Ethics statement

China CDC approved the SARE assessment as a program evaluation activity that relied on routine public health and animal health surveillance data as well as publicly available data, and therefore was exempt from institutional review board assessment.

SARE tool

The Stepwise Approach towards Rabies Elimination (SARE) assessment tool was jointly developed by FAO, GARC and WHO to support rabies-endemic countries in the development and implementation of their own sustainable rabies elimination strategy. The tool provides an expert-reviewed and non-prescriptive six-stage roadmap, ranging from ‘Stage 0’–no information on rabies, to ‘Stage 5’–valid and timely data confirming rabies elimination [12]. The tool is divided into seven categories which align with the Global Framework for the Elimination of Dog-Mediated Human Rabies (STOP-R framework) [13] and the ASEAN Strategic Plan. The categories include the following.

1. Rabies Information, Education, and Communication–advocacy initiatives implemented in country or province;
2. Dog population related issues–dog population size, turnover, and management practices;
3. Prevention and control–existing rabies intervention approaches in place (e.g., availability and use of dog vaccine, biologics and human PEP);
4. Data collection and analysis–existing surveillance network and epidemiologic analysis of rabies data;
5. Laboratory diagnosis–diagnostic capacity for human and animal rabies at national and provincial level;
6. Cross-cutting issues–collaboration across human and animal health sectors and other stakeholders;
7. Legislation–existing legislation on rabies control and elimination in country or province.

Assessment participants from human and animal sectors answer either “yes” or “no” to a set of 115 general and technical questions across the seven categories listed above. These answers are represented as 1 or 0 and totaled across the seven categories. The SARE score calculated from this total indicates the stage of progress towards rabies elimination.

1. Stage 0: No information on rabies is available, but rabies is suspected to be present
2. Stage 1: Assessment of local rabies epidemiology, elaboration of a short-term rabies action plan
3. Stage 2: Development of a national rabies prevention and control strategy
4. Stage 3: Full-scale implementation of the national rabies control strategy
5. Stage 4: Maintenance of human rabies freedom, elimination of dog rabies
6. Stage 5: Freedom from human and dog rabies, ongoing monitoring and evaluation

Each stage includes multiple essential and non-essential activities. Although not all the activities are mandatory, the essential activities determine whether a country can advance to the next stage. The non-essential activities provide additional guidance for evaluating progress within a specific stage towards the goal of eliminating dog-mediated rabies.

SARE assessment activities and next step planning

The SARE assessment tool and related materials were translated into Chinese for the assessment. Assessment participants included 33 representatives from national- and 12 provincial-level human and animal health sectors (Table 1). The 12 provincial-level teams were selected according to the current human rabies case burden (high, low and moderate), interest in participating in the assessment, and ability to aggregate the data needed to complete the assessment tool. The 33 representatives were divided into 13 teams–one for the national rabies programs and 12 individual teams for each province participating in the assessment.

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Table 1. Agencies^* participating in the Stepwise Approach towards Rabies Elimination (SARE) assessment, Beijing, China, March 2019.

https://doi.org/10.1371/journal.pntd.0009274.t001

Before starting the SARE assessment, representatives from each of the 13 teams introduced the status of human and animal rabies and current prevention and control activities for their respective national or provincial level program. Input for several provincial level scoring criteria relied on national level information, particularly for legislation and vaccine availability. The 13 teams completed the tool collaboratively with guidance from US CDC staff. This process generated national and individual provincial level scores. Due to similar findings across the provincial-level rabies programs, assessment participants collaborated to outline goals and priority activities for each of the seven SARE categories. National and provincial-level representatives were divided into seven three- to five-member groups to outline the next steps for addressing the identified gaps for each category. An international rabies consultant was assigned to each team to help guide discussions and provide examples from other countries.

Current rabies control activities in China

Human rabies has been a notifiable disease in China since the early 1950s. Since 2003, all human cases have been reported to the national notifiable disease surveillance reporting system (NNDRS). Each suspected human rabies case is investigated by county-level Center for Disease Control (CDCs) and reported directly to NNDRS which is maintained by China CDC in Beijing. China has made substantial progress in reducing human rabies since peaking with more than 3,000 reported cases in 2007. The mean number of annually reported human rabies cases declined to 661 between 2014 and 2018. This is significantly lower than global burden estimates from 2015, suggesting that 6,002 (95% CI: 1,000–11,000) human rabies cases may occur in China each year [1]. The majority of dog-mediated rabies cases occur in the rural areas of five high-risk provinces in Southern China–Hunan, Guangdong, Guangxi, Guizhou, and Yunnan [14,15] (Fig 1), and less than 2% of human cases are laboratory confirmed. The difference between reported cases and disease burden estimates, therefore, may reflect methodologic considerations (eg. age of some of the data sources used to generate these estimates from ~2010) and actual under-reporting of rabies in certain areas of the country.

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Fig 1. Location of the 12 provinces participating in the SARE Workshop by dog-mediated rabies burden, March 2019, China.

(Note: China CDC and China Animal CDC offices are located in Beijing. SARE referred to Stepwise Approach towards Rabies Elimination).

https://doi.org/10.1371/journal.pntd.0009274.g001

Health care for potential rabies exposures, including PEP, is available at county-level CDCs and township-based rabies clinics, and is administered according to recommendations and wound categories defined by WHO [16]. PEP vaccination series can be administered using either the Zagreb 2-1-1 or the five-dose Essen regimens. Rabies immune globulin is provided for WHO category III exposures (i.e., single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from animal licks, exposures due to direct contact with bats). Both human rabies immune globulin (HRIG) and equine rabies antiserum (ERA) are approved in China. The Chinese National Medical Products Administration review and approve the use of human rabies vaccines and rabies immune globulin. The full PEP series is currently paid by the patient or patient’s family as an “out of pocket” cost of approximately $US48.

The Department of Public Security (DPS) is responsible for management of the dog population in urban areas. Eight provinces and more than 70 cities have issued additional regulations on dog management. Beijing Municipality, for example, has issued a regulation limiting each household to only one dog [17]. DPS also captures or collects unlicensed, biting, wild or dead dogs identified in urban areas. Dog rabies has been a nationally notifiable animal disease since the early 1950’s. According to National Animal Rabies Prevention and Control Plan, biting dogs showing rabies-like clinical signs should be evaluated by the local ACDC as suspected rabid dogs [10]. These dogs should be tested and confirmed for rabies by the national reference laboratory for animal rabies. Provincial ACDCs submit monthly reports on suspected and confirmed dog rabies to the Animal Disease Surveillance System (ADSS), which is maintained by the China Animal CDC in Beijing. In 2017, 65 rabid dogs were reported to ADSS [18]. The majority of these dogs were reported as suspected rather than laboratory confirmed rabies. WHO estimates that China is home to approximately 28 million domestic, stray and free-roaming dogs [3].

The Department of Animal Husbandry and Veterinary Medicine in the Ministry of Agriculture and Rural Affairs are responsible for the provision of dog rabies vaccinations. These responsibilities include supplying rabies vaccine for veterinary use, administering dog rabies vaccine, recording immunization history and issuing of "domestic dog rabies immunization certificate", and monitoring rabies outbreaks among dogs. Dog owners are required by law to register pets at the local Department of Public Security annually, after which dogs are vaccinated against rabies [10,19]. The cost of annual dog registration (which includes the rabies vaccination) varies by province and can range from $28 to $140. Five international and ten domestically manufactured animal rabies vaccines are available for use in China. The China Institute of Veterinary Drugs Control (IVDC) is responsible for reviewing and approving the use of animal vaccines. According to records maintained by the Department of Public Security, approximately 40% of domestic (owned) dogs are vaccinated against rabies.

SARE assessment outcomes

Results for each of the seven assessment categories are presented in Fig 2 and S1 Table. National and provincial level programs have accomplished the greatest progress in data collection and analysis, legislation and capacity to perform laboratory diagnosis for rabies. At the same time, the prevention and control and dog population management components had the largest number of pending activities and require the most attention. Based on these accomplishments and pending activities, China received a SARE score of 1.5 out of 5. Eleven of the 12 provinces also received a score of 1.5. The exception was for Hubei Province, with a score of 0.5. This lower score was primarily due to low laboratory capacity. Low dog vaccination coverage, lack of Integrated Bite Case Management (IBCM) at local level, lack of national strategy for dog population management (DPM), no baseline number of dogs, lack of effective inter-sectoral rabies task force at any level contributed to the low SARE scores at both the national and provincial level (Table 2). A qualitative description of the SARE results is included below.

1. Collection and analysis of data:
   National surveillance systems for human and animal rabies have been established in China. Although these systems operate separately, data are analyzed on a regular basis. Feedback is provided to provincial and local level rabies programs through an annual rabies report. National support is provided to local and provincial CDCs to conduct epidemiologic investigations of human cases and to monitor use of PEP in high-risk regions. Gaps were identified in animal rabies case reporting (the number of dog rabies was far below the number of human cases). Additionally, information sharing between the human and animal health sectors was infrequent.
2. Prevention and control:
   Human rabies prevention has focused primarily on increasing availability and access to PEP following potential rabies exposures. Chinese manufacturers provide rabies vaccine for domestic use. Because the vaccine meets international standards, the manufacturers have applied for vaccine pre-certification from the WHO. China recently issued the Rabies Post Exposure Prophylaxis Guidelines (version 2009) [20] and the Rabies Prevention and Control Technical Guidelines (version 2016) [21] to standardize rabies PEP practices. These documents incorporate information included position papers and technical reports published by WHO [14,22]. The department of health has modified the medical insurance system, including implementation of the New Rural Cooperative Medical System, to allow for greater reimbursement for PEP related health care expenses in some provinces such as Guizhou, Hunan and Guangxi [23]. This health system’s approach has increased the quality and affordability of the PEP, especially in the rural areas of these high-risk provinces, and has contributed to the observed decline of human rabies cases.
   Controlling and preventing rabies in the dog population remains limited in China, partially due to the lack of uniform policies and guidelines as well as facilities for dog observation (following a bite event). Dog rabies vaccination is provided with pet registration and coverage is generally high in urban settings (e.g., above 70% in Shanghai and in the Pearl River Delta region in Guangdong Province). However, dog registration and vaccination in rural areas are weakly managed and vaccination coverage remains low. The Red-Collar Program, a pilot dog vaccination campaign project, was implemented in three counties in Guizhou, Anhui, and Shanxi Provinces [24]. The campaign achieved 92% vaccination coverage among domestic (owned) dogs. China has not yet implemented a large-scale mass dog vaccination campaign targeting stray and free-roaming dogs.
3. Controlling the number of dogs:
   China’s public security sector is responsible for the registration of dogs. Dog registration and management has greatly improved in urban settings [25,26]. Several non-governmental organizations have been established to collaborate with government agencies in providing shelter and management of stray dogs [27,28]. The lack of national and provincial level strategies and plans for dog population control was a major gap identified in the SARE assessment. During previous public emergencies (clusters of dog bites), dog population was reduced by euthanizing identified stray and free-roaming dogs. China has not yet implemented a dog census, and information on the number of both domestic and free-roaming dogs is currently based on WHO generated estimates [3].
4. Laboratory diagnosis:
   The national laboratory at China CDC, Beijing is responsible for diagnosis of human rabies using tests recommended by WHO, including the Direct Fluorescent Antibody (DFA) Test, Immunohistochemistry (IHC) Test, Direct Rapid Immunohistochemistry Test (DRIT), Real Time RT-PCR, virus isolation and rabies virus variant typing. This capacity also exists at the provincial level and in certain prefecture-level CDC laboratories. Because of challenges in obtaining specimens from human cases, less than 2% of all reported human rabies cases are laboratory confirmed. On animal side, the national and OIE reference laboratory for animal rabies, designated by Ministry of Agriculture and Rural Affairs of China and OIE respectively, is responsible for diagnosis of animal rabies at national level, but the laboratory capacity at the local levels remains weak.
5. Health promotion and rabies prevention education:
   Health promotion and rabies prevention education activities are conducted annually at the national and provincial level on World Rabies Day [23]. The National 12320 Health Hotline Management Office and the China Center for Health Education have developed and distributed rabies education material through social media channels (Weibo and WeChat). Other rabies prevention and control promotion material has been shared through national and local newspaper outlets. However, none of the provincial level representatives had developed strategies or plans for the systematic or continuous implementation of rabies prevention and education activities. Most current rabies education materials have not yet been adapted to target different socio-economic, age, and ethnic at-risk population in China.
6. Cross-department cooperation:
   During public emergencies, such as numerous bites or wounds caused by single or multiple dogs in a specific community, human and animal staff will meet on an ‘ad-hoc’ basis to develop and implement an immediate response plan. If necessary, officials will provide PEP and other treatments in the injured population. Additionally, human and animal health sector staff meet once a year to discuss rabies case reports and share prevention and control information. However, neither national nor provincial human and animal health sector officials have developed strategic and operational plans to outline the steps and actions needed to achieve the elimination of dog-mediated human rabies. The lack of a national strategic plan and a flexible “One-Health” cross-sector coordination committee were identified as major gaps.
7. Laws and regulations:
   Rabies is a notifiable human and animal disease; both human and animal health care staff must legally report identified cases within 24 hours [9]. Rabies vaccination requirements for dogs and other pets are determined according to provincial (e.g., Guizhou Province) or prefecture (e.g., Chuxiong Prefecture, Yunnan Province) level regulations. Enforcement of these laws and regulations varies by prefecture, county, and province. National level regulations for dog population management and stray or free-roaming dog rabies vaccination have not yet been developed or implemented.

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Fig 2. Summary of results for the National Rabies Program and for 12 Provincial level Programs, by the seven categories outlined in the SARE assessment tool, China, March 2019.

(Note: For each category, the number of pending and accomplished activities are presented. SARE referred to Stepwise Approach towards Rabies Elimination).

https://doi.org/10.1371/journal.pntd.0009274.g002

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Table 2. Common gaps, limitations, and barriers at provincial level ^*identified from the Stepwise Approach towards Rabies Elimination (SARE) assessment, China, March 2019.

https://doi.org/10.1371/journal.pntd.0009274.t002

Rabies elimination in China–Next steps

Although substantial progress has been made in China on reducing the burden of human rabies, the SARE assessment identified several gaps that need to be addressed to achieve the dog-mediated human rabies elimination by 2030. Short-, medium-, and long-term goals and priority activities from the group discussions are summarized in Table 3. These are described by SARE category below.

1. Collection and analysis of data:
   Government officials can facilitate routine sharing of surveillance data across the human, animal, and public security sectors through official cross-agency agreements. This should include official authorization for staff from each sector to jointly collect, review, and analyze human and animal data to inform provincial and national-level decision making related to rabies elimination program progress and activities. In the long-term, developing and implementing an integrated surveillance system (including uniform standard operating procedures [SOPs]) for effectively sharing the surveillance data of human and animal rabies will be critical for achieving and documenting rabies elimination. Integration of cross-sector data using a web-based rabies surveillance database and development of a dashboard to visualize dog rabies vaccination and information on case-reports could be helpful.
2. Prevention and control of rabies:
   Development of SOPs outlining the roles and responsibilities of each sector in the prevention and control of rabies is a short-term priority. These SOPs must clearly define the roles of the human and animal CDCs as well as the role of the public security departments in dog management, particularly in rural and high-risk areas for rabies. Additional pilot-projects are needed in the medium-term to identify best practices for increasing rabies vaccination coverage in the domestic, stray, and free-roaming dog populations.
3. Laboratory diagnosis:
   In the short-term, efforts should be made by national laboratory staff to standardize the methods used for rabies diagnostic testing and communicate these methods to provincial-level laboratory personnel through training and mentoring. The national laboratory staff should also evaluate commercial rabies diagnostic kits and inform provincial laboratories accordingly. Greater collaboration and regular communication between human and animal rabies laboratories are needed in the medium- and long-term, particularly to assess rabies elimination through laboratory testing and confirmation. A key laboratory component in the elimination plan is to increase specimen collection among probable human rabies cases. Increasing provincial level capacity to collect, test, and diagnose animal rabies cases will also be critical.
4. Controlling on the number of dogs:
   A working group of experts from the human, animal, public security sectors as well as urban management and environmental sanitation and forestry should be established as soon as possible. The working group should develop, implement and monitor a strategy for improving dog population management. Also, in the short-term, a pilot dog census should be implemented in a high-risk county to assess feasibility prior to expanding to a larger area. As a medium-term activity, cross-sector training of professional staff on dog management policies and best practices should be developed and implemented. Staff at high risk of rabies exposures (i.e., contact with stray and suspected rabid dogs) should be provided with pre-exposure rabies vaccination as part of the training program.
5. Cross-department cooperation:
   The SARE assessment provided an initial opportunity for cross-sector collaboration on rabies prevention and control. International organizations–such as WHO, FAO, and OIE–described additional opportunities for cross-sector engagement through the Tripartite Guidelines [29]. China CDC recently conducted a One Health Zoonotic Disease Prioritization (OHZDP) workshop and identified rabies as a zoonotic disease of national concern [30]. Consistent with outcomes from the OHZDP workshop, a One Health working group should be established at the government level as soon as possible and include representatives from human, animal, public security, and city administration and environmental health sectors. The group should ideally meet on a quarterly basis to initially develop, and later revise, the rabies elimination strategy, as needed. Progress updates from each sector should be provided. Provincial level officials should also establish cross-sector working groups as a short-term priority activity.
6. Health promotion and rabies prevention education:
   As a short-term priority, national and provincial level staff should develop a comprehensive communication and health education plan to address each stage of the progress towards rabies elimination. The plan should develop specific approaches and materials for key populations in the high-risk provinces and target populations with varying education levels and language skills (e.g., increase use of images and videos). All communication plans should ensure consistent messaging and be disseminated through various media channels, including Weibo and WeChat. Consistent messaging should be based on scientific information for rabies prevention, use of PEP, dog vaccination and best practices for dog population management. The Chinese Center for Health Education and China CDC 12320 Health Hotline management office should engage counterparts at the provincial level as part of this short-term priority.
7. Laws and regulations:
   National and provincial representatives agreed that laws and regulations on dog rabies vaccination and management of the dog population should be made at the national level. National laws and regulations are essential for promoting and improving dog vaccination and population management related practices at the provincial and local levels. Approval of national level legislation are short- and medium-term goals.

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Table 3. Short-, medium-, long-term goals^* and priority activities identified from Stepwise Approach towards Rabies Elimination (SARE) workshop participants representing national and 12 provincial level human and animal health sector offices, March 2019.

Goals and activities were identified following completion of the SARE assessment.

https://doi.org/10.1371/journal.pntd.0009274.t003

Improving the SARE tool

The current SARE tool consists of seven categories and 115 questions and is comprehensive and specific, and thus can play a concrete and practical role in guiding countries on the next steps towards achieving rabies elimination. However, the tool is general, and the scoring factors in each stage may not reflect the critical factors in every rabies-endemic country. Additional relevant factors could be identified and incorporated into the tool from a review of the results and feedback from countries previously completing the assessment.

In China, the affordability and appropriate use of PEP are important factors in reducing the burden of human rabies. Although mass dog vaccination is the primarily strategy for eliminating dog-mediated human rabies, appropriate and timely use of PEP remains a secondary line of defense in countries with endemic rabies. Therefore, adding two to three questions to assess the affordability and appropriate use of PEP could help improve the SARE Tool. Example questions include: 1) Is the cost of PEP fully or partial covered by the medical insurance system or by the Ministry of Health (or equivalent government agency); and 2) Does the use of PEP adhere to national and international guidelines in the rural regions of the country? In China, the New Rural Cooperative Medical System has increased the affordability of (and, therefore, access to) PEP in many rural high-risk communities. Additionally, the National Health Commission had issued revised guidelines on the use of PEP according to the WHO updated vaccine position paper [20–22], and provincial and local level CDCs have provided training of the appropriate use and timing of PEP to clinicians in rural China.