Common Fungal Infections.pdf

COMMON FUNGAL INFECTIONS Dr. Karla Guadalupe Zavala Bravo [email protected] OBJECTIVES 1. By the end of the lecture, students will be able to describe at least five of the most common fungal infections classified by the CDC. 2. Following the presentation on fungal i...

COMMON FUNGAL INFECTIONS Dr. Karla Guadalupe Zavala Bravo [email protected] OBJECTIVES 1. By the end of the lecture, students will be able to describe at least five of the most common fungal infections classified by the CDC. 2. Following the presentation on fungal infections, students will be able to classify and differentiate between the various types of fungal organisms that can cause infections in humans. 3. Given a patient scenario, students will be able to identify and evaluate risk factors that could predispose the patient to a fungal infection. 4. In a group activity, students will match a list of clinical features observed in fungal infections to the fungal pathogens known for causing those symptoms and justify their choices. 5. Students will develop a flow chart outlining a diagnostic approach to differentiate between the most common fungal infections, considering factors like clinical symptoms and potential causative agents.  There are nearly 1-5 million species of fungi but only a few hundred can make people sick. Fungal infections range from mild to life-threatening. People with weakened immune systems (from illness, age, or medical treatments like steroids) are at higher risk for most fungal infections. Worldwide, more than one billion people get a fungal infection each year. The two most common fungal infections are ringworm and vaginal yeast infections. ▪ Ringworm typically causes a ring-like rash and spreads easily between people and from pets to people. The same fungi that cause ringworm can cause jock itch, athlete's foot, and nail infections. ▪ Most women get a vaginal yeast infection at least once in their lives. Vaginal yeast infections are caused by overgrowth of a yeast called Candida in the vagina. Everyone has Candida in and on their body; it only causes symptoms when it grows out of control.  C. albicans CANDIDIASIS → Yeast Infection C. glabrata C. parapsilosis Most important opportunistic fungal pathogens. C. tropicalis C. krusei The third most common cause of central line-associated bloodstream infections. C. lusitaniae C. guilliermondii Although more than 100 species hace been described, C. dubliniensis only a few have been implicated in clinical infections. C. rugosa Candida Albanicans is the most commonly isolated. C. auris Morphology C. albicans → Oval yeastlike Other than C. C. glabrata → Germ tubes and forms → Produce glabrata → Pseudohyphae, terminal, thick- buds or Pseudohyphae germ tubes, or walled blastoconidia. and true hyphae. true hyphae. chlamydoconidia. In histologic sections: Stain poorly → Hematoxylin and eosin (H&E). Stain well → Periodic acid-Schoff (PAS), Gomori methenamine silves (GMS), and Gridley fungus stains. In culture: Most species → Form smooth, white, creamy, domed colonies. C. albicans and other species: Phenotypic switching → A single strain of Candida may change reversibly among several different morphotypes. The frequency is: Too high to result → From gene mutations. Too low to be → Attributable to mass conversion, it can response depending in the local environment. Epidemiology Primary site of colonization: GI tract → From mouth to rectum. May be found → Vagina, urethra, skin, under fingernails and toenails. C. albicans: Most common etiologic agent of human disease. 25% to 50% of healthy persons carry Candida as part of the normal flora of the mouth. Oral carriage in hospitalized patients: HIV infection, dentures, diabetes, receiving antineoplastis chemotherapy and antibiotics, children. Endogenous infection: The normally commensal host flora take advantage of the “opportunity” to cause infection. Exogenous transmisión: Use of contaminated irrigation solutions, parenteral nutrition fluids, vascular pressure transducer, cardiac valves, corneas. Second most common species: C. Glabrata → North America. C. parapsilosis and C. tropicalis → Latin American. Clinical Syndromes Liver Brain Spleen From superficial mucosal and cutaneous to hematogenous dissemination Heart Kidney  White “coottage- cheese” – like patches on mucosal surface Raw bleeding Pseudomembranous surface when scraped Flat, red, and Limited to Erythematous occasionally sore oropharynx áreas Extend to Nonremovable Mucosal infections esophagus and GI Candidal leukoplakia white thickening of (thrush) tract epithelium Sore fissures at the Vaginal mucosa in Angular cheilitis corners of the women mouth When skin surface is Hematogenous occluded and moist Onychomycosis Bladder Intraabdominal seeding in kidney Groin Recent abdominal Axillae surgery Indwelling bladder Toe webs catheter Renal abcess Peritonitis C. albicans Breast folds Diabetes Papiillary necrosis Abdominal abscess C. parapsilosis Present pruritc rash + Urinarhy obstruction “Fungus ball” of the Purulent or necrotic C. guilliermondii uréter or renal pelvis erythmatous infection ar sites of Urinary procedures vesiculopustuslar perforation or lesions anastomotic leak  Central Nervous System Heart Eye Hematogenous disease Hematogenous seeding Neurosurgical of a prosthetic or procedures damaged heart valve Myocardium Hematogenous Ventriculoperitoneal candidiasis shunts Pericardial space Chorioretinitis Mimic bacterial Clinical → resembles bacterial endocarditis endophthalmitis meningitis Embolic events more common CRYPTOCOCCOSIS → Yeast Infection Caused by → C. neoformans and C. gatii. Found as a ubiquitous saprofyte of soil, especially that which is enriched with pigeon droppings. Morphology Stains poorly → In tissue and on The capsule is a H&E. staining with India distinctive marker Stains easily → PAS ink → Spheric zones → Diameter of up and GMS stains. Spheric to oval, or halos that to 5 times that of The cell wall → encapsulated, yeast represent the the fungal cell and is Contains melanin, like. extracellular detected with a staining with the polysaccharide mucin stain, such as Fontana-Masson capsule. Mayer mucicarmine. stain. Epidemiology Acquired by inhaling aerosolized cells from the environment. Dissemination from the lungs, usually to the CNS, produces clinical disease. Most common cause of fungal meningitis. C. gattii SC was originally identified as being the gum tree, Eucalyptus camaldulensis. C. Neoformans: major opportunistic pathogen of patients with AIDS: CD4+ lymphocyte counts of less than 100/mm3. High risk for CNS and disseminated cryptococcosis.  Clinical Syndromes CNS infection Cerebromeningeal Parenchymal lesions Pulmonary infection Less often Both meninges Also called Asyntomatic involved cryptococcomas process Secondary to Uncommon in Cutaneous Fever Fulminant bilateral hematogenous and infections caused by C. lymphatic spread Headache neoformans pneumonia Mucocutaneous Meningismus Osseous from a primary Most common Nodular infiltrates Visual disturbances pulmonary focus presentation of CNS may be unilateral Visceral Abnormal mental status caused by C. gatti in Seizures or bilateral immunocompetent hosts ASPERGILLOSIS → Mold Infection Aspergillus is a ubiquitous mold that causes allergies (allergic bronchopulmonary aspergillosis). The major conditions that predispose to Aspergillus infection are neutropenia and use of corticosteroids. Aspergillus fumigatus is the most common pathogenic species of the fungus. Aspergillus spp. are transmitted as airborne conidia, and the lung is the major portal of entry. The small size of A. fumigatus spores, approximately 2 to 3 µm, enables them to reach alveoli. In immunosuppressed states, conidia can germinate into hyphae, which then invade tissues. Invasive aspergillosis is highly associated with neutropenia and impaired neutrophil defenses. Clinical Syndromes Growth in the respiratory tract with minimal or no invasión of the tissues. Colonizing Colonized cavities are the result of aspergilosis prior tuberculosis, bronchiextasis, old infarcts, or abscesses. (aspergilloma) People usually have recurrent hemoptisis. Oppportunistic infection that is Invasive confined to immunosuppressed hosts. Primary lesions are in the lung but aspergillosis widespread hematogenous dissemination: heart valves and brain MUCORMYCOSIS → Mold Infection Mucormycotina are widely distributed in nature and cause no harm to immunocompetent individuals, but they infect immunosuppressed people, causing mucormycosis, previously called Zygomycosis. Opportunistic infection caused by environmental fungi, including Mucor spp., Rhizopus spp., and Cunninghamella spp. Major predisposing factors → Neutropenia, corticosteroid use, diabetes mellitus, iron overload, and breakdown of the cutaneous barrier (e.g., as a result of burns, surgical wounds, or trauma). Mucormycotina are transmitted by airborne asexual spores. Inhalation of spores is the most common route of entry into the body, but percutaneous exposure or ingestion can also lead to infection. Mucormycetes form nonseptate hyphae of variable width (6 to 50 µm) with frequent right-angle branching, distinct from Aspergillus hyphae, which are readily demonstrated by H&E or special fungal stains. The 3 primary sites of invasion are the nasal sinuses, lungs, and gastrointestinal tract, depending on whether the spores (which are widespread in dust and air) are inhaled or ingested. Clinical Syndromes Lung involvement Individuals with The Mucormycotina Meningoencephalitis with Mucormycotina The lung lesions diabetes → may cause local tissue follows, sometimes may be secondary to combine areas of spread from nasal necrosis, invade complicated by rhinocerebral hemorrhagic sinuses to the orbit arterial walls, and cerebral infarctions disease, or it may be pneumonia with and brain, giving rise penetrate the when fungi invade primary in people vascular thrombi and to rhinocerebral periorbital tissues arteries and induce with severe distal infarctions. mucormycosis. and cranial vault. thrombosis. immunodeficiency. BLASTOMYCOSIS → Dimorphic Fungi Systemic fungal infection caused by → B. dermatitidis and B. gilchristii. Origin → Mississippi River basin, around the Great Lakes, and southeastern regios of USA. Morphology The yeast cells The yeast forms are spherical, → Hematoxylin The mold form hyaline, and eosin (H&E). B. dermatitidis in B. dermatitidis in produces round multinucleated, Fungal stains → culture → tissue → to oval or pear- and have thick Gomori Enriched media at Nonencapsulated shaped conidia “double- methenamine 37°, and white to yeastlike cells. located on long contoured” walls. silver (GMS) and tan, filamentous, or short terminal Reproduce by the periodic acid– mold colonoes. hyphal branches. formation of buds Schiff (PAS). or blastoconidia. Epidemiology Infection is acquired after the inhalation of aerosolized conidia produced by the fungus growing in soil and leaf litter.  Clinical Syndromes Cutaneous Extrapulmonary Respiratory distress (hematogenous infection (2/3) Pulmonary disease syndrome dissemination from the lung) Painless Localized to exposed areas: Face Scalp Neck Hands Skin Papular Bones High fever Acute onset Pustular or Prostate Diffuse infiltrates High fever indolent Liver Lobar infiltrates Respiratory Ulcerative-nodular Spleen Cough failure Verrucous with Kidney crusted surfaces CNS and raised serpiginous borders. COCCIDIOIDOMYCOSIS → Dimorphic Fungi Endemic mycosis caused by → C. immitis and C. posadasii. Origin → Inhalation of infectious arthroconidia. Localized → C. immitis in California and C. posadasii outside of California. Synonyms → Coccidioidal granuloma and San Joaquin Valley fever. Morphology Initial growth is white to gray, moist, and glabrous Vegetative hyphae give Exists as a mold in and occurs within 3-4 rise to fertile hyphae that nature, when cultured at days. The colony enlarges produce alternating 25°C and as into a circular “bloom.” (separated by disjunctor endosporulating spherule Mature colonies usually cells) hyaline in tissue. become tan to brown or arthroconidia. lavender. Epidemiology Regions of endemicity: Central and southern California, southern Arizona, southern New Mexico, parts of Utah and Washington, and western Texas. C. Immitis → Found in soil, and the growth of the fungus in the environment is enhanced by bat and rodent droppings. Cycles of drought and rain enhance dispersion of the organism because heavy rains facilitate the growth of the organism in the nitrogenous soil wastes. Subsequent drought and windy conditions favor aerosolization of arthroconidia.  C. Immitis is the most Clinical Syndromes virulent of all human mycotic pathogens Primary infection Extrapulmonary Allergic reactions Secondary infection infection Inhalation of only a few Secondary to immune Skin arthroconidia Symptomatic for 6 complex formation Soft tissues weeks or longer Asymptomatic Erythematous macular Bones pulmonary disease Nodules rash Joints (60%) Cavitary disease Erythema multiforme Meninges Self-limited flulike Progressive pulmonary Erythema nodosum illness disease HISTOPLASMOSIS → Dimorphic Fungi Caused by → H. capsulatum var capsulatum and H. capsulatum var duboisii. Localized → H. capsulatum var capsulatum causes pulmonary infections in the Eastern half of the USA an Latin America. Localized → H. capsulatum var duboisii causes skin and bone lesions in the tropical áreas of Africa. Morphology Mold forms Dimorphic fungi produce 2 types of The yeast cells are existing as a The mold colonies onidia: large, thick- (2) Small, oval thin walled, oval, hyaline mold in grow slowly and walled, spheric microconidia with and measure 2 to 4 nature and in develop as white macroconidia with smooth or slightly μm (var. culture at 25°C as or brown hyphal spikelike rough walls that capsulatum) or an intracelular colonies after projections are sessile or on thicker walled and budding yeast in several days to a (tuberculate short stalks. 8 to 15 μm (var. tissue and in week. macroconidia) that duboisii). culture at 37°C. arise from short conidiophores. Epidemiology Localized → Broad regions of the Ohio and Mississippi River valleys and occurs throughout Mexico and Central and South America. Localized → H. duboisii is confined to the tropical areas of Africa, including Gabon, Uganda, and Kenya. The natural habitat of the mycelial form is soil with a high nitrogen content, such as that found in areas contaminated with bird or bat droppings. Associated with exposure to bird roosts, caves, and decaying buildings or urban renewal projects involving excavation and demolition.  Clinical Syndromes Route of infection: via inhalation of microconidia. Germinate into yeasts within the lung and may remain localized or disseminate hematogenously or by the lymphatic system. Var. capsulati Inflammatory sequelae Disseminated disease Disseminated disease Disseminated disease Pulmonary infection (10%) (Chronic) (Subacute) (Acute) Septic shock–like picture → Fever, hypotension, pulmonary infiltrates, and acute respiratory distress. Asymptomatic Weight loss and Fever Fulminant process Persistent infection occurs in lymphadenopathy fatigue Weigh loss Immunosuppresse Oral and 90% With or without Malaise d with AIDS, organ gastrointestinal Bronchial Flulike illness obstruction fever Oropharyngeal transplant ulcerations and Rx: Oral ulcers ulcers recipients, bleeding, adrenal hilar or Arthritis mediastinal Hepatosplenomeg receiving steroids insufficiency, Arthralgias Hepatosplenomeg adenopathy and aly or other meningitis, and Pericarditis aly patchy pulmonary Bone marrow: immunosuppressiv endocarditis. infiltrates anemia, e chemotherapy leukopenia, and thrombocytopenia Adrenal, cardiac valves, and CNS Clinical Syndromes Var. Duboisii (chronic) Regional lymphadenopathy Osseous lesions (1/3) Secondary infection Lesions of the skin and Osteolysis and involvement Bone marrow bone. of contiguous joints. Liver Papular or nodular Cranium Spleen Progress to abscesses, Esternum Marked by fever, which then ulcerate Ribs lymphadenopathy, anemia, Vertebrae weight loss, and Long bones organomegaly LYMPHOCUTANEOUS SPOROTRICHOSIS → Dimorphic Fungi Caused by → Sporothrix schenckii, S. brasiliensis, S. globosa, and S. luriei. is ubiquitous in soil and decaying vegetation. S. Brasiliensis → Transmission occurs through stray cats. Infection is chronic and characterized by nodular and ulcerative lesions that develop along lymphatics thar drain the primary site of inoculation. Grows as mold → At room temperature. Grows at yeast → At 37 °C and in tissue.  The appearance of eosinophilic Splendore-Hoeppli material Morphology surrounding yeast cells (asteroid body) may be helpful. Microscopically → Mold form consists Mycelial form of narrow, hyaline, Yeast form consists Laboratory cultures grow septate hyphae. of spheric, oval, or confirmation may rapidly and have Produce oval elongated (“cigar- be established by wrinkled conidia borne on shaped”) yeastlike converting mycelial membranous delicate sterigmata cells with single or growth to the yeast surface that or in a rosette or (rarely) multiple firn by subculture at becomes tan, “daisy petal” bud. 37°C. Brown, or black. formation on conidiophores. Epidemiology Sporadic and is most common in warmer climates. Outbreaks of infection related to forest work, mining, and gardening. Classic infection associated with: Traumatic inoculation of soil or vegetable or organic matter contaminated with the fungus. Zoonotic transmission: Armadillo hunters. S. brasiliensis transmitted from: Bites or scratches from stray cats (primary hosts). Clinical Syndromes Lymphangitic sporotrichosis Appears after local trauma to an extremity. Initial site → Small nodule, which may ulcera. Secondary lymphatic nodules appear 2 weeks after. Linear chain of painless, subcutaneous nodules that extend along the course of lymphatic drainage of the primary lesion. BIBLIOGRAFY Cotran, R. S., Kumar, V., & Robbins, S. L. (2021). Robbins and Cotran Pathologic Basis of Disease (10th ed.). Saunders Elsevier. Chapter 8, pages 383-388. Chapter 15, pages 712-713. Patrick R. Murray, Ken S. Rosenthal, Michael A. Pfaller (2021). Subcutaneous Mycoses. En Elsevier Inc (Eds.), Medical Microbiology. Elsevier. Chapter 63, pages 623-625.