Enterovirus D68
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Enterovirus D68 (EV-D68) is a member of the ''
Picornaviridae Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm ...
'' family, an
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
. First isolated in
California California () is a U.S. state, state in the Western United States that lies on the West Coast of the United States, Pacific Coast. It borders Oregon to the north, Nevada and Arizona to the east, and shares Mexico–United States border, an ...
in 1962 and once considered rare, it has been on a worldwide upswing in the 21st century. It is suspected of causing a
polio Poliomyelitis ( ), commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe ...
-like disorder called
acute flaccid myelitis Acute flaccid myelitis (AFM) is a serious condition of the spinal cord. Symptoms include rapid onset of arm or leg weakness and decreased reflexes. Difficulty moving the eyes, speaking, or swallowing may also occur. Occasionally, numbness or pain ...
(AFM).


Virology

EV-D68 is one of the more than one hundred types of
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
es, a group of
ssRNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
viruses containing the
poliovirus Poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species '' Enterovirus C'', in the family of '' Picornaviridae''. There are three poliovirus serotypes, numbered 1, 2, and 3. Poliovirus is composed ...
es,
coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of viral envelope, nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovi ...
es, and
echovirus Echovirus is a polyphyletic group of viruses associated with enteric disease in humans. The name is derived from "enteric cytopathic human orphan virus". These viruses were originally not associated with disease, but many have since been identifi ...
es. It is unenveloped. Unlike all other enteroviruses, EV-D68 displays acid
lability Lability refers to the degree that something is likely to undergo change. It is the opposite ( antonym) of stability. Biochemistry In reference to biochemistry, this is an important concept as far as kinetics is concerned in metalloprotein ...
and a lower optimum growth temperature, both characteristic features of the human
rhinovirus The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a Positive-sense single stranded RNA virus, positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinoviru ...
es. It was previously called human rhinovirus 87 by some researchers. Since the year 2000, the original virus strains diversified and evolved a genetically distinct outbreak strain, clade B1. It is Clade B1, but not older strains, which has been associated with AFM and is neuropathic in animal models.


Epidemiology

Since its discovery in 1962, EV-D68 had been described mostly sporadically in isolated cases. Six clusters (10 or more cases) or
outbreak In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire ...
s between 2005 and 2011 have been reported from the Philippines, Japan, the Netherlands, and the
states State most commonly refers to: * State (polity), a centralized political organization that regulates law and society within a territory **Sovereign state, a sovereign polity in international law, commonly referred to as a country **Nation state, a ...
of
Georgia Georgia most commonly refers to: * Georgia (country), a country in the South Caucasus * Georgia (U.S. state), a state in the southeastern United States Georgia may also refer to: People and fictional characters * Georgia (name), a list of pe ...
,
Pennsylvania Pennsylvania, officially the Commonwealth of Pennsylvania, is a U.S. state, state spanning the Mid-Atlantic (United States), Mid-Atlantic, Northeastern United States, Northeastern, Appalachian, and Great Lakes region, Great Lakes regions o ...
and
Arizona Arizona is a U.S. state, state in the Southwestern United States, Southwestern region of the United States, sharing the Four Corners region of the western United States with Colorado, New Mexico, and Utah. It also borders Nevada to the nort ...
in the United States. EV-D68 was found in 2 of 5 children during a 2012/13 cluster of polio-like disease in California. In 2016, 29 cases were reported in
Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...
(5 in
France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...
and
Scotland Scotland is a Countries of the United Kingdom, country that is part of the United Kingdom. It contains nearly one-third of the United Kingdom's land area, consisting of the northern part of the island of Great Britain and more than 790 adjac ...
, 3 each in
Sweden Sweden, formally the Kingdom of Sweden, is a Nordic countries, Nordic country located on the Scandinavian Peninsula in Northern Europe. It borders Norway to the west and north, and Finland to the east. At , Sweden is the largest Nordic count ...
,
Norway Norway, officially the Kingdom of Norway, is a Nordic countries, Nordic country located on the Scandinavian Peninsula in Northern Europe. The remote Arctic island of Jan Mayen and the archipelago of Svalbard also form part of the Kingdom of ...
and
Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...
). Cases have been described to occur late in the enterovirus season (roughly the period of time between the spring equinox and autumn equinox), which is typically during August and September in the
Northern Hemisphere The Northern Hemisphere is the half of Earth that is north of the equator. For other planets in the Solar System, north is defined by humans as being in the same celestial sphere, celestial hemisphere relative to the invariable plane of the Solar ...
.


Predisposing factors

Children less than 5 years old and children with
asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...
appear to be most at risk for the illness, although illness in adults with asthma and
immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
have also been reported.


2014 North American outbreak

In August 2014, the virus caused clusters of
respiratory disease Respiratory diseases, or lung diseases, are pathological conditions affecting the organs and tissues that make gas exchange difficult in air-breathing animals. They include conditions of the respiratory tract including the trachea, bronchi, ...
in the United States, resulting in the largest documented outbreak of EV-D68 with 2,287 confirmed cases and 14 deaths among children.


Signs and symptoms

EV-D68 almost exclusively causes
respiratory illness Respiratory diseases, or lung diseases, are pathological conditions affecting the organs and tissues that make gas exchange difficult in air-breathing animals. They include conditions of the respiratory tract including the trachea, bronchi, bron ...
, which varies from mild to severe, but can cause a range of symptoms, from none at all, to subtle flu-like symptoms, to debilitating respiratory illness and a suspected rare involvement in a syndrome with
polio Poliomyelitis ( ), commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe ...
-like symptoms. Like all enteroviruses, it can cause variable
rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...
es, abdominal pain and soft stools. Initial symptoms are similar to those for the
common cold The common cold, or the cold, is a virus, viral infectious disease of the upper respiratory tract that primarily affects the Respiratory epithelium, respiratory mucosa of the human nose, nose, throat, Paranasal sinuses, sinuses, and larynx. ...
, including a runny nose, sore throat, cough, and fever. As the disease progresses, more serious symptoms may occur, including difficulty breathing as in
pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...
, reduced alertness, a reduction in urine production, and dehydration, and may lead to
respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a r ...
. The degree of severity of symptoms experienced seems to depend on the demographic population in question. Experts estimate that the majority of the population has, in fact, been exposed to the enterovirus, but that no symptoms are exhibited in healthy adults. In contrast, EV-D68 is disproportionately debilitating in very young children, as well as the very weak. While several hundred people (472), mostly youth, have been exposed to the disease, less than a hundred of those patients have been diagnosed with severe symptoms (such as paralysis), and during the recent outbreak in the US just a single death was recorded over the last weekend of September 2014. The death was of a 10-year-old girl in New Hampshire.


Acute flaccid myelitis

The virus is one cause of
acute flaccid myelitis Acute flaccid myelitis (AFM) is a serious condition of the spinal cord. Symptoms include rapid onset of arm or leg weakness and decreased reflexes. Difficulty moving the eyes, speaking, or swallowing may also occur. Occasionally, numbness or pain ...
, a rare muscle weakness, usually due to
polio Poliomyelitis ( ), commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe ...
. In 2014, the cases of two California children were described who tested positive for the virus and had
paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...
of one or more limbs reaching peak severity within 48 hours of onset. "Recovery of motor function was poor at 6-month follow-up." As of October 2014, the US
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...
(CDC) was investigating 10 cases of paralysis and/or cranial dysfunction in Colorado and other reports around the country, coinciding with the increase in enterovirus D68 activity. As of October 2014 it was believed that the actual number of cases might be 100 or more. As of 2018 the link of EV-D68 and the paralysis is strong, meeting six
Bradford Hill criteria The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of nine principles that can be useful in establishing epidemiologic evidence of a causal relationship between a presumed cause and an observed effect and ha ...
fully and two partially. The CDC recently issued a statement on 17 October 2018 claiming "Right now, we know that poliovirus is not the cause of these AFM cases. CDC has tested every stool specimen from the AFM patients, none of the specimens have tested positive for the poliovirus." In 2019, the CDC has published that AFM is caused by Enterovirus D68.


Diagnosis

In 2014, a real-time PCR test to speed up detection was developed by CDC.


Treatment

There is no specific treatment and no vaccine, so the illness has to run its course; treatment is directed against symptoms (
symptomatic treatment Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the com ...
). Most people recover completely; however, some need to be hospitalized, and some have died as a result of the virus. Five EV-D68 paralysis cases were unsuccessfully treated with
steroids A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter mem ...
,
intravenous immunoglobulin Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinat ...
and/or
plasma exchange Plasmapheresis (from the Greek πλάσμα, ''plasma'', something molded, and ἀφαίρεσις ''aphairesis'', taking away) is the removal, treatment, and return or exchange of blood plasma or components thereof from and to the blood circulati ...
. The treatment had no apparent benefit as no recovery of motor function was seen. A 2015 study suggested the antiviral drug
pleconaril Pleconaril (Picovir) is an antiviral drug that was being developed by Schering-Plough for prevention of asthma exacerbations and common cold symptoms in patients exposed to picornavirus respiratory infections. Pleconaril, administered either oral ...
may be useful for the treatment of EV-D68.


Prevention

The CDC recommend "avoiding those who are sick". Since the virus is spread through
saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...
and
phlegm Phlegm (; , ''phlégma'', "inflammation", "humour caused by heat") is mucus produced by the respiratory system, excluding that produced by the throat nasal passages. It often refers to respiratory mucus expelled by coughing, otherwise known as ...
as well as stool,
washing hands Hand washing (or handwashing), also known as hand hygiene, is the act of cleaning one's hands with soap or handwash and water to remove viruses, bacteria, microorganisms, dirt, grease, and other harmful or unwanted substances stuck to the han ...
is important. Sick people can attempt to decrease spreading the virus by basic sanitary measures, such as covering the nose and mouth when sneezing or coughing. Other measures including cleaning surfaces and toys. For hospitalized patients with EV-D68 infection, the CDC recommends transmission-based precautions, i.e. standard precautions, contact precautions, as is recommended for all enteroviruses, and to consider droplet precautions.


Environmental cleaning

According to the CDC in 2003, surfaces in healthcare settings should be cleaned with a hospital-grade disinfectant with an EPA label claim for non-enveloped viruses (e.g.
norovirus Norovirus, also known as Norwalk virus and sometimes referred to as the winter vomiting disease, is the most common cause of gastroenteritis. Infection is characterized by non-bloody diarrhea, vomiting, and stomach pain. Fever or headaches may ...
,
poliovirus Poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species '' Enterovirus C'', in the family of '' Picornaviridae''. There are three poliovirus serotypes, numbered 1, 2, and 3. Poliovirus is composed ...
,
rhinovirus The rhinovirus (from the "nose", , romanized: "of the nose", and the ) is a Positive-sense single stranded RNA virus, positive-sense, single-stranded RNA virus belonging to the genus ''Enterovirus'' in the family ''Picornaviridae''. Rhinoviru ...
).


See also

*
Acute flaccid myelitis Acute flaccid myelitis (AFM) is a serious condition of the spinal cord. Symptoms include rapid onset of arm or leg weakness and decreased reflexes. Difficulty moving the eyes, speaking, or swallowing may also occur. Occasionally, numbness or pain ...
* Polio-like syndrome


References


External links


Enterovirus Portal
– Enterovirus portal at the Virus Pathogen Resource (ViPR) * * {{DEFAULTSORT:Enterovirus 68 Enterovirus-associated diseases Enteroviruses Pediatrics 1962 in science Spring equinox Autumn equinox