title: Evaluation of human enterovirus 71 and coxsackievirus A16 specific immunoglobulin M antibodies for diagnosis of hand-foot-and-mouth disease.
abstract: BACKGROUND
  Hand-foot-and-mouth disease (HFMD) is caused mainly by the human enterovirus type 71 (HEV71) and the Coxsackievirus A group type 16 (CVA16). Large outbreaks of disease have occurred frequently in the Asia-Pacific region. Reliable methods are needed for diagnosis of HFMD in children. IgM-capture ELISA, with its notable advantages of convenience and low cost, provides a potentially frontline assay. We aimed to evaluate the newly developed IgM-capture ELISAs for HEV71 and CVA16 in the diagnosis of HFMD, and to measure the kinetics of IgM over the course of HEV71 or CVA16 infections.
  
  
  RESULTS
  We mapped, for the first time, the kinetics of IgM in HEV71 and CVA16 infection. HEV71- and CVA16-IgM were both detectable in some patients on day 1 of illness, and in 100% of patients by day 5 (HEV71) and day 8 (CVA16) respectively; both IgMs persisted for several weeks. The IgM detection rates were 90.2% (138 of 153 sera) and 68.0% (66 of 97 sera) for HEV71 and CVA16 infections, respectively, during the first 7 days of diseases. During the first 90 days after onset these values were 93.6% (233 of 249 sera) and 72.8% (91 of 125 sera) for HEV71 and CVA16 infections, respectively. Some cross-reactivity was observed between HEV71- and CVA16-IgM ELISAs. HEV71-IgM was positive in 38 of 122 (31.1%) CVA16 infections, 14 of 49 (28.6%) other enteroviral infections and 2 of 105 (1.9%) for other respiratory virus infected sera. Similarly, CVA16-IgM was apparently positive in 58 of 211 (27.5%) HEV71 infections, 16 of 48 (33.3%) other enterovirus infections and 3 of 105 (2.9%) other respiratory virus infected sera. Nevertheless, the ELISA yielded the higher OD450 value of main antibody than that of cross-reaction antibody, successfully identifying the enteroviral infection in 96.6% (HEV71) and 91.7% (CVA16) cases. When blood and rectal swabs were collected on the same day, the data showed that the agreement between IgM-capture ELISA and real-time RT-PCR in HEV71 was high (Kappa value = 0.729) while CVA16 somewhat lower (Kappa value = 0.300).
  
  
  CONCLUSIONS
  HEV71- and CVA16-IgM ELISAs can be deployed successfully as a convenient and cost-effective diagnostic tool for HFMD in clinical laboratories.
authors.affiliation: Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University, No, 253 Gong ye da dao zhong, Guangzhou, Guangdong 510282, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Si-Jie
authors.initials: SJ
authors.lastname: He
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Pan
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Chen
authors.forename: Xi-Xia
authors.initials: XX
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Hao
authors.forename: Ya-Di
authors.initials: YD
authors.lastname: Wang
authors.forename: Sheng-Xiang
authors.initials: SX
authors.lastname: Ge
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Che
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D001208:Asia; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000379:methods*; D003429:Cross Reactions; D004770:Enterovirus / Q000276:immunology*; D029821:Enterovirus A, Human / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000175:diagnosis*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D007223:Infant; D008297:Male; D012680:Sensitivity and Specificity
chemical_list: D000914:Antibodies, Viral; D007075:Immunoglobulin M