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Herpes Viruses

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. Family, Herpesviridae Sub families, Alpha HHV-1, HSV1 HHV-2, HSV2

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Herpes Viruses

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  1. Herpes Viruses E. McNamara.

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

  3. 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 Taxonomy

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

  5. 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

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

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

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

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

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

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

  12. 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%

  13. 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

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

  15. 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

  16. 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.

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

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

  19. 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

  20. Zoster, Shingles contd./ • DX • EM • Culture • Serology

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

  22. 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

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

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

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

  26. 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

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

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

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

  30. CMV – HIV • CD4 < 100 • Retinitis • Gastritis • CNS

  31. CMV – Diagnosis • Microscopy, Histology • 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.

  32. CMV – Diagnosis contd./ • Serology • 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

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

  34. 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

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

  36. 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)

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

  38. 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

  39. 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

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