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Overview of Enterovirus Infections

by Mary T. Caserta, MD

Enteroviruses include

  • Coxsackieviruses A1 to A21, A24, and B1 to 6

  • Echoviruses (enteric cytopathic human orphan viruses) 1 to 7, 9, 11 to 21, 24 to 27, and 29 to 33

  • Enteroviruses 68 to 71, 73 to 91, and 100 to 101

  • Polioviruses types 1 to 3

Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are picornaviruses ( pico , or small, RNA viruses). Human parechoviruses types 1 and 2 were previously named echovirus 22 and 23 but have now been reclassified. All enteroviruses are antigenically heterogeneous and have wide geographic distribution.

Enteroviruses are shed in respiratory secretions and stool and sometimes are present in the blood and CSF of infected patients. Infection is usually transmitted by direct contact with respiratory secretions or stool but can be transmitted by contaminated environmental sources (eg, water). Enteroviral diseases or epidemics in the US occur in summer and fall. Infection transmitted by a mother during delivery can cause severe disseminated neonatal infection, which may include hepatitis or hepatic necrosis, meningoencephalitis, myocarditis, or a combination.

Intact humoral immunity and B-cell function are required for control of enteroviral disease. Severe enteroviral infections (often manifesting as a slowly progressive meningoencephalitis) occur in patients with agammaglobulinemia but usually not in those with other immune deficiencies.

Diseases Caused by Enteroviruses

Enteroviruses cause various syndromes (see Syndromes Caused by Enteroviruses). Epidemic pleurodynia, hand-foot-and-mouth disease, herpangina, and poliomyelitis are caused almost exclusively by enteroviruses. Other disorders (eg, aseptic meningitis, myopericarditis) may be caused by enteroviruses or other organisms.

Syndromes Caused by Enteroviruses

Syndrome

Serotypes Most Often Implicated

Aseptic meningitis

Coxsackieviruses A2, 4, 7, 9, and others and B2–5

Poliovirus types 1–3

Echoviruses 4, 6, 7, 9, 11, and others

Human parechoviruses 1 and 2

Aseptic meningitis with rash

Coxsackieviruses A9 and B4

Echoviruses 4 and 16

Enterovirus 71

Conjunctivitis (hemorrhagic)

Enterovirus 70

Coxsackievirus A24

Epidemic pleurodynia (Bornholm disease)

Coxsackieviruses B1–6

Hand-foot-and-mouth disease

Coxsackieviruses A9, 16, and others

Coxsackieviruses B2–5

Enterovirus 71

Herpangina

Coxsackieviruses A2, 4–6, 8, and 10

Probably coxsackieviruses B3 and others

Myopericarditis

Coxsackieviruses A4 and 16 and B1–5

Echoviruses 9 and human parechovirus 1

Paralysis

Polioviruses 1–3

Coxsackieviruses A7 and others

Echoviruses 4, 6, 9, and others

Enterovirus 71

Rash

Coxsackieviruses A9 and B1, 3, 4, and 5 (also implicated, A4–6 and 16)

Echoviruses 9 and 16 (also implicated 2, 4, 11, 14, 19, and 25)

Respiratory disease

Echoviruses 4, 8, 9, 11, 20, and others

Coxsackieviruses A21 and 24 and B1 and 3–5

Aseptic meningitis

Aseptic meningitis is most common among infants and children. In infants and young children, the cause is frequently a group A or B coxsackievirus, an echovirus, or a human parechovirus. In older children and adults, other enteroviruses as well as other viruses may cause aseptic meningitis.

The course is usually benign. A rash may accompany enteroviral aseptic meningitis. Rarely, encephalitis, which may be severe, also occurs.

Enterovirus D68

Enterovirus D68 (EV-D68) causes a respiratory illness, primarily in children; symptoms usually resemble those of a cold (eg, rhinorrhea, cough, malaise, fever in a few children). Some children, particularly those with asthma, have more serious symptoms involving the lower respiratory tract (eg, wheezing, respiratory distress). Adults can be infected, but they tend to have few or no symptoms.

Every year, respiratory infections caused by EV- D68 have been identified in a few children. However, in the late summer and fall of 2014, over 1000 cases were confirmed in a large outbreak across the US. Severe respiratory distress developed in a significant number of children, and EV- D68 was detected in specimens from a few children who died. In addition, a few children developed focal limb weakness or paralysis with spinal cord lesions (seen on MRI) after a respiratory illness; EV-D68 was identified in respiratory specimens in about half of these cases. It is unclear whether EV- D68 infection was the main cause of death or paralysis or whether the virus happened to be present in children who also had other disorders. Investigation to determine the cause of death and neurologic symptoms is ongoing.

Hemorrhagic conjunctivitis

Rarely, this disorder occurs in epidemics in the US. Importation of the virus from Africa, Asia, Mexico, and the Caribbean may make outbreaks more common.

The eyelids rapidly swell. Hemorrhagic conjunctivitis, unlike uncomplicated conjunctivitis, often leads to subconjunctival hemorrhages or keratitis, causing pain, tearing, and photophobia. Systemic illness is uncommon. However, when hemorrhagic conjunctivitis is due to enterovirus 70, transient lumbosacral radiculomyelopathy or poliomyelitis-like illness (with paralysis) can occur but is rare. Recovery is usually complete within 1 to 2 wk of onset.

Coxsackievirus A24 also causes hemorrhagic conjunctivitis, but subconjunctival hemorrhage is less frequent, and neurologic complications have not been described. Most patients recover in 1 to 2 wk.

Myopericarditis

Cardiac infection may occur at any age, but most patients are 20 to 39 yr old. Patients may present with chest pain, arrhythmias, heart failure, or sudden death. Recovery is usually complete, but some patients develop dilated cardiomyopathy. Diagnosis may require reverse transcriptase (RT)–PCR of myocardial tissue.

Myocarditis neonatorum (cardiac infection at birth) is caused by group B coxsackieviruses, some echoviruses, and human parechoviruses. It causes fever and heart failure and has a high mortality rate.

Neonatal infection

Usually, several days after birth, the neonate suddenly develops a syndrome resembling sepsis with fever, lethargy, disseminated intravascular coagulation, bleeding, and multiple organ (including heart) failure. CNS, hepatic, myocardial, pancreatic, or adrenal lesions may occur simultaneously. Recovery may occur within a few weeks, but death may result from circulatory collapse or, if the liver is involved, liver failure.

Rashes

Certain coxsackieviruses, echoviruses, and human parechoviruses may cause rashes, often during epidemics. Rashes are usually nonpruritic, do not desquamate, and occur on the face, neck, chest, and extremities. They are sometimes maculopapular or morbilliform but occasionally hemorrhagic, petechial, or vesicular. Fever is common. Aseptic meningitis may develop simultaneously. The course is usually benign.

Respiratory infections

These infections may result from enteroviruses. Symptoms include fever, coryza, pharyngitis, and, in some infants and children, vomiting and diarrhea. Bronchitis and interstitial pneumonia occasionally occur in adults and children. The course is usually mild.

Diagnosis

Diagnosis of enteroviral diseases is clinical. Laboratory diagnosis is usually unnecessary but can often be made by culturing the virus, by detecting viral RNA using RT-PCR or, less commonly, by demonstrating seroconversion. Enteroviruses that cause aseptic meningitis can be detected in a sample from the throat, stool, blood, or CSF with RT-PCR tests done on blood and CSF. However, human parechoviruses are not identified by most standard enterovirus RT-PCR tests; specific parechovirus RT-PCR testing is required.

Treatment

Treatment of enteroviral disease is supportive. Patients with agammaglobulinemia are treated with IV immune globulins with variable success.

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