Pre-exposure rabies prophylaxis, also known as immunoprophylaxis before exposure to rabies, refers to preventive rabies vaccination for individuals at risk of rabies infection before rabies exposure, which is one of the important strategies for rabies prevention. Pre-exposure rabies prophylaxis can reduce the risk of individual rabies and reduce the cost of post-exposure prophylaxis by establishing an immunologic barrier in advance and the memory immune response after the booster. In view of the current situation that clinicians in China have relatively insufficient knowledge of pre-exposure rabies prophylaxis, the Rabies Prevention and Control Committee of the Chinese Preventive Medicine Association and Animal Injury Treatment Branch of China Association for Disaster and Emergency Rescue Medicine organized domestic experts in relevant fields to write this expert consensus in accordance with the latest guidelines, expert consensus, and the latest clinical evidence. This consensus describes the concept and significance of pre-exposure rabies prophylaxis, immunization procedures and cost-effectiveness respectively, and puts forward recommendations on pre-exposure rabies prophylaxis strategies. It is hoped that this consensus can improve clinicians\' understanding of pre-exposure rabies prophylaxis and increase the rate of pre-exposure rabies prophylaxis among people at high risk of exposure in China.
狂犬病暴露前预防又称狂犬病暴露前免疫预防，是指在发生狂犬病暴露前，对有感染狂犬病风险的个体进行预防性的狂犬病疫苗接种，是狂犬病预防的重要策略之一。狂犬病暴露前预防通过预先建立免疫屏障以及加强疫苗接种后的记忆免疫反应，可减少个体罹患狂犬病的风险，并降低暴露后处置的花费。针对目前我国临床医师对狂犬病暴露前预防认识相对不足的现状，中华预防医学会狂犬病预防控制工作委员会、中国医学救援协会动物伤害救治分会组织国内相关领域专家，遵循临床指南编撰国际标准，收集狂犬病暴露前预防的最新证据，参考国内外相关规范、指南和共识，结合专家临床经验等，撰写本共识。本共识对狂犬病暴露前预防的概念和意义、免疫程序等分别进行了阐述，并对狂犬病暴露前预防策略提出了推荐意见，以期提高临床医师对暴露前预防的认识，提高我国狂犬病病毒高暴露风险人群的暴露前预防普及率。.

Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies.
CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high.
A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk.
We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.

The World Health Organization (WHO) issued an updated position paper on rabies in 2018, mainly focusing on simplification of vaccination schedules and use of rabies immunoglobulin (RIG). The maximum amount of RIG anatomically feasible should be infiltrated exclusively in and around the wound and will no longer be calculated solely based on body weight. We describe the practical guideline implementing the revised RIG policy in the Netherlands on how to determine the amount of RIG for local administration. We calculated savings achieved through the revised WHO policy. We used information from a national database including rabies consultations in the Netherlands and clinical information from a public health service, clinical practitioners and national data on the amount of distributed RIG. Between 2008 and 2019, 5,164 consultations were registered. The most frequently affected anatomical location was hand or leg (43%). Around 80% concerned minor injuries (< 2 cm). From January 2016 to end December 2019, 7,361 mL RIG were distributed for 1,042 possible rabies exposures (EUR 1.4 million). Since implementing the revised policy, the amount of RIG distributed per order has sharply decreased (59%). Infiltrating RIG only locally saved large quantities of human RIG (EUR 1.1 million during 4 years) in the Netherlands.

Rabies is an acute encephalitis that is caused by rabies virus (RABV) infection, which belongs to the Rhabdoviridae family of viruses. It causes about 59,000 human deaths per year (although this number may be under-reported) and is generally fatal, once signs and symptoms begin to appear. Rabies is still very prevalent and under- reported, particularly in low to middle-income countries such as Asia and Africa, where there is lack of access to healthcare and domestic dogs are not widely vaccinated. Although not commonplace in the USA, rabies is mostly transmitted by wild animals such as bats, raccoons, skunks and foxes. Domesticated cats and dogs are also at risk of acquiring rabies, if they have not been vaccinated. Larger carnivores, such as coyotes, bobcats, mountain lions, wolves, bears, woodchucks, and beavers, should also be considered rabid (unless proven otherwise) if they are involved in an unprovoked attack on a person. The rabies vaccine can prevent 99% of deaths if administered promptly after exposure. There are two main vaccination strategies for rabies prevention: pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). This article reviews background and epidemiology of rabies and current guidelines for rabies PrEP and PEP regimens for the United States.

Rabies is a zoonotic infectious disease caused by lyssavirus and characterized by central nervous system symptoms. The fatality rate of rabies is almost 100%. About 59 000 cases die of rabies worldwide every year, mainly in Asia and Africa. China is an epidemic country of rabies. Grade II and III exposures are the main types of rabies exposures in China. Standardized post-exposure prophylaxis (PEP) can prevent rabies almost 100%. Human Rabies Vaccine Technical Working Group, National Immunization Advisory Committee and invited experts reached an expert consensus on PEP by referring to the World Health Organization\'s position paper on rabies vaccine in 2018 and related research progress in recent.
狂犬病是由狂犬病病毒属病毒感染引起的以中枢神经系统症状为主的一种动物源性传染病，病死率几乎100%。全球每年狂犬病死亡例数约59 000例，主要发生在亚洲和非洲，我国为狂犬病流行国家。我国狂犬病暴露就诊人群以Ⅱ级和Ⅲ级暴露为主。规范的狂犬病暴露后预防处置可几乎100%预防发病。中国疾病预防控制中心国家免疫规划技术工作组狂犬病疫苗工作组及特邀专家，参考WHO的2018年狂犬病疫苗立场文件及国内外相关研究进展，就狂犬病暴露预防处置达成专家共识。.

Rabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommendations for rabies immune globulin (IG) patient selection, dosing, timing of administration, and anatomical site of administration for rabies postexposure prophylaxis. This retrospective, cross-sectional study included patients who received at least one dose of rabies IG or rabies vaccine at a multi-hospital health system from January 2015 through June 2018. This study included 246 patients, and all of them received at least one dose of rabies vaccine. Two patients had a history of rabies vaccination, did not have an indication for rabies IG, and appropriately did not receive additional rabies IG. Rabies IG was administered to 91% (223 of 244) of patients with an indication. Of 223 patients who received rabies IG, 219 (98%) received doses within 10% of 20 IU/kg of body weight, and all 223 (100%) received rabies IG within 7 days of the first rabies vaccine administration. Only 56% (96 of 170) of patients with a wound that could be infiltrated with rabies IG actually received rabies IG via infiltration into and around the wound. This multi-hospital health system study demonstrated high adherence to guideline recommendations for rabies IG patient selection (91%), dosing (98%), and timing (100%). However, only 56% of eligible patients received rabies IG infiltration at wound sites as recommended by guidelines.

The possibility of enhancing the immunogenicity of the rabies virus glycoprotein antigen encoded by a DNA vaccine has been investigated. Ubiquitin-like protein FAT10 has been attached to the N-terminus of the glycoprotein to target it to the proteasome and stimulate its presentation by MHC class I. Two forms of the protein, chimeric and original, have been detected in cells transfected with the DNA construct encoding the chimeric protein. The presence of the glycoprotein on the cell surface has been detected by immunostaining of transfected cells. The production of IgG and IgG2a antibodies has been more efficiently induced in mice immunized with the plasmid that encodes the chimeric protein than in those immunized with the plas-mid that encodes unmodified glycoprotein. Moreover, the level of IgG2a antibodies exceeded the level of IgG1 antibodies, which indicates a preferential increase in the Th1 component of the immune response. The proposed DNA construct that encodes a modified glycoprotein with a proteasome degradation signal maybe a promising DNA vaccine immunogen for post-exposure prophylaxis of rabies.

Safe and effective anti-rabies vaccines are intensely sought worldwide. DNA vaccines have already shown their efficacy and safety and have occupied a special place in the field. Two prototype anti-rabies DNA vaccines were compared for the potential to induce virus-specific antibody production. One vector contained a codon-optimized gene with a territory-adapted consensus sequence of the rabies virus glycoprotein. The other one expressed the same glycoprotein in fusion with a c-CD63 lysosome targeting motif at the C terminus. ELISA of serum samples from immunized mice showed that the c-CD63 variant induced more efficient antibody production and shifted the IgG2a/IgG1 ratio towards the Th2-type immune response. The results gave grounds to believe that the approach successfully applied to the rabies glycoprotein may help to develop new-generation anti-rabies vaccines.

In order to promote the prevention and control programs on rabies in our country, to regulate the prevention and disposition of rabies and to reduce the deaths caused by rabies, the Chinese Center for Disease Control and Prevention has organized a panel of experts, in the reference with Guidelines issued by WHO, American Advisory Committee on Immunization Practices, and the latest research progress from home and abroad, and compiled this document-\"Technical Guidelines for Human Rabies Prevention and Control (2016)\". The Guidelines conducted a systematic review on the etiology, clinical characteristics, laboratory diagnosis, epidemiology of rabies and provided evidence on varieties, mechanisms, effects, side-effects and security of rabies vaccine, as well as on other preparations on passive immunity of its kind, on methods related to prevention and disposition of exposure etc, finally to have come up with the recommendation on the above mentioned various techniques. The guidelines will be used by staff working on prevention and control of rabies from the Center for Disease Control and Prevention at all levels, from the departments of outpatient and divisions of infection and emergency control in all the medical institutions. The guideline will be updated and revised, following the research progress from home and abroad.

Surveillance is a critical component of disease control programmes but is often poorly resourced, particularly in developing countries lacking good infrastructure and especially for zoonoses which require combined veterinary and medical capacity and collaboration. Here we examine how successful control, and ultimately disease elimination, depends on effective surveillance. We estimated that detection probabilities of <0.1 are broadly typical of rabies surveillance in endemic countries and areas without a history of rabies. Using outbreak simulation techniques we investigated how the probability of detection affects outbreak spread, and outcomes of response strategies such as time to control an outbreak, probability of elimination, and the certainty of declaring freedom from disease. Assuming realistically poor surveillance (probability of detection <0.1), we show that proactive mass dog vaccination is much more effective at controlling rabies and no more costly than campaigns that vaccinate in response to case detection. Control through proactive vaccination followed by 2 years of continuous monitoring and vaccination should be sufficient to guarantee elimination from an isolated area not subject to repeat introductions. We recommend that rabies control programmes ought to be able to maintain surveillance levels that detect at least 5% (and ideally 10%) of all cases to improve their prospects of eliminating rabies, and this can be achieved through greater intersectoral collaboration. Our approach illustrates how surveillance is critical for the control and elimination of diseases such as canine rabies and can provide minimum surveillance requirements and technical guidance for elimination programmes under a broad-range of circumstances.