WHO recommended pre-exposure prophylaxis for rabies using Japanese rabies vaccine

After severe exposure to suspected rabid animal, WHO recommends a complete vaccine series using a potent effective vaccine that meets WHO criteria, and administration of rabies immunoglobulin (RIG). RIG is not available globally, and is not marketed in Japan. If pre-exposure prophylaxis for rabies is given, RIG is unnecessary even after severe exposure. It is thus important to give pre-exposure prophylaxis for rabies to people who plan to go to rabies-endemic areas. In Japan, pre-exposure prophylaxis for rabies consists of 3 doses of cell-culture rabies vaccine. The first two doses are given 4 weeks apart, and the third dose is given 6-12 months after the first dose, all of which are injected subcutaneously (standard regimen). People who plan to travel abroad to rabies-endemic areas may know of their destinations only 1 or 2 months in advance at best. Therefore, it is virtually impossible to complete the 3 dose regimen for rabies in Japan. Pre-exposure prophylaxis recommended by WHO consists of 3 doses given intramuscularly on days 0, 7, and 28, making it possible to complete pre-exposure prophylaxis in one month. This WHO recommended pre-exposure prophylaxis using Japanese cell-cultured rabies vaccine (PCEC-K) has not been studied, so we elected to fill the gap using PCEC-K, administered based on the WHO recommendation and examined its efficacy and safety. Subjects were 26 healthy volunteers with no previous rabies vaccination giving oral and written consent. Vaccine was administered on days 0, 7, and 28, and rabies antibody levels were tested on days 7, 28, and 42. On day 7, every antibody level was negative. On day 28, antibody levels were between 0.7-3.5 EU/ mL, with the exception of 3 cases still negative. On day 42, all cases, including the 3 negative cases, exceeded 1.6 EU/mL, providing sufficient protection against rabies. This result was not inferior compared to the standard regimen. Local adverse effects such as erythema and pain were noted, but none were serious. In conclusion, WHO recommended pre-exposure prophylaxis for rabies using PCEC-K is considered effective and safe.     

Study of the dog population and the rabies control activities in the Mirigama area of Sri Lanka

The national health authorities of Sri Lanka have adopted a combined strategy of rabies vaccination and stray dog removal to control endemic dog rabies. Despite the control efforts, an increase of animal and human rabies cases has occurred since 1994. As a consequence, a project to evaluate the national rabies control program has been started and a study focussing on the dog population and rabies control activities in a limited area of Mirigama was conducted. Information on canine abundance and the accessibility of dogs for rabies vaccination was obtained by a household survey, vaccination of dogs against rabies at several vaccination points, collar-marking, and transect line recapture. The number of unvaccinated dogs was estimated by using Bayesian methodology. The estimated number of dogs per square kilometre was 87 (95% credibility interval: 80, 93) for owned dogs and 108 (100, 116) for owned and ownerless dogs. Coverage after the immunisation campaign was 57.6% (53.3, 61.9%) if vaccination at the vaccination points was considered and 66% (60.4, 72.0%) if recently provided vaccination by private veterinarians was also taken into account. The proportion of households with at least one dog vaccinated varied between 59.1 and 94.2% within the catchment area of the different vaccination points. Unvaccinated dogs were puppies (12%), ownerless dogs (57%), and owned dogs, which were not presented for vaccination (31%). In order to improve the rabies immunisation coverage among dogs and to achieve complete elimination of rabies it was recommended that the 95% catchment area of each vaccination point be assessed, the distribution of vaccination points in the vaccination area be redefined if necessary, a system for the vaccination of dogs missing the vaccination campaign for dog owner-specific reasons be established, and an inexpensive marking system be used for vaccinated dogs.     

Dog ecology and demography information to support the planning of rabies control in Machakos District, Kenya

A study of 150 dog-owning households from six randomly selected sublocations was conducted in Machakos District, Kenya. Initially, all households were visited to collect information on dog ecology and demography based on WHO guidelines and to collect serum for rabies antibody detection. A second visit was made 1 year later, to obtain follow-up data on births, deaths, dog movements and other events since the first visit. Dog ownership was common, with a range of 53--81% (mean=63%) of households owning dogs in the six sublocations. Dog density for the five more rural sublocations ranged from 6 to 21 dogs km(-2) and for the peri-urban sublocation was 110 dogs km(-2). The dog population was estimated to be growing at 9% p.a. (95% C.I. 4--14%). This growth was a function of very high fecundity (1.3 females per female per year) more than compensating for high mortality, particularly among females. Life expectancy from birth was 3.5 years for males and 2.4 years for females. Half the dogs at any one time were less than 1 year of age. All dogs, by design of the study, were owned. Of these, 69% were never restricted and roamed freely to forage for food and mix with other dogs. Only a small proportion of dogs (5%) were fed commercial dog food. Most households reported observing dogs scavenging their garbage, including: their own dogs (81%), their neighbours' dogs (75%) and unknown dogs (45%). Only 29% of dogs at least 3 months of age were reported to be vaccinated against rabies. The proportion vaccinated varied widely between sublocations (5--68%); 48% of dogs reportedly vaccinated had detectable antibodies, 31% at or above levels considered to indicate seroconversion. The proportion of dogs with detectable antibodies declined according to the time since last vaccination (55% if vaccinated < or = 1 year, 47% < or = 2 years and 36% > 2 years); 20% of dogs reported not to have been vaccinated had detectable rabies antibody. Compared to other dog populations in rural eastern and southern Africa, Machakos District has a high density of dogs. The Machakos dog population is growing, highly dynamic, poorly supervised and inadequately vaccinated against rabies. The main implication for rabies control is that adequate vaccination coverage is unlikely to be achieved, even under optimal delivery, using the current strategy of annual vaccination of dogs older than 3 months.     

Human rabies in India: epidemiological features, management and current methods of prevention

In most endemic countries stray dogs are the main source of rabies infection in humans. In India 95-97% of rabies patients are infected by dogs. Most pet dogs do not regularly receive booster doses of vaccine. In Thailand, most rabies patients develop the disease within 1 month of exposure. Rabies immunoglobulin is costly and usually not available. So in India nervous tissue vaccine is commonly used--it is inexpensive and freely available despite frequent neurological complications. The cost of immunization by tissue culture vaccines may be reduced by nearly 60% by intradermal vaccination.     

2011-2020年上海地区犬只狂犬病本底状况回顾性分析

目的 为掌握上海市犬只狂犬病免疫状况、抗体水平和流行情况,评估犬只狂犬病流行风险。方法 利用统计学方法对上海市2011-2020年犬只狂犬病血清学和病原学检测数据进行回顾性分析。结果 上海市注册犬只狂犬病免疫抗体平均合格率为83.8%(95%CI:83.3%~84.3%),流浪犬抗体平均合格率为17.7%(95%CI:15.8%~19.6%),一犬伤多人事件(伤人数≥2)犬只狂犬病病毒阳性率高达94.1%;从时间、空间和群间分布情况看,各年份、各区、各监测场点犬只狂犬病抗体水平存在一定的差异性;流浪犬与城镇犬、示范村农村犬、养殖场犬等不同类型犬只之间的抗体水平差异有统计学意义(P<0.01)。结论 上海市注册犬只狂犬病免疫措施扎实,效果确实;上海属于狂犬病的自然疫源地,流浪犬未构筑有效免疫屏障,不足以阻断病毒在群内的传播,是当前上海狂犬病流行的最大风险点,建议进一步强化流浪犬的免疫研究和收容管理。     

Epidemiological investigations of human rabies in China

Background  

The epidemic of rabies showed a rising trend in China in recent years. To identify the potential factors involved in the emergence, we investigated and analyzed the status and characteristics of human rabies between 1996 and 2008. Moreover, the status of rabies infection and vaccination in dogs, and prophylaxis of humans after rabies exposure were analyzed.     

狂犬病口服疫苗对消除人间狂犬病的重要作用北大核心CSCD

狂犬病严重威胁人类生命,控制狂犬病需要从病毒的源头着手。在狂犬病毒的多种宿主中,犬科动物所占比例最大。因此,消除狂犬病的关键是对犬的免疫覆盖率达到70%以上。事实证明,通过注射灭活疫苗对犬只形成免疫屏障是一件困难的事情。采用口服疫苗策略控制野生动物狂犬病的成功案例给大家提供了新的思路,因此世界卫生组织建议采用狂犬病口服疫苗对犬进行免疫,用以提高犬只的免疫覆盖率,从而达到2030年消除和控制狂犬病的目的。     

西双版纳州9例狂犬病病例临床及流行病学特征分析

2008～2011年西双版纳州报告狂犬病病例9例,全部死亡,发病高峰2010年发病5例。男性8例,女性1例;病例以青壮年工人和农民工为主;景洪市8例,勐腊县1例。潜伏期最短9d,最长15月,多为1～3个月;病程最短2d,最长15d。全部病人均为犬伤,仅1例接种狂犬疫苗。结果表明,西双版纳州狂犬病疫情上升明显,应加强犬类管理和宣传教育,规范暴露后的预防处置和免疫接种工作。     

Retrospective study of extensive vaccination programs for canine rabies control and public health in Korea

This retrospective study of the patterns and efforts of the extensive vaccination programs for canine rabies control (EVPCRC) compared the prevalence rate (PR) of rabies under two different vaccination programs for dogs in Korea between 1962 and 2007. A total of 753 cases of rabid dogs were reported between 1962 and 2007, and there were 350 human cases reported in the same period. There were 518 cases (PR, 4.11) of rabid dogs reported from 1962 to 1979, when the low-egg-passage Flury strain vaccine was used, and a total of 342 human cases were observed over the same period. However, there were 235 rabid dogs (PR, 0.83) identified from 1980 to 2007 when the Evelyn-Rokitnicki-Abelseth strain vaccine was used, and only 8 human cases of rabies were observed during the same period. The prevalence of rabies in dogs during the two periods was significantly different (P < 0.01). Moreover, the year with the largest outbreak, 1975, contained 91 cases, and the PR value was 6.3. In 1963, for humans, there were 103 cases, and the PR value was 0.4. However, in recent years, raccoon dogs have increased as a reservoir of rabies in the mountain areas linking North Korea with South Korea near the demilitarized zone, reflecting areas with poor EVPCRC.     

安徽省70例狂犬病暴露后免疫失败流行病学分析

目的 分析狂犬病暴露后免疫失败个案,探讨免疫失败的原因。方法 收集整理安徽省2005-2016年70例狂犬病暴露后免疫失败个案资料,使用Epi Data3.1软件录入数据,用SPSS 22.0软件对数据进行统计分析。结果 65.71%病例暴露后均能在24 h内赴医疗机构进行伤口的冲洗和消毒。81.43%的病例未全程接种疫苗,其原因主要是存在侥幸心理,不愿继续接种疫苗,抗血清使用率2.86%。48.57%的病例在非暴露后门诊进行处置。潜伏期中位数40 d (最短9 d,最长10.5年),暴露于头颈部的病例潜伏期较短,不同咬伤部位之间的差异有统计学意义(χ²=25.01,P<0.01)。结论 建立狂犬病暴露后补偿机制,规范狂犬病疫苗流通渠道,打击非法及伪劣产品,加强狂犬病暴露后处置门诊医疗人员的技能培训,提高公众知信行,是预防人间狂犬病暴露后免疫失败的关键。     

An important public health problem: rabies suspected bites and post-exposure prophylaxis in a health district in Turkey.

OBJECTIVE: The aim of this study was to describe rabies suspected animal bites and post-exposure prophylaxis (PEP) practices in Narlidere District in Turkey between 1999 and 2001. METHODS: One thousand five hundred and sixty-nine rabies suspected bite cases reported were identified from the District's rabies surveillance forms. RESULTS: Males comprised 66.7% of the cases, and 43.5% of the total were under 20 years old. In 74% of cases the animal involved in the bite was a dog. Only 70% of the animals had an owner, and only 17% of the animals had a rabies vaccination certificate. In terms of treatment, 68% of the human cases received PEP, and 21% of cases had an extra (sixth) vaccination dose, which is a substantial burden on the healthcare system, costing half a million US dollars per year. The place where the bite occurred (rural areas), the age of the recipient (more than 10 years old), the animal type (animals other than dogs and cats), lack of a vaccination certificate for the animal, and place of wound treatment (hospital) were significantly associated with PEP application. CONCLUSIONS: In addition to the currently recommended strategy of controlling the dog population and of vaccinating domesticated animals, adults and children should be educated about bite prevention to reduce the number of animal bites.     

Practical management of rabies and the 1982 outbreak in Zorzor District, Liberia

A rabies outbreak in Zorzor District, Liberia, in 1982 resulted in 31 known bitten and 12 known exposed patients. Human diploid cell strain (HDCS) vaccine was used to vaccinate 40 patients. Of these, 34 were vaccinated at Curran Lutheran Hospital, Zorzor, Liberia, mostly by the intradermal (i.d.) route. Five of 28 bitten patients who started their vaccinations did not complete the 4-dose course, including a 16-year-old boy who did not return after the first injection and later died of rabies. There were also 2 deaths in 3 known bitten but unvaccinated patients. None of the 23 bitten who received 4 doses of HDCS vaccine contracted rabies. The i.d. route was also used for pre-exposure prophylaxis. This method of vaccination is less expensive than the intramuscular route and in our clinical setting we would not have been able to vaccinate all the patients without using it. A practical approach to rabies vaccination in a developing country and the technique of intradermal vaccination are discussed.     

Antibody response after a four-site intradermal booster vaccination with cell-culture rabies vaccine.

The current World Health Organization recommendation for booster vaccination of previously immunized individuals with potential exposure to rabies is two doses of vaccine intramuscularly or intradermally on days 0 and 3. We report responses to two types of postexposure treatment of healthy individuals who had received preexposure rabies vaccination 1 year previously. Group A individuals received four intradermal doses (one-fifth of the diluent volume of vaccine per dose) on day 0, and group B individuals received two intramuscular doses on days 0 and 3. Immunogenicity of the two booster regimens was assessed by titrating the amount of neutralizing antibody (Nab). We found that the booster doses of vaccine produced remarkable responses in all subjects. Nab titers of > or = 0.5 IU/mL (acceptable antibody level for protection against rabies) were detected in all subjects on day 14, and they were shown to be consistently high 1 year after the booster vaccination. We also found that the Nab titers for group A were significantly higher (two- to eightfold) than those for group B on days 5, 14, 150, and 360 after the initial booster vaccination (P < .05). Our study shows that the four-site intradermal booster regimen with use of one-fifth of the diluent volume of cell-culture rabies vaccine on day 0 is associated with a significantly higher antibody response than is the conventional booster regimen for subsequent postexposure rabies treatment of individuals who have received preexposure rabies vaccination with cell-culture rabies vaccine 1 year previously.     

中山市狂犬病105例回顾性分析

目的收集105例狂犬病完整的流行病学个案资料,分析流行特征,为本市狂犬病的预防控制提供参考。方法病例个案资料录入Epidata数据库,并用spss11.0统计软件包进行分析。结果发病季节以7-12月份为高峰;男性明显多于女性,其发病比例为2.28∶1;职业以农民为主,占55.24%;本市人狂犬病病例传染源以家犬为主,占93.33%;暴露后伤口未作任何处理和接种疫苗的占63.81%,自行处理或不规范处理伤口和无及时接种疫苗的占20.00%,及时处理伤口并注射狂犬疫苗但发病的仅占病例数的7.62%。暴露后潜伏期最短13d,最长1153d,平均潜伏期78.56d。结论建议进一步加强犬类的"管、免、灭";加强宣传和健康教育,使人们在被带狂犬病毒的犬类咬伤后及时获得狂犬病暴露后的免疫预防;尽可能地对高危人群和高发地区开展暴露前免疫,降低狂犬病发病率。     

Epidemiologic trends of rabies in domestic animals in southern Thailand, 1994-2008

Rabies and associated risk factors in dogs, cats and cattle (n = 3,454) in southern Thailand during 1994-2008 were evaluated by using a mixed-effect logistic regression model. Overall prevalence was 48%. In dogs, odds of being rabid were 1.7 times higher in unvaccinated dogs than in vaccinated dogs and two times higher in dogs with bite history than in dogs with no known bite history. Similarly, aggressive dogs were more likely to be rabid than non-aggressive dogs. In cattle, aggression, pharyngeal paralysis, hyperactivity, and depression were clinical signs associated with being rabid. Annual fluctuations of the species-specific prevalence of rabies is suggestive of a positive correlation between canine and either feline (r = 0.60, P = 0.05) or bovine rabies (r = 0.78, P = 0.004). Insufficient vaccination coverage led to maintenance of rabies, which could be easily controlled by increased vaccine coverage and public education.     

广西2003-2008年狂犬病流行病学调查和综合防制

目的对广西2003-2008年的狂犬病疫情、监测和防控采用追溯、问卷等方法进行调查和分析。结果显示,广西的家犬养殖量逐年增加,免疫收费和免疫操作困难是犬免疫密度不高的主要因素;外观健康犬存在带毒;广西人的狂犬病主要由动物引起,6年间死亡2983例,伤人犬均未免疫或者免疫状况不明。     

广西1951-2010年狂犬病流行特征分析(英文)

总结和分析广西1951-2010年狂犬病流行情况,探讨疫情流行规律和发病特点,为狂犬病预防控制策略提供科学依据。[HTH]方法采用描述性流行病学方法对1951-2010年广西狂犬病疫情资料和病例个案表进行统计分析。[HTH]结果60年间广西共报告17 210例狂犬病病例,发病流行强度高,每隔10年左右出现1次流行高峰;疫源地流行范围逐年扩大,并呈现由北向南、由东往西扩散的趋势;病例主要分布在农村地区;犬为主要传染源,病例以头面部、上肢和Ⅲ级暴露为主;潜伏期平均为63 d;部分病例虽及时采取正确的暴露后预防处置,但仍然在免疫期间或全程接种后出现发病的现象,狂犬病暴露门诊监测点数据显示,接种后发病率为2.75/10万;2006-2010年外观健康犬脑狂犬病毒核酸阳性率为1.9%、0.93%、0.91%、0.40%和0.00%。[HTH]结论广西狂犬病疫情持续高发并呈周期性流行;犬密度高、免疫率低、外观健康犬只带毒率高、人群暴露率高、自我保护意识淡薄和接种疫苗费用高是狂犬病高发的重要因素;狂犬病自然疫源地的持续扩大蔓延、传染源源头管理不力和综合防制措施落实不到位,是近年我区狂犬病疫情回升的主要原因。加强组织领导和多部门合作,根据广西实际制订出更有针对性的综合措施并认真落实到位,才能有效控制广西狂犬病疫情高发态势。     

中国狂犬病口服疫苗的研究进展及其应用的紧迫性

中国科学家早在上世纪80年代开始研究狂犬病动物口服疫苗,获得数株毒力减弱的疫苗株,并进行过犬的口服免疫实验和大规模安全性和保护效果的现场观察。其中有几株减毒株的弱毒特征、遗传稳定性和免疫性与WHO认可并广泛应用的动物口服疫苗毒种相似。消除狂犬病的关键措施是对犬进行大面积免疫达到免疫覆盖率70%以上,中国犬的数量多达亿头,而且多数为散养犬,以常规的注射免疫很难达到这个水平。对犬实施口服免疫提高免疫率也是WHO和狂犬病专家积亟提倡和推荐的。中国已有多株减毒株,国家应充分发挥它们的作用,在人力、物力、财政上予以大力支持,完善这些候选株以便尽快得到批准应用,从而达到全球2030年消除人间狂犬病的目标。     

Seroepidemiological survey of rabies virus antibodies in non-vaccinated dogs in Nsukka Environs, Nigeria

Serum samples from 254 non-vaccinated and apparently healthy dogs of local breeds in Nsukka environs (Nigeria) were examined for the presence of antibodies to rabies virus by haemagglutination-inhibition technique. The prevalence rates of rabies antibodies in less than 3 months, 3-6 months and over 6 months old dogs were 17.5, 7.3 and 22.8 per cent, respectively, and overall 16.1 per cent in the dog population. This is the first documented report of rabies antibodies in non-vaccinated dogs in Eastern Nigeria. The results have been discussed with respect to the epidemiology of prototype rabies and rabies-related viruses. It is suggested that the antibodies are most probably due to the non-virulent prototype rabies or rabies-related virus strains. Presence of 83.9 per cent of susceptible dogs in the population suggests mandatory and regular vaccination of all dogs in the interest of public health and control of the disease. The study highlights the need for more studies on epidemiology of rabies and rabies-related viruses in Nigeria.     

The epidemiology of animal bite injuries in Uganda and projections of the burden of rabies

OBJECTIVES: Rabies is a global problem, although it is often under-reported in developing countries. We aimed at describing the profile of patients presenting to health centres with animal bite injuries in Uganda, and use a predictive model to estimate the mortality of rabies at a national level. METHODS: We conducted a passive surveillance study in Uganda based in a random sample of health centres supplied with rabies vaccine to determine the characteristics of bite injury patients and establish the age and sex profiles of patients, the site of bites and their severity, wound management techniques and details of the vaccination course given. We also applied a decision tree model to the data to estimate the rabies mortality from the bite injury data using an established protocol. RESULTS: We found that most patients are bitten by dogs, and that a considerable proportion of these are young children, who are at greater risk of developing rabies in the absence of treatment due to the location of the bites they receive. From conservative parameter estimates, we estimate that in the absence of post-exposure prophylaxis (PET), 592 (95% CI 345-920) deaths would occur, and that if one dose of PET is sufficient for protection following a rabid animal bite, 20 (95% CI 5-50) deaths would occur annually. If a complete course of PET is required for protection following a rabid animal bite, up to 210 (95% CI 115-359) deaths would occur, as 41% of patients did not complete their course of PET. CONCLUSIONS: Active animal bite surveillance studies are required to improve our mortality estimates and determine the true burden of rabies in the Ugandan population. We emphasize the need for small-scale active case detection studies and improved data on the recognition of rabies in dogs as inputs for improving national-level estimates of rabies mortality.