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Introduction to Microbiology

Introduction to Microbiology. Anas Abu - Humaidan M.D. Ph.D. Lecture 29. Viruses overview. The causes of hepatitis (inflammation of the liver) are varied and include infectious causes ( viruses , bacteria, and protozoa), as well as non-infectious causes (drugs and toxins like ethanol).

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Introduction to Microbiology

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  1. Introduction to Microbiology Anas Abu-Humaidan M.D. Ph.D. Lecture 29

  2. Viruses overview • The causes of hepatitis (inflammation of the liver) are varied and include infectious causes (viruses, bacteria, and protozoa), as well as non-infectious causes (drugs and toxins like ethanol). • The clinical symptoms and course of acute viral hepatitis can be similar, regardless of etiology • Hepatitis may be caused by at least five viruses belonging to different virus families • The following viruses associated with hepatitis will be discussed in this lecture: • hepatitis A virus (HAV) • hepatitis B virus (HBV) • hepatitis C virus (HCV) • hepatitis D virus (HDV) • hepatitis E virus (HEV)

  3. Hepatitis A virus (HAV) • Belongs to the Picornaviridae. Naked with icosahedral capsid , single-stranded, positive-sense RNA virus. • The assembly of the progeny viruses takes place in the cytoplasm after the packaging of viral genomes into HAV capsid proteins. • Virions are released upon cell lysis. • The response to replication in the liver consists of lymphoid cell infiltration and necrosis of liver parenchymal cells.

  4. Hepatitis A disease • The major mode of spread of HAV is person to person by fecal–oral exposure, and it occurs very frequently in nursing home settings and day care centers. • Outbreaks related to ingestion of contaminated food or water. • More than 90% of the adult population in many developing countries shows evidence of previous hepatitis A infection. • The risk of clinically evident disease is much higher in infected adults than in children.

  5. Hepatitis A disease FIGURE 13–3. Sequence of appearance of viremia, virus in feces, alanine aminotransferase (ALT), symptoms, jaundice, and IgM and IgG antibodies in hepatitis A virus (HAV) infection. • Contagion is greatest 10 to 14 days before the symptoms appear • Detectable levels of IgG antibody to HAV persist indefinitely in serum, and patients with anti-HAV antibodies are immune to reinfection.

  6. Hepatitis A disease • Manifests as Fever; anorexia (poor appetite); nausea; pain in the right upper abdominal quadrant; and, within several days, jaundice. • The infection-to-disease ratio is dependent on age; it may be as high as 20:1 in children and approximately 1:1 in older adults. • There is no specific treatment for patients with acute hepatitis A. Supportive measures include adequate nutrition and rest. • Almost all cases (99%) of HAV are self-limiting. • There is currently a vaccine for HAVwith almost 100% protection (like a natural infection)

  7. Hepatitis B virus (HBV) • Belongs to the family Hepadnaviridae. is an enveloped partially double-stranded DNA virus. • Has the smallest genome size among DNA viruses. • Aggregates of HBsAg are often found in great abundance in serum during infection A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription.

  8. Hepatitis B virus (HBV)

  9. Hepatitis B disease • The symptoms associated with acute hepatitis B are more severe and more prolonged than those of hepatitis A; however, asymptomatic infection occur (infection-to-disease ratio 3:1) • Acute hepatitis B is usually manifested by the gradual onset of fatigue, loss of appetite, nausea and pain, and fullness in the right upper abdominal quadrant. • One important difference between hepatitis A and hepatitis B is the development of chronic hepatitis, which occurs in approximately 10% of all patients with hepatitis B infection. • Chronic hepatitis may lead to cirrhosis, liver failure, or HCC in up to 25% of the patients. • There is no specific treatment recommended for acute hepatitis B. • Recombinant (HBsAg) vaccine recommended for all children and high-risk persons

  10. Hepatitis B disease • Hepatitis B infection is found worldwide, with prevalence rates varying markedly among countries, but a total of approximately 400 million persons • Chronic carriers constitute the main reservoir of infection: in some countries, particularly in the Far East, up to 5% to 15% of all persons carry the virus. • The virus is spread vertically (during child birth), parenterally (needle stick injuries), and by sexual contact (especially in men who have sex with men).

  11. Hepatitis B disease • Upon resolution of acute hepatitis B, HBsAg and HBeAg disappear from serum with the development of antibodies (anti-HBs and anti-HBe) against them. • Appearance of anti-HBssignals elimination of infection • The laboratory diagnosis of acute hepatitis B is best made by demonstrating the IgM antibody to HBcAg in serum • Past infection with hepatitis B is best determined by detecting IgG anti-HBc, or anti-HBs.

  12. Hepatitis D virus (HDV) • Enveloped, Small, single-stranded (–) circular RNA virus • HDVrequires the presence of HBsAg (HBV surface antigen) for its transmission, and is thus found only in persons with acute or chronic HBV infection. • Simultaneous infection with both delta and hepatitis B may result in clinical hepatitis that is indistinguishable from acute hepatitis A or B, but usually the disease is more severe. • Diagnosis is by detection of antibodies to delta antigen

  13. Hepatitis C virus (HCV) • Enveloped RNA virus of Flaviviridae family, positive sense, single-stranded RNA genome, • HCV is highly heterogeneous because the genome of HCV is highly mutable, which hinders the development of an HCV vaccine. • Similar to other positive-sense RNA viruses, HCV also replicates in the cytoplasm of the infected cell.

  14. Hepatitis C disease • Similar to HBV, HCV is spread parenterally (blood transfusions, childbirth). • Screening of donor blood for antibody has reduced posttransfusionhepatitis by 80% to 90%. • The highest prevalence of HCV is in the Middle East, especially in Egypt.

  15. Hepatitis C disease • After entering the blood, HCV moves to the main site of infection—the liver. • The immune response to HCV (antibodies, cytokines, cell infiltration) causes liver damage, and HCV can evade the immune system leading to chronic infection and liver damage. • The acute infection is usually asymptomatic or mild, but it results in a chronic carrier state in up to 85% of adult patients. • HCV-infected patients may develop cirrhosis of liver with increased risk of hepatocellular carcinoma (HCC). FIGURE 13–13. Inflammation in chronic hepatitis C virus (HCV) infection. Chronic inflammation of the portal area with a lymphoid aggregate in the center can be seen.

  16. Hepatitis E virus (HEV) • Naked capsid, icosahedral, positivesense RNA virus • Hepatitis E spreads in a similar manner to that of hepatitis A. Twenty million HEV infections occur every year worldwide, mostly in developing countries. • Frequently subclinical, like hepatitis A HEV acute hepatitis indistinguishable from other acute hepatitis infections

  17. Viruses overview Interferon and nucleoside and nucleotide analogs and inhibitors can be of benefit in chronic infection

  18. Viruses overview

  19. Further reading: • Sherris Medical Microbiology, sixth edition • Chapter 13

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