Viral Diseases 2024 Presentation PDF

Viruses and diseases that viruses cause, Antiviral agents Prof Dr. Necla TÜLEK 04 December 2024 Learning Objectives Development of viral diseases Transmission routes The mechanism of spread Clinical course Persistance of viruses Antiviral agents Important principles Man...

Viruses and diseases that viruses cause, Antiviral agents Prof Dr. Necla TÜLEK 04 December 2024 Learning Objectives Development of viral diseases Transmission routes The mechanism of spread Clinical course Persistance of viruses Antiviral agents Important principles Many viral infections are subclinical; the same disease may be produced by a variety of viruses the same virus may produce a variety of diseases no relationship to viral morphology the outcome in any particular case is determined by both viral and host factors and is influenced by the genetic Viral Infections No disease Asymptomatic Mild-moderate infections Severe infections Cancer Viral Pathogenesis Come in Viral clearance contact Host Viral Viral Cellular or Entry with immune replication spread injury susceptible response Persistance cells,  Viral Spread and Cell Tropism Viruses usually replicate at the primary site of entry Some produce diseases at the entry (eg Influenza viruses) Many viruses produce disease at sites distant from their point of entry (eg, enteroviruses, which enter through the gastrointestinal tract but may produce central nervous system disease. Mechanisms of viral spread : bloodstream (viremia) lymphatics neuronal (herpes simplex virüs, rabies) Viruses tend to exhibit organ and cell specificities=tropism presence of specific cell surface receptors for that virus Hepatitis B virus has a tropism for liver hepatocytes. Mechanisms of spread of virus through the body in human viral infections Outcome Acute infections Chronic infections in which replicating virus can be continuously detected, often at low levels; mild or no clinical symptoms may be evident. Hepatitis B virus Latent infections in which the virus persists in an occult (hidden or cryptic) form most of the time when no new virus is produced Herpesvirus Inapparent or subclinical infections Latent infections by herpesviruses Oncogenic viruses Hepatitis B virus HBV and HCV cause approximately 80% Hepatitis C virus of hepatocellular carcinoma , Human papillomavirus High-risk HPV strains major causes of cervical cancer, anogenital neoplasms, head and neck tumors Epstein Barr virus: Nasopharyngeal carcinoma, Hodgkin’s lymphoma, and Burkitt’s lymphoma Human herpes virus 8 : Kaposi’s sarcoma Merkel cell polyomavirus Merkel cell carcinoma HTLV-1 adult T-cell lymphoma  Bloodborne Pathogens What are bloodborne pathogens? Pathogenic microorganisms present in human blood that can lead to diseases Examples of primary concern Hepatitis B (HBV) Hepatitis C (HCV) Human Immunodeficiency Virus (HIV) Viral hemorrhagic fever (Crimean Congo Hemorrhagic Fever) Overview of hepatitis B Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. It has a worldwide distribution and currently more than 2 billion persons have been infected. WHO estimates that 296 million people were living with chronic hepatitis B infection in 2019, with 1.5 million new infections each year. In 2019, hepatitis B resulted in an estimated 820 000 deaths, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer). Hepatitis B can be prevented by vaccines that are safe, available and effective.  Transmission of Hepatitis B Transmitted through blood and infected bodily fluids as well as vaginal, and seminal fluids. Transmit through direct blood-to-blood contact, use of unsterile needles Sexual transmission ;unprotected sex, Perinatally from mother to newborn Hepatitis B is also spread by needlestick injury, tattooing, piercing and exposure to infected blood and body fluids, such as saliva and, menstrual, vaginal, and seminal fluids. Hepatitis B is not spread through food, water, or by casual contact. Epidemiology of Hepatitis B In highly endemic areas, hepatitis B is most commonly spread from mother to child at birth (perinatal transmission) or through horizontal transmission (exposure to infected blood), especially from an infected child to an uninfected child during the first 5 years of life. The development of chronic infection is common in infants infected from their mothers or before the age of 5 years. https://cdafound.org/polaris-countries-distribution/. Copyrights apply  The hepatitis B virus can survive outside the body for at least 7 days. During this time, the virus can still cause infection if it enters the body of a person who is not protected by the vaccine. The incubation period of the hepatitis B virus ranges from 30 to 180 days. The virus may be detected within 30 to 60 days after infection and can persist and develop into chronic hepatitis B, especially when transmitted in infancy or childhood HBV can survive for at least one week in dried blood Symptoms Patients with acute viral hepatitis commonly present with symptoms such as fever, malaise, fatigue, loss of appetite, vomiting, diarrhea, and abdominal pain. Patients may also report yellowish discoloration of their sclera (icterus) and /or skin (jaundice), dark-colored urine, and light-colored stools. Laboratory Diagnosis The two most important serologic tests for the diagnosis of early hepatitis B are the tests for HBsAg and for IgM antibody to the core antigen. The detection of viral DNA (viral load) in the serum is strong evidence that infectious virions are present. Reduction of the viral load in patients with chronic hepatitis B is used to monitor the success of drug therapy.  Note that there is a period Acute Hepatitis B Virus Infection with Recovery of several weeks when Typical Serologic Course HBsAg has disappeared but HBsAb is not yet detectable. This is the Symptoms window phase. At this time, the HBcAb is always HBeAg anti-HBe positive and can be used to make the diagnosis. Total anti-HBc HBcAb is present in those with acute infection and Titre chronic infection, as well as in those who have recovered from acute HBsAg IgM anti-HBc anti-HBsinfection. Therefore, it cannot be used to distinguish between acute and chronic infection. The IgM form of HBcAb is present during acute infection and disappears 0 4 8 12 16 20 24 28 32 36 52 100 approximately 6 months Weeks after Exposure after infection. Outcome of hepatitis B infection  Outcome of Hepatitis B Virus Infection 100 by Age at Infection 100 80 Chronic Infection (%) 80 Symptomatic Infection (%) 60 60 Chronic Infection 40 Chronic Infection (%) 40 20 20 Symptomatic Infection 0 0 Birth 1-6 months 7-12 months 1-4 years Older Children and Adults Age at Infection Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute Chronic (6 months) (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titre IgM anti-HBc 0 4 8 12 16 20 24 28 32 36 52 Years Weeks after Exposure  The likelihood that infection becomes chronic depends on the age at which a person becomes infected. Children less than 6 years of age who become infected with the hepatitis B virus are the most likely to develop chronic infections. In infants and children: 80–90% of infants infected during the first year of life develop chronic infections; and 30–50% of children infected before the age of 6 years develop chronic infections. In adults: less than 5% of otherwise healthy persons who are infected as adults will develop chronic infections; and 20–30% of adults who are chronically infected will develop cirrhosis and/or liver cancer. Bloodborne Pathogens Examples Hepatitis B – Relapsing fever Hepatitis C – Creutzfeldt-Jakob Hepatitis D (HDV) Disease Syphilis – Human T-Lymphotropic Malaria Virus Type I Babesiosis – Viral Hemorrhagic Fever Brucellosis Leptospirosis Arboviral Infections  Risk of Exposure Contamination sources: Blood Other potentially infectious materials Source: OSHA Human body fluids Any unfixed tissue or organ from human Cultures, culture mediums, or other solutions Experimental animal blood, tissues, or organs infected with HIV or HBV  Risk of Exposure Spread of bloodborne pathogens occurs through: Direct contact Indirect contact Respiratory transmission Vector-borne transmission Source: NIOSH  Risk of Exposure How exposure occurs: Needlesticks Cuts from other contaminated sharps Contact of mucous membrane or broken skin with contaminated blood Unbroken skin forms an impervious barrier against bloodborne pathogens. However, infected blood can enter your system through: Source: OSHA DTE Open sores Cuts Abrasions Acne Any sort of damaged or broken skin such as sunburn or blisters  Risk of Exposure Occupational exposures: Occupations at risk First responders Housekeeping personnel in some industries Nurses and other Source: OSHA healthcare personnel CDC estimates 5.6 million workers in healthcare and related occupations are at risk All occupational exposure to blood or other potentially infectious materials (OPIM) places workers at risk  Risk of Exposure The figure on left shows percent of occupational groups of healthcare workers exposed to blood or body fluids, with nurses (44%), physicians (28%), and technicians (15%) accounting for most of the incidents. The figure on the right shows healthcare work locations where exposures occurred, with inpatient facilities, such as the medical or surgical ward (20%) and intensive care unit (13%), and operating rooms (25%) accounting for the majority of exposure sites. Source: CDC (2008) Nurses are the predominant occupational group injured by needles and other sharps, in part because they are the largest segment of the workforce at most hospitals  Controlling Exposures Observe standard precautions, such as: Under circumstances in which differentiation between body fluid types is difficult or impossible, all body fluids shall be considered potentially infectious materials. Treat all blood and other potentially infectious materials with appropriate precautions such as: Use gloves, masks, and gowns if blood or body fluids exposure is anticipated. Use engineering and work practice controls to limit exposure. Treating all blood and bodily fluids as if they are contaminated Source: OSHA DTE Proper cleanup and decontamination Controlling Exposures Engineering and work practice controls: Safer medical devices Sharps disposal containers Hand hygiene Source: OSHA DTE Source: NIOSH Source: NIOSH Risk of infection after exposure What is the risk of infection after an occupational exposure to HBV ? Healthcare personnel who have received hepatitis B vaccine and developed immunity to the virus are at virtually no risk for infection. For a susceptible person, the risk from a single needlestick or cut exposure to HBV-infected blood ranges from 6-30% and depends on the hepatitis B e antigen (HBeAg) status of the source individual.  HCV; The average risk for infection after a needlestick or cut exposure to HCV infected blood is approximately 1.8%. HIV The average risk of HIV infection after a needlestick or cut exposure to HlV-infected blood is 0.3% (or about 1 in 300). The risk after exposure of the eye, nose, or mouth to HIV-infected blood is estimated to be, on average, 0.1% (1 in 1,000). The risk after exposure of non-intact skin to HlV-infected blood is estimated to be less than 0.1%. A small amount of blood on intact skin probably poses no risk at all. There have been no documented cases of HIV transmission due to an exposure involving a small amount of blood on intact skin (a few drops of blood on skin for a short period of time).  When Exposure Occurs Exposure incident: Specific eye, mouth, or other mucous membrane, non-intact skin, parenteral contact with blood or other potentially infectious materials (OPIM) that results from the performance of an Source: CDC employee’s duties.  When Exposure Occurs Immediate actions Wash exposed area with soap and water Flush splashes to nose, mouth, or skin with water Irrigate eyes with water and saline Report exposure immediately Direct employee to healthcare professional for treatment Source: OSHA When Exposure Occurs Confidential medical evaluation and follow-up Route(s) of exposure and circumstances Source individual Collect/test blood for HBV and HIV serological status Post exposure prophylaxis (when medically indicated) Counseling Evaluation  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. Copyrights apply Copyrights apply Treatment of Chronic Hepatitis B According to the guidelines Pegylated interferons Tenofovir alefenamide Tenofovir disoproxil fumarate Entecavir  Type of Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces virus blood-derived blood-derived blood-derived body fluids body fluids body fluids Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification HIV infections Human Immunodeficiency Virus. The virus infects and gradually destroys the cells in the body that usually fight infections, leaving the body vulnerable to diseases it would normally be able to fight. Without treatment the immune system becomes weaker and weaker, and a person with HIV will begin to develop infections. As the immune system becomes too weak to fight infections, a person with HIV will begin to develop particularly serious infections. At this point the person is said to have developed AIDS (Acquired Immune Deficiency Syndrome). How is HIV transmitted? HIV can only be passed on through infected blood, semen, vaginal fluids or breast milk. HIV is mainly transmitted through vaginal or anal intercourse without a condom or by sharing a needle or syringe with someone who is living with HIV. Other ways that HIV can be transmitted are: From a HIV positive mother to her baby during pregnancy, birth, or breastfeeding. From a needlestick injury in a healthcare setting. From a blood transfusion or blood products (blood is usually screened to prevent this but in some countries this may not happen so you need to check the protocol in your country of residence). HIV cannot be passed on through casual contact such as kissing, or sharing glasses or cutlery. HIV is a fragile virus that cannot survive outside the body. HIV Treatment Although there is no cure for HIV, effective treatment called antiretroviral therapy (ART) is available which can keep the virus under control and allow someone with HIV to lead an active, healthy life. Treatment is most effective if started early and it’s important HIV positive people take their drugs exactly as prescribed in order to stay well. Someone with HIV who is diagnosed early and responds well to treatment can have a near normal life expectancy. Postexposure prophylaxis PEP, or post-exposure prophylaxis, is a short course of HIV medicines taken very soon after a possible exposure to HIV to prevent the virus from taking hold in your body. You must start it within 72 hours (3 days) after a possible exposure to HIV, or it won’t work. Every hour counts! How can I prevent occupational HIV transmission? Follow Standard Precautions at all times. Assume that blood and other body fluids are potentially infectious. Use gloves, goggles, and other barriers when anticipating contact with blood or body fluids. Wash hands and other skin surfaces immediately after contact with blood or body fluids. Be careful when handling and disposing of sharp instruments during and after use. Use safety devices to prevent needle-stick injuries. Dispose of used syringes or other sharp instruments in a sharps container. What if an HIV exposure happens at work? If you are exposed to HIV at work, report your exposure to the appropriate person, and see a doctor or visit an emergency room right away. Post-exposure prophylaxis (PEP) can reduce your chance of getting HIV infection. It must be started within 72 hours (3 days) after you may have been exposed to HIV. But the sooner you start PEP, the better. Every hour counts! Acute Viral Respiratory Infections Respiratory infections are the most common cause of mortality for children younger than 5 years old, The severity of respiratory infection can range from inapparent to overwhelming. The most severe illness is usually seen in infants infected with certain paramyxoviruses (measles, parainfluenza, RSV, human metapneumovirus) and in elderly or chronically ill adults infected with influenza virus.  Influenza Flu is a contagious respiratory illness caused by influenza viruses that infect the nose, throat, and sometimes the lungs Influenza A, B, and C viruses are the only members of the Orthomyxoviridae family, Influenza A and B viruses cause significant human disease Influenza can range from a mild, self-limiting illness to respiratory failure. Influenza A infects humans, mammals, and birds (zoonosis) Hemagglutinin glycoprotein is the viral attachment protein and fusion protein; it elicits neutralizing, protective antibody responses. The segmented genome promotes genetic diversity caused by mutation and reassortment of segments on infection with two different strains. Influenza Human Influenza is caused by influenza A and influenza B. Between 3% and 11% of the population gets infected and develops flu symptoms each year Flu viruses are most common during the fall and winter. The exact timing and duration of flu seasons varies, but influenza activity often begins to increase in October. Most of the time flu activity peaks between December and February, although significant activity can last as late as May. Seasonal influenza kills up to 650 000 people every year.  Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: hemagglutinin (H) and neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1 through H18 and N1 through N11, respectively). Influenza virus are remarkable because of the frequent antigenic change that occurs in HA (hemagglutinin) or NA (neuraminidase). Large and sudden Random and Spontaneous mutation Mutation Influenza Pandemics How Flu Spreads Flu viruses spread mainly by tiny droplets made when people with flu cough, sneeze or talk. These droplets can land in the mouths or noses of people who are nearby. Less often, a person might get flu by touching a surface or object that has flu virus on it and then touching their own mouth, nose or possibly their eyes. Influenza (Flu) Symptoms The time from when a person is exposed and infected with flu to when symptoms begin is about 2 days, but can range from about 1 to 4 days. Influenza (flu) can cause mild to severe illness, and at times can lead to death. Flu is different from a cold. Flu usually comes on suddenly. People who have flu often feel some or all of these symptoms: fever* or feeling feverish/chills cough sore throat runny or stuffy nose muscle or body aches headaches fatigue (tiredness) some people may have vomiting and diarrhea, though this is more common in children than adults. Complications of Flu Bacterial pneumonia, Ear infections, sinus infections Worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes.  Involvement of major organs - brain, heart, etc.  Death  Risk groups Adults 65 years and older Children younger than 2 years old Neurologic and neurodevelopment ​conditions ;People who have had a stroke​ Blood disorders (such as sickle cell disease) Chronic lung disease (such as chronic obstructive pulmonary disease [COPD] and cystic fibrosis), asthma Endocrine disorders (such as diabetes mellitus) Heart disease (such as congenital heart disease, congestive heart failure and coronary artery disease) Kidney diseases Liver disorders Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders) People who are obese with a body mass index [BMI] of 40 or higher People younger than 19 years old on long-term aspirin- or salicylate-containing medications. People with a weakened immune system due to disease (such as people with HIV or AIDS, or some cancers such as leukemia) or medications (such as those receiving chemotherapy or radiation treatment for cancer, or persons with chronic conditions requiring chronic corticosteroids or other drugs that suppress the immune system)Pregnant people and people up to 2 weeks after the end of pregnancy People who live in nursing homes and other long-term care facilities Treatment Symptomatic When used for treatment, antiviral drugs can lessen symptoms and shorten the time you are sick by 1 or 2 days. They also can prevent serious flu complications, like pneumonia. For people at higher risk of serious flu complications, treatment with antiviral drugs can mean the difference between milder or more serious illness possibly resulting in a hospital stay. oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), zanamivir peramivir The antiviral drugs zanamivir and oseltamivir inhibit the neuraminidase protein of influenza A and B.  Although the best method for preventing influenza is vaccination, the efficacy of the vaccine depends on how well it is matched with the circulating strain. Antiviral treatment is most effective if given within a couple of days after onset of symptoms and post-exposure prophylaxis may be indicated in some patients.. Viral Infections of the Gastrointestinal Tract Acute gastroenteritis is the designation for short-term gastrointestinal disease with symptoms ranging from mild, watery diarrhea to severe febrile illness characterized by vomiting, diarrhea, and prostration Viruses able to initiate infection by this route are all resistant to acid and bile salts. There may also be virus specific secretory IgA and nonspecific inhibitors of viral replication to overcome Rotaviruses, noroviruses, and caliciviruses are major causes of gastroenteritis. Infants and children are affected most often Some enteroviruses, notably polioviruses, and hepatitis A virus are important causes of systemic disease but do not produce intestinal symptoms. Norovirus Worldwide, about one out of every five cases of acute gastroenteritis (inflammation of the stomach or intestines) that leads to diarrhea and vomiting is caused by norovirus. Norovirus is the most common cause of acute gastroenteritis, annually causing an estimated 685 million cases. About 200 million cases are seen among children under 5 years old, leading to an estimated 50,000 child deaths every year, mostly in developing countries. Norovirus illness is a problem in both low- and high-income countries. Every year, norovirus is estimated to cost $60 billion worldwide due to healthcare costs and lost productivity. Norovirus illnesses and outbreaks are usually more common in cooler winter months. The majority of all outbreaks occur from November to April in countries above the equator, and from May to September in countries below the equator.  Norovirus Norovirus is a very contagious virus that causes vomiting and diarrhea. Anyone can get infected and sick with norovirus. Having direct contact with an infected person Consuming contaminated food or water Touching contaminated surfaces and then putting your unwashed hands in your mouth Symptoms Norovirus causes inflammation of the stomach or intestines. This is called acute gastroenteritis. A person usually develops symptoms 12 to 48 hours after being exposed to norovirus. Most people with norovirus illness get better within 1 to 3 days. diarrhea vomiting nausea stomach pain Treatment Supportive care is the mainstay of norovirus treatment, especially oral or intravenous rehydration. Antidiarrheals and antiemetics are not recommended for the routine management of acute gastroenteritis in children. For adults, antiemetic, antimotility, and antisecretory agents can be useful adjuncts to rehydration. Antibiotics are not useful in treating patients with norovirus disease. Drink plenty of liquids to replace fluids that are lost from vomiting and diarrhea. Sports drinks and other drinks without caffeine or alcohol can help with mild dehydration. However, these drinks may not replace important nutrients and minerals. Oral rehydration fluids are most helpful for mild dehydration Prevention Practice proper hand hygiene Handle and prepare food safely Noroviruses are relatively resistant to heat. They can survive temperatures as high as 145°F. (63 C) Quick steaming processes that are often used for cooking shellfish may not heat foods sufficiently to kill noroviruses. Clean and disinfect surfaces You should use a chlorine bleach solution with a concentration of 1,000 to 5,000 ppm (5 to 25 tablespoons of household bleach [5% to 8%] per gallon of water (3.78 L) Wash laundry thoroughly Immediately remove and wash clothes or linens that may be contaminated with vomit or feces. Congenital Viral Infections Three principles are involved in the production of congenital defects: (1) the ability of the virus to infect the pregnant woman and be transmitted to the fetus (2) the stage of gestation at which infection occurs; (3) the ability of the virus to cause damage to the fetus directly (by infection of the fetus) or indirectly (by infection of the mother), resulting in an altered fetal environment (eg, fever). In utero infections may result in fetal death, prematüre birth, intrauterine growth retardation, or persistent postnatal infection. Developmental malformations, including congenital heart defects, cataracts, deafness, microcephaly, and limb hypoplasia, may result. HIV can be transmitted by the breast milk of an infected mother. Acquisition of Significant Perinatal Viral Infections