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 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
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
2000,000-2600,000
Stable*
37
1.34*
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
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)
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
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
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)
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
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,
Laboratory Diagnosis
Culture
Serology
Genome
Poliovirus
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 days
3,Pathogenesis,Only much less than 0.1%
subjects exposed to polio virus form the
flaccid paralysis
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
Victims of paralytic polio
Child with polio sequelae
Paralyzed child in an iron lung
Iron lung ward in the 1950's
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,
Immunity
sIgA and neutralizing antibody
(IgG,IgA,IgM) persist for life
span
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
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
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
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
Re
po
rte
d c
as
es
p
er
10
00
00
p
op
ul
ati
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
1
0
Re
po
rte
d c
as
es
1950 1955 1960 1965 1970 1975
Killed (Salk)
vaccine
Total cases
Sweden and Finland
Re
cip
roca
l v
iru
s a
ntib
od
y tite
r
512
128
32
8
2
1
Serum
IgG
Serum
IgG
Serum IgM Serum
IgM
Nasal and
duodenal IgA
Nasal
IgA Serum
IgA
Serum
IgA
Duodenal
IgA
Days Vaccination Vaccination
48 48 96 96
Killed
(Salk)
Vaccine
Live
(Sabin)
Vaccine
Coxsackie Virus
Features of coxsackievirus infection
in the labortory
Types Growth in MK Effect in
cell culture sucking mice
Coxsackie A virus 1-24 a + Paralysis
Coxsackie B virus 1-6 + Spasticity
MK,monkey kidney
a Coxsackievirus A23 now classified as echovirus 9
Features of coxsackievirus
infection in man
Coxsackievirus A 1-24
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
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,
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 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 syndromes
Aseptic meningitis
Paralysis
Rash
Respiratory disease
Other features
Pericarditis心包炎 and myocarditis
Neonatal infection
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)