Effectiveness of EV-A71 vaccination in prevention of paediatric hand, foot, and mouth disease associated with EV-A71 virus infection requiring hospitalisation in Henan, China, 2017–18: a test-negative case-control study

Yu, Li; Zhou, Yonghong; Cheng, Yibing; Wu, Peng; Zhou, Chunmei; Cui, Peng; Song, Ci; Liang, Lu; Wang, Fang; Qiu, Qi; Guo, Chun; Zeng, Mengyao; Lü, Long; Cowling, Benjamin J.; Yu, Hongjie

doi:10.1016/s2352-4642(19)30185-3

Cited by 50 publications

(38 citation statements)

References 27 publications

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“…The HFMD patients included in this analysis were recruited in a clinical study of HFMD at Henan Children's Hospital, which is a pediatric referral hospital in Zhengzhou of Henan province in central China. The clinical study has been introduced elsewhere [10]. In brief, all inpatient HFMD cases admitted to Henan Children's Hospital from February 15, 2017 to February 15, 2018 were invited to participate in the study.…”

Section: Study Participantsmentioning

confidence: 99%

Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

et al. 2020

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Background: Examining associations between viral genomic loads of enteroviruses and clinical severity is important for promoting and improving development of antiviral drugs related to hand, foot and mouth disease (HFMD). Methods: Throat swabs were collected from HFMD cases at acute phase of illness using a standardized technique in a prospective study. The viral genomic load was categorized into low, medium, and high groups using parameters of real-time reverse transcription-polymerase chain reaction. The clinical severities were assessed with four indicators, respectively. Findings: We analysed 1109 HFMD cases, including 538 children with CV-A6, 231 with CV-A16, 156 with EV-A71, 78 with CV-A10, 59 with CV-A4, and 47 with CV-A2. EV-A71 genomic load categories were associated with risks of diagnoses of CNS complications (p = 0.016), requiring systemic corticosteroids or IVIG (p = 0.011), intensive care unit admission (p = 0.002) and length of hospital stay over 5 days (p = 0.048). In the multivariate analyses, point estimates of adjusted odds ratio (OR) tended to increase with viral genomic loads for all four severe outcomes and ORs of highest viral genomic load were all significantly larger than one for EV-A71. Interpretation: HFMD clinical severities positively associate with viral genomic loads of EV-A71 in throat swabs. Specific antiviral drugs should be developed to reduce enterovirus load and to alleviate the clinical severities for HFMD cases.

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Section: Study Participantsmentioning

confidence: 99%

Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

et al. 2020

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“…(CVA-6) or CVA16, and there is no explanation for the effectiveness of other subtypes of EV71 (excluding C4a subtypes) [34]. These studies show that the vaccine research and development for EV71 combined with CVA6 and CVA16 and other multivalent vaccines could better prevent EV71 infection.…”

Section: Discussionmentioning

confidence: 89%

Molecular characteristics of VP1 region of enterovirus 71 strains in China

Sun

Gao

Cui

2020

Preprint

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Background: Enterovirus 71 (EV71) is the most commonly implicated as the causative agent of severe and fetal hand, foot, and mouth disease (HFMD) outbreaks.VP1 protein, a capsid protein of EV71, is responsible for the genotype of EV71, which is essential for vaccine development and effectiveness. However, the genotypes of EV71 isolates in China are still not completely clear.Methods: The VP1 gene sequences of 3712 EV71 virus strains from China, excluding repetitive sequences, and 30 known EV71 genotypes as reference strains, between 1986 and 2019 were obtained from GenBank. A phylogenetic tree, amino acid homology, genetic variation and genotype analysis of the EV71-VP1 protein were performed with MEGA 6.0 software.Results: The amino acid identity was 88.33%~100% among 3712 EV71 strains that was 93.47%~100% compared with vaccine strain H07, and 93.04%~100% compared with vaccine strains FY7VP5 or FY-23K-B. Since 2000, the prevalent strains of EV71 were mainly the C4 genotype. Among these the C4a subgenotype was predominant, the C4b subgenotype was the second, and other subgenotypes appeared sporadically between 2005 and 2018 in mainland China. The B4 genotype was the main genotype in Taiwan, and the epidemic strains were constantly changing. Some amino acid variations in VP1 of EV71 occurred with high frequencies: A289T (20.99%), H22Q (16.49%), A293S (15.95%), S283T (15.11%), V249I (7.76%), N31D (7.25%), and E98K (6.65%).Conclusion: The C4 genotype of EV71 in China can match the vaccine, which can effectively control EV71 epidemiology. However, the efficacy of the vaccine strain is partially affected by the continuous change in epidemic strains in Taiwan, China. These studies suggested that the genetic characteristics of the EV71-VP1 region should be continuously monitored, which is critical for epidemic control and vaccine design against EV71 infection in children.

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“…The immune effectiveness of inactivated vaccines mostly depends on the antigenic correlation between epidemic strains and vaccine strains, which are often best for preventing infection of the same subtype virus but are inferior against different subtypes [30]. Recent studies have also shown that the EV71 vaccine (especially in children who receive 2 doses) can effectively prevent and control childhood EV71-associated HFMD but has no protective effect against coxsackievirus (CV) A6 (CVA-6) or CVA16, and there is no explanation for the effectiveness of other subtypes of EV71 (excluding C4a subtypes) [34]. These studies show that vaccine research and development for EV71 combined with CVA6 and CVA16 and other multivalent vaccines might better prevent EV71 infection.…”

Section: Discussionmentioning

confidence: 99%

Molecular characteristics of the VP1 region of enterovirus 71 strains in China

2020

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Background: Enterovirus 71 (EV71) is the most commonly implicated causative agent of severe outbreaks of paediatric hand, foot, and mouth disease (HFMD).VP1 protein, a capsid protein of EV71, is responsible for the genotype of the virus and is essential for vaccine development and effectiveness. However, the genotypes of EV71 isolates in China are still not completely clear. Methods: The VP1 gene sequences of 3712 EV71 virus strains from China, excluding repetitive sequences and 30 known EV71 genotypes as reference strains, between 1986 and 2019 were obtained from GenBank. Phylogenetic tree, amino acid homology, genetic variation and genotype analyses of the EV71VP1 protein were performed with MEGA 6.0 software. Results: The amino acid identity was found to be 88.33%-100% among the 3712 EV71 strains, 93.47%-100% compared with vaccine strain H07, and 93.04%-100% compared with vaccine strains FY7VP5 or FY-23 K-B. Since 2000, the prevalent strains of EV71 were mainly of the C4 genotype. Among these, the C4a subgenotype was predominant, followed by the C4b subgenotype; other subgenotypes appeared sporadically between 2005 and 2018 in mainland China. The B4 genotype was the main genotype in Taiwan, and the epidemic strains were constantly changing. Some amino acid variations in VP1 of EV71 occurred with high frequencies, including A289T (20.99%), H22Q (16.49%), A293S (15.95%), S283T (15.11%), V249I (7.76%), N31D (7.25%), and E98K (6.65%). Conclusion: The C4 genotype of EV71 in China matches the vaccine and should effectively control EV71. However, the efficacy of the vaccine is partially affected by the continuous change in epidemic strains in Taiwan. These results suggest that the genetic characteristics of the EV71-VP1 region should be continuously monitored, which is critical for epidemic control and vaccine design to prevent EV71 infection in children.

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Effectiveness of EV-A71 vaccination in prevention of paediatric hand, foot, and mouth disease associated with EV-A71 virus infection requiring hospitalisation in Henan, China, 2017–18: a test-negative case-control study

Cited by 50 publications

References 27 publications

Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease

Molecular characteristics of VP1 region of enterovirus 71 strains in China

Molecular characteristics of the VP1 region of enterovirus 71 strains in China

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