Rabies Vaccines

狂犬病疫苗
  • 文章类型: Journal Article
    大规模疫苗接种是遏制传染病的关键公共卫生干预措施。犬狂犬病控制依赖于每年在全球举行的大规模犬疫苗接种运动(MDVC)。狗主人必须把他们的宠物带到固定的疫苗接种地点,但有时由于参与度低,目标覆盖率无法实现。到疫苗接种地点的旅行距离是参与的重要障碍。我们的目标是通过最佳地放置定点疫苗接种位置来增加MDVC在计算机上的参与。我们使用回归模型,根据步行距离到最近的疫苗接种地点量化参与概率,该回归模型适合4年收集的参与数据。我们使用计算递归互换技术来最佳地放置定点疫苗接种地点,并将预测的参与与这些最佳放置的疫苗接种地点与以前活动中使用的实际地点进行比较。最小化平均步行距离或最大化预期参与的算法提供了最佳解决方案。最佳的疫苗接种位置预计将增加7%的参与,并提高覆盖率的空间均匀性,导致更少的疫苗接种不足的口袋。然而,各站点的工作量仍然不均衡。我们的数据驱动算法以最佳方式放置有限的资源来增加总体疫苗接种参与和公平性。实地评估对于评估有效性和评估因参与增加而可能延长的等待队列至关重要。
    Mass vaccinations are crucial public health interventions for curbing infectious diseases. Canine rabies control relies on mass dog vaccination campaigns (MDVCs) that are held annually across the globe. Dog owners must bring their pets to fixed vaccination sites, but sometimes target coverage is not achieved due to low participation. Travel distance to vaccination sites is an important barrier to participation. We aimed to increase MDVC participation in silico by optimally placing fixed-point vaccination locations. We quantified participation probability based on walking distance to the nearest vaccination site using regression models fit to participation data collected over 4 years. We used computational recursive interchange techniques to optimally place fixed-point vaccination sites and compared predicted participation with these optimally placed vaccination sites to actual locations used in previous campaigns. Algorithms that minimized average walking distance or maximized expected participation provided the best solutions. Optimal vaccination placement is expected to increase participation by 7% and improve spatial evenness of coverage, resulting in fewer under-vaccinated pockets. However, unevenness in workload across sites remained. Our data-driven algorithm optimally places limited resources to increase overall vaccination participation and equity. Field evaluations are essential to assess effectiveness and evaluate potentially longer waiting queues resulting from increased participation.
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  • 文章类型: Journal Article
    背景:狂犬病是一种致命的人畜共患疾病,其发病机制尚未完全阐明,接种疫苗是预防狂犬病病毒感染的唯一有效方法。大多数灭活疫苗是使用Vero细胞生产的,非洲绿猴肾细胞,实现规模化生产。然而,由于非人类DNA污染,存在潜在的致癌风险。因此,用人二倍体细胞替代Vero细胞可能是更安全的策略。在这项研究中,我们开发了一种新的2BS细胞适应狂犬病病毒株,并分析了其序列,毒力和免疫原性,以确定其作为人二倍体细胞灭活疫苗的应用潜力。
    结果:通过传代40代并在2BS细胞中选择噬斑,建立了适应2BS细胞的狂犬病病毒株2aG4-B40。RNA序列分析揭示2BS细胞适应菌株中的突变不位于调节aG菌株中的中和抗体产生或毒力的关键位点(GQ412744.1)。毒力(从第40代到第55代保持在7.0logLD50/ml以上)和抗原的逐渐增加进一步表明,这些突变可以增加适应菌株对人二倍体细胞的亲和力。鉴定试验显示,抗狂犬病血清中和了适应2BS细胞的病毒株,中和指数为19,952。PrEP和PEP疫苗接种和NIH试验进一步表明,用2aG4-B40菌株制备的疫苗具有较高的中和抗体水平(2.24至46.67IU/ml),免疫原性(保护指数270)和效力(平均11.6IU/ml)。
    结论:在这项研究中,通过传代40代获得2aG4狂犬病病毒的2BS细胞适应株。适应株的测序分析和滴度测定结果表明,适应过程中的突变不位于病毒的关键序列区域,这些突变可以增强适应菌株对人二倍体细胞的亲和力。此外,由适应株2aG4-B40制成的疫苗具有较高的效力和免疫原性,可以作为灭活疫苗制备的理想候选狂犬病病毒株。
    BACKGROUND: Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine.
    RESULTS: The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml).
    CONCLUSIONS: In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.
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  • 文章类型: Journal Article
    背景:狗咬伤在印度构成了重大的公共卫生问题,需要了解其流行病学概况和空间分布。采用一个健康的方法,考虑到人类的相互联系,动物,和环境健康,对于制定有效的干预措施至关重要。
    目的:该研究旨在评估城市地区狗咬伤病例的流行病学特征和地理空间趋势,关注受害者的年龄和性别分布,咬伤的严重程度,和病例的空间分布,为预防策略提供信息。
    方法:对2022年在孟买一家三级医院报告的狗咬伤病例进行了回顾性二次数据分析。流行病学概况,包括年龄,性别,以及咬伤的严重程度,被检查过。利用量子地理信息系统(QGIS)进行空间分布分析,确定市区内的热点。
    结果:在3350例中,70.7%的人年龄在40岁以下,81.6%为男性,78.18%有III类咬伤,表明严重受伤。大多数病例(74%)是由流浪狗引起的。QGIS分析揭示了市区内的五个热点。
    结论:该研究强调了年轻男性中狗咬伤的优势和伤害的严重程度。空间分析确定了特定的热点,强调需要有针对性的干预措施。实施纳入GIS技术的综合监测系统并采用“一个健康”方法,可以加强对狗咬伤病例的控制和预防,并降低狂犬病暴发的风险。
    BACKGROUND: Dog bites pose a significant public health concern in India, necessitating an understanding of their epidemiological profile and spatial distribution. Adopting the One Health approach, which considers the interconnection of human, animal, and environmental health, is vital for developing effective interventions.
    OBJECTIVE: The study aimed to assess the epidemiological profile and geospatial trends of dog bite cases in an urban area, focusing on the age and gender distribution of victims, severity of bites, and spatial distribution of cases to inform prevention strategies.
    METHODS: A retrospective secondary data analysis was conducted on dog bite cases reported in 2022 at a tertiary care hospital in Mumbai. The epidemiological profile, including age, gender, and severity of bites, was examined. Quantum Geographic Information System (QGIS) was utilized for spatial distribution analysis, identifying hotspots within the urban area.
    RESULTS: Of the 3350 cases, 70.7% were below 40 years old, 81.6% were male, and 78.18% had Category III bites indicating severe injuries. Most cases (74%) were caused by stray dogs. QGIS analysis revealed five hotspots within the urban area.
    CONCLUSIONS: The study highlights the predominance of dog bites among younger males and the severity of injuries. Spatial analysis identified specific hotspots, underscoring the need for targeted interventions. Implementing a comprehensive surveillance system incorporating GIS technology and adopting a One Health approach can enhance the control and prevention of dog bite cases and reduce the risk of rabies outbreaks.
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  • 文章类型: Journal Article
    狂犬病对人类和动物都有重大的健康和经济后果。每年,印度见证了1740万只狗咬伤,然而,只有300万人接受暴露后预防(PEP)。正如许多新闻报道所引用的那样,印度的抗狂犬病疫苗短缺。在印度,缺乏以前针对动物咬伤的疫苗接种的文件,因此导致抗狂犬病疫苗的重新施用,导致显著的生物损失(抗狂犬病疫苗)。
    横截面,进行了回顾性研究。收集数据,并分析了从2021年6月到2023年6月的2年时间。
    大多数患者在被咬伤后的前24小时内报告,而大约三分之一在24小时后报告。大多数是第3类咬伤和无端咬伤。男性,中下阶层,在4291名患者中,下肢咬伤很常见。在217个再暴露病例中,185没有关于他们以前处理动物咬伤的任何文件。
    在诊所就诊的4291名患者中,大多数是下肢的3类叮咬。85.25%的再暴露病例必须进行完整的治疗,因为缺乏文件会导致狂犬病作为生物浪费。这种可避免的浪费可以成为治疗更多患者的资源。
    UNASSIGNED: Rabies has significant health and economic consequences for both humans and animals. Annually, India witnesses 17.4 million dog bites, yet only 3 million individuals receive post-exposure prophylaxis (PEP). There is a shortage of anti-rabies vaccine in India as quoted in many news reports. In India, lack of documentation of previous vaccination against animal bites is there, hence resulting in the re-administration of the anti-rabies vaccine, leading to a significant biological loss (anti-rabies vaccine).
    UNASSIGNED: A cross-sectional, retrospective study was conducted. Data was collected, and analyzed from June 2021 to June 2023 a period of 2 years.
    UNASSIGNED: Majority of the patients reported within the first 24 hours after being bitten while approximately one-third reported after 24 hours. Majority were Category 3 bites and unprovoked. Males, lower-middle class, and bites on lower extremities were common among 4291 patients attending the clinic. Out of 217 re-exposure cases, 185 did not have any documentation regarding their previous treatment of animal bites.
    UNASSIGNED: Among 4291 patients attending the clinic, majority were Category 3 bites on the lower extremities. 85.25% of re-exposure cases had to be administered a full course of treatment due to a lack of documentation leading to rabies as a biological wastage. This avoidable wastage can be a resource for treating more patients.
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  • 文章类型: Journal Article
    克罗地亚共和国已证明某些蝙蝠物种中的溶血病毒的血清流行率,但目前尚无证实的蝙蝠脑分离株阳性或与蝙蝠受伤/咬伤相关的人类死亡。这项研究包括对蝙蝠受伤/咬伤的回顾性分析,在萨格勒布反狂犬病诊所检查的人的暴露后预防(PEP)和蝙蝠伤害的地理分布,克罗地亚狂犬病参考中心。在1995-2020年期间,我们共检查了21,910名动物受伤患者,其中71例为蝙蝠相关(0.32%)。在上述患者中,4574人收到狂犬病PEP(20.87%)。然而,对于蝙蝠受伤,接受PEP的患者比例明显更高:71例患者中有66例(92.95%).其中,33只接种了狂犬病疫苗,而其他33名患者接受了人狂犬病免疫球蛋白(HRIG)疫苗。在五个案例中,没有进行PEP,因为没有治疗指征。35名受伤患者是生物学家或生物学学生(49.29%)。仅在一例暴露病例中确认了蝙蝠物种。这是一只血清型蝙蝠(Eptesicusserotinus),一种已知的汉堡病毒携带者。结果表明,与动物咬伤引起的其他人类伤害相比,蝙蝠咬伤是零星的。所有蝙蝠的伤害都应该被视为由狂犬病动物引起的,根据世卫组织的建议。强烈建议接触蝙蝠的人接种狂犬病疫苗。进入蝙蝠栖息地应谨慎行事,并符合目前的建议,全国范围的监测应由主管机构进行,并由蝙蝠专家密切合作,流行病学家和狂犬病专家。
    Seroprevalence of lyssaviruses in certain bat species has been proven in the Republic of Croatia, but there have been no confirmed positive bat brain isolates or human fatalities associated with bat injuries/bites. The study included a retrospective analysis of bat injuries/bites, post-exposure prophylaxis (PEP) and geographic distribution of bat injuries in persons examined at the Zagreb Antirabies Clinic, the Croatian Reference Centre for Rabies. In the period 1995-2020, we examined a total of 21,910 patients due to animal injuries, of which 71 cases were bat-related (0.32%). Of the above number of patients, 4574 received rabies PEP (20.87%). However, for bat injuries, the proportion of patients receiving PEP was significantly higher: 66 out of 71 patients (92.95%). Of these, 33 received only the rabies vaccine, while the other 33 patients received the vaccine with human rabies immunoglobulin (HRIG). In five cases, PEP was not administered, as there was no indication for treatment. Thirty-five of the injured patients were biologists or biology students (49.29%). The bat species was confirmed in only one of the exposure cases. This was a serotine bat (Eptesicus serotinus), a known carrier of Lyssavirus hamburg. The results showed that the bat bites were rather sporadic compared to other human injuries caused by animal bites. All bat injuries should be treated as if they were caused by a rabid animal, and according to WHO recommendations. People who come into contact with bats should be strongly advised to be vaccinated against rabies. Entering bat habitats should be done with caution and in accordance with current recommendations, and nationwide surveillance should be carried out by competent institutions and in close collaboration between bat experts, epidemiologists and rabies experts.
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  • 文章类型: Journal Article
    背景:狂犬病,由弹状病毒引起的,是一种致命的人畜共患疾病,全球每年有超过59,000人死亡。亚洲和非洲占95%,在印度的领导下,其次是中国。在巴基斯坦,它是地方性的,每年报告超过50,000例。通过疫苗接种控制狂犬病犬种群对于抑制死亡率至关重要。这项研究旨在评估医疗保健专业人员的知识,态度,关于白沙瓦狂犬病的做法,巴基斯坦。
    方法:这项研究是在白沙瓦的不同三级医院进行的,巴基斯坦从2021年8月16日至2022年2月15日。进行了横断面研究,以收集来自代表医疗保健领域不同部门的100名医护人员的数据。包括医务人员,众议院官员,教职员工,护士,和护理人员。知识数据,态度,使用标准化问卷收集有关狂犬病的实践。数据分析包括使用描述性统计和卡方检验来确定潜在的相关性。
    结果:在医疗保健专业人员中,68(68%)是男性,女性32人(32%)。职业方面,包括的专业人员是31名护士(31%),医务人员27人(27%),众议院官员26人(26%),辅助医务人员13人(13%),和教职员工3(3%)。91(91%)和9(9%)医疗保健专业人员回答说,狗和猫是狂犬病传播的原因,分别。此外,82(82%)个人回答说,动物咬伤在狂犬病的传播中起着至关重要的作用,而76人(76%)回应说狂犬病在人与人之间转移。82(82%)个人回答说,抗狂犬病疫苗(ARV)是狂犬病的首选治疗方法。此外,78(78%)个人回答说,ARV在怀孕和哺乳期是安全的。此外,在被问及卫生保健专业人员对控制狂犬病失败的看法后,他们的回答是ARV/RIG41不可用(41%),缺乏对流浪狗的控制34(34%),缺乏意识20(20%)。该研究揭示了医疗保健职业与变量之间的统计学显着相关性:负责传播狂犬病的动物知识(p=0.024)和人与人之间传播的意识(p=0.007)。在了解狂犬病通过污染水传播方面存在显着差异(p=0.002)。不同职位的态度和做法有所不同,特别是关于家庭治疗的观点(p=0.033)和清洁咬伤的有效性(p=0.010)。观察到狂犬病治疗的认知和抗狂犬病疫苗和免疫球蛋白的可及性差异,基于个人角色的变化。
    结论:本研究阐明了狂犬病知识的变化,态度,以及医护人员的实践,特别是他们各自的角色。量身定制的培训计划和标准化的做法在减轻这些差异方面发挥着至关重要的作用。加强对狂犬病的了解,提高患者治疗质量。建议未来的研究对疗法的疗效进行评估,并倡导在狂犬病管理领域采用“一个健康”协作策略。
    BACKGROUND: Rabies, caused by the rhabdovirus, is a fatal zoonotic disease with over 59,000 annual deaths globally. Asia and Africa account for 95%, with India leading, followed by China. In Pakistan, where it\'s endemic, over 50,000 cases are reported yearly. Controlling rabid dog populations through vaccination is crucial in curbing mortality. This research aimed to evaluate healthcare professionals\' knowledge, attitudes, and practices concerning rabies in Peshawar, Pakistan.
    METHODS: The study was conducted at different tertiary care hospitals in Peshawar, Pakistan from 16 August 2021 to 15 February 2022. Cross-sectional research was conducted to gather data from a total of 100 healthcare workers representing different sections within the healthcare field, including Medical Officers, House Officers, Faculty Staff, Nurses, and Paramedics. Data on knowledge, attitudes, and practices about rabies were collected using a standardized questionnaire. The data analysis included using descriptive statistics and chi-square testing to ascertain potential correlations.
    RESULTS: Among the healthcare professionals, 68 (68%) were males, and 32 (32%) were females. Profession-wise, the included professionals were Nurses 31 (31%), Medical Officers 27 (27%), House officers 26 (26%), paramedical staff 13 (13%), and faculty staff 3 (3%). 91 (91%) and 9 (9%) healthcare professionals responded that dogs and cats are responsible for rabies transmission, respectively. Moreover, 82 (82%) individuals responded that animal bite plays a vital role in the transmission of rabies, whilst 76 (76%) individuals responded that rabies transferred from human to human. 82 (82%) individuals replied that the anti-rabies vaccine (ARV) is the treatment of choice for rabies. Furthermore, 78 (78%) individuals responded that ARV is safe in pregnancy and lactation. Moreover, after being asked about the perception of the health care professionals about the failure in controlling rabies, their responses were unavailability of ARV/RIG 41 (41%), lack of control of stray dogs 34 (34%), lack of awareness 20 (20%). The study revealed statistically significant correlations between healthcare occupations and variables: knowledge of animals responsible for transmitting rabies (p = 0.024) and awareness of human-to-human transmission (p = 0.007). Significant disparities were noted in understanding rabies transmission through contaminated water (p = 0.002). There were variations in attitudes and practices seen across different positions, particularly about views about home treatments (p = 0.033) and the perceived effectiveness of cleansing bite wounds (p = 0.010). Disparities in perceptions of rabies treatment and the accessibility of anti-rabies vaccines and immunoglobulin were observed, with variations based on individual roles.
    CONCLUSIONS: The present research elucidates variations in rabies knowledge, attitudes, and practices among healthcare workers, specifically concerning their respective roles. Tailored training programs and standardized practices play a crucial role in mitigating these discrepancies, fostering a greater understanding of rabies, and enhancing the quality of patient treatment. It is recommended that future studies undertake an assessment of the efficacy of therapies and advocate for the adoption of collaborative One Health strategies in the realm of rabies management.
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  • 文章类型: Journal Article
    目的:狂犬病是一种被忽视的热带病毒性疾病,最常通过被感染动物的叮咬传播。
    目的:这项研究评估了知识水平,态度,以及Shone镇社区对狂犬病的做法。
    方法:在Shone镇进行了一项基于调查的横断面研究,埃塞俄比亚,从2022年11月到2023年4月。沃雷达是有目的地选择的,而Kebeles和研究人群是通过简单随机抽样选择的。使用半结构化问卷对416名受访者进行了采访。
    结果:所有受访者都从不同来源听说过狂犬病,大多数听证会来自非正式来源(62%)。约51.9%,0.7%,47.4%的人知道唾液接触,狂犬病动物咬伤,作为传输手段,分别。调查显示,一旦出现临床症状,64.4%的参与者就知道狂犬病100%致命,35.6%没有。大约51.4%的受访者认为杀死流浪狗是预防狂犬病的有效方法。在这项研究中,72.6%的受访者曾与宠物有过接触,36.8%的受访者为他们的狗接种了疫苗。只有教育水平(p=0.03)与传播途径的知识有关。年龄(p=0.04)和教育水平(p=0.01)与不给狗接种疫苗的风险知识具有统计学上的显着关联。
    结论:社区缺乏正规教育,教育水平低,大多数受访者从非官方来源获得知识是造成意识低下的重要因素。
    OBJECTIVE: Rabies is a neglected tropical viral disease most often transmitted through the bite of an infected animal.
    OBJECTIVE: This study assessed the level of knowledge, attitudes, and practices of the Shone Town community toward rabies.
    METHODS: A survey-based cross-sectional study was conducted in Shone town, Ethiopia, from November 2022 to April 2023. Woreda was selected purposefully, while Kebeles and the study populations were selected by simple random sampling. Four hundred and sixteen respondents were interviewed using a semi-structured questionnaire.
    RESULTS: All respondents had heard about rabies from different sources, with the majority hearing from informal sources (62%). Approximately 51.9%, 0.7%, and 47.4% of individuals were aware of saliva contact, rabid animal bites, and both as means of transmission, respectively. The survey showed that 64.4% of participants knew the 100% fatal nature of rabies once the clinical signs developed, and 35.6% did not. Approximately 51.4% of respondents agreed that killing stray dogs was an effective method for rabies prevention. In this study, 72.6% of the respondents had contact with pets, and 36.8% of the interviewees had vaccinated their dogs. Only the educational level (p = 0.03) was associated with knowledge of the transmission route. Age (p = 0.04) and educational level (p = 0.01) had a statistically significant association with knowledge of the risk of not vaccinating dogs.
    CONCLUSIONS: A lack of formal education in the communities, low levels of education, and the majority of respondents acquiring their knowledge from unofficial sources are important contributors to the low levels of awareness.
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  • 文章类型: Journal Article
    狂犬病病毒(RABV)导致致命的神经系统疾病。使用灭活病毒疫苗的暴露前预防(PrEP)和暴露后预防(PEP)是预防狂犬病的最有效措施。在日本,HEP-Flury,病毒株,用作人类狂犬病疫苗,历史上已在源自鸡胚的原代成纤维细胞中繁殖。在本研究中,为了降低疫苗生产的成本和劳动力,我们试图使原始的HEP-Flury(HEP)适应Vero细胞。HEP在Vero细胞中反复传代以产生十种(HEP-10V)和三十种传代(HEP-30V)菌株。HEP-10V和HEP-30V在Vero细胞中的生长明显优于HEP,具有类似于HEP的毒力和抗原性。完整基因组与HEP的比较揭示了HEP-10V中的三个非同义突变和HEP-30V中的另外四个非同义突变。通过反向遗传学构建的18个重组HEP菌株与用RABV糖蛋白假型的水泡性口炎病毒之间的比较表明,磷蛋白中的P(L115H)和糖蛋白中的G(S15R)的取代改善了HEP-10V中的病毒繁殖,在HEP-30V中,G(V164E),G(L183P),糖蛋白中的G(A286V)增强了进入Vero细胞的能力。获得的重组RABV菌株,rHEP-PG4菌株,有了这五个替换,是生产人类狂犬病疫苗的有力候选者。
    Rabies virus (RABV) causes fatal neurological disease. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) using inactivated-virus vaccines are the most effective measures to prevent rabies. In Japan, HEP-Flury, the viral strain, used as a human rabies vaccine, has historically been propagated in primary fibroblast cells derived from chicken embryos. In the present study, to reduce the cost and labor of vaccine production, we sought to adapt the original HEP-Flury (HEP) to Vero cells. HEP was repeatedly passaged in Vero cells to generate ten- (HEP-10V) and thirty-passaged (HEP-30V) strains. Both HEP-10V and HEP-30V grew significantly better than HEP in Vero cells, with virulence and antigenicity similar to HEP. Comparison of the complete genomes with HEP revealed three non-synonymous mutations in HEP-10V and four additional non-synonymous mutations in HEP-30V. Comparison among 18 recombinant HEP strains constructed by reverse genetics and vesicular stomatitis viruses pseudotyped with RABV glycoproteins indicated that the substitution P(L115H) in the phosphoprotein and G(S15R) in the glycoprotein improved viral propagation in HEP-10V, while in HEP-30V, G(V164E), G(L183P), and G(A286V) in the glycoprotein enhanced entry into Vero cells. The obtained recombinant RABV strain, rHEP-PG4 strain, with these five substitutions, is a strong candidate for production of human rabies vaccine.
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  • 文章类型: Journal Article
    背景:狂犬病是150个国家被忽视的热带病地方病,包括印度,它存在于除安达曼和尼科巴群岛Lakshadweep以外的所有州和联邦领土。喀拉拉邦报告动物咬伤的发生率很高。本文讨论了喀拉拉邦一名17岁部落女孩因狂犬病而可预防的死亡及其引起的公平问题。
    方法:案例研究是使用定性方法进行的,例如快速关键线人访谈,部落集会会议中的互动,非结构化参与者观察,文件验证。使用主题分析,结果以人种学摘要的形式呈现,并使用引号来证实观察结果。
    结果:这个女孩和她的妹妹去了一个小镇几天,当时她出现了进食困难,行为异常,还有她身上的伤.后来她死了,验尸发现Negri的尸体在她的大脑中,确认狂犬病是死因.这个女孩八个月前被森林里的小狗咬了,但她没有接受暴露后预防.定居点的每个家庭都养了多条狗,社区很好地照顾他们,因为他们保护他们免受野生动物的侵害。然而,对暴露后预防需求的认识很低,对于这个人群来说,很难获得它。定居点中的社会问题影响着他们的生活质量以及与外界的互动。
    结论:为了防止此类死亡,必须提高认识,并确保在难以到达的部落地区公平获得救生疫苗和免疫球蛋白。应对该部落定居点等高风险地区的儿童进行暴露前预防的成本效益进行评估,并与世卫组织推荐的大规模犬类疫苗接种和“一个健康”战略进行比较。
    BACKGROUND: Rabies is a neglected tropical disease endemic in 150 countries, including India where it is present in all states and union territories except Andaman and Nicobar Islands Lakshadweep. Kerala reports high incidence of animal bites. This article discusses the preventable death of a 17-year-old tribal girl due to rabies in Kerala and the equity concerns it raises.
    METHODS: The case study was conducted using qualitative methods such as rapid key informant interviews, interactions in tribal assembly meetings, unstructured participant observations, and document verification. Thematic analysis was used, and the results are presented as an ethnographic summary with the use of quotes to substantiate the observations.
    RESULTS: The girl had gone to a town with her sister for a few days when she developed difficulty in eating, behavioral abnormalities, and injuries on her body. She subsequently died, and a post-mortem revealed Negri bodies in her brain, confirming rabies as the cause of death. The girl had been bitten by a puppy from the forest eight months prior, but she did not receive post-exposure prophylaxis. Multiple dogs are kept in each household in the settlement, and the community takes good care of them since they protect them from wild animals. However, awareness about the need for post-exposure prophylaxis is low, and access to it is difficult for this population. The social problems in the settlement affect their quality of life and their interactions with the outside world.
    CONCLUSIONS: To prevent such deaths, it is essential to increase awareness and ensure equitable access to life-saving vaccines and immunoglobulin in hard-to-reach tribal areas. The cost-effectiveness of pre-exposure prophylaxis for children in high-risk areas such as this tribal settlement should be evaluated and compared with the WHO-recommended strategies of mass canine vaccination and One Health.
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  • 文章类型: Journal Article
    泰国狂犬病发病率在2018年达到峰值,有18人死亡。因此,建议对高危人群进行暴露前预防(PrEP)疫苗接种。世卫组织最近建议,暴露于疑似狂犬病动物并已免疫狂犬病的患者应在第0天和第3天接受0.1mL的1位皮内(ID)注射,作为暴露后预防(PEP)。在泰国,负责每年狗疫苗接种的乡村卫生和牲畜志愿者通常只接受一次终生PrEP剂量,并且仅在确认动物咬伤后才接受随后的助推器。然而,在这一高危人群中,单一PrEP剂量用于启动和维持免疫力的充分性尚未得到评估.因此,我们的研究旨在解决两个关键问题:(1)单剂量PrEP的充分性-确定单一IDPrEP剂量是否为在接种疫苗期间暴露于大量狗的高危个体提供足够的长期免疫保护.(2)免疫成熟的加强效力-以研究一个或两个额外的ID加强剂量是否有效地刺激该群体中的成熟和持续的抗体应答。通过比较疫苗接种组之间的免疫原性和加强效力来确定狂犬病抗体的水平和持久性。我们的研究表明,狂犬病抗体在具有成本效益的IDPrEP或第一次或第二次单次ID加强剂量后持续超过180天,通过CEE-cELISA和间接ELISA在超过95%的参与者中检测到足够的抗体水平。此外,狂犬病特异性抗体的亲和力成熟发生在第1次单次ID加强剂量后.这种较小的ID加强方案足以产生足够的免疫应答并增强抗狂犬病抗体的成熟。建议使用这种安全有效的PrEP方案和一次单剂量ID加强检查,在泰国和其他发展中国家的高危人群中,可以公平地实施至少一种单剂量ID加强方案。然而,在加强之前,应监测足够的抗体水平。
    The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.
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