Viral Agents of Diarrhea PDF

Viral Agents of Diarrhea 1  Introduction Acute infectious gastroenteritis is a common illness that affects persons of all ages worldwide – Mainly is a major cause of childhood morbidity and mortality worldwide –It is a leading cause of...

Viral Agents of Diarrhea 1  Introduction Acute infectious gastroenteritis is a common illness that affects persons of all ages worldwide – Mainly is a major cause of childhood morbidity and mortality worldwide –It is a leading cause of mortality among children in developing countries, accounting for an estimated 2 million deaths each year Several enteric viruses have been recognized as important etiologic agents Illness caused by these viruses is characterized by the acute onset of vomiting and/or diarrhea, –Which may be accompanied by fever, nausea, abdominal cramps, anorexia, and malaise. 2 Common viral agents 3 REOVIRIDAE 4  REOVIRIDAE The name reovirus is derived from the abbreviation for respiratory enteric orphan virus – No diseases were associated with the virus upon its discovery (hence “orphan virus”) This family consists of – Orthoreoviruses : they are not known to cause serious human disease – Rotavirus – Orbiviruses, – Coltiviruses causes Colorado tick fever The orbiviruses and coltiviruses are spread by arthropods and are arboviruses. 5  General characteristics Reoviridae is 60-80nm with double stranded segmented RNA genome Contains10- 12 genome segments Capsid is composed of two layered shells The capsid is like wheel (rota means wheel) The virion is icosahedral in symmetry without envelope 6  General characteristics cont’d…. Rotaviruses are stable to heat at 50°C, to range of pH 3.0–9.0, and to lipid solvents, such as ether and chloroform, They are inactivated by 95% ethanol, phenol, and chlorine The family includes human rotaviruses, the most important cause of infantile gastroenteritis around the world Replication occurs in cytoplasm of host cell 7 8 Morphology of Rotavirus 9  Rotaviruses It causes infantile diarrhea and sometimes in adults Among the top sixth vaccine preventable killer in the world’s global killers Antigenic properties of rotaviruses: – There are three major subgroups (A, B, C) and nine serotypes exists. – Outer capsid protein are important antigens 10  Rotaviruses – Rotaviruses associated with human gastroenteritis are classified as group A rotaviruses. – But antigenically distinct rotaviruses have also caused diarrheal outbreaks in adults Cell culture: – They are fastidious agents to culture 11  Virus replication Infectious subviral particle (ISVP) The virion or ISVP binds, penetrates the cell, and loses its outer capsid. The inner capsid contains the enzymes for messenger ribonucleic acid (mRNA) Virus-encoded enzymes within the core add a 5′-methyl guanosine cap and a 3′-polyadenylate tail. RNA is then packaged into new double-layered particle (DLPs) within viroplasms Triple-layered particle assembly involves the binding of newly formed DLPs to non-structural protein 4 (NSP4), – Which serves as an intracellular receptor, followed by the budding of DLPs into the endoplasmic reticulum (ER) The virion leaves the cell upon cell lysis. 12 Virus replication 13  Pathogenesis: Rotaviruses infect cells in villi of small intestine They multiply in cytoplasm of enterocytes and damage their transport mechanisms A Rotavirus encoded protein may act as viral enterotoxin and induces secretion by triggering signal transduction pathway The non-structural protein 4(NSP4) protein of rotavirus acts in a toxin-like manner to promote calcium ion influx into enterocytes – Release of neuronal activators, and a neuronal alteration in water absorption. 14  Pathogenesis: cont’d…. Damaged cells slough into lumen of intestine and release large quantities of virus in the stool As many as 1010 viral particles per gram of stool may be released during disease. Viral excretion may last up to 2 – 12 days It may be prolonged in malnourished patients Diarrhea is due to impaired sodium and glucose absorption The loss of fluids and electrolytes can lead to severe dehydration and even death 15  Immunity Immunity to infection requires the presence of antibody, primarily immunoglobulin A (IgA), in the lumen of the gut Actively or passively acquired antibody can lessen the severity of disease In the absence of antibody, the inoculation of even small amounts of virus causes infection and diarrhea Infection in infants and small children is generally symptomatic – Whereas in adults, it is usually asymptomatic. 16  Clinical features Incubation period is 1 to 4 days Typical symptoms include diarrhea, fever, abdominal pain, vomiting leading to dehydration Of interest, the diarrhea also promotes spread and transmission of the virus. In infants and children, severe loss of electrolytes and fluids may be fatal unless treated Asymptomatic infections may occur Common source of infection is contact with pediatric cases – Epidemics in adults have occurred. Group B rotaviruses are associated with some outbreaks of diarrhea in adult patients in some countries. 17  Epidemiology In fact, rotaviruses account for approximately 50% of all cases of diarrhea Rotavirus infections predominate during winter seasons 80% of the population have antibody against rotavirus by the age of 3 Symptomatic infections are most common in children between 6 months and 2 years Transmission is by faecal-oral route Nosocomial infections are frequent 18  Epidemiology Diarrhea is a leading killer of children in Ethiopia Rotavirus, the most common cause of severe and fatal diarrhea in young children 19 Annual Rotavirus diarrhea deaths in the world ( Much greater in developing countries) 20  Laboratory diagnosis Demonstration of virus in stool collected in early in illness and on a rise in antibody titer – Virus can be observed by IEM (immune electron microscopy), immunodiffusion, ELISA or PCR – Antibody titer rise can be detected by ELISA. Electron micrograph of Rotavirus 21  Treatment & Control: It is supportive, to correct the loss of water and electrolytes that may lead to dehydration, acidosis, shock and death Management consists of replacement of fluids and restoration of electrolyte balance – Either intravenously or orally Live attenuated vaccines now available for use in children 22  Coltiviruses and Orbiviruses The coltiviruses cause Colorado tick fever and related human disease The orbiviruses mainly cause disease in animals Colorado tick fever, an acute disease characterized by fever, headache, and severe myalgia Colorado tick fever viruses have 12 double-stranded RNA genomic segments, and orbiviruses have 10. 23  The difference with Rotavirus The outer capsid of the orbiviruses has no visible capsomeric structure, even though the inner capsid is icosahedral. The virus causes viremia, infects erythrocyte precursors, and remains in the mature red blood cells, protected from the immune response. The orbivirus life cycle includes vertebrates and invertebrates (insects). 24 Noroviruses/Norwalk virus 25  Noroviruses/Norwalk Virus Previously named Norwalk virus for an outbreak in school in Norwalk, Ohio in 1969. Norwalk – genus name for original Norwalk virus and other Norwalk-like viruses. Family Caliciviridae Caliciviridae found worldwide, infecting humans, primates, and cattle, among others. Increasingly being recognized as leading cause of food- borne illness. Occur frequently at institutional settings, Schools, nursing homes. restaurants, dorms. Crowded quarters and poor hygiene contribute to its spread 26  Properties Noroviruses resemble and are approximately the same size as the picornaviruses Non enveloped capsid/nucleocapsid. Icosahedral, 35-39 nm diameter and positive sense RNA Virus has many serotypes Five geno-groups have been identified. Most human infections are caused by members of geno-group II. There is no polymerase within the virion 27  Mode of transmission The norovirus strains that infect humans can only infect humans. The virus found in stool and vomit of infected person – Very infectious – few virus particles up to 10 needed to start large outbreak. – Primarily fecal-oral. – Vomit – airborne particles, capable of covering large radius Very contagious – infection via eating contaminated food 28  Epidemiology Human caliciviruses have worldwide distribution. Noroviruses are the most common cause of nonbacterial gastroenteritis in USA The viruses are most often associated with epidemic outbreaks of waterborne, food borne, and shellfish- associated gastroenteritis Relatively stable in the environment 29  Clinical features Acute gastroenteritis. Characterized by sudden onset of vomiting and diarrhea accompanied Illness begins suddenly, from 12-48 hours after ingestion Infection causes an acute onset of diarrhea, nausea, vomiting, and abdominal cramps, especially in children Bloody stools do not occur Low grade fever may occur in as many as a third of patients. Certain patients manifest signs of central nervous system involvement such as meningitis (Neck stiffness, photophobia and headache), and obtundation. In most cases could be asymptomatic infections, as determined by the detection of antibodies 30  Clinical features cont’d….. Very young, elderly, and those with weakened immune systems may experience more severe symptoms. Infectiousness may last up to 2 weeks, no evidence of long-term carriers Antibody developed has a protective role for short term against re-infection with the same virus 31  Diagnosis No efficient techniques have been developed to culture it in a lab setting Electron Microscope RT-PCR-for detection of the Norovirus genome in stool or emesis samples ELISA 32  Treatment and Prevention Treatment is symptomatic, oral rehydration or intravenous fluids. Effective hand washing, careful processing of food is important to prevent food-borne outbreaks Purification of drinking water decreases outbreaks 33  Astroviruses Small RNA viruses, ss +, none- enveloped, named because of star-shaped surface morphology, 28–30nm in diameter. Have a characteristic five- or six pointed star-like surface Associated with cases of endemic gastroenteritis, usually in young children and neonates The main symptoms are diarrhoea, followed by nausea, vomiting, fever, malaise and abdominal pain. 34  Astroviruses cont’d Can cause occasional outbreaks. Responsible for up to 10% of cases of gastroenteritis. Similar disease to rota and adenoviruses. Most people have antibodies by the age of three Diagnosed by electron microscopy, but often very difficult because of small size., PCR can be employed to diagnose the disease 35 Human astrovirus particle by EM observation 36  ADENOVIRUSES General characteristics  Non-enveloped DNA virus  70-90 nm in size  Linear ds DNA genome with core proteins  Humans, animals and birds  DNA virus first isolated from adenoidal tissue in 1953 37  General characteristics cont’d…. More than 100 serotypes of which at least 52 infect humans All human serotypes are included in a single genus within the family Adenoviridae. There are 7 subgroups for human adenoviruses (A through G) The viruses in each subgroup share many properties The first human adenoviruses to be identified, numbered 1 to 7, are the most common 38  ADENOVIRUS - Ultrastructure Icosahedral capsid with 252 capsomeres (12 pentons at vertices and 240 hexons) Each penton has a fibers with terminal knob projecting from it 39  General characteristics cont’d…. Common disorders caused by the adenoviruses include Respiratory Gastroenteritis (GIT) Pharyngoconjunctivitis (pinkeye) Hemorrhagic cystitis, Genito- urinary tract 40  Gastrointestinal Infections Types 40, 41 Age