Skip to main content
SpringerLink
Log in

Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Enterovirus 71 (EV71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. This study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ADE) in EV71. All EV71-infected patients during the outbreak of 2008 were recruited. In total, 134 patients were enrolled and categorized into two age groups, 0–12 months (n = 18) and >12 months (n = 116). Pulmonary edema/hemorrhage more commonly occur in patients younger than 12 months. No difference in the occurrence of herpangina/hand-foot-and-mouth disease (HFMD), uncomplicated brainstem encephalitis (BE), or autonomic nervous system (ANS) dysregulation was noted between the two age groups. Patients with pulmonary edema/hemorrhage (11.9 ± 14.7 months) were younger than patients with herpangina/HFMD (35.8 ± 26.4 months) or ANS dysregulation (33.9 ± 20.9 months). Our findings are in agreement with the data regarding the outbreak in Taiwan, in which a decrease in age corresponded to an increase in disease severity with regard to central nervous system complications. A reduction of maternal antibodies to the subneutralizing level within 1 year of age may be associated with the ADE of the infection. This study could provide possible clinical significance with regard to ADE phenomena in young infants infected by EV71.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wang SM, Liu CC, Tseng HW, Wang JR, Huang CC, Chen YJ et al (1999) Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications. Clin Infect Dis 29:184–190

    Article  PubMed  CAS  Google Scholar 

  2. Wang SM, Liu CC, Yang YJ, Yang HB, Lin CH, Wang JR (1998) Fatal coxsackievirus B infection in early infancy characterized by fulminant hepatitis. J Infect 37:270–273

    Article  PubMed  CAS  Google Scholar 

  3. Centers for Disease Control and Prevention (CDC) (1998) Deaths among children during an outbreak of hand, foot, and mouth disease—Taiwan, Republic of China, April–July 1998. MMWR Morb Mortal Wkly Rep 47:629–632

    Google Scholar 

  4. Liu CC, Tseng HW, Wang SM, Wang JR, Su IJ (2000) An outbreak of enterovirus 71 infection in Taiwan, 1998: epidemiologic and clinical manifestations. J Clin Virol 17:23–30

    Article  PubMed  CAS  Google Scholar 

  5. Ho M, Chen ER, Hsu KH, Twu SJ, Chen KT, Tsai SF et al (1999) An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med 341:929–935

    Article  PubMed  CAS  Google Scholar 

  6. Ooi MH, Wong SC, Podin Y, Akin W, del Sel S, Mohan A et al (2007) Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study. Clin Infect Dis 44:646–656

    Article  PubMed  Google Scholar 

  7. Pérez-Vélez CM, Anderson MS, Robinson CC, McFarland EJ, Nix WA, Pallansch MA et al (2007) Outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge. Clin Infect Dis 45:950–957

    Article  PubMed  Google Scholar 

  8. Lum LC, Wong KT, Lam SK, Chua KB, Goh AY, Lim WL et al (1998) Fatal enterovirus 71 encephalomyelitis. J Pediatr 133:795–798

    Article  PubMed  CAS  Google Scholar 

  9. McMinn PC, Stratov I, Nagarajan L, Davis S (2001) Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis 32:236–242

    Article  PubMed  CAS  Google Scholar 

  10. Chan KP, Goh KT, Chong CY, Teo ES, Lau G, Ling AE (2003) Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore. Emerg Infect Dis 9:78–85

    PubMed  Google Scholar 

  11. Van Tu P, Thao NTT, Perera D, Huu TK, Tien NT, Thuong TC et al (2007) Epidemiologic and virologic investigation of hand, foot, and mouth disease, southern Vietnam, 2005. Emerg Infect Dis 13:1733–1741

    PubMed  CAS  Google Scholar 

  12. Mao LX, Wu B, Bao WX, Han FA, Xu L, Ge QJ et al (2010) Epidemiology of hand, foot, and mouth disease and genotype characterization of enterovirus 71 in Jiangsu, China. J Clin Virol 49:100–104

    Article  PubMed  Google Scholar 

  13. Wang SM, Lei HY, Huang KJ, Wu JM, Wang JR, Yu CK et al (2003) Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 188:564–570

    Article  PubMed  CAS  Google Scholar 

  14. Huang MC, Wang SM, Hsu YW, Lin HC, Chi CY, Liu CC (2006) Long-term cognitive and motor deficits after enterovirus 71 brainstem encephalitis in children. Pediatrics 118:e1785–e1788

    Article  PubMed  Google Scholar 

  15. Lu CY, Lee CY, Kao CL, Shao WY, Lee PI, Twu SJ et al (2002) Incidence and case-fatality rates resulting from the 1998 enterovirus 71 outbreak in Taiwan. J Med Virol 67:217–223

    Article  PubMed  Google Scholar 

  16. Chen KT, Chang HL, Wang ST, Cheng YT, Yang JY (2007) Epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus 71 in Taiwan, 1998–2005. Pediatrics 120:e244–e252

    Article  PubMed  Google Scholar 

  17. van der Sanden S, van der Avoort H, Lemey P, Uslu G, Koopmans M (2010) Evolutionary trajectory of the VP1 gene of human enterovirus 71 genogroup B and C viruses. J Gen Virol 91:1949–1958

    Article  PubMed  Google Scholar 

  18. Shih SR, Ho MS, Lin KH, Wu SL, Chen YT, Wu CN et al (2000) Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998. Virus Res 68:127–136

    Article  PubMed  CAS  Google Scholar 

  19. Cardosa MJ, Krishnan S, Tio PH, Perera D, Wong SC (1999) Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu, Sarawak. Lancet 354:987–991

    Article  PubMed  CAS  Google Scholar 

  20. Wang SM, Lei HY, Yu CK, Wang JR, Su IJ, Liu CC (2008) Acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated brainstem encephalitis. J Infect Dis 198:1002–1006

    Article  PubMed  CAS  Google Scholar 

  21. Luo ST, Chiang PS, Chao AS, Liou GY, Lin R, Lin TY et al (2009) Enterovirus 71 maternal antibodies in infants, Taiwan. Emerg Infect Dis 15:581–584

    Article  PubMed  Google Scholar 

  22. Ooi EE, Phoon MC, Ishak B, Chan SH (2002) Seroepidemiology of human enterovirus 71, Singapore. Emerg Infect Dis 8:995–997

    PubMed  Google Scholar 

  23. Takada A, Kawaoka Y (2003) Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol 13:387–398

    Article  PubMed  CAS  Google Scholar 

  24. Hawkes RA (1964) Enhancement of the infectivity of arboviruses by specific antisera produced in domestic fowls. Aust J Exp Biol Med Sci 42:465–482

    Article  PubMed  CAS  Google Scholar 

  25. Halstead SB, O’Rourke EJ (1977) Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody. J Exp Med 146:201–217

    Article  PubMed  CAS  Google Scholar 

  26. Palmer P, Charley B, Rombaut B, Daëron M, Lebon P (2000) Antibody-dependent induction of type I interferons by poliovirus in human mononuclear blood cells requires the type II Fc gamma receptor (CD32). Virology 278:86–94

    Article  PubMed  CAS  Google Scholar 

  27. Kishimoto C, Kurokawa M, Ochiai H (2002) Antibody-mediated immune enhancement in coxsackievirus B3 myocarditis. J Mol Cell Cardiol 34:1227–1238

    Article  PubMed  CAS  Google Scholar 

  28. Wang SM, Chen IC, Su LY, Huang KJ, Lei HY, Liu CC (2010) Enterovirus 71 infection of monocytes with antibody-dependent enhancement. Clin Vaccine Immunol 17:1517–1523

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the National Science Council, Taiwan (NSC-95-2314-B-006-109, NSC 96-2314-B-006-033-MY2, NSC 98-2314-B-006-002-MY3), Multidisciplinary Center of Excellence for Clinical Trial and Research, Department of Health, Executive Yuan, Taiwan (DOH100-TD-B-111-102), and the Center of Infectious Disease and Signaling Research, National Cheng Kung University, Taiwan.

Conflicts of interest

There are no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Emergency Medicine, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan

    S.-M. Wang & T.-S. Ho

  2. Centers for Disease Control, 5th branch, Kaohsiung, Taiwan

    H.-C. Lin

  3. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    H.-Y. Lei

  4. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    J.-R. Wang

  5. Department of Pediatrics, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan

    C.-C. Liu

  6. Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan

    S.-M. Wang, T.-S. Ho, H.-Y. Lei, J.-R. Wang & C.-C. Liu

Authors
  1. S.-M. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T.-S. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H.-C. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H.-Y. Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J.-R. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C.-C. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to S.-M. Wang or C.-C. Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, SM., Ho, TS., Lin, HC. et al. Reemerging of enterovirus 71 in Taiwan: the age impact on disease severity. Eur J Clin Microbiol Infect Dis 31, 1219–1224 (2012). https://doi.org/10.1007/s10096-011-1432-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-011-1432-6

Keywords

Search

Navigation