Enteroviruses

Prepared By: Eriwan Osman Daban Azad Dastan Hadi Omer Ahmed Zanyar Qadr

Introduction
Viruses of the gut Member of the Picornaviridae family Stable at a pH of 3-10 Resist lipid solvents, chloroform and alcohol Inactivated at temperatures >500C Infectious at refrigerator temperature Inactivated by ionizing radiation, formaldehyde and phenol

Picornaviridae Family
Includes
Aphtoviruses Cardioviruses Hepatoviruses Rhinoviruses Enteroviruses

History
First identified in 1909 First grown in cell cultures in 1949

Classification
1st Classification, includes 5 species:
Polioviruses 1-3 Group A Coxsackieviruses A1-A22,A24 Group B Coxsackieviruses B1-B6 Echoviruses E1-E9,E11-E27,E29-E32 Enteroviruses EV68-EV71

Classification
2nd Classifcation, includes 2 main groups:
Polioviruses: Type 1,2, and 3 Non-polioviruses:
Echoviruses Coxsackieviruses Enteroviruses Unclassified Enteroviruses

Classification
3rd Classification
According to ICTV (March 2010) Includes:
Bovine enterovirus Human enterovirus A Human enterovirus B Human enterovirus C Human enterovirus D Human rhinovirus A Human rhinovirus B Human rhinovirus C Porcine enterovirus B Simian enterovirus A

Viral Proteins
Have 11 known proteins 4 used to construct the icosahedral capsid (VP1-VP4) VPg is involved in viral replication 3 are non-structural and are used as proteases Another is RNA-dependent RNApolymerase enzyme

Structure
Naked virus Icosahedral symmetry Apprixmately 30 nm in diameter Linear,+ive sense, single stranded RNA Capsid consists of 60 capsomeres Each capsomere consists of 4 viral proteins VP1-VP4

Pathophysiology
Upon entry into the oropharynx, the virus replicates in the submucosal tissues of the distal pharynx and alimentary tract Incubation period is 3-10 days During incubation, the virus migrates to regional lymphoid tissue and replicates, causing minor viremia, onset of symptoms and spread to RES Dissemination to target organs (CNS,skin) follows, producing major viremia Neuropathy of paralytic polio is due to direct neuronal destruction, with lesions occuring mainly in the anterior horn of the spinal cord All 3 poliovirus serotypes bind to CD155

Clinical Manifestations
Aseptic Meningitis
Inflammation of the meninges Most common in <5 years Caused by CV-A and CV-B EV-71 also associated with meningitis and sever CNS infections, including polio like paralysis

Clinical Manifestations
Encephalitis
Acute inflammation of the brain Caused by ECHO-9 and 6, CV-A9,B2, B5 and poliovirus

Cardiac Arrhythmia
Abnormal electrical activity of the heart Heart beat maybe too fast, too slow Associated with CV-B and EV-71

Clinical Manifestations
Acute Hemorrhagic Conjunctivitis
Ocular infection, highly contagious Pain, burning and swelling of the eyelids Sensation of a foreign body in the eye Self-limiting, improvement in 2-3 days Recovery in 7-10 days Caused by EV-70 and CV-A24

Clinical Manifestations
Attention Deficit Hyperactivity Disorder
Neurobehavioral, developmental disorder Persistent pattern of inattention/hyperactivity Associated to EV-71

Clinical Manifestations
Diabetes Mellitus Type 1
Environmental triggers of T1DM Associated with CV-B4 and B5

Guillian-Barre Syndrome
AIDP Auto-immune disease Associated with Coxsackie viruses

Clinical Manifestations
Hand, Foot, and Mouth Disease (HFMD)
Common in infants and children Fever, and blister-like eruptions in the mouth and/or a skin rash Most common causative agent is CV-A16 Also caused by EV-71 and other CVserotypes

Clinical Manifestations
Birth Defects and Problems During Pregnancy
Spontaneous abortion Stillbirth Congenital anomalies CVS,UGS, and digestive system anomalies associated with CV-B2,B3,B4, and A9 CV-B antibodies found in infants with severe CNS defects

Summary of clinical sydromes associated with enteroviruses

Syndrome Paralytic disease Polio + Cox A + Cox B + Echo +

Meningitis-encephalitis
Carditis Neonatal disease Pleurodynia Herpangina Rash disease Respiratory infections Undifferentiated fever Diabetes/pancreatitis Disease in immunocomp.

+
+ + + +

+
+ + + + + +

+
+ + + + + + + -

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+ + + + + +

Laboratory Diagnosis
Virus Isolation
Fecal samples or rectal swabs More than 1 specimens must be collected in an interval of 24-48 hrs During acute infection, pharyngeal swabs may also be useful Sterile body fluids are more significant Primary monkey kidney and embryo lung fibroblasts are commonly used Sensitivity is 60-75%

Laboratory Diagnosis
Serological Techniques
Neutralization tests are most common Labour intensive Takes at least 3 days to give results IgM-antibody capture assays recently became available for CV-A and CV-B IgM antibody has cross-reactivity for different enteroviruses, including Hepatoviruses Too slow for clinical purposes

Laboratory Diagnosis
Direct Detection of Viral Genomes
PCR-assays Particularly useful for cases of suspected enteroviral meningitis Sterile body fluids should be used Rapid and highly sensitive 100% sensitivity and 97% specificity RT-PCR are recent methods to detect common genetic area in the serotypes

Other Tests
ESR: elevated Cardiac enzymes: to detect cardiac involvement Urinalysis: to odd out bacterial infections WBC count: <500 cells/mL

Imaging Studies
Not specific, includes
Chest radiographs Echocardiographs ECG EEG

Used to detect extent of the infection

Treatment
Symptomatic and supportive treatment, includes
Anti-pyretics Analgesics Immunoglobulins Immuneboosters

Antiviral agents, includes

Pleconaril (Picovir) Beta Interferon

Treatment
Drugs to avoid
Antibiotics: do no good Corticosteroids: shifts the immune response in the wrong direction

Epidemiology
Transmission:
Fecal-oral: most common transmission mode Transmission:
Direct: contact with faeces Indirect: contaminated water, food, fingers, fomites, contaminated ophthalmological instruments

Respiratory-oral: for CV-A21

Epidemiology
Infections distributed worldwide Affected by seasons and climates

Declaration of polio eradication by WHO in the western hemisphere Last case of polio seen in Peru in 1991 1,652 confirmed cases of paralytic polio worldwide reported in 2008

In temperate areas, during summer and early fall In tropical and semi-tropical areas, all year round

Epidemiology
Morbidity/Mortality
90% of non-polio infections are asymptomatic Myopericarditis: Mortality Rate of 0-4% Myocarditis has more mortality rate than pericarditis Mortality rate in polio epidemics were 57% Risk of OPV-related disease is about 1 in 2.6 million doses of OPV

Epidemiology
Sex
Male-Female ratio of myopericarditis in 2:1 Risk of cardiac involvement increases during pregnancy and immediately postpartum Polio infection is equal in boys and girls Paralysis more common in boys Aseptic meningitis twice as common in males than females

Epidemiology
Age
Most common in younger children Herpangia: 3 months 16 years Poliomyelitis: <15 years Aseptic meningitis: more common in infants Pleurodynia: In children, adults<30 years Myopericardits: more common in young adults AHC: most prevalent in adults 20-50 years Neonates: at high risk of severe sepsis due to infection

Prevention
Poliomyelitis
Vaccination, includes
Inactivated Salk Vaccine:
Intramuscular, no risk of VAPP More invasive Poor local immunity, no herd immunity

Live Attenuated Sabin Vaccine:

Oral, risk of VAPP Not invasive Provides localized and general immunity, herd immunity

Prevention
Non-Polio Infections
No vaccine available Hygiene