C hair of Medical biology, M icrobiology, V irology, and I mmunology

1. Chair of Medical biology, Microbiology, Virology, and Immunology Hepatitis Viruses Human Immunodeficiency Virus By as. E.V. Pokryshko

2. Hepatitis is an inflammation of the liver. Human hepatitis is caused by at least six genetically and structurally distinct viruses. The diseases caused by each of these viruses are distinguished in part by the length of their incubation periods and the epidemiology of the infection.

3. Characteristics of Human Hepatitis Viruses

4. Characteristics of Human Hepatitis Viruses

5. HepatitisAvirus Electron microscopy of fecal extracts

6. HepatitisA virus

7. Global Prevalence of Hepatitis A Infection HAV Prevalence High Intermediate Low Very Low

8. Hepatitis A Transmission • Fecal-oral contamination of food or water Food handlers Raw shellfish Travel to endemic areas Close personal contact Household or sexual contact Daycare centers Natural infection with HAV is seen only in human.

9. Hepatitis A - Clinical Features • Incubation period: Average 30 days • Range 15-50 days • Jaundice by <6 yrs, <10%age group: 6-14 yrs, 40%-50% >14 yrs, 70%-80% • Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis • Chronic sequelae: None

10. Clinical Variants of Hepatitis A Infection • Asymptomatic (anicteric) disease Children under 6 years of age, > 90% Children from 6-14 years old, 40-50% • Symptomatic (icteric) disease Adults and children over 14, 70-80%

11. Pathogenesis of Hepatitis A virus infections During an asymptomatic incubation period, the liver is infected and large amounts of virus can be shed in the feces. Symptoms usually begin abruptly with fever, nausea, and vomiting. The major area of cell necrosis occurs in the liver, and the resulting enlargement of the liver frequently causes blockage of the biliary excretions, resulting in jaundice, dark urine, and clay colored stool. A fulminant form of hepatitis A occurs in only 1% to 4% of patients. Complete recovery can require 8 to 12 weeks, especially in adults.

12. Concentration of Hepatitis A Virusin Various Body Fluids Body fluid Feces Serum Saliva Urine 102 104 100 106 108 1010 Infection Doses per ml

13. During convalescence, patients frequently remain weak and occasionally mentally depressed. In humans, the severity of the disease varies considerably with age, most cases occurring in young children are mild and undiagnosed, resolving without sequelae. In contrast to HBV, HAV infections result in no extrahepatic manifestations of acute infection and no long term carrier state, and they are not associated with either cirrhosis or primary hepatocellular carcinoma.

14. Diagnosis of Hepatitis A virus infections. The diagnosis of individual cases of hepatitis A usually is not possible without supporting laboratory findings. Virus particles frequently can be detected in fecal extracts by use of IFT. Standard RIA also can be used to detect the presence of HAV antigens in fecal extracts. An ELISA using anti-HAV linked to either horseradish peroxidase or alkaline phosphatase also is used to detect fecal HAV. In addition, a specific diagnosis of hepatitis A can be made by demonstrating at least a four fold rise in anti-HAV antibody levels in serum.

15. Symptoms ALT Total anti-HAV Fecal HAV IgM anti-HAV 4 5 6 12 24 0 1 2 3 Months after exposure Typical Serologic Course of Acute Hepatitis A Virus Infection

16. Control of Hepatitis A virus infections. Proper sanitation to prevent fecal contamination of water and food is the most effective way to interrupt the fecal-oral transmission of hepatitis A. Pooled immune serum globulin from a large number of individuals can be used to treat potentially exposed poisons, and its effectiveness has been well established.

17. Control of Hepatitis A virus infections. Formalin inactivated HAV vaccines have been developed and some have been licensed. Additional approaches using recombinant DNA techniques also are being used to generate subunit vaccines or novel recombinant vaccine strains.

18. Structure of the Hepatitis B virion HBe

19. FIGURE. Fraction of the blood serum from a patient with a severe ease of hepatitis. The larger spherical particles, or Dane particles, are 42 nm in diameter and are the complete hepatitis B virus. Also evident are filaments of capsid protein (HBsAg).

20. Hepatitis B virus

21. HBV - Epidemiology About 300 million people world-wide are thought to be carriers of HBV, and many carriers eventually die of resultant liver disease. Many HBV infections are asymptomatic (especially in children). However, many infections become persistent, leading to a chronic carrier state. This can lead to chronic active hepatitis and cirrhosis later in life. The HBV carrier state also is strongly associated with one of the most common visceral malignancies world-wide, primary hepatocellular carcinoma.

22. >8% 2-8% <2% HBV - Epidemiology Prevalence of HBsAg Carrier State

23. Epidemiology of Hepatitis B virus infections. For years, it was believed that a person could become infected only by the injection of blood or serum from an infected person or by the use of contaminated needles or syringes. As a result, the older name for this disease wasserum hepatitis. It has now been shown that this supposition is not true.

24. Epidemiology of Hepatitis B virus infections. Using serologic techniques, HBsAg has been found in feces, urine, saliva, vaginal secretions, semen, and breast milk. Undoubtedly, the mechanical transmission of infected blood or blood products is one of the most efficient methods of viral transmission, and infections have been traced to tattooing, ear piercing, acupuncture, and drug abuse. Neonatal transmission also appears to occur during childbirth. Virus can be sexually transmitted.

25. Hepatitis B Transmission 1. HBV spread mainly by parenteral route 2.directpercutaneous inoculation of infected serum or plasma 3. indirectly through cuts or abrasions 4. absorption through mucosal surfaces 5. absorption of other infectious secretions (saliva or semen during sex) 6.possible transfer via inanimate environmental surfaces 7.vertical transmission soon after childbirth (transplacental transfer rare) 8.close, intimate contact with an infected person

26. Who is at greatest risk for HBV infection? • drug abusers • blood product recipients • accounts for 5-10% postransfusion hepatitis • hemodialysis patients • people from southeast asian countries (70-80%)

27. Who is at greatest risk for HBV infection? • lab personnel working with blood products • sexually active homosexuals • persons with multiple and frequent sex contacts • medical/dental personnel In hospitals, HBV infections are a risk for both hospital personnel and patients because of constant exposure to blood and blood products.

28. Pathogenesis of hepatitis B virus infections. Acute hepatitis caused by HBV cannot be clinically distinguished from hepatitis caused by HAV. HBV infections are characterized by a long incubation period, ranging from 50 to 180 days. Symptoms such as fever, rash, and arthritis begin insidiously, and the severity of the infection varies widely. Mild cases that do not result in jaundice are termed anicteric.

29. In more severe cases, characterized by headache, mild fever, nausea, and loss of appetite, icterus (jaundice) occurs 3 to 5 days after the initial symptoms. The duration and severity of the disease vary from clinically inapparent to fatal fulminating hepatitis.The overall fatality rate is estimated to be 1% to 2%, with most deaths occurring in adults older than 30 years of age.

30. Differential Characteristics of Hepatitis A and Hepatitis B

31. Differential Characteristics of Hepatitis A and Hepatitis B

32. Chronic Hepatitis B Virus Infections. Between 6% and 10% of clinically diagnosed patients with hepatitis B become chronically infected and continue to have HBsAg in their blood for at least 6 months, and sometimes for life. Chronic infections can be subdivided into two general categories: 1. chronic persistent hepatitis 2. and chronic active hepatitis.

33. Chronic Hepatitis B Virus Infections. The latter is the most severe and often eventually leads to cirrhosis or the development of primary hepatocellular carcinoma. The prevalence of chronic carriers varies widely in different parts of the world, from 0.1% to 0.5% in the United States to up to 20% in China, Southeast Asia, and some African countries.

34. Diagnosis of Hepatitis B virus infections. As in all cases of viral hepatitis, abnormal liver function is indicated by increased levels of liver enzymes such as serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT). The presence of HBsAg confirms a diagnosis of hepatitis B, and its serologic detection is routinely carried out in diagnostic laboratories and blood banks using radioimmunoassays or enzyme-linked immunosorbent assay's.

35. Diagnosis of Hepatitis B virus infections. HBV core protein presence in serum is believed to reflect active replication of HBV and is a marker for active disease. The appearance of anti-HBc antibodies generally correlates with a good prognosis and a decline in virus replication.

36. Diagnosis of Hepatitis B virus infections. All carriers have antibodies to HBcAg, and some have antibodies to HBeAg. Those who do not possess antiHBe may have circulating HBeAg. Carriers with high concentrations of Dane particles and circulating HBeAg appear to be more likely to suffer liver damage than those in whom only HBsAg can be detected. However, such persons are much more likely to be transmitters of the disease than are those who have solely HBsAg in their blood.

37. PRACTICE • HBsAg N. • HBcAB (TOTAL) N. • HBsAB N. • HAV-IGM N. • HCV N. NO evidence of viral hepatitis viruses.

38. PRACTICE • HBsAG N. • HBcAB (TOTAL) P. • HBsAB P. • HAV-IGM N. • HCV N. PAST INFECTION.

39. PRACTICE • HBsAg N. • HBcAB (total) N. • HBsAB P. • HAV-IGM N. • HCV N. IMMUNIZATION.

40. PRACTICE • HBsAg P. • HBcAB (Total) P. • HBsAB N. • HAV-IGM N. • HCV N. MAY BE ACUTE OR CHRONIC. Order Hep. B Core IgM to clarify. The IgM will be positive , If Acute.

41. PRACTICE • HBsAg P. • HBcAB (TOTAL) P. • HBsAB N. • HAV-IGM P. • HCV P. Co-infection with HBV, HAV, and HCV

42. PRACTICE • HBsAG P. • HBcAB (total) P. • HBsAB P. • HAV-IGM N. • HCV N. Past infection with recovery, and then re-infection that has become chronic, this is very rare but does happen.

43. CONTROL OF HEPATITIS B VIRUS INFECTIONS. • The examination of all donor blood for the presence of HBsAg. • Passive immunization with hepatitis B immune globulin (HBIG). One important and effective use for HBIG, however, is the prevention of active hepatitis B infections in neonates born to mothers who are chronic carriers of HBsAg. HBIG also can be given to nonimmune individuals known to have been exposed to HBV. • Active immunization with HBsAg promises to provide a vehicle for the control of hepatitis B.

44. Hepatitis C virus. HCV is RNA virus. Sequence analysis has revealed that HCV is organized in a manner similar to the flaviviruses and that it shares biologic characteristics with this family. Structural model of the Hepatitis C virus.

45. Model of Human Hepatitis C Virus Lipid Envelope Capsid Protein Nucleic Acid Envelope Glycoprotein E2 Envelope Glycoprotein E1

46. Hepatitis C viruses

48. Hepatitis C: A Global Health Problem 170-200 Million (M) Carriers Worldwide Far East Asia 60 M Eastern Europe 10 M Western Europe 5 M United States 3-4 M Southeast Asia 30-35 M Africa 30-40 M Americas 12-15 M Australia 0.2 M

49. HCV • accounts for 90-95% of post transfusion hepatitis • risk of sexual transmission lower than for HBV • risk through casual contact low • vertical transmission possible • risk increased if mother is positive for HCV RNA • risk increased if mother is HIV positive • overall prevalence estimated at 1.4%

50. WHO IS ATGREATEST RISKFOR HCV INFECTION? • drug abusers • blood product recipients (anti-HCV screening has greatly reduced risk) • hemodialysis patients • lab personnel working with blood products • sexually active homosexuals • persons with multiple and frequent sexual contacts • medical/dental personnel (3-10% via needlestick from infected patient)