1. Enteroviruses

2. Genera of Picornaviruses
Enterovirus
Polio
Coxsackie A and B
Echo
Other enteroviruses
Diseases of the human (and other) alimentary tract
(e.g. polio virus)
Rhinovirus
Disease of the nasopharyngeal region (e.g. common cold virus)
Cardiovirus
Murine encephalomyocarditis, Theiler's murine encephalomyelitis virus
Aphthovirus
Foot and mouth disease in cloven footed animals
Hepatovirus
Human hepatitis virus A
Others
Drosophila C virus, equine rhinoviruses, cricket paralysis virus

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

4. Properties of enteroviruses
Property
Enteroviruses
Size (nm)
Capsid
form
Polypeptide
RNA type
RNA molecular weight
Acid
Optimal temperature for growth(oC)
Density in caesium chloride (g/m)
22-30
Icosahedral
VP1, VP2, VP3, VP4
SS-PS
2000, ,000
Stable* 37
1.34*

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) ASYMPTOMATIC All enteroviruses PARALYSIS - permanent
Polio 1, 2, 3 Coxsackie A7
PARALYSIS - temporary Coxsackie B1-6
MENINGITIS (aseptic) Echo, Coxsackie A and B Polio, Entero 71
ENCEPHALITIS Entero 71 Polio, Echo

9. Pathogenicity(2)
RASH - macular Many enteroviruses - vesicular - (e.g. 'Hand Foot Mouth') Coxsackie A
SUMMER FEBRILE ILLNESS Many enteroviruses
VESICULAR PHARYNGITIS ('Herpangina') Coxsackie A
MYOCARDITIS Coxsackie B

10. Pathogenicity(3) EPIDEMIC MYALGIA ('Bornholm') Coxsackie B
UPPER RESPIRATORY INFECTION (cold) Echo, Coxsackie A
PANCREATITIS Coxsackie B
GASTRO-ENTERITIS Many enteroviusess
CONJUNCTIVITIS (Haemorrhagic) Entero 70
HEPATITIS Entero 72 (hepatitis A virus)

11. Human diseases caused by enteroviruses
Polio
Cox A
Cox B
Echo
Other
Asymptomatic infection
Yes
Meningitis(脑膜炎)
Paralysis(麻痹,瘫痪) No
Febrile exanthems(热疹）
Acute respiratory disease
Myocarditis(心肌炎)
Orchitis(睾丸炎

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 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 Cell culture involves fibroblastic MRC-5 cells
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
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
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. Cases per 100,000 population United States
Reported cases per population
100 10 1
0.1
0.001
0.01
1950
1960
1970
1980
1990
Inactivated (Salk) vaccine
Oral vaccine
Cases per 100,000 population United States

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

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

35. Coxsackie Virus

36. Features of coxsackievirus infection in the labortory
Types Growth in MK Effect in
cell culture sucking mice
Coxsackie A virus a Paralysis
Coxsackie B virus Spasticity
MK , monkey kidney
a Coxsackievirus A23 now classified as echovirus 9

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 Hepatovirus( Hepatitis A)