Medical Virology (Part 4) PDF

Medical virology (Part4) By Dr. Amr Shaker Lecturer of Microbiology & Immunology Content A. Viral hepatitis B. Viral hemorrhagic fevers A. Viral hepatitis  Viral hepatitis Hepatitis is an inflammation of the liver. The condition can be self- limiting or can...

Medical virology (Part4) By Dr. Amr Shaker Lecturer of Microbiology & Immunology Content A. Viral hepatitis B. Viral hemorrhagic fevers A. Viral hepatitis  Viral hepatitis Hepatitis is an inflammation of the liver. The condition can be self- limiting or can progress to fibrosis (scarring), cirrhosis or liver cancer. Hepatitis viruses are the most common cause of hepatitis in the world Other infections, toxic substances (e.g. alcohol, certain drugs), and autoimmune diseases can also cause hepatitis. Viral hepatitis is a cause of considerable morbidity and mortality in the human population, both from acute and chronic infections Hepatocellular carcinoma which is one of the ten most common cancers worldwide, is closely associated with hepatitis B, and at least in some regions of the world with hepatitis C virus. There are 5 main hepatitis viruses, referred to as types A, B, C, D and E.  Hepatitis viruses HAV HBV HCV HDV HEV Viral genome ssRNA dsDNA ssRNA ssRNA ssRNA Delta agent (RNA Classification Picornavirus Hepadnavirus Flavivirus Calicivirus genome in HBV capsid) Route of Feco-oral transmission Feco-oral Blood/blood products/body fluids Chronic No Yes No infection Vaccine Yes Yes No Yes No  Hepatitis A virus (HAV) HAV belongs to picornavirus family HAV is non-enveloped, (+)ssRNA Mode of transmission Feco-oral route 1. Ingestion of food or water that has been contaminated with the faeces of an infected person (Sewage-contaminated water) 2. Infected food handlers  Hepatitis A virus (HAV) Symptoms The incubation period is usually 14–28 days Symptoms of hepatitis A range from mild to severe and can include: 1. Fever, malaise, loss of appetite (anorexia) 2. Diarrhea, nausea, abdominal discomfort 3. Joint pain 4. Upper right quadrant pain 5. Elevated liver enzymes (ALT & AST) 6. Dark-coloured urine and jaundice (a yellowing of the eyes and skin) (High Bilirubin) Adults have signs and symptoms of illness more often than children Hepatitis A virus (HAV)  Hepatitis A virus (HAV) Diagnosis Cases of hepatitis A are not clinically distinguishable from other types of acute viral hepatitis 1. Detection of HAV-specific immunoglobulin G (IgM) antibodies in the blood using ELISA kits 2. RT-PCR to detect the hepatitis A virus RNA Treatment and prevention There is no specific treatment for hepatitis A. Recovery from symptoms following infection may be slow and can take several weeks or months A. Improved sanitation, food safety B. Immunization  Adequate supplies of safe drinking Children need 2 doses of hepatitis water A vaccine (Inactivated vaccine)  Proper disposal of sewage  First dose: 12 through 23 months  Personal hygiene practices such as of age regular handwashing before meals and  Second dose: at least 6 months after going to the bathroom. after the first dose  Hepatitis E virus (HEV) HAV belongs to calicivirus family HAV is non-enveloped, (+)ssRNA Mode of transmission The same as HAV Symptoms Diagnosis 1. Detection of HEV-IgM antibodies in the blood 2. RT-PCR to detect the hepatitis E virus RNA Treatment and prevention No FDA-approved vaccine for hepatitis The same as HAV E is currently available in the United States; however, in 2012 a recombinant vaccine was approved for use in China.  Hepatitis B virus (HBV) HBV belongs to hepadnavirus family HBV is enveloped, dsDNA Disease Hepatitis B Hepatitis B is a liver infection caused by the hepatitis B virus Some people with hepatitis B are sick for only a few weeks (Acute infection), but for others, the disease progresses to a serious, lifelong illness (Chronic infection) Mode of transmission 1) Blood and blood products Blood transfusions, serum products, Sharing of needles, razors, acupuncture Renal dialysis / Organ donation 2) Sexual intercourse 3) Vertical transmission from a carrier mother to her baby (Transplacental)  Hepatitis B virus (HBV) Symptoms Signs and symptoms of hepatitis B range from mild to severe They usually appear about one to four months after you've been infected Some people, usually young children, may not have any symptoms The same classical symptoms as HAV Diagnosis A. Serology: Based on detecting the viral antigens or antibody response B. HBV-PCR: For detection of viral nucleic acid C. Liver biopsy: For detection of degree of liver damage  Hepatitis B virus (HBV) Viral antigens Antigen Significance Hepatitis B  Is the earliest indicator of acute infection and is also surface indicative of chronic infection if its presence persists antigen for more than 6 months. (HBsAg)  It is useful for the diagnosis of HBV infection and for screening of blood.  Its specific antibody is anti-HBs.  HBsAg indicates that the person is potentially infectious. Hepatitis B e  HBeAg appearing during weeks 3 to 6 indicates an antigen acute active infection and means that the patient (HBeAg) is infectious  Continuous presence of anti-HBe indicates chronic or chronic active liver disease  HBeAg is not incorporated into virions, but is instead secreted into the serum  Its specific antibody is anti-HBe Hepatitis B  Is derived from the protein coat that encloses core antigen the viral DNA (HBcAg)  It is not detectable in the bloodstream  Its specific antibody is anti-HBc  Hepatitis B virus (HBV) Antigen & Antibody profiles Acute infection  Hepatitis B virus (HBV) Antigen & Antibody profiles Chronic infection  Interpretation of Hepatitis B Serologic Test Results Ag/Ab profile Result Interpretation HBsAg Negative Susceptible anti-HBc Negative anti-HBs Negative HBsAg Negative Immune due to natural infection anti-HBc Positive anti-HBs Positive HBsAg Negative Immune due to hepatitis B vaccination anti-HBc Negative anti-HBs Positive HBsAg Positive Acutely infected (Recent) anti-HBc Positive IgM anti-HBc Positive anti-HBs Negative HBsAg Positive Chronically infected anti-HBc Positive IgM anti-HBc Negative anti-HBs Negative Interpretation unclear; four possibilities: HBsAg Negative 1. Resolved infection (most common) anti-HBc Positive 2. False-positive anti-HBc, thus susceptible anti-HBs Negative 3. ―Low level‖ chronic infection 4. Resolving acute infection  Hepatitis B virus (HBV) Complications Signs and symptoms of hepatitis B range from mild to severe They usually appear about one to four months after you've been infected 1. Liver cirrhosis The inflammation associated with a hepatitis B infection can lead to extensive liver scarring (cirrhosis), which may impair the liver's ability to function. 2. Hepatocellular carcinoma (HCC) 3. Fulminant Hepatitis  Hepatitis B virus (HBV) Treatment Entecavir (Baraclude), tenofovir (Viread), lamivudine (Epivir)®, adefovir (Hepsera)®, telbivudine (Tyzeka)® Interferon alpha 2a (Pegylated IFN 2a (Pegasys)® In 2015 the World Health Organization recommended tenofovir or entecavir as first line agents  Hepatitis B virus (HBV) Prevention 1. Active immunization: Hepatitis B surface antigen (HBsAg) vaccine Is a recombinant vaccine is based on Hepatitis B surface antigen (HBsAg) gene inserted into yeast Hepatitis B vaccine can prevent hepatitis B (Acute & Chronic cases) Hepatitis B vaccine is usually given as 2, 3, or 4 shots. Hepatitis B vaccine is also recommended for certain unvaccinated adults: 1. Travelers to regions with increased rates of hepatitis B 2. People with chronic liver disease, kidney disease, HIV infection, infection with hepatitis C, or diabetes 3. People who have household contact with someone infected with the hepatitis B virus 2. Passive immunization Hepatitis B immune globulin should be administered to non immune individuals following single episode exposure to HBV-infected blood For example: needle stick injuries  Hepatitis D virus (Delta agent) Hepatitis D virus (HDV) is found in nature only as a coinfection or superinfection with HBV It is significant because its presence results in more severe acute disease, with a greater risk of fulminant hepatitis and, in chronically infected patients, a greater risk of cirrhosis and liver cancer. Mode of transmission The same as HBV EXCEPT It does not appear to be transmitted sexually as frequently as HBV Treatment  No specific treatment for HDV infection is available. Because HDV depends on coinfection with HBV  The approaches for preventing HBV infection are also effective in preventing HDV infection  Hepatitis C virus (HCV) HCV belongs to flaviavirus family HCV is enveloped, (+)ssRNA Disease Hepatitis C virus (HCV) causes both acute and chronic infection. Acute HCV infections are usually asymptomatic and most do not lead to a life-threatening disease. Around 30% (15–45%) of infected persons spontaneously clear the virus within 6 months of infection without any treatment. The remaining 70% (55–85%) of persons will develop chronic HCV infection. Of those with chronic HCV infection, the risk of cirrhosis ranges from 15% to 30% within 20 years. Mode of transmission Blood and blood products Blood transfusions, serum products, Sharing of needles, razors, acupuncture  Hepatitis C virus (HCV) Symptoms The incubation period for hepatitis C ranges from 2 weeks to 6 months Following initial infection, approximately 80% of people do not exhibit any symptoms Those who are acutely symptomatic may exhibit: fever, fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark urine, pale faeces, joint pain and jaundice (yellowing of skin and the whites of the eyes) Complications 1) Chronic liver disease 2) Hepatocellular carcinoma  Hepatitis C virus (HCV) Diagnosis Diagnosed by detection of METAVIR system 1. Anti-HCV HCV RNA (FibroTest- antibodies ActiTest®) To determine the degree of liver damage Rapid HCV-RT PCR immunoassay (15 100 000 000 IU/ml) 3rd 15-200.000 (low) generation >200.000-1000,000 (moderate) ELISA > 1000,000 -100,000,000 (high)  Biopredictive tests work by using an algorithm based on the patients’ sex, age, weight, height and specific blood biomarkers providing a an assessment of the liver histological status.  FibroTest® : assesses hepatic fibrosis ActiTest® : assesses viral necro-inflammatory activity  Hepatitis C virus (HCV) Treatment 1. Combination of Sofosbuvir (Sovaldi)® with ribavirin and pegylated interferon alpha or beta for a period of 24 or 48 weeks 2. Sofosbuvir and Simiprevir (Olysio)® orally. 3. Ledipasvir-sofosbuvir (Harvoni)® 4. Daclatasvir (Daklinza)®–sofosbuvir (Sovaldi)® B. Viral hemorrhagic fevers  Viral hemorrhagic fevers The term ―viral hemorrhagic fever‖ refers to a condition that affects many organ systems of the body, damages the overall cardiovascular system, causing bleeding, or hemorrhaging Some VHFs cause relatively mild illness, while others can cause severe, life-threatening disease Most VHFs have no known cure or vaccine Although VHFs are caused by several families of viruses, these viruses share some common characteristics: 1. They are RNA viruses 2. They are covered, or enveloped, in a lipoprotein outer layer, making it easier to destroy these viruses with physical (heat, sunlight, gamma rays) and chemical (bleach, detergents, solvents) methods 3. They naturally exist in animal or insect populations, referred to as host populations, and are generally restricted to the geographical areas where the host species live 4. They spread to people when a person encounters an infected animal or insect host. After the initial spread into the human population, some VHF viruses can continue to spread from person-to-person  Viral hemorrhagic fevers The most important examples of VHF viruses: Ebola Virus Hantaviruses 01 02 Dengue viruses Lassa fever virus 03 04  1. Ebola Virus Disease: Ebola Ebola Virus Disease (EVD) is a rare and deadly disease in people and non-human primates (such as monkeys, gorillas, and chimpanzees) Mode of transmission The virus spreads through direct contact (such as through broken skin or mucous membranes in the eyes, nose, or mouth) with: 1. Blood or body fluids (urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen) of a person who is sick with or has died from Ebola virus disease (EVD) 2. Objects (such as clothes, bedding, needles, and medical equipment) contaminated with body fluids from a person who is sick with or has died from EVD 3. Semen from a man who recovered from EVD (through oral, vaginal, or anal sex)  1. Ebola Virus Signs and symptoms  Incubation period from 2 to 21 days after contact with the virus, with an average of 8 to 10 days  The course of the illness typically progresses from ―dry‖ symptoms initially (such as fever, aches and pains, and fatigue), and then progresses to ―wet‖ symptoms (such as diarrhea, vomiting, bleeding) as the person becomes sicker  EVD is a rare but severe and often deadly disease Recovery from EVD depends on good supportive clinical care and the patient’s immune response  1. Ebola Virus Diagnosis  To determine whether EVD is a possible diagnosis, there must be a combination of symptoms suggestive of EVD AND a possible exposure to EVD within 21 days before the onset of symptoms Specimen: Blood Lab test: RT-PCR Treatment A. Supportive care: B. Therapeutics: 1. Providing fluids and electrolytes (body salts) orally or through infusion into the vein (intravenously) Inmazeb ™ Monoclonal 2. Using medication to support blood pressure, reduce vomiting and diarrhea, and to manage fever and pain antibodies ebanga™ 3. Treating other infections, if they occur Prevention Ervebo® (Single dose vaccine)  This is the first FDA-approved vaccine for Ebola (Since December 2019)  For adults ≥ 18 years of age in the U.S. population who are at potential occupational risk of exposure to Zaire ebolavirus  2. Hantaviruses Hantaviruses are a family of viruses spread mainly by rodents Some strains cause potentially fatal diseases in humans, such as hantavirus hemorrhagic fever with renal syndrome (HFRS), or hantavirus pulmonary syndrome (HPS) Mode of transmission Hantaviruses are transmitted by contact with the bodily fluids of rodents: A. from saliva from bites B. especially from inhalation of viral particles from urine and No person to person feces in aerosols transmission  2. Hantaviruses Signs and symptoms Hantavirus Pulmonary Hemorrhagic Fever with Renal Syndrome (HPS) Syndrome (HFRS) Initial symptoms: muscle aches, intense headaches, back and especially in the large abdominal pain, fever, chills, nausea, muscle groups— and blurred vision, redness of the thighs, hips, back eyes, or a rash Later symptoms: Four to 10 days after low blood pressure, acute shock, the initial phase of vascular leakage, and acute kidney illness failure, which can cause severe fluid overload HPS can be fatal. It has a mortality rate of 38% HFRS fatality ranges from 5-15%  2. Hantaviruses Treatment Hantavirus Pulmonary Hemorrhagic Fever with Renal Syndrome (HPS) Syndrome (HFRS) There is no specific treatment, cure, or vaccine for hantavirus infection Only supportive therapy 1. careful management of the patient’s fluid (hydration) and electrolyte (e.g., sodium, potassium, chloride) levels 2. maintenance of correct oxygen and blood pressure levels 3. appropriate treatment of any secondary infections 4. Intravenous ribavirin, an antiviral drug 5. Dialysis may be required to correct severe fluid overload  3. Dengue viruses Disease: dengue fever There are four serotypes of dengue viruses that can cause dengue fever Person can be infected with a dengue virus as many as four times in his or her lifetime Mode of transmission  Dengue viruses are spread to people mainly through the bites of infected Aedes species mosquitoes Aedes aegypti mosquito  Vertical transmission (from mother to child) during pregnancy or at birth  3. Dengue viruses Signs and symptoms Severe dengue About 1 in 20 people  Mild symptoms of who get sick with dengue can be Symptoms of dengue will develop confused with dengue can other illnesses that become severe severe dengue cause fever, aches within a few can result in shock, hours and pains, or a rash internal bleeding, and even death  Symptoms of dengue typically Infants and pregnant last 2–7 days. Most women are at higher people will recover risk for developing after about a week severe dengue Treatment 1. Rest as much as possible Severe dengue is a medical 2. Take paracetamol to control fever and relieve pain emergency. It requires immediate medical care at a clinic or hospital 3. Drink plenty of fluids to stay hydrated  4. Lassa fever virus Lassa virus is an arenavirus that causes Lassa hemorrhagic fever It is endemic in West African countries, especially Sierra Leone, the Republic of Guinea, Nigeria, and Liberia Mode of transmission  The reservoir, or host, of Lassa virus is a rodent known as Mastomys natalensis  Mastomys rodents shed the virus in urine and droppings and direct contact with these materials, through touching soiled objects, eating contaminated food, or exposure to open cuts or sores, can lead to infection Transmission of Lassa virus to humans occurs most commonly through ingestion or inhalation  4. Lassa fever virus Signs and symptoms Treatment A. Supportive care: The most 1. maintenance of appropriate common fluid and electrolyte balance, complication oxygenation and blood of Lassa pressure fever is deafness 2. treatment of any other complicating infections B. Therapeutics: Ribavirin (most effective when given early in the course of the illness) THANKS! 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