EnterovirusesAn Overview

Enteroviruses A genus of the picornavirus family Naked ssRNA virus Are stable in acidic pH Enter the body mainly via ingestion Primary site of replication is lymphoid

tissue in the gut. Spread to blood and into lumen of gut to

be excreted in feces

Enterovirus Particles

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

At least 71 serotypes are known: divided into 5 groups Polioviruses Coxsackie A viruses Coxsackie B viruses Echoviruses Enteroviruses

Enteroviruses

Poliovirus First identified in 1909 First grown in cell culture in 1949 which

became the basis for vaccines. 3 serotypes of poliovirus (1, 2, and 3)

but no common antigen. Humans are the only susceptible hosts. Polioviruses are distributed globally. Immunization has eradicated poliovirus

in most regions of the world except in the Indian Subcontinent and Africa.

Pathogenesis Incubation period : 7 - 14 days. After ingestion, the virus multiplies

in the tonsils and Peyer's patches of the ileum

Transient viraemia occurs In few cases, involves the CNS Spreads along axons of peripheral

nerves to involve anterior horn cells of spinal cord, intermediate grey ganglia and even posterior horn cells

Poliomyelitis: Flaccid Paralysis

Clinical ManifestationsSubclinical infection (90 - 95%) A minor influenza-like illness Recovers within a few days May be accompanied by aseptic meningitis

Major illness (1 - 2%) Signs of aseptic meningitis. Infection of anterior horn cells: flaccid paralysis. Infection of medulla: respiratory paralysis and death.

Laboratory Diagnosis Virus Isolation

Mainstay of diagnosis Can be readily isolated in cell culture

from throat swabs, feces, rectal swabs & CSF.

Serology Very rarely used

Support for Polio Patient

Prevention No specific antiviral therapy is available.

Intramuscular Poliovirus Vaccine (IPV) Formalin inactivated virus of all 3 serotypes.

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.

Prevention 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 2005 Eradicated from most regions of the

world except the Indian subcontinent and sub-Saharan Africa.

Current Status of Wild Poliovirus Transmission

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, 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, encephalitis, febrile illness. Echovirus 31 types + E - Aseptic meningitis, rash, febrile (1-9, 11-27 illness, conjunctivitis, severe 29-33) generalized neonatal disease. Enterovirus 5 types + + - Polio-like illness, aseptic (68-72) meningitis, hand, foot and mouth (E71), epidemic conjunctivitis (E70) hepatitis A (E72)

Poliovirus Replication

Coxsackieviruses Coxsackieviruses are distinguished from other

enteroviruses by their pathogenicity for suckling rather than adult mice.

Two groups on the basis of the lesions in suckling mice. Group A: diffuse myositis with acute inflammation

and necrosis of fibers of voluntary muscles. Has 23 serotypes

Group B: 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. Have 6 serotypes

Echoviruses Were accidentally discovered in human

feces, unassociated with human disease during epidemiological studies of polioviruses. The viruses were named echoviruses (enteric, cytopathic, human, orphan viruses).

Altogether, There are 32 echoviruses (types 1-9, 11-27, 29-34

New Enteroviruses Newly identified picornaviruses that are not

polioviruses, coxsackie, and echovirus : 5 types (68 - 72).

Enterovirus 70 causes acute haemorrhagic conjunctivitis

Enterovirus 71 has been associated with epidemics of aseptic meningitis, encephalitis, paralytic poliomyelitis-like disease and hand-foot-mouth disease.

Diseases associated with Enteroviruses

Syndrome Polio Cox A Cox B EchoParalytic disease + + + +Meningitis-encephalitis + + + +Carditis + + + +Neonatal disease - - + +Pleurodynia - - + -Herpangina - + - -Rash disease - + + +Haemorr. conjunctivitis - + - -Respiratory infections + + + +Undifferentiated fever + + + +Diabetes/pancreatitis - - + -

Laboratory Diagnosis Virus Isolation

Mainstay of diagnosis of enterovirus infection Coxsackie B and Echoviruses can be readily grown in cell culture from

throat swabs, feces, and rectal swabs. They can also be isolated from the CSF

Coxsackie A viruses cannot be easily isolated in cell culture. Can be isolated readily in suckling mice. Molecular techniques may provide a better alternative.

Serology Very rarely used for diagnosis since cell culture is efficient. Neutralization tests or EIAs

Cytopathic Effect

(Virology Laboratory, New-Yale Haven Hospital)

Management and Prevention No specific antiviral therapy available IVIG in the treatment of neonatal

infections or severe infections in immunocompromised individuals.

HNIG to prevent outbreaks of neonatal infection with good results.

No vaccine available