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

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