PLoS Med:疾控中心余宏杰课题组阐明手足口病疫苗免疫策略

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中国疾控中心余宏杰课题组围绕手足口病传播动力学规律和疫苗免疫策略等问题开展了系统研究，并于日前取得重要进展。相关成果发表于《公共科学图书馆·医学》杂志。

据了解，由肠道病毒多种血清型引起的手足口病是严重威胁儿童健康的常见传染病，主要血清型有EV-A71和CV-A16。由我国三家疫苗企业自主研发的单价EV-A71灭活疫苗的三期临床试验证明，对EV-A71相关手足口病有很好的保护效力，但对CV-A16引起的手足口病无保护作用。

研究人员创建了EV-A71和CV-A16双重循环的时间序列易感—感染—康复流行病学模型，有效拟合了实际观察的发病序列。结果显示，群体免疫驱动了由多种肠道病毒血清型引起的手足口病流行，证明EV-A71和CV-A16两种血清型间可产生短暂的交叉免疫保护。其中，单价EV-A71疫苗使用后，不会引起CV-A16所致血清型替换现象。

同时，研究人员在EV-A71疫苗的实际成本确定前，以有效疫苗成本的形式，对EV-A71疫苗免疫进行了卫生经济学研究。结果证明，与无疫苗免疫相比，如果疫苗免疫成本低于12～18.3美元，常规儿童免疫项目将具有成本效果。

来源：中国科学报

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Routine Pediatric Enterovirus 71 Vaccination in China: a Cost-Effectiveness Analysis

Joseph T. Wu,#1,* Mark Jit,#2,3 Yaming Zheng,#4 Kathy Leung,1 Weijia Xing,4 Juan Yang,4 Qiaohong Liao,4 Benjamin J. Cowling,1 Bingyi Yang,1 Eric H. Y. Lau,1 Saki Takahashi,5 Jeremy J. Farrar,6 Bryan T. Grenfell,5,7 Gabriel M. Leung,1,‡ and Hongjie Yu

Background
China accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (HFMD) cases reported to WHO during 2010–2014. Enterovirus 71 (EV71) is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6–71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China.

Methods and Findings
We characterized the economic and health burden of EV71-associated HFMD (EV71-HFMD) in China using (i) the national surveillance database, (ii) virological surveillance records from all provinces, and (iii) a caregiver survey on the household costs and health utility loss for 1,787 laboratory-confirmed pediatric cases. Using a static model parameterized with these data, we estimated the effective vaccine cost (EVC, defined as cost/efficacy or simply the cost of a 100% efficacious vaccine) below which routine pediatric vaccination would be considered cost-effective. We performed the base-case analysis from the societal perspective with a willingness-to-pay threshold of one times the gross domestic product per capita (GDPpc) and an annual discount rate of 3%. We performed uncertainty analysis by (i) accounting for the uncertainty in the risk of EV71-HFMD due to missing laboratory data in the national database, (ii) excluding productivity loss of parents and caregivers, (iii) increasing the willingness-to-pay threshold to three times GDPpc, (iv) increasing the discount rate to 6%, and (v) accounting for the proportion of EV71-HFMD cases not registered by national surveillance. In each of these scenarios, we performed probabilistic sensitivity analysis to account for parametric uncertainty in our estimates of the risk of EV71-HFMD and the expected costs and health utility loss due to EV71-HFMD. Routine pediatric EV71 vaccination would be cost-saving if the all-inclusive EVC is below US$10.6 (95% CI US$9.7–US$11.5) and would remain cost-effective if EVC is below US$17.9 (95% CI US$16.9–US$18.8) in the base case, but these ceilings could be up to 66% higher if all the test-negative cases with missing laboratory data are EV71-HFMD. The EVC ceiling is (i) 10%–14% lower if productivity loss of parents/caregivers is excluded, (ii) 58%–84% higher if the willingness-to-pay threshold is increased to three times GDPpc, (iii) 14%–19% lower if the discount rate is increased to 6%, and (iv) 36% (95% CI 23%–50%) higher if the proportion of EV71-HFMD registered by national surveillance is the same as that observed in the three EV71 vaccine phase III trials. The validity of our results relies on the following assumptions: (i) self-reported hospital charges are a good proxy for the opportunity cost of care, (ii) the cost and health utility loss estimates based on laboratory-confirmed EV71-HFMD cases are representative of all EV71-HFMD cases, and (iii) the long-term average risk of EV71-HFMD in the future is similar to that registered by national surveillance during 2010–2013.

Conclusions
Compared to no vaccination, routine pediatric EV71 vaccination would be very cost-effective in China if the cost of immunization (including all logistical, procurement, and administration costs needed to confer 5 y of vaccine protection) is below US$12.0–US$18.3, depending on the choice of vaccine among the three candidates. Given that the annual number of births in China has been around 16 million in recent years, the annual costs for routine pediatric EV71 vaccination at this cost range should not exceed US$192–US$293 million. Our results can be used to determine the optimal vaccine when the prices of the three vaccines are known.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792415/