Since 2016, enterovirus 71 (EV71) vaccines have been approved for market entry, and little is known about how the epidemiology of hand, foot, and mouth disease (HFMD) has been affected by the introduction of the vaccines in Yunnan Province. The study describes the epidemiological characteristics of HFMD before and after the introduction of EV71 vaccination in Yunnan Province.Surveillance data collected between 2008 and 2019 were analyzed to produce epidemiological distribution on cases, etiologic composition, and EV71 vaccination coverage, as well as to compare these characteristics before and after EV71 vaccination.A total of 1,653,533 children received EV71 vaccines from 2016 through 2019 in Yunnan. The annual EV71 vaccination coverage rate ranged from 5.53 to 15.01% among children ≤5 years old. After the introduction of EV71 vaccines, the overall incidence of HFMD increased and reached over 200 cases per 100,000 population-years in 2018 and 2019. However, the case severity and case fatality rate decreased and remained lower than 1 and 0.005% after 2016, respectively. EV71-associated mild, severe and fatal cases sharply decreased. The predominant viral serotype changed to non-EV71/non-CV-A16 enteroviruses which were detected across the whole province.Non-EV71/non-CV-A16 enteroviruses became the predominant strain and led to a higher incidence in Yunnan. Expanding EV71 vaccination and strengthening laboratory-based surveillance could further decrease the burden of severe HFMD and detect and monitor emerging enteroviruses.© 2021. The Author(s).

Hand, foot, and mouth disease (HFMD) has posed a serious threat to children’s health. Three inactivated monovalent enterovirus 71 (EV71) vaccines are proved to be highly efficacious in phase III clinical trials and are now available in China.

Background: Vaccination is a highly effective strategy for the prevention of enterovirus A71 (EV-A71)—hand, foot, and mouth disease (HFMD). Three inactivated EV-A71 vaccines in China have demonstrated remarkable efficacy against EV-A71-HFMD during clinical trials, exhibiting vaccine effectiveness (VE) exceeding 90% and few adverse events (AEs). However, the effectiveness of vaccines in the real world and its impact on the epidemiological characteristics of HFMD after the use of EV-A71 inactivated vaccine are uncertain. Methods: The odd ratio (OR) and 95% confidence (CI) were used as the effect estimates of the meta-analysis in the test-negative design (TND), and the OR was used to calculate VE: VE = (1 − OR) × 100%. Results: According to the literature search strategy, a comprehensive search was conducted in PubMed, Web of Science (including Chinese Science Citation Database and MEDLINE), and Embase, and 18 records were ultimately included in this study. Subsequently, the overall VE and 95% CI of different vaccine doses were analyzed, with the one-dose vaccine at 66.9% (95% CI: 45.2–80.0%) and the two-dose vaccine at 84.2% (95% CI: 79.4–87.9%). Additionally, the most reported AEs were mild general reactions without any rare occurrences. Simultaneously, the widespread use of the EV-A71 vaccine would lead to a reduction in both the incidence of EV-A71-associated HFMD and severe cases caused by EV-A71. Conclusion: The administration of the two-dose EV-A71 vaccine is highly effective in preventing HFMD in the real world, and the widespread use of the EV-A71 vaccine leads to a reduction in the incidence of EV-A71-associated HFMD and that of severe cases caused by EV-A71. The findings suggest that administering the two-dose EV-A71 inactivated vaccine to children aged 6 months to 71 months can be effective in preventing EV-A71-associated HFMD, highlighting the need for developing a multivalent HFMD vaccine for preventing cases not caused by EV-A71.

Measuring vaccination coverage rates and equity is crucial for informing immunization policies in China.

目的 观察肠道病毒71型（enterovirus 71，EV71）疫苗III期临床试验接种5年的免疫持久性。方法 在III期临床试验免疫原性亚组中，对完成全程两针次免疫的免前抗EV71中和抗体阴性人群进行免疫后5年采血并检测抗EV71中和抗体，对0 d、56 d、8个月、14个月、26个月、64个月同时具有抗EV71中和抗体检测数据人群评价免疫持久性。结果 共614名受试者完成5年免疫持久性血样采集并获得中和抗体检测结果，其中490名受试者同时具有0天、56 d、8个月、14个月、26个月、64个月抗EV71中和抗体检测数据，疫苗组和安慰剂对照组分别为235名和255名。EV71疫苗免疫后5年，疫苗组抗EV71中和抗体阳性率（100.00%）和抗体几何平均滴度（geometric mean titer，GMT）（369.57）均高于对照组（69.02%和55.58）。分别以抗体滴度8、16、32为阳性判定标准，疫苗组阳性率（100%、99.57%、97.87%）均高于对照组（69.02%、61.96%、59.61%）。对不同年龄亚组进行分析，6~11、12~35月龄受试者免疫后疫苗组5年抗EV71中和抗体阳性（滴度≥8）率（均为100.00%）和抗体GMT（367.14、370.64）均高于对照组（66.67%、71.27%和53.43、63.66）。在EV71疫苗免疫后的各个时间点，疫苗组抗EV71中和抗体阳性率和GMT均高于对照组。结论 该EV71疫苗两针基础免疫后能够诱导良好的免疫原性，在免疫后5年依然保持较好的免疫持久性。