Enteroviral Infections

What are enteroviruses?
Enteroviruses are small viruses that are made of ribonucleic acid (RNA) and protein. Enteroviruses belong to the Picornaviridae family of viruses and are divided into 5 groups with many types within each group, including polioviruses (3 types), coxsackieviruses A (23 types), coxsackieviruses B (6 types), echoviruses (33 types), and other enteroviruses (4 types).

How common are infections with these viruses?
All three types of polioviruses have been eliminated from the Western Hemisphere, as well as Western Pacific and European regions, by the widespread use of vaccines. Non-polio enteroviruses are a very common cause of disease, particularly in children and are second only to the "common cold" viruses, the rhinoviruses, as the most common viral infectious agents in humans. At least 90% of enteroviral infections are either asymptomatic or result in non-specific febrile illness. Enteroviral infections are less common in adults but when they do occur their severity is usually greater than in childhood infections. They are also the most common cause of viral meningitis with echoviruses and group B coxsackie viruses accounting for 90% of all cases.

What are the symptoms of infection?
Most infections are asymptomatic or with only mild clinical syndromes. Symptoms include mild upper respiratory symptoms, flu-like illness with fever and muscle aches, or fever with rash. On rare occasions a person may develop "aseptic" or viral meningitis. Rarely, a person may develop an illness that affects the heart (myocarditis) or the brain (encephalitis) or causes paralysis. Enterovirus infections are suspected to play a role in the development of juvenile-onset diabetes mellitus (sugar diabetes). Newborns infected with an enterovirus may rarely develop a severe illness and die from infection.

Clinical features of enteroviral infections: 

• Nonfocal, Acute Febrile Illness
  The non-polio enteroviruses are a common cause of fever without an apparent focus among infants seen in casualty departments. During the summer and autumn, enteroviruses account for at least 53-63% of these cases. Fever is often the sole finding, although some infants will also have irritability, lethargy, poor feeding, vomiting, diarrhoea, rashes, or signs of upper respiratory tract infection. Upon evaluation, approximately half of enterovirus-infected infants will have aseptic meningitis, although there are no clinical features that distinguish those with meningitis before performing a lumbar puncture. Infants with enterovirus-induced fever recover within 2-10 days without complications.
• Hand-Foot-Mouth Disease (HFMD)
  This should not be confused with Foot and Mouth Disease, an animal disease caused by an unrelated virus. HFMD is one of the common presentations of enterovirus infections. It is associated with fever, painless bubbles and rash on the hands, feet and buttocks. Painful ulcers may be present in the mouth and around the tongue, causing difficulties in swallowing. It is most common in children and is usually caused by coxsackie viruses. The incubation period is 3 to 6 days. The condition usually last for 7-10 days and resolves spontaneously. A large outbreak of HFMD, due to enterovirus 71, has been reported from Hong Kong. Cases due to enterovirus 71 in this outbreak tended to be more severe than in previously reported outbreaks of HFMD.
• Viral Meningitis
  Enteroviruses are the commonest cause of viral meningitis. Children under four years of age are most at risk, with the highest incidence in children aged less than one year. There is usually a sudden onset of fever. Neck stiffness is present in about half of all cases, but is usually absent in children aged less than one year. Older children and adults will usually have a severe headache and aversion to bright light. Other symptoms such as rashes, vomiting, diarrhoea, cough, sore throat and muscle aches may also be present. A purpuric rash, which may be confused with a meningococcal rash, has been described with echovirus 9 and coxsackievirus A9 infections. The illness is sometimes biphasic, with an initial non-specific febrile illness for a few days that resolves, followed by fever and neck stiffness 2-10 days later. Viral meningitis usually resolves spontaneously in less than one week, though the illness may be more prolonged in adults. Complications such as seizures, lethargy, coma and movement disorders may occur early in the course of the illness in 5-10% of cases. Long-term complications are rare, except in neonates and patients with deficient humoral immunity.
• Encephalitis
  The enteroviruses account for approximately 10% to 20% of cases of frank encephalitis of proven viral etiology. The group A coxsackieviruses have been conspicuous among the agents isolated from infants and children with focal enteroviral encephalitis. The clinical manifestations range from mental status changes to coma and decerebration; partial complex seizures, hemichorea, and acute cerebellar ataxia, findings that in some cases suggested a diagnosis of herpes simplex virus encephalitis.
• Myelitis
  The non-polio enteroviruses rarely cause a syndrome of acute motor weakness and paralysis that is clinically and pathologically indistinguishable from poliomyelitis. However, myelitis caused by the non-polio enteroviruses is less severe, muscle weakness is less likely to persist and bulbar involvement is less common. Enterovirus 71 is known to have been responsible for large outbreaks of acute paralysis involving hundreds of individuals, mostly children.
• Myopericarditis
  Group B coxsackieviruses account for one third to one half of all cases of sporadic, acute myopericarditis, and for virtually all cases reported to have occurred during epidemics. Physically active adolescents and young adults may have the highest risk; males have at least twice the risk of females. Enteroviral myopericarditis is clinically indistinguishable from disease caused by other cardiotropic viruses, including adenoviruses, influenza A virus, and mumps virus. Fatalities occur in only 5% of diagnosed cases.
• Ophthalmic Infection
  Acute hemorrhagic conjunctivitis (AHC) is a highly contagious infection characterized by eye pain, eyelid swelling, and subconjuntival hemorrhages. AHC is transmitted directly form person to person via fingers and fomites. Contagion is favoured by crowding and poor sanitation; reuse of water for bathing and sharing towels. After an incubation period of 1 or 2 days, symptoms of infection appear abruptly with ocular pain, photophobia, watery discharge, and swelling of the eyelids. Fever and headache are observed in 20% of cases. The distinctive physical finding is subconjuntival hemorrhage, which is found in 60-90% or cases caused by enterovirus 70, but in fewer cases caused by coxsackievirus A24. Common associated clinical findings include conjuntival edema and follicle formation, punctate epithelial keratitis, and periauricular adenopathy.
• Neonatal Infections
  Neonates are at risk of serious and sometimes fatal disease resulting from enterovirus infection acquired during the perinatal period. The most severe manifestations, which are usually limited to infants younger than 10 days, are myocarditis with or without encephalitis, hepatitis, and pneumonia.

Who is at risk of infection and illness from these viruses?
Everyone is at risk of infection. Infants, children, and adolescents are more likely to be susceptible to infection and illness from these viruses, because they are less likely to have antibodies and be immune from previous exposures to them, but adults can also become infected and ill if they do not have immunity to a specific enterovirus.

How does someone become infected with one of these viruses?
Enteroviruses enter the body via ingestion and they are shed in the faeces and respiratory secretions (e.g., saliva, sputum, or nasal mucus) of an infected person. The viruses are readily transmitted by the faecal-oral route but can also be spread by direct contact with respiratory secretions or by contact with contaminated surfaces or objects. Parents, teachers, and childcare workers may also become infected by contamination of the hands with stool from an infected infant or toddler during nappy changes. Because adults infected with enteroviruses are more likely to develop symptoms enteroviral outbreaks in childcare settings are often detected through clinical cases in adult household contacts and staff.

What time of year is someone at risk for infection/illness?
Enteroviral infections tend to peak in summer and autumn in temperate regions. Outbreaks of infections have been reported worldwide and may be very large, affecting entire countries. Nationwide outbreaks of viral meningitis have been reported from Romania (4,734 cases), Japan (4,061 cases) and other countries.

How is infection diagnosed?
Laboratory diagnosis traditionally relied upon isolation of the virus in culture but PCR is replacing culture particularly for CSF samples.

Can these infections be prevented?
No vaccine is currently available for the non-polio enteroviruses. Because most persons who are infected with enteroviruses do not become sick, it can be difficult to prevent the spread of the virus. Hand washing is the single most important preventative measure for controlling the spread of enterovirus infections in the community, childcare and hospital settings. Cleaning of environmental surfaces, shared equipment and toys is also important, particularly in outbreak settings. Additional measures for the control of viral meningitis in the Community and Childcare Settings are outlined below:

• The Health Protection Agency, UK (HPA) do not recommend keeping children out of school or nurseries because of viral meningitis. This is based on the assumption that it is a mild disease and that the risk of transmission and period of infectiousness are not known. In addition they point out that outbreaks are rare. In the event of an outbreak, however, they recommend seeking the advice of a Specialist in Public Health Medicine in Communicable Disease Control.
• CDC does not recommend exclusion of ill children from childcare settings, even in the setting of an outbreak with Hand-Foot-and-Mouth disease. The Hong Kong Dept of Health, who dealt with a large outbreak of Hand-Foot-and-Mouth disease, does recommend exclusion of children with symptoms of HFMD. It should be noted, however, that the cases seen in the Hong Kong outbreak were more severe and the causative virus (enterovirus 71) appeared to be more transmissible than in other reported outbreaks.
• The decision to exclude children from childcare settings during an enteroviral outbreak will depend on the severity of symptoms and the likely transmissibility of the causative virus. In general, children with HFMD should be excluded while unwell and the childcare facility should have a policy of heightened hand hygiene frequency while the disease is present.
• Interventions needed to control very large enteroviral outbreaks have included school closures, closing of public swimming areas. Educational campaigns, emphasising hygiene and preventative measures, may be required.
• CDC state that the period of infectivity is from day 3 after exposure to about 10 days after the onset of symptoms. Presumably this is based on the period of respiratory shedding and maximal GI shedding.
• The American Academy of Pediatrics Red Book states that respiratory shedding of enteroviruses is limited to the first week of infection, but faecal shedding can continue for several weeks.
• Hand washing is the mainstay of prevention of transmission and control of outbreaks. Children and carers should wash their hands before eating or preparing food, after using the toilet or handling nappies, after contact with an ill child, after contact with animals and whenever hands are visibly soiled.
• Most authorities recommend using soap and running water for effective hand washing. There is some evidence that disinfectant hand rubs, containing >80% ethanol, are effective in neutralising enteroviruses on hands, provided the hands are already physically clean. Solutions containing isoproponol, n-proponol or lower concentrations of ethanol do not appear to be effective. Consideration should be given to using hand disinfectants in outbreak settings, particularly where hand-washing facilities are less than optimal.
• Children in nappies are likely to be a source for spreading enteroviruses, even if they are asymptomatic. Carers should be advised to pay particular attention to hand washing after changing nappies.
• Children should not share food or utensils.
• Environmental surfaces, toys and any shared items should be cleaned and disinfected with hypochlorite 1000 ppm (one part household bleach to ten parts water). In outbreak settings common surfaces should be wiped with this solution at least once every day and more frequently if visibly soiled.

Created: 08 December 2006