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. Taxonomy 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

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

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 (1 st 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 1 st 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