1. Herpes Viruses
E. McNamara.

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

3. 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

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 Reactivation
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 Complications – neonatal infections
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 Culture, CPE – cell line specific SerologyEM
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 Significant symptomatic 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 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.

32. 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

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