& VIRAL EYE PATHOGENS

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1 FUNGAL, MYCOBACTERIAL, & VIRAL EYE PATHOGENS Dr. WILLIAM J. BENJAMIN Eye Physiology & Ocular Prosthetics Laboratory University of Alabama at Birmingham School of Optometry Presented at the UAB School of Optometry as Part of OPT 121: MICROBIOLOGY and IMMUNOLOGY November 20, 2009

2 FUNGI, MYCOBACTERIA, AND VIRUSES FUNGI: YEASTS & MOLDS ACTINOMYCETES MYCOBACTERIA NOCARDIA VIRUSES

3 FUNGI THAT COMMONLY INVADE OCULAR TISSUES YEASTS Candida albicans & Other Species Pityrosporum ovale & orbicularis now Malassezia furfur MOLDS Histoplasma capsulatum Cryptococcus neoformins Fusarium solani & Other Species Aspergillus fumigatus

4 FUNGI THAT COMMONLY INVADE OCULAR TISSUES YEASTS Candida albicans

5 FUNGI THAT COMMONLY INVADE OCULAR TISSUES YEASTS Candida albicans Malassezia furfur (Pityrosporum ovale)

6 FUNGI THAT COMMONLY INVADE OCULAR TISSUES MOLDS

7 ETIOLOGY OF OCULAR FUNGAL INFECTIONS VEGETABLE MATTER TRAUMA IMMUNOSUPPRESSION CHRONIC USE OF STEROIDS ANTIBACTERIALS SECONDARY INFECTION SUPERINFECTION

8 TYPES OF INFECTION PRIMARY INFECTION: Original invasion and multiplication of microorganisms in body tissues, resulting in local cellular injury due to competitive metabolism, toxins, intracellular replication, or immunological response. SECONDARY INFECTION: Opportunistic infection by a microorganism following a primary infection by a different microorganism, located at the same site. SUPERINFECTION: Opportunistic infection of microorganism resistant to the antimicrobial agent used for the primary infection, located at the same site or a remote site.

9 CLASSES OF TOPICAL ANTIFUNGAL MEDICATIONS POLYENES: Act on Cell Membranes Natamycin: Topical Drug of Choice Nystatin Amphotericin B: Most Use Systemic IMIDAZOLES: Act on Cell Membranes Thiabendazole Ketoconazole Miconazole Econazole Clotrimazole PYRIMIDINES: Act on Protein Synthesis Flucytosine

10 CHARACTERISTICS OF TREATMENT OF FUNGAL INFECTIONS FUNGAL INFECTIONS SLOW TO PROGRESS At early stage, may not be recognized as fungal Antibacterial may have a limited antifungal effect Fungal infection typically gets slightly better, but POOR PENETRATION OF ANTIFUNGALS Natamycin: The only antifungal available in an ophthalmic preparation Amphotericin B: Tertiary sites mix up their own NORMAL OCULAR DEFENSES NECESSARY

11 CHARACTERISTICS OF TREATMENT OF FUNGAL INFECTIONS SLOW IMPROVEMENT WITH THERAPY PROLONGED THERAPY NECESSARY TOXICITY TO DRUGS COMMON RESISTANT STRAINS DEVELOP CORTICOSTEROIDS CONTRAINDICATED Must be wary at early stage if steroids are used, before infection is suspected fungal

12 MICROBIOLOGICAL DIAGNOSIS OF FUNGAL INFECTIONS CLINICAL PRESENTATION OCULAR SURFACE CYTOLOGY: PMNs

13 MICROBIOLOGICAL DIAGNOSIS OF FUNGAL INFECTIONS STAINING: GIEMSA,PAS,METHYLENE BLUE Yeasts vs. Molds: Morphology CULTURE ON STERILE GROWTH MEDIA Yeasts Grow on Blood Agar Molds Require Sabouraud s Agar (with Antibacterial?)

14 MICROBIOLOGICAL DIAGNOSIS OF FUNGAL INFECTIONS CULTURE ON STERILE GROWTH MEDIA Alternaria sp.

15 MICROBIOLOGICAL DIAGNOSIS OF FUNGAL INFECTIONS CULTURE ON STERILE GROWTH MEDIA Aspergillus niger

16 MYCOBACTERIA EYE PATHOGENS MOLD-LIKE BACTERIA: LID GRANULOMAS Mycobacterium leprae Mycobacterium tuberculosis MOLD-LIKE LIKE BACTERIA: KERATITIS / ULCER Mycobacterium fortuitum Mycobacterium chelonei NOCARDIA sp. (Actinomycete) Mycobacterium tuberculosis

17 MYCOBACTERIA EYE PATHOGENS Nocardia sp.

18 MYCOBACTERIA EYE PATHOGENS Mycobacterium tuberculosis Nocardia sp.

19 MICROBIOLOGICAL DIAGNOSIS OF MYCOBACTERIAL INFECTION CLINICAL PRESENTATION OCULAR SURFACE CYTOLOGY: PMNs STAINS: ACID-FAST STAIN, SEVERAL OTHERS OF ATYPICAL TYPE CULTURE ON STERILE GROWTH MEDIA Lowenstein-Jenson Agar

20 VIRUSES ANATOMICAL CHARACTERISTICS DNA and RNA Viruses RETROVIRUS: RNA Virus with REVERSE VIRAL INFECTION TRANSCRIPTASE VIRULENCE LATENCY INTRACELLULAR PARASITE TISSUE TROPISM COMMUNICABILITY / INFECTIOUSNESS ANTIVIRAL MEDICATIONS

21 VIRUSES ANATOMICAL CHARACTERISTICS DNA and RNA Viruses RETROVIRUS: RNA Virus with REVERSE TRANSCRIPTASE

22 5 STEPS TO VIRAL INFECTION ATTACHMENT TO THE CELL UNCOATING REPLICATION OF RNA / DNA AND PROTEIN ASSEMBLY: VIRAL INCLUSIONS EXIT FROM CELL CELL LYSIS BUDDING, OR EXOCYTOSIS

23 5 STEPS TO VIRAL INFECTION

24 VIRAL AFFINITY FOR TISSUES (TISSUE TROPISM) HEPATITIS B VIRUS POLIO VIRUS MYXOVIRUSES VARIOUS VIRUSES LIVER NEUROMUSCULAR JUNCTIONS RESPIRATORY SYSTEM (FLU) BRAIN (ENCEPHALITIS)

25 VIRAL AFFINITY FOR TISSUES (TISSUE TROPISM) AIDS / HIV VIRUS T4 LYMPHOCYTES

26 VIRAL TRANSMISSION IN THE OFFICE MANY TYPES OF VIRUSES IN TEAR FLUID, THOUGH IN LOW CONCENTRATIONS DIRECT vs. INDIRECT CONTACT KILL = INACTIVATE (?) METHODS OF CONTROL CHLORINE BLEACH 70% ISOPROPYL ALCOHOL HYDROGEN PEROXIDE HEAT TREATMENT TONOCOVERS AND DISPOSABLE CLs

27 COMMUNICABILITY OF ENVELOPED VIRUSES DISRUPTION OF ENVELOPE GENERALLY INACTIVATES THE VIRUS KILLED BY COLD, HEAT, DRYING, ph, OSMOLARITY / TONICITY REQUIRE MORE DIRECT CONTACT NOT GENERALLY CONTAGIOUS EXAMPLES: Herpes simplex & zoster Hepatitis B AIDS / HIV Virus

28 COMMUNICABILITY OF NON- ENVELOPED VIRUSES NO ENVELOPE TO DISRUPT NOT AS MUCH AFFECTED BY COLD, HEAT, DRYING, ph, OSMOLARITY, ETC. CAN EASILY SPREAD INDIRECTLY GENERALLY VERY CONTAGIOUS EXAMPLES: Polio Virus Adenovirus Types 8 & 19 (EKC- Pink Eye) Enterovirus 70 & Coxsackie Virus A24

29 MULTIPLICITY OF INFECTION HOW MANY VIRUSES TO GET INFECTION? CAN YOU GET AIDS FROM SINGLE VIRUS? CAN YOU GET AIDS FROM TEAR FLUID? BARRIERS & DEFENSES NECESSARY OTHER CONDITIONS VERY FEW VIRUSES, RECEPTOR CELLS IN TEAR FLUID BEST GUESS: HUNDREDS OR THOUSAND +

30 THEORY OF ANTIVIRAL MEDICATIONS & AGENTS INTERFERE WITH 1 / 5 STEPS TO INFECTION MULTIPLE DRUG THERAPY FUNCTIONAL ONLY WHEN VIRUS IS REPLI- CATING, NOT WHEN DORMANT OR LATENT. MOST DRUG THERAPY IS BASED ON THE FACT THAT THE MICROORGANISM GROWS FASTER THAN THE HOST.

31 ANTIVIRAL MEDICATIONS & AGENTS BLOCK ATTACHMENT TO CELL Amantidine IgA BLOCK PROTEIN SYNTHESIS Interferon

32 ANTIVIRAL MEDICATIONS & AGENTS BLOCK RNA / DNA REPLICATION Idoxuridine: The 1 st Anti-Viral, Now Obsolete, Initially developed as topical ophthalmic drop Vidaribine (Vira-A): 2nd, Also Obsolete Trifluridine (Viroptic): Topical Drug of Choice for Herpes simplex keratitis Acyclovir Ganciclovir Zidovudine (AZT) BASICALLY, THESE ARE ALL DEFECTIVE NUCLEIC ACIDS

33 LARGE VIRUSES CAPSID HAS SPACE FOR MORE RNA / DNA LESS DEPENDENT ON HOST CELL MACHINERY FOR FUNCTION LESS DISGUISED WITHIN HOST CELL ANTIVIRALS CAN BE DESIGNED TO ATTACK VIRUS DIRECTLY EXAMPLES: POX VIRUSES Variola: Smallpox Vaccinia: Cowpox

34 SMALL VIRUSES CAPSID HAS LITTLE SPACE FOR RNA / DNA MORE DEPENDENT ON HOST CELL MACHINERY FOR FUNCTION MORE DISGUISED WITHIN THE HOST CELL DIFFICULT TO DESIGN ANTIVIRALS TO ATTACK VIRUS EXAMPLES: ADENOVIRUSES

35 WHY VIRUSES ARE POTENTIALLY THE SCARIEST SPREAD OF NON-ENVELOPED VIRUSES LATENCY OR DORMANCY TROPISM FOR HOST DEFENSE SYSTEM DISGUISE OF SMALL VIRUSES IN HOST RAPID ABILITY TO MUTATE COMPARE TO SPORE- & CYST-FORMERS

36 EYE VIRUSES ADENOVIRUSES: NOSE & THROAT (EKC) ACUTE HEMHORRHAGIC CONJUNCTIVITIS ENTEROVIRUS 70 COXSACKIE VIRUS A24 MOLLUSCUM CONTAGIOSUM (a POX) VIRUS VERRUCAE VIRUS (WARTS) HUMAN PAPILLOMA VIRUS HERPES AND HERPES-LIKE VIRUSES

37 EYE VIRUSES ADENOVIRUSES: NOSE & THROAT EKC: PINK EYE ACUTE HEMHORRHAGIC CONJUNCTIVITIS ENTEROVIRUS 70 COXSACKIE VIRUS A24

38 EYE VIRUSES MOLLUSCUM CONTAGIOSUM: AN UNCLASSIFIED POX VIRUS VERRUCAE VIRUS (WARTS) VERRUCAE VIRUS (WARTS) HUMAN PAPILLOMA VIRUS HERPES AND HERPES-LIKE VIRUSES

39 HERPES SIMPLEX VIRUS HSV-1 = Oral; HSV-2 = Genital TRIGEMINAL & CERVICAL GANGLIA SINGLE STRAIN OF HSV-1 PER INDIVIDUAL STRAINS PREFER DIFFERENT TEMP. (33 C) STRAINS PREFER DIFFERENT SITES SHAPE, SIZE OF DENDRITIC ULCER IS RELATED TO THE STRAIN

40 HERPES SIMPLEX VIRUS TRIGGERS: Fever, Trauma, Stress, etc. RECURRENCES: EACH CAUSES PERMAN- ENT STRUCTURAL DAMAGE Herpes-like Dendritic Corneal Ulceration

41 OTHER HERPES-LIKE EYE VIRUSES CAN CAUSE SIMILAR EYE INFECTIONS Herpes-like Dendritic Corneal Ulceration

42 OTHER HERPES-LIKE EYE VIRUSES EPSTEIN-BARR VIRUS: Mononucleosis CYTOMEGALOVIRUS: Only in Immunoc. POX VIRUSES: Variola & Vaccinia VARICELLA / ZOSTER VIRUS (VZV) Trigeminal Ganglion Latency Chicken Pox = Varicella Shingles = Zoster Herpes zoster Ophthalmicus Thus, characteristic infections are called, Herpes-like or Presumed Herpes

43 MICROBIOLOGICAL DIAGNOSIS OF VIRAL INFECTIONS CLINICAL PRESENTATION OCULAR SURFACE CYTOLOGY MONONUCLEAR CELLS Lymphocytes & Monocytes Presumed Herpes Keratitis with Immune Ring

44 MICROBIOLOGICAL DIAGNOSIS OF VIRAL INFECTIONS STAINS: PAPANICOLAOU (PAP) VIRAL INCLUSIONS: Nuclear, Visible with Trans. Electron Microscopy TISSUE CULTURE: UNRELIABLE