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Human enteroviruses are a genus in the family Picornaviridae (small positive-sense single-stranded RNA viruses) that were originally classified or named as polioviruses, Coxsackie A viruses, Coxsackie B viruses, echoviruses, and enteroviruses. Rhinoviruses are included as enteroviruses by many researchers but not all. There are well over 100 types of known enteroviruses (genus Enterovirus). The virus that causes hand, foot, and mouth disease belongs to the group of so-called non-polio enteroviruses.
These enteroviruses usually spread from person to person by direct contact with the viruses that shed from the gastrointestinal tract or upper respiratory tract. In general, health care providers categorize these viruses 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, an infected person 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. 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, acute hemorrhagic conjunctivitis
- rhinovirus: the common cold (over 100 different serotypes), mild respiratory illness
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, enteroviruses may contaminate environmental sources such as water. 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 and infants) or compromised immune systems (for example, children with type 1 diabetes) also are at higher risk for enterovirus infections than normal children or adults. Pregnant females and individuals with respiratory problems like asthma are at higher risk. Individuals are at highest risk during the fall and summer months.
Are enteroviruses contagious?
Yes, enteroviruses are contagious often by direct contact from person to person with respiratory secretions or by contact with fecal material. Some enteroviruses spread indirectly when uninfected people come in contact with food or fluids contaminated by secretions (feces, oral secretions, or droplets) from infected individuals. The viruses are capable of surviving on surfaces like tables and door handles for several days.
What is the incubation period for an enterovirus infection?
The average incubation period (time from exposure to first symptoms) ranges from about three to 10 days. Symptoms, when present in uncomplicated infections, last about a week.
What is the contagious period for an enterovirus infection?
In general, individuals are contagious about three days after exposure to the virus and remain contagious until about 10 days after they develop symptoms. Individuals can shed infectious viruses even if they have no symptoms or during the incubation period and/or after symptoms stop.
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, often without diarrhea) 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, physicians diagnose enterovirus infections by clinical symptoms. Health care professionals infrequently perform blood tests. 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, health care professionals isolate the infecting enterovirus 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 designed to reduce the symptoms because there are no antiviral medications currently approved for the treatment of these types of enterovirus infections. Many doctors recommend using over-the-counter medications to reduce symptoms.
Doctors may use immunoglobulins 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.
Since March 2018, Pleconaril, a 3C protease inhibitor drug, has been awaiting FDA approval as an intranasal spray to treat rhinoviral infections. In the past, doctors have used the drug for compassionate treatment only in life-threatening enteroviral infections.
What types of doctors treat enterovirus infections?
Many individuals are treated with supportive measures only; primary physicians (usually a pediatrician but possibly a specialist in family practice or internal medicine) treat some. In other instances, especially with individuals with complications, infectious-disease specialists, critical care specialists, cardiologists, and/or lung specialists may treat patients. Rarely, a neurology specialist may be consulted.
Non-polio enterovirus outbreaks, including enterovirus D68 (EV-D68) and 71
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, especially China. Some infections from this virus have been associated with severe neurologic disease, such as brainstem encephalitis.
- Enterovirus D 68 had a nationwide outbreak in the U.S. from August 2014 to January 2015. A total of 1,153 people in 49 states and the District of Columbia had confirmed D68 infection. Almost all the individuals infected were children who also had a history of asthma or wheezing. Health officials detected D68 enteroviruses in 14 patients who died. However, the CDC indicated that there were likely millions of enterovirus D68-infected individuals (infants, toddlers, and children) with mild illness who did not seek medical treatment or get tested for the infection in the United States.
- Thailand, in 2017, reported an outbreak of enterovirus A71 with 163 infected patients.
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. Health care professionals routinely vaccinate people against certain enteroviruses (polioviruses). As a result, polio is rarely seen in developing countries.
Unfortunately, no vaccines are available for non-polio enteroviruses, although Chinese investigators have indicated they have two vaccines against enterovirus 71 in successful phase 3 trials. 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 and a vaccine developed against one subtype is usually not effective against another subtype.
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United States. Centers for Disease Control and Prevention. "Non-Polio Enterovirus: Enterovirus D68." Oct. 20, 2017. <http://www.cdc.gov/non-polio-enterovirus/about/ev-d68.html#outbreak>.
United States. Centers for Disease Control and Prevention. "Non-Polio Enteroviruses." Oct. 20, 2017. <http://www.cdc.gov/non-polio-enterovirus/>.
United States. Centers for Disease Control and Prevention. "Severe Respiratory Illness Associated with Enterovirus D68 -- Missouri and Illinois, 2014." MMWR 63.36 Sept. 12, 2014: 798-799. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm63e0908a1.htm>.