Herpes Viruses E. McNamara.

History 1900. Epidemiological linkage of varicella and zoster. 1943. EM of vesicle fluid 1953. Isolation of virus. 1986. DNA sequence published.

Taxonomy Beta HHV-5, CMV HHV-6, HHV-7 Alpha. Rapid, Neuron Family, Herpesviridae Sub families, Alpha HHV-1, HSV1 HHV-2, HSV2 HHV-3, VZV Gamma HHV-4, EBV HHV-8 Beta HHV-5, CMV HHV-6, HHV-7 Alpha. Rapid, Neuron Gamma. Lymphotrophic Beta. Slow, Mesothelial

Structure ds DNA core Capsid enveloped (glycopeptide) Capsid enveloped 150mm diameter

Herpes Simplex 2 Serotypes - HSV-1, HSV-2 Primary, muco-cutanens Latent infection in Neuronal cells, dorsal root ganglia Viral reactivation Transmission, direct contact Cross immunity, HSV-1 and HSV-2

H. Simplex - I Primary HS I Reactivation Gingivostomatitis / asymptomatic Lesions, vesicle, ulcer, crust Reactivation Orolabial infections (gential infection) Conjunctivitis Deratitis Herpetic whitlow Encephalitis (untreated mortility of 70%)

H. Simplex 2 Primary HS-2 Complications – neonatal infections Genital Herpes (85%), recurrent/asymptomatic Complications – neonatal infections Skin Eyes Mucosa CNS Disseminated (mortality untreated > 70%)

H. Simplex in immunocompromised Primary or reactivation Severe Locally invasive Dessiminate Oesphagitis Proctitis Meningo-encephalitis Pneumonitis Hepatitis Coagulopathy Secondary bacterial infections

H. Simplex - Diagnosis Early dx, rapid rx. Samples Swabs Vesicle fluid CSF Tissue Serum

H. Simplex – Diagnosis contd./ Direct microscopy – E.M. Culture, CPE, typing Serology Paired sera (Ab) Cross reactivity, HS1, HS2 Antigen

Varicella Zoster (VZV) Varicella – Chickenpox, Primary Zoster – Shingles, Reactivation (sensory ganglia) Same agent

Varicella, Chicken Pox Transmission – respiratory, vertical, contact Incubation, 2 weeks Prodromal, flu like symptoms, 1º viraemia Rash, fever (centripetal), 2º viraemia Crops macules, papules, vesicles, crusts Infectious, 2 days pre-rash to 3-5 days post-rash eruption Secondary attack rates of 85%

Varicella, Chicken Pox contd./ Complications Secondary bacterial infections Haemorrhagic chicken pox Pneumonia Encephaliis Immunocompromised/Impaired cell mediated immunity/have increased mortality Adults more severe disease

Varicella Chicken Pox contd./ Epidemiology Increase winter/early spring Highest rate in 4-10 year olds Life long immunity to exogenous infection

Varicella in Pregnancy Early (20 weeks) (sero-negative mother) Congenital varicella syndrome Very rare (3% those infected) Cortical atrophy Chorioretinitis Hypoplasia of limbs Muscular atrophy <50% survive beyond 20 months

Varicella in Pregnancy contd./ Late Varicella Varicella onset 8 days or more pre-delivery Maternal ab. Present Mild/asymptomatic infection in-intero Varicella onset 7 days or less pre-delivery No maternal ab. Risk of severe dessiminated neonatal disease.

Varicella – Infection Control Sero Prevalance, HCW Vaccine Air/contact precautions

Diagnosis VZV Microscopy Culture, CPE – cell line specific Serology EM Immunoflurescence Culture, CPE – cell line specific Serology PCR - CSF

Herpes Zoster, Shingles Reactivation latent virus > 50 years old Single dermatome (very painful) Trigeminal – opthalmic branch Sacral ganglia – acute retention Facial nerve – Ramsey Hunt Complications 2º bacterial infections Neuralgia Encephalitis (rare) Ocular defects

Zoster, Shingles contd./ DX EM Culture Serology

EBV (Epstein Barr Virus) Primary Infection Children – asymptomtic Young adults – infectious mononucleosis (mild – severe) Reactivations – intermittent (B. lymphocyte)

EBV (Epstein Barr Virus) contd./ Infectious mononucleosis Triad. Fever, phargngitis, cervical lymphadenopathy Duration 1-4 weeks Complications Spleenomegaly Hepatitis Pericarditis CNS, meningo-encephalitis Guillam-Barre Syndrome

EBV (Epstein Barr Virus) contd./ Neoplasia Burkitts lymphoma Nasopharyngeal carcinoma B. cell lymphtomas, Tx., HIV Oral hairy leucoplakia

EBV (Epstein Barr Virus) contd./ Diagnosis Blood film – atypical lymphocytes Monospot LFT’s Microscopy – immunofluorescence Culture Serology

CMV - Cytomegalovirus CMV Infection Significant symptomatic infection Primary Reactivation Majority is asymptomatic (21% Infect.Mono.) Significant symptomatic infection Congenital / perinatal Immunosuppressed (Tx. HIV)

CMV – Cytomegalovirus contd./ Congenital CMV 1º infection in pregnancy – 55% risk Timing in pregnancy (1st 20 weeks) Sero positive minimum – low transmission Symptoms, mild – severe Intra uterine growth retardation Jaundice/Hepathospleenomegaly CNS – neurological damage Chorioretinitis Early asymptomatic – later, hearing and vision impairment

CMV – Cytomegalovirus contd./ Perinatal Generally asymptomatic Excrete virus, 3 months Immunosuppressed and CMV: Transplant, AIDS Primary - more severe (Blood, Graft) Reactiviation - majority

CMV – TX Type of Transplant Mismatch, Donor (+ve), recipient (-ve) Duration immunosuppression Rx. Symptoms Fever Leucopenia Pneumonitis Hepatitis Retinitis Encephalitis Super infections / mortality

CMV – TX contd./ Prevention Prophylaxis Screen blood products Aggressive Rx.

CMV – HIV CD4 < 100 Retinitis Gastritis CNS

CMV – Diagnosis Microscopy, Histology Culture Nuclear inclusions “owls eye” Immunofluorescence – Tissue Culture Urine, saliva, Buffy coat, BAL, swabs Tissue culture 1-4 weeks – inclusions Shell vials+ MAb, Rapid 1-2 days “Deaff” test.

CMV – Diagnosis contd./ Serology Viral antigen in neutrophils Paired sera Igm Viral antigen in neutrophils CMV viraemia Quantitative, rapid, monitor pre-symtoms Use MAb against the phospho protein PP65 But neutropaenic, may not have sufficient leucocytes

CMV – Diagnosis contd./ PCR Primers CMV early Ag Detects small amount of CMV DNA V. sensitive Specificity – problematic (false positives)

CMV – Diagnosis contd./ SUMMARY Dx. Acute CMV difficult Infection common in population Positive culture normal from cervical, semen specimens Congenital infections – culture Positive in the 1st 3 weeks of life PCR – CMV in many body fluids

Novel Human Herpes Viruses HHV 6, 1986 (T. cells) HHV 7, 1990 (T. cells) HHV 8, 1994 Kaposis sarcoma associated Herpes (B. cells)

Novel Human Herpes Viruses contd./ HHV 6 Ubiquitous, childhood (6 months to 3 years old) Roseola (exauthem subitum) Fever 40º Erythematous maculopapular rash (1-3 days) Irritability and drowsiness Self limiting Neuro complications – rare Transmission Saliva Perinatal (cervical secretions)

Novel Human Herpes Viruses contd./ Dx. Culture of blood mononuclear cells PCR – blood cells Serology – ab. Paired sera Cross reactivity with CMV, HHV 7.

Novel Human Herpes Viruses contd./ HHV 7 40% homology with HHV 6 genome No clinical human disease Co factor with HIV? 90% adults – seropositive Transmission – saliva Dx. – Culture, PCR

Novel Human Herpes Viruses contd./ HHV 8 Discovered by comparing DNA sequences of Kaposi’s sarcoma lesions and normal skin. Causative role in KS questioned (association v causation) B. cell lymphomas Unknown Prevalence in general population Transmission Disease pathogenesis Dx. - PCR