535:
have mutated with increased virulence made it more easily contractible or that the population and genetics became more susceptible to contraction of the disease. Studies for serial serum antibody titers to the
Enterovirus 71 in blood samples taken yearly from 81 children born in 1988 was conducted from 1989 to 1994 and 1997 to 1999. They discovered an increase in EV71 seroconversion (increased susceptibility to the disease) from 3% to 11% from 1989 to 1997 and by 1997 68% of the children had evidence of being infected by the virus. The virus was also evident in HFMD patients from as early on as 1981. Other studies conducted in early 1999 showed that half the adult population of Taiwan had antibodies against the enterovirus 71 prior to the 1998 outbreak meaning the population of children were more susceptible to the virus. It is possible that prior to the outbreak in 1998 there were severe and fatal cases that went unrecognised as EV71 cases in children who died of unexplained illnesses and studies are still ongoing.
518:
rate. The 1998 outbreak came in two waves to Taiwan. The first wave reached its peak of fatalities in the week of June 7 with cases in all four regions of Taiwan. There were approximately 405 severe cases and 91% of fatal cases were children of under the age of five. After further investigation into the fatalities among children 16% were six months or younger, 43% were from seven to twelve months meaning it was more fatal for children under the age of one. 65 out of 78 patients died from pulmonary edema or haemorrhage making it the most lethal effect which results from the virus. The second wave occurred in the week of
October 4 and had fewer cases that were more confined to Southern Taiwan. Total number of cases of Hand Foot and Mouth Disease (HFMD) and herpangina in Taiwan was 129,106.
527:
more susceptive. In July 1989 a sentinel surveillance system for infectious diseases was established in Taiwan by
Disease, Surveillance and Quarantine Service, Ministry of Health of Taiwan. The sentinel surveillance system is physician based and has approximately 850 Taiwanese physicians participating from various regions all over Taiwan. Public health officers contact the physicians on a weekly basis collecting disease information and on the occasion where there is a suspected outbreak of an infectious disease they are responsible for public notification. After the observed outbreak of HFMD and herpangina in Malaysia in 1997, they were included in the detection system.
357:(CFDA) approved the first EV71 vaccine. The vaccine was administered to approximately 10,000 children between the ages of 6 and 35 months. Of the placebo group, there were 30 cases of hand, foot, and mouth disease (HFMD) reported, and 41 cases of any EV71-associated illness. This can be compared to only 3 cases of HFMD and eight cases of any EV71-related illness reported in the vaccine group. Participants were surveilled from day 56 until the end of the 14-month experiment period, in addition to checkups at months five, eight, eleven, and fourteen. Other experimental vaccines and antiviral agents are being researched. For example, "both
40:
531:
epidemic a warning was released on May 12 for the virus and preventative measures were advised to the public such as practicing better hygiene and isolating infected children. Although public notification had been given and preventatives taken, the number of HFMD cases continued to rise. On May 29 another report system, based on hospitals rather than just physicians, was developed in response to this where all severe and fatal cases were more carefully monitored from 597 hospital and medical centres.
68:
319:
279:. This virus appears to have evolved only recently with the first known strain isolated in 1965. It was associated with an outbreak of neurological disease in the United States in 1969. It then spread to Europe with outbreaks there in Bulgaria (1975) and Hungary (1978). It has since spread to various countries in Asia where it has been responsible for several outbreaks, most recently in Cambodia (2012).
556:
514:
from 1999 to 2000 belonged to genotype B. This study indicated that two genogroups of EV71 capable of inducing severe clinical illness have been circulating in Taiwan. Furthermore, the predominant EV71 genotypes responsible for each of the two major HFMD outbreaks within the 3-year period in Taiwan were different.
526:
The outbreaks of the
Enterovirus 71 in Taiwan and the number of cases and fatalities that resulted became an indication of the significance of the threat of the virus. New anti-viral drugs should be developed and vaccination of children under five years old should be considered in areas the virus is
513:
and VP1 regions of EV71 isolates by reverse transcription-PCR and sequencing were performed to understand the diversity of EV71 in these outbreaks of HFMD. Most EV71 isolates from the 1998 epidemic belonged to genotype C, while only one-tenth of the isolates were genotype B. All EV71 isolates tested
480:
On May 3, 2008, Chinese health authorities reported a major outbreak of EV71 enterovirus in Fuyang City and other localities in Anhui, Zhejiang, and
Guangdong provinces. As of May 3, 2008, 3736 cases occurring mainly in children were reported, with 22 dead and 42 critically ill. Some 415 new cases
534:
Exact reasons behind the outbreaks are hard to and yet to be defined however through the reporting systems developed, detection of the virus is of large significance and gives way for further study and investigation. Possible reasons behind the developments of the outbreaks are that the virus may
385:
determined the structure of EV71 in 2012. Researchers observed movements resembling breathing in the virus, and found that this accompanied the infection process, together with a small molecule picked up from the body's cells and used to switch state. This particular molecule must be discarded in
517:
Significant outbreaks of the
Enterovirus 71 (EV71) occurred in 1998, 2000 and 2001 with 78 deaths in 1998, 25 in 2000 and 26 in 2001. There are two patterns observed in outbreaks of the virus where they may be small with occasional cases resulting in death or they are severe with a high fatality
530:
In March 1998, under the sentinel surveillance system, it was noticed that there was an increasing number of HFMD cases and herpangina in Taiwan. By the end of April that year, numbers of cases involving children HFMD had increased significantly. Due to the presence of a possible threat of an
282:
The strains fall into six genogroups named A to F. Both the B and C genogroups have been subdivided into B0–B5 and C1–C5. The genogroup C appears to have evolved ~1970 while the A and B taxa evolved prior to this. Genogroup D was identified in India only and genogroups E and F in Africa only.
508:
Enteroviruses were isolated from a total of 1,892 patients in this laboratory during this period. Of the virus isolates, enterovirus 71 (EV71) was diagnosed in 44.4% of the patients (132 of 297) in 1998, 2% (13 of 646) in 1999, and 20.5% (195 of 949) in 2000. Genetic analyses of the
1165:
411:. Most died within 24 hours and had exhibited symptoms including respiratory illnesses, fever and generalized neurological abnormalities. An initial sampling taken from 24 patients found that 15 tested positive for EV71 on July 6, 2012. The
1518:
Zheng, Z. M.; He, P. J.; Caueffield, D.; Neumann, M.; Specter, S.; Baker, C. C.; Bankowski, M. J. (1995). "Enterovirus 71 isolated from China is serologically similar to the prototype E71 BrCr strain but differs in the 5'-noncoding region".
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HFMD was recognized in China in the 1980s, and EV71 was first isolated in China from HFMD vesicle fluid in 1987 by Zhi-Ming Zheng at Virus
Research Institute, Hubei Medical University. From 1999 to 2004, there were no epidemics of
286:
An analysis of strains isolated in Europe (Austria, France and
Germany) showed that the clades C1b and C2b originated in 1994 (95% confidence interval 1992.7–1995.8) and 2002 (95% confidence interval 2001.6–2003.8), respectively.
722:
543:
Vietnam recorded 63,780 cases of hand, foot and mouth disease in the first seven months of 2012. According to Tran Minh Dien, vice director of the
National Hospital for Children, about 58.7% percent were caused by EV71.
1646:
453:, but each year there were small, local outbreaks associated with only a few cases of neurological disease and no reported fatalities. Genetic analysis revealed 19 cases of EV71 among 147 children who had
1161:
461:
during this time. Until 2008, no large EV71 epidemic had been reported on the
Chinese mainland, but sporadic infections were common in the southeast coastal area as well as in inland regions, such as
399:
In June 2013, an outbreak of four cases was noted in Sydney. Approximately 100 more children are believed to have been infected, and a panel of doctors are monitoring the situation at present.
1023:
Ma E, Fung C, Yip SH, Wong C, Chuang SK, Tsang T (Aug 2011). "Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks".
908:
Huang SW, Cheng D, Wang JR. Enterovirus A71: virulence, antigenicity, and genetic evolution over the years. J Biomed Sci. 2019 Oct 21;26(1):81. doi: 10.1186/s12929-019-0574-1. Review.
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1399:
1117:
Mao, Qun-ying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun (May 2016). "EV71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (HFMD)".
1939:
1679:
1650:
1189:"Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial"
956:
Bernstein H, Bernstein C, Michod RE. Sex in microbial pathogens. Infect Genet Evol. 2018 Jan;57:8-25. doi: 10.1016/j.meegid.2017.10.024. Epub 2017 Oct 27. Review.
940:
Barr JN, Fearns R. How RNA viruses maintain their genome integrity. J Gen Virol. 2010 Jun;91(Pt 6):1373-87. doi: 10.1099/vir.0.020818-0. Epub 2010 Mar 24. Review.
1478:
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order to start an infection, and new research will be aimed at creating a synthetic replica that would bond strongly to the virus and stop the infection process.
1499:
Zheng ZM, Zhang JH, Zhu WP, He PJ (1989). "First isolation of enterovirus type 71 from vesicle fluid of an adult patient with hand-foot-mouth disease in China".
418:
On 15 July 2012, it was announced that no further cases had been noted in Cambodia, and that the deaths were a result of a combination of infections with EV 71,
1993:
1452:
353:
Ltd., a pharmaceutical company in China, conducted an experimental trial for an EV71 vaccination, which was completed in March 2013. In December 2015, the
1426:
808:"Molecular Comparison and Evolutionary Analyses of VP1 Nucleotide Sequences of New African Human Enterovirus 71 Isolates Reveal a Wide Genetic Diversity"
496:) were reported in China. All the children infected were aged below 6, with most of them being under 2. As of May, 7 contagious HFMD led to 28 deaths.
1725:
1603:
473:. From 1998 to 2004, the only EV71 viruses identified on mainland China belonged to the genotype C4, indicating far less variety in China than in
1700:
337:
The basic reproductive number (R0) for enterovirus 71 (EV71) was estimated to a median of 5.48 with an interquartile range of 4.20 to 6.51.
481:
were reported in 24 hours in Fuyang City alone. As of May 5, 2008, 6,300 were sickened by the viral outbreak which killed another child in
1910:
865:
Mirand A, Schuffenecker I, Henquell C, Billaud G, Jugie G, Falcon D, Mahul A, Archimbaud C, Terletskaia-Ladwig E, et al. (2009).
354:
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1343:
1624:
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From April through July 2012, at least 64 children died and two survived from a disease affecting children under 7 years old in
327:
47:
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1671:
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450:
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254:
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Zhu, Feng-Cai; Liang, Zheng-Lun; Li, Xiu-Ling; Ge, Heng-Ming; Meng, Fan-Yue; Mao, Qun-Ying; et al. (23 March 2013).
674:"Change of Major Genotype of Enterovirus 71 in Outbreaks of Hand-Foot-and-Mouth Disease in Taiwan between 1998 and 2000"
599:
299:
1373:
67:
283:
Phylogenetic studies performed on partial sequences of viruses from India suggest that additional genogroups exist.
1998:
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1448:
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province, with scores more in 4 other provinces. 8,531 cases of children infected with hand-foot-mouth disease (
1422:
924:
Kirkegaard K, Baltimore D. The mechanism of RNA recombination in poliovirus. Cell. 1986 Nov 7;47(3):433-43.
1733:
867:"Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries"
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are present in the same host cell. The mechanism of recombination likely involves strand switching by the
2021:
1961:
291:
39:
819:
62:
485:, raising the death toll to 26 children, with 1,198 other children affected in that province alone.
1704:
262:
178:
626:"Lactoferrin inhibits enterovirus 71 infection of human embryonal rhabdomyosarcoma cells in vitro"
415:
noted that the cause of the outbreak has not been fully solved and that more analysis was needed.
273:
This virus is a member of the enterovirus species A. Species A was formerly assigned to the genus
1544:
1216:
1142:
1048:
424:
199:
1701:"news.xinhuanet.com, Xinhua's tally: Death toll of hand-foot-mouth disease rises to 28 in China"
1914:
1892:
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1794:
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1134:
1099:
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1005:
957:
941:
925:
909:
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703:
647:
1287:"Ribavirin reduces mortality in enterovirus 71-infected mice by decreasing viral replication"
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occur commonly in EV-A71 virus infections. Recombination can occur when at least two viral
322:
Enterovirus genome, polyprotein processing cascade, and architecture of enterovirus capsid.
257:
in children. It was first isolated and characterized from cases of neurological disease in
1335:
350:
318:
128:
1647:"www.inthenews.co.uk, Hand-foot-mouth epidemic continues to infect children across China"
823:
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2015:
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family, notable for its role in causing epidemics of severe neurological disease and
104:
1548:
1220:
1146:
1052:
723:"Laboratory Investigation of a Suspected Enterovirus 71 Outbreak in Central Taiwan"
419:
116:
1130:
1036:
832:
668:
Wang, Jen-Ren; Tuan, Yen-Chang; Tsai, Huey-Pin; Yan, Jing-Jou; Liu, Ching-Chuan;
1833:
1816:
689:
362:
243:
164:
1984:
1236:"DNA vaccine constructs against enterovirus 71 elicit immune response in mice"
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50:
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669:
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1936:"Bệnh TCM tăng 10 lần so với năm trước-Benh tay chan mieng |Suc khoe"
1540:
1252:
929:
1978:
572:, a similar, related virus also first isolated in California in the 1960s
482:
458:
446:
408:
306:. In addition to being a source of sequence diversity, recombination in
756:"Pan-viral serology implicates enteroviruses in acute flaccid myelitis"
500:
reported the number of people infected also rose from 4,000 to 15,799.
462:
555:
1449:"Officials make break in baffling disease killing Cambodian children"
497:
474:
382:
358:
331:
295:
17:
1955:
1302:
642:
625:
489:
470:
317:
238:
79:
54:
349:
agent known to be effective in treating EV71 infection. However,
493:
1959:
1765:"Enterovirus 71 outbreaks, Taiwan: Occurrence and Recognition"
1672:"6,300 sick, 26 dead in China viral outbreak | The Star"
1066:
Lin, Jing-Yi; Kung, Yu-An; Shih, Shin-ru (3 September 2019).
378:
365:
were found to be potent inhibitors of EV71 infection" and "
801:
799:
754:
Schubert, Ryan D.; Hawes, Isobel A.; et al. (2019).
488:
Specifically, an additional 5,151 cases were reported in
326:
The receptors for EV71 and CVA16 have been identified as
310:
appears to be an adaptation for repairing genome damage.
302:(copy-choice recombination), a mechanism demonstrated in
1863:"Sentinel Surveillance for Enterovirus 71, Taiwan, 1998"
1423:"Mystery illness claims dozens of Cambodian children"
975:"Cellular receptors for human enterovirus species A."
721:
SY Wang; CL Lin; HC Sun; HY Chen (25 December 1999).
596:"Human enterovirus 71 polyprotein gene, complete cds"
1604:
China orders heightened efforts to stop deadly virus
578:, mouth blisters that can be caused by enteroviruses
1968:
1366:"Flu drug 'shows promise' in overcoming resistance"
1856:
1854:
1852:
1911:"WPRO | Hand, Foot and Mouth Disease (HFMD)"
1475:"Mystery illness in Cambodia solved, doctors say"
1703:. News.xinhuanet.com. 2008-05-07. Archived from
1285:Li ZH, Li CM, Ling P, et al. (March 2008).
684:(1). American Society for Microbiology: 10–5.
1234:Tung WS, Bakar SA, Sekawi Z, Rosli R (2007).
1068:"Antivirals and vaccines for Enterovirus A71"
261:in 1969. Enterovirus 71 infrequently causes
8:
1758:
1756:
1754:
1752:
1750:
904:
902:
377:A joint UK and Chinese team working at the
1956:
1810:
1808:
1162:"Vaccine Blocks Hand, Foot, Mouth Disease"
330:and scavenger receptor class B, member 2 (
38:
29:
1886:
1832:
1817:"An Epidemic of Enterovirus 71 in Taiwan"
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831:
779:
697:
641:
1560:
1558:
663:
661:
624:Lin TY, Chu C, Chiu CH (October 2002).
587:
1336:"Diamond to shine light on infections"
1168:from the original on February 17, 2018
381:'s national synchrotron facility near
369:could be a potential anti-EV71 drug."
1376:from the original on 24 February 2013
1346:from the original on 17 February 2013
806:Bessaud M, et al. (March 2014).
619:
617:
602:from the original on 12 December 2014
7:
1726:"28 Chinese children die from virus"
432:in the treatment of the infections.
334:); both are transmembrane proteins.
1821:The New England Journal of Medicine
355:China Food and Drug Administration
25:
1649:. Inthenews.co.uk. Archived from
1617:"China virus toll continues rise"
1575:"China on alert as virus spreads"
1402:from the original on 22 June 2013
1396:"Fatal fears over 'modern polio'"
1861:Wu, Trong-Neng (May–June 1999).
1627:from the original on May 8, 2008
1585:from the original on May 6, 2008
1455:from the original on 8 July 2012
1429:from the original on 6 July 2012
678:Journal of Clinical Microbiology
554:
328:P-selectin glycoprotein ligand-1
66:
1942:from the original on 2012-05-29
1815:Ho, Monto (23 September 1999).
1682:from the original on 2017-10-22
1481:from the original on 2012-07-12
973:Nishimura Y, Shimizu H (2012).
1913:. Wpro.who.int. Archived from
1:
1763:Lin, Tzou-Yien (March 2003).
1334:Amos, J. (17 February 2013).
1205:10.1016/S0140-6736(12)61764-4
1131:10.1586/14760584.2016.1138862
1072:Journal of Biomedical Science
736:(12): 215–219. Archived from
455:hand, foot, and mouth disease
443:hand, foot, and mouth disease
255:hand, foot, and mouth disease
1867:Emerging Infectious Diseases
1769:Emerging Infectious Diseases
1037:10.1097/INF.0b013e3182116e95
833:10.1371/journal.pone.0090624
300:RNA-dependent RNA polymerase
1834:10.1056/nejm199909233411301
1521:Journal of Medical Virology
1421:Kwok, Yenni (5 July 2012).
1160:Walsh, Nancy (2013-05-29).
690:10.1128/JCM.40.1.10-15.2002
2043:
451:People's Republic of China
1477:. CNN.com. 11 July 2012.
1119:Expert Review of Vaccines
1085:10.1186/s12929-019-0560-7
772:10.1038/s41591-019-0613-1
522:Development and detection
413:World Health Organization
205:
198:
61:
57:. Scale bar, 50 nm.
46:
37:
32:
2027:Infraspecific virus taxa
991:10.3389/fmicb.2012.00105
1398:. 7News. 19 June 2013.
290:Intra- and inter-typic
1879:10.3201/eid0503.990321
1781:10.3201/eid0903.020285
1533:10.1002/jmv.1890470209
884:10.1099/vir.0.021741-0
323:
1253:10.1186/1479-0556-5-6
730:Epidemiology Bulletin
321:
265:permanent paralysis.
208:Enterovirus 71 (EV71)
1451:. CNN. 8 July 2012.
1372:. 21 February 2013.
1025:Pediatr Infect Dis J
211:Human rhinovirus A71
63:Virus classification
1240:Genet Vaccines Ther
1199:(9871): 1037–1045.
824:2014PLoSO...990624B
263:polio-like syndrome
214:Human rhinovirus 71
53:of Enterovirus A71
425:Streptococcus suis
324:
2009:
2008:
1962:Taxon identifiers
1938:. Hn.24h.com.vn.
1501:Virologica Sinica
1164:. MedPage Today.
766:(11): 1748–1752.
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672:(January 2002).
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1623:. May 5, 2008.
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