Myco Lec9-10 (Opportunistic Mycosis) PDF: Candida, Cryptococcus, Aspergillus

Mycology / Lectures: 9 &10 Opportunistic Lecture:1Mycoses Dr. Nada A. Abdelrahim 1 1. Candida 2. Cryptococcus 3. Aspergillus 4. Mucor & Rhizopus 5. Pneumocystis 6. Penicillium marneffei 7. Pseudallescheria boydii 8. Fusarium solani...

Mycology / Lectures: 9 &10 Opportunistic Lecture:1Mycoses Dr. Nada A. Abdelrahim 1 1. Candida 2. Cryptococcus 3. Aspergillus 4. Mucor & Rhizopus 5. Pneumocystis 6. Penicillium marneffei 7. Pseudallescheria boydii 8. Fusarium solani 2  Opportunistic fungi do not induce disease in most immunocompetent persons, but can do so in those with impaired host defenses Five genera are medically important fungi: o Candida o Cryptococcus o Aspergillus o Mucor o Rhizopus Important features of opportunistic fungal diseases are summarized in the following Table 3 4 1. Candida 5  Approximately 90% of infections are caused by: o Candida albicans Pathogenic non-albicans Candida (NCAC) species include: o Candida glabrata o Candida tropicalis o Candida parapsilosis o Candida krusei o Candida auris o Candida guilliermondii 6  Diseases The Most Important species of Candida is Candida albicans It causes: Thrush o Vaginitis o Esophagitis o Diaper Rash & o Chronic Mucocutaneous Candidiasis It also causes: o Disseminated infections (such as Right-Sided Endocarditis [especially in intravenous drug users]) o Bloodstream infections (Candidemia) & o Endophthalmitis Other important infections are those related to indwelling intravenous & urinary catheters 7  Properties C. albicans is an oval yeast with a single bud (see next slides) It is Part of Normal Flora of Mucous Membranes of: Upper Respiratory, Gastrointestinal & Female Genital Tracts In Tissues: it may appear as Yeasts or as Pseudohyphae (see next slides) Pseudohyphae are: Elongated Yeasts that visually resemble hyphae but are not True Hyphae True hyphae are also formed when C. albicans invades tissues Carbohydrate Fermentation Reactions differentiate it from other species (e.g., Candida tropicalis, Candida parapsilosis, Candida krusei & Candida glabrata) 8 9 10  Transmission C. albicans is already present on Skin & Mucous Membranes (as member of the normal flora) Presence of C. albicans on the skin predisposes to infections involving instruments that penetrate the skin (such as Needles [intravenous drug use] & Indwelling Catheters) 11  Pathogenesis & Clinical Findings Disease usually occurs when local or systemic host defenses are impaired Overgrowth of C. albicans in Mouth produces Pseudomembrane ---- the white, creamy patches that appear on oral mucosa, can be gently scraped off to reveal red, inflamed area underneath, often described as looking like Cottage Cheese --- called: Oral Thrush (see next slide) Vaginitis with itching & discharge (favored by High pH, Diabetes, Antibiotics) Antibiotics suppress normal flora Lactobacillus (keep pH low) ---- pH Rises ---- favoring growth of Candida Skin Invasion occurs in Warm & Moist areas --- become Red & Weeping 12 Oral Candidiasis (Oral Thrush): Characterized by lacy, white patches on top of reddened areas on tongue, throat & mouth. Can include fever & burning sensation in the mouth. 13 - Thrush on the tongue and soft palate. Also called: Oral Candidiasis, Mycotic Stomatitis, or White Mouth - Characterized by raised white patches on the tongue. When gently scraped off, reveal inflamed tissue that tends to bleed easily. - Beginning on the tongue, the creamy white spots can spread to the gums, palate, tonsils, throat, and elsewhere. 14 15  Candidal Intertrigo: occurs in moist overlapping skin folds, such as areas in the inner thighs, Cutaneous Candidiasis armpits, under the breasts. It is (Candida Skin characterized by red, raw skin Infection) surrounded by scaling & lesions that itch, ooze, or hurt. 16  Fingers & Nails become involved when repeatedly immersed in water (persons employed as dishwashers in restaurants are commonly affected) ---- Thickening or loss of the nail can occur ❖ Candidal Intertrigo: superficial skin-fold infection caused by candida. Triggered by combination of: o Hot & Damp environment of skin folds (conducive to growth of Candida albicans) o Increased skin friction Immunocompromise ❖ Risk of developing Candidal Intertrigo include: o Occlusive clothing, gloves and footwear Obesity o Excessive sweating (hyperhidrosis) Diabetes mellitus o Incontinence causing irritant contact dermatitis (incontinence-associated dermatitis) o Immune deficiency conditions (such as HIV infection or immune suppression by medications (chemotherapy, systemic corticosteroids) Diaper Rash in Infants occurs when wet diapers are not changed promptly (see next slide) 17 Candida infection in nail (Paronychia): starts near the nail fold, or cuticle. Redness & Swelling at the base of the nail. White, Yellow, Green, or Black marks on nail. The nail may lift off its bed. The nail may be tender when pressed. Candidal Intertrigo Candidal Intertrigo Candida Paronychia Candida Paronychia 18 Candida Paronychia & Onychodystrophy as a manifestation of mucocutaneous candidiasis in hyper-IgE syndrome before (A) and after (B) long-term therapy with fluconazole. ❖ Candida Paronychia: is nail infection caused by Candida albicans. It is an inflammation of the skin around the nail. ❖ Onychodystrophy: is a term for nail changes, such as discoloration or shedding. 19 Diaper Rash: Some diaper rashes are caused by yeast infections. 20  Candida may Disseminate to many organs Or cause Chronic Mucocutaneous Candidiasis in immunosuppressed individuals Chronic Mucocutaneous Candidiasis: is a prolonged infection of the Skin, Oral & Genital Mucosa, & Nails that occurs in individuals deficient in T-cell immunity Patients with Mutations in the Gene Encoding Interleukin-17 (IL-17) & the Receptor for IL-17 are Predisposed to Chronic Mucocutaneous Candidiasis After organ transplantation, patients receiving immunosuppressive drugs to prevent rejection are Predisposed to invasive Candida infections 21 Chronic Mucocutaneous Candidiasis 22 Chronic Mucocutaneous Candidiasis 23 Chronic Mucocutaneous Candidiasis 24  Intravenous Drug Abuse, Indwelling Intravenous Catheters & Hyperalimentation also Predispose to Disseminated Candidiasis (especially Right-Sided Endocarditis & Endophthalmitis) Candida Esophagitis (often accompanied by involvement of Stomach & Small Intestine) is seen in patients with Leukemia & Lymphoma Subcutaneous Nodules are often seen in Neutropenic Patients with Disseminated Disease C. albicans is the most common species to Cause Disseminated Disease in these patients C. tropicalis & C. parapsilosis are important pathogens also 25  Candida Esophagitis in Immunocompetent Individuals 26 A Child with Subcutaneous Nodules Subcutaneous Nodules: Firm lumps of tissue under the skin that form from inflammation 27  Laboratory Diagnosis In Exudates or Tissues: Budding Yeasts & Pseudohyphae appear Gram-Positive & can be visualized by using calcofluor-white staining In Culture: Typical yeast colonies are formed that resemble large staphylococcal colonies Germ Tube Test (GTT): Form in serum at 37°C (distinguishes C. albicans from most other Candida species [see next slide]) Chlamydospores: Typically formed by C. albicans But Not by other species of Candida Serologic testing is Rarely helpful 28 Branching Budding Yeast Cells & Pseudohyphae in Urine Specimen 29  Pseudohyphae from Candida albicans Phase contrast images of C. albicans: (A) Budding Yeast in vaginal smear (10% KOH) (B) Germ Tube (100X) (C) Chlamydospores & Pseudohyphae (lactophenol cotton blue, 100X). 30  Candida reproduces by budding from a chain of connected spores called blastospores Blastospores can be elongated, ovoid, or spherical Candida albicans tends to have elongated blastospores (called Pseudohypha) with lateral out growths of blastospores forming off the pseudohypha It can be either white or an opaque light grey 31  Blastospores: o Considered the "typical yeast" form of Candida o Divide asexually by budding o Appear as single, rounded cells Pseudohyphae: o Elongated yeast cells connected in a chain with visible constrictions at the points where they budded off from each other o Often considered intermediate stage between blastospores & true hyphae Hyphae: o Long, tubular, branched filaments with no visible constrictions between cells o Considered the most invasive form of Candida, allowing for deeper tissue penetration 32 33 ❖ Macroscopic morphology Colonies on Sabouraud dextrose agar are white to cream, soft, & smooth to wrinkled ❖ Microscopic morphology On culture media following 72 hours incubation at 25°C: abundant branched pseudohyphae & true hyphae with blastoconidia are present Blastoconidia are formed in grape-like clusters along the length of hyphae Terminal chlamydoconidia may be formed with extended incubation 34 Candida albicans chlamydoconidia, grown on Candida albicans chlamydoconidia, cornmeal agar (with 10% tween) grown on cornmeal agar with 10% tween, Dalmau method 35 Candida albicans pure culture on Sabouraud & on Blood Agar Plates 36 Chrome Agar Plate showing different Candida species: (a) Candida albicans (b) C. dubliniensis (c) C. tropicalis (d) C. glabrata (e) C. krusei 37  Skin Tests with Candida antigens: Uniformly positive in immunocompetent adults & used as indicator that the person can mount cellular immune response A person who does not respond to Candida antigens in the Skin Test: is Presumed to Have Deficient Cell-Mediated Immunity Such a person is Anergic; other skin tests cannot be interpreted If a person has Negative Candida Skin Test: A negative Purified Protein Derivative (PPD) Skin Test for Tuberculosis could be a False-Negative Result 38  Treatment & Prevention Drug of choice for Oropharyngeal or Esophageal Thrush is Fluconazole Itraconazole & Voriconazole are also Effective Caspofungin or Micafungin can be used for Esophageal Candidiasis Treatment of Skin Infections consists of Topical Antifungal Drugs (e.g., Clotrimazole or Nystatin) Candida Vaginitis is treated either with Topical (Intravaginal) Azole Drugs (such as Clotrimazole or Miconazole, or with Oral Fluconazole Ketoconazole for controlling Mucocutaneous Candidiasis Amphotericin B or Fluconazole for treatment of Disseminated Candidiasis Liposomal Amphotericin B is used in patients with Preexisting Kidney Damage 39  These two drugs can be used with or without Flucytosine Treatment of Candidal Infections with Antifungal Drugs should be supplemented by reduction of predisposing factors Strains of C. albicans Resistant to Azole Drugs have Emerged in patients with AIDS receiving long-term prophylaxis with Fluconazole Certain Candidal Infections (e.g., Thrush) can be Prevented by Oral Clotrimazole Troches, Buccal Miconazole Tablets, or Nystatin “swish & swallow” Fluconazole is useful in Preventing Candidal Infections in High-Risk Patients (such as those undergoing bone marrow transplantation & premature infants) Micafungin can also be used There is No Vaccine 40 1. Candida 2. Cryptococcus 3. Aspergillus 4. Mucor & Rhizopus 5. Pneumocystis 6. Penicillium marneffei 7. Pseudallescheria boydii 8. Fusarium solani 41 2. Cryptococcus 42  Disease Cryptococcus neoformans causes Cryptococcosis Especially: Cryptococcal Meningitis Cryptococcosis is the most common, life-threatening invasive fungal disease worldwide ---- especially in AIDS patients Another species (Cryptococcus gattii) causes human disease less frequently than C. neoformans 43  Properties C. neoformans is oval, budding yeast surrounded by a wide polysaccharide capsule (see next slide) It is Not Dimorphic It forms a narrow-based bud --- (the yeast form of Blastomyces dermatitidis forms a broad-based bud) 44 45 46  Transmission C. neoformans occurs widely in nature & grows abundantly in soil containing bird droppings (especially pigeon) Birds are not infected Human infection results from inhalation of the organism No human-to-human transmission C. gattii is associated with eucalyptus trees (northwestern states of US) It is also found in subtropical and tropical areas of many countries 47  Pathogenesis & Clinical Findings Lung infection is often Asymptomatic Or may produce Pneumonia Disease caused by C. neoformans occurs mainly in patients with reduced cell- mediated immunity (especially AIDS patients) In AIDS patients, the organism disseminates to CNS (meningitis) & other organs Subcutaneous nodules are often seen in disseminated disease Roughly half the patients with cryptococcal meningitis fail to show evidence of immunosuppression 48  In some patients with AIDS who are infected with Cryptococcus : treating patient with Highly Active Antiretroviral Therapy (HAART) cause Exacerbation of Symptoms This phenomenon is called: Immune Reconstitution Inflammatory Syndrome Explanation: HAART increases the number of CD4 cells, which increases the inflammatory response Some patients Die as a result of cryptococcal IRIS To prevent IRIS: patients should be treated for the underlying infection before starting HAART C. gattii causes human disease less frequently but is more capable of causing disease in an immunocompetent person than C. neoformans C. gattii is more likely to cause Cryptococcomas (Granulomas) [especially in Brain] than C. neoformans 49  Cryptococcus Skin Lesions on Different Locations 50 Disseminated cryptococcosis as primary manifestation of HIV infection 51  Laboratory Diagnosis In CSF mixed with India ink: Yeasts are surrounded by wide, unstained capsule Appearance in Gram stain is unreliable. Stains such as Methenamine Silver, Periodic Acid–Schiff & Mucicarmine will allow the organism to be visualized It can be cultured from spinal fluid & other specimens Colonies are Highly Mucoid ---- b/c of large amount of capsular polysaccharide Serologic tests can be done for both antibody & antigen In infected spinal fluid: Capsular antigen occurs in High Titer & can be detected by Latex Particle Agglutination Test ---- Cryptococcal Antigen Test “crag” Distinguishing between C. neoformans & C. gattii in laboratory requires specialized media not generally available ---- So many C. gattii infections may go undiagnosed 52 India ink stain to reveal the polysaccharide capsule on yeast cells of AIDS-associated pathogen Cryptococcus neoformans India ink stain of CSF showing large polysaccharide capsule of Cryptococcus neoformans 53  C. neoformans has characteristic “Soap Bubble” CSF Gram stain with multiple encapsulated, appearance in tissue sections (Brain) due to rounded yeast forms surrounded by a halo, thick polysaccharide capsule surrounding thin- indicative of Cryptococcus neoformans walled yeast body (arrows) 54 - SDA without cycloheximide - Colony morphology are creamy & shiny, smooth, mucoid colony 55 Most Cryptococcus neoformans yeasts that proliferate by budding or division have a tubular form 56  Treatment & Prevention Combined treatment with Amphotericin B & Flucytosine is used in Meningitis & Other Disseminated Disease Liposomal Amphotericin B should be used in patients with Preexisting Kidney Damage No specific means of prevention Fluconazole is used in AIDS patients for long term suppression of cryptococcal meningitis C. gattii is less responsive to antifungal drugs than is C. neoformans 57 3. Aspergillus 58 59  The name Aspergillus is adapted from the Latin name Aspergillum, which means: holy water sprinkler (As the fungus has a sprinkler-like appearance when viewed under microscope) Aspergillus is a Genus of about 132 species (see table on next slide) Aspergillus niger is the most common species (popularly known as Black Mould) Few species of Aspergillus (such as A. flavus, A. niger & A. fumigatus) are human & animal pathogens (cause Aspergillosis [a group of lung diseases]) 60 61  Properties Aspergillus species exist only as Molds; they are Not Dimorphic Have Septate Hyphae that form V-shaped (Dichotomous) Branches (see next slide) Walls are more or less Parallel (in contrast to Mucor & Rhizopus walls which are Irregular) (see next slide) Conidia of Aspergillus form Radiating Chains (in contrast to those of Mucor & Rhizopus which are enclosed within a sporangium) (see next slide) Galactomannan antigen: is a polysaccharide found in the cell walls of fungi like Aspergillus & Penicillium. It can be detected in body fluids (such as blood & bronchoalveolar lavage) and is used to diagnose invasive aspergillosis 62 63  Transmission These molds are Widely Distributed in Nature Most of species are saprophytes, Grow on Decaying Vegetation, Fruits, Vegetables, Bread, Jams, Jellies, Butter, Leather, Fabrics, etc. producing Chains of Conidia Some species (e.g., A. fumigatus) can also grow on soil Transmission is by Airborne Conidia 64  Disease Aspergillus species (especially Aspergillus fumigatus) cause: o Infections of the Skin, Eyes, Ears & Other Organs o Fungus Ball in the Lungs o Allergic Bronchopulmonary Aspergillosis 65  Pathogenesis & Clinical Findings A. fumigatus can colonize & later invade Abraded Skin, Wounds, Burns, Cornea, External Ear, or Paranasal Sinuses A. fumigatus is the most common cause of Fungal Sinusitis In immunocompromised persons (especially those with Neutropenia): A. fumigatus can invade the Lungs & other Organs, producing Hemoptysis & Granulomas Neutropenic patients are also predisposed to Intravenous Catheter Infections caused by this organism In 2012, outbreak of A. fumigatus infections (especially Meningitis) occurred caused by injectable corticosteroid solutions that were contaminated with the fungus 66  Aspergilli are well-known for their ability to grow in cavities within the lungs, especially cavities caused by Tuberculosis Within cavities: they produce an Aspergilloma (Fungus Ball), which can be seen on Chest X-Ray (as a radiopaque structure that changes its position when patient is moved from an Erect to a Supine position) Allergic Bronchopulmonary Aspergillosis (ABPA): is a hypersensitivity reaction to presence of Aspergillus in the bronchi Patients with ABPA have: Asthmatic Symptoms & High IgE titer against Aspergillus antigens. They Expectorate Brownish Bronchial Plugs containing Hyphae Asthma also occurs (is caused by inhalation of airborne conidia especially in certain occupational settings) Aspergillus flavus growing on Cereals or Nuts produces Aflatoxins that may be Carcinogenic or Acutely Toxic 67  Clinical appearance of self-induced Aspergillus Otomycosis caused by Aspergillus flavus Left Lower Eyelid Aspergillosis infection (for the past 2 weeks) mimicking pyogenic granuloma in a 34-year-old pregnant woman Aspergillus Onychomycosis induced by trauma in a vegetable vendor patient caused by Aspergillus flavus 68 Primary Cutaneous Aspergillus ustus infection Aspergillus fumigatus 69 Primary Cutaneous Aspergillosis Caused by Aspergillus ochraceus 70 Nearly-Round Fungus Ball (white arrow) formed in a Prior Tuberculous Cavity (yellow arrows). Patient is Supine so the Aspergilloma has moved to the dependent portion of the cavity in which it formed Thin-Walled Upper Lobe Cavity (white arrows) presumably from old TB, with Fungus Ball in the dependent portion (black arrow) 71  Chest Radiograph of an Allergic Bronchopulmonary Aspergillosis patient shown with left-sided perihilar opacity (blue arrow) along with non-homogeneous infiltrates (transient pulmonary infiltrates indicated by red arrows) in all zones of both lung fields Conidiophore of the causative agent Aspergillus fumigatus 72  Laboratory Diagnosis Biopsy specimens show: Septate, Branching Hyphae Invading Tissue (see next slide) Cultures show: colonies with characteristic Radiating Chains of Conidia (see next slide) Positive cultures Do Not prove disease because colonization is common In Persons with Invasive Aspergillosis: there may be High Titers of Galactomannan antigen in serum Patients with Allergic Bronchopulmonary Aspergillosis: have High Levels of IgE specific for Aspergillus antigens & prominent Eosinophilia IgG Precipitins are also present 73 74 Aspergillus in tissue 75 Cytology on bronchoalveolar lavage: septate hyphae, suggestive for Aspergillus, and foamy macrophages 76 Colonies of Aspergillus showing characteristic Radiating Chains of Conidia seen microscopically 77  Aspergillus fumigatus Aspergillus flavus Aspergillus Aspergillus niger terreus Aspergillus versicolor78  Treatment & Prevention Invasive Aspergillosis is treated with Voriconazole or Amphotericin B Liposomal Amphotericin B should be used in patients with Preexisting Kidney Damage Caspofungin may be effective in cases of Invasive Aspergillosis that do not respond to Amphotericin B A Fungus Ball growing in sinus or in pulmonary cavity can be Surgically Removed Patients with Allergic Bronchopulmonary Aspergillosis can be treated with Corticosteroids & Antifungal Agents (such as Itraconazole) There are no specific means of prevention 79 4. Mucor & Rhizopus 80  Properties Mucormycosis (Zygomycosis, Phycomycosis) is a disease caused by saprophytic molds (e.g., Mucor, Rhizopus & Absidia) found widely in the environment They are Not Dimorphic Transmitted by Airborne Asexual Spores & invade tissues of patients with Reduced Host Defenses They Proliferate in the Walls of Blood Vessels, particularly of Paranasal Sinuses, Lungs, or Gut, and cause Infarction & Necrosis of tissue distal to the blocked vessel (see next slide) 81  Pathogenesis & Clinical Findings Patients with Diabetic Ketoacidosis, Burns, Bone Marrow Transplants, or Leukemia are Particularly Susceptible Diabetic patients are Particularly Susceptible to Rhinocerebral Mucormycosis (in which mold spores in sinuses germinate to form hyphae that invade blood vessels that supply the brain) One species (Rhizopus oryzae) causes about 60% of cases of Mucormycosis Complications: Death Prognosis: High mortality, Rapidly progressive 82  Characteristic hyphae from tissue specimen showing broad, irregularly branching & rare septations A 42 year-old female with diabetic ketoacidosis presented with Rhinocerebral Mucormycosis 83  A 50-year-old man with extensive burns over his arms, torso, and legs. Has uncontrolled diabetes. Has Black Eschar over his nares & palate, which reveals Non-Septate Hyphae Branching at Wide Angles indicating Mucor & Rhizopus spp. 84 COVID-19-Associated Mucormycosis (An Opportunistic Fungal Infection) A 63-year-old female presented with a recently developed deformation of her right cheek & nose combined with loosening of teeth. Further examination revealed Mucormycosis of the 85maxilla 86  Laboratory Diagnosis In Biopsy Specimens organisms are seen microscopically as: Non-Septate Hyphae with Broad, Irregular Walls & Branches that form at Right Angles (see next slides) Cultures: show colonies with Spores contained within a Sporangium (see next slide) These organisms are Difficult to Cultivate: because they are single & very long ---- therefore damage to any part of it can limit its ability to grow 87 88 89 90  H&E-stained specimen, revealed the presence of mycelial fungal filaments (Mucor) in tissue sample, from a patient with Mucormycosis 91 Growth of Mucor sp. From patient with Mucormycosis & COVID-19 92  Treatment & Prevention If diagnosis is made early: treatment of the underlying disorder & administration of Amphotericin B & Surgical Removal of Necrotic Infected Tissue ---- resulted in some Remissions & Cures Liposomal Amphotericin B should be used in patients with Preexisting Kidney Damage Posaconazole can also be used 93 6. Pneumocystis 94  Pneumocystis jiroveci is classified as a yeast on the basis of molecular analysis, but medically many still think of it as a Protozoan or as an “unclassified” organism In 2002, taxonomists renamed the human species of Pneumocystis as P. jiroveci They recommended that P. carinii be used only to describe the rat species of Pneumocystis 95  FUNGI OF MINOR IMPORTANCE 7. Penicillium marneffei 96  Penicillium marneffei is Dimorphic fungus that causes Tuberculosis-Like Disease in AIDS patients (particularly in Southeast Asian countries [Thailand]) It grows as Mold that produces Rose-Colored Pigment at 25°C At 37°C grows as Small Yeast that resembles Histoplasma capsulatum Bamboo rats are the only other known hosts Diagnosis is made either by growing the organism in culture or by using fluorescent antibody staining of affected tissue Treatment of choice: Amphotericin B for 2 weeks followed by Oral Itraconazole for 10 weeks Relapses can be prevented with prolonged administration of Oral Itraconazole 97  FUNGI OF MINOR IMPORTANCE 8. Pseudallescheria boydii 98  Pseudallescheria boydii is Mold that causes disease primarily in immunocompromised patients Clinical findings & Microscopic appearance of Septate Hyphae in Tissue closely resemble those of Aspergillus In culture: Appearance of Conidia (Pear-Shaped) & color of Mycelium (Brownish-Gray) are different from those of Aspergillus Drug of choice: is either Ketoconazole or Itraconazole (because response to Amphotericin B is poor) Debridement of necrotic tissue is important as well 99 FUNGI OF MINOR IMPORTANCE 9. Fusarium solani 100  Fusarium solani is Mold that causes disease primarily in neutropenic patients Fever & Skin Lesions are the most common clinical features It is similar to Aspergillus in that it is Mold with Septate Hyphae that tends to Invade Blood Vessels Blood cultures are often positive in disseminated disease In culture: Banana-Shaped Conidia are seen Drug of choice: Liposomal Amphotericin B Indwelling catheters should be removed or replaced In 2006, an outbreak of Fusarium keratitis (infection of the cornea) occurred in people who used certain contact lens solution 101 Questions? 102 Source of Lecture + Number of Web Pages & Research and Review Articles and Online Books 103