Kinetics of the neutralising antibody response in patients with hand, foot, and mouth disease caused by EV-A71: A longitudinal cohort study in Zhengzhou during 2017-2019
Qi Qiu,
Jiaxin Zhou,
Yibing Cheng,
Yonghong Zhou,
Lu Liang,
Peng Cui,
Yingying Xue,
Lili Wang,
Kai Wang,
Haijun Wang,
Peng Li,
Junbo Chen,
Yu Li,
Lance Turtle,
Hongjie Yu
Affiliations
Qi Qiu
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Jiaxin Zhou
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Yibing Cheng
Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Yonghong Zhou
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Lu Liang
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
Peng Cui
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Yingying Xue
Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Lili Wang
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Kai Wang
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Haijun Wang
Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Peng Li
Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China
Junbo Chen
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China
Yu Li
Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Centre for Disease Control and Prevention, Beijing, China; WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
Lance Turtle
NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom; Tropical & Infectious Disease Unit, Royal Liverpool University Hospital (member of Liverpool Health Partners), Liverpool, United Kingdom
Hongjie Yu
School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; Department of infectious diseases, Huashan Hospital, Fudan University, Shanghai, China; Corresponding author at: School of Public Health, Fudan University, Shanghai, China, No.130, Dong An Road, Xuhui District, Shanghai 200032, China.
Background: Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) poses a serious threat to children's health. Kinetics of the neutralising antibody (NAb) response in EV-A71 infected HFMD patients remains unclear. The ideal sampling time of paired serum samples for serological diagnosis of EV-A71 infection is not well defined. Methods: HFMD inpatients admitted to Henan Children's Hospital between February 15, 2017 and February 15, 2018 were enrolled. Serial serum samples collected during hospitalisation and up to 1.5 years after discharge were tested for NAb against EV-A71. Random intercept modelling with B-spline was conducted to characterize the kinetics of the EV-A71 NAb response over time after illness onset. Findings: A total of 524 serum samples from 264 EV-A71 RNA positive HFMD inpatients were collected. NAb titres of EV-A71 infected patients were estimated to increase from 40 (95% CI: 9-180) at the day of onset to the peak of 2417 (95% CI: 1859-3143) at day 13, then remained above 1240 until 26 months. For serological diagnosis of EV-A71 infection, if at least a 4-fold rise in titre was used as the criteria, the acute phase serum should be collected at 0-4 days, the corresponding convalescent serum should be collected 14.9 days (95% CI: 9.1-23.8) after illness onset. Interpretation: EV-A71 infection induced a strong and persistent humoral immune response in HFMD patients. The findings provide a scientific support for determining the collection time of paired serum samples for serological diagnosis of EV-A71 infected HFMD patients. Funding: National Science Fund for Distinguished Young Scholars
