Herpes Viruses - 2013 (FN)

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    HERPES VIRUSES

    Dr F Noordeen

    Department of Microbiology

    Faculty of Medicine

    Peradeniya

    April 2013

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    Mechanisms by which herpes viruses cause

    disease in humans

    Host defenses against viruses

    Main clinical features of viral infections/disease

    Principles of diagnosis treatment and prevention

    viral infections/disease in humans

    Learning outcomes

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    EM of a Herpes Virus

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    CLASSIFICATION

    Genome - DNA Viruses

    Morphology - Icosahedral

    - Large baggy envelope

    Enzymes - DNA polymerase

    - HSV & VZV thymidine kinase

    Reproduction - Nucleus of host cell

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    CLASSIFICATION

    Alphaherpesvirinae

    Herpes Simplex Virus type 1 HSV-1

    Herpes Simplex Virus type 2 HSV-2

    Varicella-Zoster Virus VZV

    Betaherpesvirinae

    Cytomegalovirus CMV

    Human Herpesvirus type 6 HHV- 6

    Human Herpesvirus type 7 HHV- 7

    Human Herpesvirus type 8 HHV- 8

    Gammaherpesvirinae

    Epstein-Barr virus EBV

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    HERPES SIMPLEX VIRUS

    Primary infection - Contact with HSV

    Latent infection - Virus persists in root ganglia

    Reactivation - Production of infective virus

    by latently infected cell

    Recurrence - Clinical disease produced

    by reactivation

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    Pathogenesis

    Entry by skin or mucous membranes

    viral multiplication sensory nerve

    lysis of cells root ganglia

    vesicles latency

    ulcersREACTIVATION

    ColdFever

    Surgery

    Unknown

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    Stomatitis with secondary skin lesions

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    Primary infection of the skin

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    Recurrent

    infection

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    Herpetic infection of the eye

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    Herpetic whitlowHerpetic whitlow

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    Vulvovaginitis in child

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    Genital herpes inan adult male

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    Genital herpes inan adult female

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    Genital herpes in

    adult female(Herpetic cervicitis)

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    Epidemiology

    Childhood infections common

    Second peak at onset of sexual activity

    Viral shedding/reservoirs

    persons with recurrences infected but asymptomatic persons

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    Laboratory diagnosis

    Useful

    Genital & eye infections

    HVZ & HSV in immunocompromised

    Herpes encephalitis

    Specimens

    Aspirate from vesicle

    Scraping from base of ulcer

    Serum/CSF for antibody

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    Laboratory diagnosis

    1. Microscopy

    - Light - giant cells & inclusions

    - Electron microscopy

    2. Antigen detection - ELISA and IFT

    3. Virus culture & identification

    4. DNA detection - PCR (Encephalitis)

    5. Antibody detection - ELISA and IFT

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    Treatment for HSV infections

    1. Acyclovir : Topical and oral formulations

    2. Idoxyuridine

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    HERPES VARICELLA ZOSTER - HVZ

    Chicken pox - Fever + characteristic rash

    Variable incubation period 14-21 days

    Usually mild in children and more severe in adults

    Complications

    Secondary infection - uncommon

    Varicella pneumonia

    Secondary bacterial pneumonia S aureus & pneumococci

    Post-infectious encephalitis

    Generalised varicella (in immunocompromised patients)

    Congenital and neonatal varicella

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    Varicella rash in child

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    Varicella vesicleson palate

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    Varicella vesicles

    on conjunctiva

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    HERPES ZOSTER

    Reactivation of VZV

    Dermatomal distribution and may recur

    Can disseminate in immunocompromised

    patients

    Complications

    Post herpetic pain

    Ophthalmic zoster - corneal scarring and loss of vision

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    Diagnosis of Zoster

    Clinical features and lesion distribution

    EM/IFA of vesicle fluid

    Serology - IgM detection

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    Skin supplied by cervical roots 4 & 5 are affected

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    Thoracic segments are affected

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    Prevention of chicken pox

    Children & adults living in close proximity

    Do nothing Immunise with

    live attenuated

    vaccine

    Protect contact

    with patient with

    chickenpox and

    at risk of severe

    disease

    Zoster Immuno

    Globulin (ZIG)

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    EPSTEIN-BARR VIRUS - EBV

    Discovered in 1964 by Epstein and Barr

    Definite association with malignancy

    Is able to transform cells resulting inimmortalisation of cells

    2 types of virus A & B which may co-exist

    in a same person

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    Infectious mononucleosis

    Affects adolescents and young adults

    Worldwide distribution

    Called kissing disease

    IP - one month

    Presents with fever,

    sore throat, rash and swollen lymph nodes

    DIAGNOSIS

    Raised WBC with >20% lymphocytes

    Paul-Bunnell test (heterophil antibodies) or mono spot

    DIAGNOSIS

    Raised WBC with >20% lymphocytes

    Paul-Bunnell test (heterophil antibodies) or mono spot

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    Blood film with abnormal

    mononuclear cells

    1st week - normal/raised

    neutropenia

    2nd week - leukoctosis with

    (lymphoctosis)

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    EnanthumEnanthum -- Rashes on the palateRashes on the palate

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    Inflamed throat

    without exudate

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    Follicular

    exudate

    Patches of

    white exudate

    Patch of

    white exudate

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    Syndromes caused by EBV

    Burkitts lymphoma Children 4-12 years

    Subsaharan Africa and New Guinea

    Nasopharyngeal carcinoma Adults 20-50 years old

    Southern China

    B cell lymphoma

    Children and adults

    Primary immunodeficiency

    Patients with AIDS

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    BURKITTS LYMPHOMA

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    NASOPHARYNGEAL CARCINOMA

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    Cytomegalovirus infections

    Ubiquitous virus

    Most populations - infections in early childhood

    Often asymtomatic

    Latency

    Clinical disease increasing due to increasing

    number of immunocompromised patients

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    Cytomegalovirus infections

    Foetal infection Transmission from mother via placenta

    Clinically normal 80%

    Causes congenital CMV

    Death 1%

    Cytomegalic inclusion disease 4%

    Late onset hearing defect/mental retardation 15%

    Infantile infections

    Transmission during birth or breast feeding

    Usually asymptomatic

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    Cytomegalovirus infections

    Young children Transmission from other children

    Usually asymptomatic

    Adolescent/adult Transmission during kissing, sexual intercourse or blood

    transfusion

    Occasionally IM like syndrome

    Immunocompromised Exogenous PRIMARY INFECTION

    Endogenous REACTIVATION

    Pneumonitis, GI infection

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    Cytomegalovirus infections

    Diagnosis - Difficult Presence of virus or antibody to CMV does not indicate

    a current CMV infection/disease

    Different strategies used in different clinical situations

    Isolation of virus from urine

    within 30 days of birth

    Antigen detection in

    buffy coat - indicates

    viraemia

    * CMV specific IgG positive indicates past infection

    Congenital CMV

    Immunocompromised

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    Treatment and prevention

    Congenital CMV Prevention not possible

    CMV in transplant recipients Prevention

    Treatment

    Test IgG before transplant

    Use only seronegative donors

    Early diagnosis

    Reduce immunosuppression

    Ganciclovir

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    OTHER HUMAN HERPES VIRUSES

    Human Herpes Virus 6 (HHV6) Discovered in 1988

    Worldwide

    Virus replicates in T and B cells

    Infection occurs in first 3 years of life

    Clinical disease - Exanthem subitum (Roseola infantum)

    Mild acute febrile illness

    Incubation period of 2 weeks

    Fever lasts several days

    Macular papular rash appears within 2 days of fever

    85% of adults carry virus in saliva

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    Exanthem subitum

    (Roseola infantum)

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    OTHER HUMAN HERPES VIRUSES

    HHV7 Isolated from CD4 positive cells

    Virus present in saliva of >75% of adults

    Role in disease is unclear Evidence of infection present (seroconversion)

    HHV8

    Detected in epithelial cells of Kaposi sarcoma

    Also present in semen

    Postulated as cause of Kaposi sarcoma

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    1.1 Name three (5) herpes viruses that causedisease in humans

    (25 Marks)

    1.2 How can you make an aetiological diagnosisof 3 diseases you have named in 1.1?

    (75 Marks)

    SAQ September 2011