1. Dr. Gulácsy Vera Herpes virus and Enterovirus infections

2. Herpes virus family Herpes simplex virus -1(Humán herpesvirus 1, HHV-1) Herpes simplex virus -2(HHV-2) Varicella-zoster virus (HHV-3) Cytomegalovirus (HHV-5) Human herpesvirus 6 (HHV-6A,6B) Human herpesvirus 7 (HHV-7) Epstein-Barr virus (HHV-4) Humán herpesvirus 8 (HHV-8) Alfa (Neuronos) Béta (leukocytes) Gamma (Immunsystem, B-cells) oncogenic

3. HSV-1 and HSV-2 Cytolytic type DNA viruses Latent infection (sensory ganglia – trigeminus, sacralis) Herpes labialis – HSV1 Genital herpes HSV 2 and HSV1 (30%) Spread by direkt contact (saliva, sexual mucosa, urine) Primer infection: 1-3 yrs age Fever, gingivo-stomatitis, group of vesicules on mucosa Trigger- reactivation

4. HSV-1 and HSV-2 Keratitis, keratoconjunctivitis Enchephalitis (temporal lobe) Immunocompromised Generalised infection Visceral manifestation: pneumonitis, hepatitis Connatal infection: intrapartum 90% Congenital – very rare

5. HSV-1 and HSV-2 Congenital HSV: Skin scars, microcephalia, ocular involvement (keratoconjunctivitis) Intranatal infection: Keratoconjunctivitis, chorioretinitis (days 2-14) Skin vesicules (days 9-12) Haematogenic dissemination (days 9-11) Hepatomegalia, jaundice, liver failure, pneumonitis, coagulopathy Encephalitis (days 16-28)

6. HSV-1 and HSV-2 Diagnosis Clinical signs Isolations of virus from vesicules, antigen detection, PCR Serology only useful in primary infection Therapy Herpes labialis - local Stomatitis – dehydration → hospitalisation Acyclovir: During pregnancy in genital herpes Neonatal herpes infection Immunocompromised Encephalitis

7. Varicella-Zoster virus Primary infection: varicella (chicken pox) VZV reactivation: herpes zoster (shingles) Spread by air Skin and mucosal vesicules Different types of rashes (macule, papule, vesicule, pustule, crust) Incubation: 14 days Very contagious: 2 days before symptomes till crusts

8. Varicella

9. Herpes-zoster VZV in paravertebral ganglia-latent infection Ganglion teritory group of vesicules, painful No fever Postherpetic neuralgia

10. Varicella-Zoster virus Complications (varicella) Cellulitis, varicella phlegmone, impetigo, necrotic fasciitis (S. aureus, S. pyogenes, H. infl.), STSS Arthritis Cerebellitis Enchephalitis Ramsey-hunt sy. Guillan-Barre sy. Pneumonitis Cytopenia

11. Varicella-Zoster virus Pregnancy and VZV infection I. trimester (weeks 8-20) – congenital varicella syndrome limb hypoplasia, eyes (chorioretinitis) és CNS damage II. trimester – No severe complications 5 days before or 2 days after birth - connatal varicella syndrome Neonatal serious, progressiv varicella (VZIG, acyclovir th.)

12. Varicella-Zoster virus Immunocompromised patients No hyperaemia around the vesicules No crusts One stage Haemorrhage Visceral involvement: Pneumonitis, ARDS Hepatitis Intestinal bleeding

13. Varicella-Zoster virus Therapy- acyclovir Controversial with healthy immunity Immunocompromised Serious cases, atypical varicella Neonates Complications Zoster cures without treatment in immunocompetents

14. Varicella-Zoster virus Prevention Passive immunization: VZIG- postexpozition (Varitect) 72 hours Immunsuppression In pregnancy - controversial Connatal varicella Activ immunization: live attenuated (Varilrix) > 1 yr, 2 doses, mild varicella, less zoster Zostavax USA, >60 yrs, postherpetic neuralgia ↓

15. EBV – Mononucleosis infectiosa Adolescence Spread by saliva, „kissing disease” Population >90% get infected <25 yrs Lytic infection of pharyngeal mucosa CD-21 receptor – B cells No B cells No mononucleosis (XLA) XLP – fulminant infection (fatal mononucleosis)

16. EBV infection Clinical presentations Incubation: 2-8 weeks Prodroma : weakness, elevated tempr. Fever Confluent tonsillitis Lypmhadenopathy Hepato-splenomegaly Maculo-papular rash (penicillins) Chronic fatigue

17. EBV infection Lab tests Blood count: lymphomonocytosis, activated lymphocytes, platelet↓ Liver enzymes ↑ Serology (VCA, EA, EBNA antibody) Heterophil agglutination -Paul-Bunnel test

18. EBV infection Complications Spleen rupture Bacterial superinfections: Necrotic tonsillitis, pneumonia, otitis, sinusitis Haematology complications: Thrombocytopenia, haemolyticus anaemia, neutropenia Pericarditis, atrialfibrillation - rare Hepatitis, haematuria, proteinuria- rare Neurological complications : Periferal, central mononeuritis, Guillain-Barré sy.

19. EBV infection Complications Fatal mononucleosis- XLP Burkitt lymphoma Nasopharingeal carcinoma Polyclonalis B sejtes lymphoma – stem cell transpl., AIDS Therapy: symptomatic, NSAID

20. CMV infection No symptomes in healthy people Mild disease (1%) Mononucleosis syndrome: fever, malaise, lymphomonocytosis, liver enzymes↑ T cell deficiency - opportunistic TX: pneumonitis, colitis, hepatitis HIV: retinitis, polyradikulopathia, ulceral colitis Primary infection, latency, reactivation No cell proliferation Incubation: 4-12 weeks

21. CMV infection Complications Interstitial pneumonia (improves spontanously ) Granulomar hepatitis Guilla-Barré sy. Meningoenchephalitis Thrombocytopenia

22. CMV infection Congenital infection Transplacentar spreading Intranatal Postnatal- contaminated blood transfusion, breast feeding

23. CMV infection Manifest congenital CMV infection Premature birth Hepatosplenomegaly, jaundice, petechia Thrombocytopenia Chorioretinitis Microcephalia Sensoneural deafness (both side, progressiv) Psychomotor retardation Teeth development problems

24. CMV infection Intra- and postnatal CMV infection Recurrent maternal infection No symptomes, but virus shedding for years (urine) 10% pneumonitis Thrombocytopenia Hepatosplenomegaly Therapy- gancyclovir, foscarnet, cidofovir

25. HHV-6,7,8 HHV-6 (7): Exanthema subitum/Roseola infantum („3 days fever”) <2 yrs, high fever for 3-5 days, no special symptomes Rash after fever stops Fever seizure, hepatitis, encephalitis HHV-8 Kaposi-sarcoma

27. Non-polio enteroviruses Only human pathogenes Fecal-oral spreading, summer-autumn Echo 4,6,9,11,30 Coxsackie B2-5; A9,A16 Enterovirus 70, 71 Asymptomatic infection: 50-90 % Non specific fever syndrome Fever, headache, muscle pain, malaise, loss of apetite, sore throat, nausea, vomiting, abdominal pain, loose stool („summer influenza” )

28. Non-polio enterovirus Hand-foot-mouth disease Coxsackie 16, Enterovírus 71 Vesicules in the mouth Painfull vesicules on soles and palms Herpangina fever, headache, vomitus Vesicules on pharyngeal wall, tonsills Symptomatic treatment

29. Non-polio enteroviruses Acut hemorrhagial conjunctivitis Pharyngitis, tonsillitis, laryngitis, bronchitis Pleurodynia (Bornholm-betegség) Acut gastroenteritis Hepatitis Aseptikus meningitis, encephalitis Guillen-Barré szindróma Peri-, myocarditis Polymyositis

30. Non-polio enteroviruses Neonatal infection Perinatal days, Coxsackie, Echo Epidemic Sepsis-like syndrome, rash Meningitis, meningoencephalitis Necrotic hepatitis Myocarditis → early congestiv heartfailure Treatment: IVIG?

31. Thank you!