Enterovirus Infections

Definition

Enteroviruses are so named because they reproduce initially in the gastrointestinal tract after infection occurs. Despite, this, they usually do not lead to intestinal symptoms; rather it is their spread to organs, such as the nervous system, heart, skin, and others that causes disease. Enteroviruses are part of a larger group of viruses known as Picornaviruses. The word comes from the combination of "pico" (Spanish, meaning "a little bit"), and RNA (ribonucleic acid, an important component of genetic material).

Description

There are four groups of enteroviruses: Coxsackievirus, Echovirus, ungrouped Enterovirus, and Y Poliovirus.

Viruses are generally divided into those that use DNA (deoxyribonucleic acid) or RNA as their genetic material; all enteroviruses are RNA viruses. They are found worldwide, but infection is more common in areas of poor hygiene and overcrowding.

Although most cases of enterovirus do not produce symptoms, some five to 10 million individuals in the United States each year suffer from one of the enteroviral diseases. Illness is more common in the very young. While there are close to 70 different strains of enteroviruses, over 70% of infections are caused by only 10 types.

The virus is most commonly transmitted by the fecal-oral route (contamination of fingers or objects by human waste material); in some instances transmission is through contaminated food or water. Passage of some strains of virus by way of air droplets can lead to respiratory illness. Infection of fetuses by way of the placenta also has been documented. Breast milk contains antibodies which can protect newborns.

The incubation period for most enteroviruses ranges from two to 14 days. In areas of temperate climate, infections occur mainly in the summer and fall.

Causes and symptoms

Enteroviruses are believed to be the cause of at least 10 distinct illnesses. Once they enter the body, they multiply in the cells that line the gastrointestinal tract, and eventually reach sites of lymphatic tissue (such as the tonsils). While most of these diseases are of short duration and do not cause significant injury, some can produce severe illness. Each presents its own unique symptoms. And a 2003 report to the Infectious Diseases Society of America reminded physicians that infants with enteroviral infections often present early in their illnesses with no signs of fever, complicating diagnosis.

The main syndromes caused by the various enteroviruses are the following:

• Summer grippe (nonspecific febrile illness). This is the most common syndrome, and is characterized by flu-like symptoms of fever, headache, and weakness, that typically last three to four days. Many patients also develop upper respiratory symptoms and some nausea and vomiting. One of the major ways to distinguish this disease from influenza, is the fact that grippe most often occurs in the summer.
• Generalized disease of the newborn is a potentially serious infection in which infants from one week to three months of age develop a syndrome that can be difficult to distinguish from a severe bacterial infection. Fever, irritability, and decreased responsiveness or excessive sleepiness are the major symptoms. Inflammation of heart muscle (myocarditis ), low blood pressure, hepatitis, and meningitis sometimes complicate the illness.
• Aseptic meningitis encephalitis is a well known syndrome caused by this group of viruses. In fact, enteroviruses are responsible for over 90% of cases of aseptic meningitis, and most often hit children and young adults. Headache, fever, avoidance of light, and eye pain are characteristic. Drowsiness may be prominent, and other symptoms include sore throat, cough, muscle pain, and rash. Occasionally, not only the meninges;mdash;the covering around the brain and spinal cord;mdash;is infected, but also brain tissue itself, producing encephalitis. The illness resolves after about a week or so, and permanent damage is unusual. Enteroviruses can also produce the Guillian-Barré syndrome, which involves weakness and paralysis of the extremities and even the muscles of respiration.
• Pleurodynia (Bornholm's disease) is due to viral infection and inflammation of the chest and abdominal muscles used for breathing. Pain occurs as acute episodes, lasting 30 minutes or so. Coxsackie B virus is the usual cause of the illness.
• Myocarditis and/or pericarditis involves infection of the heart muscle (myocardium) and the covering around the heart (pericardium). Infants and young adults are the most susceptible, and for some reason, more than two-thirds of cases occur in males. The disease usually begins as an upper respiratory tract infection with cough, shortness of breath, and fever. Chest pain, increasing shortness of breath, irregularities of cardiac rhythm, and heart failure sometimes develop. Some patients wind up with long-term heart failure if the heart muscle is significantly affected.
• Exanthems is the medical term for rashes, and enterovirus is the number one cause of summer and fall rashes in children. They occur anywhere on the body, and often resemble diseases such as measles.
• Hand-foot-and-mouth disease occurs initially as a sore throat (often involving the tongue as well), and is followed by a rash on the hands, and sometimes the feet. The rash often forms small blisters, which lead to ulcers. Symptoms generally resolve within a week. A specific Coxsackievirus (A16) is the most frequent cause of this highly infectious disease.
• Herpangina is most often caused by one of the Coxsackie A viruses, and appears as the acute onset of fever and sore throat. This last symptom is particularly severe, as the virus produces multiple ulcers in the throat. Swallowing becomes very painful; symptoms can persist for several weeks.
• Acute hemorrhagic conjunctivitis involves viral infection of the conjunctiva, which is a covering around the eye. Pain, blurred vision, aversion to light, and a discharge from the eye are the main symptoms. Headache and fever occur in about one in five patients. The disease runs its course in about 10 days.

A number of other illnesses have been attributed to enteroviruses, including pneumonia and other respiratory infections, myositis or muscle inflammation, arthritis, and acute inflammation of the kidneys. It is clear then that these viruses produce a number of various illnesses, most often in younger age groups.

Diagnosis

In the majority of cases, diagnosis is based on the characteristic symptoms that the virus produces (such as the chest pain in pleurodynia). Rarely is it necessary to identify a specific strain of virus causing the illness. It is more important to be certain that the infection is due to a virus that does not require treatment with antibiotics.

Culture, or growing the organism outside of the body, is helpful only when obtained from areas that tend to indicate recent infection, such as from swollen joints, cerebrospinal fluid, or blood. Cultures from other areas, such as the throat, can be misleading. This is because the virus may remain for long periods of time in places with a large amount of lymphatic tissue. As a rule, cultures done early in the illness are more likely to identify the virus.

New techniques that involve identification of viral genetic material (PCR) are useful in certain cases, but are not indicated for routine testing.

Treatment

As noted above, enterovirus is capable of attacking many different organs and producing a variety of symptoms. Most infections are mild and improve without complications, requiring no specific therapy. When the virus attacks critical organs however, such as the heart, respiratory muscles, nervous system, etc., specialized care is often needed.

As of 2001, no effective antiviral medication for enterovirus has undergone investigation in patients, though some drugs appeared promising for the future. In some patients who are unable to produce antibodies (hypogammaglobunemia), administrating antibodies themselves is helpful.

Prognosis

The overall outlook for enterovirus infection depends on the organs involved, and the immune condition of the individual patient. Unless vital organs are involved or immunity is abnormal, infection causes few problems. On the other hand, patients who have diseases that affect antibody production can develop chronic infection of the brain or meninges. A 2003 study found that enterovirus infections can increase the risk of type 1 diabetes in children who are genetically predisposed to diabetes.

Prevention

In the hospital setting, the best means of avoiding transmission of infection is the use of good hand-washing practices and other appropriate precautions (gowns and gloves for hospital staff). The virus is found in feces for up to one week after infection; therefore precautions that isolate waste material (enteric precautions) will help decrease the chance of spreading the illness.

KEY TERMS

Antibodies— Proteins that are formed by the body and play a role in defense against infection.

Antibiotic— A medication that is designed to kill or weaken bacteria.

Meninges— Outer covering of the spinal cord and brain. Infection is called meningitis, which can lead to damage to the brain or spinal cord and lead to death.

Resources

PERIODICALS

"Enterovirus Infections Increase Risk of Type 1 Diabetes in High-Risk Children." Diabetes Week June 16, 2003: 22.

Tucker, Miriam E. "Fever Often Absent in Early Enteroviral Illness (Severe Cases)." Pediatric News January 2003: 20-22.

OTHER

"Hand, Foot and Mouth Disease." The Picarnovirus Home Page. 〈http://www.iah.bbsrc.ac.uk/virus/Picornaviridae/picornavirus.htm〉.

"Weekly Clinicopathological Exercises: Case 47- 1993: A 28-Year-Old Man with Recurrent Ventricular Tachycardia and Dysfunction of Multiple Organs." New England Journal of Medicine Online. 〈http://content.nejm.org〉.

Enterovirus infections

Enteroviruses are a group of viruses that contain ribonucleic acid as their genetic material. They are members of the picornavirus family. The various types of enteroviruses that infect humans are referred to as serotypes, in recognition of their different antigenic patterns. The different immune response is important, as infection with one type of enterovirus does not necessarily confer protection to infection by a different type of enterovirus. There are 64 different enterovirus serotypes. The serotypes include polio viruses, coxsackie A and B viruses, echoviruses and a large number of what are referred to as non-polio enteroviruses.

The genetic material is enclosed in a shell that has 20 equilateral triangles (an icosahedral virus). The shell is made up of four proteins.

Despite the diversity in the antigenic types of enterovirus, the majority of enterovirus cases in the United States is due to echoviruses and Coxsackie B viruses. The infections that are caused by these viruses are varied. The paralytic debilitation of polio is one infection. The importance of polio on a global scale is diminished now, because of the advent and worldwide use of polio vaccines. Far more common are the cold -like or flu-like symptoms caused by various enteroviruses. Indeed, the non-polio enteroviruses rival the cause of the "common cold," the rhinovirus, as the most common infectious agent in humans. In the United States, estimates from the Centers for Disease Control are that at least ten to fifteen million people in the United States develop an enterovirus infection each year.

Enterovirus infection is spread easily, as the virus is found in saliva, sputum or nasal secretions, and also in the feces of those who are infected. Humans are the only known reservoir of enteroviruses. Following spread to water via feces, enteroviruses can persist in the environment. Thus, surface and ground water can be a source of enterovirus.

Spread of an enterovirus occurs by direct contact with the fluids from an infected person, by use of utensils that have been handled by an infected person, or by the ingestion of contaminated food or water. For example, coughing into someone's face is an easy way to spread enterovirus, just as the cold-causing rhinoviruses are spread from person to person. Fecal contact is most common in day care facilities or in households where there is a newborn, where diapers are changed and soiled babies cleaned up.

The spread of enterovirus infections is made even easier because some of those who are infected do not display any symptoms of illness. Yet such people are still able to transfer the infectious virus to someone else.

The common respiratory infection can strike anyone, from infants to the elderly. The young are infected more frequently, however, and may indeed be the most important transmitters of the virus. Common symptoms of infection include a runny nose, fever with chills, muscle aches and sometimes a rash. In addition, but more rarely, an infection of the heart (endocarditis), meninges (meningitis ) or the brain (encephalitis) can develop. In newborns, enterovirus infection may be related to the development of juvenile-onset diabetes, and, in rare instances, can lead to an overwhelming infection of the body that proves to be lethal.

Although enterovirus-induced meningitis is relatively rare, it afflicts between 30,000 and 50,000 people each year in the United States alone.

Evidence is accumulating that suggests that enterovirus infections may not only be short in duration (also referred as acute) but may also become chronic. Diseases such as chronic heart disease and chronic fatigue syndrome may well have an enterovirus origin. Moreover, juvenile diabetes may involve an autoimmune response.

The climate affects the prevalence of the infections. In tropical climates, where warm temperatures are experienced throughout the year, enterovirus infections occur with similar frequency year-round. But, in more temperate climates, where a shift in seasons is pronounced, enterovirus infections peak in the late summer and fall.

Another factor in the spread of enterovirus infections is the socio-economic conditions. Poor sanitation that is often coincident with lower economic standing is often associated with the spread of enterovirus infections.

Following inhalation or ingestion of enterovirus, viral replication is thought to occur mainly in lymphoid tissues of the respiratory and gastrointestinal tract that are in the immediate vicinity of the virus. Examples of tissues include the tonsils and the cells lining the respiratory and intestinal tracts. The virus may continue to replicate in these tissues, or can spread to secondary sites including the spinal cord and brain, heart or the skin.

As with other viruses, enteroviruses recognize a receptor molecule on the surface of host cells and attach to the receptor via a surface molecule on the virus particle. Several viral molecules have been shown to function in this way. The virus then enters the host cell and the genetic material is released into the cytoplasm (the interior gel-like region) of the host cell. The various steps in viral replication cause, initially, the host cell nucleus to shrink, followed by shrinkage of the entire. Other changes cause the host cell to lose its ability to function and finally to explode, which releases newly made virus.

Currently, no vaccine exists for the maladies other than polio. One key course of action to minimize the chances of infection is the observance of proper hygiene . Handwashing is a key factor in reducing the spread of many microbial infections, including those caused by enteroviruses. Spread of enteroviruses is also minimized by covering the mouth when coughing and the nose when sneezing.

See also Cold, common; Viruses and responses to viral infection