Excerpt from Enteroviruses

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Background

Enteroviruses belong to the Picornaviridae family of viruses and are further organized into the subgenera polioviruses, coxsackieviruses (groups A and B), and echoviruses. More than 60 serotypes have been identified, but only the first 61 are classified; 3 serotypes comprise the polioviruses, 23 serotypes comprise coxsackievirus group A, 6 serotypes comprise coxsackievirus group B, and 29 serotypes comprise the echoviruses. More recently identified enteroviruses are not included in the original classification; serotypes 68-71 are known as the newer enteroviruses.

The enteroviruses are icosahedral nonenveloped viruses that are approximately 30 nm in diameter. The genome is made of a single-stranded linear molecule of RNA. Enteroviruses resist lipid solvents and tolerate a wide range of pH and temperature. They are inactivated at temperatures of more than 50°C but remain infectious at refrigerator temperatures.

Enteroviruses cause a wide range of infections. Poliovirus infections can be subclinical or can cause mild illness, aseptic meningitis, or poliomyelitis. Coxsackievirus infection is the most common cause of viral heart disease. Group A viruses cause flaccid paralysis, while group B viruses cause spastic paralysis. Other diseases associated with coxsackievirus infections include hand-foot-and-mouth (HFM) disease and hemorrhagic conjunctivitis, caused by group A, while group B coxsackievirus is associated with herpangina, pleurodynia, myocarditis, pericarditis, and meningoencephalitis. Aseptic meningitis and colds are associated with both groups. Echovirus infections range from the common cold and fever to aseptic meningitis and acute hemorrhagic conjunctivitis (AHC).

Pathophysiology

Enteroviruses are transmitted predominantly via the fecal/oral route, although respiratory-oral spread and spread by fomites are also possible. Upon entry into the oropharynx, the virus replicates in submucosal tissues of the distal pharynx and alimentary tract. Viral particles are shed in the feces and in upper respiratory secretions for days prior to symptom onset. The average incubation period is 3-10 days, during which the virus migrates to regional lymphoid tissue and replicates. Minor viremia results, which is associated with the onset of symptoms and viral spread to the reticuloendothelial system (spleen, liver, bone marrow). Dissemination to target organs follows, and viral replication in target organs causes major viremia with secondary seeding of the CNS. Target organs include the skin, heart, and CNS.

The neuropathy of paralytic diseases caused by enteroviruses is due to direct cellular destruction. Neuronal lesions occur mainly in anterior horn cells of the spinal cord. The 3 serotypes of poliovirus all bind to the cell surface receptor CD155.

Intact humoral immunity is required for the control and eradication of enteroviral disease. Immunoglobulin (Ig) A, IgM and IgG are all produced in response to Enterovirus infection.

Frequency

United States

Nonpolio enteroviruses are responsible for 10-20 million symptomatic infections per year. The prevalence is higher in southern areas than in northern areas. Between 2002 and 2004, echoviruses 9 and 30 were the most commonly reported Enterovirus serotypes in the United States. AHC was first recognized in the United States in 1981 during an epidemic in Florida; few cases have been reported since.

International

Enteroviruses are distributed worldwide and are influenced by season and climate. Infections occur in summer and early fall in temperate areas, while tropical and semitropical areas bear the brunt all year.

AHC occurs as epidemics in tropical countries during the hot and rainy season. It was first recognized in 1969 in Ghana and Indonesia. AHC is an epidemic in India and the Far East.

The worldwide prevalence of poliomyelitis has decreased significantly because of improved economic conditions and availability of vaccines. The last case of wild polio in the Americas occurred in Peru in 1991. In 1994, the World Health Organization declared polio eradicated from the Western Hemisphere. Polio remains a significant disease in the developing world, and, in 2003, 6 endemic countries were identified: Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan. Between 2002 and 2005, wild-type poliovirus imported from these nations was recognized in 21 previously polio-free countries.

Mortality/Morbidity

• Myopericarditis is associated with a mortality rate of 0-4%. Myocarditis carries a higher mortality rate than pericarditis does. Additionally, murine model studies have suggested that a deficiency of complement receptors 1 and 2 leads to increased morbidity in coxsackie B3 infections, including myocarditis, dilated cardiomyopathy, and fibrosis.
• Prior to the vaccine era, the mortality rate in polio epidemics was 5-7%.
• The overall risk of oral poliovirus vaccine (OPV)–related disease is estimated to be 1 case per 2.6 million doses of OPV. In 1999, the inactivated poliovirus vaccine (IPV) was incorporated into the routine polio vaccination schedule; the incidence of vaccine-associated polio has subsequently decreased.

Sex

• The male-to-female ratio of myopericarditis is 2:1. The risk of cardiac involvement is higher during pregnancy and immediately postpartum.
• The prevalence of polio infection is equal in boys and girls, although paralysis is more common in boys. Among adults, women are at increased risk of infection and the postpolio syndrome compared with men.
• Aseptic meningitis is approximately twice as common in boys as it is in girls.

Age

• Enterovirus infections are most common in young children. Herpangina primarily affects children aged 3 months to 16 years. Poliomyelitis is observed in children younger than 15 years. Aseptic meningitis due to Enterovirus infection is more common in infants than in adults. Most cases of pleurodynia occur in children and adults younger than 30 years.
• Myopericarditis is most prevalent in young adults, especially those who are physically active. AHC is most prevalent in adults aged 20-50 years.
• Neonates are at high risk for severe sepsis due to Enterovirus infections.

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