Overview of Enterovirus Infections

Human parechoviruses types 1 and 2 are picornaviruses that were previously named echovirus 22 and 23. However, the parechoviruses have been reclassified into a separate genus, parechoviruses, which have 2 species, A and B. Parechovirus A can infect humans and has 16 types; most cause mild gastrointestinal and respiratory illness similar to the enteroviruses but some types, particularly type 3, are a common cause of viral sepsis and/or meningitis in infants. Human parechoviruses are not identified by most standard enterovirus RT-PCR tests; specific parechovirus RT-PCR testing is required (1 General references Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more ).

Aseptic meningitis Overview of Meningitis is most common among infants and children. In infants and young children, the cause is frequently one of the following:

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 Encephalitis Encephalitis is inflammation of the parenchyma of the brain, resulting from direct viral invasion or occurring as a postinfectious immunologic complication caused by a hypersensitivity reaction... read more , which may be severe, also occurs.

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 Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , have more serious symptoms involving the lower respiratory tract (eg, wheezing, respiratory distress).

Healthy adults can be infected, but they tend to have few or no symptoms. Immunocompromised adults may have severe respiratory disease.

Every year, respiratory infections caused by EV-D68 are identified in a few children, and small outbreaks tend to occur every other year. 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 a few children died. At the same time, case clusters of children with focal limb weakness or paralysis with spinal cord lesions (seen on MRI) consistent with acute flaccid myelitis after a respiratory illness also were reported; EV-D68 was identified in respiratory specimens in two thirds of cases in two distinct outbreak clusters and in the blood of one child during the progression of the paralysis. Sequenced viruses were nearly identical and shared homology with poliovirus and enterovirus D70, which are known to be associated with acute flaccid myelitis and supports a potential causal role of EV-D68 in acute flaccid myelitis paralysis (2 General references Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more ). Ongoing surveillance by the Centers for Disease Control and Prevention (CDC) detected 120 cases of acute flaccid myelitis in the fall of 2014, coinciding with the EV-D68 outbreak (3 General references Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more ). After no reported cases of EV-D68 and only 22 sporadic cases of acute flaccid myelitis reported in 2015, 2016 saw another rise in acute flaccid myelitis with 153 cases reported in the US during a peak of EV-D68 activity (see CDC: AFM Cases and Outbreaks).

Another large outbreak of EV-D68-associated respiratory illness peaked in the US in September 2018. Active CDC surveillance detected the virus in 13.9% of pediatric patients with acute respiratory illness at several large US medical centers, compared to only 0.08% of similar patients in 2017. Two-thirds of the patients with EV-D68 required hospitalization, highlighting the severity of illness. There was also a contemporaneous increase in reported acute flaccid myelitis, with over 200 CDC-confirmed cases in 2018 compared to only 38 in 2017, which further supports an association between EV-D68 infection and acute flaccid myelitis (4 General references Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more ). Overall, these epidemiologic links along with animal model data strongly suggest a causal relationship between EV-D68 infection and acute flaccid myelitis (5 General references Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more ).

EV-D68 should be considered as an etiology for otherwise unexplained severe respiratory infection, particularly if associated with a cluster of cases in late summer to fall. Specific testing in potential outbreaks is recommended and can be arranged through public health officials.

Rarely, hemorrhagic conjunctivitis due to enterovirus 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 weeks 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 weeks.

Cardiac infection due to enterovirus may occur at any age, but most patients are 20 to 39 years old. Patients may present with chest pain Chest Pain Chest pain is a very common complaint. Many patients are well aware that it is a warning of potential life-threatening disorders and seek evaluation for minimal symptoms. Other patients, including... read more , arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more , heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , or sudden death. Recovery is usually complete, but some patients develop dilated cardiomyopathy Dilated Cardiomyopathy Dilated cardiomyopathy is myocardial dysfunction causing heart failure in which ventricular dilation and systolic dysfunction predominate. Symptoms include dyspnea, fatigue, and peripheral edema... read more . Diagnosis of myopericarditis 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 Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more and has a high mortality rate.

Usually, several days after birth, the neonate suddenly develops a syndrome resembling sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more with fever, lethargy, disseminated intravascular coagulation, bleeding, and multiple organ (including heart Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more ) failure. Central nervous system, 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 Acute Liver Failure Acute liver failure is caused most often by drugs and hepatitis viruses. Cardinal manifestations are jaundice, coagulopathy, and encephalopathy. Diagnosis is clinical. Treatment is mainly supportive... read more .

Certain coxsackieviruses, certain 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 Aseptic meningitis Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more may develop simultaneously.

The course is usually benign.

These infections may result from enteroviruses. Symptoms include fever, coryza, pharyngitis, and, in some infants and children, vomiting and diarrhea. Bronchitis Acute Bronchitis Acute bronchitis is inflammation of the tracheobronchial tree, commonly following an upper respiratory infection in the absence of chronic lung disorders. The cause is almost always a viral... read more and interstitial pneumonia Acute Interstitial Pneumonia Acute interstitial pneumonia (AIP) is a rare and fulminant idiopathic pulmonary disorder that manifests similarly to acute respiratory distress syndrome ( ARDS) . Acute interstitial pneumonia... read more occasionally occur in adults and children.

The course is usually mild but can be severe as evidenced by the 2014 enterovirus D68 outbreak Enterovirus D68 Enteroviruses, along with rhinoviruses (see Common Cold) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous... read more .