SYSTEMIC MYCOSES Ma. Rosario L. Lacandula, MD, MPH Department of Microbiology & Parasitology College of Medicine Our Lady of Fatima University

General Characteristics: True Pathogenic fungi- causes infection in normal host Highly virulent organism MOT: Inhalation; Respiratory droplet Primary site of infection- LUNGS, 90% of infection is asymptomatic or they resolved spontaneously accompanied by high degree of specific resistance to infections Causes dissemination to other sites Geographically restricted Dimorphic 25 C- grows as filamentous mold 37C- yeast cell

Small budding yeast 2-5 um in diameter and found inside macrophages HISTOPLASMOSIS Darling’s disease, Reticuloendothelial cytomycosis, Cave disease & Spelunker’s disease Thin branching hyphae that produce microconidia and tuberculate macroconidia Small budding yeast 2-5 um in diameter and found inside macrophages

Histoplasmosis

Histoplasmosis

Histoplasmosis

Histoplasmosis Etiologic agent: H. capsulatum var. capsulatum, H. capsulatum var duboisii Natural reservoir: grows in soil with high nitrogen content especially areas contaminated by excreta of bats and birds( starlings & chicken) High endemicity- Ohio & Mississippi Valley regions of the United States Southern provinces of Ontario & Quebec in Canada Scattered areas of Central & South America Cases- Europe & Asia Africa- H. capsulatum var. duboisii

HISTOPLASMOSIS CLINICAL SYNDROMES: Normal Host Asymptomatic or mild flu like illness N exposure Acute Pulmonary Histoplasmosis H exposure Rare complications Pericarditis,mediastinal fibrosis Opportunistic infection Disseminated histoplasmosis Chronic Pulmonary histoplasmosis

Laboratory Diagnosis: HISTOPLASMOSIS Laboratory Diagnosis: Serologic Test- complement fixation- standard test – (+) later in the disease 6 weeks or longer after symptoms, fourfold rise Immunodiffusion- detects H & M antigens, more specific but less sensitive Microscopic examination of infected tissue Skin test- Histoplasmin test- ( +) after 2 weeks of exposure, no diagnostic value Treatment: Amphotericin B

Mold phase – typical pyriform microconidia 2-4 um in diameter Blastomycosis Chicago Disease,Gilchrist’s disease, North American blastomycosis Mold phase – typical pyriform microconidia 2-4 um in diameter Tissue phase – 8-15 um in diameter; buds are produced singly & attached to parent cell by a broad base

Blastomycosis

Blastomycosis Etiologic Agent: Blastomyces dermatitidis North America Continent & parts of Africa Endemicity overlaps with histoplasmosis Other endemic areas: Minnesota, Southern Manitoba, & Southwest Ontario Epidemics- Wisconsin, Minnesota, Illinois, Eastern State of Virginia & North Carolina Natural reservoir : not known, rarely cultured from soil of endemic areas Infection can also occur among dogs and horses

Blastomycosis Clinical Syndromes: Primary infection in the lungs- Inapparent Ulcerative lesions of the skin & lytic bone lesion Laboratory Diagnosis: Serology Microscopic findings Treatment: Amphoterecin B

Blastomycosis

Blastomycosis

No typical pattern of sporulation Paracoccidiodomycosis South American blastomycosis, Lutz Splendore-Almeida’s disease Yeast with several budding cells attached to a parent cell; “pilot’s wheel”; 2-3 um in diameter No typical pattern of sporulation

Paracoccidiodomycosis Etiologic Agent: P. brazieliensis Central & South America & has high incidence in Brazil, Venezuela & Colombia Natural reservoir: isolated in soil that have high humidity & average temperature of 23 C Equal distribution among males & females, but clinical disease is about 9X higher in males Transition of fungi from mold to yeast can be induced in vitro by raising the temperature of 25 C to 37 C M-17-beta- estradiol inhibits transformation of the fungi Testosterone,corticosterone & 17 alpha estradiol had NO inhibitory on the transformation

Paracoccidiodomycosis Clinical Syndromes: Primary lung infection- asymptomatic Ulcerative lesions of the buccal, nasal & occasionally GIT mucosa Laboratory Diagnosis: Serology Microscopic findings Treatment : Amphotericin B

Mycelia fragment to produce cylindrical arthroconidia Coccidiodomycosis Posada’s Disease, San Joaquin Valley fever & Desert rheumatism Spherule; multinucleated structure that undergoes internal cleavage to produce endospore Mycelia fragment to produce cylindrical arthroconidia

Coccidioidomycosis

Coccidioidomycosis

Coccidioidomycosis Etiologic Agent: Coccidiodes immitis “ New World”- North, Central & South American Continents Highest endemicity- San Joaquin Valley in California, Maricopa & Pima Countries in Arizona, Texas Endemic- Northern states of Mexico, parts of Venezuela, Paraquay & Argentina Isolated in soil samples during summer Inhibited by P. jantheniluem & B.subtilis during rainy season

Coccidioidomycosis Clinical Syndromes 60 % asymptomatic 40 % develop symptomatic pulmonary infection.Most common symptoms of primary disease are cough, fever, and chest pain. Night sweats and joint pains are not unusual Primary infections usually self limited Dissemination mainly in the meninges and/or skin HLA A9, Type B blood, do not develop toxic erythemas Blacks/ Asian are susceptible

Coccidioidomycosis Laboratory Diagnosis Complement fixation and tube precepitin Latex agglutination and agar immunodiffusion- two lines of precipitation appear to be significant 2 sources of antigen, both cell-free culture filtrates Coccidiodin Spherulin Treatment: Amphotericin B, ketoconazole

Coccidioidomycosis

OPPORTUNISTIC MYCOSES Ma. Rosario L. Lacandula, MD, MPH Department of Microbiology & Parasitology College of Medicine Our Lady of Fatima University

Opportunistic mycoses General Characteristic: Low virulent fungi Monomorphic Causes infection in immunocompromised host Healthy individual develop high degree of innate resistance to fungal colonization

Crytococcosis Busse-Buschke’s disease, torulosis, and European Blastomycosis Etiologic agent: Crytococcus neoformans Monomorphic Encapsulated- inhibits phagocytosis Phenoloxidase- converts phenolic compounds to melanin Lungs- Primary site of infection High predilection for systemic spread to the brain- leading cause of fungal meningitis

Cryptococcosis

Cryptococcosis Survive well in dessicated, alkaline, nitrogen rich, and hypertonic environment- recovered from excreta and debris of pigeons Organism that not cause infection of pigeons Worldwide distribution Clinical Syndromes: Primary pulmonary infection-asymptomatic detected as an incidental finding on routine chest X ray- solitary nodule Symptomatic pneumonia-diffuse pulmonary infiltrates Skin cryptococcosis, Cryptococcal meningitis, osteolytic bone lesions

Cryptococcosis

Cryptococcosis

Cryptococcosis Laboratory Diagnosis Detection based on the presence of antigen Latex agglutination test for detection of the capsule Rapid test- use of India Ink preparation of CSF- seen as clear halo Treatment: Amphotericin B

Candidiasis Etiologic agent: Specie of Candida Endogenous normal flora Major disease problem of immunocompromised host Clinical disease ranges from superficial skin infection to systemic life threatening disease Rarely isolated from the surface of human skin except from certain intertrigenous areas Organs involved- lungs, spleen,kidney,liver,heart and brain Pseudohyphae & septate hyphae

Candidiasis Clinical Syndromes CMC Chronic mucocutaneous candidiasis- heterogenous group of clinical syndromes characterized by chronic, treatment resistant superficial Candida infections of the skin, nails and oropharynx No dissemination seen in visceral organs Defect in CMI Laboratory Diagnosis Rapid diagnosis- germ tube test Budding yeast cells, pseudohyphae and septate hyphae Treatment: Amphotericin B , 5-fluorocytosine, ketoconazole and fluconazole

Development of germ tubes by Candida albicans yeast cells after incubation in serum x 2 hours @ 37oC

Candidiasis (Moniliasis)

Candidiasis (Moniliasis)

Aspergillosis Etiologic agent: A. fumigatus; A. niger; A. flavus Common in the environment Exogenous source Normal individual not susceptible to systemic aspergillosis

Aspergillosis Clinical syndromes Mycotoxicosis- ingestion of contaminated peanuts Allergic aspergillosis- allergic bronchopulmonary disease Secondary Colonization- fungal colonization of pre existing cavity ( e.g. pulmonary abscess) w/o invasion. Fungus ball- spherical mass of intertwined septate branching hyphal elements Systemic disease- Invasive disease involving multiple organs Laboratory Diagnosis: septate hyphae that branch at regular intervals seen in clinical specimens

Mucormycosis Susceptibility to the fungi- metabolic acidosis, DM, leukopenis and hyperglycemia Grows rapidly on all laboratory media Form coenocytic hyphae Ubiquitous in the environment and encountered as contaminants Clinical Syndromes Rhinocerebral zygomycosis-most common-originate in the paranasal sinuses can involve the ocular orbit and palate with extension to the brain Lungs, GIT, subcutaneous tissue

Mucormycosis In severely burned patients- colonize the damaged tissues and tend to become invasive. In disseminated disease- predilection for invading major bood vessel. Clot that result can cause ischemia and necrosis of adjacent tissues. Laboratory Diagnosis: Microscopic findings

Mucormycosis

Mucormycosis