Pediatric Echovirus

Updated: Jan 07, 2021
  • Author: Jorge M Quinonez, MD; Chief Editor: Russell W Steele, MD  more...
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Practice Essentials

Echoviruses (EVs) are RNA viruses of the genus Enterovirus and the family Picornaviridae. EVs were first isolated from the feces of asymptomatic children early in the 1950s, soon after the development of cell culture techniques. EVs cause cytopathic effects in primate cell cultures, although not initially associated with any disease condition. These orphan viruses were initially termed ECHO, an acronym for enteric cytopathic human orphan virus, which was later simplified to echovirus.



A committee sponsored by the National Foundation for Infantile Paralysis categorized EVs and other enteroviruses (ie, coxsackievirus group A and group B, polioviruses) together in 1957. They are grouped together and distinguished from other viruses on the basis of physicochemical characteristics and because they share common epidemiology, clinical manifestations, and pathogenesis. Enterovirus groups are differentiated based on host specificity. To date, 67 serotypes of enterovirus have been identified, 32 of which belong to the echovirus group.

EVs cause a wide range of common and uncommon clinical presentations. These agents and other members of the Enterovirus group are among the leading causes of acute febrile illness in infants and young children; they are the most common cause of aseptic meningitis. Infection in the first 2 weeks of life is particularly troublesome because it can cause severe systemic disease and is associated with high fatality rates. Another significant concern with enteroviral infections is that they can mimic symptoms caused by other common bacteria and viral infections; thus, enteroviral infections are often treated with therapies aimed for other infections.

EVs are small, measuring 24-30 nanometers (nm) under electron microscopy. They are composed of a naked protein capsid, constituting about 75% of the particle and enclosing a dense central core of single-stranded RNA. This RNA is approximately 7.5 kilobase (kb) long and contains an RNA replicase, viral-coded proteases, a single polyprotein that is responsible for forming structural polypeptides, and other proteins necessary for cellular replication. All EVs contain polypeptide chains (eg, virus protein 1 [VP1], virus protein 4 [VP4]). These structural proteins are important to determine host range and tropism, and they play a crucial role in delivering the RNA genome into the cytoplasm of new host cells.

Although EVs originally were classified into 34 serotypes, EV-10 later was reclassified as a reovirus and EV-28 as rhinovirus type 1; EV-9 now is considered the same as coxsackievirus A23.

At least 2 cellular receptors for EV have been identified: a subunit of the integrin molecule VLA-2 that binds types 1 and 8, and a complement regulatory protein (ie, a decay accelerating factor) that binds types 6, 7, 12, and 21.

The neonatal Fc receptor (FcRn) has been recognized as a pan-echovirus receptor expressed on intestinal enterocytes (primary site of infection) and liver hepatocytes and microvascular endothelial cells lining the blood-brain barrier (secondary sites of infection). This finding may explain the increased susceptibility of neonates to EV infection. [1]



Some viral replication occurs in the nasopharynx after exposure, with spread to regional lymph nodes. However, most inoculum is swallowed and reaches the lower GI tract, where the virus presumably binds to specific receptors on enterocytes. The virus traverses the intestinal epithelium, probably undergoing replication in the process but without causing any cellular effects, and reaches the Peyer patches in the lamina propria mucosae. Here, the virus undergoes substantial multiplication. A minor viremia develops on about the third day, seeding many secondary infection sites, including the CNS, liver, spleen, bone marrow, heart, and lungs. [2] Additional replication at these sites causes a major viremia that coincides with onset of clinical disease, usually 4-6 days after exposure. The delayed appearance of CNS disease symptoms suggests viral spread can develop during both the minor and the major viremia.

Enteroviruses can infect all tissues of the human body. The tropism of each virus for certain tissues is not well understood and is neither unique nor specific. Infections involving a single serotype may vary widely in their presentation; multiple serotypes can produce the same clinical syndrome.

The incubation period for EV is difficult to establish because both symptomatic and healthy individuals spread the virus. Incubation is believed to range between 2 days and 2 weeks. EV is communicable over a long period of time. The virus can be shed from the upper respiratory tract for 1-3 weeks and in stools for more than 8 weeks after primary infection.



Overcrowded conditions and poor hygiene easily explain the high prevalence of EV infections among lower socioeconomic groups.

EV is transmitted person-to-person; the fecal-oral route is the predominant mode, and transmission sometimes occurs via respiration of oral secretions.

Indirect transmission occurs through numerous routes, including contaminated water, food, and fomites. Contaminated swimming and wading pools can transmit the virus. Well-documented reports detail transmission via the contaminated hands of hospital personnel.

EV is communicable over a long period of time. The virus can be shed from the upper respiratory tract for 1-3 weeks and in stools for more than 8 weeks after primary infection.



United States data

Several studies confirm enteroviruses account for more than 50% of spring and fall emergency department visits by infants and young children for fever without a source. EV infections only sporadically develop in other seasons. In addition to this seasonality, EV types vary strikingly in their contribution to human disease. Some EVs remain endemic in patterns that vary from area to area each year in the United States. Other serotypes (eg, EV-9, EV-11, EV-30) can cause widespread outbreaks in which the responsible strain can account for more than 90% of all isolated strains of enterovirus.

According to the National Enterovirus Surveillance System (NESS), from 2014 to 2016, enterovirus D68 was the most frequently reported enterovirus type, followed by EV-30, coxsackievirus A6, EV-18, and coxsackievirus B3. [3]

International data

EV infections occur in all human populations. Transmission and infection occur throughout the year in the tropics and predominantly during summer and fall in temperate regions, with sporadic cases in other seasons. A few epidemics have been nearly global, such as one caused by EV-9 at the end of the 1950s and another by EV-11 in 1979 and 1980. More recently, an outbreak of EV-13 and EV-30 was reported in Germany, [4] and outbreaks of EV-13 were reported in Lithuania and Israel. [5, 6] An outbreak of EV-11 has also been reported in neonates in Taiwan. [7] Outbreaks have also been reported in Korea, [8] Cyprus, [9] Taiwan, [10] Finland, [11]  Greece, [12]  and China. [13] Particular serotypes are endemic or epidemic for unknown reasons. One hypothesis is that some epidemic strains such as EV-9 may spread rapidly in a "critical mass" of susceptible patients necessary for continuous transmission, whereas endemic strains may not be as contagious.

A study by Rodà et al collected clinical and epidemiological data at a pediatric hospital in Barcelona on 195 children, younger than 3 months, with confirmed EV infection. The study reported that the most common EV types were Echovirus-5 and Echovirus-11. The study also added that the majority of types appeared in spring, but E5 and E25 were found mainly during summer. E21 was associated with high-grade fever and E5 with exanthema more often than the other types. [14]

Sex- and age-related demographics

For unknown reasons, forms of EV disease such as meningitis and neonatal sepsis are far more common among male patients.

Although EV infections can occur in all age groups, incidence inversely relates to age; specific antibodies directly increase with time. Several studies performed during epidemics and for surveillance show that infants become infected at significantly higher rates than older children and adults.



Neonates with disseminated encephalitis have a poor prognosis and many die. Children and older patients have a better prognosis, but the disease is occasionally fatal.

The short-term prognosis for children with EV and enteroviral meningitis early in life appears to be good. The long-term prognosis for similarly affected children is controversial in regard to cognitive, developmental, and language abnormalities. Some recent prospective reports have indicated virtually no measurable long-term effects, even among patients with neurologic findings during their illness.

The prognosis is generally poor for patients with chronic meningoencephalitis who have coxsackievirus or EV infections and acquired or congenital B-lymphocyte function defects.


EV infections during the first 2 weeks of life can cause severe systemic disease associated with high fatality rates. EV and other enteroviruses account for 10-20% of documented viral causes of encephalitis. Neonates with disseminated encephalitis have a poor prognosis and many die. Infant death rates from perinatal EV infection are unknown, although some studies report high numbers. Neonatal mortality is usually caused by either overwhelming liver failure or myocarditis, rather than CNS involvement.

Children and older patients with disseminated encephalitis have a better prognosis, but fatalities occasionally occur. Acute myopericarditis, resulting from the well-established tropism of enterovirus for the heart, can be fatal in approximately 5% of cases, although most patients recover without major sequelae.