enter o viruses

7/29/2019 Enter o Viruses

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ENTEROVIRUSES

dr. Sahrun


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ENTEROVIRUSES

Enteroviruses are a genus of the picornavirus family which replicatemainly in the gut.

Single stranded naked RNA virus with icosahedral symmetry

Unlike rhinoviruses, they are stable in acid pH Capsid has 60 copies each of 4 proteins, VP1, VP2, VP3 and VP4

arranged with icosahedral symmetry around a positive sense genome.

At least 71 serotypes are known: divided into 5 groups

Polioviruses

Coxsackie A viruses

Coxsackie B viruses

Echoviruses

Enteroviruses (more recently, new enteroviruses subtype have beenallocated sequential numbers (68-71))


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FAMILY: PICORNAVIRIDAE

ENTEROVIRUSES

Over 72+

RHINOVIRUS

Type 1-100+

POLIO virus type 1,2,3

COXSACKIE A virus type 1-22,24COXSACKIE B virus type 1-6

E.C.H.O virus type 1-7,11-27,29-34

Numbered ENTEROVIRUSES type 68-71,73

Since 1967-all new ones are numbered

Cardiovirus

Aphthousviru

etc

E.C.H.O = enteric cytopathic human orphan


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Traditional Taxonomy Current Taxonomy

Polioviruses

PV13

Coxsackie A viruses

CAV122, 24

Coxsackie B viruses

CBV16

Echoviruses

E17, 9, 1121, 2427, 2933

Numbered enteroviruses

EV6871

Human enterovirus A (HEV-A)

CAV28, 10, 12, 14, 16; EV71, 76, 8991

Human enterovirus B (HEV-B)

CAV9; CBV16; E17, 9, 1121, 2427,

2933; EV69, 7375, 7778, 7988, 100

101

Human enterovirus C (HEV-C)

CAV1, 11, 13, 17, 1922, 24; PV13

Human enterovirus D (HEV-D)

EV68, 70


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ENTEROVIRUS PARTICLES

Courtesy of Linda M. Stannard, University of Cape Town, S.A.h


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CHARACTERISTICS Rhinovirus labile to

acidic p H

Genome of

Enteroviruses is m

RNA

Naked genome is

sufficient for infection

Replication in

cytoplasm

Cytolytic viruses


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PROPERTIES OF ENTEROVIRUSES

CPE in cell cultures

Monkey Human cell Pathology in

Group Virus types kidney culture newborn mice Major disease associations

Poliovirus 3 types + + - Paralytic poliomyelitis, aseptic

(1 - 3) meningitis, febrile illness.

Coxsackie 23 types - or E - or E + Aseptic meningitis, herpangina,

group A (A1-22, A24) febrile illness, conjunctivitis

(A24), hand, foot and mouth disease.

Coxsackie 6 types + + + Aseptic meningitis, severe neonatal

group B (B1-6) disease, myopericarditis, Bornholm

disease, encephalitis, febrile

illness.

Echovirus 31 types + E - Aseptic meningitis, rash, febrile

(1-9, 11-27 illness, conjunctivitis, severe29-33) generalized neonatal disease.

Enterovirus 5 types + + - Polio-like illness, aseptic

(68-72) meningitis, hand, foot and mouth

(E71), epidemic conjunctivitis (E70)

hepatitis A (E72)


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EPIDEMIOLOGY

Transmission from person to person:

Fecal-Oral

Respiratory Peak incidence : Summer & Fall

Male =Female

Age: Young children Incubation period: 3-6 Days


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PATHOGENESIS

URI Infection

Regional lymph nodes involvement

Low-Grade viremia (Heart,Skin,Pericardium ,Lung..)Clinical illness & Major viremia

Antibody appearance on 7th day

GI Replication


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1. POLIOVIRUS

3 serotypes of poliovirus (1, 2, and3) but no common antigen.

Humans are the only susceptible hosts.

Polioviruses are distributed globally. Before the availability ofimmunization, almost 100% of the population in developing countries

before the age of 5.

The availability of immunization and the poliovirus eradication

campaign has eradicated poliovirus in most regions of the world except

in the Indian Subcontinent and Africa. Poliovirus is on course of being eradicated worldwide by the end of

2000 or 2001.


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POLIOMYELITIS


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CLINICAL MANIFESTATIONS OF POLIOMIELITIES

There are 3 possible outcomes of infection:

Subclinical infection (90 - 95%) - inapparent subclinical infection account

for the vast majority of poliovirus infections. Abortive infection (4 - 8%) - a minor influenza-like illness occurs,

recovery occurs within a few days and the diagnosis can only be made by

the laboratory. The minor illness may be accompanied by aseptic

meningitis

Major illness (1 - 2%) - the major illness may present 2 - 3 days followingthe minor illness or without any preceding minor illness. Signs of aseptic

meningitis are common. Involvement of the anterior horn cells lead to

flaccid paralysis. Involvement of the medulla may lead to respiratory

paralysis and death.


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LABORATORY DIAGNOSIS

Virus Isolation

Mainstay of diagnosis of poliovirus infection

poliovirus can be readily isolated from throat swabs, faeces, andrectal swabs. It is rarely isolated from the CSF

Can be readily grown and identified in cell culture

Requires molecular techniques to differentiate between the wild

type and the vaccine type.

Serology Very rarely used for diagnosis since cell culture is efficient.

Occasionally used for immune status screening for

immunocompromised individuals.


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DIAGNOSIS Clinical

Presentation

LaboratoryDiagnosis

Faecal, Throat (2

or more samples),

CSF(Culture and

RT-PCR)


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TREATMENT/PREVENTION Supportive

Prevention is by Vaccination.

Global Eradiation Programme

Part of Routine immunisation schedule andtravellers to endemic areas should be vaccinated


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GLOBAL ERADICATION PROGRAMME


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PREVENTION (1)

No specific antiviral therapy is available. However the disease may be

prevented through vaccination. There are two vaccines available.

Intramuscular Poliovirus Vaccine (IPV)

consists of formalin inactivated virus of all 3 poliovirus serotypes.

Produces serum antibodies only: does not induce local immunity and thus will

not prevent local infection of the gut.

However, it will prevent paralytic poliomyelitis since viraemia is essential for

the pathogenesis of the disease.

Oral Poliovirus Vaccine (OPV)

Consists of live attenuated virus of all 3 serotypes.

Produces local immunity through the induction of an IgA response as well as

systemic immunity.

Rarely causes paralytic poliomyelitis, around 1 in 3 million doses.


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PREVENTION (2)

Most countries use OPV because of its ability to induce local immunity and

also it is much cheaper to produce than IPV.

The normal response rate to OPV is close to 100%.

OPV is used for the WHO poliovirus eradication campaign.

Poliovirus was targeted for eradication by the WHO by the end of year 2000

(now 2005). To this end, an extensive monitoring network had been set up.

Poliovirus has been eradicated from most regions of the world except the

Indian subcontinent and sub-Saharan Africa. It is possible that the WHO target

may be achieved.


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CURRENT STATUS OF WILD POLIOVIRUS

TRANSMISSION


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2. COXSACKIEVIRUSES

They are divided into 2 groups on the basis of the lesions

observed in suckling mice.

Group A viruses produce a diffuse myositis with acute

inflammation and necrosis of fibers of voluntary

muscles.

Group B viruses produce focal areas of degeneration in

the brain, necrosis in the skeletal muscles, and

inflammatory changes in the dorsal fat pads, the

pancreas and occasionally the myocardium.

Each of the 23 group A and 6 group B coxsackieviruses

have a type specific antigen.


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HAND/FOOT/MOUTH

CoxsackieA16


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H/F/M


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3. ECHOVIRUSES

The first echoviruses were accidentally discovered in human faeces.

The viruses were named echoviruses (enteric, cytopathic, human,

orphan viruses).

These viruses were produced CPE in cell cultures, but did not induce

detectable pathological lesions in suckling mice.

Altogether, There are 32 echoviruses (types 1-34; echovirus 10 and 28

were found to be other viruses and thus the numbers are unused)

There is no group echovirus Ag but heterotypic cross-reactions occurbetween a few pairs.


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4. NEW ENTEROVIRUSES

4 new enteroviruses have been identified (68 - 72). Enterovirus 70 is the

causative agent epidemics of acute haemorrhagic conjunctivitis that

swept through Africa, Asia, India and Europe from 1969 to 1974. The

virus is occasionally neurovirulent. Enterovirus 71 appears to be highly pathogenic and has been associated

with epidemics of a variety of acute diseases, including aseptic

meningitis, encephalitis, paralytic poliomyelitis-like disease and hand-

foot-mouth disease.

Enterovirus 72 was originally assigned to hepatitis A virus, but it hadnow been assigned to a new family called heptoviruses.


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DISEASES ASSOCIATED WITH ENTEROVIRUSES

Syndrome Polio Cox A Cox B Echo

Paralytic disease + + + +

Meningitis-encephalitis + + + +

Carditis + + + +

Neonatal disease - - + +

Pleurodynia - - + -

Herpangina - + - -

Rash disease - + + +

Haemorr. conjunctivitis - + - -Respiratory infections + + + +

Undifferentiated fever + + + +

Diabetes/pancreatitis - - + -


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LABORATORY DIAGNOSIS

Virus Isolation Mainstay of diagnosis of enterovirus infection

Coxsackie B and Echoviruses can be readily grown in cell culture from

throat swabs, faeces, and rectal swabs. They can also be isolated from theCSF

Coxsackie A viruses cannot be easily isolated in cell culture. They can beisolated readily in suckling mice but this is not offered by most diagnosticlaboratories because of practical considerations. Molecular techniquesmay provide a better alternative.

Serology Very rarely used for diagnosis since cell culture is efficient.

Neutralization tests or EIAs are used but are very cumbersome and thusnot offered by most diagnostic laboratories


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CYTOPATHIC EFFECT

(Virology Laboratory, New-Yale Haven Hospital)


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MANAGEMENT AND PREVENTION

There is no specific antiviral therapy available against enteroviruses

other than polio.

Some authorities use IVIG in the treatment of neonatal infections or

severe infections in immunocompromised individuals. However, the

efficacy is uncertain.

HNIG have been to prevent outbreaks of neonatal infection with good

results.

There is no vaccine available mainly because of the multiplicity ofserotypes.

enter o viruses

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