Cost-effectiveness of bivalent versus monovalent vaccines against hand, foot and mouth disease

Clin Microbiol Infect. 2020 Mar;26(3):373-380. doi: 10.1016/j.cmi.2019.06.029. Epub 2019 Jul 4.


Objectives: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) were responsible for 43.3% (235 123/543 243) and 24.8% (134 607/543 243) of all laboratory-confirmed hand, foot and mouth disease (HFMD) cases during 2010-2015 in China. Three monovalent EV71 vaccines have been licensed in China while bivalent EV71/CA16 vaccines are under development. A comparative cost-effectiveness analysis of bivalent EV71/CA16 versus monovalent EV71 vaccination would be useful for informing the additional value of bivalent HFMD vaccines in China.

Methods: We used a static model parameterized with the national HFMD surveillance data during 2010-2013, virological HFMD surveillance records from all 31 provinces in mainland China during 2010-2013 and caregiver survey data of costs and health quality of life during 2012-2013. We estimated the threshold vaccine cost (TVC), defined as the maximum additional cost that could be paid for a cost-effective bivalent EV71/CA16 vaccine over a monovalent EV71 vaccine, as the outcome. The base case analysis was performed from a societal perspective. Several sensitivity analyses were conducted by varying assumptions governing HFMD risk, costs, discounting and vaccine efficacy.

Results: In the base case, choosing the bivalent EV71/CA16 over monovalent EV71 vaccination would be cost-effective only if the additional cost of the bivalent EV71/CA16 compared with the monovalent EV71 vaccine is less than €4.7 (95% CI 4.2-5.2). Compared with the TVC in the base case, TVC increased by up to €8.9 if all the test-negative cases were CA16-HFMD; decreased by €1.1 with an annual discount rate of 6% and exclusion of the productivity loss; and increased by €0.14 and €0.3 with every 1% increase in bivalent vaccine efficacy against CA16-HFMD and differential vaccine efficacy against EV71-HFMD, respectively.

Conclusions: Bivalent EV71/CA16 vaccines can be cost-effective compared with monovalent EV71 vaccines, if suitably priced. Our study provides further evidence for determining the optimal use of HFMD vaccines in routine paediatric vaccination programme in China.

Keywords: Bivalent vaccine; Cost-effectiveness; Coxsackievirus A16; Enterovirus 71; Hand, foot and mouth disease.

MeSH terms

  • Algorithms
  • Child, Preschool
  • China / epidemiology
  • Cost-Benefit Analysis
  • Enterovirus A, Human / classification
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Hand, Foot and Mouth Disease / prevention & control*
  • Humans
  • Infant
  • Models, Theoretical
  • Outcome Assessment, Health Care
  • Vaccination
  • Viral Vaccines / immunology*


  • Viral Vaccines