AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Echoviruses belong to the genus Enterovirus. Other viruses of this genus are the polioviruses, group A and B coxsackieviruses, and enteroviruses identified only by a type number. Enteroviruses of all types are members of the Picornaviridae family.

The term enterovirus reflects the fact that most of the species inhabit the alimentary (enteric) tract. The prefix echo in the term echovirus is an acronym for enteric cytopathic human orphan. Most echoviruses, however, no longer are considered orphans. Various human diseases, ranging from minor GI syndromes to significant infection of the CNS, are associated with infection with these viruses. Experts recognize at least 33 echovirus serotypes. Serotypes 22 and 23 will be reclassified most likely as a distinct picornaviral genus because of the substantial genetic divergence from the other viruses in the group.

Pathophysiology

Human infection is the result of ingestion of fecally contaminated materials. Host susceptibility to these viruses depends on the presence of a specific cellular membrane receptor protein that binds 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 a subunit of the very late antigen (VLA) integrin molecule.

Susceptible individuals ingest the virus, which then is replicated 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. Within 1-3 weeks after ingestion, enteroviral replication is detectable in the ileal lymphoid tissue. In general, the maximal duration of viral excretion is 3-4 weeks in the pharynx and longer than 5-6 weeks in the feces.

Following replication, enteroviruses spread to regional lymph nodes (eg, cervical, mesenteric) and cause a subclinical and transient minor viremia. During this low-grade viremia, the virus spreads to various reticuloendothelial tissues (eg, liver, spleen, bone marrow), as well as distant lymph nodes. In most individuals who are infected, a subclinical infection occurs and viral replication ceases, presumably because of host defense mechanisms. In a minority of individuals who are infected, further replication of the virus may occur, leading to a major (sustained) viremia that appears clinically as a nonspecific febrile illness.

Clinicians have documented viremia with echovirus 9, resulting in dissemination to target organs (eg, CNS, heart, skin). In these tissues, necrosis and inflammatory lesions are visible; however, histopathologic lesions are not observed in the gut or lymphoreticular tissues. In target organs, the degree of inflammatory change and tissue necrosis corresponds to the titer of infectious virus present, and stimuli, such as induced exercise, cold exposure, malnutrition, pregnancy, and immunosuppression with either corticosteroids or radiation, can enhance the severity of infection.

More than 90% of patients with these infections are asymptomatic or present with only an undifferentiated febrile illness. When disease occurs, the spectrum and severity of clinical manifestations vary with the age, gender, and immune status of the host and with the subgroup and serotype of the enteroviral strain.

Frequency

United States

Echovirus infections clearly are common. Although researchers accurately have measured the incidence and prevalence of nonpolio enteroviral infections in selected populations, the overall incidence is unknown. Documentation of viral isolation clearly is incomplete because clinicians tend to report viral isolation only from patients with symptomatic illnesses. Serologic surveys are not feasible due to the large number of nonpoliovirus (including echoviruses) serotypes.

Antibody prevalence rates indicate that 15-90% of the adult population has type-specific neutralizing antibodies. This often is dependent on the socioeconomic class of the population surveyed.

In urban areas, usually 1-3 nonpolio enteroviral serotypes predominate each season. Some serotypes are isolated, with low frequency in the same locality yearly, whereas others produce epidemics one year, only to completely disappear other years. Occasionally, epidemics are global, as was the epidemic due to echovirus 9 in the late 1950s. During 1993-1996, the 10 most common nonpolio enteroviral isolates submitted to the Enterovirus Surveillance Program of the Centers for Disease Control and Prevention accounted for 59-81% of all isolates within a given year. Echoviruses represented slightly less than half of the total of these isolates, including type 9 (12.7%), type 6 (5.1%), and type 11 (4.4%).

International

Echoviruses are found worldwide. Infection rates vary with the season, geography, and with both the age and socioeconomic status of the population sampled. In the tropics, the infections occur throughout the year. In temperate climates in the northern hemisphere, infections are strikingly more prevalent during the summer and autumn months.

Race

No racial predilection for echovirus infection exists.

Sex

Among young children, boys are at greater risk for clinical illness following infection, whereas asymptomatic infection is more common in girls. Aseptic meningitis occurs nearly twice as often in boys as in girls. After puberty, the reverse appears to be true, perhaps because women have greater exposure to children who are shedding the virus. Pregnancy also appears to enhance the severity of enteroviral infections.

Age

Three quarters of the enteroviral infections, including echoviral infections, reported to the World Health Organization occur in children younger than 15 years. In the United States, attack rates for both infection with and illness from enteroviruses overall are highest in infants younger than 1 year. Symptomatic enteroviral infection rates are lower in older children but remain higher than for adults. Aseptic meningitis is recognized most commonly in young children, whereas other illnesses (eg, pleurodynia, myopericarditis) are recognized predominantly in adolescents and adults. Symptomatic infections are uncommon in elderly patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Approximately 50-80% of patients with nonpolio enteroviral infections are completely asymptomatic. Patients who are symptomatic usually have undifferentiated febrile illnesses lasting only a few days that often are accompanied by symptoms of an upper respiratory tract infection. These illnesses may be caused by virtually any enteroviral serotype and are indistinguishable clinically from infection with many other viral agents. Disease syndromes characteristic of enteroviruses (eg, aseptic meningitis, pericarditis) are, in fact, unusual manifestations of infection.

• Acute aseptic meningitis
• • Acute aseptic meningitis is manifested by signs and symptoms of meningeal irritation and a lymphocytic cerebrospinal fluid (CSF) pleocytosis. Overall, the severity of clinical symptoms is less than that caused by bacterial meningitis.
  • Disease onset can be as abrupt as bacterial meningitis, but often it is more gradual. Typically, individuals will have a brief prodrome of fever and chills, and headache almost always is a prominent feature of the illness. Findings of meningeal irritation, such as Kernig and Brudzinski signs, are present in approximately one third of patients, and neck stiffness often is only moderate. Pharyngitis and other symptoms of upper respiratory tract infections often are present.
  • Enteroviral meningitis may have a biphasic component. Fever and myalgias occur for a few days followed by clinical defervescence and an absence of symptoms for several days. Sudden reappearance of fever and headache herald the onset of meningitis, similar to what is observed in poliomyelitis.
  • A variety of complications may occur early in the course of enteroviral meningitis. Complication incidence is about 5-10% and includes febrile seizures, lethargy, coma, and movement disorders. These symptoms may overlap with an encephalitis-type illness. Adults have been observed to have a longer period of fever and illness than younger patients and may require weeks to return to normal activity. A period of postviral asthenia, or even chronic fatigue, may occur.
• Encephalitis
• • Encephalitis is a well-described, but unusual, manifestation of coxsackievirus and echovirus CNS infection.
  • Symptoms include lethargy, drowsiness, personality changes, seizures, paresis, and coma.
  • Although quite rare, enteroviral CNS infections have been reported to cause an encephalitis lethargica–type picture with oculogyric crisis, cranial nerve palsies, and a parkinsonismlike picture.
• Rash
• • Echoviruses cause a variety of cutaneous rashes. Note, however, that except for hand-foot-and-mouth (HFM) disease, the manifestations usually are not distinctive enough to allow diagnosis just based on the rash.
  • Although the rash itself seldom causes any significant symptoms, it can be used as a marker for echoviruses in the community. The rash may be confused with other infective ones, some of which have implications that are more serious.
  • The rashes may be classified according to their morphology as follows: rubella- or measleslike, roseolalike, vesicular, and petechial. Overlap clearly is noted when comparing the rash in different patients infected with the same virus and with varying lesion types in the same patient.
• Rubella- and measleslike rash
• • Maculopapular-type rashes similar to rubella (german measles) occurring during the summer are well described in echoviral infection, often with other symptoms such as fever.
  • Higher rash attack rates are observed with echovirus 9, which is the most common serotype associated with rubellalike rash. In one reported echovirus 9 outbreak, 57% of persons younger than 5 years and 41% of patients aged 5-9 years had the rash, yet only 6% of those older than 10 years were similarly affected.
  • Usually occurring with the fever, this rash begins on the face, spreading inferiorly. It consists of faint pink macules 1-3 mm in diameter and occurs without pruritus or subsequent desquamation. This rash is most likely to be confused with rubella, but the absences of pruritus and posterior cervical lymphadenopathy are distinguishing features. An enanthem, with appearance similar to Koplik spots, may occur and, therefore, may be confused with measles, but the cough, coryza, and conjunctivitis characteristic of measles are absent.
• Roseolalike rash
• • This enteroviral rash is more distinctive due to its timing in relation to the fever. As in roseola (a disease caused by human herpes virus 6), the rash classically does not appear until temperature diminishes.
  • The most noteworthy of this group is the Boston exanthem, the first of the enterovirus exanthems to be recognized, now thought to be due to echovirus 16. Cases can spread within a household setting, with as many as 25% of young children being infected. Most patients are only mildly ill, with low-grade fever and pharyngitis. Fever can persists for 1-2 days and declines, usually at the same time as the development of the rash. The rash is described as nonpruritic and maculopapular, involving the face and upper part of the chest with less involvement of the extremities. It can last for 1-5 days.
  • Other echovirus serotypes (eg, echoviruses 11, 25) also have been associated with a roseolalike illness.
  • Vesicular eruptions occasionally occur and may be confused with chickenpox (varicella).
• Respiratory illness
• • Echovirus, similar to many enteroviruses, may be associated with an undifferentiated pyrexial illness (the so-called summer grippe) with sore throat, cough, or coryza. Echoviruses can be isolated from many children with summertime virallike upper respiratory tract infections.
  • Echovirus 11 can be associated with croup.
• Herpangina
• • Herpangina is a well-characterized, vesicular, oral mucosal process involving the tonsillar fossa and soft palate. Symptoms include elevated temperature, pharyngitis, and dysphagia.
  • It commonly is observed in summer outbreaks involving younger children, often younger than 10 years old, and less commonly is observed in adolescents and young adults.
  • Herpangina begins abruptly with fevers as high as 104°F and is associated with nonpersistent vomiting, myalgia, and headache. Sore throat and dysphagia are the most prominent symptoms and precede the appearance of the oral lesions.
• Epidemic pleurodynia
• • An acute illness, it is marked by fever and sharp spasmlike pain in the chest or upper abdomen. The name is associated with the common symptom of pain in the intercostal muscle, and, as such, it is not a pleural disease.
  • Other synonyms of the disease include epidemic myalgia, epidemic benign dry pleurisy, devil's grippe, and Bornholm disease. First described by William Cooper, MD, the term "devil's grip" was used to describe cases from an outbreak in 1888, but, over time, grip became grippe based on the influenzal aspects of the disease.
  • Major epidemics have occurred at infrequent intervals, often 10-20 years, with attack rates during epidemics higher in sparsely populated areas than in urban centers. Usually, persons with pleurodynia are older than those with other enteroviral diseases. The contagiousness of the infection is such that it may attack several family members either simultaneously or in succession.
  • The illness usually is self-limited, with resolution in most individuals within 1 week. Children often have milder disease than adults, who often need confinement. The first episode of pain usually is the most symptomatic, with subsequent episodes shorter in duration and accompanied by lower temperature elevation. Although dull aching of involved muscles may be reported between episodes, the patient usually appears well between the paroxysms.
  • Twenty-five percent of affected individuals may have multiple recurrences. In approximately half of these, the pain recurs at the original area. Late relapses have occurred after a month of being symptom free.
• Myocardial/pericardial disease
• • Enteroviral myocarditis may occur at any age but seems to be particularly prominent in adolescents and young adults. Males are affected twice as often as females. In many cases, an upper respiratory tract illness is reported within 2 weeks prior to the onset of cardiac manifestations.
  • Common symptoms are shortness of breath, chest pain, fever, and weakness, each of which is noted in 60-90% of cases.

Physical

• Acute aseptic meningitis
• • Infants who are younger than 3 months are reported to have the highest rates of clinically recognized aseptic meningitis. This observation may, in part, be related to the practice of performing lumbar punctures for pyrexia in this age group.
  • Only a small number of the infants have clinical evidence of neurologic disease.
• Encephalitis
• • In neonates with enteroviral infection, encephalitis may be only one part of a systemic infection. Beyond this period, encephalitis, albeit not frequent, primarily affects children and young adults.
  • Encephalitis sometimes complicates the course of aseptic meningitis, but it can dominate the clinical illness in the presence or absence of meningitis.
  • Focal encephalitis can manifest with a spectrum of signs, including partial motor seizures, hemichorea, or acute cerebellar ataxia.
• Paralysis (and other neurologic complications) of echovirus infections
• • Paralytic disease caused by nonpolio enteroviruses usually is less prominent than the typical poliovirus-associated paralysis. Muscle weakness is more common than flaccid paralysis and usually is not permanent. Cranial nerve involvement has been reported and usually presents with oculomotor palsy. Reported cases of fatal bulbar involvement exist.
  • Guillain-Barré syndrome has been reported rarely in patients infected with echovirus serotypes 6 and 22. The virus has been isolated from the CNS in some cases.
  • Transverse myelitis has been reported in a patient with echovirus 5 recovered from CSF.
  • Enteroviruses have been isolated from multiple sites, including the brain and CSF in children with Reye syndrome. However, no clear link between the virus and Reye syndrome has been established.
• Vesicular rashes
• • Vesicular rashes caused by enteroviruses are similar to the lesions of HFM disease, but they occur in crops on the head, trunk, and extremities.
  • Unlike chickenpox, these vesicles do not form pustules and scabs. Herpetiform rash caused by echovirus 11 has been reported in adult patients who are immunocompromised. An acute eruption resembling dermatomal zoster also has been reported in which echovirus 6 was isolated from the lesions.
• Petechial rash and other skin findings: Petechial and purpuric rashes have been reported with echovirus 9 and coxsackievirus A9 infections. When these rashes have a hemorrhagic component, the illness can be confused with meningococcal disease, particularly when aseptic meningitis occurs.
• Acute respiratory disease: Enteroviral upper respiratory tract illness is clinically similar to diseases caused by other agents, including rhinovirus or mycoplasma.
• Herpangina
• • The pharynx reveals redness and mild exudate of the tonsils, which can lead to a diagnosis of pharyngitis or tonsillitis if the characteristic enanthem is not appreciated.
  • The lesions originate as small macules, evolving over a day to erythematous centrally ulcerated papules that are 2-4 mm. The lesions are moderately painful, number no more than 10-12, and are located on the soft palate, most frequently on the free-hanging margin between the tonsils and the uvula. Pyrexia resolves over 2-4 days, but the enanthem may persist for as long as a week. Most individuals are not very ill, needing only symptomatic treatment.
• Pleurodynia
• • Despite its name, pleurodynia is a disease of muscle, not of the pleura or peritoneum. It probably results from direct viral invasion of muscles, but virologic evidence to support this is lacking. In many cases, the pain is reproduced by pressure on the affected muscles. Palpable, sometimes visible, muscle swelling can be found.
  • The illness begins abruptly with spasmodic pain, usually involving the lower part of the rib cage or adjacent abdominal area. Pyrexia as high as 39.5°C occurs within 1 hour after the onset of the spasm, subsiding with the pain. Sore throat and headache can be found, but cough and rhinitis notably are absent.
  • The pain often is poorly localized, and its severity varies substantially. It is described as sticking, a stitch in the side, lancinating, stabbing, constricting, or viselike. The most common location is the area of the costal margin on either or both sides. Some patients, especially adults, have pain primarily in the muscles of the thorax, especially the intercostals. In other cases, pain occurs in the upper part of the abdomen (internal and external obliques, transversus abdominis) or the epigastrium (rectus abdominis). Periumbilical pain and pain in the lower abdominal quadrants also can occur, especially in children.
  • Although the location and severity vary, the spasmodic nature of the pain is the sine quo non of the disease. With severe pain, the patient may remain still in bed, seemingly acutely ill. Chest pain may produce thoracic splinting with shallow and rapid respiration, and movement exacerbates the pain.
• Chronic meningoencephalitis in hosts who are agammaglobulinemic and in other hosts who are immunocompromised
• • Enteroviruses have been found to be responsible for persistent, sometimes fatal, infections of the CNS associated with B-lymphocyte defective function. Most cases occur in children with X-linked agammaglobulinemia. Persistent skeletal muscle involvement causes a dermatolike or polymyositislike picture in more than half of these patients.
  • Nervous system manifestations may be totally absent or may present as meningismus, headache, lethargy, papilledema, seizure disorders, motor weakness, tremors, and ataxia. These abnormalities may fluctuate in severity, disappear, or progress steadily.
  • In many individuals, possibly most, the disease ends fatally. Autopsy findings include features of chronic meningitis and encephalitis. Pathology demonstrates lymphocytic perivascular cuffing, focal loss of neurons, and gliosis of both gray and white matter. Widespread destruction of motor neurons, such as in poliomyelitis, is not observed.
• Myopericarditis
• • Enteroviruses rarely attack the pericardium solely; therefore, myopericarditis better characterizes the heart disease caused by these viruses. Clinically, however, the signs of either myocardial or pericardial disease may predominate.
  • The manifestations of myopericarditis can vary from totally asymptomatic disease to fulminant disease with intractable heart failure and death.
  • Epidemic enteroviral myopericarditis appears to be rare. Most cases have been sporadic, even during enteroviral epidemics.
  • Chest pain occurs in as many as 90% of cases and often is dull in nature, but it can resemble angina pectoris. If pericarditis is prominent, it may be described as pleuritic and aggravated by movement. A transient friction rub has been observed in 35-80% of cases.

Causes

• Acute aseptic meningitis
• • More than 90% of community-acquired cases of viral meningitis are caused by group B coxsackieviruses or echoviruses. Group B coxsackievirus serotypes 2-5 and echovirus serotypes 4, 6, 9, 11, 16, and 30 are found most commonly.
  • Infection with certain serotypes, particularly the group B coxsackieviruses and echovirus 30, is more likely to be accompanied by aseptic meningitis than with other enterovirus serotypes.
• Encephalitis
• • Enteroviruses, including poliovirus, account for 10-20% of proven cases of viral encephalitis. This ranks behind arboviruses, herpes simplex virus, and lymphocytic choriomeningitis virus.
  • Many serotypes have been implicated as causes of encephalitis; coxsackievirus types A9, B2, and B5 and echovirus types 6 and 9 are the serotypes reported most often. The evidence linking each of these serotypes to encephalitis is quite variable.
• Paralysis and other neurologic complications of echovirus infections
• • Sporadic cases of flaccid motor paralysis are associated with echoviruses 6 and 9.
  • Less frequently implicated serotypes include echoviruses 1-4, 7, 11, 14, 16-18, and 30.
• Rash
• • The virus can be isolated from the vesicular lesions of patients with HFM disease; therefore, these lesions appear to be a direct result of viral invasion of the skin after viremia. Reports do not document attempts to isolate the virus from the skin in cases of other rashes; consequently, whether these lesions are caused by direct viral invasion or by immunologic mechanisms is not known.
  • Serotypes associated with rubellalike rash include coxsackievirus A9 and echoviruses 2, 4, 11, 19, and 25.
  • Vesicular herpetiform rash: Generalized vesicular eruptions have been linked to coxsackievirus A9 and echovirus 11.
• Respiratory tract infection
• • Among the echoviruses, serotype 11 is the most firmly established cause of respiratory disease, though serotypes 4, 8, 9, 20, 22, and 25 may be causal.
  • In volunteers infected experimentally and, occasionally, in patients with naturally acquired disease, some coxsackieviruses and echoviruses may be linked with lower respiratory tract disease. The role of enteroviruses in lower respiratory illness is not clearly defined; at present, they should be thought of as rare causes of pneumonia.
• Group A coxsackieviruses (serotypes 1-10, 16, and 22) most commonly are recovered from patients with herpangina. Other serotypes isolated less commonly from herpangina include group B coxsackieviruses 1-5 and echoviruses 3, 6, 9, 16, 17, 25, and 30.
• Group B coxsackievirus is the most important cause of epidemic pleurodynia. Other agents implicated less commonly in pleurodynia include some group A coxsackieviruses and echoviruses 1, 6, 9, 16, and 19.
• Chronic meningoencephalitis in hosts who are agammaglobulinemic and other hosts who are immunocompromised
• • Echoviruses (and polioviruses) appear to cause worse infections in these patients, probably because picornaviruses require an extracellular phase for cell-to-cell transfer, during which the virus can be inactivated by antibody-mediated mechanisms.
  • Most cases have been caused by echoviruses, including types 5, 6, 7, 11, and 27. Records document single cases caused by group A and B coxsackievirus serotypes.
• Myopericarditis
• • Enteroviruses appear to be the most common viral etiology of acute myopericarditis, reported to cause at least half of cases.
  • Proof of causation exists for all group B coxsackievirus serotypes, group A coxsackievirus types 4 and 16, and echovirus types 9 and 22 by demonstration of infectious virus or viral antigens in the myocardium or pericardial fluid. The evidence is less for echoviruses 1-4, 6-8, 11, 14, 19, 25, and 30.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Poliovirus infections

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Viral isolation through cell culture
• • The opportunity to recover a virus in cell culture is optimized by sampling multiple sites.
  • Late in the course of echoviral illness, clinicians use viral cultures of feces because the lower intestine may be the only site from which the agent is still excreted. Physicians can confirm an etiologic diagnosis by isolating virus from CSF, pericardial fluid, tissue, or blood, depending on the clinical syndrome. Remember that the isolation of an echovirus from the stool does not necessarily signify that a systemic or focal illness is due to that virus because it may be an innocent bystander unrelated to pathology elsewhere.
  • With the identification of a characteristic cytopathic effect in any 3 or 4 appropriately chosen cell lines, the laboratory can report a presumptive diagnosis of echoviral infection within several days.
  • In the future, echoviral strains likely will be characterized by genomic sequencing.
• Polymerase chain reaction
• • Reverse transcriptase–polymerase chain reaction (RT-PCR) is a rapid, sensitive, and specific method of detecting echoviral RNA in clinical specimens.
  • RT-PCR has detected echoviral RNA from CSF, throat swabs, serum, and stool samples. It also has detected echoviral RNA in endomyocardial biopsy specimens from cases of acute myocarditis and is the standard method for the diagnosis of enteroviral meningitis.
• Serology
• • The optimal use of antibodies for the diagnosis of echoviral infections involves acute and convalescent sera, which should be run in parallel, if possible. A single high antibody result can be misleading.
  • The microneutralization test is the most widely employed method for the determination of antibodies to echoviruses.
• CSF analysis
• • In chronic meningoencephalitis in hosts who are agammaglobulinemic and other hosts who are immunocompromised, the CSF exhibits lymphocytic pleocytosis and a higher protein concentration than usually is observed in cases of acute enteroviral aseptic meningitis. Enteroviruses can be recovered repeatedly from the CSF over a period of months to years, usually in high titer.
  • In some cases, the virus is isolated only intermittently from CSF or detected only by polymerase chain reaction (PCR). For unknown reasons, finding the virus in the feces usually is more difficult than finding the virus in the CSF. Clinicians have recovered enteroviruses from many other sites in these patients, including the brain, lung, liver, spleen, kidney, myocardium, pericardial fluid, skeletal muscle, and bone marrow. Some patients have been infected with more than one enterovirus serotype, either concurrently or sequentially.

Imaging Studies

• Radiography: In myopericarditis, enlargement of the cardiac silhouette on chest radiograph films is present in approximately 50% of cases and may be due to either pericardial effusion or cardiac dilatation.
• Echocardiography: Echocardiography may confirm the presence of acute ventricular dilatation or a diminished cardiac ejection fraction.

Other Tests

• Electrocardiography: Patients invariably have electrocardiographic abnormalities. With pericarditis or mild myocarditis, these abnormalities consist of ST-segment elevation or nonspecific ST-segment and T-wave abnormalities. More severe myocardial disease may lead to the development of Q waves, ventricular tachyarrhythmias, and all degrees of heart block.

Histologic Findings

In enteroviral myopericarditis, viruses reach the heart during the viremia that follows replication in the GI or respiratory tract. Experimental studies in a murine model strongly suggest that virus replication occurs in the myocytes. A chronic inflammatory response persists for weeks to months when the replicating virus is no longer present in the heart, and this lingering response is the subject of keen interest. Some investigators consider the late-phase inflammatory response to be due to virus-induced, cytotoxic T-lymphocyte destruction of myocytes. Others postulate the development of a myocardial neoantigen or cross-reactivity between viral and myocardial cell antigens. A variable degree of interstitial fibrosis and evidence of myocyte loss accompany healing.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Antivirals to treat echoviral infections are not available commercially; medical treatment is supportive and symptomatic. Pleconaril, an experimental agent with good in vitro activity against most enteroviruses, is being evaluated in clinical trials and can be obtained for myocarditis, neonatal sepsis, meningoencephalitis, and vaccine-associated polio on a compassionate use basis (call ViroPharma at 610-651-0200). Physicians also use intravenous, intrathecal, and intraventricular gamma globulin with high type-specific antibodies for chronic meningoencephalitis caused by echovirus, but the results are not uniformly effective.

• Chronic meningoencephalitis in hosts who are agammaglobulinemic and other hosts who are immunocompromised
• • Intravenous gamma globulin therapy has now replaced immune serum globulin for routine replacement therapy for patients with B-cell immunodeficiency and has been used to treat this disease. This therapy may prove more effective because a much higher serum immunoglobulin G (IgG) concentration can be maintained.
  • Use of intravenous immunoglobulin (IGIV) in the treatment of chronic enteroviral meningitis generally has been ineffective, even when using IGIV lots with relatively high concentrations of type-specific antibody. Intrathecal and intraventricular administration of high-titer type-specific antibody preparations have been used, but relapse of infection has occurred even after long-term therapy.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

As noted earlier, no approved drugs for enteroviral infections exist. Pleconaril can be obtained through the manufacturer on a compassionate basis for neonatal sepsis, chronic meningoencephalitis, myocarditis, and enteroviral complications of marrow transplantation and vaccine-associated polio. Call ViroPharma at 610-651-0200 for information/eligibility for this experimental agent.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Deterrence/Prevention:

• The ubiquitous nature of echoviruses, and of enteroviruses in general, and the ease of person-to-person transmission make prevention of echoviral infections difficult. As in other enteroviral infections, good overall public health, including adequate clean and potable water, sanitation, and clean living conditions can act as deterrents.
• No vaccines are available for echovirus infections.

Complications:

• Acute aseptic meningitis
• • Complications (eg, febrile seizures, complex seizures, lethargy, coma, movement disorders) occur early in the course of aseptic meningitis in 5-10% of patients.
  • Adults may experience a more prolonged period of fever and headache than infants and children; some adult patients may require weeks to return to normal activity.
• Paralysis and other neurologic complications
• • Sporadic cases of flaccid motor paralysis are associated with echoviruses 6 and 9. Serotypes implicated less frequently include echoviruses 1-4, 7, 11, 14, 16-18, and 30.
  • Paralytic disease caused by nonpolio enteroviruses characteristically is less severe than poliovirus-associated paralysis. In fact, muscle weakness is more common than flaccid paralysis, and the paresis usually is not permanent.
  • Cranial nerve involvement occasionally has resulted in complete unilateral oculomotor palsy. Cases of fatal bulbar involvement occur rarely.
  • Guillain-Barré syndrome is reported in a small number of patients in association with echovirus serotypes 6 and 22. In a few cases, the implicated virus was isolated from CSF or the brain stem.
  • Specialists report transverse myelitis in one patient whose CSF contained echovirus 5.

Prognosis:

• Chronic meningoencephalitis in hosts who are agammaglobulinemic and other hosts who are immunocompromised may end in death.

Patient Education:

• Inform patients that, even if person-to-person transmission of an echovirus occurs, any complication that occurs in one person and is related to the particular type will not necessarily occur in other people.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Neurologic disease can be confused with the flaccid asymmetrical paralysis caused by poliovirus. The presentation of such a case should always bring up the specter of polio; public health officials must be alerted promptly to initiate investigation.
• Meningoencephalitides caused by echoviruses are summertime diseases, and they may occur in areas where the newly implanted West Nile virus is found (ie, middle Atlantic area of the United States). The differentiation can be suspected clinically and may only be made with certainty in the laboratory.
• In the setting of epidemic pleurodynia, approaching every case with close scrutiny so those individuals with myocardial infarction or pulmonary embolus are not missed is important.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Jun 29, 2006