Viral encephalitis - InDepth

Highlights

Encephalitis is an inflammation of the brain, most commonly caused by a viral infection. The main causes of viral encephalitis are:

Symptoms of viral encephalitis appear within several days to weeks of exposure to the virus. Some people who are infected do not develop any symptoms at all. However, most develop headache, fever, weakness, nausea, or sleepiness. Those with a severe case of encephalitis may develop:

Because encephalitis can on rare occasions be dangerous, it needs to be diagnosed and treated promptly. Treatment for mild cases focuses primarily on supportive care. If herpes is a possible cause, the standard treatment is the antiviral medications acyclovir or valacyclovir. Unfortunately, for most other viruses causing encephalitis, including cases caused by West Nile virus and other arboviruses, antiviral medications are not available or not effective.

Arboviruses, one of the most common causes of encephalitis, are transmitted by blood-sucking insects such as mosquitoes and, less commonly, ticks. The best way to prevent infection with a mosquito-borne virus is to avoid being bitten. Use insect repellant when you go outside, especially during the peak mosquito hours of dusk and dawn. Remove mosquito-breeding environments such as stagnant water from your property.

Introduction

Encephalitis is an uncommon but potentially life-threatening inflammation of the brain that can occur in people of all ages.

The most common cause of encephalitis is infection by a virus. In very rare cases, encephalitis can also be caused by bacterial infection, protozoa, or as a complication from other infectious diseases. This report focuses on viral encephalitis.

Many viruses can cause encephalitis. In the United States, the most common viral causes of encephalitis are arboviruses, herpes viruses, enteroviruses, and coxsackieviruses.

In the United States, the viruses that cause encephalitis generally fall into the following groups:

Viral infections can cause inflammation in multiple areas of the central nervous system, the area of the body that contains the brain and spinal cord. When both the brain and meninges (protective membranes covering the brain and spinal cord) are affected, the condition is called meningoencephalitis.

Many people exposed to encephalitis-causing viruses have no symptoms. Others may experience a mild transient illness, but do not develop full-blown encephalitis. People with mild encephalitis generally recover spontaneously over a period of several weeks.

Severe cases of encephalitis can, however, have devastating effects, including:

Such severe encephalitis can be fatal. Many survivors of severe encephalitis have long-term mental or physical problems, depending on the specific areas of the brain affected. Fortunately, this is quite uncommon.

Causes

The herpes virus family includes at least 8 distinct viruses that cause infections in humans. These viruses include the herpes simplex virus, varicella-zoster virus (the cause of chickenpox and shingles), Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and herpes virus 6. Although any herpes virus can cause encephalitis, the herpes simplex virus (HSV) is the most common cause of encephalitis.

HSV is the second most common cause of encephalitis in the United States. Herpes simplex encephalitis (HSE) can be caused by either a new HSV infection or reactivation of a latent pre-existing herpes infection. HSE tends to be most severe when it affects young children and older people. Most adults who contract HSE are older than age 50.

There are two distinct types of the herpes simplex virus:

Herpes simplex encephalitis is the only type of viral encephalitis that is treatable. Due to its severity, treatment with acyclovir is administered promptly if suspicion for herpes simplex encephalitis is raised, even while awaiting diagnostic procedures. If left untreated, herpes simplex encephalitis can be fatal. Death may occur even with acyclovir treatment, and many survivors are left with moderate or severe neurological impairments.

Arboviruses, including the West Nile virus, are transmitted by blood-sucking insects such as mosquitoes and ticks. West Nile virus initially develops in birds, which function as the reservoir of infection. Mosquitoes transmit the virus when they bite a susceptible host such as an animal or a human. (The mosquito itself remains quite healthy.) The insects that play a role in this disease-transmission process are referred to as vectors.

Arboviruses multiply in blood-sucking vectors. In fact, the word arbovirus is an acronym for ARthropod-BOrne virus. Insects are arthropods and mosquitoes, ticks, and the other blood-sucking insects may carry such arboviruses. Mosquitoes are the most common vector for arboviruses.

In general, the virus first passes through an insect before infecting a person. These infections are not transmitted through casual contact from one person (or animal) to another. (However, a very small number of West Nile virus infections have occurred through blood transfusions, organ transplantation, and possibly breastfeeding.) Only a small percentage of people who are infected by an arbovirus develop encephalitis.

Arboviruses that cause encephalitis are primarily found among three virus families: Togaviridae, Bunyaviridae, and Flaviviridae.

In the United States, the main mosquito-borne encephalitis strains are Eastern equine, Western equine, St. Louis, La Crosse, Jamestown Canyon, and, in particular, West Nile. Equine encephalitis causes disease in both humans and, as its name implies, horses. Powassan encephalitis is caused by a less common tick-borne flavivirus that occurs primarily in the northern United States. Jamestown Canyon virus disease is caused by a bunyavirus closely related to the La Crosse encephalitis virus.

Japanese encephalitis, which is also transmitted by mosquito, is the most common form of viral encephalitis outside of the United States. It is endemic in rural areas in east, south, and southwest Asia, especially China and Korea. Venezuelan equine encephalitis is found in South and Central America. Dengue and chikungunya are arboviruses found in Central and Southern America, Africa, and Asia that may also cause inflammatory diseases of the nervous system, including encephalitis. The mosquito species that transmits dengue and chikungunya, Aedes aegypti, also carries the Zika virus. There have been a few recent reports of encephalitis associated with Zika virus infection.

Different arboviruses cause different forms of encephalitis. Although the overall disease is the same, there are subtle differences in symptoms and the type of brain damage they produce.

Virus Family

Togaviridae (genus Alphavirus)

U.S. Geographic Areas

Atlantic and Gulf coasts and the Great Lakes region. States most affected are Florida, Georgia, Michigan, and Pennsylvania.

Symptom Onset

Symptoms appear 4 to 10 days following infection and can range from mild flu-like symptoms to full-blown encephalitis.

Incidence and Mortality Rates

About 5 to 10 cases are reported each year. About a third of people who contract EEE die from it, and survivors usually have significant mental and physical impairment.

Age Risk Groups

Adults over age 50 and children under age 15.

Virus Family

Togaviridae (genus Alphavirus)

U.S. Geographic Areas

Farming areas in western and central Plains and Rocky Mountain states west of the Mississippi.

Symptom Onset

5 to 10 days following infection.

Incidence and Mortality Rates

Very rare. Low mortality rate but many survivors have complications afterward. Most severe in children, especially those younger than 1 year. Infants may develop permanent neurological damage.

Age Risk Groups

Infants younger than 12 months.

Virus Family

Flaviviridae (genus Flavivirus)

U.S. Geographic Areas

Takes its name from an epidemic in St. Louis, but primarily occurs in central and southern states.

Symptom Onset

5 to 15 days following infection.

Incidence and Mortality Rates

About 7 cases per year on average. Mortality rate ranges between 5% to 15%, with highest rates among elderly.

Age Risk Groups

Most people experience only mild symptoms. Older adults (over age 60) are at highest risk for severe disease, including encephalitis.

Virus Family

Bunyaviridae (genus Bunyavirus)

U.S. Geographic Areas

The most common cause of arboviral disease after West Nile virus. La Crosse encephalitis virus occurs most frequently in states in the East North Central and South Atlantic divisions. Most cases have occurred in Ohio, West Virginia, and Wisconsin.

Unlike other encephalitis viruses which originate in birds, La Crosse encephalitis is transmitted to mosquitoes from infected chipmunks and squirrels. Jamestown Canyon virus is closely related to La Crosse encephalitis virus. It has been reported in Montana, Minnesota, Massachusetts, Tennessee, and Wisconsin.

Symptom Onset

5 to 15 days following infection.

Incidence and Mortality Rates

About 80 to 100 cases of LaCrosse encephalitis or neuroinvasive disease are reported each year. Mortality rates are less than 1%.

Age Risk Groups

Children younger than 16 years are most at risk for severe disease.

Virus Family

Flaviviridae (genus Flavivirus).

U.S. Geographic Areas

Cases have been reported throughout the mainland United States and Alaska.

Symptom Onset

3 to 14 days following infection.

Incidence and Mortality Rates

In 2018, 2647 cases of West Nile virus (WNV) diseases were reported to the CDC, with 167 deaths. Of all the reported cases, 63% were WNV neuroinvasive disease, which includes meningitis and encephalitis. Less than 1% of people who are infected with WNV go on to develop neurological complications. About 6% of people who developed WNV neuroinvasive disease in 2018 died from this illness.

Age Risk Groups

Adults over age 50.

West Nile Virus (WNV)

Until 1999, the West Nile virus was generally restricted to Africa, the Middle East, southwestern Asia, Eastern Europe, and Australia. It emerged in the United States with the first outbreak in New York City in 1999. WNV is now found in birds and mosquitoes in every state except Alaska and Hawaii.

Human cases of West Nile encephalitis have been reported throughout the continental United States and Alaska. In 2018, states with the highest incidence of neuroinvasive WNV included North Dakota, Nebraska, South Dakota, Montana, and Iowa.

How WNV is Transmitted

WNV, discovered in Uganda in 1937, circulates primarily between birds and mosquitoes and can be carried long distances by migrating birds. In a given geographic area, the appearance of the virus among birds and mosquitoes generally precedes infection in humans. WNV has infected over 110 species of birds. It can be deadly to some types of birds such as crows and jays.

During the season when mosquitoes are prevalent, a sampling of dead birds is analyzed to determine if they died of WNV. This sampling technique is used to predict a potential outbreak of WNV in humans.

In addition to mosquito-to-human transmission, other causes of human infection have included blood transfusions and organ transplantation. (The U.S. now uses screening tests to detect West Nile virus in all donated blood and organs.) There have also been very rare cases of mother-to-child transmission during pregnancy, and one confirmed case of transmission through breastfeeding.

Severity of WNV

About 80% of people infected with WNV will not develop symptoms. Twenty percent will develop West Nile fever (which includes fever, headache, and occasional skin rash). Less than 1% of infected people will develop neuroinvasive disease, the most severe form of WNV, which includes encephalitis and meningitis. WNV neuroinvasive disease is fatal in about 10% of cases. Survivors often experience lingering physical and mental neurological effects, which are sometimes permanent.

Neuroinvasive disease symptoms include high fever, headache, stiff neck, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. There are currently no vaccines to prevent WNV or specific antiviral drugs to treat it.

Tick-borne encephalitis (TBE) is commonly found in many countries throughout Europe, Asia, and the former Soviet Union, but it is reported only rarely in the U.S. Powassan encephalitis is the main tick-borne encephalitis found in the United States and Canada. The first human encephalitis fatality caused by deer tick virus, which is closely related to Powassan virus, was reported in 2009. Cases of tick-borne encephalitis have also been reported in association with Rocky Mountain spotted fever, but this is a bacterial (rickettsial), not viral, infection.

Rabies

The rabies virus is transmitted from the saliva of an infected animal. The encephalitis it causes is virtually always fatal but although it is more common in Eastern Europe, it is very rare in the U.S. Only 1 or 2 cases are typically reported each year, usually from contact with raccoons, bats, or other wild animals.

Encephalitis Associated with Childhood Diseases

Vaccines have virtually eliminated encephalitis caused by common childhood infections such as measles, mumps, rubella, and chickenpox. Encephalitis can still occur in rare cases, particularly with immunocompromised children.

Adenoviruses

Adenoviruses typically cause respiratory or eye infections but, in rare cases, can cause encephalitis as well. The risk is greatest for people who have weakened immune systems.

Enteroviruses

Enteroviruses consist of a large group of viruses (including coxsackieviruses) that enter the body through the gastrointestinal tract and are often responsible for a "stomach flu." They account for only a small percentage of viral encephalitis cases, especially in children. Polio (or poliomyielitis), a disease that has been virtually eliminated in North America through the widespread use of vaccines against the polio virus, is caused by a member of the Enterovirus family. Polio can rarely cause encephalitis, particularly in children.

Risk Factors

Encephalitis is a relatively rare disease. People at highest risk for encephalitis, and its complications include the very young, the very old, and people with weakened immune systems.

Encephalitis can occur at any age. Age-associated risks depend on the type of encephalitis virus. Newborn infants are particularly at risk for herpes simplex encephalitis.

For arboviruses, infants are most vulnerable to Western equine encephalitis. Older children and teenagers are more susceptible to Eastern equine and La Crosse encephalitis. Older adults are at higher risk for Eastern equine, St. Louis, and West Nile virus encephalitis.

People whose immune systems are compromised by conditions such as HIV-AIDS, cancer therapies, or organ transplantation are not especially more susceptible than other individuals to any form of encephalitis, but they are prone to develop a more severe case and more long term damage.

Other medical conditions that may increase the risk for viral encephalitis include chronic kidney disease, diabetes, and alcohol use disorder.

Geography

The primary risk factor for arbovirus encephalitis is living or working in areas of possible exposure to virus-carrying mosquitoes. People who work outdoors or spend time in outdoor recreational activities are particularly at risk.

Most arbovirus outbreaks occur in rural or farming areas, but they can also occur in cities. While some forms of arbovirus are limited to specific geographical regions, the West Nile virus has become endemic throughout the mainland United States. However, encephalitis occurs in only a small percentage of West Nile infections.

Season

Transmission of arboviruses correlates with the mosquito season and is highest during the months of July through September (late summer through early fall). The ideal conditions for mosquito breeding are a wet spring followed by a hot, dry summer. Transmission for enteroviruses is highest in the summer and fall seasons. There is no seasonal variation in the incidence for HSV infections.

Prognosis

Mild cases of encephalitis generally present with fatigue, weakness, possibly low grade fever, and headache. Most people who have mild cases of encephalitis make a full recovery within 2 to 4 weeks, although many will continue to feel fatigued and "out of sorts" for many weeks thereafter.

Prognosis for severe encephalitis depends on many factors, including:

In very severe cases of encephalitis, the swelling of the brain inside the skull places downward pressure on the brain stem. The brain stem controls vital functions, such as respiration and heartbeat. If the pressure becomes too severe, these vital functions can cease, and death can occur.

Survivors of severe encephalitis often experience neurologic consequences, which can be long-term and even permanent. The degree and type of brain damage can vary from mild-to-severe and from focal (in one part of the brain) to multifocal (several parts of the brain) to diffuse (throughout the brain).

The location and severity of the infection largely determines the pattern of brain damage and its effects, which can be:

While coma can occur in people with severe encephalitis, it does not necessarily predict a fatal or severe outcome. Some people experience only mild-to-moderate complications after awakening from an encephalitis-associated coma.

Symptoms

Symptoms of encephalitis usually appear within several days to weeks of exposure to the virus. Some people have no or very mild symptoms. In other cases, symptoms may be severe or life-threatening.

In milder cases, symptoms may include:

Severe symptoms that require immediate medical attention include:

Symptoms in Infants

Infants with herpes virus encephalitis may develop lesions in the mouth, in the eye, or on the skin 1 to 45 days after birth. Other symptoms in infants may include fever, lethargy, poor feeding, irritability, crying more than usual, vomiting, and body stiffness. The fontanels, the soft spots on their head where the skull has not yet closed, may bulge outward.

Diagnosis

The various types of encephalitis produce similar symptoms so doctors cannot rely strictly on clinical features to differentiate among the many viral causes. The primary objective in diagnosing viral encephalitis is to determine if it is caused by:

Encephalitis needs to be treated right away, and time is of the essence. Even though acyclovir or valacyclovir are only effective for herpes encephalitis (not encephalitis caused by West Nile virus or other viruses), health care providers will start immediate treatment with these medications.

The results of diagnostic tests, which may take several days to complete, can help determine whether or not anti-viral medications should be continued, or if the focus should be on symptom management alone.

If encephalitis is suspected, imaging tests are often the first diagnostic step. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans can show the extent of the inflammation in the brain and help differentiate encephalitis from other conditions.

MRIs are recommended over CT scans because they can detect injuries in parts of the brain that suggest infection with herpes virus at the onset of the disease, while CT scans cannot.

Electroencephalogram (EEG), which records brain waves, may reveal abnormalities in the temporal lobe that are suggestive of herpes simplex encephalitis.

When encephalitis is suspected, a sample of cerebrospinal fluid (CSF) is taken using lumbar puncture (spinal tap). This procedure involves inserting a needle between two vertebrae in the lower back. The CSF pressure is measured, and a fluid sample is collected. The sample is sent to a lab to evaluate white blood cell count and check for signs of infection or inflammation.

Cerebrospinal fluid is used to test for herpes viruses, as well as other viruses, and to look for the presence of the West Nile virus itself or antibodies to other virus types. While a cerebrospinal fluid test is necessary to diagnose encephalitis and to determine which virus is causing the infection, it cannot provide information on how severe the disease will be.

Blood tests may be used to test for West Nile virus and other arbovirus infections. Such blood tests may determine whether a particular virus infection is present but, by themselves, cannot distinguish between viral infection of the brain and viral infection at other sites in the body.

If necessary, tiny samples of brain tissue can be surgically removed for examination and testing for the presence of the virus. Brain biopsy is uncommonly performed but may be warranted in cases of severe or worsening encephalitis where the diagnosis remains in doubt even after all the above tests.

Treatment

Most treatments for encephalitis focus on supportive care (rest, nutrition, and fluids) to help the body fight the infection and relieve inflammation. Antiviral drugs can only treat herpes simplex encephalitis (and more rare types of herpes encephalitis). There are no antiviral drugs to specifically treat the other viral forms of encephalitis.

People with very severe encephalitis are at risk for body-wide (systemic) complications, including shock, low oxygen, low blood pressure, and low sodium levels. Any potentially life-threatening complication should be addressed immediately with appropriate treatments. It is very important to lower fever and ease the pressure caused by swelling of the brain.

Although it is difficult to quickly diagnose the cause of encephalitis, rapid treatment is essential. Clinical guidelines recommend immediately administering intravenously the antiviral drug acyclovir (Zovirax, generic) without waiting to confirm if herpes simplex is the cause. Ganciclovir (Cytoyene, generic) and foscarnet (Foscavir, generic) are other antiviral medications that are used to treat some types of herpes encephalitis.

Other encephalitis treatments are aimed at reducing symptoms.

Severe encephalitis can cause neurological impairments. Physical therapy, speech therapy, and occupational therapy may be helpful. Even those with "mild" encephalitis should be aware that they can feel fatigued and unwell for weeks or even months after the infection has resolved.

Vaccines

Certain vaccines can help prevent the diseases that can lead to encephalitis.

Measles Virus

Measles used to be a very common cause of viral encephalitis. Fortunately, vaccination programs have nearly eliminated this dreaded disease. (Unfortunately, there has been an increase in cases in recent years due to parents opposing childhood vaccines.) Children now receive immunization against measles as part of a combined vaccine (MMR) for measles, mumps, and rubella.

Varicella-Zoster Virus

The varicella-zoster virus (VZV) is a type of herpes virus that causes both chickenpox (varicella) and shingles (herpes zoster). Chickenpox occurs from first-time exposure to the virus and usually affects children. Shingles is a later reactivation of the virus that typically strikes adults. Uncommonly, the varicella-zoster virus can cause encephalitis. In the United States, children are vaccinated against chickenpox as part of their regular immunization schedule either with a vaccine for chickenpox by itself or together with the MMR vaccine (MMRV vaccine). A vaccine for shingles (Zostavax) is available for adults age 50 years and older.

A vaccine (Ixiaro) is available for children and adults traveling from the United States to regions where Japanese encephalitis is endemic. Countries with high rates of Japanese encephalitis include Vietnam, Cambodia, Myanmar (Burma), India, Pakistan, Nepal, Malaysia, Korea, northern Thailand, Malaysia, Sri Lanka, and the Philippines.

Another type of vaccine is used to prevent tick-borne encephalitis (TBE) in travelers visiting regions where this type of encephalitis is prevalent. TBE is found mainly in Eastern and Central Europe. Two types of these vaccines (FSME-IMMUN and Encepur) are available in Canada and many European countries, but they are not approved or available in the United States.

Scientists are investigating several types of experimental vaccines for West Nile virus, but this research is still in its early stages. In the United States, several vaccine candidates against West Nile virus are currently in clinical trials.

There are two types of rabies vaccines: pre-exposure and post-exposure. The pre-exposure vaccine is for people who face occupational risks for rabies or who will be traveling to countries where rabies is endemic. The post-exposure vaccine is for anyone bitten by an animal suspected of having rabies.

People who never received pre-exposure vaccination may also receive a shot of rabies immune globulin unless they were previously vaccinated. The regimen is 1 shot of rabies immune globulin and 4 shots of post-exposure rabies vaccine given over a period of 2 weeks.

The current types of rabies vaccines cause much less discomfort and fewer adverse effects than the older ones. Side effects may include mild reactions such as pain, redness, or swelling at the injection site. Pain at the injection site and low-grade fever may follow the rabies immune globulin shot.

Polio has been virtually eliminated from North America and the rest of the world through the use of polio vaccine, although rare cases continue to be found in areas of social disruption such as the Middle East and some parts of Africa.

Two types of vaccines are available:

The attenuated vaccine is the preferable material, although the heat-killed vaccine is occasionally used in people who have a weakened immune system.

Prevention

The risk for mosquito-borne infections is highest between dusk and dawn when mosquitoes feed. A good insect repellent is very helpful in reducing the risk for vector-borne encephalitis. The most complete personal protection program is to apply the insect repellant DEET to the skin and permethrin to clothing. Additional steps to prevent mosquito bites include wearing long-sleeved shirts and long pants and sleeping in rooms with air conditioning or screens on windows and doors.

DEET

Most insect repellents contain the chemical DEET, which remains the gold standard for mosquito and tick repellents. Concentrations in repellant products range from 10% to 98%. The concentration level determines the duration of protection: a 30% concentration supplies protection for 5 hours.) DEET is approved for both adults and children, but it should not be used on infants younger than 2 months.

When applying DEET or other insect repellant products:

Other Insect Repellent Products

The CDC also recommends the mosquito repellents picaridin, oil of lemon eucalyptus, IR3535, and 2-undecanone.

Picaridin is an alternative to DEET. Some of the advantages of picaridin are that it is odorless and does not stain or damage fabrics. Picaridin is available in concentrations ranging from 5% to 20%. Stronger concentrations can last up to 8 hours. Picaridin is safe for adults and children but, like all insect repellants, should not be applied on children younger than 2 months.

Oil of lemon eucalyptus is a chemically synthesized version of an extract found in lemon eucalyptus trees. In comparative tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years due to risks for skin irritation.

Permethrin is an insect repellent used to treat clothing and bed nets, not for skin. Items sprayed or soaked in permethrin remain protective against mosquitoes and ticks for 5 to 6 washes. Allow clothing to air dry for several hours before using it. You can also buy clothing commercially pre-treated with permethrin, which can last for up to 70 washes.

Eliminate Sources of Standing Water

The best way for homeowners to reduce mosquito populations is to eliminate sources of standing water:

Mosquito Traps and Bug Zappers

Mosquito traps use various methods for repelling or attracting and trapping female mosquitoes, which are the primary transmitters of arboviruses. These methods include electricity or propane. However, there is little evidence to support their effectiveness.

Insect light traps (commonly called bug zappers), which attract and electrocute insects, are not effective for mosquito control. An additional concern is that they can kill beneficial insects.

Citronella Candles

Burning citronella candles can modestly reduce the likelihood of bites. (Indeed, burning any candle helps to some extent, perhaps because the generation of carbon dioxide diverts mosquitoes toward the flame.)

Your home environment, personal hygiene, and what you wear can also help reduce your risk for mosquito bites:

Spraying

Public health measures are the most effective methods for controlling mosquitoes. Local communities that experience outbreaks of encephalitis or West Nile virus from mosquitoes often have public spraying programs that target mosquito larvae during breeding season as well as adult mosquitoes.

The U.S. Environmental Protection Agency (EPA) approves the safety of the insecticides used. While these pesticides are generally considered safe for humans, people with asthma or other respiratory problems should avoid exposure by staying indoors while spraying takes place.

Report Dead Birds

Dead birds may be indicators that the West Nile virus has reached a specific region. Report any dead birds to your local public health authorities. Although it is unlikely that you can contract West Nile virus from a dead bird, you should never touch a dead animal with your bare hands.

Resources

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Review Date: 9/2/2019
Reviewed By: Alireza Minagar, MD, MBA, Professor, Department of Neurology, LSU Health Sciences Center, Shreveport, LA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
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