Surveillance and Analysis of Animal Rabies — China, 2004–2024

Sheng Sun¹; Jihong Ma²; Yu Xu³; Zheng Zeng⁴; Jian Liu⁵; Hada⁶; Zhongzhong Tu¹; Weidi Xu¹; Huachao Feng¹; Zihan Zhao¹; Changchun Tu^1,7,#; Ye Feng^1,8,#

1. State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun City, Jilin Province, China.

2. Department of Wildlife and Plant Conservation, National Forestry and Grassland Administration, Beijing, China.

3. Center for Biological Disaster Prevention and Control, National Forestry and Grassland Administration, Shenyang City, Liaoning Province, China.

4. Chongqing Animal Disease Prevention and Control Center, Chongqing, China.

5. Shanghai Animal Disease Prevention and Control Center, Shanghai, China.

6. Xilingol League Animal Disease Prevention and Control Center, Xilingol League, Inner Mongolia, China.

7. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou City, Jiangsu Province, China.

8. State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.

^# Corresponding author: Ye Feng, fengye621@126.com; Changchun Tu, changchun_tu@hotmail.com .

To address China's rabies situation, this study systematically summarized animal rabies surveillance data from the past two decades based on the Ministry of Agriculture and Rural Affairs' Rabies Surveillance Program. Suspected rabies cases collected through the Program between 2004–2024 underwent confirmatory diagnosis at the National Reference Laboratory (NRL) for animal rabies using national standard protocols: direct fluorescent antibody testing (FAT) and real-time RT-PCR. Epidemiological data from confirmed cases were analyzed using Geographic Information System (GIS) mapping and statistical evaluation methods. Laboratory diagnosis confirmed 331 of 433 suspected cases (76.44%) as rabies-positive. These confirmed cases originated from 15 provincial-level administrative divisions (PLADs) and revealed two distinct transmission patterns: a) dog-mediated rabies, accounting for 47.13% of cases and predominantly endemic in southern PLADs where it poses ongoing human exposure risks; and b) wildlife-mediated rabies in livestock, comprising 52.87% of cases and primarily transmitted by foxes in northern PLADs, with the Inner Mongolia Autonomous Region (IMAR) experiencing the highest burden. This nationwide surveillance has elucidated current rabies transmission dynamics across China, revealing persistent threats from dog rabies to human health in southern PLADs and emerging threats from wildlife-mediated rabies to livestock in northern border regions. These findings underscore the critical need for enhanced surveillance systems and targeted vaccination strategies addressing both domestic dog populations and wildlife reservoirs to achieve effective rabies control.

动物狂犬病监测分析 — 中国，2004–2024年

孙盛¹；马继红²；徐钰³；曾政⁴；刘健⁵；哈达⁶；涂忠忠¹；许炜迪¹；冯华超¹；赵梓含¹；涂长春^1,7,#；冯烨^1,8,#

1. 病原微生物生物安全全国重点实验室，吉林省人畜共患病预防与控制重点实验室，长春兽医研究所，中国农业科学院，长春市，吉林省，中国；

2. 野生动物保护司，国家林业和草原局，北京，中国；

3. 生物灾害预防与控制中心，国家林业和草原局，沈阳市，辽宁省，中国；

4. 重庆市动物疫病预防控制中心，重庆，中国；

5. 上海市动物疫病预防控制中心，上海，中国；

6. 锡林郭勒盟动物疫病预防控制中心，锡林郭勒盟，内蒙古自治区，中国；

7. 江苏高校动物重要疫病与人兽共患病防控协同创新中心，扬州大学，扬州市，江苏，中国；

8.病原微生物生物安全全国重点实验室，军事医学研究院，北京，中国。

^# 通讯作者：冯烨，fengye621@126.com；涂长春，changchun_tu@hotmail.com。

为应对中国狂犬病疫情，本研究基于农业农村部狂犬病监测计划，系统总结分析了近20年动物狂犬病监测数据。根据2004–2024年农业农村部狂犬病监测计划，收集疑似动物狂犬病病例，国家动物狂犬病参考实验室根据国家狂犬病检测标准方法（直接荧光抗体试验和实时RT-PCR试验）进行确诊，同时运用统计学方法和Geographic Information System (GIS)软件分析了中国动物狂犬病流行情况。433例疑似动物狂犬病病例中确诊331例（76.44%），阳性病例分布于15个省份，呈现两种传播模式：其一，犬相关的狂犬病占47.13%，主要流行于南方省份；其二，野生动物相关的家畜狂犬病占52.87%，狐狸是主要的传播来源，发生在北方省份，内蒙古自治区最为严重。本次全国性监测揭示了中国动物狂犬病流行特征：南方省份犬传人狂犬病持续威胁公共卫生安全，北方边境省份野生动物引发的家畜狂犬病日益凸显。建议通过强化监测和实施犬类/野生动物定向免疫策略来实现有效防控中国的动物狂犬病。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2025.208

Efficacy Evaluation of Virus Clearance of SYN023 in A Murine Rabies Model — China, 2025

Yixiang Ma^1,&; Zixin Fang^2,&; Xiaoyan Tao²; Shuqing Liu²; Qian Liu²; Minghui Zhang²; Pengcheng Yu^2,#; Si Liu^1,#; Wuyang Zhu²

1. Emergency Department of Peking University First Hospital, Beijing, China;

2. National Health Commission Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

^& Joint first authors.

^# Corresponding author: Pengcheng Yu, yupc@ivdc.chinacdc.cn; Si Liu, docleo@pku.edu.cn.

Rabies is a lethal yet preventable viral disease caused by lyssaviruses. It is recommended that post-exposure prophylaxis (PEP) be administered as early as possible after viral exposure. The application of passive rabies immune preparations is an important measure of rabies PEP, especially for high-risk exposures. However, owing to various factors, patients exposed to the rabies virus may not receive passive immune agents in a timely manner, thereby increasing the risk of infection. We evaluated the clearance efficacy of SYN023, an anti-rabies cocktail monoclonal antibody (mAb), in mice infected with the rabies virus strain SC16. Our results demonstrated that SYN023 rescued 69% of the infected mice at a late stage (5 days post-inoculation). Multiple daily injections of high-dose SYN023 reversed rabies infection during the late exposure stage. These findings provide a critical scientific groundwork to guide the design and implementation of future clinical trials for rabies therapy.

SYN023在狂犬病小鼠模型清除病毒效果的评价 — 中国，2025年

马义祥^1,&；方梓莘^2,&；陶晓燕²；刘淑清²；刘茜²；张明慧²；于鹏程^2#；刘斯^1,#；朱武洋²

1. 第一医院急诊科，北京大学，北京，中国；

2. 中国疾病预防控制中心病毒病预防控制所，国家卫生健康委员会生物安全重点实验室，北京，中国。

^& 共同第一作者。

^# 通信作者：于鹏程，yupc@ivdc.chinacdc.cn；刘斯，docleo@pku.edu.cn。

狂犬病是一种致死性疾病，及时、规范的狂犬病暴露预防处置（PEP）可预防发病，应用狂犬病被动免疫制剂是PEP尤其是对高危暴露患者的重要措施之一。然而，由于各种因素，暴露于狂犬病病毒的患者可能不能及时接受被动免疫制剂，从而增加了感染的风险。本研究评价了狂犬病鸡尾酒单克隆抗体SYN023对狂犬病病毒SC16株感染小鼠模型的治疗效果，69%狂犬病小鼠使用SYN023（接种后5天）后存活。狂犬病感染过程中，每日多次注射大剂量SYN023可逆转狂犬病进程。这些发现为治疗人狂犬病临床试验的设计和实施提供了重要的科学基础和支持。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2025.209

Active Surveillance on Safety and Compliance of Freeze-dried Human Rabies Vaccine (Vero Cell) — Jiangsu Province, China, 2023–2024

Yanjun Chen^1,&; Mingwei Wei^1,2,&; Xiaoteng Xu³; Yunfeng Shi¹; Shixuan Zhang³; Chenhao Wang³; Qi Liang¹; Xue Guo^3,#; Hongxing Pan^1,2,#

1. Jiangsu Provincial Center for Disease Control and Prevention (Jiangsu Provincial Academy of Preventive Medicine), Nanjing City, Jiangsu Province, China

2. School of Public Health, Nanjing Medical University, Nanjing City, Jiangsu Province, China

3. Changchun Institute of Biological Products Co., Ltd., Changchun City, Jilin Province, China.

^& Joint first authors.

^# Corresponding author: Hongxing Pan, jsphx@jscdc.cn; Xue Guo, guoxue@sinopharm.com.

Rabies vaccination compliance and safety are critical for post-exposure prophylaxis. This study compared the freeze-dried human rabies vaccine (Vero cell) under 4-dose (Zagreb) and 5-dose (Essen) regimens in real-world settings. In this open-label, randomized trial across Jiangsu Province, China between 2023 and 2024, 2,000 participants received Zagreb (n=999) or Essen (n=1,001) regimens. Active mobile-app surveillance monitored adverse reactions for 28 days post-vaccination. Compliance was assessed through dropout (discontinuation) and out-of-window administration (delayed dosing). Safety and compliance differences were analyzed using the chi-squared or Fisher’s exact tests. Overall adverse reaction rates were comparable (Zagreb: 2.10%; Essen: 2.70%; P=0.385). Solicited local adverse reactions (pain, induration, swelling, and itching) occurred at rates of 1.50% for Zagreb and 2.10% for Essen. Solicited systemic adverse reactions (fever, diarrhea, and vomiting) were 0.60% for both. Dropout rates were statistically similar (8.51% vs 8.69%; P=0.884), but Zagreb had significantly fewer out-of-window administrations (8.41% vs 16.38%; P<0.001). Compliance factors differed: Zagreb was associated with age/marital status/exposure level; Essen additionally involved education and perceived convenience. Both regimens demonstrated comparable safety profiles. The Zagreb regimen showed significantly superior schedule adherence through reduced out-of-window administrations while maintaining similar dropout rates to the Essen regimen.

冻干人用狂犬病疫苗（Vero细胞）四针法与五针法接种程序安全性与依从性主动监测研究 — 江苏省，中国，2023–2024年

陈彦君^1,&；魏明伟^1,2,&；徐晓腾³；史云凤¹；张适轩³；王辰皓³；梁祁¹；郭雪^3,#；潘红星^1,2,#

1. 江苏省疾病预防控制中心（江苏省预防医学科学院），南京市，江苏省，中国；

2. 公共卫生学院，南京医科大学，南京市，江苏省，中国；

3. 长春生物制品研究所有限责任公司，长春市，吉林省，中国。

^& 共同第一作者。

^# 通讯作者: 潘红星，jsphx@jscdc.cn；郭雪，guoxue@sinopharm.com。

狂犬病疫苗接种的依从性和安全性对暴露后预防至关重要。本研究旨在真实世界条件下比较冻干人用狂犬病疫苗（Vero细胞）分别采用四针法（Zagreb）与五针法（Essen）接种程序的安全性和依从性。 2023-2024年在江苏省开展的一项上市后安全性与依从性主动监测试验，将2000名受试者随机分配至四针法组（n=999）或五针法组（n=1001）。通过小程序进行安全性主动监测，随访全程接种后28天内的不良反应。通过脱落率（中断接种）和超窗接种率（延迟给药）评估依从性。安全性与依从性的组间差异采用卡方检验或Fisher精确检验分析。共纳入2000名受试者，其中1828人完成全程免疫。两组总体不良反应率相当（四针法：2.10%；五针法：2.70%；P=0.385）。征集性局部不良反应（疼痛、硬结、肿胀、瘙痒）发生率四针法组为1.50%，五针法组为2.10%；征集性全身不良反应（发热、腹泻、呕吐）两组均为0.60%。脱落率无显著组间差异（8.51% vs 8.69%；P=0.884），但四针法组超窗接种率显著低于五针法组（8.41% vs 16.38%；P<0.001）。依从性影响因素分析显示，四针法组依从性与年龄、婚姻状况及暴露等级相关；而五针法组还涉及教育程度及对接种程序便利性的认知。四针法与五针法接种狂犬病疫苗的安全性相当。四针法组超窗接种率显著低于五针法组，但两组脱落率无统计学差异。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2025.210

Metagenomic Next-Generation Sequencing Unmasks Atypical Rabies — Guangxi Zhuang Autonomous Region, China, 2024

He Li^1,2&; Jing Wei ^3,&; Shuwu Zhou⁴; Zhiqun Zhan⁵; Jinfang Tang⁶; Wei Wang^1,#; Huamin Tang^5,#

1. Department of Emergency Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Zhuang Autonomous Region, China;

2. Department of Emergency Medicine, The Sixth Affiliated Hospital of Guangxi Medical University, Yulin City, Guangxi Zhuang Autonomous Region, China;

3. Department of Intensive Care Unit, The Fourth People's Hospital of Nanning, Nanning City, Guangxi Zhuang Autonomous Region, China;

4. Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, Nanning City, Guangxi Zhuang Autonomous Region, China.

5. Department of Emergency, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning City, Guangxi Zhuang Autonomous Region, China;

6. Nanning Center for Disease Control and Prevention, Nanning City, Guangxi Zhuang Autonomous Region, China;

^& Joint first authors.

^# Corresponding authors: Wei Wang, wangwei@stu.gxmu.edu.cn; Huamin Tang, tanghm@gxtcmu.edu.cn.

This study reports a confirmed case of human rabies diagnosed through metagenomic next-generation sequencing (mNGS). The patient was a 22-year-old female who developed symptoms 3 months after sustaining a scratch on the upper lip from a domesticated dog, without receiving postexposure prophylaxis (PEP). She initially presented with urinary symptoms and was misdiagnosed with a urinary tract infection. Neurological symptoms subsequently emerged, prompting intensive life support interventions including mechanical ventilation, recombinant human interferon-α2b, ribavirin, norepinephrine, veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and continuous renal replacement therapy. Clinical data were collected from hospital records, including exposure history, symptoms, treatments, and outcomes. Saliva specimens were tested by reverse transcription polymerase chain reaction (RT-PCR) and mNGS. Sequencing data were processed by standard bioinformatics pipelines, and phylogenetic analysis was performed with MAFFT alignment and IQ-TREE maximum-likelihood reconstruction. Rabies virus infection was confirmed through reverse transcription polymerase chain reaction (RT-PCR) and mNGS analysis of saliva samples. The detected strain, JSTZ190314, represents the first documented case of this genotype in Guangxi, China. Despite initial stabilization with ECMO support, the patient's neurological condition deteriorated progressively, leading to brain death 28 days after neurological onset (34 days from initial urinary symptoms). mNGS proves invaluable as a diagnostic tool for atypical rabies presentations. Enhancing early clinical recognition capabilities, ensuring timely and standardized PEP implementation, and strengthening regional viral strain surveillance represent critical components for effective rabies prevention and control strategies.

宏基因组二代测序揭示非典型人狂犬病病例 — 广西壮族自治区，中国，2024年

1.急诊医学科，广西医科大学第一附属医院，南宁市，广西壮族自治区，中国；

2. 急诊科，广西医科大学第六附属医院，玉林市，广西壮族自治区，中国；

3. 重症医学科，南宁市第四人民医院，南宁市，广西壮族自治区，中国；

4.广西壮族自治区疾病预防控制中心，南宁市，广西壮族自治区，中国；

5. 急诊科，广西中医药大学附属国际壮医医院，南宁市，广西壮族自治区，中国；

6. 南宁市疾病预防控制中心，南宁市，广西壮族自治区，中国。

^& 共同第一作者。

^# 通信作者：王威，wangwei@stu.gxmu.edu.cn；唐华民，tanghm@gxtcmu.edu.cn。

本研究报告一例由宏基因组二代测序（mNGS）确诊的人类狂犬病病例。患者为一名22岁女性，于被家养犬咬伤上唇3个月后发病，既往未接受暴露后预防（PEP）。患者早期出现泌尿系统症状，误诊为泌尿系感染，随后逐渐出现神经系统症状，并接受机械通气、重组人干扰素-α2b、利巴韦林、去甲肾上腺素、静脉-动脉体外膜肺氧合（VA-ECMO）及连续性肾脏替代治疗（CRRT）等综合生命支持治疗。收集患者的临床资料，包括暴露史、症状、治疗经过和转归。采集唾液标本进行逆转录聚合酶链反应（RT-PCR）检测及 mNGS 分析。测序数据经标准生物信息学流程处理，并利用 MAFFT 软件进行序列比对，采用 IQ-TREE 软件在最大似然框架下进行系统发育重建。唾液标本的逆转录聚合酶链反应（RT-PCR）检测提示狂犬病毒核酸阳性，进一步mNGS分析确认感染，并鉴定出毒株为JSTZ190314型，为广西首次报道的该基因型人类感染病例。尽管ECMO在病程中被撤除，患者仍于神经症状出现28天后（自最初泌尿系统症状起34天）进展为脑死亡。mNGS在狂犬病非典型临床表现的诊断中具有重要价值。加强早期临床识别、确保PEP的及时和规范实施、并完善区域狂犬病毒毒株监测，是有效预防和控制人类狂犬病的关键措施。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2025.211

The Clinical Advantages of Anti-Rabies Monoclonal Antibodies in Post-Exposure Prophylaxis — Worldwide, 2016–2025

Qingjun Chen¹; Wenwu Yin²; Zhenggang Zhu^3,#; Chuanlin Wang^4,#

1. Emergency Medicine Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China;

2. Infectious Disease Management Department, Chinese Center for Disease Control and Prevention, Beijing, China;

3. Immunization Program, Wuhan Center for Disease Prevention and Control, Wuhan City, Hubei Province, China;

4. Emergency Department/Trauma Center, Peking University People's Hospital, Beijing, China.

^# Corresponding authors: Chuanlin Wang, wangchuanlinvip@163.com; Zhenggang Zhu 13308645379@163.com.

Post-exposure prophylaxis (PEP) represents the critical intervention for preventing rabies and comprises three essential components: thorough wound cleansing, vaccination, and administration of rabies immunoglobulin (RIG) or monoclonal antibodies (mAb) for category III exposures. The World Health Organization (WHO) endorses the use of mAb cocktails as an effective replacement for RIG in PEP protocols. Since 2016, four anti-rabies monoclonal antibodies (RmAb) have received clinical approval for use in India and China. This article provides an overview of the current research status of RmAb. By reviewing clinical studies related to RmAb, it highlights the clinical advantages of RmAb over HRIG in terms of efficacy, accessibility, safety, acceptability, and clinical application in special populations. Additionally, it explores the future clinical prospects of RmAb, including their use in extremely high-risk cases, their impact on circulating antibodies, and their potential role in rabies treatment.

抗狂犬病单克隆抗体在暴露后预防中的临床优势 — 世界范围，2016–2025年

陈庆军¹; 殷文武²; 朱政纲^3,#; 王传林^4,#

1. 急诊医学临床研究中心，北京朝阳医院，首都医科大学，北京市，中国；

2. 传染病管理处，中国疾病预防控制中心，北京市，中国；

3. 免疫规划所，武汉市疾病预防控制中心，武汉市，湖北省，中国

4. 人民医院急诊科/创伤救治中心，北京大学，北京市，中国。

^# 通信作者：王传林，wangchuanlinvip@163.com; 朱政纲，13308645379@163.com。

狂犬病是一种致死率接近100%的人畜共患传染病，目前尚无有效治疗狂犬病的抗病毒药物，而狂犬病暴露后预防（PEP）是临床上处理狂犬病的关键措施，包括伤口处理、疫苗接种和被动免疫。被动免疫制剂目前最常用的是人狂犬病免疫球蛋白（HRIG），然而随着技术发展，狂犬病单克隆抗体制剂（RmAb）多个方面表现出了优势，世界卫生组织（WHO）也推荐使用鸡尾酒单克隆抗体代替HRIG用于PEP。本文就RmAb的研究现状进行概述；通过综述RmAb相关临床研究，从有效性、可及性、安全性、易接受性和特殊人群中临床应用等方面，说明RmAb相比HRIG的临床优势；并对RmAb在极高危病例中的临床应用，RmAb对循环抗体和狂犬病治疗等方面展望RmAb未来临床应用。

For more information: https://weekly.chinacdc.cn/en/article/doi/10.46234/ccdcw2025.212