Early Evidence of Inactivated Enterovirus 71 Vaccine Impact Against Hand, Foot, and Mouth Disease in a Major Center of Ongoing Transmission in China, 2011–2018: A Longitudinal Surveillance Study

• Published in: Clinical infectious diseases 2020-12, Vol.71 (12), p.3088-3095
• Main Authors: Head, Jennifer R, Collender, Philip A, Lewnard, Joseph A, Skaff, Nicholas K, Li, Ling, Cheng, Qu, Baker, Julia M, Li, Charles, Chen, Dehao, Ohringer, Alison, Liang, Song, Yang, Changhong, Hubbard, Alan, Lopman, Benjamin, Remais, Justin V
• Format: Article
• Language: English
• Subjects: Asia; Child; China - epidemiology; Enterovirus; Enterovirus A, Human; Hand, Foot and Mouth Disease - epidemiology; Hand, Foot and Mouth Disease - prevention & control; Humans; Infant; Major and Commentaries; Vaccines, Inactivated
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciz1188

Abstract Background Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), associated with severe manifestations of the disease. Pediatric immunization with inactivated EV71 vaccine was initiated in 2016 in the Asia-Pacific region, including China. We analyzed a time series of HFMD cases attributable to EV71, coxsackievirus A16 (CA16), and other enteroviruses in Chengdu, a major transmission center in China, to assess early impacts of immunization. Methods Reported HFMD cases were obtained from China’s notifiable disease surveillance system. We compared observed postvaccination incidence rates during 2017–2018 with counterfactual predictions made from a negative binomial regression and a random forest model fitted to prevaccine years (2011–2015). We fit a change point model to the full time series to evaluate whether the trend of EV71 HFMD changed following vaccination. Results Between 2011 and 2018, 279 352 HFMD cases were reported in the study region. The average incidence rate of EV71 HFMD in 2017–2018 was 60% (95% prediction interval [PI], 41%–72%) lower than predicted in the absence of immunization, corresponding to an estimated 6911 (95% PI, 3246–11 542) EV71 cases averted over 2 years. There were 52% (95% PI, 42%–60%) fewer severe HFMD cases than predicted. However, the incidence rate of non-CA16 and non-EV71 HFMD was elevated in 2018. We identified a significant decline in the trend of EV71 HFMD 4 months into the postvaccine period. Conclusions We provide the first real-world evidence that programmatic vaccination against EV71 is effective against childhood HFMD and present an approach to detect early vaccine impact or intended consequences from surveillance data. The number of cases of severe hand, foot, and mouth disease (HFMD) and enterovirus 71 (EV71) declined by an estimated 52% and 60%, respectively, following initiation of a pediatric EV71 immunization program in Chengdu, China.