LPSp对狂犬病疫苗佐剂效应及安全性研究

目的研究成团泛菌脂多糖(LPSp)作为狂犬病疫苗佐剂的可行性。方法将Balb/c小鼠32只随机分为空白对照组(注射生理盐水)、LPSp对照组(注射LPSp)、狂犬病病毒蛋白组(注射狂犬病病毒蛋白)、LPSp实验组(注射LPSp和狂犬病病毒蛋白),分别在第0、7、15、21天经背部皮下免疫接种共4次。在免疫接种后第7、14、21、30、45、60天采集小鼠眼内眦静脉血,分离血清,末次采血后处死小鼠。用酶联免疫吸附试验(ELISA)检测血清抗狂犬病病毒IgG,并进行血液学、血液生化、脏器指数等检查。结果免疫接种4次后,LPSp能明显增强狂犬病病毒蛋白免疫小鼠产生IgG的能力(P<0.05);实验期间各组小鼠未发现明显异常表现,体质量、血液学、血液生化和脏器指数等各组间未见明显差异(P>0.05)。结论 LPSp对狂犬病病毒蛋白具有较好佐剂效应;在本实验条件下,LPSp对小鼠安全性好。     

The Cost of Canine Rabies on Four Continents

We estimated the economic impacts of canine rabies in Latin America, Africa and Asia. Direct and indirect costs of rabies post‐exposure prophylaxis, dog vaccination and control, rabies diagnostic testing and cattle mortality‐related costs were accounted for. The number of human deaths was updated from previous estimates based on population growth, and the costs associated with the risk of human mortality were incorporated. We accounted for uncertainty associated with the parameter estimates using a Monte Carlo simulation and estimated that the global burden of canine rabies is approximately $124 billion annually. This result illustrates the potential benefits that could be realized if canine rabies was eliminated and provides an important benchmark against which the cost of any potential elimination campaign can be compared.     

Rabies Virus Neutralizing Activity,Safety, and Immunogenicity of Recombinant Human Rabies Antibody Compared with Human Rabies Immunoglobulin in Healthy Adults

ObjectivePreliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults.MethodsSubjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days –7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection.ResultsAll 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU /mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0–14 days and 0–42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed.ConclusionThe rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.     

济宁市2011—2015年狂犬病暴露人群流行病学特征分析

目的了解山东省济宁市狂犬病暴露人群暴露流行病学特征及暴露后处置情况,为狂犬病防控提供科学参考依据。方法收集2011—2015年济宁市狂犬病暴露登记资料进行统计分析。结果 2011—2015年共接诊狂犬病暴露病例221 272例,性别比为1.49:1,0~14岁儿童最多,占32.71%;各月均有暴露者发生,7—8月为高峰,占22.51%;致伤动物以犬类为最多,占83.92%;暴露者到狂犬病处置门诊处理为主,占79.22%,全程接种人用狂犬病疫苗的145 092例,占Ⅱ、Ⅲ级暴露的72.16%,注射过狂犬病被动免疫制剂的12 783例,占Ⅲ级暴露的18.6%。结论济宁市群众对狂犬病防控知识缺乏,狂犬病暴露规范处置率较低,应加强狂犬病监测和健康教育,提高狂犬病防治知识。     

Survival of rabid rabbits after intrathecal immunization

Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti‐apoptotic and anti‐inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4–8 days post‐inoculation (dpi) of RABV. All of the rabbits died within 8–12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11–18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies.     

1993-2013年泸州市狂犬病流行特征及防控对策

目的了解狂犬病流行特征,分析流行因素,为制定控制措施提供依据。方法采用描述流行病学方法对四川省泸州市1993-2013年的疫情数据和2006-2013年个案资料进行分析。结果 21年共报告狂犬病49例,年均报告发病率0.055/10万,病死率100.00%,1993-2006年报告4例,报告发病率在0-0.024/10万,从2007年起发病率在0.047/10万-0.237/10万之间,呈波动上升趋势;71.43%的病例分布在古蔺县、泸县、叙永县;男女比为1.72∶1,农民、学生、散居儿童为主（81.63%）,40-64岁占48.98%;无明显季节性。46例个案,主要症状为烦躁、恐水、怕风,平均潜伏期2月零10d（6 d-2年）,平均病程4 d（1-12 d）;91.30%被犬咬伤,52.17%为流浪犬,家养犬猫均无免疫史;86.96%的伤口未处理或自行处理,95.65%未接种狂犬疫苗;Ⅲ级暴露占80.43%,均未注射狂犬病免疫球蛋白。结论 2007-2013年泸州市狂犬病疫情呈上升趋势;犬为主要传染源,农村为重点防控地区,农民、学生和散居儿童为重点人群。犬只免疫率低、群众防病意识差、暴露后伤口规范处置率低、人用狂犬病疫苗和免疫球蛋白接种率低,是泸州市狂犬病流行的主要原因。     

河南省狂犬病门诊暴露人群监测

目的掌握河南省狂犬病门诊监测点暴露人群流行病学特征及暴露后处理情况。方法对河南省南阳、郑州两市狂犬病门诊暴露人群监测月报表进行统计分析。结果暴露人群男性多于女性,少儿组是狂犬病暴露危险人群,时间分布上夏秋季节较为集中,暴露部位主要为下肢和上肢,以浅表单处伤居多。暴露后绝大多数人都能及时处理伤口,到门诊就医者基本上都能坚持全程疫苗接种,注射抗血清的为数不多。暴露人群免疫后抽样检测,抗体全为阳性。结论重视全民,尤其是少儿狂犬病健康教育,增强防范意识,做到暴露后及时处理伤口、接种疫苗和抗血清注射。加强犬只管理,减少暴露发生。     

Ongoing rabies outbreak in dogs of unprecedented scale and human cases in Nelson Mandela Bay Municipality,South Africa,up to 13 February 2022

More than 430 cases of rabies have been confirmed in dogs in the Nelson Mandela Bay Metropolitan Municipality of South Africa since July 2021. We describe the ongoing outbreak, its geographical spread and six related human deaths that have occurred. Further investigation of the outbreak and vaccination of the dog population is required. Raising awareness among healthcare providers, the public, and among international travellers planning to visit the region, is key for action to protect human and animal health.     

Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice

Mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers. Optogenetic stimulation of wS1 drove retraction of contralateral whiskers while stimulation of wM1 drove rhythmic whisker protraction. To map brainstem pathways connecting these cortical areas to whisker motor neurons, we used a combination of anterograde tracing using adenoassociated virus injected into neocortex and retrograde tracing using monosynaptic rabies virus injected into whisker muscles. Our data are consistent with wS1 driving whisker retraction by exciting glutamatergic premotor neurons in the rostral spinal trigeminal interpolaris nucleus, which in turn activate the motor neurons innervating the extrinsic retractor muscle nasolabialis. The rhythmic whisker protraction evoked by wM1 stimulation might be driven by excitation of excitatory and inhibitory premotor neurons in the brainstem reticular formation innervating both intrinsic and extrinsic muscles. Our data therefore begin to unravel the neuronal circuits linking the neocortex to whisker motor neurons.