Transcript Rotavirus
Medical Virology Lecture 03/04 Viruses associated with gastrointestial tract infections Enterovirus of picornaviridae & acute gastroenterities virus Youjun Feng Center for Infection & Immunity, Zhejiang University School of Medicine [email protected] Viruses infected through gastrointestinal tract Enteroviruses of picornaviridae Acute gastroenteritis viruses • Polioviruses • Rotavirus • Coxsackieviruses • Calicivilus • Echoviruses • New enteroviruses Norovirus Sapovirus • Astrovirus • Enteric adenovirus Parenteral disease Viral gastroenteritis/viral diarrhea Enterovirus of picornaviridae PICORNAVIRUSES Small RNA Viruses icosahedral symmetry Non-enveloped + strand RNA + Strand RNA is infectious, serves as mRNA Most are very cytolytic to cells PICORNAVIRUSES Members Virus Disease Enterovirus Poliovirus Poliomyelitis Coxsackie Virus A Herpangina, Hand Foot and Mouth disease Coxsackie B Myocarditis, Pericarditis Echovirus other Enterovirus Rhinovirus 100 serotypes Heparnavirus Hepatitis A virus Common Cold Hepatitis Enterovirus of picornaviridae parenteral disease DISEASE MECHANISMS Transmission route: Fecal-oral Season: summer DISEASE MECHANISMS Viremia Enterovirus of picornaviridae Poliovirus Poliovirus Members Serotypes Disease Poliovirus Coxsackie Virus A Coxsackie B Echovirus other Enterovirus 1-3 1-22, 24 1-6 1-9, 11-27, 29-34 Poliomyelitis Herpangina, Hand Foot and Mouth disease Myocarditis, Pericarditis Poliovirus & poliomyelitis Poliovirus & poliomyelitis In spinal paralysis one or more limbs may be affected or complete flaccid paralysis may occur. Iron lung • • In bulbar paralysis cranial nerves and the respiratory center in the medulla are affected leading to paralysis of neck and respiratory muscles. no sensory loss Polio vaccines Decline in Poliomyelitis World Polio Map World Polio Map World Polio Map Current situation In 2011, only four countries (Afghanistan, India, Nigeria and Pakistan) remain polio-endemic, down from more than 125 in 1988. In 2012, only three countries (Afghanistan, Nigeria and Pakistan) remain polio-endemic, down from more than 125 in 1988. Current situation http://www.who.int/csr/don/2011_09_01/en/index.html Enterovirus of picornaviridae Coxsackieviruses Echoviruses &New Enteroviruses Other enteroviruses & diseases PATHOGENESIS Fecal-Oral route trasmission Spread in the body like polioviruses Disease Associations Paralytic Disease Meningitis Enc ephalitis Undifferentiated febrile illness Hand foot mouth disease. Herpangina Epidemic Pleurodynia (Bornholm disease) Myocarditis Respiratory Infections Rubelliform rashes. Neonatal Infection Conjunctivitis Pancreatitis/Diabetes Exanthems - Rubelliform rashes - EV leading cause in summer & fall. All types of rash Herpangina/ •Herpangina – usually coxackie A • acute onset, fever, sore throat, dysphagia • lesions – posterior pharynx • no gingivitis Hand-foot-and-mouth disease • Hand-foot-and-mouth Hand food and mouth disease(HFMD) disease: • mostly coxackie A 14, HEV71 – fever, malaise, sore throat, vesicles on bucal mucosa, tongue, hands, feet, buttocks • highly infectious • resolution – 1w Typical lesions around the Mouth of an 11 month old male Management and Prevention • no specific antiviral therapy available • no vaccine available mainly because of the multiplicity of serotypes Viruses infected through gastrointestinal tract Enteroviruses of picornaviridae Acute gastroenteritis viruses • Polioviruses • Rotavirus • Coxsackieviruses • Calicivilus • Echoviruses • New enteroviruses parenteral disease Norovirus sapovirus • Astrovirus • Enteric adenovirus viral gastroenteritis/viral diarrhea Viruses infected through gastrointestinal tract rotavirus Rotavirus Pathogenesis • Universal disease – All children are exposed and acquire antibodies by age 5 • Leading cause of severe dehydrating diarrhea in infants and young children • Sudden onset of watery diarrhea, fever and vomiting • Recovery in 4-5 days Rotavirus Transmission • Fecal-oral? – Improvements in water, sanitation, hygiene have not decreased incidence Diagnosis • Rapid diagnosis - antigen detection in stool by ELISA (uses a monoclonal antibody). • Electron microscopy Rotavirus vaccines • Wyeth - Rotashield (Sept. 1998) – Live, oral, tetravalent – human/simian re-assortant viruses – withdrawn in 1999 due to increased incidence of intus-susception • Merck - Rotateq (Feb. 2006) – Live, oral, penta-valent – Bovine/human re-assortant viruses Rotavirus vaccines • GSK - Rotarix; not yet available in U.S. – Live, oral, attenuated, human – Mono-valent – Cross-protective, replicates well in GI Treatment and prevention • Treatment Supportive - rehydration (oral / intravenous) Antiviral agents not known to be effective • Prevention of spread Hand washing with good technique Disinfection of surfaces, toilets, toys Norwalk virus •First discovered in Norwalk, Ohio •Has been at the root of several epidemics or outbreaks of gastroenteritis across North America in hospital emergency rooms, schools and even on cruise ships •There is a group of similar or related viruses that are referred to as Norwalk-like viruses or agents. •Can infect people of any age and usually cause profuse watery diarrhea, vomiting and fatigue. •The infection lasts a few days and there is no specific treatment. •Most of the time, it spreads form one person to another through direct or indirect contact with infected feces or vomit. •The infection develops within 1-2 days after contact with an infected person. SUMMARY 1. Know the common viruses infected through gastrointestial tract: Enterovirus of picornaviridae and acute gastroenteritis virus. 2. Understand the properties of picornaviruses. 3. Master the clinical findings as a result of rotavirus infection. Self control questions 1.Each of the following statements regarding rotavirus is correct EXCEPT: (A)the infection mainly affects children younger than 3 years (B)it is a major cause of death in children in developing countries (C)a high viral concentration is necessary for a efficient transfer of the virus (D)in the northern hemisphere the virus is transmitted during the winter/spring season 2.Each of the following statements regarding norovirus is correct EXCEPT: (A)the infection mainly affects younger children and older people as well (B)epidemics occur every 2 to 3 years (C)the first line diagnostics is the detection of the virus by PCR from fecal samples (D)a vaccine is available that protects people from norovirus infection 3. Each of the following statements regarding the mode of action of the viruses/bacteria is correct EXCEPT: A. noroviruses possess an enzyme that inhibits proteinsynthesis of the host cell B. rotaviruses induce cell death (apoptosis) thereby causing diarrhea C. Shigella produces a N-glycosidase that has a specificity for 28S ribosomal RNA and upon this action stops protein synthesis of the host cell D. Vibrio cholerae ADP-ribosylates G-proteins and thereby activates an adenylate cyclase which indirectly affects the efflux of water 4. Each of the following statements regarding the treatment of severe diarrhea is correct EXCEPT: A. if possible glucose should be given the oral way at a concentration of 20g/L B. Chloride and bicarbonate losses should be included in the glucose/electrolyte solution to compensate anionic loss C. sodium and potassium losses should be included in the glucose/electrolyte solution to compensate cationic loss D. coca cola contains all the electrolytes and the glucose to compensate the loss of glucose and electrolytes that are lost during diarrhea 5. Each of the following statements regarding the infectious dose of the viruses/bacteria is correct EXCEPT: A. B. C. D. noroviruses have an infectious dose lower than 100 particles rotaviruses have an infectious dose higher than 1000 particles campylobacter requires 1000 to 10.000 particles to become infective Vibrio cholerae requires > 1.000.000 particles to become infective 6. Please describe the general properties of picornaviruses. 7. What are the clinical findings as a result of rotavirus infection versus Norwalk virus infection? 8. What causes poliomyelitis? What is the route of infection? What is the global situation of the disease? How about the vaccine?