Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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