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Hand-Foot-Mouth Disease and Other Enterovirus Infections

Enteroviruses (polioviruses, coxsackieviruses, echoviruses) are among the most common and significant causes of infectious illness in infants and children. They are associated with a broad spectrum of clinical syndromes, including aseptic meningitis, herpangina, hand-foot-mouth disease, conjunctivitis, pleurodynia, myopericarditis, poliomyelitis, various exanthems, and nonspecific febrile illness. In the neonate, enteroviral infection can cause a sepsis-like picture or meningoencephalitis, either of which can be severe. Newer technologies such as polymerase chain reaction (PCR) may provide rapid and sensitive testing methods for diagnosis of enteroviral infections, which may expand the list of diseases attributable to this group of pathogens. Although treatment of enteroviral infections remains unsatisfactory, immunization against poliovirus has been remarkably successful, and new immunization regimens using live and killed virus vaccines have been developed. A role has been postulated for enteroviruses in the pathogenesis of hand-foot-mouth disease.

Epidemiology

Enteroviruses are commonly referred to as "summer viruses" because resulting infections occur primarily during the warmer, summer months (May through October) in temperate northern hemisphere climates such as in the United States. In tropical climates, enteroviral infection is seen all year without seasonal variation.

Humans are the only known natural hosts for enteroviruses.

Human Enteroviruses
GROUP SEROTYPES
Poliovirus 1-3
Coxsackievirus group A 1-22, 24
Coxsackievirus group B 1-6
Echovirus 1-9, 11-27, 29-33
Enterovirus 68-72 *
*Hepatitis A virus was enterovirus type 72, but recently has been reclassified as a Heparnavirus.


The fecal-oral route is the most common mode of transmission, but oral-oral and respiratory spread also are possible. Risk factors for infection include poor sanitation, crowded living conditions, and low socioeconomic class. Children younger than 5 years of age are the most susceptible to infection
.

Sixty-eight enteroviral serotypes have been identified, but most infections are caused by a small number of these. During annual epidemics of clinical disease, certain serotypes predominate.

Pathogenesis

The incubation period for most enteroviral infections ranges from 3 to 10 days. The virus enters the host via the oral cavity and/or respiratory tract, then invades and replicates in the upper respiratory tract.

Clinical Presentations of Infection With Nonpolio Enteroviruses

Nonpolio enteroviruses are estimated to cause 10 to 15 million symptomatic infections in the United States annually. They cause a wide spectrum of disease that can involve almost any organ system (Table 3) . Disease severity can range from life-threatening with significant morbidity.

NONSPECIFIC FEBRILE ILLNESS

The most common clinical presentation of nonpolio enterovirus infection is a nonspecific febrile illness.

ASEPTIC MENINGITIS

Nonpolio enteroviruses are the leading causes of aseptic meningitis, accounting for 80% to 90%.

HERPANGINA

Herpangina is an enanthemous (mucous membrane) disease characterized by a painful vesicular eruption of the oral mucosa associated with fever, sore throat, and pain on swallowing.

HAND-FOOT-MOUTH (hand-foot-mouth) DISEASE

hand-foot-mouth disease is characterized clinically by a vesicular eruption on the hands and feet and in the oral cavity. Toddlers and school-age children are affected most commonly. Coxsackie-virus A16 is the

Patients present with fever of 38 to 39C (100.4 to 102.2F) that lasts 1 to 2 days, sore mouth or throat, and the characteristic exanthem/enanthem. The oral vesicles usually are located on the buccal mucosa and tongue and are only mildly painful. They are surrounded by erythematous rings and eventually ulcerate (Fig 2) (Figure Not Available) . The exanthem involves vesicles on the palms, soles, and interdigital surfaces of the hands and feet. Less commonly, lesions (nonvesicular) can be seen on the buttocks, proximal extremities, and genitalia. Most children recover within 1 week.

The differential diagnosis for hand-foot-mouth disease includes infection by herpes simplex or varicella-zoster virus, herpangina, and aphthous stomatitis. In contrast to hand-foot-mouth, varicella lesions are located more centrally, are more extensive, and usually spare the palms and soles. Additionally, resolution of

NONSPECIFIC EXANTHEM

Nonpolio enteroviruses are the leading cause of exanthems in children during the summer and fall