Herpes Viruses E. McNamara.. History 1900. Epidemiological linkage of varicella and zoster. 1943. EM...
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Transcript of Herpes Viruses E. McNamara.. History 1900. Epidemiological linkage of varicella and zoster. 1943. EM...
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
• 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– Skin– Eyes– Mucosa– CNS– Disseminated (mortality untreated > 70%)
Genital Herpes
H. Simplex in immunocompromised
• Primary or reactivation– Severe– Locally invasive– Dessiminate
• Oesphagitis• Proctitis• Meningo-encephalitis• Pneumonitis• Hepatitis• Coagulopathy• Secondary bacterial infections
H. Simplex - Diagnosis
• Early dx, rapid rx.
• Samples– 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
• 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
– 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– 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– 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
– 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• Type of Transplant• Mismatch, Donor (+ve), recipient (-ve)• Duration immunosuppression Rx.• Symptoms
– Fever– Leucopenia– Pneumonitis– Hepatitis– Retinitis– Encephalitis– Super infections / mortality
CMV – TX contd./
• Prevention– Prophylaxis– Screen blood products– Aggressive Rx.
CMV – HIV
• 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– 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)
• 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.– 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– 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