2 Genera of Picornaviruses EnterovirusPolioCoxsackie A and BEchoOther enterovirusesDiseases of the human (and other) alimentary tract(e.g. polio virus)RhinovirusDisease of the nasopharyngeal region (e.g. common cold virus)CardiovirusMurine encephalomyocarditis, Theiler's murine encephalomyelitis virusAphthovirusFoot and mouth disease in cloven footed animalsHepatovirusHuman hepatitis virus AOthersDrosophila C virus, equine rhinoviruses, cricket paralysis virus
3 Categories of Enteroviruses Viral meningitis, rash,ARD4 types(68-71)Other EnterovirusesViral meningitis, with orchitis32 typesEchiovirusesViral meningitis, but no orchitis6 types (B1-B6)Coxsackie B virusesViral meningitis plus, rash, ARD, myocarditis, orchitis23 types ( A1-A22, A24)Coxsackie A virusesAsymptomatic infection, viral meningitis, paraalytic disease, poliomyelitis3 typesPoliovirusesClinical DiseasesSerotypesVirus
4 Properties of enteroviruses PropertyEnterovirusesSize (nm)CapsidformPolypeptideRNA typeRNA molecular weightAcidOptimal temperature for growth(oC)Density in caesium chloride (g/m)22-30IcosahedralVP1, VP2, VP3, VP4SS-PS2000, ,000Stable*371.34*
5 TransmissionFecal – oral route: poor hygiene, dirty diapers( especially in day-care settings)Ingestion via contaminated food and waterContact with infected handsInhalation of infectious aerosols
7 Pathogenesis of enterovirus infection Replication in oropharynxRhino,echo,coxsackie,polioPrimary viremiaSecondary viremiaTarget TissueSkin Muscle Brain Meninges LiverEchoCoxsackieAEchoCoxsackieA, BPolioCoxsackieEchoPolioCoxsackieEchoCoxsackie
8 Pathogenicity(1) ASYMPTOMATIC All enteroviruses PARALYSIS - permanent Polio 1, 2, 3 Coxsackie A7PARALYSIS - temporary Coxsackie B1-6MENINGITIS (aseptic) Echo, Coxsackie A and B Polio, Entero 71ENCEPHALITIS Entero 71 Polio, Echo
9 Pathogenicity(2)RASH - macular Many enteroviruses - vesicular - (e.g. 'Hand Foot Mouth') Coxsackie ASUMMER FEBRILE ILLNESS Many enterovirusesVESICULAR PHARYNGITIS ('Herpangina') Coxsackie AMYOCARDITIS Coxsackie B
10 Pathogenicity(3) EPIDEMIC MYALGIA ('Bornholm') Coxsackie B UPPER RESPIRATORY INFECTION (cold) Echo, Coxsackie APANCREATITIS Coxsackie BGASTRO-ENTERITIS Many enteroviusessCONJUNCTIVITIS (Haemorrhagic) Entero 70HEPATITIS Entero 72 (hepatitis A virus)
11 Human diseases caused by enteroviruses PolioCox ACox BEchoOtherAsymptomatic infectionYesMeningitis(脑膜炎)Paralysis(麻痹,瘫痪)NoFebrile exanthems(热疹）Acute respiratory diseaseMyocarditis(心肌炎)Orchitis(睾丸炎
12 ImmunityAntibody is the major protective immune response to the enteroviruses . Secretory antibody can prevent the initial establishment of infection in the oropharynx and gastrointestinal tract, and serum antibody prevents viremic spread to the target tissue and therefore disease.Cell-mediated immunity is not usually involved in protection but may play a role in pathogenesis.
16 Important Characteristics D or N antigen: Type specific (CFA)C or H antigen: Common antigen (CFA)Type 1-3
17 Pathogenesis Source of infection: Apparent and subclinical patients Incubation: 7-14 daysPathogenesis: Only much less than 0.1% subjects exposed to polio virus form the flaccid paralysis
18 Clinical Syndromes Asymptomatic illness: 90% Abortive poliomyelitis, the minor illness: 5% infected peopleNonparalytic poliomyelitis or aseptic meningitis: 1%-2% of patients with poliovirus infections.Paralytic polio, the major illness: 0.1% to 2%of persons with poliovirus
24 Franklin D. RooseveltBorn in 1882 at Hyde Park, New York--now a national historic site--he attended Harvard University and Columbia Law School. On St. Patrick's Day, 1905, he married Eleanor Roosevelt.Following the example of his fifth cousin, President Theodore Roosevelt, whom he greatly admired, Franklin D. Roosevelt entered public service through politics, but as a Democrat. He won election to the New York Senate in President Wilson appointed him Assistant Secretary of the Navy, and he was the Democratic nominee for Vice President in 1920.In the summer of 1921, when he was 39, disaster hit-he was stricken with poliomyelitis. Demonstrating indomitable courage, he fought to regain the use of his legs, particularly through swimming. At the 1924 Democratic Convention he dramatically appeared on crutches to nominate Alfred E. Smith as "the Happy Warrior." In 1928 Roosevelt became Governor of New York.He was elected President in November 1932, to the first of four terms.
25 ImmunitysIgA and neutralizing antibody (IgG, IgA, IgM) persist for life span
26 Lab Diagnosis Cell culture involves fibroblastic MRC-5 cells Definitive diagnosis is made by osolation of the virus from stool, CFS, oropharyngeal secretionsCell culture involves fibroblastic MRC-5 cellsCPE is usually evident within 36 hoursSerotyping is based on neutralization of CPE by standardized antisera using intersecting pool followed by specific sera.ELISAIFAneutralizing TestCFT
27 PreventionBoth 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
28 Advantages and disadvantages of opv EffectivenessLifelong immunityInduction of secretory antibody response similar to that of natural infectionPossibility of attenuated virus circulating in community by spread to contacts (indirect immunization)(herd immunity)Ease of administrationLack of need for repeated boostersDisadvantagesRisk of vaccine-associated poliomyelites in vaccine recipients or contactsSpread of vaccine to contacts without their consentUnsafe administration for immunodeficient patients
29 Advantages and disadvantages of IPV EffectivenessGood stability during transport and in storageSafe administration in immunodeficient patientsNo risk of vaccine-related diseaseDisadvantagesLack of induction of local (gut) immunityNeed for booster vacine for lifelong immunityFact that injection is more painful than oral administrationFact that higher cominity immunization levels are needed than with live vaccine
30 Cases per 100,000 population United States Reported cases per population1001010.10.0010.0119501960197019801990Inactivated (Salk) vaccineOral vaccineCases per 100,000 population United States
31 Total cases Sweden and Finland 10000Killed (Salk) vaccine1000Reported cases100101195019551960196519701975
36 Features of coxsackievirus infection in the labortory Types Growth in MK Effect incell culture sucking miceCoxsackie A virus a ParalysisCoxsackie B virus SpasticityMK , monkey kidneya Coxsackievirus A23 now classified as echovirus 9
37 Features of coxsackievirus infection in man Coxsackievirus A 1-24Asptic meningitisFebrile illnessHerpangina疱疹性咽峡炎Hand-foot-and-mouth diseaseCoxsackievirus B 1-6Neonatal diseaseMyocarditis, hepatitisMeningitis
38 Disease AssociationsParalytic Disease - most commonly associated with polioviruses but other enteroviruses may also be responsible, notably enterovirus 71Meningitis - caused by all groups of enteroviruses, most commonly seen in children under 5 years of age.Encephalitis - focal or generalized encephalitis may accompany meningitis. Most patients recover completely with no neurological deficit.Undifferentiated febrile illness - may be seen with all groups of enteroviruses.Hand foot mouth disease - usually caused by group A coxsackieviruses although group B coxsackieviruses and other enteroviruses have been caused outbreaks.Herpangina疱疹性咽峡炎- caused by group A coxsackieviruses.Epidemic Pleurodynia胸膜痛(Bornholm disease) - normally caused by group B coxsackieviruses.
39 Myocarditis - group B coxsackieviruses are the major cause of myocarditis, although it may be caused by other enteroviruses. It may present in neonates as part of neonatal infection and is often fatal. In adults, the disease is rarely fatal.Respiratory Infections - several enteroviruses are associated with the common cold.Rubelliform rashes - a rash disease resembling rubella may be seen with several coxsackie A, B, and echoviruses.Neonatal Infection - some coxsackie B viruses and echoviruses may cause infection in newborn infants. The virus is usually transmitted perinatally during the birth process and symptoms vary from a mild febrile illness to a severe fulminating multisystem disease and death.Conjunctivitis - associated with several types of enteroviruses, notably Coxsackie A24 and Enterovirus 70 (haemorrhagic conjunctivitis)Pancreatitis胰腺炎/Diabetes - associated with Coxsackie B virus infection. The extent of the role of the virus in diabetes is unknown.
40 Exanthems – Rubelliform rashes - EV leading cause in summer & fall. All types of rash
44 Important Characteristics Not produce diseases in sucking mice, rabbits, or monkeys;Cause aseptic meningitis, infantile diarrhea,Monkey kidney and human embryonated kidney cell culture
45 Clinical syndromes associated with echoviruses Main syndromesAseptic meningitisParalysisRashRespiratory diseaseOther featuresPericarditis心包炎and myocarditisNeonatal infection
46 Illness associated with recently identified enteroviruses Enterovirus 68 Pneumonia and bronchiolitisEnterovirus 69Isolated from an ill person in MexicoEnterovirus 70Acute hameorrhagic conjunctivitisEnterovirus 70, 71Paralysis, meningo-encephalitisEnterovirus 71 hand-foot-and-mouth diseaseEnterovirus Hepatovirus( Hepatitis A)
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