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  • Farida Jamal Department of Medical Microbiology & Parasitology

    FPSK UPM August 2013

  • Superficial/Deep/Systemic

    Localized/Spreading

    Invasive Mycoses

    Endemic : exogenous agents

    Opportunistic: exogenous & endogenous

  • Increase in Cases of Invasive Mycoses Worldwide

  • Increase in population at risk and longer survival:

    Malignancies

    Transplants

    Extremes of age

    Major surgery

    HIV

    Increased exposure to endemic fungal infections:

    Travel

    Climate

    Shifting population

  • Invasive candidiasis: >1996 to 2003

    Europe, USA, Canada

    Candida species :Fourth leading cause of nosocomial blood stream infection (BSI)

    Temporal & geographical variation in

    species distribution, resistance

    M.A.Pfaller D.J. Diekema Epidemiology of invasive candidiasis: A persistent

    public health problem Clinical Microbiology Reviews 2007 20(1) 133-163

  • Increasing demand for laboratory support

    Increase in use of antifungals

    Formulation of new and more effective antifungal agents

    Research & documentation

    Improved understanding of fungal pathogenesis

  • Increase in Types of Fungal Species Implicated

  • Past

    Candida , Aspergillus, Cryptococcus

    Pneumocystis jiroveci

    Current

    Additional , previously unrecognized opportunistic pathogens

    Yeasts, other than candida

    Nondematiaceous/hyaline molds

    Pigmented or dematiaceous molds

    Dermatophytes

  • Histoplasma capsulatum

    Blastomyces dermatitidis

    Paracoccidioides brasiliensis

    Coccidioides immitis

    Penicillium marnifii

  • Better Diagnostic Techniques

  • Clinical examination

    Skin tests

    Radiology

    Histopathology

    Microbiology

    Serology

    Molecular & genetic methods

  • Level & type of diagnostic service

    Assessment of institutional needs

    Assessment of type of practice & patient population

    Melinda B. Nye Melodie A. Beard Barbara A. Body Diagnostic mycology :

    controversies & consensus What shuld Laboratories do ? Part I Clinical microbiology Newsletter 2006 28(16) 121-127

    Melinda B. Nye Melodie A. Beard Barbara A. Body Diagnostic mycology : controversies & consensus What shuld Laboratories do ? Part II Clinical microbiology Newsletter 2006 28(17) 129-134

  • Systemic fungal infections: Beta D glucan

    Cryptococcus neoformans : antigen & antibody to capsular antigen

    Candida : antigen & antibody to mannan

    Aspergillus : Galactomannan

  • Sequencing

    Identification of:

    Yeasts

    Filamentous fungi

    Dermatophytes

    Detection of resistance genes

  • Yeasts, yeast like fungus in tissue

    Blastomyces

    Cryptococcus

    Histoplasma

    Coccidioido immitis

    Candida

    Hyphae in tissue

    Aspergillus, mucor fusarium

    Bipolaris/curvularia

    Dermatophytes

  • Histochemical staining

    Immunohistochemistry

    In situ hybridization

    PCR-Based Methods

    Laser based micro dissection

    Jeannette Guarner and Mary E. Brandt Histopathologic diagnosis of fungal

    infections in the 21st century Clinical microbiology Reviews 2011, 24(2):247.DOI:10.1128/CMR.00053-10

  • Radiological diagnosis

    Advances in diagnostic & treatment radiology

    Greater ability to collect tissue biopsy material for laboratory investigation.

  • Increase in Number and Use of Antifungal Agents

  • Allylamines: Terbinafine

    Antimetbolites: Flucytosine

    Azoles : Clotrimazole, Fluconazole, Ketoconazole, Itraconazole, Voriconazole

    Echinocandins

    Polyenes: Amphotericin B, Nystatin

    Others: Griseofulvin, Tolnaftate, etc.

  • Recently developed & standardized

    Performed in referral centres & special

    laboratories

    Expensive

    Not routine in small labs

    How do doctors select antifungal agents for treatment?

  • Early treatment:

    Better prognosis, chance of recovery

    Improved diagnostic techniques

    Rapid, accurate diagnosis

    Antifungal sensitivity testing

    Need for empirical antifungal therapy?

    J. Peter Donnelly, Johan Maertens The end of road for empirical

    antifungal treatment ? www.thelancet.com/infection 2013 13:470-471

    http://www.thelancet.com/infection

  • Singh H., Jamal F., Marhakim M.N. Song C.C. Fusarium solani keratitis: First report from Malaysia. Malaysian Medical Journal. 1980; 2: 89-91.

    Phelim Y.V.C, Chong P.P, Lau L.Y, Yeoh S.C.R, Jamal F. Report on Molecular Identification of Candida orthopsilosis isolated from blood culture. Mycopathologica. 2008; 165: 81-87

    Madhavan P. , Jamal F., Chong P. P , Ng K.P. In vitro activity of fluconazole and voriconazole against clinical isolates of Candida spp by E-test method . Tropical Biomedicine 2010; 27(2) 200-207

  • Management of fungal infections: The way forward

  • Mycology consultation service

    Advice on antifungal therapy

    Rapid, accurate diagnosis

    Team Work

    Follow up on outcome

    Research & training

  • Utilization of new diagnostic tools

    Communication with laboratory staff

    Development of consensus guidelines

    Implementation of the above

  • Improved Understanding of Fungal Pathogenesis

  • Limitations of antifungal therapy

    Resistance of emerging fungal pathogens to existing agents

    Difficulty in rapid and accurate diagnosis

    Antonio Cassone Fungal Vaccines: Real progress from real challenges

    Lancet Infectious Disease 2008; 8: 114-124

  • Jeannette Guarner and Mary E. Brandt Histopathologic diagnosis of fungal infections in the 21st century Clinical microbiology Reviews 2011, 24(2):247.DOI:10.1128/CMR.00053-10

    John R. Perfect Fungal Diagnosis: how do we do it and can we do it better Current Medical Research and Opinion 2013 29(4) 3-11

    J. Peter Donnelly, Johan Maertens The end of road for empirical antifungal treatment ? www.thelancet.com/infection 2013 13:470-471

    Melinda B. Nye Melodie A. Beard Barbara A. Body Diagnostic mycology : controversies & consensus What shuld Laboratories do ? Part I Clinical microbiology Newsletter 2006 28(16) 121-127

    Melinda B. Nye Melodie A. Beard Barbara A. Body Diagnostic mycology : controversies & consensus What shuld Laboratories do ? Part II Clinical microbiology Newsletter 2006 28(17) 129-134

    M.A.Pfaller D.J. Diekema Epidemiology of invasive candidiasis: A persistent public health problem Clinical Microbiology Reviews 2007 20(1) 133-163

    Antonio Cassone Fungal Vaccines: real progress from real challenges Lancet Infectious Disease 2008; 8: 114-124

    http://www.thelancet.com/infection