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

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

7. 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

8. 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%)

9. Herpes Simplex

10. Herpes Simplex

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

12. Genital Herpes

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

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

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

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

17. 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%

18. 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

19. Disseminated Varicella

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

21. 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

22. 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.

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

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

25. VZV

26. 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

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

28. Herpes Zoster

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

30. 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

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

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

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

34. CMV

35. 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

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

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

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

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

40. 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.

41. DEAFF

42. 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

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

44. 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

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

46. 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)

47. HHV-6 cytopathic effect

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

49. 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

50. 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