VIRAL AGENTS CAUSING GASTROENTERITIS Dr. Osama AL Jiffri

1. VIRAL AGENTS CAUSINGGASTROENTERITISDr. Osama AL Jiffri

2. Viral gastroenteritis • Inflammation of stomach and small and large intestines • Infection caused by a variety of viruses that results in vomiting or diarrhea (stomach flu)

3. VIRAL AGENTS CAUSINGGASTROENTERITIS Major Viruses Rotavirus Enteric adenoviruses Noroviruses : a. Norwalk-like viruses b. Calicivirus c. Astrovirus

4. Noroviruses Norwalk-like Caliciviruses Astroviruses other viruses viruses

5. Viruses associated with gastroenteritis (cont) : • Other viruses (minor): • Coronaviruses • Parvoviruses • Pestiviruses • Toroviruses

6. ROTAVIRUS FamilyReoviridae GenusRotavirus

7. ROTAVIRUS • First isolated in 1973 from children with diarrhea • EM identification from duodenal biopsies • Human and animal strains

8. Rotavirus- EM Structure

9. ROTAVIRUS • 60-80nm in size • Non-enveloped virus • Double capsid • EM appearance of a wheel with radiating spokes • double stranded (ds) RNA in 11 segments (double – double)

10. Rotavirus

11. ROTAVIRUS- ultrastructure

12. STRUCTURE • Double capsid (outer and inner capsid) • Core with genome

13. ROTAVIRUS- 3D STRUCTURE

14. Outer structural proteins - VP7 and VP4 VP7=glycoprotein VP4=protease-cleaved, P protein, viral hemagglutinin, and forms spikes from the surface Inner core structural proteins VP 1, 2, 3, 6 VP6 is an important antigenic determinant Viral Structural Proteins (VP)

15. Gene coding assignment

16. Genome is composed of 11 segments of double-stranded RNA, • six structural • coding for proteins • five nonstructural

17. Groups, subgoups, serotypes based on viral capsid proteins Group A is the most common and has 2 subgroups 10 human serotypes based on G protein (VP 7) 8 P protein serotypes Classification • Seven serological groups have been identified (A-G), three of which (groups A, B, and C) infect humans .

18. Rotavirus - Properties • Virus is stable in the environment • Relatively resistant to handwashing agents • Susceptible to disinfection with 95% ethanol, ‘Lysol’, formalin

19. Rotavirus Epidemiology • Leading cause of severe gastroenteritis in children aged <5 years worldwide • Millions are affected • 600,000-850,000 deaths/year • A major cause of diarrhea-associated hospitalizations • Seroprevalence studies show that antibody is present in most by age 3y.

20. Estimated Global Distribution of The 800,000 Annual Deaths Caused By Rotavirus Diarrhea

21. Epidemiology • Age- 4mo - 2 yearsProtection of younger infants through transplacental antibody transfer • Asymptomatic infectionsare common, especially in adults • Nosocomial infections • Outbreaks

22. Epidemiology (contd.) • Seasonality Winter months (Nov. through May in US) Gradual spread W to E Year-round in the tropics • Incubation period- thought to be <4 days

23. Epidemiology (transmission) • Mainly person to person via fecal-oral route • Fomites • Food and water-borne spread is possible • Spread via respiratory route is speculated

24. EPIDEMIOLOGYDifferences in Groups • Group Ainfections are most common • Group Bhas been associated with outbreaks in adults in China • Group Cis responsible for sporadic cases of diarrhea in infants around the world

25. Clinical Features • Incubation period-thought to be <4 days • Fever-can be high grade (>102F in 30%) • Vomiting, nauseaprecede diarrhea • Diarrhea - usually watery (no blood or leukocytes) - lasts 3-9 days • Dehydrationis the main contributor to mortality

26. Recovery is usually complete. • However, severe diarrhea without fluid and electrolyte • replacement may result in dehydration and death .

27. Diagnosis • Antigen detection in stool by ELISA, Latex Agglutination (for Group A rotavirus) • EM- non-Group A viruses also • Culture- Group A rotaviruses can be cultured in monkey kidney cells • Serology for epidemiologic studies

28. Treatment and Prevention • Treatment- Supportive - oral, IV rehydration • Prevention- Handwashing and disinfection of surfaces

29. Vaccine (old) • Live tetravalent rhesus-human reassortant vaccine (Rotashield) • Licensed for use in August 1998 • Removed from the market in October 1999 due to risk of intussusception • Cases were seen 3-20 days after vaccination • Approx. 15 cases/1.5 million doses

30. Vaccine (New) • New licensed vaccine ( RotaTeq) • No elevated risk of intussusception • In U.S.A. recommendation made to routinely vaccinate all children at 2,4,6 months • Considered for routine immunization in many countries

31. GASTROENTERITIS DUE TO ENTERIC ADENOVIRUS

32. ADENOVIRUS • A nonenveloped double-stranded DNA virus • First isolated in the 1950s in adenoid tissue • Gastroenteritis, upper and lower respiratory tract infection, ocular infections

33. GASTROENTERITIS DUE TO ADENOVIRUS • Types 40, 41 • Belong to serogroup F • Some cases due to types 31, 3, 7

34. Clinical features of Enteric Adenovirus gastroenteritis • Age <4 years • Incubation period 3 -10 days • Diarrhea lasts for 10 -14 days

35. Laboratory Diagnosis • Isolation standard cell cultures of human neonatal kidney cells • ELISA for rapid detection is available • Complement fixation for antibody level

36. HUMAN CALICIVIRUSES

37. Belong to Family Caliciviridae Non-enveloped RNA viruses with ss RNA 27-35 nm in diameter Contain a single capsid protein HUMAN CALICIVIRUSES(HuCV)

38. HUMAN CALICIVIRUSES • Genomic analysis divides it into 4 groups • Human caliciviruses belong to 2 genera

39. NLV (Norovirus) Norwalk virus Hawaii virus Snow Mountain virus Montgomery county virus Taunton (England) SLV (Sapovirus) Sapporo virus Manchester virus Houston/86 London/92 CLASSIFICATION OF HuCV

40. Typical morphology EM appearance of “Star of David” E.g.- Sapporo-like viruses Morphology of HuCV- typical

41. HUMAN CALICIVIRUSES - SLV

42. Atypical morphology Smooth surface Small Round Structured viruses E.g.- Norwalk-like viruses Morphology of HuCV- atypical

43. Diagnosis- Human Caliciviruses • Specimen- stool , vomitus, environmental swabs, [not yet on foods] • Immune EM • RT-PCR in state public health labs. • Serology for epidemiologic purposes

44. SRSV- NORWALK VIRUS

45. CLINICAL FEATURES • Epidemic in Adults and Children • Usual incubation Period is <24-48 hours (ranges from 12hrs. to 4 days) • Short duration of illness <3 days • Nausea, vomiting, fever, headache • Abdominal cramping • Watery diarrhea

46. Epidemiology-Noroviruses • Worldwide distribution • >23 million cases/year in the U.S. • Outbreaks of foodborne, waterborne and shellfish • Most people have had infections by age 4 years (by seroprevalence studies)

47. Spread of Norwalk virus • Person-to-person Fecal-oral spread (stool/vomitus) • Fecal contamination of food or water • Spread through fomites?

48. Epidemiology-Noroviruses Asymptomatic infections- seroconversion but asymptomatic shedding of virus Low infective dose Viral excretion during recovery (up to 2 weeks) Ability to survive in water chlorination at routine levels

49. Epidemiology of Outbreaks • Cruise ships, schools, nursing homes, etc. • Can involve infants and school-age children • Source usually is contaminated food and water (seafood-oyster and shellfish etc.)

50. HUMAN ASTROVIRUS