1. GIT- Pathogenic Virus Viral Hepatitis & Gastroenteritis Dr. Yasir A Hussein, MD – Pathology – Microbiology & Medical education. 2016-1017

2. List names; and the major structural features, pathogenetic mechanisms, clinical significance and laboratory findings of the main viruses that cause GIT infections. Objectives :

3. Hepatitis is the term used to describe inflammation of the liver. It's usually the result of a viral infection or liver damage caused by drinking alcohol. There are several different types of hepatitis, most of which are outlined below. Some types will pass without any serious problems, while others can be long-lasting (chronic) and cause scarring of the liver (cirrhosis), loss of liver function and, in some cases, liver cancer Introduction of Viral Hepatitis

4. Source of virus fecesblood/ blood-derived body fluids blood/ blood-derived body fluids blood/ blood-derived body fluids feces Route of transmission fecal-oralpercutaneous sexually percutaneous Sexually percutaneous Sexually fecal-oral Chronic infection noyes no Preventionpre/post- exposure immunization pre/post- exposure immunization blood donor screening; risk behavior modification pre/post- exposure immunization; risk behavior modification ensure safe drinking water Type of Hepatitis ABCDE

5. Fecal-oral route (contaminated water, food or milk). Direct personal contact(hands). Blood transfusion. Sharing contaminated syringes or other sharp or cutting objects. Mother to baby during pregnancy. Sexual transmission (a rarer form of infection). General Mode of Transmission

6. Incubation period:Average 30 days Range 15-50 days Complications:Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Chronic sequelae:None Hepatitis A - Clinical Features

7. Close personal contact (e.g., household contact, child day care centers) Contaminated food, water (e.g., infected food handlers, raw shellfish) Blood exposure (rare) (e.g., injecting drug use, transfusion) Hepatitis A Virus Transmission

8. The risk of hepatitis A infection is associated with a lack of safe water, and poor sanitation and hygiene (such as dirty hands). A safe and effective vaccine is available to prevent hepatitis A. Preventive, Safe water supply, food safety, improved sanitation, hand washing. The hepatitis A vaccine are the most effective ways to combat the disease. CONT:

9. Endemicity Disease Rate Peak Age of InfectionTransmission Patterns HighLow to High Early childhood Person to person; outbreaks uncommon ModerateHighLate childhood/ young adults Person to person; food and waterborne outbreaks Low Young adultsPerson to person; food and waterborne outbreaks Very low AdultsTravelers; outbreaks uncommon Global Patterns of Hepatitis A Virus Transmission

10. Laboratory Diagnosis Acute infection is diagnosed by the detection of HAV-IgM in serum by ELISA. Past Infection i.e. immunity is determined by the detection of HAV-IgG by ELISA. The total HAV antibody test detects both IgM and IgG antibodies and thus may be used to identify both current and past infections

11.  Incubation period:Average 60-90 days Range 45-180 days  Clinical illness (jaundice):<5 yrs, <10% 5 yrs, 30%-50%  Acute case-fatality rate:0.5%-1%  Chronic infection:<5 yrs, 30%-90% 5 yrs, 2%-10%  Premature mortality from chronic liver disease:15%-25% Hepatitis B - Clinical Features

12.  Sexual - sex workers and homosexuals are particular at risk.  Parenteral - IVDA, Health Workers are at increased risk.  Perinatal - Mothers who are HBeAg positive are much more likely to transmit to their offspring than those who are not. Perinatal transmission is the main means of transmission in high prevalence populations. Hepatitis B Virus Modes of Transmission

13. Sequels of Chronic Hepatitis B Diseases 1.Chronic Persistent Hepatitis- asymptomatic 2.Chronic Active Hepatitis - symptomatic exacerbations of hepatitis 3. Cirrhosis of Liver 4. Hepatocellular Carcinoma

14. HighModerate Low/Not Detectable BloodSemenUrine SerumVaginal fluidFeces Wound exudatesSalivaSweat Tears Breast milk Concentration of Hepatitis B Virus in Various Body Fluids

15. Diagnosis A battery of serological tests are used for the diagnosis of acute and chronic hepatitis B infection. HBsAg - used as a general marker of infection. HBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection. anti-HBcIgG - past or chronic infection. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe The appearance of antibodies to Hepatitis B “e” antigen is an indicator of resolution of acute infection. HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape mutants. Used mainly for monitoring response to therapy.

16. Treatment Interferon - for HBeAg +ve carriers with chronic active hepatitis. Response rate is 30 to 40%. Lamivudine - It can inhibit both types (1 and 2) of HIV reverse transcriptase. Another problem is the rapid emergence of drug resistance. Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA.

17. Prevention Vaccination - highly effective recombinant vaccines are now available. Vaccine can be given to those who are at increased risk of HBV infection such as health care workers. It is also given routinely to neonates as universal vaccination in many countries. Hepatitis B Immunoglobulin - HBIG may be used to protect persons who are exposed to hepatitis B. It is particular efficacious within 48 hours of the incident. It may also be given to neonates who are at increased risk of contracting hepatitis B i.e. whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions.

18. Incubation period:Average 6-7 wks Range 2-26 wks Clinical illness (jaundice):30-40% Chronic hepatitis:70% Persistent infection:85-100% Hepatitis C - Clinical Features

19.  Transfusion or transplant from infected donor  Injecting drug use  Hemodialysis (yrs on treatment)  Accidental injuries with needles/sharps  Sexual/household exposure to anti-HCV-positive contact  Multiple sex partners  Birth to HCV-infected mother Risk Factors Associated with Transmission of HCV

20. Chronic Hepatitis C Infection The spectrum of chronic hepatitis C infection is essentially the same as chronic hepatitis B infection. All the manifestations of chronic hepatitis B infection may be seen, with a lower frequency i.e. chronic persistent hepatitis, chronic active hepatitis, cirrhosis, and hepatocellular carcinoma.

21. Laboratory Diagnosis HCV antibody - generally used to diagnose hepatitis C infection. Not useful in the acute phase as it takes at least 4 weeks after infection before antibody appears. HCV-RNA - various techniques are available e.g. PCR and branched DNA. May be used to diagnose HCV infection in the acute phase. However, its main use is in monitoring the response to antiviral therapy. HCV-antigen - an ELISA for HCV antigen is available. It is used in the same capacity as HCV-RNA tests but is much easier to carry out.

22. Treatment Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. Ribavirin - there is less experience with ribavirin than interferon. However, recent studies suggest that a combination of interferon and ribavirin is more effective than interferon alone.

23.  Screening of blood, organ, tissue donors  High-risk behavior modification  Blood and body fluid precautions Prevention of Hepatitis C

24.  Percutanous exposures  injecting drug use  Permucosal exposures  sex contact Hepatitis D Virus Modes of Transmission

25. Incubation period:Average 40 days Range 15-60 days Case-fatality rate:Overall, 1%-3% Pregnant women, 15%-25% Illness severity:Increased with age Chronic sequelae:None identified Hepatitis E - Clinical Features

26. Diarrhoeal Viruses An Overview

27. Viral Gastroenteritis It is thought that viruses are responsible for up to 3/4 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. Many different types of viruses are found in the gut but only some are associated with gastroenteritis.

28. Viruses found in the gut A. Associated with gastroenteritis Rotaviruses Adenoviruses Caliciviruses Norwalk like viruses. Astroviruses SRV (Small Round Viruses) Coronaviruses Toroviruses

29. Viruses found in the gut B. Found in the gut, not normally associated with gastroenteritis Polio Coxsackie A Coxsackie B Echo Enteroviruses 68-71 Hepatitis A Hepatitis E Adenoviruses 1-39 Reoviruses C. Found in the gut as opportunistic infection CMV HSV VZV HIV

30. Rotaviruses Also found in other mammals and birds, causing diarrhoea. Account for 50-80% of all cases of viral gastroenteritis, dehydration &malabsorption. Usually endemic, but responsible for occasional outbreaks. Causes disease in all age groups but most severe symptoms in neonates and young children. Asymptomatic infections common in adults and older children. Symptomatic infections again common in people over 60. Up to 30% mortality rate in malnourished children, responsible for up to half a million deaths per year.

31. Rotaviruses 80% of the population have antibody against rotavirus by the age of 3. More frequent during the winter. Transmission of rotaviruses is primarily by the fecal–oral route, which can happen directly from person to person, or indirectly via contaminated fomites. Pathology, defect in enterocytes. 24-48 hr incubation period followed by an abrupt onset of vomiting and diarrhoea, a low grade fever may be present. Diagnosed by electron microscopy or by the detection of rotavirus antigens in faeces by ELISA or other assays. Live attenuated vaccines now available for use in children.

32. ونسال الله القبول وما توفيقي الا بالله