Enteroviruses

  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

Categories of Enteroviruses

Viral meningitis, rash,ARD

4 types(68-71)Other Enteroviruses

Viral meningitis, with orchitis

32 typesEchioviruses

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 typesPolioviruses

Clinical DiseasesSerotypesVirus

Properties of enterovirusesProperty EnterovirusesSize (nm)Capsid form PolypeptideRNA typeRNA molecular weightAcidOptimal temperature for growth(o

C)Density in caesium chloride (g/m)

22-30

Icosahedral VP1, VP2, VP3, VP4SS-PS2000,000-2600,000Stable*371.34*

Transmission

Fecal – oral route: poor hygiene, dirty diapers( especially in day-care settings) Ingestion via contaminated food and waterContact with infected hands Inhalation of infectious aerosols

Pathogenesis of enterovirus infection

Rhino,echo,coxsackie,polio

Replication in oropharynx

Primary viremia

Target Tissue Secondary viremia

Skin Muscle Brain Meninges Liver

Echo

Coxsackie

A

Echo

Coxsackie

A, B

Polio

Coxsackie

Echo

Polio

Coxsackie

Echo

Coxsackie

Pathogenicity(1)

ASYMPTOMATICAll enteroviruses PARALYSIS - permanent

Polio 1, 2, 3Coxsackie A7 PARALYSIS - temporaryCoxsackie B1-6MENINGITIS (aseptic)Echo, Coxsackie A and BPolio, Entero 71 ENCEPHALITISEntero 71Polio, Echo

Pathogenicity(2)RASH- macularMany enteroviruses- vesicular - (e.g. 'Hand Foot Mouth')Coxsackie ASUMMER FEBRILE ILLNESSMany enterovirusesVESICULAR PHARYNGITIS ('Herpangina')Coxsackie AMYOCARDITISCoxsackie B

Pathogenicity(3)EPIDEMIC MYALGIA ('Bornholm')Coxsackie BUPPER RESPIRATORY INFECTION (cold)Echo, Coxsackie APANCREATITISCoxsackie BGASTRO-ENTERITISMany enteroviusessCONJUNCTIVITIS (Haemorrhagic)Entero 70HEPATITISEntero 72 (hepatitis A virus)

Human diseases caused by enteroviruses 

Polio Cox A  Cox B Echo Other

Asymptomatic infection Yes Yes Yes Yes Yes

Meningitis( 脑膜炎 ) Yes Yes Yes Yes Yes

Paralysis( 麻痹 , 瘫痪 ) Yes Yes Yes Yes No

Febrile exanthems( 热疹） No Yes Yes Yes Yes

Acute respiratory disease No Yes Yes Yes Yes

Myocarditis( 心肌炎 ) No Yes Yes Yes No

Orchitis( 睾丸炎 No No Yes Yes No

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.

Laboratory Diagnosis

Culture

Serology

Genome

PoliovirusPoliovirus

Important Characteristics

Important Characteristics

D or N antigen: Type specific (CFA)C or H antigen: Common antigen (CFA)Type 1-3

Pathogenesis

1. Source of infection: Apparent and subclinical patients

2. Incubation: 7-14 days3. Pathogenesis: Only much less than 0.1% su

bjects exposed to polio virus form the flaccid paralysis

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

Victims of paralytic polio

Child with polio sequelae

Paralyzed child in an iron lung

Iron lung ward in the 1950's

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 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.

Immunity

sIgA and neutralizing antibody (IgG, IgA, IgM) persist for life span

Lab DiagnosisDefinitive 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

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

Advantages and disadvantages of opv

AdvantagesEffectivenessLifelong immunity Induction 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 administration Lack 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

Advantages and disadvantages of IPV

AdvantagesEffectivenessGood stability during transport and in storage Safe 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

Rep

ort

ed c

ases

per

100

000

po

pu

lati

on

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

10000

1000

100

10

10

Rep

ort

ed c

ases

1950 1955 1960 1965 1970 1975

Killed (Salk) vaccine

Total casesSweden and Finland

Rec

ipro

cal v

irus

antib

ody

titer

512

128

32

8

2

1

Serum IgG

Serum IgG

Serum IgM Serum IgM

Nasal and duodenal IgA

Nasal IgASerum Ig

A

Serum IgA

Duodenal IgA

DaysVaccination Vaccination

48 4896 96

Killed (Salk) Vaccine

Live (Sabin) Vaccine

Coxsackie VirusCoxsackie Virus

Features of coxsackievirus infection in the labortory

Types Growth in MK Effect in cell culture sucking mice

Coxsackie A virus 1-24 a + ParalysisCoxsackie B virus 1-6 + Spasticity MK , monkey kidney a Coxsackievirus A23 now classified as echovirus 9

Features of coxsackievirus infection in man

Coxsackievirus A 1-24Asptic meningitis

Febrile illnessHerpangina 疱疹性咽峡炎

Hand-foot-and-mouth disease

Coxsackievirus B 1-6Neonatal disease

Myocarditis, hepatitisMeningitis

Disease AssociationsParalytic 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.

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.

Exanthems – Rubelliform rashes

- EV leading cause in summer & fall. All types of rash

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

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

ECHO virusECHO virus

Important Characteristics

Not produce diseases in sucking mice, rabbits, or monkeys;Cause aseptic meningitis, infantile diarrhea, Monkey kidney and human embryonated kidney cell culture

Clinical syndromes associated with echoviruses

Main syndromesAseptic meningitisParalysisRashRespiratory diseaseOther featuresPericarditis 心包炎 and myocarditisNeonatal infection

Illness associated with recently identified enteroviruses

Enterovirus 68 Pneumonia and bronchiolitisEnterovirus 69

Isolated from an ill person in MexicoEnterovirus 70

Acute hameorrhagic conjunctivitisEnterovirus 70, 71

Paralysis, meningo-encephalitisEnterovirus 71 hand-foot-and-mouth diseaseEnterovirus 72 Hepatovirus( Hepatitis A)