AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Acute hemorrhagic conjunctivitis
Adenovirus keratoconjunctivitis

Myopericarditis
Acute myocardial infarction
Angina

Aseptic meningitis
Arbovirus infection
Lyme disease
Rocky Mountain spotted fever
Ehrlichiosis
Incompletely treated bacterial meningitis

Hand-foot-and-mouth disease
Herpes simplex
Aphthous stomatitis
Erythema multiforme
Atypical varicella

Abortive polio
Aseptic meningitis

Paralytic polio
Guillain-Barré (GB) syndrome
Botulism
Arthropod borne viral encephalitis

Herpangina
Bacterial tonsillitis
Aphthous stomatitis
Other viral tonsillitis

Pleurodynia
Pneumonia
Pulmonary infarction
Rib fracture
Costochondritis
Herniated intervertebral disc
Renal colic
Myocardial infarction
Prodromal phase of zoster
Acute abdomen

Guillain-Barré syndrome is an acute demyelinating polyneuropathy and, in the postpolio era, is the most common cause of generalized paralysis. The major symptom is rapidly progressive paralysis, which, unlike in polio, is symmetrical. Paralysis of the lower extremities is followed by paralysis of the upper extremities, and both proximal and distal muscle groups are involved. Deep tendon reflexes are initially reduced and are later absent. A mild sensory disturbance or paresthesia occurs. The cerebrospinal fluid (CSF) typically has an elevated protein level and a normal cell count (albuminocytologic dissociation).

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Diagnosis of Enterovirus infections is often clinical. Laboratory diagnosis can be achieved with serological tests, viral isolation by cell culture, and polymerase chain reaction (PCR).
• • Serology: Serological examination reveals a 4-fold increase in antibodies to enteroviruses between the acute and convalescent phases of illness. This diagnostic modality is infrequently used since it does not identify the specific serotype of Enterovirus.
  • Viral isolation: This is the criterion standard for diagnosing enteroviral infections. The virus can be isolated from CSF, blood, or feces, depending on the site affected, and the yield is increased if multiple sites are sampled. Poliovirus is easily cultured from stool and nasopharyngeal secretions, but isolation from the CSF is more difficult. The serotype of enteroviruses isolated by this method can be identified with neutralizing assays using type-specific antisera. The sensitivity of viral culture ranges from 60-75%.
  • Polymerase chain reaction: This test is highly sensitive and specific for detecting enteroviral RNA in CSF specimens, with a sensitivity of 100% and specificity of 97%. PCR provides rapid results and is becoming the favored diagnostic test but is limited by availability and cost in underdeveloped regions.
  • Cardiac enzyme levels may be elevated in persons with myopericarditis, indicating myocardial damage.
  • Cerebrospinal fluid analysis: The CSF profile of patients with aseptic meningitis reveals a mildly elevated white blood cell count. Glucose levels are normal or mildly decreased, while the protein level is normal or slightly increased.

Imaging Studies

• Chest radiography: In patients with myopericarditis, the chest radiograph may reveal cardiomegaly secondary to pericardial effusion or cardiac dilation. In pleurodynia, chest radiograph findings are normal.
• Echocardiography: Transient wall motion abnormalities may be revealed with echocardiography. Severe cases can reveal acute ventricular dilation and reduced ejection fraction.

Other Tests

• ECG: Nonspecific ST-T changes may be observed in persons with myopericarditis. Severe disease may cause Q waves, ventricular tachyarrhythmias, and heart block. ECG findings may demonstrate evolution through several stages of myopericarditis, as follows:
• • Stage I - Diffuse ST elevation with PR depression
  • Stage II - Normalization of ST and PR segments
  • Stage III - Deep symmetric inversion of T waves
  • Stage IV - May revert to normal or permanent T-wave inversions
• Electroencephalography: This test may be useful for evaluating the extent and severity of illness in patients with encephalitis.
• Ophthalmic slit-lamp examination: In persons with AHC, corneal erosions may visualized using a fluorescein stain. Enterovirus 70 and coxsackievirus A24 can be recovered from conjunctival swabs during the first 3 days of infection.

Histologic Findings

Histopathologic findings in most Enterovirus infections are usually nonspecific, consisting primarily of lymphocytic infiltrates and cell destruction.

Histologic findings in patients with polio have been well studied. Evidence of infection is pronounced in the spinal cord, medulla, pons, and mid brain. Neuronal destruction is observed, along with an inflammatory infiltrate composed of lymphocytes, macrophages, and polymorphonuclear leukocytes.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Polio management is supportive in nature.
• • Abortive polio: Treatment with bed rest and minimized exertion may be done at home. Supportive treatment with analgesics and sedatives is required.
  • Nonparalytic polio: Management is similar to that of abortive polio. Combine analgesic therapy with hot packs for pain relief.
  • Paralytic polio: In contrast to abortive and nonparalytic polio, which can be managed at home, patients with paralytic polio require hospitalization.
  • Bed rest is required during the early stages of the disease because exertion may worsen the degree of paralysis.
  • Applying hot packs to affected muscles may alleviate pain.
  • Align the body in a neutral position to minimize deformity. Patients should start physical therapy soon after the disappearance of pain. Physical therapy should include both active and passive exercises.
  • Mechanical ventilation may be required if respiratory muscles are affected.
  • Postural drainage and suction should be implemented in mild bulbar polio.
  • Patients with weakness or paralysis of the bladder may be treated with cholinergic agents, the sound of running water, or catheterization.
• Pleurodynia: Treatment is symptomatic, using analgesics and heat application for pain relief. Severe pain may require opiate analgesics.
• Aseptic meningitis: Treatment is symptomatic, with analgesics for headache relief.
• Myopericarditis
• • Treatment is mainly supportive in nature and involves management of pericardial pain, pericardial effusion, arrhythmias, and heart failure.
  • Bed rest is important since exercise can increase the degree of myocardial necrosis.
  • Avoid fluid overload.
  • Capsid-binding inhibitors belong to a new class of drugs that have shown benefit in some immunosuppressed patients with myocarditis. However, these drugs are not available for use in the United States.
  • Corticosteroids are contraindicated during the acute phase of viral myocarditis because they have been shown to cause clinical deterioration.
• Acute hemorrhagic conjunctivitis
• • Treatment is primarily symptomatic in nature.
  • Antimicrobial agents are not indicated unless bacterial superinfection occurs. Corticosteroids are contraindicated.
  • Cold compresses may be used, along with antihistamine/decongestant eye drops.
• Herpangina and hand-foot-and-mouth disease
• • Symptomatic treatment for sore throat is the mainstay of treatment, including analgesics, topical anesthetics, mouth wash, and saline rinses.
  • Viscous lidocaine (2% solution) may be helpful.

Consultations

• Consultation with a physiatrist is helpful to plan specific exercise programs, physical therapy, and adaptive equipment for patients with paralytic polio.
• Consultation with a cardiologist may be requested in myopericarditis for management of arrhythmias.
• Consultation with an ophthalmologist is appropriate for AHC.
• Consultation with a neurologist is requested in cases of paralytic polio if the diagnosis is uncertain.
• Physical and occupational therapists help patients with polio to establish a safe exercise program, adapt the home environment, and use mechanical aids (eg, grab bars).

Diet

• Encourage patients with paralytic polio to maintain a high fluid intake.
• • The application of hot packs leads to sweating, and these increased fluid losses should be replenished.
  • High fluid intake protects against nephrocalcinosis and urinary tract infections due to prolonged immobilization.
  • A diet rich in L-carnitine is under research for postpolio syndrome.
  • Patients with herpangina should consume soft bland foods and fluids, and avoid pain-inducing salty foods and citrus fruits.

Activity

• Bed rest is required for patients in the early stages of paralytic polio. Physical therapy should begin as soon as possible after the resolution of pain. Isometric exercises for select muscle groups can help increase muscle strength. Muscle capacity can also be increased with bracing and orthotics.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Management is supportive and addresses symptoms. No antiviral medications are currently approved for the treatment of Enterovirus infections.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In/Out Patient Meds

• Pleconaril is a drug that interferes with Enterovirus attachment and uncoating by binding to the virus protein capsid. It was the most promising candidate for the treatment of Enterovirus infections because of its oral bioavailability, penetration into the CNS, and efficacy in reducing the duration of symptoms and morbidity in neonatal sepsis and adult meningitis. It had been used on a compassionate basis until 2003, when the US Food and Drug Administration (FDA) declined its license. Pleconaril is currently being investigated for intranasal treatment of rhinovirus infections.
• Immunoglobulins have been used therapeutically with some success for severe Enterovirus infections in neonates and immunocompromised hosts. Preexposure prophylaxis with immunoglobulins reduces the risk of paralysis in patients with poliovirus infections.

Deterrence/Prevention

• Hygienic measures such as hand washing and adequate disposal of infected secretions help prevent the spread of enteroviral infections.
• Poliovirus vaccines have been instrumental in the effort to eradicate polio; the vaccine is available in 2 forms.
• • The OPV is a live attenuated vaccine that contains all 3 serotypes. It was developed by Sabin. OPV administration decreases replication of the virus in the small intestine and increases production of high titers of IgA in the mucosa. The advantages of OPV include easy administration, stimulation of local and generalized immunity, and herd immunity. Adverse effects include vaccine-associated paralytic poliomyelitis. OPV should not be administered to patients who are immunocompromised or to household contacts of these patients.
  • The IPV was originally developed by Salk in 1955. Current formulations of IPV are more immunogenic than those available before 1987. This vaccine elicits higher IgG antibody titers and has no adverse effects. It is the recommended polio vaccine in United States.
• The spread of acute hemorrhagic conjunctivitis is prevented by hand washing and using separate towels.

Complications

• Polio
• • Respiratory failure secondary to paralysis of respiratory muscles or to lesions of the respiratory center is a life-threatening complication of paralytic polio.
  • Pharyngeal paralysis may occur.
  • Myocarditis is rarely diagnosed clinically.
  • Gastrointestinal hemorrhage results from intestinal erosions and may require transfusion. Gastric dilation is abrupt in onset, and immediate gastric aspiration should be performed.
  • Hypertension is a common complication and may progress to hypertensive encephalopathy.
  • The postpolio syndrome occurs 3-4 decades after acute paralytic polio. It is characterized by muscle pain, worsening of prior weakness, or new paralysis. This is more common in females than in males.
  • Vaccine-associated poliomyelitis occurs in approximately 1 per 2.6 million people overall and in 1 per 750,000 people who receive the OPV.
• Aseptic meningitis: Complications include lethargy, febrile seizures, and coma.
• Myopericarditis
• • Dilated cardiomyopathy may develop as a result of past enteroviral infections.
  • Rarely, chronic constrictive pericarditis may develop 5 weeks to 1 year after resolution.
• Acute hemorrhagic conjunctivitis
• • Secondary bacterial infection may occur.
  • Motor paralysis may follow AHC by 2-5 weeks. It is clinically indistinguishable from polio, although it occurs exclusively in patients older than 20 years. Males are affected more frequently than females.
  • Neurological complications occur in epidemics caused by Enterovirus 70 but not by coxsackievirus A24.

Prognosis

• Polio: Paralytic polio leads to permanent weakness in the affected limb. Postpolio syndrome is slowly progressive.
• Aseptic meningitis: Fever and signs of meningeal irritation resolve within 1 week. Long-term prognosis is excellent.
• Pleurodynia: Patients with epidemic pleurodynia completely recover.
• Myopericarditis: The prognosis is good, and mortality rates in acute infection are low. Severe cases can result in dilated or restrictive cardiomyopathy. Twenty percent of patients may have recurrent myopericarditis.

Patient Education

• HFM disease is very contagious, particularly from 2 days before to 2 days after the rash; however, isolation is not necessary.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Avoid the nosocomial spread of AHC, particularly in ophthalmology clinics, where AHC can be spread by infected fingers or instruments.

Special Concerns

• In contrast with other viruses, intact humoral immunity is required for the eradication of Enterovirus infection. Children with primary immunodeficiency disease are at an increased risk of chronic enteroviral infections, and they may also develop paralytic polio from the OPV.
• Enteroviruses and insulin-dependent diabetes mellitus (type 1 DM): Many studies have evaluated the role of Enterovirus infections (particularly coxsackieviruses B4 and B5) as environmental triggers of insulin-dependent diabetes mellitus. Although a causal association has not been established, Enterovirus infection may increase susceptibility or hasten the onset of type 1 DM in children with impaired immunity or autoimmunity to pancreatic beta cells.
• Enteroviruses and coronary heart disease (CHD): Research suggests that Enterovirus infection may increase the risk of CHD and myocardial infarction in men with normal cholesterol levels.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Agre JC, Rodriquez AA, Tafel JA. Late effects of polio: critical review of the literature on neuromuscular function. Arch Phys Med Rehab. Oct 1991;72(11):923-31.
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• Desmond RA, Accortt NA, Talley L. Enteroviral meningitis: natural history and outcome of pleconaril therapy. Antimicrob Agents Chemother. Jul 2006;50(7):2409-14.
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• Fairweather D, Frisancho-Kiss S, Njoku DB. Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1beta, and immune complex deposition in the heart. J Immunol. Mar 15 2006;176(6):3516-24.
• Honeyman M. How robust is the evidence for viruses in the induction of type 1 diabetes?. Curr Opin Immunol. Dec 2005;17(6):616-23.
• Hsiung GD, Wang JR. Enterovirus infections with special reference to enterovirus 71. J Microbiol Immunol Infect. Mar 2000;33(1):1-8. [Medline].
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• Lonnrot M, Korpela K, Knip M, et al. Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study. Diabetes. Aug 2000;49(8):1314-8. [Medline].
• Melnick JL. Enteroviruses: polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses. Fields Virology. 1996;3rd ed. Philadelphia, Pa: Lippincott-Raven:655-712.
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Article Last Updated: Aug 1, 2006