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Overview of Enterovirus Infections

By

Brenda L. Tesini

, MD, University of Rochester School of Medicine and Dentistry

Last full review/revision Jul 2021| Content last modified Jul 2021
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Enteroviruses, along with rhinoviruses (see Common Cold Common Cold The common cold is an acute, usually afebrile, self-limited viral infection causing upper respiratory symptoms, such as rhinorrhea, cough, and sore throat. Diagnosis is clinical. Handwashing... read more ) and human parechoviruses, are a genus of picornaviruses (pico, or small, RNA viruses). All enteroviruses are antigenically heterogeneous and have wide geographic distribution.

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 are shed in respiratory secretions and stool and sometimes are present in the blood and cerebrospinal fluid 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 are more common in summer and fall.

Infection transmitted by a mother during delivery can cause severe disseminated neonatal infection Neonatal infection 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 , which may include hepatitis or hepatic necrosis, meningoencephalitis, myocarditis, or a combination of these, and can lead to sepsis or death.

Intact humoral immunity and B-cell function are required for control of enteroviral disease. Severe enteroviral infections (often manifesting as a slowly progressive meningoencephalitis, dermatomyositis, and/or hepatitis) occur in patients with defects in B lymphocyte function such as X-linked agammaglobulinemia X-linked Agammaglobulinemia X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections with encapsulated bacteria. (See also Overview... read more , but usually not in those with other immune deficiencies.

Parechoviruses

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 ).

Diseases Caused by Enteroviruses

The following are caused almost exclusively by enteroviruses:

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Aseptic meningitis

  • A group A or B coxsackievirus

  • An echovirus

  • A human parechovirus

In older children and adults, other enteroviruses as well as other viruses may cause aseptic meningitis.

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 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.

Hemorrhagic conjunctivitis

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.

Myopericarditis

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 failure causes shortness of breath and fatigue, and right ventricular failure causes peripheral and abdominal fluid... read more Heart Failure (HF) and has a high mortality rate.

Neonatal infection

Rashes

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.

Respiratory infections

General references

  • 1. de Crom SC, Rossen JW, van Furth AM, et al: Enterovirus and parechovirus infection in children: a brief overview. Eur J Pediatr 175(8):1023-9, 2016. Epub 2016 May 7. PMID: 27156106; PMCID: PMC4930465. doi: 10.1007/s00431-016-2725-7

  • 2. Greninger AL, Naccache SN, Messacar K, et al: A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): A retrospective cohort study. Lancet Infect Dis 15(6):671–682, 2015. doi: 10.1016/S1473-3099(15)70093-9

  • 3. Sejvar JJ, Lopez AS, Cortese MM, et al: Acute flaccid myelitis in the United States, August-December 2014: Results of nationwide surveillance. Clin Infect Dis 63(6):737-745, 2016. doi: 10.1093/cid/ciw372

  • 4. Kujawski SA, Midgley CM, Rha B, et al: Enterovirus D68-associated acute respiratory illness - New Vaccine Surveillance Network, United States, July-October, 2017 and 2018. MMWR Morb Mortal Wkly Rep 68(12):277-280, 2019. doi: 10.15585/mmwr.mm6812a1

  • 5. Messacar K, Asturias EJ, Hixon AM, et al: Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality. Lancet Infect Dis 18(8):e239-e247, 2018. doi: 10.1016/S1473-3099(18)30094-X

Diagnosis of Enterovirus Infections

  • Clinical evaluation

  • Sometimes culture or reverse transcriptase–polymerase chain reaction (RT-PCR)

Diagnosis of enteroviral diseases is usually clinical.

Laboratory diagnosis is usually unnecessary but can often be made by

  • Culturing the virus

  • Detecting viral RNA using RT-PCR

  • Less commonly, demonstrating seroconversion

Enteroviruses can be detected using RT-PCR testing on a sample from the involved site (eg, throat or nasopharynx, blood, cerebrospinal fluid) or from stool, in which the organism is often present even when the clinically involved site is elsewhere; identifying the causative organism is important mainly in cases of aseptic meningitis Overview of Meningitis Meningitis is inflammation of the meninges and subarachnoid space. It may result from infections, other disorders, or reactions to drugs. Severity and acuity vary. Findings typically include... read more . Commercially available multiplex PCR panels for respiratory pathogens often cannot distinguish between rhinoviruses and enteroviruses and may not identify all enteroviruses.

Treatment of Enterovirus Infections

  • Supportive

Treatment of enteroviral disease is supportive.

The oral antiviral drug pleconaril, which has shown activity against a number of picornaviruses, is being investigated for treatment of severe neonatal enteroviral disease (1 Treatment reference 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 ).

Treatment reference

  • 1. Abzug MJ, Michaels MG, Wald E, et al: A randomized, double-blind, placebo-controlled trial of pleconaril for the treatment of neonates with enterovirus sepsis. J Pediatric Infect Dis Soc 5 (1):53–62, 2016. doi: 10.1093/jpids/piv015

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