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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.
Taxonomy
•
•
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•
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•
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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
Structure
• ds DNA core
• Capsid enveloped (glycopeptide)
• Capsid enveloped 150mm diameter
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
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%)
Herpes Simplex
Herpes Simplex
H. Simplex 2
• Primary HS-2
– Genital Herpes (85%), recurrent/asymptomatic
• Complications – neonatal infections
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–
–
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Skin
Eyes
Mucosa
CNS
Disseminated (mortality untreated > 70%)
Genital Herpes
H. Simplex in
immunocompromised
• Primary or reactivation
– Severe
– Locally invasive
– Dessiminate
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•
•
•
•
•
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Oesphagitis
Proctitis
Meningo-encephalitis
Pneumonitis
Hepatitis
Coagulopathy
Secondary bacterial infections
H. Simplex - Diagnosis
• Early dx, rapid rx.
• Samples
–
–
–
–
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Swabs
Vesicle fluid
CSF
Tissue
Serum
H. Simplex – Diagnosis contd./
• Direct microscopy – E.M.
• Culture, CPE, typing
• Serology
• Paired sera (Ab)
– Cross reactivity, HS1, HS2
• Antigen
Varicella Zoster (VZV)
• Varicella – Chickenpox, Primary
• Zoster – Shingles, Reactivation (sensory
ganglia)
• Same agent
Varicella, Chicken Pox
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•
•
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•
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%
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
Disseminated Varicella
Varicella Chicken Pox contd./
• Epidemiology
– Increase winter/early spring
– Highest rate in 4-10 year olds
– Life long immunity to exogenous infection
Varicella in Pregnancy
Early (20 weeks) (sero-negative mother)
• Congenital varicella syndrome
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–
–
–
–
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Very rare (3% those infected)
Cortical atrophy
Chorioretinitis
Hypoplasia of limbs
Muscular atrophy
<50% survive beyond 20 months
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.
Varicella – Infection Control
• Sero Prevalance, HCW
• Vaccine
• Air/contact precautions
Diagnosis VZV
• Microscopy
– EM
– Immunoflurescence
• Culture, CPE – cell line specific
• Serology
• PCR - CSF
VZV
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
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–
–
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2º bacterial infections
Neuralgia
Encephalitis (rare)
Ocular defects
Zoster, Shingles contd./
• DX
– EM
– Culture
– Serology
Herpes Zoster
EBV (Epstein Barr Virus)
• Primary Infection
– Children – asymptomtic
– Young adults – infectious mononucleosis (mild
– severe)
• Reactivations – intermittent (B.
lymphocyte)
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
EBV (Epstein Barr Virus) contd./
– Neoplasia
•
•
•
•
Burkitts lymphoma
Nasopharyngeal carcinoma
B. cell lymphtomas, Tx., HIV
Oral hairy leucoplakia
EBV (Epstein Barr Virus) contd./
• Diagnosis
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–
–
–
–
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Blood film – atypical lymphocytes
Monospot
LFT’s
Microscopy – immunofluorescence
Culture
Serology
CMV - Cytomegalovirus
• CMV Infection
– Primary
– Reactivation
– Majority is asymptomatic (21% Infect.Mono.)
• Significant symptomatic infection
– Congenital / perinatal
– Immunosuppressed (Tx. HIV)
CMV
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
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–
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Intra uterine growth retardation
Jaundice/Hepathospleenomegaly
CNS – neurological damage
Chorioretinitis
Early asymptomatic – later, hearing and vision
impairment
CMV – Cytomegalovirus contd./
Perinatal
• Generally asymptomatic
• Excrete virus, 3 months
Immunosuppressed and CMV:
• Transplant, AIDS
• Primary - more severe (Blood, Graft)
• Reactiviation - majority
CMV – TX
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Type of Transplant
Mismatch, Donor (+ve), recipient (-ve)
Duration immunosuppression Rx.
Symptoms
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Fever
Leucopenia
Pneumonitis
Hepatitis
Retinitis
Encephalitis
Super infections / mortality
CMV – TX contd./
• Prevention
– Prophylaxis
– Screen blood products
– Aggressive Rx.
CMV – HIV
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•
•
•
CD4 < 100
Retinitis
Gastritis
CNS
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.
DEAFF
CMV – Diagnosis contd./
• Serology
– Paired sera
– Igm
• Viral antigen in neutrophils
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–
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–
CMV viraemia
Quantitative, rapid, monitor pre-symtoms
Use MAb against the phospho protein PP65
But neutropaenic, may not have sufficient leucocytes
CMV – Diagnosis contd./
• PCR
– Primers CMV early Ag
– Detects small amount of CMV DNA
– V. sensitive
• Specificity – problematic (false positives)
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
Novel Human Herpes Viruses
• HHV 6, 1986 (T. cells)
• HHV 7, 1990 (T. cells)
• HHV 8, 1994 Kaposis sarcoma associated
Herpes (B. cells)
Novel Human Herpes Viruses contd./
• HHV 6
– Ubiquitous, childhood (6 months to 3 years old)
– Roseola (exauthem subitum)
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•
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Fever 40º
Erythematous maculopapular rash (1-3 days)
Irritability and drowsiness
Self limiting
Neuro complications – rare
– Transmission
• Saliva
• Perinatal (cervical secretions)
HHV-6 cytopathic effect
Novel Human Herpes Viruses contd./
• Dx.
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Culture of blood mononuclear cells
PCR – blood cells
Serology – ab. Paired sera
Cross reactivity with CMV, HHV 7.
Novel Human Herpes Viruses
contd./
• HHV 7
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40% homology with HHV 6 genome
No clinical human disease
Co factor with HIV?
90% adults – seropositive
Transmission – saliva
Dx. – Culture, PCR
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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