Viral and Parasitic Gastroenteritis

1. Viral and Parasitic Gastroenteritis

2. Viral Gastroenteritis • Inflammation of the stomach and intestines caused by viruses, which is also known as the stomach flu • This highly contagious illness spreads through • close contact with people who are infected • contaminated food or water • It can easily spread in close quarters • childcare facilities • Schools • nursing homes • cruise ships

3. Viruses are responsible for up to ¾ of all infective diarrhoeas • Viral gastroenteritis is the second most common viral illness after upper respiratory tract infection • In developing countries, viral gastroenteritis is a major killer of infants who are undernourished • Rotaviruses are responsible for half a million deaths a year

4. HEPATITIS • Hepatitis is inflammation of the liver • The disease can be caused by infections from parasites, bacteria, or viruses • Liver damage can also result from alcohol, drugs, or poisonous mushrooms • Hepatitis A, B, and C are clinically the most important forms of viral liver disease

5. Persons at risk of hepatitis B infection include • 1) individuals with multiple sex partners • 2) men who have sex with men • 3) sex contacts of infected persons • 4) injection drug users • 5) household contacts of chronically infected persons • Death from chronic hepatitis B occurs in 15 to 25 percent of chronically infected persons

6. Most hepatitis C infections result from illegal injection drug use • Transfusion-associated cases occurred prior to blood donor screening • now the incidence is less than 1 per 2 million transfused blood units • Fifty percent of those with hepatitis C go on to have • chronic liver disease • liver failure (cirrhosis) • liver cancer • Hepatitis C is the number one reason for receiving a liver transplant in the United States

7. Classification of hepatitis viruses based on mode of transmission Classification of major viral agents causing hepatitis

8. Hepatitis A Virus: Structure and Classification • Virus classification • Group: Group IV ((+)ssRNA) • Family: Picornaviridae • Genus: Hepatovirus • Species: Hepatitis A virus • Separate genus because ofdifferences with other enteroviruses • Naked icosahedral capsid • SS RNA (740 nucleotides) • Single serotype worldwide • Humans only reservoir Electron micrograph of hepatitis A virions

9. Hepatitis A Virus Transmission • Fecal-oral • Close personal contact • e.g., household contact, sex contact, child day care centers • Contaminated food, water • e.g., infected food handlers • Blood exposure • rare

10. Estimated prevalence of hepatitis A virus

11. Hepatitis A: Pathogenesis • Incubation 4 weeks (range 2-6 weeks) • Oral cavity GI tract liver via blood • Replicates in hepatocytes (little damage to cells) released via bile to intestines 7-10 days prior to clinical symptoms • Liver damage and clinical syndrome result of immune response and not direct effect of virus

12. Hepatitis A: Clinical Features • An acute illness with • discrete onset of symptoms • e.g. fatigue, abdominal pain, loss of appetite, nausea, vomiting • Jaundice • elevated serum aminotransferase levels, dark urine, light stool • Adults are usually more symptomatic • Patients are infective while they are shedding the virus in the stool- usually before the onset of symptoms • Most cases resolve spontaneously in 2-4 weeks • Complete recovery 99%

13. Hepatitis A - Diagnosis • Detection of IgM antibody • IgG positive 1-3 weeks later; suggests prior infection or vaccination

14. Hepatitis A - Treatment • Supportive: no specific role of antiviral therapy • Lifelong immunity likely after infection or vaccination

15. PREVENTING HEPATITIS A • Hygiene • e.g., hand washing • Sanitation • e.g., clean water sources • Hepatitis A vaccine • pre-exposure

16. HEPATITIS A VACCINES • Inactivated vaccine • Highly immunogenic • 97%-100% of children, adolescents, and adults have protective levels of antibody within 1 month of receiving first dose • essentially 100% have protective levels after second dose • Highly efficacious • In published studies, 94%-100% of children protected against clinical hepatitis A after equivalent of one dose

17. HEPATITIS A VACCINES • 1st dose at time 0 • 2nd dose 6-12 months afterwards

18. POST-VACCINATION TESTING • Not recommended • High response rate among vaccinees • Commercially available assay not sensitive enough to detect lower (protective) levels of vaccine-induced antibody

19. DURATION OF PROTECTION AFTER VACCINATION • Protection begins 4 weeks after vaccine • Persistence of antibody • At least 5-8 years among adults and children • Efficacy • No cases in vaccinated children at 5-6 years • Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years • Other mechanisms, such as cellular memory, may contribute

20. Hepatitis A Vaccine • Pre-exposure Vaccination • Persons at increased risk for infection • travelers to intermediate and high HAV-endemic countries • MSM (Men who have sex with men) • Drug users • Persons who have clotting factor disorders • persons with chronic liver disease • Communities with historically high rates of hepatitis A -routine childhood vaccination

21. Hepatitis A Vaccine Immunogenicity, Side Effects • Immunogenicity in children, adolescents, adults • 94-100% positive 1 month after dose 1 • 99-100% positive after dose 2 • Most common side effects • Sore injection site (50%), headache (15%), malaise (7%) • No severe reactions known • Safety in pregnancy unknown (risk likely is low) • Currently licensed for aged 1 year and older

22. Hepatitis B

23. Hepatitis B: Structure • Member of the hepadnavirus group • Virionalso referred to as Dane particle • 42nm enveloped virus • Core antigens located in the center (nucleocapsid)

24. Structure and Replication • Circular partially double stranded DNA of virus • Initial replication to complete circular DNA with subsequent transcription to make several mRNAs some of which are translated into viral proteins • One of the mRNAs is replicated with a reverse transcriptase making the DNA that will eventually be the core of the progeny virion • Some DNA integrates into host genome causing carrier state • Virus stable and resist many stresses making them more infectious

25. Hepatitis B Virus TEM micrograph showing hepatitis B viruses The structure of hepatitis B virus

26. Prevalence of chronic infection with hepatitis B virus, 2006

27. Global Patterns of Chronic HBV Infection • High (>8%): 45% of global population • lifetime risk of infection >60% • early childhood infections common • Intermediate (2%-7%): 43% of global population • lifetime risk of infection 20%-60% • infections occur in all age groups • Low (<2%): 12% of global population • lifetime risk of infection <20% • most infections occur in adult risk groups

28. Possible Outcomes of HBV Infection Acute hepatitis B infection 95% of infant-acquired infections 3-5% of adult-acquired infections Chronic HBV infection Chronic hepatitis 12-25% in 5 years Cirrhosis 20-23% in 5 years 6-15% in 5 years Hepatocellular carcinoma Liver failure Liver transplant Death Death

29. 100 100 80 80 60 60 Chronic Infection 40 40 20 20 Symptomatic Infection 0 0 Birth 1-4 yrs 1-6 mos 7-12 mos Older Children and Adults Outcome of Hepatitis B Virus Infection by Age at Infection Chronic Infection (%) Symptomatic Infection (%)

30. HBV Modes of Transmission • Sexual • Parenteral • Perinatal

31. Low/Not High Moderate Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breast milk Concentration of HBV in Various Body Fluids

32. Hepatitis B Symptoms • About 50%-60% of adults with HBV infection have no signs or symptoms • Those who do have symptoms might experience: • Jaundice • Fatigue • Abdominal pain • Loss of appetite • Nausea, vomiting • Joint pain

33. HBV Pathogenesis • Virus enters hepatocytes via blood • Immune response (cytotoxic T cell) to viral antigens expressed on hepatocyte cell surface responsible for clinical syndrome • 5 % become chronic carriers (HBsAg> 6 months) • Higher rate of hepatocellular in chronic carriers, especially those who are “e” antigen positive • Hepatitis B surface antibody likely confers lifelong immunity • Hepatitis B Ab indicates low transmissibility

34. Elimination of HBV Transmission • Prevent perinatal HBV transmission • Routine vaccination of all infants • Vaccination of children in high-risk groups • Vaccination of adolescents • all children up through age 18 • Vaccination of adults in high-risk groups

35. Hepatitis B Vaccine • Licensed in 1982 • 3 dose series, typical schedule 0, 1-2, 4-6 months • 2 dose series (adult dose) • Protection ~30-50% dose 1; 75% - 2; 96% - 3 • lower in older, immunosuppressive illnesses • e.g., HIV, chronic liver diseases, diabetes, obese, smokers

36. Hepatitis B Vaccine Safety • Side effects rare • Anaphylaxis estimated to occur in 1/600,000 doses given • No scientific data to link hepatitis B vaccine with multiple sclerosis (MS), other autoimmune diseases, autism

37. Hepatitis B Vaccination • Routine infant • Ages 11-15 and through age 18 • Over 18 – high risk • Occupational risk • Hemodyalisis patients • All STD clinic clients • Multiple sex partners or prior STD • Inmates in Correctional settings • MSM • IDU • Institution for developmental disability

38. Hepatitis C Virus

39. Hepatitis C Structure and Classification • Member of the flavivirusfamily • Enveloped single stranded RNA virus • Humans and chimpanzees only known reservoirs • 6 serotypes (genotypes) and multiple subtypes • based on high variability of envelope glycoproteins

40. Occupational Transmission of HCV • Inefficient by occupational exposures • Average incidence 1.8% following needle stick from HCV-positive source • Case reports of transmission from blood splash to eye • Prevalence 1-2% among health care workers

41. Perinatal Transmission of HCV • Transmission only from women HCV-RNA positive at delivery • Average rate of infection 6% • Higher (17%) if woman co-infected with HIV • No association with • Delivery method • Breastfeeding • Infected infants do well • Severe hepatitis is rare

42. Sexual Transmission of HCV • Occurs, but efficiency is low • Rare between long-term steady partners • Factors that facilitate transmission between partners unknown • Accounts for 15-20% of acute and chronic infections in the United States Partner studies

43. Household Transmission of HCV • Rare but not absent • Could occur through percutaneous/mucosal exposures to blood • Contaminated equipment used for home therapies • Through sharing of contaminated personal material (razors, toothbrushes)

44. Other Potential Exposures to Blood • No or insufficient data showing increased risk • intranasal cocaine use, tattooing, body piercing, acupuncture, military service

45. Hepatitis C: Clinical Features • Acute infection asymptomatic in over 80% of patients, when present, acute illness usually mild • Acute symptoms include jaundice, nausea, abdominal pain, loss of appetite, dark urine

47. Chronic Hepatitis C Factors Promoting Progression or Severity • Increased alcohol intake • Age > 40 years at time of infection • HIV co-infection • Other • Male gender • Chronic HBV co-infection

48. Hepatitis C: Diagnosis • ELISA • usually positive within 2-5 months after infection • PCR • positive 1-2 weeks post infection

49. Hepatitis D • Defective virus that requires co-infection with hepatitis B for replication • Enveloped with SS RNA genome • Only antigen encoded in the delta antigen

50. Hepatitis D Virus Modes of Transmission • Percutaneous exposures • injecting drug use • Permucosalexposures • sex contact