eMedicine Specialties > Infectious Diseases > Viral Infections

Enteroviruses

Author: Smeeta Sinha, MD, Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School
Coauthor(s): Rajendra Kapila, MD, MBBS, Associate Professor, Department of Medicine, UMDNJ, New Jersey Medical School; Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Pratibha Dua, MD, MBBS, Staff Physician, Department of Internal Medicine, The Brooklyn Hospital Center; Leonard B Berkowitz, MD, Chief, Divisions of Infectious Diseases and HIV/AIDS Services, Brooklyn Hospital Center; Clinical Assistant Professor, Department of Medicine, State University of New York at Brooklyn
Contributor Information and Disclosures

Updated: Aug 1, 2006

Introduction

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.

Clinical

History

• Polio
  • Patients with abortive polio present with symptoms similar to those of other viral infections, including fever, headache, sore throat, loss of appetite, vomiting, and abdominal pain. Neurologic symptoms are typically not reported.
  • The symptoms of nonparalytic polio are similar to those of abortive polio but are more intense. Patients report stiffness of the posterior muscles of the neck, trunk, and limbs.
  • Paralytic polio presents similarly to nonparalytic polio, along with weakness of one or more muscle groups. Exercise increases the severity of paralytic polio, especially during the first 3 days of major illness. Intramuscular injections or skeletal muscle injury predisposes to localization of polio to that extremity (termed provocation poliomyelitis).
    • Spinal: Patients have a prolonged prodrome, with features of aseptic meningitis followed in 1-2 days by weakness and, eventually, paralysis.
    • Bulbar: Cranial nerves are involved, most commonly IX, X, and XII. Tonsillectomy increases the risk of bulbar polio. Patients are unable to swallow smoothly. They accumulate pharyngeal secretions; have a nasal twang to the voice; and develop paralysis of vocal cords, causing hoarseness, aphonia, and, eventually, asphyxia.
    • Polioencephalitis: This form is principally reported in children. Unlike in other forms of polio, seizures are common and paralysis may be spastic.
• Pleurodynia
  • Group B coxsackieviruses, particularly B3 and B5, are the most important causes of epidemic pleurodynia. Multiple family members may be affected.
  • Pleurodynia manifests with a sudden onset of fever accompanied by muscular pain in the chest and abdomen. The pain is spasmodic in nature, with spasms lasting 15-30 minutes and worsening during inspiration or coughing. This paroxysmal pain is characteristically associated with fever, peaking within 1 hour after onset of each paroxysm and subsiding with the subsequent paroxysm. Headache, nausea, and vomiting are also frequently reported.
• Myopericarditis
  • Enteroviruses do not infect the pericardium without myocardial involvement, but signs of either myocarditis or pericarditis supervene.
  • Neonatal infections typically develop within the first week of life, and involvement is predominantly myocardial. In contrast, older children and adults usually present with symptoms of pericarditis.
  • The typical presentation is shortness of breath, chest pain, and fever approximately 1-2 weeks following an upper respiratory infection. Chest pain may be dull or sharp; it is worsened by inspiration and may improve with sitting and leaning forward. It can be differentiated from angina by lack of response to nitroglycerin.
• Acute hemorrhagic conjunctivitis
  • This highly contagious ocular infection can cause large-scale epidemics. AHC was first described in 1969. Enterovirus 70 is the most common etiology in epidemics. Coxsackievirus A24 causes a similar disease. AHC was initially recognized in Ghana and Indonesia and is epidemic in India and the Far East.
  • The mode of transmission is from finger or fomite to eye. AHC is highly contagious, and crowding and unsanitary conditions favor spread.
  • Onset is abrupt, and the most common symptoms include ocular pain and burning, swelling of the eyelids, and the sensation of a foreign body in the eye. Patients may also experience photophobia and watery discharge. The other eye becomes involved a few hours after the first eye.
  • Nonspecific symptoms such as fever, malaise, and headache may be present. The symptoms typically improve by the second or third day of infection, and recovery is complete within 7-10 days.
• Nonspecific febrile illness
  • This is the most common presentation of Enterovirus infection.
  • Nonspecific febrile illness manifests with sudden fever (temperature, 101-104°F). Fever may last for as long as a week and may show a biphasic pattern.
  • Patients may report myalgia, headache, sore throat, nausea, vomiting, mild abdominal discomfort, and diarrhea.
• Aseptic meningitis
  • The clinical presentation of aseptic meningitis varies greatly among patients. Prodromal symptoms include fever, chills, headache, photophobia, and nuchal rigidity. Rash and upper respiratory symptoms are also common.
  • Fever and meningeal signs subside within 2-7 days.
  • Coxsackievirus B and echoviruses are the most common causes of aseptic meningitis. Enterovirus 71 causes a particularly aggressive CNS infection.
• Herpangina
  • Symptoms include sudden onset of fever, sore throat, and difficulty swallowing, followed one day later by a painful vesicular eruption of the oral mucosa. The posterior pharynx and tonsils may also be involved.
  • Patients may report anorexia, malaise, irritability, headache, backache, and diarrhea. Symptoms resolve in 3-4 days.
• Hand-foot-and-mouth disease
  • This is mainly a disease of children; most patients are younger than 10 years. Epidemics of HFM disease occur approximately every 3 years.
  • Coxsackievirus A16 is the most common etiologic agent, although Enterovirus 71 and numerous other Coxsackievirus serotypes may also cause the disease.
  • Following an incubation period of 3-6 days, patients experience prodromal symptoms such as fever, cough, sore throat, malaise, and anorexia. The prodrome lasts from 12-36 hours, and, subsequently, patients report vesicular eruptions of the hands, feet, and oral cavity. This may cause decreased oral intake in young children. The lesions self-resolve within 5-7 days.
  • Infection with Enterovirus 71 may be accompanied by severe neurologic disease including encephalitis, meningitis, and poliolike paralysis.
• Encephalitis
  • This is an uncommon manifestation of Enterovirus infection.
  • Echovirus 9 is the most common etiologic agent.

Physical

Physical examination findings in Enteroviral disease vary greatly depending on the type of illness caused by each etiologic agent.

• Nonspecific febrile illness: Physical findings are those of general viral illness, and mild pharyngeal erythema or conjunctivitis may be present.
• Pleurodynia: Paroxysmal chest pain is characteristic, and the initial paroxysm is usually the most severe. During paroxysms, respirations are rapid and shallow and patients look ill. The pain is reproducible, and patients appear healthy between paroxysms of pain. Auscultation may reveal a pleural friction rub.
• Myopericarditis: A pericardial friction rub is transient, if present. Signs of congestive heart failure are present in 20% of cases.
• AHC: The hallmark physical findings include ocular erythema and subconjunctival hemorrhage. Palpebral edema, chemosis, and ocular discharge may also be noted. Preauricular lymphadenopathy is an associated finding in AHC.
• Aseptic meningitis: Meningeal signs (nuchal rigidity, bulging fontanelles in infants) may be present, along with positive Kernig and/or Brudzinski sign. Some patients develop a rash.
• Herpangina: Examination of the oral mucosa reveals punctate macular lesions that evolve into vesicles and eventually ulcerate. The most common site of involvement is the anterior tonsillar pillar and soft palate. The lesions are tender and subside within one week.
• HFM disease: Vesicular lesions develop on the hands and feet and in the oral cavity. Hands are involved more commonly than feet. The vesicles appear gray and are surrounded by erythematous rings. Lesions are tender and resemble those of herpes simplex or varicella zoster infection. They resolve in approximately one week.
• Poliomyelitis
  • Nonparalytic polio: Signs of meningeal irritation are present, and patients may have positive Kernig and Brudzinski signs. In infants, the head drop sign can be elicited.
  • Paralytic polio: In early stage disease, reflexes are normally active. A change in the character of reflexes precedes paralysis by 12-24 hours. Superficial reflexes are the first to decrease, followed in 8-24 hours by loss of deep tendon reflexes. The resultant paralysis is flaccid and characteristically asymmetric in distribution. Proximal limb muscles are involved more than distal muscles. The lower extremities are affected more commonly than the upper extremities.
• Orchitis and epididymitis: Enteroviruses are the most common viral cause of orchitis. Orchitis is usually associated with pleurodynia.

Causes

• The most common mode of transmission of enteroviruses is by the fecal-oral route. Poor sanitation, low socioeconomic status, and crowded living conditions all facilitate the spread of infection.

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