* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download VIRUS
Herpes simplex wikipedia , lookup
Chagas disease wikipedia , lookup
Poliomyelitis wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Eradication of infectious diseases wikipedia , lookup
Sexually transmitted infection wikipedia , lookup
2015–16 Zika virus epidemic wikipedia , lookup
Oesophagostomum wikipedia , lookup
Schistosomiasis wikipedia , lookup
Hospital-acquired infection wikipedia , lookup
Neonatal infection wikipedia , lookup
Leptospirosis wikipedia , lookup
Ebola virus disease wikipedia , lookup
Human cytomegalovirus wikipedia , lookup
Middle East respiratory syndrome wikipedia , lookup
Orthohantavirus wikipedia , lookup
Influenza A virus wikipedia , lookup
West Nile fever wikipedia , lookup
Herpes simplex virus wikipedia , lookup
Marburg virus disease wikipedia , lookup
Antiviral drug wikipedia , lookup
Henipavirus wikipedia , lookup
Lymphocytic choriomeningitis wikipedia , lookup
Microbiology, virology, immunology department RNA-VIRUSES: PICORNAVIRUSES ORTHOMYXOVIRUSES PARAMYXOVIRUSES CAUSATIVE AGENTS OF HEPATITIS VIRUS Genera of Picornaviruses Enterovirus Polio, types 1-3 Coxsackie A , 1-24 types Diseases of the human (and other) alimentary tract (e.g. polio virus) Coxsackie B, types 1-6 Echo, types 1-34 Other enteroviruses, types 68-71 Rhinovirus, types 1-115 Cardiovirus Aphthovirus Hepatovirus Others Disease of the nasopharyngeal region (e.g. common cold virus) Murine encephalomyocarditis, Theiler's murine encephalomyelitis virus Foot and mouth disease in cloven footed animals Human hepatitis virus A Drosophila C virus, equine rhinoviruses, cricket paralysis virus Pathogenesis of enterovirus infection Replication in oropharynx Rhino,echo, coxsackie,polio Primary viremia Secondary viremia Target Tissue Skin Muscle Brain Meninges Liver Echo Echo Polio Echo Echo Coxsackie Coxsackie Coxsackie Polio Coxsackie A A, B Coxsackie Clinical Picornavirus Syndromes Virus Polioviruses (types 1-3) Diseases (Virus Type) Undifferentiated febrile illnesses (types 1- 3) Aseptic memingitis (types 1-3) Paralisis and encephalitic diseases (types 1-3) Coxsackievirus group A (A1-A, A-24)* Acute hemorrhagic conjunctivitis (type 24) Herpangina (types 2-6, 8, 10, 22) Exanthem (types 4, 5, 6, 9, 16) Hand-foot-mouth disease (types 5, 10, 16) Aseptic memingitis (types 1, 2, 4-7, 9, 10, 14, 16, 22) Paralysis and encephalitic diseases (occasional types 4, 7, 9, 10) Hepatitis (types 4, 9) Virus Diseases (Virus Type) Upper and lower respiratory illnesses Coxsackievirus 9, 10, 16, 21, 24) group A (A1-A, A- (types Lymphonodular pharyngitis (10) 24)* Infantile diarrhea (types 18, 20, 21, 22, 24 variant) Undifferentiated febrile illnesses (types 1- 6) Pleurodinia (types 1-5) Pericarditis, myocarditis (types 1-5) Aseptic meningitis types (1-6) Paralysis and encephalitic diseases (occasional types 1-5) Severe systemic infection in infants, meningoencephalitis and myocarditis (types 1-5) Upper and lower respiratory illnesses (types 4, 5) Exanthem, hepatitis, diarrhea (types 5) Virus Echoviruses (1-7, 9, 11, 29-33)* Diseases (Virus Type) Aseptic meningitis (many seroypes ) Paralysis and encephalitic diseases (occasional types 1, 2, 4, 6, 7, 9, 11, 14-16, 18, 22, 30) Exanthem (types 1-9, 11, 14, 16, 18, 19, 25, 30, 32) Hand-foot-mouth disease (19) Pericarditis, myocarditis (types 1, 6, 9, 19, 22) Upper and lower respiratory illnesses (types 4, 9, 11, 20, 22, 25) Neanatal diarrhea (types 11, 14, 18, 20, 32) Epidemic mialgia (types 1, 6, 9) Hepatitis (types 4, 9) Virus New enteroviruses Diseases (Virus Type) Pneumonia and bronchiolitis (types 68, 69) Acute hemorrhagic conjunctivitis (type 70) Rhinoviruses (1-115) Hepatovirus (Hepatitis A) Aseptic meningitis, meningoencephalitis Hand-foot-mouth disease (71) Hepatitis (type 72) Upper and lower respiratory illnesses (types 1-115) Gastroenteritis and hepatitis A * Reclassification of coxsackievirus A23 as echovirus 9, echovirus 8 as 1, echovirus 10 as reovirus, echovirus 28 as rhinovirus type 1A, and echovirus 34 as coxsackievirus A24. Properties of enteroviruses Property Enteroviruses Size (nm) 22-30 Capsid form Icosahedral Polypeptide VP1, VP2, VP3, VP4 ‘+’, single RNA type stain Stable Acid Optimal temperature for growth(oC) 37 RNA Properties of enteroviruses This genome RNA serves as an mRNA and initiates the synthesis of virus macromolecules. The poliomyelitis virus has neither an outer membrane nor lipids and is therefore not sensitive to the effect of ether and sodium desoxycholate. POLIOMYELITIS Picornavirus 3 types: Poliovirus 1,2,3 30 nm in size Cultivation. SPE. The poliomyelitis virus is cultivated on kidney cells of green African monkeys and on diploid human cells devoid of latent SV40 viruses. The cytopathic effect is attended by destruction and the formation of granules in the infected cells. Pathogenesis Source of infection: Apparent and subclinical patients Incubation: is usually 7-14 days, but it may range from 3 to 35 days. Transmission Fecal – oral route: poor hygiene, dirty diapers (especially in day-care settings) Ingestion via contaminated food and water Contact with infected hands Inhalation of infectious aerosols Pathogenesis 1. The mouth is the portal of entry of the virus. 2. The virus first multiplies in the tonsils, the lymph nodes of the neck, Peyer's patches, and the small intestine. 3. Viremia 4. The central nervous system may then be invaded by way of the circulating blood. Poliovirus can spread along axons of peripheral nerves to the central nervous system , and there it continues to progress along the fibers of the lower motor neurons to increasingly involve the spinal cord or the brain. The anterior horn cells of the spinal cord are most prominently involved. Clinical Findings. When an individual susceptible to infection is exposed to the virus, one of the following responses may occur: inapparent infection without symptoms (asymptomatic illness), the minor illness – 90% infected people aseptic meningitis – 1%-2% of patients with poliovirus infections, paralytic poliomyelitis, the major illness 0.1% to 2% of persons with poliovirus Only about 1% recognized clinically. of infections are Abortive Poliomyelitis. This is the commonest form of the disease. The patient has only the minor illness, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, and sore throat in various combinations. The patient recovers in a few days. The diagnosis of abortive poliomyelitis can be made only when the virus is isolated or antibody development is measured. Nonparalytic Poliomyelitis (Aseptic Meningitis). In addition to the above symptoms and signs, the patient with the nonparalytic form presents stiffness and pain in the back and neck. The disease lasts 2-10 days, and recovery is rapid and complete. In a small percentage of cases, the disease advances to paralysis. Paralytic Poliomyelitis. The major illness usually follows the minor illness described above, but it may occur without the antecedent first phase. The predominating complaint is flaccid paralysis resulting from lower motor neuron damage. The maximal recovery usually occurs within 6 months, with residual paralysis lasting much longer. Child with polio sequelae Lab Diagnosis Definitive diagnosis is made by osolation of the virus from stool, CFS, oropharyngeal secretions Cell culture involves fibroblastic MRC-5 cells CPE is usually evident within 36 hours Serotyping is based on neutralization of CPE by standardized antisera using intersecting pool followed by specific sera. ELISA IFA neutralizing Test CFT Prevention Both oral polio vaccine (OPV live, attenuated, Sabin, 1957) and inactivated poliovirus vaccine (IPV, Salk, 1954) are avilable IPV is used for adult immunization and Immunocopromised patients COXSACKIEVIRUSES The coxsackieviruses comprise a large subgroup of the enteroviruses. They produce a variety of illnesses in human beings, including aseptic meningitis, herpangina, pleurodynia, hand, foot, and mouth disease, myo- and pericarditis, common colds, and possibly diabetes. Coxsackieviruses have been divided into 2 groups, A and B, having different pathogenic potentials for mice. Group A viruses produce widespread myositis in the skeletal muscles of newborn mice, resulting in flaccid paralysis without other observable lesions. Group B viruses may produce spasticity effect in sucking mice, focal myositis, encephalitis, and, most typically, necrotizing steatitis involving mainly fetal fat lobules. Some B strains also produce pancreatitis, myocarditis, endocarditis, and hepatitis in both suckling and adult mice. Normal adult mice tolerate infections with group B coxsackieviruses. Herpangina: There is an abrupt onset of fever, sore throat, anorexia, dysphagia, vomiting, or abdominal pain. The pharynx is usually hyperaemic, and characteristic discrete vesicles occur on the anterior pillars of the fauces, the palate, uvula, tonsils, or tongue. The illness is self-limited and most frequent in small children. Exanthems – Rubelliform rashes Hand, Foot, and Mouth Disease: The syndrome is characterized by oral and pharyngeal ulcerations and a vesicular rash of the palms and soles that may spread to the arms and legs. Vesicles heal without crusting, which clinically differentiates them from the vesicles of herpes- and poxviruses. The rare deaths are caused by pneumonia. Hand-foot-and-mouth disease Hand-foot-and-mouth disease: mostly coxackie A fever, malaise, sore throat, vesicles on bucсal mucosa, tongue, hands, feet, buttocks highly infectious resolution – 1w ECHOVIRUSES (enteric cytopathogenic human orphan viruses) Not produce diseases in sucking mice, rabbits, or monkeys. Monkey kidney and human embryonated kidney cell culture Aseptic meningitis, febrile illnesses with or without rash, common colds, and acute hemorrhagic conjunctivitis are among the diseases caused by echoviruses. Boston exanthem disease. Rashes are commonest in young children. RHINOVIRUSES Rhinoviruses are isolated commonly from the nose and throat but very rarely from feces. These viruses cause upper respiratory tract infections, including the "common cold." Orthomyxovirus Family The name myxovirus was originally applied to influenza viruses. It meant virus with an affinity for mucins. A model of the influenza virion Types: A, B, C Influenza A: In Birds 16 H variants 9 N variants In Humans 3 H variants (H1, H2, and H3) 2 N variants (N1 and N2) Subtypes: H1N1, H2N2,H2N3 Influenza Viruses: Antigenic Shift Avian Reservoir Human virus Avian virus Other mammals? Swine New Reassorted virus Influenza Viruses: Antigenic Drift Gradual accumulation of mutations that allow the hemagglutinin to escape neutralizing antibodies (Point mutation in HA gene) Epidemic strains thought to have changes in three or more antigenic sites Pathogenesis and Pathology The virus enters the respiratory tract in airborne droplets. Viremia is rare. Virus is present in the nasopharynx from 1-2 days before to 1-2 days after onset of symptoms. Inflammation of the upper respiratory tract causes necrosis of the ciliated and goblet cells of the tracheal and bronchial mucosa but does not affect the basal layer of epithelium. Interstitial pneumonia may occur with necrosis of bronchiolar epithelium and may be fatal. The pneumonia is often associated with secondary bacterial invaders: staphylococci, pneumococci, streptococci, and Haemophilus influenzae. Clinical Findings The incubation period is 1 or 2 days. Chills, malaise, fever, muscular aches, prostration, and respiratory symptoms may occur. The fever persists for about 3 days; complications are not common, but pneumonia, myocarditis, pericarditis, and central nervous system complications occur rarely. The latter include encephalomyelitis, polyneuritis, Guillain-Barre syndrome, and Reye's syndrome (see below). Influenza Vaccines Whole virus vaccine: inactivated virus vaccine grown in embryonated eggs; 7090% effective in healthy persons <65 years of age, 30-70% in persons ≥65 years Split virus vaccine: previously associated with fewer systemic reactions among the elderly and children <12 years Subunit vaccine: composed of H and N Live, attenutated influenza virus vaccines under development Influenza: Chemoprophylaxis Amantadine and rimantadine: effective against type A, but not type B, influenza viruses; block the M2 ion channel 70-90% effective in preventing illness Administered to individuals at high risk of complications who are vaccinated after outbreak of infection, persons with immune defficiency Influenza: Chemotherapy Amantadine (adults and children ≥ 1 year) and rimantadine (adults) Zanamivir and oseltamivir: neuraminidase inhibitors active against both type A and B influenza viruses Reduce duration of illness by ~1 day when administered within 2 days of the onset of illness (uncomplicated influenza) Laboratory Diagnosis Throat washings or garglings are obtained within 3 days after onset and should be tested at once or stored frozen. Penicillin and streptomycin are added to limit bacterial contamination. For rapid detection of influenza virus in clinical specimens, positive smears from nasal swabs may be demonstrated by specific staining with fluorescein-labeled antibody. Paired sera are used to detect rises in HI, CF, or Nt antibodies. Family Paramyxoviridae Genes: Morbillivirus – measles virus, Respirovirus – parainfluenza virus (serotypes 1 and 3) Rubulavirus - mumps virus, parainfluenza virus 2, 4а, 4b), Pneumovirus – RS-virus (serotypes PARAMYXOVIRUSES pleomorphic HN/H/G glycoprotein SPIKES F glycoprotein SPIKES helical nucleocapsid (RNA minus NP protein) lipid bilayer membrane polymerase complex M protein STRUCTURE-PARAMYXOVIRUSES Cell fusion. In the course of infection, paramyxo- viruses cause cell fusion, long recognized as giant cell formation. MUMPS (Epidemic Parotitis) Mumps is an acute contagious disease characterized by a nonsuppurative enlargement of one or both of the parotid glands, although other organs may also be involved. Properties of the Virus: The mumps virus particle has the typical paramyxovirus morphology. Typical also are the biologic properties of hemagglutination, neuraminidase, and hemolysin. Epidemiology The disease reaches its highest incidence in children age 5-15 years, but epidemics occur in army camps. Humans are the only known reservoir of virus. The virus is transmitted by direct contact, airborne droplets, or fomites contaminated with saliva and, perhaps, urine. The period of communicability is from about 4 days before to about a week after the onset of symptoms. Pathogenesis and Pathology The virus travels from the mouth to the parotid gland, where it undergoes primary multiplication. This is followed by a generalized viremia and localization in testes. ovaries, pancreas, thyroid, or brain. The ducts of the parotid glands show desquamation of the epithelium, and polymorphonuclear cells are present in the lumens. There are interstitial edema and lymphocytic infiltration. Orchitis PARAINFLUENZA VIRUS The parainfluenza viruses are paramyxoviruses with morphologic and biologic properties typical of the genus. They grow welt in primary monkey or human epithelial cell culture but poorly or not at all in the embryonated egg. They produce a minimal cytopathic effect in cell culture but are recognized by the hemadsorption method. Laboratory diagnosis may be made by the HI, CF, and Nt tests. PIV STRUCTURE MEASLES (Rubeola) Measles is an acute, highly infectious disease characterized by a maculopapular rash, fever, and respiratory symptoms. Properties of the Virus: Measles virus is a typical paramyxovirus. It lacks neuraminidase activity. Measles virus Pathogenesis and Pathology Infection is contracted by inhalation of droplets expelled in sneezing or coughing. Measles is spread during the catarrhal prodromal period; they are infectious from 1-2 days prior to the onset of symptoms until a few days after the rash has appeared The virus enters the respiratory tract, enters cells, and multiplies there. During the prodrome, the virus is present in the blood, throughout the respiratory tract, and in nasopharyngeal, tracheobronchial, and conjunctival secretions. It persists in the blood and nasopharyngeal secretions for 2 days after the appearance of the rash. Transplacental transmission of the virus can occur. Pathogenesis and Pathology Koplik's spots are vesicles in the mouth formed by focal exudations of serum and endothelial cells, followed by focal necrosis. In the skin the superficial capillaries of the corium are first involved, and it is here that the rash makes its appearance. Generalized lymphoid tissue hyperplasia occurs. Multinucleate giant cells are found in lymph nodes, tonsils, adenoids, spleen, appendix, and skin. In encephalomyelitis, there are petechial hemorrhages, lymphocytic infiltration, and later, patchy demyelination in the brain and spinal cord. Koplik's spots RESPIRATORY SYNCYTIAL (RS) VIRUS This labile paramyxovirus produces a characteristic syncytial effect, the fusion of cells in human cell culture. It is the single most serious cause of bronchiolitis and pneumonitis in infants. Properties of the Virus: RS virus does not hemagglutinate. RSV- Structure immunofluoresent stain RSV- syncytium formation Pathogenesis and Pathology This disease is transmitted by coughing, sneezing, sharing wash cloths towels and other things with someone with RSV. This disease is extremely serious when it comes to children and infants under the age of 3 and elders. This disease can result in death. Symptoms for this disease are: sneezing, runny nose, sore throat, low fever, common cold symptoms just more severe. Treatment: Supportive Fluids, oxygen, respiratory support, bronchodilators Antiviral Agents Ribavirin (Virazole), a synthetic guanosine analogue, given as an aerosol RSV Bronchiolitis- clinical features Prophylaxis Combination live virus (measles-mumps-rubella) vaccines Live attenuated measles virus vaccine effectively prevents measles. 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. Characteristics of Human Hepatitis Viruses Virus Family/ Genus Size/ Genome Length Transmi of ssion of Incuba Infection tion Vaccine HAV Picornaviridae (enterovirus 72) 27-30 nm, ss RNA 15-40 days Mostly oralfecal No HBV Hepadnaviridae (hepadnavirus) 142 nm, circular ds DNA 50180 days Parenteral Recombi nant subunit vaccine HCV Flaviviridae 30-50 nm ssd RNA 14-28 days Parenteral No Characteristics of Human Hepatitis Viruses Size/ Genome Length of Incubation Transmis Vaccine sion of Infection Virus Family/ Genus HDV Unclassified 35-40 nm ss RNA 50-180 days* Parenteral No HEV Caliciviridae 27-34 nm sst RNA 6 weeks Oralfecal No Hepatitis A virus Electron microscopy of fecal extracts Hepatitis A virus Family Genus Virion Envelope Genome Stability Transmission Prevalence Fulminant disease Chronic disease Oncogenic Picornaviridae Hepatovirus 27 nm icosahedral No ssRNA Heat- and acid-stable Fecal-oral High Rare Never No Global Prevalence of Hepatitis A Infection HAV Prevalence High Intermediate Low Very Low 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. Hepatitis A - Clinical Features • Incubation period: • Jaundice by age group: • Complications: • Chronic sequelae: Average 30 days Range 15-50 days <6 yrs, <10% 6-14 yrs, 40%-50% >14 yrs, 70%-80% Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis None 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% 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. Concentration of Hepatitis A Virus in Various Body Fluids Body fluid Feces Serum Saliva Urine 100 102 104 Infection Doses per ml 106 108 1010 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. 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. Typical Serologic Course of Acute Hepatitis A Virus Infection Symptoms ALT Total anti-HAV Fecal HAV 0 1 IgM anti-HAV 2 3 4 5 6 Months after exposure 12 24 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. 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. Structure of the Hepatitis B virion HBe 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). Hepatitis B virus Family Genus Envelope Genome Stability Transmission Prevalence Fulminant disease Chronic disease Oncogenic Hepadnaviridae Orthohepadnavirus Yes (HBsAg) dsDNA Acid-sensitive Parenteral High Rare Often Yes 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. 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 was serum hepatitis. It has now been shown that this supposition is not true. 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. Hepatitis B Transmission 1. HBV spread mainly by parenteral route 2. direct percutaneous 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 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%) 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. 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. 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. Differential Characteristics of Hepatitis A and Hepatitis B Characteristic Hepatitis A Hepatitis B Length of incubation period 15-40 days 50-180 days Host range Humans and possibly nonhuman primates Humans and some nonhuman primates Seasonal occurrence Higher in fall and winter Year round Age incidence Much higher in children All ages Occurrence of jaundice Much higher in adults Higher in adults Virus in blood 2-3 weeks before illness to 1-2 weeks after recovery Several weeks before illness to months or years after recovery Differential Characteristics of Hepatitis A and Hepatitis B Characteristic Hepatitis A Hepatitis B Virus in feces 2-3 weeks before illness to 1-2 weeks after recovery Rarely present, or present in very small amounts Size of virus 27-32 nm 42 nm Diagnosis based on Liver function tests, clinical symptoms, and history Liver function tests, clinical symptoms, history, and presence of HBsAg in blood Effective vaccine No Yes 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. 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. 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. 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. 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. PRACTICE HBsAg HBcAB (TOTAL) HBsAB HAV-IGM HCV N. N. N. N. N. NO evidence of viral hepatitis viruses. PRACTICE HBsAG HBcAB (TOTAL) HBsAB HAV-IGM HCV PAST INFECTION. N. P. P. N. N. PRACTICE HBsAg HBcAB (total) HBsAB HAV-IGM HCV IMMUNIZATION. N. N. P. N. N. PRACTICE HBsAg HBcAB (Total) HBsAB HAV-IGM HCV P. P. N. N. N. MAY BE ACUTE OR CHRONIC. Order Hep. B Core IgM to clarify. The IgM will be positive , If Acute. PRACTICE HBsAg HBcAB (TOTAL) HBsAB HAV-IGM HCV P. P. N. P. P. Co-infection with HBV, HAV, and HCV PRACTICE HBsAG HBcAB (total) HBsAB HAV-IGM HCV P. P. P. N. N. Past infection with recovery, and then re-infection that has become chronic, this is very rare but does happen. 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. 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. Model of Human Hepatitis C Virus Lipid Envelope Capsid Protein Nucleic Acid Envelope Glycoprotein E2 Envelope Glycoprotein E1 Hepatitis C viruses Family Genus Virion Envelope Flaviviridae Hepacivirus 60 nm spherical Yes Genome Stability Transmission ssRNA Ether-sensitive, acid-sensitive Parenteral Prevalence Fulminant disease Chronic disease Oncogenic Moderate Rare Often Yes Hepatitis C: A Global Health Problem 170-200 Million (M) Carriers Worldwide United States 3-4 M Americas 12-15 M Western Europe 5M Eastern Europe 10 M Far East Asia 60 M Southeast Asia 30-35 M Africa 30-40 M Australia 0.2 M 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% WHO IS AT GREATEST RISK FOR 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) HCV - Diagnosis Diagnostic Tests Hepatitis C antibody tests Qualitative HCV RNA tests Quantitative HCV RNA tests Genotyping Hepatitis Delta virus. Vírus da Hepatite Delta (HDV) Vírus da Hepatite B Vírus da Hepatite Delta Envelope AgHBs Envelope AgHBs DNA polimerase RNA 42 nm DNA Core (27 nm) AgHBc AgHBe Vírus Delta Core (27 nm) Virus Delta Characteristics of hepatitis D viruses Family Genus Envelope Genome Stability Transmission Prevalence Fulminant disease Chronic disease Oncogenic Unclassified Deltavirus Yes (HBsAg) ssRNA Acid-sensitive Parenteral Low, regional Frequent Often ? Two principal models of HDV infection have been described 1. coinfection (the simultaneous introduction of both HBV and HDV into a susceptible host), 2. superinfection (the infection of an HBV carrier with HDV). HDV INFECTION PATTERNS Coinfection acute simultaneous infection with HBV and HDV often results in fulminant infection (70% cirrhosis) survivors rarely develop chronic infection Superinfection (< 5%) results in HDV superinfection in an HBsAg carrier (chronic HBV) can occur anytime during chronic disease usually results in rapidly progressive subacute or chronic hepatitis HDV Transmission Percutaneous Sexual - Common - Yes, rare Incubation period - 21 - 45 (days) Clinical illness at presentation jaundice 10%, higher with superinfection Fulminant - 2 – 7.5% Case-fatality rate - 1 – 2% Chronic infection Superinfection – 80% Coinfection < 5% HDV Diagnostic tests Acute infection Chronic infection IgM anti-HDV IgG anti-HDV, HBsAg + Immunity Not applicable Hepatitis E virus. HEV is a small, nonenveloped RNA virus. Recent information about the genomic organization and other properties of the virus strongly suggests that it is a calicivirus. Hepatitis E virus Family Genus Virion Envelope Caliciviridae Unnamed 30-32 nm, icosahedral No Genome Stability Transmission ssRNA Heat-stable Fecal-oral Prevalence Fulminant disease Chronic disease Regional In pregnancy Never Oncogenic No Hepatitis E virus. Epidemiology Many cases of acute viral hepatitis in Asia, Middle East and North Africa are caused by HEV. Mainly young adults Can infect primates, swine, sheep, rats It is transmitted through the fecal-oral route (human to human) but is unrelated to HAV. The disease usually is caused by the ingestion of fecally contaminated water. Maternal-infant transmission occurs and is often fatal. HEV Clinical Characteristics Similar to hepatitis A Incubation period 15 – 60 (days) Clinical Illness at presentation - 70 – 80% in adults Can cause severe acute hepatitis Subclinical infection is common Jaundice Common Fulminant <1%, in pregnancy up to 30% Case-fatality rate 0.5 – 4% 1.5 – 21% in pregnant women Chronic infection None HEV Diagnostic tests Acute infection IgG anti-HEV (sero-conversion) Chronic infection Not applicable Immunity Not applicable Hepatitis E Prevention Passive (Immune serum globulin) Does not prevent infection May ameliorate hepatitis Active (Vaccine) Anti-ORF2 prevents infection in chimps and humans Clinical trials in progress