Medical Mycology (MLSM 507) Lecture Notes PDF

LECTURE NOTE ON: EPIDEMIOLOGY, PATHOLOGY, DIAGNOSIS & CONTROL OF SYSTEMIC MYCOSES By DR. DADA, M.O. (08033376440) E-mail: [email protected] DEPARTMENT OF MEDICAL LABORATORY SCIENCE SCHOOL OF PUBLIC & ALLIED...

LECTURE NOTE ON: EPIDEMIOLOGY, PATHOLOGY, DIAGNOSIS & CONTROL OF SYSTEMIC MYCOSES By DR. DADA, M.O. (08033376440) E-mail: [email protected] DEPARTMENT OF MEDICAL LABORATORY SCIENCE SCHOOL OF PUBLIC & ALLIED HEALTH  Mycosis (plural: mycoses) is a fungal infection of animals, including humans.  It is of mainly four types – 1. Superficial mycoses 2. Cutaneous mycoses 3. Subcutaneous mycoses 4. Systemic mycoses  Systemic mycoses are fungal infections affecting internal organs.  Fungi enter the body via lungs, through the gut, para- nasal sinuses or skin  Then spread via bloodstream to multiple organs including the skin  Can cause a tremendous variety of health problems including digestive difficulties, skin problems , asthma, breathing difficulties etc.  Often causing multiple organs to fail and eventually resulting in the death of the patient Systemic mycoses is of two types –  Systemic mycoses due to primary pathogens  Systemic mycoses due to opportunistic pathogens  Systemic mycoses due to primary pathogens  Originateprimarily in the lungs and may spread to many organ systems  Pathogens are dimorphic  Also known as endemic respiratory infections. These are mainly of 5 types  Histoplasma capsulatum (causing histoplasmosis)  Coccidioides immitis (causing coccidioidomycosis)  Blastomyces dermatitidis (causing blastomycosis)  Paracoccidioides brasiliensis (causing paracoccidiodomycosis)  Penicillium marneffei (causing penicilliosis)  Systemic granulomatous disease caused by a dimorphic fungus, Histoplasma capsulatum.  Species name is misnomer as it is not capsulated.  Attacking lungs, liver, spleen, bone marrow and occasionally kidneys, adrenals and intestines Symptoms- Fever, chills, headache, dry cough, chest discomfort, liver enlargement etc. Treatment- Antifungal drugs through vein depending on the stage of the disease  Transmitted by- inhalation of spores (i.e. microconidia) which usually circulate in the air after the contaminated soil is disturbed.  Spores enter into the lungs engulfed inside the alveolar macrophages transform into yeast forms.  Yeastssurvive within the phagolysosome of the macrophage by producing alkaline substances (bicarbonate and ammonia).  Specimens:  Sputum, aspirate from bone marrow & lymph node, blood and biopsies from skin & mucosa.  Direct microscopy:  Histopathological staining (PAS, Giemsa or GMS stain) – Shows tiny oval yeast cells (2-4 µm size) with narrow based budding within macrophages with an underlying granulomatous response.  Culture:  Gold standard method of diagnosis.  Media- SDA, blood agar and BHI agar  Incubated simultaneously at 25°C and 37°C.  At 25°C:  Mycelial phase  Produces white to buff brown colonies, consist of 2 types of conidia or spores: 1) Tuberculate macroconidia- typical thick walls and finger-like projections which is a characteristic feature 2) Microconidia are smaller, thin, and smooth-walled.   At 37°C:  Gets converted into yeast form (creamy white colonies), which is best developed in special media like Kelley's media.  Serology:  Antibodies in serum - detected by CFT and imununodiffusion test.  Antibodies appear after 1 month of infection; hence are more useful in chronic stage (often negative in early course and in disseminated stage).  False positive result may occur due to past infection or cross infection with blastomyces. Skin test:  May be done to demonstrate delayed type hypersensitivity response to histoplasmin antigen, which indicates prior exposure  Also called desert rheumatism or Valley fever or California fever  Is a systemic fungal disease caused by a dimorphic soil dwelling fungus- Coccidioides (C. immitis and C. posadasii).  It may occur as either an acute, benign, self-limited disease or a chronic, malignant disseminated disease Symptoms- Rashes, myalgia, shortness of breath, weight loss, night sweats, influenza etc. Treatment-  Fluconazole & intravenous amphotericin B  Itraconazole or ketoconazole are used for immucompromised patients  Transmitted by inhalation of arthroconidia.  In lungs, they enlarge, become rounded, and develop internal septations to form large sac like structures of size up 10-200 µm called spherules- encompass numerous endospores.  Spherulesmay rupture and release packets of endospores that can disseminate and develop into new spherules.  Ifspherules returned to artificial media or soil, they revert back to the mycelial stage.  Histopathological staining H and E stain, PAS or CMS of sputum or tissue biopsy specimens demonstrates spherules which are large sac like structures (20-80 µm size), have thick, double refractile wall, and are filled with endospores Cultures on SDA –  produces mycelial growth, described as fragmented hyphae consisting of barrel-shaped arthrospores with alternate cells distorted (empty cells)  Coccidioides differs from other dimorphic fungi as it grows as mold at both 25°C and 37°C in usual culture media (forms spherules at 37°C in certain special culture media only).  Cultures are highly infectious: lead to accidental inhalation of spores in laboratories, require biosafety level-3 precautions.  Serology: Antibodies are detected by immunodiffusion test and CFT.  Skin test: It is done by fungal extaracts (coccidioidin or spherulin);  produces at least a 5 mm induration within 48 hours after injection (delayed hypersensitivity reaction) indicates past infection.  Also known as North American blastomycosis or Gilchrist's disease or Chicago disease  Is a fungal infection of humans and other animals also- dogs and cats, caused, Blastomyces dermatitidis.  Lung infection can occur after a person inhales airborne, microscopic fungal infection from environment Symptoms- Fever, chills, cough, muscle ache, joint pain, chest pain etc. Treatment-  Initial phase-  Oral Ketoconazole  Itraconazole  Life threatening infections-  AMB(Amphotericin B)  Transmitted by  Inhalation of the conidia of B. dermatitidis.  Spores enter into the lungs, and are engulfed by alveolar macrophages, where they get converted into yeast phase.   This yeast expresses a 120-kDa glycoprotein called BAD-I (B. dermatitidis adhesin-1) which is an essential virulence factor and also a major inducer of cellular and humoral immune responses.  Antibody detection: lmmunodiffusion test specific for B. dermatitidis has been developed against yeast phase antigens such as antigen-A, BAD- I and ASWS antigen (alkali soluble water soluble).  Antigendetection assay- detect Blastomyces antigen in urine (more sensitive) and in serum is commercially available.  Molecularmethods- DNA probe hybridization and real time PCR  Histopathologicalstaining of the tissue biopsy specimens reveals thick-walled round yeast cells of 8- 15 µm size with single broad-based budding  Culture media - SDA, blood agar and BH I.  At 250C- Mycelia form containing hyphae with small pear-shaped conidia are produced;  At 370C- mold to yeast conversion takes place.  Skin test: done to demonstrate delayed type hypersensitivity to blastomycin antigen.  Also known as South American blastomycosis, Lutz- Splendore-de Almeida disease  Is a systemic disease caused by the dimorphic fungus Paracoccidioides brasiliensis.  Acute or chronic, granulomatous infection primarily of lungs & disseminates to skin, mucosa & other internal organs Symptoms- Acute pneumonia Treatment-  Long term therapy  AMB combined with sulfonamides  Oral Itraconazole  Histopathological staining - of pus, tissue biopsies or sputum  revealsround thick-walled yeasts, which multiple narrow- necked buds attached circumferencially giving rise to Mickeiy mouse or pilot wheel appearance.  Culture on SDA  yields mycelial form at 250C  converts in to yeast phase at 370C when grown in BHI agar supplemented with blood and glutamine.  Serology:  Antibodiesare detected by immunodiffusion, and by ELISA, using gp43 antigen of P. brasiliensis.  Skin test:  demonstrates delayed hypersensitivity response against paracoccidioidin antigen. A. Schematic representation of mycelial and yeast forms; B. Methenamine silver staining shows yeast from (pilot wheel appearance)  Caused by Penicillium marnefferei  Persons affected by penicilliosis usually have aids with low cd4 lymphocyte counts Symptoms- Fever, skin lesions, anaemia, lymphadenopathy etc. Treatment-  Ketoconazole  Itraconazole  Miconazole  Flucytosine  Amphotericin B  Systemic  Fungi that only result in systemic infection in immune- compromised or sick people  Examples of immune compromised conditions include AIDS, alteration of normal flora by antibiotics, immunosuppressive therapy, and metastatic cancer  Its main types are-  Candida species (causing candidiasis)  Aspergillus species (causing aspergillosis)  Cryptococcus (causing cryptococcosis)  Zygomycetes (causing zygomycosis)  Caused by yeast- like fungi of genus candida i.e. Candida albicans  It is of 2 types- Infectious and Allergic Symptoms- depend on area affected, some common symptoms are redness, itching and discomfort etc. Treatment- Antifungal drugs include-  Topical clotrimazole  Topical nystatin  Fuconazole  Topical ketoconazole Fig.- oral candidiasis  caused by Aspergillus fumigatus  Aspergillus has the tendency to invade blood vessels Symptoms- superficial lesions, coughing up of blood,cheast pain, etc. Treatment-  Voriconazole  liposomal amphotericin B  Caused by Cryptococcus neoformans  It is an encapsulated yeast and is present in soil and bird (especially pigeon) droppings Symptoms- pneumonia like illness, shortness of breath, skin lesions may occur, fever, cough etc. Treatment-  Intravenous combined with flucytosine  Amphotericin B and flucytosine  Fluconazole with amphotericin  Zygomycosis (also called Mucomycosis) is a generic term which refers to infections of the class Zygomycetes (also called Phycomycetes) Symptoms- Facial swelling, bulging eye,headache,blurred & double vision, bleeding from nose etc. Treatment-  Antifungal agents  amphotericin B  Fungizone,amphocine,ambisome  Liposomal amphotericin B  ablecet Immune compromised people are at risk of systemic mycoses. Immunodeficiency can result from:  Human immunodeficiency virus(HIV) infection  Systemic malignancy (cancer)  Neutropaenia (low white blood cell count)  Organ transplant recipients  After a major surgical operation  Poorly controlled diabetes mellitus  Very old or very young  The most reliable tests to confirm infection are skin biopsy for histological (microscopic) analysis, and fungal culture.  Blood can also be cultured. Fig :- culture of Histoplasma capsulatum (histoplasmosis)  Fungal infections are diseases caused by fungi. Only about 180 types of fungi on the existing 1,00,000 are pathogenic for humans.  Itching, unsightly staining of certain areas of the skin, burning, mainly mucosal are the common symptoms  As fungal infections are very stubborn, several preparations, which specifically inhibit the proliferation of fungi, are available to treat fungal infections.  Depending on the location of the infection, local preparations in the form of creams or sprays are used. For the systemic treatment, tablets are used. o Systemic Mycoses: An Overview for Modern Natural Health Professionals By R. Thiel, Ph.D., Nutrition Scientist and Clinical Naturopath o MYCOLOGY - CHAPTER SEVEN,OPPORTUNISTIC MYCOSES,by Dr. Art DiSalvo o Fitzpatrick's Dermatology in General Medicine, 6th Edition o DermNetNZ.com o Patient.co.uk o http://www.healthresearch.com o www.wikipedia.com for mycoses,penicilliosi,aspergilliosis,candidiasis,coccidiodomyc oses,cryptococcosis,zygomycosis. o www.rightdiagnosis.com o www.nytimes.com Thank you