Enteroviruses

1. Enteroviruses

2. Genera of Picornaviruses

3. Virus Serotypes Clinical Diseases Polioviruses 3 types Asymptomatic infection, viral meningitis, paraalytic disease, poliomyelitis Coxsackie A viruses 23 types ( A1-A22, A24) Viral meningitis plus, rash, ARD, myocarditis, orchitis Coxsackie B viruses 6 types (B1-B6) Viral meningitis, but no orchitis Echioviruses 32 types Viral meningitis, with orchitis Other Enteroviruses 4 types(68-71) Viral meningitis, rash,ARD Categories of Enteroviruses

4. Properties of enteroviruses

5. 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

7. Pathogenesis of enterovirus infection Replication in oropharynx Rhino,echo, coxsackie,polio Primary viremia Secondary viremia Target Tissue Skin Muscle Brain Meninges Liver Echo Coxsackie A Echo Coxsackie A, B Polio Coxsackie Echo Polio Coxsackie Echo Coxsackie

8. Pathogenicity(1) • ASYMPTOMATICAll enteroviruses • PARALYSIS - permanent Polio 1, 2, 3Coxsackie A7 • PARALYSIS - temporaryCoxsackie B1-6 • MENINGITIS (aseptic)Echo, Coxsackie A and BPolio, Entero 71 • ENCEPHALITISEntero 71Polio, Echo

9. Pathogenicity(2) • RASH- macularMany enteroviruses- vesicular - (e.g. 'Hand Foot Mouth')Coxsackie A • SUMMER FEBRILE ILLNESSMany enteroviruses • VESICULAR PHARYNGITIS ('Herpangina')Coxsackie A • MYOCARDITISCoxsackie B

10. Pathogenicity(3) • EPIDEMIC MYALGIA ('Bornholm')Coxsackie B • UPPER RESPIRATORY INFECTION (cold)Echo, Coxsackie A • PANCREATITISCoxsackie B • GASTRO-ENTERITISMany enteroviusess • CONJUNCTIVITIS (Haemorrhagic)Entero 70 • HEPATITISEntero 72 (hepatitis A virus)

11. Human diseases caused by enteroviruses

12. Immunity • Antibody 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.

13. Laboratory Diagnosis • Culture • Serology • Genome

14. Poliovirus

15. Important Characteristics

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 days • Pathogenesis: 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 people • Nonparalytic poliomyelitis or aseptic meningitis: 1%-2% of patients with poliovirus infections. • Paralytic polio, the major illness: 0.1% to 2%of persons with poliovirus

19. Victims of paralytic polio

20. Child with polio sequelae

21. Paralyzed child in an iron lung

22. Iron lung ward in the 1950's

24. Franklin D. Roosevelt • Born 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 1910. 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. Immunity • sIgA and neutralizing antibody (IgG, IgA, IgM) persist for life span

26. 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

27. 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

28. Advantages and disadvantages of opv • Advantages • Effectiveness • Lifelong immunity • Induction of secretory antibody response similar to that of natural infection • Possibility of attenuated virus circulating in community by spread to contacts (indirect immunization)(herd immunity) • Ease of administration • Lack of need for repeated boosters • Disadvantages • Risk of vaccine-associated poliomyelites in vaccine recipients or contacts • Spread of vaccine to contacts without their consent • Unsafe administration for immunodeficient patients

29. Advantages and disadvantages of IPV • Advantages • Effectiveness • Good stability during transport and in storage • Safe administration in immunodeficient patients • No risk of vaccine-related disease • Disadvantages • Lack of induction of local (gut) immunity • Need for booster vacine for lifelong immunity • Fact that injection is more painful than oral administration • Fact that higher cominity immunization levels are needed than with live vaccine

30. 100 Inactivated (Salk) vaccine Cases per 100,000 population United States 10 Oral vaccine 1 Reported cases per 100000 population 0.1 0.01 0.001 1950 1960 1990 1970 1980

31. Total casesSweden and Finland 10000 Killed (Salk) vaccine 1000 Reported cases 100 10 1 0 1950 1955 1960 1965 1970 1975

32. Killed (Salk) Vaccine Live (Sabin) Vaccine Serum IgG 512 Serum IgG 128 32 Serum IgM Serum IgM Reciprocal virus antibody titer Nasal IgA Serum IgA 8 Serum IgA 2 Duodenal IgA Nasal and duodenal IgA 1 48 96 48 96 Vaccination Days Vaccination

35. Coxsackie Virus

36. Features of coxsackievirus infection in the labortory

37. Features of coxsackievirus infection in man • Coxsackievirus A 1-24 • Asptic meningitis • Febrile illness • Herpangina疱疹性咽峡炎 • Hand-foot-and-mouth disease • Coxsackievirus B 1-6 • Neonatal disease • Myocarditis, hepatitis • Meningitis

38. Disease Associations • Paralytic Disease - most commonly associated with polioviruses but other enteroviruses may also be responsible, notably enterovirus 71 • Meningitis - 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

41. Hand-foot-and-mouth disease • Hand-foot-and-mouth disease: mostly coxackie A • fever, malaise, sore throat, vesicles on bucal mucosa, tongue, hands, feet, buttocks • highly infectious • resolution – 1w

42. Herpangina疱疹性咽峡炎 • Herpangina – usually coxackie A • acute onset, fever, sore throat, dysphagia • lesions – posterior pharynx • can persist w’s • no gingivitis

43. ECHO virus

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 syndromes • Aseptic meningitis • Paralysis • Rash • Respiratory disease • Other features • Pericarditis心包炎and myocarditis • Neonatal infection

46. Illness associated with recently identified enteroviruses • Enterovirus 68 Pneumonia and bronchiolitis • Enterovirus 69 Isolated from an ill person in Mexico • Enterovirus 70 Acute hameorrhagic conjunctivitis • Enterovirus 70, 71 Paralysis, meningo-encephalitis • Enterovirus 71 hand-foot-and-mouth disease • Enterovirus 72 Hepatovirus( Hepatitis A)