Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in Korea, 2009

  • Cho, Hye-Kyung (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Lee, Na-Yong (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Lee, Hyun-Ju (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Kim, Hae-Soon (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Seo, Jeong-Wan (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Hong, Young-Mi (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Lee, Seung-Joo (Department of Pediatrics, School of Medicine, Ewha Womans University) ;
  • Lee, Sun-Wha (Department of Radiology, School of Medicine, Ewha Womans University) ;
  • Cheon, Doo-Sung (Division of Enteric and Hepatitis Viruses, Korea National Institute of Health, Korea Centers for Disease Control and Prevention) ;
  • Hong, Ji-Young (Division of Enteric and Hepatitis Viruses, Korea National Institute of Health, Korea Centers for Disease Control and Prevention) ;
  • Kang, Byung-Hak (Division of Enteric and Hepatitis Viruses, Korea National Institute of Health, Korea Centers for Disease Control and Prevention) ;
  • Kim, Jong-Hyun (Division of Enteric and Hepatitis Viruses, Korea National Institute of Health, Korea Centers for Disease Control and Prevention) ;
  • Kim, Kyung-Hyo (Department of Pediatrics, School of Medicine, Ewha Womans University)
  • Received : 2009.10.21
  • Accepted : 2010.01.14
  • Published : 2010.05.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Hand-foot-mouth disease (HFMD) is a common viral illness in children, which is usually mild and self-limiting. However, in recent epidemics of HFMD in Asia, enterovirus 71 (EV71) has been recognized as a causative agent with severe neurological symptoms with or without cardiopulmonary involvement. HFMD was epidemic in Korea in the spring of 2009. Severe cases with complications including death have been reported. The clinical characteristics in children with neurologic manifestations of EV71 were studied in Ewha Womans University Mokdong Hospital. Methods: Examinations for EV71 were performed from the stools, respiratory secretion or CSF of children who presented neurologic symptoms associated with HFMD by realtime PCR. Clinical and radiologic data of the patients were collected and analyzed. Results: EV71 was isolated from the stool of 16 patients but not from respiratory secretion or CSF. Among the 16 patients, meningitis (n=10) was the most common manifestation, followed by Guillain-Barre syndrome (n=3), meningoencephalitis (n=2), poliomyelitis-like paralytic disease (n=1), and myoclonus (n=1). Gene analysis showed that most of them were caused by EV71 subgenotype C4a, which was prevalent in China in 2008. Conclusion: Because EV71 causes severe complications and death in children, a surveillance system to predict upcoming outbreaks should be established and maintained and adequate public health measures are needed to control disease.

Keywords

References

  1. Yang F, Ren L, Xiong Z, Li J, Xiao Y, Zhao R, et al. Enterovirus 71 outbreak in the People's Republic of China in 2008. J Clin Microbiol 2009;47:2351-2. https://doi.org/10.1128/JCM.00563-09
  2. Huang KY, Zhang X, Chung PH, Tsao KC, Lin TY, Su LH, et al. Enterovirus 71 in Taiwan, 2004-2006: epidemiological and virological features. Scand J Infect Dis 2008;40:571-4. https://doi.org/10.1080/00365540701799359
  3. Ang LW, Koh BK, Chan KP, Chua LT, James L, Goh KT. Epidemiology and control of hand, foot and mouth disease in Singapore, 2001-2007. Ann Acad Med Singapore 2009;38:106-12.
  4. Chang LY, Lin TY, Huang YC, Tsao KC, Shih SR, Kuo ML, et al. Comparison of enterovirus 71 and coxsackievirus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998. Pediatr Infect Dis J 1999;18:1092-6. https://doi.org/10.1097/00006454-199912000-00013
  5. Schmidt NJ, Lennette EH, Ho HH. An apparently new enterovirus isolated from patients with disease of the central nervous system. J Infect Dis 1974;129:304-9. https://doi.org/10.1093/infdis/129.3.304
  6. Ortner B, Huang CW, Schmid D, Mutz I, Wewalka G, Allerberger F, et al. Epidemiology of enterovirus types causing neurological disease in Austria 1999-2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes. J Med Virol 2009;81:317-24. https://doi.org/10.1002/jmv.21374
  7. McMinn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 2002;26:91-107 https://doi.org/10.1111/j.1574-6976.2002.tb00601.x
  8. Tu PV, Thao NT, Perera D, Huu TK, Tien NT, Thuong TC, et al. Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005. Emerg Infect Dis 2007;13:1733-41. https://doi.org/10.3201/eid1311.070632
  9. Bible JM, Iturriza-Gomara M, Megson B, Brown D, Pantelidis P, Earl P, et al. Molecular epidemiology of human enterovirus 71 in the United Kingdom from 1998 to 2006. J Clin Microbiol 2008;46:3192-200. https://doi.org/10.1128/JCM.00628-08
  10. Shindarov LM, Chumakov MP, Voroshilova MK, Bojinov S, Vasilenko SM, Iordanov I, et al. Epidemiological, clinical, and pathomorphological characteristics of epidemic poliomyelitis-like disease caused by enterovirus 71. J Hyg Epidemiol Microbiol Immunol 1979;23:284-95.
  11. Nagy G, Takatsy S, Kukán E, Mihály I, Domok I. Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. Arch Virol 1982;71:217-27. https://doi.org/10.1007/BF01314873
  12. Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, et al. Deaths of children during an outbreak of hand, foot, and mouth disease in sarawak, malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group. Clin Infect Dis 2000;31:678-83. https://doi.org/10.1086/314032
  13. Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT, Tsai SF, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 1999;341:929-35. https://doi.org/10.1056/NEJM199909233411301
  14. Huang CC, Liu CC, Chang YC, Chen CY, Wang ST, Yeh TF. Neurologic complications in children with enterovirus 71 infection. N Engl J Med 1999;341:936-42. https://doi.org/10.1056/NEJM199909233411302
  15. Wang SM, Liu CC, Tseng HW, Wang JR, Huang CC, Chen YJ, et al. Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clin Infect Dis 1999;29:184-90. https://doi.org/10.1086/520149
  16. McMinn P, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis 2001;32:236-42. https://doi.org/10.1086/318454
  17. Abzug MJ. Nonpolio Enteroviruses. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson textbook of pediatrics. 18th ed. Philadelphia: WB Saunders Co, 2007:1350-6.
  18. Wang SM, Ho TS, Shen CF, Liu CC. Enterovirus 71, one virus and many stories. Pediatr Neonatol 2008;49:113-5. https://doi.org/10.1016/S1875-9572(08)60024-8
  19. Wang SM, Lei HY, Huang KJ, Wu JM, Wang JR, Yu CK, et al. Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 2003;188:564-70. https://doi.org/10.1086/376998
  20. Zhang Y, Tan XJ, Wang HY, Yan DM, Zhu SL, Wang DY, et al. An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China. J Clin Virol 2009;44:262-7. https://doi.org/10.1016/j.jcv.2009.02.002
  21. Shimizu H, Utama A, Onnimala N, Li C, Li-Bi Z, Yu-Jie M, et al. Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region. Pediatr Int 2004;46:231-5. https://doi.org/10.1046/j.1442-200x.2004.01868.x
  22. Qiu J. Enterovirus 71 infection: a new threat to global public health? Lancet Neurol 2008;7:868-9. https://doi.org/10.1016/S1474-4422(08)70207-2
  23. Chan KP, Goh KT, Chong CY, Teo ES, Lau G, Ling AE. Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore. Emerg Infect Dis 2003;9:78-85. https://doi.org/10.3201/eid0901.020112
  24. AbuBakar S, Sam IC, Yusof J, Lim MK, Misbah S, MatRahim N, et al. Enterovirus 71 outbreak, Brunei. Emerg Infect Dis 2009;15:79-82. https://doi.org/10.3201/eid1501.080264
  25. Sarawak Health Department/Ministry of Health Malaysia. Hand, foot and mouth disease [cited 2008 Sep1]. Available from: URL:// http://www.sarawak.health.gov.my/hfmd.htm#INFO9
  26. Lin TY, Twu SJ, Ho MS, Chang LY, Lee CY. Enterovirus 71 outbreaks, Taiwan: occurrence and recognition. Emerg Infect Dis 2003;9:291-3. https://doi.org/10.3201/eid0903.020285
  27. Chong CY, Chan KP, Shah VA, Ng WY, Lau G, Teo TE, et al. Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases. Acta Paediatr 2003;92:1163-9. https://doi.org/10.1111/j.1651-2227.2003.tb02478.x
  28. Cho EY, Kang MK, Hong SC, Kim KS, Park YS, Park IS, et al. A review on aseptic meningitis epidemic in Seoul during 1989-1990. J Korean Pediatr Soc 1991;34:1565-72.
  29. Yoo HS, Kim GH, Lee HS. An epidemic of aseptic meningitis in 1993. Korean J Infect Dis 1995;27:365-70.
  30. Wee JS, Lee SK, Seon KJ. Paralytic Disease Related to Enterovirus 71 Infection: A report of 4 cases. J Korean Acad Rehabil Med 1999;23:1046- 51.
  31. Jee YM, Cheon DS, Kim K, Cho JH, Chung YS, Lee J, et al. Genetic analysis of the VP1 region of human enterovirus 71 strains isolated in Korea during 2000. Arch Virol 2003;148:1735-46. https://doi.org/10.1007/s00705-003-0133-6
  32. Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP, et al. Molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the Asia-Pacific region: comparative analysis of the VP1 and VP4 genes. Emerg Infect Dis 2003;9:461-8. https://doi.org/10.3201/eid0904.020395
  33. McMinn P, Lindsay K, Perera D, Chan HM, Chan KP, Cardosa MJ. Phylogenetic analysis of enterovirus 71 strains isolated during linked epidemics in Malaysia, Singapore, and Western Australia. J Virol 2001;75:7732-8. https://doi.org/10.1128/JVI.75.16.7732-7738.2001
  34. Yoke-Fun C, AbuBakar S. Phylogenetic evidence for inter-typic recombination in the emergence of human enterovirus 71 subgenotypes. BMC Microbiol 2006;6:74-84. https://doi.org/10.1186/1471-2180-6-74
  35. Chang LY, Tsao KC, Hsia SH, Shih SR, Huang CG, Chan WK, et al. Transmission and clinical features of enterovirus 71 infections in household contacts in Taiwan. JAMA 2004;291:222-7. https://doi.org/10.1001/jama.291.2.222
  36. Chung PW, Huang YC, Chang LY, Lin TY, Ning HC. Duration of enterovirus shedding in stool. J Microbiol Immunol Infect 2001;34:167- 70.
  37. Ho M. Enterovirus 71: the virus, its infections and outbreaks. J Microbiol Immunol Infect 2000;33:205-16.

Cited by

  1. How Do We Manage Oral Infections in Allogeneic Stem Cell Transplantation and Other Severely Immunocompromised Patients? vol.23, pp.4, 2010, https://doi.org/10.1016/j.coms.2011.07.012
  2. High Risk Factors for Severe Hand, Foot and Mouth Disease: A Multicenter Retrospective Survey in Anhui Province China, 2008-2009 vol.57, pp.4, 2010, https://doi.org/10.4103/0019-5154.97683
  3. Detection of human enterovirus 71 and Coxsackievirus A16 in an outbreak of hand, foot, and mouth disease in Henan Province, China in 2009 vol.46, pp.1, 2010, https://doi.org/10.1007/s11262-012-0814-x
  4. Human enterovirus 71 epidemics: what's next? vol.6, pp.None, 2010, https://doi.org/10.3402/ehtj.v6i0.19780
  5. Epidemiology and Clinical Characteristics of Enterovirus Infections in Children: A Single Center Analysis from 2006 to 2010 vol.20, pp.2, 2010, https://doi.org/10.14776/kjpid.2013.20.2.81
  6. Severe Enterovirus Type 71 Nervous System Infections in Children in the Shanghai Region of China : Clinical Manifestations and Implications for Prevention and Care vol.33, pp.5, 2014, https://doi.org/10.1097/inf.0000000000000194
  7. The significance of Notch ligand expression in the peripheral blood of children with hand, foot and mouth disease (HFMD) vol.14, pp.None, 2010, https://doi.org/10.1186/1471-2334-14-337
  8. Neurologic Manifestations of Enterovirus 71 Infection in Korea vol.31, pp.4, 2010, https://doi.org/10.3346/jkms.2016.31.4.561
  9. Enterovirus 71 infection and neurological complications vol.59, pp.10, 2010, https://doi.org/10.3345/kjp.2016.59.10.395
  10. A literature review and case report of hand, foot and mouth disease in an immunocompetent adult vol.9, pp.None, 2016, https://doi.org/10.1186/s13104-016-1973-y
  11. The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection vol.8, pp.8, 2010, https://doi.org/10.1007/s13238-017-0405-7
  12. Transcriptome analysis reveals dynamic changes in coxsackievirus A16 infected HEK 293T cells vol.18, pp.suppl1, 2010, https://doi.org/10.1186/s12864-016-3253-6
  13. Enterovirus 71 infection and vaccines vol.6, pp.1, 2010, https://doi.org/10.7774/cevr.2017.6.1.4
  14. Molecular epidemiology and clinical features of hand, foot and mouth disease in northern Thailand in 2016: a prospective cohort study vol.18, pp.None, 2018, https://doi.org/10.1186/s12879-018-3560-4
  15. Enterovirus A71 Infection Activates Human Immune Responses and Induces Pathological Changes in Humanized Mice vol.93, pp.3, 2019, https://doi.org/10.1128/jvi.01066-18
  16. Meningitis gone viral: description of the echovirus wave 2013 in Germany vol.19, pp.1, 2010, https://doi.org/10.1186/s12879-019-4635-6