensals of humans, particularly in the mouth and vagina. • Morphology • Gram – positive fungi • They grow as budding yeast cells but could form pseudohyphae(except C. glabrata which doesn’t) in cultures and tissues • Candida albicans is dimorphic as it also forms true hyphae • Other species of Candida are not dimorphic • Candida albicans is identified on the basis of their ability to form large thick walled spores(diagnostic) called chlamydosphores on nutritionally deficient media or corn meal agar at 20ᵒC • Candida albicans form germ tubes (Reynolds Braude phenomenon) • Accurate identification of Candida species other than C. albicans require biochemical tests • Pathogenesis • Invasive candidiasis is usually preceded by increased colonization of the mouth and vagina due to broad spectrum antibiotics • Majority of non-albican vagina species enter the blood through intravascular catheterization • CLINICAL MANIFESTATION • 1. Cutaneous and mucosal candidiasis: • - Risk factors with superficial candidiasis include AIDS, pregnancy, DM, infants and elders, oral contraceptives, steroids and trauma • Risk factors associated with invasive candidiasis include: prolonged neutropenia, recent surgery, broad spectrum antibiotic therapy, presence of intravascular catheterization and intravenous drug use • Oral Thrush: • - painless discrete and confluent adherent white plagues on the oral and pharyngeal mucosa which is seen in AIDS px with CD4 <50/ųl bottle fed infants, debilitated patients. • Cutaneous candidiasis may be intertriginous , ie, erythematous scaling or moist lesion or paronychial (seen in occupations requiring constant immersion of fingers in water) • Esophageal candidiasis: • Most lesions are in the distal 3rd of the esophagus. Usually diagnosed by biopsy. • Vulvovaginal candidiasis: • Mostly in the 3rd trimester of pregnancy • Chronic mucocutaneous candidiasis: mostly onset is in early childhood and associated with cellular immunodeficiencies and endocrinopathy. Presents as hyperkeratotic skin lesion, partial alopecia and both oral and vagina thrush. • Deeply invasive (systemic) candidiasis: • Haematogenous seeding (candidemia) is common to retina, kidney, spleen and liver • In immunocompetent patient, white retinal exudates appear within 2 weeks of onset of candidemia. • Hepatosplenic candidiasis (Chronic disseminated candidiasis)- usually occur in patients with acute leukemia. • - Originates from intestinal seeding of portal and venous circulation • - Mostly occur in neutropenic patient • - Candida can cause arthritis of knee in patient who have received chronic glucocorticoid injections in the joint • - Endocarditis in previously damaged prosthetic valve. • Diagnosis: • Superficial candidiasis- demonstration of pseudohyphae or hyphae on wet smear with confirmation by culture or staining ( Gram’s, PAS, Methenamine silver) • Invasive candidiasis- histologic section or biopsies or by culture of CSF, blood and joint fluids. • NB: C. albicans are identified by production of germ tubes or chlamydospores. Treatment: Mucocutaneous – 1. Cutaneous - Tropical azoles 2. Vulvovaginal - Azole cream or oral Fluconazole • 3. Oropharyngeal – Clotrimazole or Fluconazole • 4. Esophageal – Fluconazole or Itraconazole • • • • • Deeply invasive: • 1. Non-neutopenic – Fluconazole or Amphotericin B • 2. Neutropenic – Amphotericin B • Candida endopthalmitis – IV Polyene + Flucytosine CRYPTOCOCCUS NEOFORMANS • This is mainly an opportunistic infection causing cryptococcosis or life threatening meningo-encephalitis in AIDS / immunosuppressed px. • In areas of high HIV prevalence, cryptococcal meningitis is the leading cause of adult meningitis. • • Cryptococcosis can be contracted via inhalation of desiccated yeast cells or basidiophores. • Note: the organism alongside C. gatti are basidiomycetous yeasts • Morphology • In cultures, they produce whitish mucoid colonies within 2-3 days • Microscopy- seen are spherical budding yeasts (5-10ųm in diameter) surrounded by a thick non-staining capsule • All cryptococcal species are encapsulated and possess urease. • C. neoformans and C. gatti differ from non-pathogenic strains by their ability to grow at 37ᵒC and the production of laccase which is a phenol oxidase that catalyse formation of melanin from phenolic substrates like catecholamines • NB: Capsule and laccase are virulence factors • Pathogenesis • Infection is initiated by inhalation of dry, minimally encapsulated, easily aeosolized yeast cells • Pry infection may be asymptomatic or mimic flu-like respiratory infection that resolve spontaneously • In immunocompromised px, there is dissemination following multiplication to distal sites like CNS causing cryptococcal meningoencephalitis • Sites of dissemination apart from CNS include eye, adrenal, bone, prostate. • Inflammatory reaction is mild or granulomatous • • • • • • • • Clinical features Chronic meningitis Headache Neck stiffness ↑ CSF and protein pressure ↑ cell count Glucose is normal or low Person to person transmission • Treatment • Combination of Amphotericin B and Flucytosine • Give HAART to HIV/AIDS patients • NB: ⅓ of HAART treated AIDS Px with cryptococcal meningitis develop immune reconstitution inflammatory syndrome (IRIS), which further exacerbates the illness. • Histoplasma capsulatum • A dimorphic fungus • Yeast (parasitic phase in tissues and culture) at 37ᵒC and spore/filamentous mould form(saprophytic phase in soil and culture) at 22-25ᵒC • Other dimorphic fungi include: Candida albicans, Histoplasma capsulatum, Sporothrix schenckii, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasilensis and Penicillium marneffi • H. capsulatum is a non-capsulated intracellular (in macrophages) fungus with septate hyphae that cause primarily a disease of the reticuloendothelial system • Sources of Infection: Inhalation of spores present on moist surfaces of alkaline soils enriched with bat and bird droppings • Pathology • It forms 2 types of asexual spores viz: • a. Large tuberculate macroconidia • b. Small elliptical microconidia • NB: Microconidia reach the alveoli and initiate granulomatous reaction • Clinical Features • 1. Majority of infections are asymptomatic or mild (acute primary pulmonary histoplasmosis): characterized by cough, fever, malaise with chest X-ray showing hilar adenopathy due to caseation necrosis or calcification (which mimics TB) • 2. a few patients who lack a history of APPH, develop progressive disease in either form: • a. Chronic pulmonary histoplasmosis or chronic fibrocalvitary pneumonia • b. Disseminated disease among immunosuppressed and users of TNF α antagonist infliximab. It mimic disseminated TB. • Diagnosis • Culture: • NB: Tuberculate spore is diagnostic • Chronic pulmonary histoplasmosissputum culture is done • Disseminated histoplasmosis, culture of bone marrow, mucosa lesion are done • Blood culture is best performed by lysis centrifugation method • Treatment • Acute – None • Chronic – Itraconazole or Amphotericin B • Disseminated – intraconazole, Amphotericin B. • MYCETOMA • Mycetoma is a painless localized woody induration without systemic symptoms usually found on the lower extremities (foot) • The granulomatous involvement of subcutaneous and deeper tissue is induced by traumatic inoculation of saprophytic fungi or bacteria • Thus we have either fungi causing mycetoma (Eumycetoma) or a bacteria being responsible ( Actinomycotic mycetoma) • The course of the infection are basically the same, but while eumycotic mycetoma is insidous, actinomycotic mycetoma is aggressive and invasive literally. • Clinical features • MC site is the foot • Presents as tumour with multipe discharging sinuses called Madura foot • MC cause is fungi, thus called eumycotic mycetoma/Maduramycosis/Madura foot • For eumycotic mycetoma, microscopy reveal black granules and stout filaments • Implicated fungi include: Pseudallescheria boydii, Exophiala jeanselmei, Madurella mycetomatis, Acremonium falciforme and Madurella grisea • Bacterial mycetoma are usually caused by Actinomyces, Norcardia, Streptomyces and Nocardiopsis • NB: Even Staph. aureas and other pyogenic bacteria can cause mycetoma like lesion called botryomycosis • In actinomycotic mycetoma, microscopy will reveal granules that are white to yellow as well as thin filaments • Diagnosis of Actinomycosis • Specimen: Sputum, aspirates and biopsies • Add same to test tubes containing saline and shake- sulphur granules can be seen with the naked eyes in some cases and in others, seen with microscope • Microscopy • Granules are bacterial colonies • Gram-positive filaments appearing as club-shaped/sun ray appearance • Club is formed due to antigenantibody reaction • Colonies on solid media show spidery colonies which later develop into molar-tooth colonies • Treatment • Actinomycetoma – Streptomycin + Dapsone or Cotrimoxazole • Eumycetoma of Madurella mycetoma – Ketoconazole/ Itraconazole • Other Eumycetoma practically do not respond to chemotherapy