Surveillance for Adverse Events Following Immunization with Domestic Sabin-Strain Inactivated Poliovirus Vaccine — China, 2015–2022

Chunxiang Fan¹; Keli Li¹; Lina Zhang¹; Yuan Li¹; Yifan Song¹; Yan Li¹; Minrui Ren¹; Lance E. Rodewald¹; Zundong Yin^1,#

1. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Immunization Programme, Chinese Center for Disease Control and Prevention, Beijing, China.

^# Corresponding author: Zundong Yin，yinzd@chinacdc.cn.

Domestic Sabin-strain inactivated poliovirus vaccine (sIPV) was approved for use in China in 2015 and introduced into the national immunization schedule in a sequential schedule with oral poliovirus vaccine (OPV) in May 2016. However, a comprehensive analysis describing the characteristics, occurrences, and incidences of adverse events following immunization (AEFI) with sIPV in China is lacking. Data on sIPV doses administered and AEFI reported from 2015 to 2022 were obtained from the CNIIS. Descriptive epidemiological methods and statistics were used to analyze and describe the characteristics, occurrences, and incidences of AEFI following sIPV in China from 2015 to 2022. From 2015 to 2022, over 110,000,000 sIPV doses were administered, and 46,748 sIPV AEFIs were reported, resulting in an AEFI reporting rate of 42.44/100,000 doses. Most AEFIs (46,333, 99.11%) were non-serious. Causality assessment determined 46,061 (98.53%) AEFIs were vaccine product-related reactions, including 44,001 (94.12%) common and 2,060 (4.41%) rare vaccine reactions. Among common vaccine reactions, reporting rates for fever >38.5°C, local redness and swelling ≥2.6 cm, and local induration ≥2.6 cm were 12.02/100,000, 5.13/100,000, and 1.67/100,000, respectively. Among rare vaccine reactions, reporting rates for anaphylactic rash, thrombocytopenic purpura, and febrile convulsion were 1.56/100,000, 0.09/100,000, and 0.03/100,000, respectively. Most reported sIPV AEFIs were non-serious, and the reporting rate of rare vaccine reactions has been very low since sIPV was approved for use in China. As sIPV remains in use in China, surveillance of AEFIs associated with this vaccine needs to be maintained.

国产Sabin株脊髓灰质炎灭活疫苗疑似预防接种异常反应监测数据分析 — 中国，2015–2022年

樊春祥¹；李克莉¹；张丽娜¹；李媛¹；宋祎凡¹；李燕¹；任敏睿¹；Lance E. Rodewald¹；尹遵栋^1，#

1.传染病溯源预警与智能决策全国重点实验室(NITFID)，免疫规划中心，中国疾病预防控制中心，北京，中国。

^# 通信作者: 尹遵栋，yinzd@chinacdc.cn。

国产Sabin株脊髓灰质炎灭活疫苗（sIPV）已于2015年获批上市使用，并于2016年5月纳入国家免疫规划疫苗儿童免疫程序，与口服脊髓灰质炎减毒活疫苗（OPV）序贯接种。此前尚未有中国整体的sIPV疑似预防接种异常反应（AEFI）报告情况和分布特征的描述分析。本研究使用中国疾病预防控制信息系统免疫规划子系统（CNIIS）中收集的中国2015-2022年sIPV接种信息和AEFI报告数据，利用描述性流行病学方法对sIPV AEFI的报告情况和基本特征进行了初步分析。2015-2022年，全国共接种超过1.10亿剂次sIPV，报告46748例AEFI，报告发生率为42.44/10万剂次。报告的AEFI中，绝大多数为非严重病例（46333例，占99.11%）。报告的AEFI分类中，46061例（98.53%）被分类为不良反应，其中44001例（94.12%）为一般反应，2060例（4.41%）为异常反应。在一般反应中，发热＞38.5℃、局部红肿直径≥2.6cm、局部硬结直径≥2.6cm的报告发生率分别为12.02/10万剂次、5.13/10万剂次、1.67/10万剂次。在异常反应中，过敏性皮疹、血小板减少性紫癜和高热惊厥的报告发生率分别为1.56/10万剂次、0.09/10万剂次和0.03/10万剂次。自sIPV在中国获批上市使用后，报告的AEFI以非严重为主，异常反应的报告发生率非常低。随着sIPV在人群中的推广使用，需继续开展该疫苗的AEFI监测。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2024.261

Impact of Immunization Strategies on Rubella Incidence During Progress Toward Rubella Control and Elimination — China, 2004–2023

Siyu Liu¹; Xia Xu¹; Qianqian Liu¹; Lin Tang¹; Xiaoqi Wang¹; Aodi Huang¹; Jiuhong Li¹; Yuexin Xiu¹; Hong Yang¹; Ning Wen¹; Lance E. Rodewald¹; Zundong Yin¹; Fuzhen Wang^1,#

1. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Immunization Programme, Chinese Center for Disease Control and Prevention, Beijing, China.

^# Corresponding author: Fuzhen Wang, wangfz@chinacdc.cn.

Since rubella was incorporated into the national disease surveillance system in 2004, rubella incidence has changed dramatically. This study analyzed the impact of immunization strategies on the age-specific and sex-specific incidence of rubella in China from 2004 to 2023 to inform efforts to accelerate rubella elimination. Annual rubella-containing vaccine (RCV) coverage levels, reported rubella cases and incidence, and vaccination status of cases were obtained from the National Immunization Program Information Management System, the National Notifiable Diseases Reporting System, and the Measles Surveillance System, and used to describe temporal trends. Incidence trends and annual percent changes (APC) by age group and sex were estimated using joinpoint regression. In 2008, RCV coverage was 51.5% for the first dose and 39.0% for the second dose, increasing to and stabilizing at 95% or above for both doses by 2012. There were 584,758 cases of rubella reported in China during 2004–2023. Joinpoint regression showed that rubella incidence initially increased, peaked in 2008, and then decreased (APC_2004–2008=47.12%, APC_2008–2023=–18.95%, P<0.05). Adolescents, aged 10–19 years, accounted for 67.8% of cases at a peak incidence in 2019 (APC_2016–2019=103.70%, APC_2016–2019=–89.76%, P<0.05); 77.8% of cases had no or unknown RCV history. The decrease in rubella incidence is closely associated with vaccination. Nationwide inclusion of RCV had a significant impact on the prevention and control of rubella. Targeted measures to address immunization gaps and maintain high surveillance sensitivity are necessary to promote rubella elimination.

风疹控制和消除进展阶段免疫策略对风疹发病率的影响 — 中国，2004–2023年

刘斯宇¹；许侠¹；刘倩倩¹；唐林¹；王晓琪¹；黄澳迪¹；李玖洪¹；修乐欣¹；杨宏¹；温宁¹；Lance E. Rodewald¹；尹遵栋¹；王富珍^1，#

1.传染病溯源预警与智能决策全国重点实验室，免疫规划中心，中国疾病预防控制中心，北京，中国。

^# 通信作者: 王富珍，wangfz@chinacdc.cn。

自2004年风疹被纳入疾病监测系统以来，风疹的发病率发生了巨大变化。本研究分析了中国2004–2023年免疫策略对风疹分年龄、性别发病率的影响，为推动消除风疹进程和预防先天性风疹综合征提供依据。通过国家免疫规划信息管理系统、国家法定传染病报告系统和麻疹监测信息报告管理系统获取含风疹疫苗（rubella-containing vaccine, RCV）接种率、风疹报告病例数和发病率、报告病例疫苗免疫史数据，描述时间变化趋势。使用Joinpoint回归分析各年龄组、性别的发病趋势和年度变化百分比（annual percent changes, APC）。2008年第1剂和第2剂RCV覆盖率分别为51.5%和39.0%，随后逐渐提高，到2012年持续维持在95%以上。2004–2023年中国共报告584,758例风疹病例。Joinpoint回归分析显示，风疹发病率逐年上升，并在2008年达到高峰，随后下降（APC_2004–2008=47.12%,APC_2008–2023=-18.95%, P<0.05）。10–19岁青少年占2019年发病高峰病例总数的67.8%（APC_2016–2019=103.70%, APC_2016–2019=-89.76%, P<0.05），其中77.8%的病例无RCV免疫史或不详。风疹发病率的降低与疫苗接种密不可分，在全国范围内纳入RCV对风疹防控工作产生了重要影响。有必要采取有针对性的措施，在保持高度监测敏感性的同时，填补人群免疫空白，持续推动消除风疹进程。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2024.262

Post-Marketing Surveillance of Adverse Events Following Meningococcal Vaccination — China, 2013–2021

Yuyang Xu ^1,2,3; Keli Li^2,3,#; Yan Li^2,3; Yuan Li^2,3; Lina Zhang^2,3; Chunxiang Fan^2,3; Minrui Ren^2,3; Zundong Yin^2,3

1. Department of Expanded Program on Immunization, Hangzhou Center for Disease Control and Prevention, Hangzhou City, Zhejiang Province, China;

2. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Immunization Programme, Chinese Center for Disease Control and Prevention, Beijing, China. 

^# Corresponding author: Keli Li, likl@chinacdc.cn.

The surveillance data of suspected adverse events following immunization (AEFI) after meningococcal meningococcal vaccine (MenV) vaccination were analyzed to understand the safety of MenV vaccine. Via Chinese National Immunization Information System (CNIIS), the AEFI case information and the number of inoculations reported after MenV vaccination in China from 2013 to 2021 were collected, and the occurrence characteristics and reported incidence of AEFI after MenV vaccination were descriptively analyzed. During the period 2013–2021, the overall reported incidence of AEFI for MenV vaccine was 37.87 per 100,000 doses. Among them, the reported incidence of adverse reactions, coincidental disorders, psychogenic reactions, and others (including unclassified, etc.) were 37.39/100,000 doses, 0.43/100,000 doses, 0.02/100,000 doses, and 0.02/100,000 doses, respectively. Among the adverse reactions, the reported incidence of general reactions and abnormal reactions were 35.47/100,000 doses and 1.93/100,000 doses, respectively. In general, the reported incidences of high fever (≥38.6°C), redness and swelling (>5.0 cm) and induration (>5.0 cm) were 14.52/100,000 doses, 0.60 per 100,000 doses, and 0.21/100,000 doses, respectively. The main abnormal reactions were allergic reactions, among which the top 5 reported incidences were allergic rash, angioedema, Henoch-Schonlein purpura, thrombocytopenic purpura and anaphylactic shock. Febrile seizures predominate in neurological cases (0.05/100,000 doses). The adverse reactions after MenV vaccination in China were mainly general reactions such as fever and local reactions, and the reported incidence of abnormal reactions was very low, mainly allergic rash, and severe abnormal reactions were extremely rare. AEFI surveillance should continue to be strengthened, especially for severe allergic reactions, to improve the sensitivity of surveillance reports and the quality of investigation and handling.

脑膜炎球菌疫苗疑似预防接种异常反应监测分析 — 中国，2013-2021年

许玉洋^1,2,3；李克莉^2,3,#；李燕^2,3；李媛^2,3；张丽娜^2,3；任敏睿^2,3；樊春祥^2,3；尹遵栋^2,3

1.杭州市疾病预防控制中心，杭州市，浙江省，中国；

2.传染病溯源预警与智能决策全国重点实验室，免疫规划中心，中国疾病预防控制中心，北京，中国。

^# 通信作者：李克莉，likl@chinacdc.cn。

分析流行性脑膜炎球菌性脑膜炎（Meningitis vaccine，MenV）疫苗接种后疑似预防接种异常反应（Adverse events following immunization，AEFI）监测数据，了解MenV疫苗使用安全性。通过中国疾病预防控制信息系统（Chinese National Immunization Information System，CNIIS）收集2013-2021年期间，在中国上市使用的MenV疫苗接种后报告的AEFI个案信息和接种剂次数，描述性分析MenV接种后AEFI的发生特征和报告发生率。在2013-2021年期间，MenV疫苗的AEFI总报告发生率为37.87/10万剂。其中，不良反应、偶合症、心因性反应和其他（包括未分类等）报告发生率分别为37.39/10万剂、0.43/10万剂、0.02/10万剂和0.02/10万剂。不良反应中，一般反应和异常反应报告发生率分别为35.47/10万剂和1.93/10万剂。一般反应中，高热(≥38.6℃)、红肿(>5.0cm)和硬结(>5.0cm)的报告发生率分别为14.52/10万剂、0.60/10万剂和0.21/10万剂。异常反应以过敏反应为主，其中报告发生率居前5位为过敏性皮疹、血管性水肿、过敏性紫癜、血小板减少性紫癜和过敏性休克。神经系统病例以热性惊厥为主(0.05/10万剂)。中国MenV疫苗接种后不良反应以发热、局部反应等一般反应为主，异常反应报告发生率极低，主要为过敏性皮疹，严重异常反应极其罕见。应继续加强AEFI监测，特别是对严重过敏反应的监测，提高监测报告敏感性和调查处置质量。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2024.263

Immunogenicity of Short-Course, High-Dose Hepatitis B Vaccination in Patients with Chronic Kidney Disease — Shanxi Province, China, 2019–2020

Linying Gao^1,2,3; Xufeng Cui^1,2,3; Xinyuan Mo^1,2,3; Zhaoyue Men1^,2,3; Xiuyang Xu^1,2,3; Tian Yao^1,3,4; Jianmin Wang⁵; Hongting Liu⁶; Hongping Guo⁷; Guowei Chai⁸; Liming Liu⁵; Fuzhen Wang⁹; Xiaofeng Liang^10,11,12,#; Suping Wang^1,2,3; Yongliang Feng^1,2,3,#

1. School of Public Health, Shanxi Medical University, Taiyuan City, Shanxi Province, China;

2. Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan City, Shanxi Province, China;

3. Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan City, Shanxi Province, China;

4. First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan City, Shanxi Province, China;

5. Department of Nephrology, Linfen Central Hospital, Linfen City, Shanxi Province, China;

6. Department of Nephrology, Yuncheng Central Hospital, Yuncheng City, Shanxi Province, China;

7. Department of Nephrology, Linfen People's Hospital, Linfen City, Shanxi Province, China;

8. Department of Nephrology, Houma People's Hospital, Houma City, Shanxi Province, China;

9. National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China;

10. Institute of Vaccine Industry, Jinan University, Guangzhou City, Guangdong Province, China;

11. Institute of Disease Control and Prevention, Jinan University, Guangzhou City, Guangdong Province, China.

12. Chinese Preventive Medicine Association, Beijing, China.

^# Corresponding authors: Yongliang Feng, yongliang.feng@sxmu.edu.cn; Xiaofeng Liang, liangxf@Jnu.edu.cn.

As one of the populations at high risk of hepatitis B virus (HBV) infection, patients with chronic kidney disease (CKD) require rapid and effective development of hepatitis B surface antibodies (anti-HBs). This study aimed to assess the immunogenicity of a triple dose of hepatitis B (HepB) vaccine in CKD patients following a 0-1-2 months program. This prospective study was conducted between May 2019 and February 2020 at four hospitals in Shanxi province, China. A total of 273 subjects were recruited. All the subjects were randomized into three groups. Two groups were inoculated with 20 μg HepB vaccine on the routine immunization schedule (at months 0,1,6) and a rapid-schedule (at months 0,1,2), the other group was administered the 60 μg HepB vaccine with a rapid-schedule (at months 0,1,2). Blood samples were collected for detecting the geometric mean concentrations (GMCs) of anti-HBs after 1 month following administration of the last dose of vaccine. The short-course, high-dose regimen of hepatitis B vaccination rapidly induced comparable immunological responses to the routine regimen, achieving a seroconversion rate of 88.5%, a high-response rate of 64.1%, and anti-HBs geometric mean concentrations of 824.1 mIU/mL. The short-course, high-dose regimen represents an effective rapid immunization strategy for CKD patients, particularly when administered prior to immunosuppressive therapy. This study provides compelling evidence for optimizing immunization protocols in the CKD population.

慢性肾脏病患者短程高剂量乙型肝炎疫苗接种的免疫原性 —中国，2019–2020年

高林英^1,2,3；崔旭锋^1,2,3；莫新元^1,2,3；门朝月^1,2,3；许修洋^1,2,3；姚添^1,3,4；王建民⁵；柳红⁶；郭红萍⁷；柴国伟⁸；刘黎明⁵；王富珍⁹；梁晓峰^10,11,12,#；王素萍^1,2,3；冯永亮^1,2,3,#

1. 山西医科大学公共卫生学院，太原市，山西省，中国；

2. 煤炭环境致病与防治教育部重点实验室，太原市，山西省，中国；

3. 山西医科大学临床流行病学与循证医学中心，太原市，山西省，中国；

4. 山西医科大学第一医院(第一临床医学院)，太原市，山西省，中国；

5. 临汾市中心医院肾内科，临汾市，山西省，中国；

6. 运城市中心医院肾内科，运城市，山西省，中国；

7. 临汾市人民医院肾内科，临汾市，山西省，中国；

8. 侯马市人民医院肾内科，侯马市，山西省，中国；

9. 免疫规划中心，中国疾病预防控制中心，北京，中国；

10. 暨南大学疫苗产业研究院, 广州市，广东省，中国；

11. 暨南大学疾病预防控制研究院, 广州, 广东省，中国；

12. 中华预防医学会, 北京，中国。

^# 通信作者：冯永亮，yongliang.feng@sxmu.edu.cn; 梁晓峰，liangxf@Jnu.edu.cn。

作为乙型肝炎病毒（HBV）感染的高危人群之一，慢性肾脏病（Chronic Kidney Disease, CKD）患者需要快速有效地诱导乙型肝炎表面抗体（抗 HBs）。本研究旨在评估 CKD 患者按0-1-2 月接种60μg乙肝疫苗后的免疫原性。这项前瞻性研究于 2019 年 5 月至 2020 年 2 月在山西省的四家医院进行。本研究共招募了 273 名18-70岁的受试者，所有受试者被随机分为三组，分别按照0-1-6月20μg、0-1-2月20μg、0-1-2月60μg方案接种乙肝疫苗。检测三组全程接种后 1个月的抗 HBs，分析抗体阳性率和几何平均浓度(GMC) 、不良反应发生率和全程接种完成率。结果显示，短程高剂量乙肝疫苗接种方案能迅速诱导出与常规接种方案相当的免疫应答，血清转换率达到88.5%，强应答率达到64.1%，抗-HBs几何平均浓度达到824.1 mIU/mL。因此，针对慢性肾脏病患者而言，短程高剂量方案是一种有效的快速免疫策略，尤其是在免疫抑制治疗前使用。本研究为优化 CKD 患者的免疫方案提供了科学可靠的证据。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2024.264

Cost-Effectiveness Analysis of Vaccination Compliance Strategies Using a Novel Hybrid Model for Influenza Vaccination

Dongfang You^1,2; Yi Zhou¹; Yan Yan³; Feng Chen^1,4; Mengyi Lu^2,4,#; Fang Shao^1,#

1. Department of Biostatistics, School of Public Health, National Vaccine innovation Platform, Nanjing Medical University, Nanjing City, Jiangsu Province, China;

2. Pharmaceutical Industry Technology Research Institute of Nanjing Medical University, Taizhou City, Jiangsu Province, China;

3. Nanjing Hanwei Public Health Research Institute Co., Ltd, Nanjing City, Jiangsu Province, China;

4. China International Cooperation Center for Environment and Human Health, Center for Global Health, Nanjing Medical University, Nanjing City, Jiangsu Prvoince, China;

^# Corresponding author: Fang Shao, shaofang@njmu.edu.cn; Mengyi Lu, mylunjyk@njmu.edu.cn.

The cost-effectiveness of vaccination strategies plays a crucial role in managing infectious diseases such as influenza within public health systems. This study evaluated the cost-effectiveness of vaccination compliance strategies by comparing an "adherence" strategy, which promoted continuous vaccination uptake, with a "volunteer" strategy through model-based simulations. We developed a novel hybrid model that integrates continuous-time agent-based models (ABMs) with a Markov model to simulate vaccination behaviors and disease dynamics at the individual level. The model incorporated socioeconomic factors, vaccine efficacy, and population interactions to evaluate the long-term health outcomes and associated costs of different vaccination compliance strategies. Simulation results demonstrated that the "adherence" strategy significantly enhanced vaccination coverage and reduced influenza cases, yielding an incremental cost-effectiveness ratio (ICER) of Chinese Yuan (CNY) 33,847 per quality-adjusted life year (QALY) gained, indicating superior cost-effectiveness compared to the "volunteer" strategy. Our findings support implementing targeted influenza vaccination compliance strategies, presenting an innovative approach to strengthen public health interventions and enhance vaccination program effectiveness. The hybrid model shows promise in informing public health policy and practice, warranting further investigation of its applications across diverse public health contexts.

利用创新的连续时间基于智能体马尔可夫混合模型的流感疫苗接种依从性策略成本效益分析

尤东方^1,2；周屹¹；闫艳³；陈峰^1,4；陆梦依^2,4,#；邵方^1,#

1. 南京医科大学国家疫苗创新平台公共卫生学院生物统计学系，南京市，江苏省，中国；

2. 南京医科大学泰州医药产业研究院，泰州市，江苏省，中国；

3. 南京汉卫公共卫生研究院有限公司，南京市，江苏省，中国；

南京医科大学全球健康中心中国环境与人类健康国际联合研究中心，南京市，江苏省，中国。

^# 通信作者：邵方，shaofang@njmu.edu.cn；陆梦依，mylunjyk@njmu.edu.cn。

在公共卫生方面，疫苗接种策略的成本效益对流感等传染病的管理至关重要。本研究聚焦于评估疫苗接种依从性策略的成本效益，特别是通过模型的模拟仿真，将鼓励持续接种的“坚持”策略与“志愿”策略进行比较。利用连续时间基于智能体模型（ABM）和马尔可夫模型，提出了一种创新的混合模型来模拟个体水平的疫苗接种行为和疾病动力学。该模型纳入了社会经济因素、疫苗效力和人口交互，以评估不同疫苗接种依从性策略相关的长期健康结局和成本。模拟仿真结果显示，“坚持”策略显著增加了疫苗接种并减少了流感病例，每个质量调整生命年（QALY）的增量成本效益比（ICER）为人民币（CNY）33,847，表明与“志愿”策略相比，“坚持”策略在成本效益上更具优势。研究结果支持采用针对性的流感疫苗接种依从性策略，为加强公共卫生干预和促进更有效的疫苗接种计划提供了一种新方法。该混合模型展示了为公共卫生政策和实践提供信息的潜力，值得进一步探索其在不同的公共卫生背景下的应用。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2024.265