Herpes Viruses

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

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Structure

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

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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

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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 gt 70)

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H. Simplex in immunocompromised

• Primary or reactivation
• Severe
• Locally invasive
• Dessiminate
• Oesphagitis
• Proctitis
• Meningo-encephalitis
• Pneumonitis
• Hepatitis
• Coagulopathy
• Secondary bacterial infections

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H. Simplex - Diagnosis

• Early dx, rapid rx.
• Samples
• Swabs
• Vesicle fluid
• CSF
• Tissue
• Serum

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H. Simplex Diagnosis contd./

• Direct microscopy E.M.
• Culture, CPE, typing
• Serology
• Paired sera (Ab)
• Cross reactivity, HS1, HS2
• Antigen

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Varicella Zoster (VZV)

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

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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

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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

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Varicella Chicken Pox contd./

• Epidemiology
• Increase winter/early spring
• Highest rate in 4-10 year olds
• Life long immunity to exogenous infection

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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
• lt50 survive beyond 20 months

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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.

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Varicella Infection Control

• Sero Prevalance, HCW
• Vaccine
• Air/contact precautions

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Diagnosis VZV

• Microscopy
• EM
• Immunoflurescence
• Culture, CPE cell line specific
• Serology
• PCR - CSF

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Herpes Zoster, Shingles

• Reactivation latent virus gt 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

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Zoster, Shingles contd./

• DX
• EM
• Culture
• Serology

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EBV (Epstein Barr Virus)

• Primary Infection
• Children asymptomtic
• Young adults infectious mononucleosis (mild
  severe)
• Reactivations intermittent (B. lymphocyte)

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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

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EBV (Epstein Barr Virus) contd./

• Neoplasia
• Burkitts lymphoma
• Nasopharyngeal carcinoma
• B. cell lymphtomas, Tx., HIV
• Oral hairy leucoplakia

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EBV (Epstein Barr Virus) contd./

• Diagnosis
• Blood film atypical lymphocytes
• Monospot
• LFTs
• Microscopy immunofluorescence
• Culture
• Serology

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CMV - Cytomegalovirus

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

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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

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CMV Cytomegalovirus contd./

• Perinatal
• Generally asymptomatic
• Excrete virus, 3 months
• Immunosuppressed and CMV
• Transplant, AIDS
• Primary - more severe (Blood, Graft)
• Reactiviation - majority

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CMV TX

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

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CMV TX contd./

• Prevention
• Prophylaxis
• Screen blood products
• Aggressive Rx.

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CMV HIV

• CD4 lt 100
• Retinitis
• Gastritis
• CNS

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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.

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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

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CMV Diagnosis contd./

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

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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

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Novel Human Herpes Viruses

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

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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)

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Novel Human Herpes Viruses contd./

• Dx.
• Culture of blood mononuclear cells
• PCR blood cells
• Serology ab. Paired sera
• Cross reactivity with CMV, HHV 7.

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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

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Novel Human Herpes Viruses contd./

• HHV 8
• Discovered by comparing DNA sequences of Kaposis
  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