Disease: Enterovirus
(Non-Polio Enterovirus Infection)

    Enterovirus facts

    • Enteroviruses are small RNA viruses that can cause illnesses such as colds, meningitis, hand, foot and mouth disease, hypoxia (decreased blood oxygen levels), hemorrhagic conjunctivitis, myopericarditis, rashes, herpangina, pleurodynia, respiratory infections, and infrequently, paralysis.
    • There have been several outbreaks of enterovirus infections; the most recent (August 2014) is by the strain named enterovirus D68, or EV-D68, an enterovirus that causes more severe symptoms of respiratory problems, mainly in children, than has been seen previously.
    • Symptoms and signs of enterovirus infection include flu-like symptoms (such as fever, cough, body aches, runny nose, and sneezing) that may become more severe and include difficulty breathing and/or wheezing.
    • Enteroviruses cause various infections most often in children; risk factors include association with infected individuals, immune system problems, pregnancy, and respiratory problems with risk increased during the summer and early fall months.
    • Enterovirus infections are diagnosed by clinical features and, less frequently, by PCR tests or culturing the enterovirus from individual's blood, cerebrospinal fluid, or other bodily fluids.
    • The treatment for enterovirus infections is mainly supportive and designed to reduce the symptoms caused by the various enterovirus types.
    • Most individuals with enterovirus infections have no complications; however, more severe infections can lead to hypoxia, meningitis, eye problems, heart involvement (myopericarditis), and rarely paralysis and/or muscle weakness.
    • In most cases, the prognosis (outcomes) of enterovirus infections is good with no complications; however, the prognosis worsens as the severity of infection increases and when complications develop.
    • It is possible to prevent or reduce the chance of getting an enterovirus infection. A vaccine is available to prevent polio, but there are no vaccines available to prevent non-polio enterovirus infections. However, avoiding contact with infected individuals, using good hand washing techniques, and disinfecting items that contact infected individuals can reduce the chance of becoming infected.
    Picture of a rash on a child's face due to enterovirus (echovirus-9); SOURCE: CDC/Heinz F. Eichenwald, MD, New York Hospital, Cornell Univ.; Ann Cain

    What is an enterovirus?

    Human enteroviruses are a genus in the family of Picornaviridae (small RNA viruses) that were originally classified or named as polioviruses, Coxsackie viruses (groups A and B), echoviruses, and enteroviruses. Rhinoviruses are included as enteroviruses by many researchers but not all. There are well over 100 types of known enteroviruses. These viruses are usually transmitted person to person by direct contact with the viruses that are shed from the gastrointestinal tract or upper respiratory tract. In general, these viruses are usually categorized as either polio or non-polioviruses. Polioviruses (only three types, P1-3) and non-polioviruses may have similar initial symptoms. In the majority of infections caused by both polio and non-polioviruses, individuals may be asymptomatic (not show any symptoms) or only have mild symptoms, including fever, headache, sore throat, loss of appetite, and abdominal discomfort that resolves with no sequelae (complications). However, in some patients, especially children, these infections may cause serious disease that may produce lifelong problems and, infrequently, may cause death.

    Recently, non-enterovirus species names were revised to remove host names (human, bovine, simian, and porcine) and replaced with the group designation (A through J) and serotype number. The group is based on the similarity within the RNA region that codes for the outer protein of the virus, and serotype number corresponds to a specific neutralizing serum (antibody). Consequently, human enterovirus 68, for example (also called HEV- 68 and ED68) is now termed EV-D68. There will be confusion and overlap of enterovirus names for the next few years as researchers and clinicians adjust to this extensive name change. In this article, both new and currently accepted names of these viruses and the disease(s) they may cause will be used. For example, Coxsackie viruses could be labeled CV-A4 or CV-B5, depending on their group and/or serotype; similarly echovirus=E-14 or rhinovirus=RV-A25, RV-B79, or RV-C41.

    What types of illnesses do enteroviruses cause?

    As stated previously, enteroviruses cause two main types of human disease, polio, and non-polio disease. In this article, the focus will be on the non-polio disease-causing enteroviruses. The polioviruses that cause paralysis and other symptoms have been extensively covered in other articles. Non-polio enteroviruses may cause a wide range of infections that overlap; for example...

    • enterovirus: aseptic meningitis with rash, conjunctivitis, hand, foot, and mouth disease (EV-71), paralysis (EV-71), myopericarditis
    • group A Coxsackie virus: flaccid paralysis, hand, foot, and mouth disease, hemorrhagic conjunctivitis, herpangina, aseptic meningitis (with or without rash)
    • group B Coxsackie virus: spastic paralysis, herpangina, pleurodynia, myocarditis, pericarditis, and meningoencephalitis
    • echovirus: common cold, rash, aseptic meningitis, myopericarditis, paralysis, hemorrhagic conjunctivitis
    • rhinovirus: the common cold (over 100 different serotypes).

    The symptoms of these illnesses are described below.

    What are causes and risk factors for an enterovirus infection?

    The causes for enterovirus infections are simply the passage of one of the many enteroviruses from one person directly to another, usually by contact with respiratory secretions and/or stool from infected individuals. Occasionally, environmental sources such as water may be contaminated with enteroviruses that can infect individuals. The most common risk factor for getting an enterovirus infection is direct contact with any bodily secretions (especially respiratory and/or fecal) from an infected individual. Individuals with immature (neonates) or compromised immune systems also are at higher risk for enterovirus infections. Pregnant females and individuals with respiratory problems like asthma are at higher risk. Individuals are at highest risk during the fall and summer months.

    What are symptoms and signs of an enterovirus infection in children and adults?

    Stated previously, many individuals who become infected with enteroviruses have no or only mild symptoms (fever, headache, sore throat, loss of appetite, and abdominal discomfort) of infection that may last about a week and resolve with no further problems. However, those people at higher risk may develop one or more of the following symptoms:

    • Common cold: nasal discharge, cough, mild fever, mild malaise
    • Hypoxia (low oxygen in the blood): shortness of breath, wheezing, coughing, rapid breathing, skin coloration change (bluish to cherry red), rapid heart rate
    • Aseptic meningitis: most common among infants and children; may also occur with a rash (on face, neck, and extremities), fever, painful headache, stiff neck, body aches, sensitivity to light, nausea and vomiting, irritability
    • Conjunctivitis (hemorrhagic): eye pain, bleeding seen in the whites of the eyes, photophobia (avoidance of light due to discomfort)
    • Myopericarditis: shortness of breath, chest pain, fever, weakness
    • Herpangina: small flat sores on the oral mucosa (tonsils and soft palate) that may produce blisters and ulcerate
    • Pleurodynia: intermittent chest pain usually over the lower part of the rib cage; some individuals may have a plural friction rub that can be heard when the doctor examines the chest with a stethoscope
    • Hand, foot, and mouth disease (HFMD): small nodules and blisters that are tender and appear gray that occur on the hands, feet, and in the oral cavity
    • Encephalitis: Symptoms range from lethargy and drowsiness to personality changes, seizures, and coma.
    • Paralysis (infrequent in both polio and non-polio intro viral infections): flaccid paralysis that is often asymmetric with proximal extremity muscles affected; lower extremities affected more commonly than upper extremities (poliovirus, enterovirus 71, and coxsackievirus A7); other non-polio enteroviruses usually have less severe symptoms (for example, muscle weakness and oculomotor palsy) if paralysis develops

    As noted above, some strains of enteroviruses produce different symptoms, some of which are much more severe than others. In addition, some strains occasionally appear to be more transmissible and cause more intense or severe symptoms. Two recent examples are enterovirus 71 (EV-71) and EV-D68.

    How do physicians diagnose an enterovirus infection?

    In general, enterovirus infections are most often diagnosed by clinical symptoms. Blood tests are done infrequently; the best test is polymerase chain reaction (PCR) that is available from specialized laboratories and used most often during outbreaks of viral infections. In addition, it is useful to distinguish between enterovirus infections and other viral infections like rotavirus and influenza viruses. Infrequently, the infecting enterovirus will be isolated by cell cultures taken from the blood, feces, or cerebrospinal fluid and then identified by further immunologic tests. Other tests such as chest X-rays, echocardiography, lumbar puncture, and ECGs may help determine the extent of infection.

    What is the treatment for an enterovirus infection?

    Briefly, the best treatment for an enterovirus infection is prevention. For poliovirus, an effective vaccine is available; unfortunately, for non-polio enteroviruses the treatment is supportive and is designed to reduce the symptoms because there are no antiviral medications currently approved for the treatment of these types of enterovirus infections. Immunoglobulins have been used in infected neonates and immunocompromised hosts to both treat and prevent non-polio enterovirus central nervous system infections, but these immunoglobulin treatments are not always very effective. Consequently, supportive measures such as fever control, assisted-breathing methods (ranging from inhaled steroids to intubation), pain-control medications, and topical skin and oral mucosal medications to reduce symptoms are given.

    Non-polio enterovirus outbreaks, including enterovirus D68 (EV-D68)

    The recent outbreaks of various non-polio enteroviruses are listed below; (the data is modified from reports from the U.S. Centers for Disease Control and Prevention (CDC).

    • Coxsackievirus A16 is the most common cause of hand, foot, and mouth disease (HFMD) in the United States. However, in 2011 and 2012, coxsackievirus A6 was a common cause of HFMD in this country; some of the infected people became severely ill.
    • Coxsackievirus A24 and enterovirus 70 have been associated with outbreaks of conjunctivitis.
    • Echoviruses 13, 18, and 30 have caused outbreaks of viral meningitis in the United States.
    • Enterovirus 71 has caused large outbreaks of HFMD worldwide, especially in children in Asia. Some infections from this virus have been associated with severe neurologic disease, such as brainstem encephalitis.
    • Enterovirus D68 (EV-D68) is the most recent ongoing outbreak; this strain was noted to cause multiple infections in children in August 2014. According to the CDC, to date hundreds of children across the U.S. Midwest have been stricken by this virus that is currently causing serious respiratory illnesses. Particularly hard hit has been the state of Missouri, where more than 400 cases of the respiratory illness have been reported in a Kansas City hospital; about 15% of those children with the infection needed treatment in an intensive-care unit. Since mid-August 2014, other states such as Kansas, Kentucky, Iowa, Colorado, Ohio, Oklahoma, North Carolina, and Georgia have seen an outbreak of this fairly severe respiratory illness caused mainly by EV-D68 (about 75% of patients were confirmed to be infected by EV-D68 in a single Colorado hospital). To date, fortunately, there have been no deaths attributed to this virus outbreak. Major symptoms include difficulty breathing, coughing, and a rash; some patients develop wheezing. The virus has been found mainly in children and those children who have any respiratory compromise (patients with asthma) often get more severe symptoms. The CDC is concerned that the large numbers of individuals infected with this virus only represent "the tip of the iceberg," suggesting this outbreak may be very large while pediatricians at some hospitals consider the outbreak to be "unprecedented." Currently, the CDC does not have an accurate count of infected individuals; there is no vaccine available to prevent EV-D68 infections, and treatment is mainly supportive care.

    What are complications of an enterovirus infection?

    The majority of enterovirus infections last about a week to 10 days and have no complications. However, complications can occur in some patients and range from mild (rash, mild conjunctivitis, skin lesions) to more severe (shortness of breath, encephalitis, myopericarditis, chest pains, weakness with paralysis, coma and rarely, death).

    What is the prognosis of an enterovirus infection?

    The prognosis of most enterovirus infections is good; most individuals will spontaneously resolve their infection in about seven to 10 days and have no complications. Some patients, especially those who are immunocompromised in any way, may develop more severe infections. The more severe infections can have a prognosis that can range from good to poor, depending upon the severity of the viral strain causing the infection and the strength (or weakness) of the individual's immune response. Consultation with an appropriate specialist (cardiologist, pulmonologist or others, depending on the particular complications) is recommended.

    Is it possible to prevent an enterovirus infection? Is there a vaccine for enteroviruses?

    Individuals can reduce the chance of getting an enterovirus infection simply by avoiding direct contact with people who are infected with enteroviruses and by using such techniques as good hand washing and cleaning or disinfecting items that come in contact with infected individuals. People are routinely vaccinated against certain enteroviruses (polioviruses); as a result, polio is rarely seen in developing countries. Unfortunately, no vaccines are currently available for non-polio enteroviruses. Part of the reason there are no vaccines for these viruses is that there is a very large number of subtypes of non-polio enteroviruses.

    What is an enterovirus?

    Human enteroviruses are a genus in the family of Picornaviridae (small RNA viruses) that were originally classified or named as polioviruses, Coxsackie viruses (groups A and B), echoviruses, and enteroviruses. Rhinoviruses are included as enteroviruses by many researchers but not all. There are well over 100 types of known enteroviruses. These viruses are usually transmitted person to person by direct contact with the viruses that are shed from the gastrointestinal tract or upper respiratory tract. In general, these viruses are usually categorized as either polio or non-polioviruses. Polioviruses (only three types, P1-3) and non-polioviruses may have similar initial symptoms. In the majority of infections caused by both polio and non-polioviruses, individuals may be asymptomatic (not show any symptoms) or only have mild symptoms, including fever, headache, sore throat, loss of appetite, and abdominal discomfort that resolves with no sequelae (complications). However, in some patients, especially children, these infections may cause serious disease that may produce lifelong problems and, infrequently, may cause death.

    Recently, non-enterovirus species names were revised to remove host names (human, bovine, simian, and porcine) and replaced with the group designation (A through J) and serotype number. The group is based on the similarity within the RNA region that codes for the outer protein of the virus, and serotype number corresponds to a specific neutralizing serum (antibody). Consequently, human enterovirus 68, for example (also called HEV- 68 and ED68) is now termed EV-D68. There will be confusion and overlap of enterovirus names for the next few years as researchers and clinicians adjust to this extensive name change. In this article, both new and currently accepted names of these viruses and the disease(s) they may cause will be used. For example, Coxsackie viruses could be labeled CV-A4 or CV-B5, depending on their group and/or serotype; similarly echovirus=E-14 or rhinovirus=RV-A25, RV-B79, or RV-C41.

    What types of illnesses do enteroviruses cause?

    As stated previously, enteroviruses cause two main types of human disease, polio, and non-polio disease. In this article, the focus will be on the non-polio disease-causing enteroviruses. The polioviruses that cause paralysis and other symptoms have been extensively covered in other articles. Non-polio enteroviruses may cause a wide range of infections that overlap; for example...

    • enterovirus: aseptic meningitis with rash, conjunctivitis, hand, foot, and mouth disease (EV-71), paralysis (EV-71), myopericarditis
    • group A Coxsackie virus: flaccid paralysis, hand, foot, and mouth disease, hemorrhagic conjunctivitis, herpangina, aseptic meningitis (with or without rash)
    • group B Coxsackie virus: spastic paralysis, herpangina, pleurodynia, myocarditis, pericarditis, and meningoencephalitis
    • echovirus: common cold, rash, aseptic meningitis, myopericarditis, paralysis, hemorrhagic conjunctivitis
    • rhinovirus: the common cold (over 100 different serotypes).

    The symptoms of these illnesses are described below.

    What are causes and risk factors for an enterovirus infection?

    The causes for enterovirus infections are simply the passage of one of the many enteroviruses from one person directly to another, usually by contact with respiratory secretions and/or stool from infected individuals. Occasionally, environmental sources such as water may be contaminated with enteroviruses that can infect individuals. The most common risk factor for getting an enterovirus infection is direct contact with any bodily secretions (especially respiratory and/or fecal) from an infected individual. Individuals with immature (neonates) or compromised immune systems also are at higher risk for enterovirus infections. Pregnant females and individuals with respiratory problems like asthma are at higher risk. Individuals are at highest risk during the fall and summer months.

    What are symptoms and signs of an enterovirus infection in children and adults?

    Stated previously, many individuals who become infected with enteroviruses have no or only mild symptoms (fever, headache, sore throat, loss of appetite, and abdominal discomfort) of infection that may last about a week and resolve with no further problems. However, those people at higher risk may develop one or more of the following symptoms:

    • Common cold: nasal discharge, cough, mild fever, mild malaise
    • Hypoxia (low oxygen in the blood): shortness of breath, wheezing, coughing, rapid breathing, skin coloration change (bluish to cherry red), rapid heart rate
    • Aseptic meningitis: most common among infants and children; may also occur with a rash (on face, neck, and extremities), fever, painful headache, stiff neck, body aches, sensitivity to light, nausea and vomiting, irritability
    • Conjunctivitis (hemorrhagic): eye pain, bleeding seen in the whites of the eyes, photophobia (avoidance of light due to discomfort)
    • Myopericarditis: shortness of breath, chest pain, fever, weakness
    • Herpangina: small flat sores on the oral mucosa (tonsils and soft palate) that may produce blisters and ulcerate
    • Pleurodynia: intermittent chest pain usually over the lower part of the rib cage; some individuals may have a plural friction rub that can be heard when the doctor examines the chest with a stethoscope
    • Hand, foot, and mouth disease (HFMD): small nodules and blisters that are tender and appear gray that occur on the hands, feet, and in the oral cavity
    • Encephalitis: Symptoms range from lethargy and drowsiness to personality changes, seizures, and coma.
    • Paralysis (infrequent in both polio and non-polio intro viral infections): flaccid paralysis that is often asymmetric with proximal extremity muscles affected; lower extremities affected more commonly than upper extremities (poliovirus, enterovirus 71, and coxsackievirus A7); other non-polio enteroviruses usually have less severe symptoms (for example, muscle weakness and oculomotor palsy) if paralysis develops

    As noted above, some strains of enteroviruses produce different symptoms, some of which are much more severe than others. In addition, some strains occasionally appear to be more transmissible and cause more intense or severe symptoms. Two recent examples are enterovirus 71 (EV-71) and EV-D68.

    How do physicians diagnose an enterovirus infection?

    In general, enterovirus infections are most often diagnosed by clinical symptoms. Blood tests are done infrequently; the best test is polymerase chain reaction (PCR) that is available from specialized laboratories and used most often during outbreaks of viral infections. In addition, it is useful to distinguish between enterovirus infections and other viral infections like rotavirus and influenza viruses. Infrequently, the infecting enterovirus will be isolated by cell cultures taken from the blood, feces, or cerebrospinal fluid and then identified by further immunologic tests. Other tests such as chest X-rays, echocardiography, lumbar puncture, and ECGs may help determine the extent of infection.

    What is the treatment for an enterovirus infection?

    Briefly, the best treatment for an enterovirus infection is prevention. For poliovirus, an effective vaccine is available; unfortunately, for non-polio enteroviruses the treatment is supportive and is designed to reduce the symptoms because there are no antiviral medications currently approved for the treatment of these types of enterovirus infections. Immunoglobulins have been used in infected neonates and immunocompromised hosts to both treat and prevent non-polio enterovirus central nervous system infections, but these immunoglobulin treatments are not always very effective. Consequently, supportive measures such as fever control, assisted-breathing methods (ranging from inhaled steroids to intubation), pain-control medications, and topical skin and oral mucosal medications to reduce symptoms are given.

    Non-polio enterovirus outbreaks, including enterovirus D68 (EV-D68)

    The recent outbreaks of various non-polio enteroviruses are listed below; (the data is modified from reports from the U.S. Centers for Disease Control and Prevention (CDC).

    • Coxsackievirus A16 is the most common cause of hand, foot, and mouth disease (HFMD) in the United States. However, in 2011 and 2012, coxsackievirus A6 was a common cause of HFMD in this country; some of the infected people became severely ill.
    • Coxsackievirus A24 and enterovirus 70 have been associated with outbreaks of conjunctivitis.
    • Echoviruses 13, 18, and 30 have caused outbreaks of viral meningitis in the United States.
    • Enterovirus 71 has caused large outbreaks of HFMD worldwide, especially in children in Asia. Some infections from this virus have been associated with severe neurologic disease, such as brainstem encephalitis.
    • Enterovirus D68 (EV-D68) is the most recent ongoing outbreak; this strain was noted to cause multiple infections in children in August 2014. According to the CDC, to date hundreds of children across the U.S. Midwest have been stricken by this virus that is currently causing serious respiratory illnesses. Particularly hard hit has been the state of Missouri, where more than 400 cases of the respiratory illness have been reported in a Kansas City hospital; about 15% of those children with the infection needed treatment in an intensive-care unit. Since mid-August 2014, other states such as Kansas, Kentucky, Iowa, Colorado, Ohio, Oklahoma, North Carolina, and Georgia have seen an outbreak of this fairly severe respiratory illness caused mainly by EV-D68 (about 75% of patients were confirmed to be infected by EV-D68 in a single Colorado hospital). To date, fortunately, there have been no deaths attributed to this virus outbreak. Major symptoms include difficulty breathing, coughing, and a rash; some patients develop wheezing. The virus has been found mainly in children and those children who have any respiratory compromise (patients with asthma) often get more severe symptoms. The CDC is concerned that the large numbers of individuals infected with this virus only represent "the tip of the iceberg," suggesting this outbreak may be very large while pediatricians at some hospitals consider the outbreak to be "unprecedented." Currently, the CDC does not have an accurate count of infected individuals; there is no vaccine available to prevent EV-D68 infections, and treatment is mainly supportive care.

    What are complications of an enterovirus infection?

    The majority of enterovirus infections last about a week to 10 days and have no complications. However, complications can occur in some patients and range from mild (rash, mild conjunctivitis, skin lesions) to more severe (shortness of breath, encephalitis, myopericarditis, chest pains, weakness with paralysis, coma and rarely, death).

    What is the prognosis of an enterovirus infection?

    The prognosis of most enterovirus infections is good; most individuals will spontaneously resolve their infection in about seven to 10 days and have no complications. Some patients, especially those who are immunocompromised in any way, may develop more severe infections. The more severe infections can have a prognosis that can range from good to poor, depending upon the severity of the viral strain causing the infection and the strength (or weakness) of the individual's immune response. Consultation with an appropriate specialist (cardiologist, pulmonologist or others, depending on the particular complications) is recommended.

    Is it possible to prevent an enterovirus infection? Is there a vaccine for enteroviruses?

    Individuals can reduce the chance of getting an enterovirus infection simply by avoiding direct contact with people who are infected with enteroviruses and by using such techniques as good hand washing and cleaning or disinfecting items that come in contact with infected individuals. People are routinely vaccinated against certain enteroviruses (polioviruses); as a result, polio is rarely seen in developing countries. Unfortunately, no vaccines are currently available for non-polio enteroviruses. Part of the reason there are no vaccines for these viruses is that there is a very large number of subtypes of non-polio enteroviruses.

    Source: http://www.rxlist.com

    Briefly, the best treatment for an enterovirus infection is prevention. For poliovirus, an effective vaccine is available; unfortunately, for non-polio enteroviruses the treatment is supportive and is designed to reduce the symptoms because there are no antiviral medications currently approved for the treatment of these types of enterovirus infections. Immunoglobulins have been used in infected neonates and immunocompromised hosts to both treat and prevent non-polio enterovirus central nervous system infections, but these immunoglobulin treatments are not always very effective. Consequently, supportive measures such as fever control, assisted-breathing methods (ranging from inhaled steroids to intubation), pain-control medications, and topical skin and oral mucosal medications to reduce symptoms are given.

    Source: http://www.rxlist.com

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