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| {{CMG}}; {{AE}} {{chetan}}, {{VB}} | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| {{SK}} EV-68, EV-D68, HRV-87, human rhinovirus type 87 | | {{CMG}}; {{AE}} {{AL}}; {{JS}} {{HK}} |
| | {{Enterovirus 68}} |
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| {{Taxobox | | {{SK}} Enterovirus D-68, EV68, EV-68, EV-D68, EVD68, Acute flaccid paralysis with anterior myelitis, polio-like syndrome |
| | name = ''Enterovirus 68''
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| | virus_group = iv
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| | familia = ''[[Picornaviridae]]''
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| | genus = ''[[Enterovirus]]''
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| | species = ''[[Enterovirus D]]''
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| | subdivision_ranks = Subtype
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| | subdivision = ''Enterovirus 68''
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| | synonyms = Human rhinovirus 87<ref name="Ishiko-2002">{{Cite journal | last1 = Ishiko | first1 = H. | last2 = Miura | first2 = R. | last3 = Shimada | first3 = Y. | last4 = Hayashi | first4 = A. | last5 = Nakajima | first5 = H. | last6 = Yamazaki | first6 = S. | last7 = Takeda | first7 = N. | title = Human rhinovirus 87 identified as human enterovirus 68 by VP4-based molecular diagnosis. | journal = Intervirology | volume = 45 | issue = 3 | pages = 136-41 | month = | year = 2002 | doi = 65866 | PMID = 12403917 }}</ref>
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| ==Overview== | | ==[[Enterovirus 68 overview|Overview]]== |
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| '''Enterovirus 68''' is a member of the genus [[Enterovirus]] in the [[Picornaviridae]] family. It is a non-enveloped, positive-sense, [[RNA virus#Single-stranded RNA viruses and RNA Sense|single-stranded RNA virus]]. It is detected more frequently among pediatric patients in the United States and other countries. While enteroviruses can cause a wide range of symptoms ranging from mild febrile illness to fatal [[meningitis]] and [[encephalitis]], EV-68 is mostly associated with acute respiratory symptoms. In 2014, EV-68 was isolated from 2 children with a [[polio]]-like [[flaccid paralysis]]. However, in 3 more kids with a similar presentation the virus could not be isolated.
| | ==[[Enterovirus 68 historical perspective|Historical Perspective]]== |
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| ==Origin and Serotypes== | | ==[[Enterovirus 68 pathophysiology|Pathophysiology]]== |
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| Enteroviruses were divided into four subgroups based on the diseases they cause in humans. The Four subgroups were [[poliovirus]], [[coxsackie A virus]], [[coxsackie B virus]], and [[echovirus]]. However, on further studies it was found and understood that, some coxsackie and echoviruses had overlapping antigenic properties with respect to the diseases they caused in mice. As a result, they were all later described as [[enterovirus]] and numbered sequentially, beginning with enterovirus 68 (EV68). Current classifications systems are based on molecular, [[antigenic]] as well as biological properties of these viruses. The enterovirus family is presently subgrouped into 5 categories: [[Poliovirus]], [[Enterovirus|Human enterovirus A (HEV-A)]], [[Enterovirus|HEV-B]], [[Enterovirus|HEV-C]] and [[Enterovirus|HEV-D]]. Enterovirus 68 is one of the 3 serotypes in HEV-D subgroup.<ref>{{Cite web | last = | first = | title = ICTV Virus Taxonomy | url = http://www.ictvonline.org/virusTaxonomy.asp?version=2012 | publisher = | date = | accessdate = 28 February 2014 }}</ref>
| | ==[[Enterovirus 68 causes|Causes]]== |
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| EV68 first came into picture when it caused [[pneumonia]] and [[bronchiolitis]] in four children in California in 1962.<ref name="Schieble-1967">{{Cite journal | last1 = Schieble | first1 = JH. | last2 = Fox | first2 = VL. | last3 = Lennette | first3 = EH. | title = A probable new human picornavirus associated with respiratory diseases. | journal = Am J Epidemiol | volume = 85 | issue = 2 | pages = 297-310 | month = Mar | year = 1967 | doi = | PMID = 4960233 }}</ref> Ten times EV68 has been isolated the most recent being 2014. The other isolation's were in the years 1970, 1987, 1994, 1997, 2000 and 2003.<ref name="Khetsuriani-2006">{{Cite journal | last1 = Khetsuriani | first1 = N. | last2 = Lamonte-Fowlkes | first2 = A. | last3 = Oberst | first3 = S. | last4 = Pallansch | first4 = MA. | title = Enterovirus surveillance--United States, 1970-2005. | journal = MMWR Surveill Summ | volume = 55 | issue = 8 | pages = 1-20 | month = Sep | year = 2006 | doi = | PMID = 16971890 }}</ref> Antigen typing reagents are not available in all facilities and hence EV68 involvement might be underestimated.
| | ==[[Enterovirus 68 differential diagnosis|Differentiating Enterovirus 68 from Other Diseases]]== |
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| Human rhinovirus 87 was isolated at the same time as EV68. Corn is a prototype of HRV87 and is very unique in its receptor quality. Cross neutralization and partial capsid sequence studies shave revealed that HRV-87 Corn belongs to the same group as EV68.<ref name="Ishiko-2002">{{Cite journal | last1 = Ishiko | first1 = H. | last2 = Miura | first2 = R. | last3 = Shimada | first3 = Y. | last4 = Hayashi | first4 = A. | last5 = Nakajima | first5 = H. | last6 = Yamazaki | first6 = S. | last7 = Takeda | first7 = N. | title = Human rhinovirus 87 identified as human enterovirus 68 by VP4-based molecular diagnosis. | journal = Intervirology | volume = 45 | issue = 3 | pages = 136-41 | month = | year = 2002 | doi = 65866 | PMID = 12403917 }}</ref> A study on 1962 isolates of EV68 have shown [[genome]] sequences of the 5′-non-translated (NTR) and 3D [[polymerase]] coding regions and complete VP1 [[capsid]] protein coding region sequence. These are closely related with the genome sequence of human rhinovirus 87 (HRV 87) and consistent with the fact that the two viruses are closely related.
| | ==[[Enterovirus 68 epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Epidemiology== | | ==[[Enterovirus 68 risk factors|Risk Factors]]== |
| Enterovirus 68 infection is an extremely rare condition, [[CDC|Center for disease control (CDC)]] found a total of 26 cases in USA from 1987-2005, the most being 11 in the year 2003.<ref name="Khetsuriani-2006">{{Cite journal | last1 = Khetsuriani | first1 = N. | last2 = Lamonte-Fowlkes | first2 = A. | last3 = Oberst | first3 = S. | last4 = Pallansch | first4 = MA. | title = Enterovirus surveillance--United States, 1970-2005. | journal = MMWR Surveill Summ | volume = 55 | issue = 8 | pages = 1-20 | month = Sep | year = 2006 | doi = | PMID = 16971890 }}</ref> The first ever case was discovered in the year 1962 in California from four children with pneumonia and bronchioloitis<ref name="Schieble-1967">{{Cite journal | last1 = Schieble | first1 = JH. | last2 = Fox | first2 = VL. | last3 = Lennette | first3 = EH. | title = A probable new human picornavirus associated with respiratory diseases. | journal = Am J Epidemiol | volume = 85 | issue = 2 | pages = 297-310 | month = Mar | year = 1967 | doi = | PMID = 4960233 }}</ref> and since then only a few cases have been discovered, however there have been recent outbreaks in other parts of the world as well.<ref name="Lauinger-2012">{{Cite journal | last1 = Lauinger | first1 = IL. | last2 = Bible | first2 = JM. | last3 = Halligan | first3 = EP. | last4 = Aarons | first4 = EJ. | last5 = MacMahon | first5 = E. | last6 = Tong | first6 = CY. | title = Lineages, sub-lineages and variants of enterovirus 68 in recent outbreaks. | journal = PLoS One | volume = 7 | issue = 4 | pages = e36005 | month = | year = 2012 | doi = 10.1371/journal.pone.0036005 | PMID = 22536453 }}</ref> | |
| <ref name="Oberste-2004">{{Cite journal | last1 = Oberste | first1 = MS. | last2 = Maher | first2 = K. | last3 = Schnurr | first3 = D. | last4 = Flemister | first4 = MR. | last5 = Lovchik | first5 = JC. | last6 = Peters | first6 = H. | last7 = Sessions | first7 = W. | last8 = Kirk | first8 = C. | last9 = Chatterjee | first9 = N. | title = Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. | journal = J Gen Virol | volume = 85 | issue = Pt 9 | pages = 2577-84 | month = Sep | year = 2004 | doi = 10.1099/vir.0.79925-0 | PMID = 15302951 }}</ref>
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| <ref name="Tokarz-2012">{{Cite journal | last1 = Tokarz | first1 = R. | last2 = Firth | first2 = C. | last3 = Madhi | first3 = SA. | last4 = Howie | first4 = SR. | last5 = Wu | first5 = W. | last6 = Sall | first6 = AA. | last7 = Haq | first7 = S. | last8 = Briese | first8 = T. | last9 = Lipkin | first9 = WI. | title = Worldwide emergence of multiple clades of enterovirus 68. | journal = J Gen Virol | volume = 93 | issue = Pt 9 | pages = 1952-8 | month = Sep | year = 2012 | doi = 10.1099/vir.0.043935-0 | PMID = 22694903 }}</ref> Recently, five cases of unexplained [[flaccid paralysis]] were reported in California. In two of these enterovirus 68 was isolated. However, a clear role in the pathophysiology still needs to be explained.
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| '''Philippines:''' During October 2008-March 2009, an outbreak of HEV68 was detected in the Eastern Visayas region of the Philippines among pediatric patients hospitalized with pneumonia.<ref name="Imamura-2011">{{Cite journal | last1 = Imamura | first1 = T. | last2 = Fuji | first2 = N. | last3 = Suzuki | first3 = A. | last4 = Tamaki | first4 = R. | last5 = Saito | first5 = M. | last6 = Aniceto | first6 = R. | last7 = Galang | first7 = H. | last8 = Sombrero | first8 = L. | last9 = Lupisan | first9 = S. | title = Enterovirus 68 among children with severe acute respiratory infection, the Philippines. | journal = Emerg Infect Dis | volume = 17 | issue = 8 | pages = 1430-5 | month = Aug | year = 2011 | doi = 10.3201/eid1708.101328 | PMID = 21801620 }}</ref>
| | ==[[Enterovirus 68 natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| '''Japan:''' In Japan, first cases were picked up in the year 2005. Since 2005 to 2010 < 10 cases were discovered almost every year, till 2010 where almost 120 cases occurred. Most of these presented with an acute respiratory illness with cough, breathing difficulty, wheezing etc.<ref name="-2011">{{Cite journal | title = Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010. | journal = MMWR Morb Mortal Wkly Rep | volume = 60 | issue = 38 | pages = 1301-4 | month = Sep | year = 2011 | doi = | PMID = 21956405 }}</ref>
| | ==Diagnosis== |
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| '''Netherlands:''' In 2010, all patients with pneumonia and pneumonia like symptoms were prospectively studied and their samples were sequenced. A total of 24 of these were found to be due to enterovirus 68. 50% of them being in the age group < 20 years.
| | [[Enterovirus 68 history and symptoms|History and Symptoms]] | [[Enterovirus 68 physical examination|Physical Examination]] | [[Enterovirus 68 laboratory findings|Laboratory Findings]] | [[Enterovirus 68 chest x ray|Chest X Ray]] |
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| ==Identification of Isolates== | | ==Treatment== |
| Oberste etal used rabbit [[antisera]] for typing of isolates. To the isolates, [[serotype]] specific rabbit [[antisera]] was added. Other method used for sequencing was partial [[sequencing]] of VP1 [[capsid]] [[gene]], using [[primer]] 292 (5'-MIGCIGYIGARACNGG-3') and 222 (5'-CICCIGGIGGIAYRWACAT-3'). The [[serotype]] was determined by comparing partial sequence of isolates with a database containing partial sequences of all known [[enterovirus]] serotypes as described previously by the same group. <ref name="Oberste-2004">{{Cite journal | last1 = Oberste | first1 = MS. | last2 = Maher | first2 = K. | last3 = Schnurr | first3 = D. | last4 = Flemister | first4 = MR. | last5 = Lovchik | first5 = JC. | last6 = Peters | first6 = H. | last7 = Sessions | first7 = W. | last8 = Kirk | first8 = C. | last9 = Chatterjee | first9 = N. | title = Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. | journal = J Gen Virol | volume = 85 | issue = Pt 9 | pages = 2577-84 | month = Sep | year = 2004 | doi = 10.1099/vir.0.79925-0 | PMID = 15302951 }}</ref>
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| Two commercially available, FDA approved multipathogen detection systems - Luminex xTAG RVP and Idaho Technologies (Salt Lake City, Utah) Film array respiratory panel are currently being used in the united states. Both use broadly reactive primers that can pick up both enterovirus as well as human rhinovirus. The results are reported by them as rhino-enterovirus present or absent.<ref name="-2011">{{Cite journal | title = Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010. | journal = MMWR Morb Mortal Wkly Rep | volume = 60 | issue = 38 | pages = 1301-4 | month = Sep | year = 2011 | doi = | PMID = 21956405 }}</ref>
| | [[Enterovirus 68 medical therapy|Medical Therapy]] | [[Enterovirus 68 primary prevention|Primary Prevention]] | [[Enterovirus 68 future or investigational therapies|Future or Investigational Therapies]] |
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| ==Life Cycle== | | ==Case Studies== |
| Enterovirus 68 is acid labile and prefers a lower temperature similar to rhinovirus 87. While other [[enterovirus|enteroviruses]] are more acid stable and can survive at higher temperatures. In a study to predict the effect of acidity and temperature on viral growth, 5 clinical isolates were tested for acid stability versus EV-68 FERMON strain. 10 folds serial dilutions of viral samples were inoculated onto 96 culture plates. They were then incubated at a temperature of 33 or 37° C, in an atmosphere of 5% CO<sub>2</sub>. They were then observed for 7 days to notice any [[cytopathic]] effects. It was shown that all strains showed 100-1000 fold reduction in [[infectivity]] [[titre|titres]], after incubation for 1 hour in pH 3 buffer. The results were in agreement with a similar study done by Blomqvist et al. Also, in the study each of EV 68 strains also grew to a lower titre at 37 °C than at 33 °C.<ref name="Oberste-2004">{{Cite journal | last1 = Oberste | first1 = MS. | last2 = Maher | first2 = K. | last3 = Schnurr | first3 = D. | last4 = Flemister | first4 = MR. | last5 = Lovchik | first5 = JC. | last6 = Peters | first6 = H. | last7 = Sessions | first7 = W. | last8 = Kirk | first8 = C. | last9 = Chatterjee | first9 = N. | title = Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. | journal = J Gen Virol | volume = 85 | issue = Pt 9 | pages = 2577-84 | month = Sep | year = 2004 | doi = 10.1099/vir.0.79925-0 | PMID = 15302951 }}</ref><ref name="Blomqvist-2002">{{Cite journal | last1 = Blomqvist | first1 = S. | last2 = Savolainen | first2 = C. | last3 = Råman | first3 = L. | last4 = Roivainen | first4 = M. | last5 = Hovi | first5 = T. | title = Human rhinovirus 87 and enterovirus 68 represent a unique serotype with rhinovirus and enterovirus features. | journal = J Clin Microbiol | volume = 40 | issue = 11 | pages = 4218-23 | month = Nov | year = 2002 | doi = | PMID = 12409401 }}</ref> It is due to this survivability at lower temperatures and higher pH that most strains are isolated from respiratory specimens. Classically enteroviruses have a predominance of occurrence in summer-fall season and outbreaks occurs in cycles spaced out by several years. EV-68 also shows a similar seasonal distribution, with most cases occurring within and sometimes in later part of the typical enterovirus season.<ref name="-2011">{{Cite journal | title = Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010. | journal = MMWR Morb Mortal Wkly Rep | volume = 60 | issue = 38 | pages = 1301-4 | month = Sep | year = 2011 | doi = | PMID = 21956405 }}</ref>
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| ==Pathogenesis==
| | [[Enterovirus 68 case study one|Case #1]] |
| The clinical role of EV-68 needs to be well defined. A number of cases with pulmonary involvement have been identified in different parts of the world. The clinical sign & symptoms of enterovirus 68 range from mild illness to more severe complications that require hospitalization and in rare cases have been fatal. Major symptoms associated with enterovirus infection includes pharyngeal congestion, headache, myalgia, chills, and sore throat but not increased respiratory rate or difficulty breathing. In a few cases associated specifically with enterovirus 68 some respiratory difficulty along with other symptoms was observed. Most symptomatic cases were among the younger age groups. However, its role in polio like flaccid paralysis needs to be established by further research.
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| ==Prevention and Treatment==
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| ===Prevention===
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| There is no vaccine against non-polio enterovirus infection. Since many people infected with this virus are asymptomatic, it is difficult to prevent non-polio enteroviruses from spreading. Washing your hands often with soap and water, especially after using the toilet and changing diapers, avoiding close contact, such as touching and shaking hands, with people who are sick, and cleaning and disinfecting frequently touched surfaces.
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| ===Treatment===
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| There is no specific treatment for non-polio enterovirus infection. People with mild illness caused by non-polio enterovirus infection typically only need symptomatic treatment. They usually recover completely. However, some illnesses caused by non-polio enteroviruses can be severe enough to require hospitalization.
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| ==Surveillance==
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| Click [[http://www.cdph.ca.gov/programs/vrdl/Documents/Enhanced%20Enterovirus%20Surveillance%20-%20Epi%20Info%20and%20%20Submittal%20Form.doc|here]] to download California department of public health's '''Enterovirus Enhanced Surveillance Submittal Form'''. It provides information onwhen to collect samples, what samples to be collected and how to collect them, their storage and transportation.
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| Click [[http://www.cdph.ca.gov/programs/vrdl/Documents/HospitalizedEnterovirusCaseReport062408.doc|here]] to download California department of public health's '''Hospitalized Enterovirus Case Report Form''' report suspected EV 68 infections in hospitalized patients.
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| == References ==
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| {{Reflist|2}}
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| [[Category:Picornaviruses]]
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| [[Category:Enterovirus]]
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| [[Category:Poliomyelitis]]
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