Background
Coxsackieviruses belong to the family Picornaviridae and the genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens. Coxsackieviruses share many characteristics with poliovirus. With control of poliovirus infections in much of the world, more attention has been focused on understanding the nonpolio enteroviruses such as coxsackievirus.
Coxsackieviruses are nonenveloped viruses with linear single-stranded RNA. Coxsackieviruses are divided into group A and group B viruses based on early observations of their pathogenicity in mice. Group A coxsackieviruses were noted to cause a flaccid paralysis, which was caused by generalized myositis, while group B coxsackieviruses were noted to cause a spastic paralysis due to focal muscle injury and degeneration of neuronal tissue. At least 23 serotypes (1-22, 24) of group A and 6 serotypes (1-6) of group B are recognized.
In general, group A coxsackieviruses tend to infect the skin and mucous membranes, causing herpangina, acute hemorrhagic conjunctivitis (AHC), and hand-foot-and-mouth (HFM) disease. Group B coxsackieviruses tend to infect the heart, pleura, pancreas, and liver, causing pleurodynia, myocarditis, pericarditis, and hepatitis. Both group A and group B coxsackieviruses can cause nonspecific febrile illnesses, rashes, upper respiratory tract disease, and aseptic meningitis.
The development of insulin-dependent diabetes (IDDM) has recently been associated with recent enteroviral infection, particularly coxsackievirus B infection. This relationship is currently being studied further.
Pathophysiology
Coxsackieviruses are transmitted primarily via the fecal-oral route and respiratory aerosols, although transmission via fomites is possible. The viruses initially replicate in the upper respiratory tract and the distal small bowel. They have been found in the respiratory tract up to 3 weeks after initial infection and in feces up to 8 weeks after initial infection. The viruses have been found to replicate in the submucosal lymph tissue and disseminate to the reticuloendothelial system. Further dissemination to target organs occurs following a secondary viremia.
Epidemiology
Frequency
United States
Approximately 10 million symptomatic enteroviral infections are estimated to occur annually in the United States. From 2002-2004, an estimated 16.4-24.3% of these illnesses were attributed to coxsackievirus serotypes. For 2 of the 3 years, coxsackievirus B1 was the predominant serotype. The Centers for Disease Control and Prevention (CDC) found that coxsackievirus infections accounted for approximately 25% of all neonatal enterovirus infections (26,737) from 1983 to 2003.[1] Those due to coxsackievirus B4 were associated with a higher mortality rate than any other serotype.
International
Coxsackievirus infections have worldwide distribution. They can be isolated year-round in tropical climates, with a decreasing incidence of disease and seasonality in areas of higher latitude.
Mortality/Morbidity
Mortality due to coxsackievirus infection is uncommon. Neonates and immunocompromised individuals are at most risk for complications secondary to all enteroviral infections.
Sex
During the first decade, enteroviral infections are more common in males, with a male-to-female ratio of 2:1. The reason for this increased incidence is not well known.
Age
Coxsackievirus infection occurs in all age groups but is more common in young children and infants. Children are at higher risk of infection during the first year of life. The rate of illness decreases greatly following the first decade of life.
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