Enterovirus 68

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Enterovirus D68
Ev-d68-photo-1.jpg
Enterovirus D68
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Picornavirales
Family: Picornaviridae
Genus: Enterovirus
Species:
Enterovirus D
Serotype:
Enterovirus D68
Synonyms
  • EV-D68
  • Human rhinovirus 87 [1]

Enterovirus D68 (EV-D68) is a member of the Picornaviridae family, an enterovirus. First isolated in California in 1962 and once considered rare, it has been on a worldwide upswing in the 21st century. [2] [3] [4] It is suspected of causing a polio-like disorder called acute flaccid myelitis (AFM).

Contents

Virology

Enterovirus genome, polyprotein processing cascade, and architecture of enterovirus capsid. DOI 10.5772 52087 Image1.png
Enterovirus genome, polyprotein processing cascade, and architecture of enterovirus capsid.

EV-D68 is one of the more than one hundred types of enteroviruses, a group of ssRNA viruses containing the polioviruses, coxsackieviruses, and echoviruses. It is unenveloped. Unlike all other enteroviruses, EV-D68 displays acid lability and a lower optimum growth temperature, both characteristic features of the human rhinoviruses. It was previously called human rhinovirus 87 by some researchers. [5]

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. [6]

Epidemiology

Since its discovery in 1962, EV-D68 had been described mostly sporadically in isolated cases. Six clusters (10 or more cases) or outbreaks between 2005 and 2011 have been reported from the Philippines, Japan, the Netherlands, and the states of Georgia, Pennsylvania and Arizona in the United States. [7] EV-D68 was found in 2 of 5 children during a 2012/13 cluster of polio-like disease in California. [8] In 2016, 29 cases were reported in Europe (5 in France and Scotland. 3 each in Sweden, Norway and Spain). [9]

Cases have been described to occur late in the enterovirus season (roughly the period of time between the spring equinox and autumn equinox), [7] which is typically during August and September in the Northern Hemisphere.

Predisposing factors

Children less than 5 years old and children with asthma appear to be most at risk for the illness, [10] although illness in adults with asthma and immunosuppression have also been reported. [7]

2014 North American outbreak

In August 2014, the virus caused clusters of respiratory disease in the United States, [11] resulting in the largest documented outbreak of EV-D68 [12] with 2,287 confirmed cases and 14 deaths among children. [13]

Signs and symptoms

EV-D68 almost exclusively causes respiratory illness, 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-like symptoms. Like all enteroviruses, it can cause variable rashes, abdominal pain and soft stools. Initial symptoms are similar to those for the common cold, including a runny nose, sore throat, cough, and fever. [14] As the disease progresses, more serious symptoms may occur, including difficulty breathing as in pneumonia, reduced alertness, a reduction in urine production, and dehydration, and may lead to respiratory failure. [7] [14]

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. [15]

Acute flaccid myelitis

The virus is one cause of acute flaccid myelitis, a rare muscle weakness, usually due to polio. In 2014, the cases of two California children were described who tested positive for the virus and had paralysis of one or more limbs reaching peak severity within 48 hours of onset. "Recovery of motor function was poor at 6-month follow-up." [16] As of October 2014, the US Centers for Disease Control and Prevention (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. [17] As of October 2014 it was believed that the actual number of cases might be 100 or more. [18] [19] As of 2018 the link of EV-D68 and the paralysis is strong, meeting six Bradford Hill criteria fully and two partially. [6] [20] 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." [21] In 2019, the CDC has published that AFM is caused by Enterovirus D68. [22]

Diagnosis

In 2014, a real-time PCR test to speed up detection was developed by CDC. [23]

Treatment

There is no specific treatment and no vaccine, so the illness has to run its course; treatment is directed against symptoms (symptomatic treatment). Most people recover completely; however, some need to be hospitalized, and some have died as a result of the virus. [7] Five EV-D68 paralysis cases were unsuccessfully treated with steroids, intravenous immunoglobulin and/or plasma exchange. The treatment had no apparent benefit as no recovery of motor function was seen. [16] A 2015 study suggested the antiviral drug pleconaril may be useful for the treatment of EV-D68. [24]

Prevention

The CDC recommend "avoiding those who are sick". Since the virus is spread through saliva and phlegm as well as stool, washing hands is important. [14] Sick people can attempt to decrease spreading the virus by basic sanitary measures, such as covering the nose and mouth when sneezing or coughing. [10] Other measures including cleaning surfaces and toys. [14]

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, [25] and to consider droplet precautions. [26]

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, poliovirus, rhinovirus). [27]

See also

Related Research Articles

<span class="mw-page-title-main">Polio</span> Infectious disease caused by poliovirus

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 symptoms develop such as headache, neck stiffness, and paresthesia. These symptoms usually pass within one or two weeks. A less common symptom is permanent paralysis, and possible death in extreme cases. Years after recovery, post-polio syndrome may occur, with a slow development of muscle weakness similar to what the person had during the initial infection.

<span class="mw-page-title-main">Bornholm disease</span> Medical condition

Bornholm disease, also known as epidemic pleurodynia, is a condition characterized by myositis of the abdomen or chest caused by the Coxsackie B virus or other viruses. The myositis manifests as an intermittent stabbing pain in the musculature that is seen primarily in children and young adults.

<span class="mw-page-title-main">Rhinovirus</span> Genus of viruses (Enterovirus)

The rhinovirus is a positive-sense, single-stranded RNA virus belonging to the genus Enterovirus in the family Picornaviridae. Rhinovirus is the most common viral infectious agent in humans and is the predominant cause of the common cold.

<span class="mw-page-title-main">Hand, foot, and mouth disease</span> Common human disease caused by a group of viruses

Hand, foot, and mouth disease (HFMD) is a common infection caused by a group of enteroviruses. It typically begins with a fever and feeling generally unwell. This is followed a day or two later by flat discolored spots or bumps that may blister, on the hands, feet and mouth and occasionally buttocks and groin. Signs and symptoms normally appear 3–6 days after exposure to the virus. The rash generally resolves on its own in about a week. Fingernail and toenail loss may occur a few weeks later, but they will regrow with time.

Myelitis is inflammation of the spinal cord which can disrupt the normal responses from the brain to the rest of the body, and from the rest of the body to the brain. Inflammation in the spinal cord can cause the myelin and axon to be damaged resulting in symptoms such as paralysis and sensory loss. Myelitis is classified to several categories depending on the area or the cause of the lesion; however, any inflammatory attack on the spinal cord is often referred to as transverse myelitis.

<span class="mw-page-title-main">Coxsackievirus</span> Virus that causes digestive upset and sometimes heart damage

Coxsackieviruses are a few related enteroviruses that belong to the Picornaviridae family of nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus Enterovirus, which also includes poliovirus and echovirus. Enteroviruses are among the most common and important human pathogens, and ordinarily its members are transmitted by the fecal–oral route. Coxsackieviruses share many characteristics with poliovirus. With control of poliovirus infections in much of the world, more attention has been focused on understanding the nonpolio enteroviruses such as coxsackievirus.

<span class="mw-page-title-main">Pulse Polio</span> Indian governmental immunisation campaign

Pulse Polio is an immunisation campaign established by the government of India to eliminate poliomyelitis (polio) in India by vaccinating all children under the age of five years against the polio virus. The project fights polio through a large-scale, pulse vaccination programme and monitoring for poliomyelitis cases.

<i>Enterovirus</i> Genus of viruses

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.

<span class="mw-page-title-main">Pleconaril</span> Antiviral drug

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 orally or intranasally, is active against viruses in the Picornaviridae family, including Enterovirus and Rhinovirus. It has shown useful activity against the dangerous enterovirus D68.

Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause. This abnormal condition may be caused by disease or by trauma affecting the nerves associated with the involved muscles. For example, if the somatic nerves to a skeletal muscle are severed, then the muscle will exhibit flaccid paralysis. When muscles enter this state, they become limp and cannot contract. This condition can become fatal if it affects the respiratory muscles, posing the threat of suffocation. It also occurs in the spinal shock stage in complete transection of the spinal cord occurring in injuries such as gunshot wounds.

<span class="mw-page-title-main">Vincent Racaniello</span> American biologist

Vincent R. Racaniello is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University's College of Physicians and Surgeons. He is a co-author of a textbook on virology, Principles of Virology.

<span class="mw-page-title-main">Enterovirus 71</span> Species of virus

Enterovirus 71 (EV71), also known as Enterovirus A71 (EV-A71), is a virus of the genus Enterovirus in the Picornaviridae family, notable for its role in causing epidemics of severe neurological disease and hand, foot, and mouth disease in children. It was first isolated and characterized from cases of neurological disease in California in 1969. Enterovirus 71 infrequently causes polio-like syndrome permanent paralysis.

<span class="mw-page-title-main">W. Ian Lipkin</span> Professor, microbiologist, epidemiologist

Walter Ian Lipkin is the John Snow Professor of Epidemiology at the Mailman School of Public Health at Columbia University and a professor of Neurology and Pathology at the College of Physicians and Surgeons at Columbia University. He is also director of the Center for Infection and Immunity, an academic laboratory for microbe hunting in acute and chronic diseases. Lipkin is internationally recognized for his work with West Nile virus, SARS and COVID-19.

<span class="mw-page-title-main">Acute hemorrhagic conjunctivitis</span> Medical condition

Acute hemorrhagic conjunctivitis (AHC) is a derivative of the highly contagious conjunctivitis virus, otherwise known as pink eye. Symptoms include excessively red, swollen eyes as well as subconjunctival hemorrhaging. Currently, there is no known treatment and patients are required to merely endure the symptoms while the virus runs its five- to seven-day course. While it was first identified in Ghana, the virus has now been seen in China, India, Egypt, Cuba, Singapore, Taiwan, Japan, Pakistan, Thailand, and the United States.

<i>Enterovirus C</i> Species of virus

Enterovirus C is a species of enterovirus. Its best known subtype is poliovirus, the cause of poliomyelitis. There are three serotypes of poliovirus, PV1, PV2, and PV3. Other subtypes of Enterovirus C include EV-C95, EV-C96, EV-C99, EV-C102, EV-C104, EV-C105, EV-C109, EV-C116, EV-C117, and EV-C118. Some non-polio types of Enterovirus C have been associated with the polio-like condition AFP, including 2 isolates of EV-C95 from Chad.

<i>Enterovirus D</i> Species of virus

Enterovirus D is a species of enterovirus which causes disease in humans. Five subtypes have been identified to date:

Polio-like syndrome is a general description of a group of symptoms which mimic polio, including rarely permanent paralysis. Various triggers have been found, including some viruses from the same virus group as polio: enterovirus 68, enterovirus 71, and coxsackievirus A7. These are suspected in many cases of acute flaccid myelitis. Other non-virus causes of polio-like symptoms are observed, though rarely, from snake bite, spider bite, scorpion sting, tick bite, or chemicals such as arsenic and organophosphorus insecticides.

<span class="mw-page-title-main">2014 enterovirus D68 outbreak</span> Disease outbreak in the United States

In August 2014, enterovirus D68 caused clusters of respiratory disease in the United States. Cases of EV-D68 have occurred in the U.S. for decades, having first been detected in California in 1962. According to the Division of Viral Diseases at the National Center for Immunization and Respiratory Diseases EV-D68 "is one of the most rarely reported serotypes, with only 26 reports throughout the 36-year study period ."

<span class="mw-page-title-main">Acute flaccid myelitis</span> Condition of the spinal cord with symptoms of rapid onset of arm or leg weakness

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 may be present. Complications can include trouble breathing.

The 1997 Sarawak HFMD outbreak is a hand, foot, and mouth disease (HFMD) outbreak from April until June caused by the Enterovirus 71 (EV-71) affecting 600 children in the state of Sarawak in Malaysia. Sarawak is the first state in Malaysia that reported HFMD outbreak. An estimated 28 to 31 of the infected children died as a result. The affected children are aged between five months to six years.

References

  1. ↑ Ishiko, H.; Miura, R.; Shimada, Y.; Hayashi, A.; Nakajima, H.; Yamazaki, S.; Takeda, N. (2002). "Human Rhinovirus 87 Identified as Human Enterovirus 68 by VP4-Based Molecular Diagnosis". Intervirology. 45 (3): 136–41. doi:10.1159/000065866. PMID   12403917. S2CID   29128353.
  2. ↑ Oberste, M. S. (2004). "Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses". Journal of General Virology. 85 (9): 2577–2584. doi: 10.1099/vir.0.79925-0 . PMID   15302951.
  3. ↑ Lauinger, I. L.; Bible, J. M.; Halligan, E. P.; Aarons, E. J.; MacMahon, E.; Tong, C. Y. W. (2012). "Lineages, Sub-Lineages and Variants of Enterovirus 68 in Recent Outbreaks". PLOS ONE. 7 (4): e36005. Bibcode:2012PLoSO...736005L. doi: 10.1371/journal.pone.0036005 . PMC   3335014 . PMID   22536453.
  4. ↑ Tokarz, R.; Firth, C.; Madhi, S. A.; Howie, S. R. C.; Wu, W.; Sall, A. A.; Haq, S.; Briese, T.; Lipkin, W. I. (2012). "Worldwide emergence of multiple clades of enterovirus 68". Journal of General Virology. 93 (Pt 9): 1952–1958. doi:10.1099/vir.0.043935-0. PMC   3542132 . PMID   22694903.
  5. ↑ Blomqvist, S.; Savolainen, C.; Raman, L.; Roivainen, M.; Hovi, T. (2002). "Human Rhinovirus 87 and Enterovirus 68 Represent a Unique Serotype with Rhinovirus and Enterovirus Features". Journal of Clinical Microbiology. 40 (11): 4218–23. doi:10.1128/JCM.40.11.4218-4223.2002. PMC   139630 . PMID   12409401.
  6. 1 2 Dyda, Amalie; Stelzer-Braid, Sacha; Adam, Dillon; Chughtai, Abrar A; MacIntyre, C Raina (2018). "The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) – what is the evidence for causation?". Eurosurveillance. 23 (3). doi:10.2807/1560-7917.ES.2018.23.3.17-00310. PMC   5792700 . PMID   29386095.
  7. 1 2 3 4 5 "Clusters of Acute Respiratory Illness Associated with Human Enterovirus 68 — Asia, Europe, and United States, 2008–2010". Morbidity and Mortality Weekly Report (MMWR). 60(38): CDC. 30 September 2011. pp. 1301–1304. Retrieved 9 September 2014.{{cite web}}: CS1 maint: location (link)
  8. ↑ Brown, Eryn (23 February 2014). "Mysterious polio-like illnesses reported in some California children". LA Times. Retrieved 25 February 2014.
  9. ↑ Knoester, Marjolein (September 2018). "Twenty-Nine Cases of Enterovirus-D68 Associated Acute Flaccid Myelitis in Europe 2016; A Case Series and Epidemiologic Overview". The Pediatric Infectious Disease Journal. 38 (1): 16–21. doi:10.1097/INF.0000000000002188. PMC   6296836 . PMID   30234793.
  10. 1 2 Gillian Mohney (6 September 2014). "Respiratory Virus Sickening Children in Colorado". ABC News.
  11. ↑ "Severe Respiratory Illness Associated with Enterovirus D68 — Missouri and Illinois, 2014". Morbidity and Mortality Weekly Report (MMWR). 63(Early Release). CDC: 1–2. 8 September 2014. Retrieved 9 September 2014.
  12. ↑ Grizer, Cassandra S.; Messacar, Kevin; Mattapallil, Joseph J. (15 February 2024). "Enterovirus-D68 – a reemerging non-polio enterovirus that causes severe respiratory and neurological disease in children". Frontiers in Virology. 4. doi: 10.3389/fviro.2024.1328457 . ISSN   2673-818X. PMC   11378966 . PMID   39246649.
  13. ↑ Shi, Yingying; Ran, Qinqin; Wang, Xiaochen; Shi, Lu (2023). "Seroprevalence of Enterovirus D68 Infection among Humans: A Systematic Review and Meta-Analysis". Intervirology. 66 (1): 111–121. doi:10.1159/000531853. ISSN   1423-0100. PMC   10614446 . PMID   37793363.
  14. 1 2 3 4 "Enterovirus D68: 3 confirmed cases in B.C.'s Lower Mainland". CBC News. 16 September 2014. Retrieved 17 September 2014.
  15. ↑ "Rhode Island Child Dies From Complications Of Enterovirus That Has Been Affecting Kids Nationwide". CBS Connecticut. 1 October 2014.
  16. 1 2 Alexandra Roux; Sabeen Lulu; Emmanuelle Waubant; Carol Glaser; Keith Van Haren (29 April 2014). "A Polio-Like Syndrome in California: Clinical, Radiologic, and Serologic Evaluation of Five Children Identified by a Statewide Laboratory over a Twelve-Months Period". Poster Session III: Child Neurology and Developmental Neurology III. Archived from the original on 10 September 2014. Retrieved 9 September 2014.
  17. ↑ "CDC continues investigation of neurologic illness; will issue guidelines". AAP News. The American Academy of Pediatrics. 3 October 2014. Retrieved 6 October 2014.
  18. ↑ Dan Hurley (24 October 2014). "The mysterious polio-like disease affecting American kids". The Atlantic.
  19. ↑ Hurley, Dan (2014). "Cases of Acute Flaccid Myelitis in Children Suspected in Multiple States, Prompting Comparisons to Polio". Neurology Today. 14 (21): 1. doi:10.1097/01.NT.0000457136.07281.dd.
  20. ↑ Peter Dockrill. We May Finally Know The Cause of Polio-Like Illness Paralysing Children Around The World 23 January 2018, Sciencealert
  21. ↑ "Transcript for CDC Telebriefing: Update on Acute Flaccid Myelitis (AFM) in the U.S. | CDC Online Newsroom | CDC". www.cdc.gov. 12 April 2019.
  22. ↑ "Notes from the Field: Six Cases of Acute Flaccid Myelitis in Children — Minnesota, 2018". CDC. CDC. 19 April 2019. Retrieved 25 October 2019.
  23. ↑ "real-time PCR test to speed up EV-D68 detection" . Retrieved 17 October 2014.
  24. ↑ Liu, Y; Sheng, J; Fokine, A; Meng, G; Shin, W.-H; Long, F; Kuhn, R. J; Kihara, D; Rossmann, M. G (2015). "Structure and inhibition of EV-D68, a virus that causes respiratory illness in children". Science. 347 (6217): 71–4. Bibcode:2015Sci...347...71L. doi:10.1126/science.1261962. PMC   4307789 . PMID   25554786.
  25. ↑ Siegel JD; Rhinehart E; Jackson M; Chiarello L & Healthcare Infection Control Practices Advisory Committee (December 2007). "2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings". Am J Infect Control. 35 (10 Suppl 2): S65-164. doi:10.1016/j.ajic.2007.10.007. PMC   7119119 . PMID   18068815.
  26. ↑ "Severe Respiratory Illness Associated with Enterovirus D68 – Multiple States, 2014". CDCHAN-00369. CDC-Health Alert Network. 12 September 2014. Archived from the original on 17 September 2014. Retrieved 17 September 2014.
  27. ↑ CDC (2003). "Guidelines for Environmental Infection Control in Health-Care Facilities" (PDF). Retrieved 17 September 2014.

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