Echovirus Infection

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Echoviruses are members of the Enterovirus genus in the Picornaviridae family. They make up the largest Enterovirus subgroup, consisting of 29 serotypes. Echoviruses are common human pathogens that cause a range of illnesses, from minor febrile illness to severe, potentially fatal conditions (eg, aseptic meningitis, encephalitis, paralysis, myocarditis). ^[1] Individual serotypes have different temporal patterns of circulation and cause different clinical manifestations. Changes in circulating serotypes and variations in the genotype of the same subtype can be associated with large-scale outbreaks. ^{[1, 2]}

Enteroviruses are divided into 5 subgenera: polioviruses, group A coxsackieviruses, group B coxsackieviruses, echoviruses, and the newer enteroviruses. Each subgenus contains numerous unique enterovirus serotypes differentiated based on neutralization of specific antisera. ^[3]

The term enterovirus reflects enteric transmission of the virus via person-to-person spread. ECHO is an acronym for enteric cytopathic human orphan. ^[4]

Echoviruses were first isolated from the feces of asymptomatic children in the context of epidemiological studies of polioviruses. The viruses produced cytopathic effects in cell cultures but failed to cause detectable pathologic lesions in suckling mice. ^[5] Most echoviruses are no longer considered orphans.

Echoviruses were originally classified into 34 serotypes. Echovirus 10 has been reclassified as reovirus 1 and echovirus 28 as rhinovirus 1. Echovirus 9 is now recognized as the same as coxsackievirus A23. Echovirus 22 and 23 have been reclassified as members of the Parechovirus genus, and echovirus 34 is a variant of coxsackievirus A24. ^[6]

Echoviruses are small nonenveloped viruses with an icosahedral configuration. A capsid composed of 60 subunits is formed from 4 proteins—VP1 to VP4. These proteins play important roles in terms of determining host range and tropism and in delivering the RNA genome into the cytoplasm of the host’s cells. ^[7] Echoviruses are infective over a wide range of pH (3-10) and are resistant to ether and alcohol.

Human echoviral infection occurs via fecal-oral transmission. Host susceptibility depends on the presence of specific cellular membrane receptor proteins that bind different enteroviral types along taxonomic lines. Decay-accelerating factor (DAF) appears to be a major echovirus receptor, binding many echovirus serotypes, including 6, 7, 11, 12, 20, 21, 29, and 33. Echovirus serotypes 1 and 8 bind to the α₂ subunit of the very late antigen (VLA) integrin molecule.

Following ingestion of fecally contaminated material, viral replication begins in the pharynx or gut. The precise site of viral entry and initial replication in the GI tract is not well established, but researchers have demonstrated the presence of enteroviruses in mucosal M cells. Ileal lymphoid tissue demonstrates enteroviral replication within 1-3 days after ingestion. The maximal duration of viral excretion is 3-4 weeks in the pharynx and 5-6 weeks in stool.

Following replication, enteroviruses spread to regional lymph nodes and cause subclinical transient viremia. During this low-grade viremia, the virus spreads to reticuloendothelial tissues, including the liver, spleen, bone marrow, and distant lymph nodes. Secondary sites of infection include the CNS, liver, spleen, bone marrow, heart, and lungs. More than 90% of echoviral infections are asymptomatic. When disease occurs, symptoms vary from undifferentiated febrile illness to severe illness, depending on the age, gender, and immune status of the host and the subgroup, serotype, and enteroviral strain. ^[8]

For additional information, please also refer to Medscape Reference’s Enteroviruses topic.

United States

Echoviruses are common and are associated with both epidemic and endemic patterns of infection in individuals of all ages. The voluntary and passive nature of viral illness reporting complicates the true estimate of disease. ^[1] Serologic surveys are not feasible because of the large number of nonpoliovirus serotypes.

In temperate climates, enteroviral activity peaks during the summer and early fall. Serotype-based surveillance provides a mechanism for determining patterns of circulation and for identifying predominant serotypes. ^[1] Changes in predominant serotypes can be associated with large-scale outbreaks of enteroviral illnesses. From 2009-2013, the National Enterovirus Surveillance System (NESS) reported that the frequency with which individual types circulated from year to year varied considerably, with only echovirus 18 constituting at least 5% of reported annual detections in at least 4 of the 5 years. The most common types during the 5-year period were coxsackievirus A6 (12.3%) and human parechovirus 3 (12.3%). ^[9]

In the United States, peaks in nationwide hospitalization for aseptic meningitis have been observed in years when echovirus 9 was predominant. Echovirus 9 was the most commonly reported enterovirus from 1970-2005 and accounted for 11.8% of reports with known serotypes. ^[1]

International

Echoviruses are found worldwide and affect people of all races and cultures. Infection rates vary with the season, geography, and the age and socioeconomic status of the population sampled. Infection among lower socioeconomic groups is attributed to overcrowded living conditions and poor hygiene. Infections occur throughout the year in tropical climates. In temperate climates, infections are more prevalent during the summer and early fall.

Epidemics have been reported in Panama, Mexico, Switzerland, Cuba, the United States, and Turkey. Asian-Pacific countries have reported major enteroviral epidemics with significant morbidity and mortality. ^{[10, 11]} A Thai hospital reported the first nosocomial outbreak of hand-foot-and-mouth disease due to echovirus type 11, underscoring the importance of strict infection control and hand washing in preventing disease. ^[12]

Echovirus infection has no racial predilection.

For unclear reasons, males are at greater risk for clinical illness following infection, by as much as 50%. ^[13] Aseptic meningitis is nearly twice as common in boys as in girls. After puberty, the reverse appears to be true, perhaps because women tend to have more exposure to children who are shedding the virus. Echovirus infection in pregnancy is common; case reports have described vertical transmission or transmission shortly after birth, with potentially serious outcomes. ^{[14, 15]}

Three quarters of enteroviral infections, including echoviral infections, reported to the World Health Organization occur in children younger than 15 years. In the United States, attack rates in infants younger than 1 year greatly exceed those in older children and adults. ^{[16, 17]} Children younger than one year accounted for 44.2% of reported cases. A male predominance was noted among patients younger than 20 years, but not among patients aged 20 years or older. ^[1]

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Madhu Chhanda Choudhary, MD Associate Professor, Department of Medicine, University of Pittsburgh School of Medicine

Madhu Chhanda Choudhary, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Received income in an amount equal to or greater than $250 from: Gilead Sciences- Honorarium for consulting on scientific advisory board.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Larry I Lutwick, MD, FACP Editor-in-Chief, ID Cases; Moderator, Program for Monitoring Emerging Diseases; Adjunct Professor of Medicine, State University of New York Downstate College of Medicine

Larry I Lutwick, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for the Study of Liver Diseases, American College of Physicians, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, Infectious Diseases Society of New York, International Society for Infectious Diseases, New York Academy of Sciences, Veterans Affairs Society of Practitioners in Infectious Diseases

Disclosure: Nothing to disclose.

Mary T Busowski, MD Chief, Division of Infectious Diseases, Orlando VA Medical Center; Infectious Disease Faculty Practice/Internal Medicine Faculty Practice, Orlando Health; Assistant Professor of Medicine, Florida State University College of Medicine; Assistant Professor of Medicine, University of Central Florida College of Medicine

Mary T Busowski, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, Florida Medical Association, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Echovirus Infection

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