Hand, foot, and mouth disease: Current scenario and Indian perspective

Indian Journal of Dermatology, Venereology and Leprology

Volumn 79, Issue 2, 2013, Pages 165-175

  Sarma, Nilendu ^a  

^a NRS Medical College   (India)

Author keywords

Coxsackievirus A16; hand foot and mouth disease; human enterovirus 71; India; Southeast Asia

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HLA A ANTIGEN; HLA DR ANTIGEN; IMMUNOGLOBULIN M ANTIBODY; MESSENGER RNA; NEUTRALIZING ANTIBODY; P SELECTIN GLYCOPROTEIN LIGAND 1; SCAVENGER RECEPTOR B;

ANTIBODY DETECTION; ANTIVIRAL THERAPY; AWARENESS; CELLULAR IMMUNITY; COXSACKIE VIRUS; COXSACKIE VIRUS A; COXSACKIE VIRUS B; DISEASE ACTIVITY; DISEASE SEVERITY; ENTEROVIRUS 71; ENZYME LINKED IMMUNOSORBENT ASSAY; EPIDEMIC; FECES CULTURE; GENETIC SUSCEPTIBILITY; GENOTYPE; HAND FOOT AND MOUTH DISEASE; HERPANGINA; HUMAN; INCIDENCE; INDIA; LUNG EDEMA; LYMPHOCYTE PROLIFERATION; MORBIDITY; NONHUMAN; OUTCOME ASSESSMENT; PAPULOVESICULAR RASH; PHYLOGENY; PLEOCYTOSIS; PROGNOSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SEROPREVALENCE; SKIN DEFECT; THROAT CULTURE; VACCINATION; VIRUS ENTRY; VIRUS STRAIN; VIRUS VIRULENCE;

ANIMALS; DISEASE MANAGEMENT; ENTEROVIRUS; ENTEROVIRUS A, HUMAN; HAND, FOOT AND MOUTH DISEASE; HUMANS; INDIA;

EID: 84875744451     PISSN: 03786323     EISSN: 09733922     Source Type: Journal    
DOI: 10.4103/0378-6323.107631     Document Type: Review

References (109)

1. Zhu Z, Zhu S, Guo X, Wang J, Wang D, Yan D, et al. Retrospective seroepidemiology indicated that human enterovirus 71 and coxsackievirus A16 circulated wildly in central and southern China before large-scale outbreaks from 2008. Virol J 2010;7:300.
2. 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.
3. Hagiwara A, Tagaya I, Yoneyama T. Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection. Intervirology 1978;9:60-3.
4. Chatproedprai S, Theanboonlers A, Korkong S, Thongmee C, Wananukul S, Poovorawan Y. Clinical and molecular characterization of hand-foot-and-mouth disease in Thailand, 2008-2009. Jpn J Infect Dis 2010;63:229-33.
5. Ooi MH, Wong SC, Mohan A, Podin Y, Perera D, Clear D, et al. Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak. BMC Infect Dis 2009;9:3.
6. Cardosa MJ, Krishnan S, Tio PH, Perera D, Wong SC. Isolation of subgenus B adenovirus during a fatal outbreak of enterovirus 71-associated hand, foot, and mouth disease in Sibu, Sarawak. Lancet 1999;354:987-91.
7. Chang LY, Lin TY, Hsu KH, Huang YC, Lin KL, Hsueh C, et al. Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease. Lancet 1999;354:1682-6.
8. Huang FL, Jan SL, Chen PY, Chi CS, Wang TM, Fu YC, et al. Left ventricular dysfunction in children with fulminant enterovirus 71 infection: an evaluation of the clinical course. Clin Infect Dis 2002;34:1020-4.
9. 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.
10. 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.
11. 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.
12. Hsueh C, Jung SM, Shih SR, Kuo TT, Shieh WJ, Zaki S, et al. Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies. Mod Pathol 2000;13:1200-5.
13. Prager P, Nolan M, Andrews IP, Williams GD. Neurogenic pulmonary edema in enterovirus 71 encephalitis is not uniformly fatal but causes severe morbidity in survivors. Pediatr Crit Care Med 2003;4:377-81.
14. 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.
15. Li L, He Y, Yang H, Zhu J, Xu X, Dong J, et al. Genetic characteristics of human enterovirus 71 and coxsackievirus A16 circulating from 1999 to 2004 in Shenzhen, People's Republic of China. J Clin Microbiol 2005;43:3835-9.
16. Perera D, Podin Y, Akin W, Tan CS, Cardosa MJ. Incorrect identification of recent Asian strains of coxsackievirus A16 as human enterovirus 71: Improved primers for the specific detection of human enterovirus 71 by RT PCR. BMC Infect Dis 2004;4:11.
17. 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.
18. Chan YF, Sam IC, AbuBakar S. Phylogenetic designation of enterovirus 71 genotypes and subgenotypes using complete genome sequences. Infect Genet Evol 2010;10:404-12.
19. Li C, Wang H, Shih SR, Chen TC, Li ML. The efficacy of viral capsid inhibitors in human enterovirus infection and associated diseases. Curr Med Chem 2007;14:847-56.
20. Lim XF, Jia Q, Khong WX, Yans B, Premanand B, Alonso S, et al. Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection. PLoS One 2012;7:e29751.
21. Tee KK, Lam TT, Chan YF, Bible JM, Kamarulzaman A, Tong CY, et al. Evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the VP1 gene. J Virol 2010;84:3339-50.
22. Deshpande JM, Nadkarni SS, Francis PP. Enterovirus 71 isolated from a case of acute flaccid paralysis in India represents a new genotype. Curr Sci 2003;84:1350-3.
23. Shimizu H, Utama A, Onnimala N, Li C, Li-Bi Z, Yu-Jie M, et al. Molecular epidemiology of enterovirus 71 in the Western Pacific region. Pediatr Int 2004;46:231-5.
24. 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.
25. van der Sanden S, Koopmans M, Uslu G, van der Avoort H. Dutch Working Group for Clinical Virology. Epidemiology of enterovirus 71 in the Netherlands, 1963 to 2008. J Clin Microbiol 2009;47:2826-33.
26. Bek EJ, McMinn PC. Recent advances in research on human enterovirus 71. Future Virol 2010;5:453-68.
27. Nishimura Y, Shimojima M, Tano Y, Miyamura T, Wakita T, Shimizu H. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nat Med 2009;15:794-7.
28. Yamayoshi S, Yamashita Y, Li J, Hanagata N, Minowa T, Takemura T, et al. Scavenger receptor B2 is a cellular receptor for enterovirus 71. Nat Med 2009;15:798-801.
29. Patel KP, Bergelson JM. Receptors identified for hand, foot and mouth virus. Nat Med 2009;15:728-9.
30. Blomberg J, Lycke E, Ahlfors K, Johnsson T, Wolontis S, von Zeipel G. New enterovirus type associated with epidemic of aseptic meningitis and-or hand, foot, and mouth disease. Lancet 1974;2:112.
31. Ishimaru Y, Nakano S, Yamaoka K, Takami S. Outbreaks of hand, foot,and mouth disease by enterovirus 71: high incidence of complication disorders of central nervous system. Arch Dis Child 1980;55:583-8.
32. Melnick JL. Enterovirus type 71 infections: a varied clinical pattern sometimes mimicking paralytic poliomyelitis. Rev Infect Dis 1984;6(Suppl 2):S387-90.
33. Gilbert GL, Dickson KE, Waters MJ, Kennett ML, Land SA, Sneddon M. Outbreak of enterovirus 71 infection in Victoria, Australia, with a high incidence of neurologic involvement. Pediatr Infect Dis J 1988;7:484-8.
34. Alexander JP, Baden L, Pallansch MA, Anderson LJ. Enterovirus 71infections and neurologic disease: United States, 1977-1991. J Infect Dis 1994;169:905-8.
35. da Silva EE, Winkler MT, Pallansch MA. Role of enterovirus 71 in acute flaccid paralysis after the eradication of poliovirus in Brazil. Emerg Infect Dis 1996;2:231-3.
36. Shindarov LM, Chumakov MP, Voroshilova MK, Bojinov S, Vasilenko SM, Iordanov I, et al. Epidemiological, clinical and pathomorphological characteristics of epidemic poliomyelitislike disease caused by enterovirus 71. J Hyg Epidemiol Microbiol Immunol 1979;23:284-95.
37. Nagy G, Takatsy S, Kukan E, Mihaly 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.
38. 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.
39. WPRO. WHO warns of growing threat from severe form of hand, foot and mouth disease. Available at:http://www.wpro. who.int/mediacentre/releases/2010/ PR20100622/en/index.html
40. Centers for Disease Control and Prevention (CDC). Deaths among children during an outbreak of hand, foot and mouth disease-Taiwan, Republic of China, April-July 1998. MMWR Morb Mortal Wkly Rep 1998;47:629-32.
41. Yang C, Deng C, Wan J, Zhu L, Leng Q. Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications. Virol J 2011;8:306.
42. Zheng ZM, He PJ, Caueffield D, Neumann M, Specter S, Baker CC, et al. Enterovirus 71 isolated from China is serologically similar to the prototype E71 BrCr strain but differs in the 5'-noncoding region. J Med Virol 1995;47:161-7.
43. Zhang Y, Zhu Z, Yang WZ, Ren J, Tan XJ, Wang Y, et al. An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of hand foot and mouth disease in Fuyang city of China. Virol J 2010;7:94.
44. Fujimoto T, Chikahira M, Yoshida S, Ebira H, Hasegawa A, Totsuka A, et al. Outbreak of central nervous system disease associated with hand, foot, and mouth disease in Japan during the summer of 2000: detection and molecular epidemiology of enterovirus 71. Microbiol Immunol 2002;46:621-7.
45. 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.
46. Sarma N, Sarkar A, Mukherjee A, Ghosh A, Dhar S, Malakar R. Epidemic of hand, foot and mouth disease in West Bengal, India in August, 2007: A multicentric study. Indian J Dermatol 2009;54:26-30.
47. 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.
48. 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. Clin Infect Dis 2000;31:678-83.
49. 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.
50. Chen SC, Chang HL, Yan TR, Cheng YT, Chen KT. An eight-year study of epidemiologic features of enterovirus 71 infection in Taiwan. Am J Trop Med Hyg 2007;77:188-91.
51. Lee TC, Guo HR, Su HJ, Yang YC, Chang HL, Chen KT. Diseases caused by enterovirus 71 infection. Pediatr Infect Dis J 2009;28:904-10.
52. Sasidhran CK, Sugathan P, Agarwal R, Khare S, Lal S, Jayaram Paniker CK. Hand-Foot and Mouth disease in Calicut. Indian J Pediatr 2005;72:17-21.
53. Dwibedi B, Kar BR, Kar SK. Hand, foot and mouth disease (HFMD): a newly emerging infection in Orissa, India. Natl Med J India 2010;23:313.
54. Ghosh SK, Bandyopadhyay D, Ghosh A, Dutta A, Biswas S, Mandal RK, et al. Mucocutaneous features of hand, foot, and mouth disease: a reappraisal from an outbreak in the city of Kolkata. Indian J Dermatol Venereol Leprol 2010;76:564-6.
55. Mehta KI, Mahajan VK. Hand foot and mouth disease. Indian Pediatr 2010;47:345-6.
56. Arora S, Arora G, Tewari V. Hand foot and mouth disease: emerging epidemics. Indian J Dermatol Venereol Leprol 2008;74:503-5.
57. Saoji VA. Hand, foot and mouth disease in Nagpur. Indian J Dermatol Venereol Leprol 2008;74:133-5.
58. Chen KT, Chang HL, Wang ST, Cheng YT, Yang JY. Epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus 71 in Taiwan, 1998-2005. Pediatrics 2007;120: e244-52.
59. McMinn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 2002;26:91-107.
60. Shimizu H, Utama A, Yoshii K, Yoshida H, Yoneyama T, Sinniah M, et al. Enterovirus 71 from fatal and nonfatal cases of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 1997-1998. Jpn J Infect Dis 1999;52:12-15.
61. Wang LC, Tang SQ, Li YM, Zhao HL, Dong CH, Cui PF, et al. A comparison of the biological characteristics of EV71 C4 subtypes from different epidemic strains. Virol Sin 2010;25: 98-106.
62. Chang LY, Lin TY, Huang YC, Tsao KC, Shih SR, Kuo ML, et al. Comparison of enterovirus 71 and coxsackie-virus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998. Pediatr Infect Dis J 1999;18:1092-6.
63. Ong KC, Devi S, Cardosa MJ, Wong KT. Formaldehydeinactivated whole-virus vaccine protects a murine model of enterovirus 71 encephalomyelitis against disease. J Virol 2010;84:661-5.
64. Xu J, Qian Y, Wang S, Serrano JM, Li W, Huang Z, et al. EV71: an emerging infectious disease vaccine target in the Far East Vaccine 2010;28:3516-21.
65. Zhang D, Lu J, Lu J. Enterovirus 71 vaccine: Close but still far. Int J Infect Dis 2010;14:e739-43.
66. Huang SW, Hsu YW, Smith DJ, Kiang D, Tsai HP, Lin KH, et al. Reemergence of enterovirus 71 in 2008 in Taiwan: Dynamics of genetic and antigenic evolution from 1998 to 2008. J Clin Microbiol 2009;47:3653-62.
67. Ho HY, Cheng ML, Weng SF, Chang L, Yeh TT, Shih SR, et al. Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection. J Gen Virol 2008;89:2080-9.
68. Chang LY, Hsiung CA, Lu CY, Lin TY, Huang FY, Lai YH, et al. Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71. Pediatr Res 2006;60:466-71.
69. Yang KD, Yang MY, Li CC, Lin SF, Chong MC, Wang CL, et al. Altered cellular but not humoral reactions in children with complicated enterovirus 71 infections in Taiwan. J Infect Dis 2001;183:850-6.
70. 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.
71. Lin TY, Chang LY, Huang YC, Hsu KH, Chiu CH, Yang KD. Different proinflammatory reactions in fatal and non-fatal enterovirus 71 infections: Implications for early recognition and therapy. Acta Paediatr 2002;91:632-5.
72. Lin TY, Hsia SH, Huang YC, Wu CT, Chang LY. Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system. Clin Infect Dis 2003;36:269-74.
73. Chang GH, Lin L, Luo YJ, Cai LJ, Wu XY, Xu HM, et al. Sequence analysis of six enterovirus 71 strains with different virulences in humans. Virus Res 2010;151:66-73.
74. Ljubin-Sternak S, Slavic-Vrzic V, Vilibi-avlek T, Aleraj B, Gjenero-Margan I. Outbreak of hand, foot and mouth disease caused by Coxsackie A16 virus in a childcare centre in Croatia, February to March 2011. Euro Surveill 2011;16:pii=19875. Available online: http://www.eurosurveillance.org/ ViewArticle. aspxArticleId=19875
75. Wang YF, Chou CT, Lei HY, Liu CC, Wang SM, Yan JJ, et al. A mouse-adapted enterovirus 71 strain causes neurological disease in mice after oral infection. J Virol 2004;78:7916-24.
76. Diamond SE, Kirkegaard K. Clustered charged-to-alanine mutagenesis of poliovirus RNA-dependent RNA polymerase yields multiple temperature-sensitive mutants defective in RNA synthesis. J Virol 1994;68:863-76.
77. Gromeier M, Alexander L, Wimmer E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc Natl Acad Sci USA 1996;93:2370-5.
78. Pallansch M, Roos R. Enteroviruses: Polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses. In: Knipe DM, Howley PM, editors. Fields virology. 5th ed. Philadelphia: Lippincot WandWWolters Kluwer; 2007. p. 839-93.
79. Kirkegaard K, Baltimore D. The mechanism of RNA recombination in poliovirus. Cell 1986;47:433-43.
80. Liu Y, Franco D, Paul AV, Wimmer E. Tyrosine 3 of poliovirus terminal peptide VPg(3B) has an essential function in RNA replication in the context of its precursor protein, 3AB. J Virol 2007;81:5669-84.
81. Mueller S, Papamichail D, Coleman JR, Skiena S, Wimmer E. Reduction of the rate of poliovirus protein synthesis through large-scale codon deoptimisation causes attenuation of viral virulence by lowering specific infectivity. J Virol 2006;80: 9687-96.
82. Tung WH, Hsieh HL, Yang CM. Enterovirus 71 induces COX-2 expression via MAPKs, NF-kB, and AP-1 in SK-N-SH cells: Role of PGE2 in viral replication. Cell Signal 2010;22:234-46.
83. 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.
84. Ghukasyan V, Hsu YY, Kung SH, Kao FJ. Application of fluorescence resonance energy transfer resolved by fluorescence lifetime imaging microscopy for the detection of enterovirus 71 infection in cells. J Biomed Opt 2007;12:024016
85. Grandien M, Fosgren M, Ehrnst A. Enterovirus. In: Lennette EH, Lennette DA, Lennette ET, editors. Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections. 7th ed. Washington, DC: American Public Health Association; 1995. p. 279-98.
86. Tran CB, Nguyen HT, Phan HT, Tran NV, Wills B, Farrar J, et al. The Seroprevalence and Seroincidence of Enterovirus71 Infection in Infants and Children in Ho Chi Minh City, Viet Nam. PLoS One 2011;6:e21116.
87. Chang LY, King CC, Hsu KH, Ning HC, Tsao KC, Li CC, et al. Risk Factors of Enterovirus 71 Infection and Associated Hand, Foot, and Mouth Disease/Herpangina in Children During an Epidemic in Taiwan. Pediatrics 2002;109:e88.
88. Yu N, Guo M, He SJ, Pan YX, Chen XX, Ding XX. Evaluation of human enterovirus 71 and coxsackievirus A16 specific immunoglobulin M antibodies for diagnosis of hand-foot-andmouth disease. Virol J 2012;9:12.
89. Xu F, Yan Q, Wang H, Niu J, Li L, Zhu F, et al. Performance of detecting IgM antibodies against enterovirus 71 for early diagnosis. PLoS One 2010;5:e11388.
90. Wang SY, Lin TL, Chen HY, Lin TS. Early and rapid detection of enterovirus 71 infection by an IgM-capture ELISA. J Virol Methods 2004;119:37-43.
91. Xu F, He D, He S, Wu B, Guan L, Niu J, et al. Development of an IgM-capture ELISA for Coxsackievirus A16 infection. J Virol Methods 2011;171:107-10.
92. Brown BA, Kilpatrick DR, Oberste MS, Pallansch MA. Serotypespecific identification of enterovirus 71 by PCR. J Clin Virol 2000;16:107-12.
93. Leitch EC, Harvala H, Robertson I, Ubillos I, Templeton K, Simmonds P. Direct identification of human enterovirus serotypes in cerebrospinal fluid by amplification and sequencing of the VP1 region. J Clin Virol 2009;44:119-24.
94. Oberste MS, Nix WA, Maher K, Pallansch MA. Improved molecular identification of enteroviruses by RT-PCR and amplicon sequencing. J Clin Virol 2003;26:375-7.
95. Thao NT, Ngoc NT, Tú PV, Thúy TT, Cardosa MJ, McMinn PC, et al. Development of a multiplex polymerase chain reaction assay for simultaneous identification of human enterovirus 71 and coxsackievirus A16. J Virol Methods 2010;170:134-9.
96. Naze F, Le Roux K, Schuffenecker I, Zeller H, Staikowsky F, Grivard P, et al. Laurent P. Simultaneous detection and quantitation of Chikungunya, dengue and West Nile viruses by multiplex RT-PCR assays and dengue virus typing using high resolution melting. J Virol Methods 2009;162:1-7.
97. Wang W, Ren P, Sheng J, Mardy S, Yan H, Zhang J, et al. Simultaneous detection of respiratory viruses in children with acute respiratory infection using two different multiplex reverse transcription-PCR assays. J Virol Methods 2009; 162:40-5.
98. Ministry of Health, Singapore: Surveillance of hand, foot and mouth disease in Singapore. Epidemiol Bull 2000;26:3-5.
99. Wu TN, Tsai SF, Li SF, Lee TF, Huang TM, Wang ML, et al. Sentinel surveillance for enterovirus 71, Taiwan, 1998. Emerg Infect Dis 1999;5:458-60.
100. Barnes D, Kunitomi M, Vignuzzi M, Saksela K, Andino R. Harnessing endogenous miRNAs to control virus tissue tropism as a strategy for developing attenuated virus vaccines. Cell Host Microbe 2008;4:239-48.
101. Chen HF, Chang MH, Chiang BL, Jeng ST. Oral immunization of mice using transgenic tomato fruit expressing VP1 protein from enterovirus 71. Vaccine 2006;24:2944-51.
102. Wu CN, Lin YC, Fann C, Liao NS, Shih SR, Ho MS. Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1vaccines and inactivated virus. Vaccine 2001;20:895-904.
103. Tung WS, Bakar SA, Sekawi Z, Rosli R. DNA vaccine constructs against enterovirus 71 elicit immune response in mice. Genet Vaccines Ther 2007;5:6.
104. Chen HL, Huang JY, Chu TW, Tsai TC, Hung CM, Lin CC, et al. Expression of VP1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection. Vaccine 2008;26:2882-9.
105. Chung CY, Chen CY, Lin SY, Chung YC, Chiu HY, Chi WK, et al. Enterovirus 71 virus-like particle vaccine: Improvedproduction conditions for enhanced yield. Vaccine 2010;28:6951-7.
106. Arita M, Shimizu H, Nagata N, Ami Y, Suzaki Y, Sata T, et al. Temperature-sensitive mutants of enterovirus 71 show attenuation in cynomolgus monkeys. J Gen Virol 2005;86: (Pt 5):1391-401.
107. 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.
108. Lal SK, Kumar P, Yeo WM, Kar-Roy A, Chow VT. The VP1 protein of human enterovirus 71 selfassociates via an interaction domain spanning amino acids 66-297. J Med Virol 2006;78:582-90.
109. Sarma N. Pediatric Dermatology. In: Dermatology Jewels-An Approach to Diagnosis. Gurgaon: MacMilan Medical Com; 2011. p. 12-41.