A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study
A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study
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DOI：
10.1016/s1473-3099(19)30311-1
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发表时间：
2019-12-01
影响因子：
56.3
通讯作者：
Tarantola, Arnaud
中科院分区：
文献类型：
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作者：
Cantaert, Tineke;Borand, Laurence;Tarantola, Arnaud
国际卫生当局正在支持到2030年消除犬媒人类狂犬病的努力。这一努力将需要改善获得充分和及时的狂犬病暴露后预防的机会，因为对世卫组织推荐的治疗方案（在1个月内进行4至5次就诊）的依从性较低。通过缩短接种方案以减少剂量、直接和间接成本，并通过更好地分享现有疫苗来改善疫苗公平性，可大大改善获得疫苗的机会。我们的目的是比较第四次访问前后的狂犬病毒中和抗体滴度，以确定是否需要这一疗程或当前的方案可以缩短。方法采用快速荧光焦点抑制法对116例实验室确诊狂犬病犬咬伤者和20例对照者进行狂犬病毒中和抗体效价测定。流式细胞术检测循环浆母细胞百分比。根据2010年世卫组织的建议，所有人都被转诊到柬埔寨巴斯德研究所的狂犬病预防诊所，并在第0、3、7和28天（泰国红十字会方案）接受两次皮内注射，含或不含马狂犬病免疫球蛋白。结果所有人在最后一次注射前28天均有狂犬病毒中和抗体效价（>= 0.5 IU/mL）和血浆母细胞激活。被狂犬病毒阳性犬咬伤个体第7天的狂犬病病毒中和抗体中位数为1.08 IU/mL (IQR 0.37-3.09)，第28天为26.86(22.68-49.50)，第42天为26.74（11.78-49.06）。在滴度达到平台后的第28天和第42天，滴度没有显著差异。无论马是否使用狂犬病免疫球蛋白、年龄、性别、营养状况（儿童上臂围或成人BMI）或犬感染状况如何，均达到上述滴度。从最后一次注射当天到2周后，滴度或浆母细胞百分比没有增加。所有患者在暴露后预防1年后仍然存活。第28天的第四次疫苗接种没有提供额外的益处。狂犬病暴露后预防可以简化为两剂、三次、1周的治疗方案，以提高暴露后预防的覆盖率和公平性，对患者没有风险。巴斯德基金研究所。版权所有2019 Elsevier Ltd.版权所有。
Background The international health authorities are backing an effort to eliminate canine-mediated rabies in humans by 2030. This effort will require improving access to adequate and timely rabies post-exposure prophylaxis as compliance is low with WHO-recommended regimens (given in four to five visits over 1 month). Access could be substantially improved by an abridged regimen to reduce doses, direct and indirect costs, and improve vaccine equity by better sharing of available vaccine. We aimed to compare rabies virus neutralising antibody titres before and after the fourth visit to determine whether that session was needed or the current regimen could be abridged.Methods In this obse rvational cohort study, we measured rabies virus neutralising antibody titres using rapid fluorescent focus inhibition tests in 116 people bitten by dogs with laboratory-confirmed rabies and 20 control individuals. Percentages of circulating plasmablasts were determined by flow cytometry. All individuals had been referred to the rabies prevention clinic at Institut Pasteur in Cambodia and received two intradermal injections of post-exposure prophylaxis on days 0, 3, 7, and 28 (Thai Red Cross regimen) with or without equine rabies immunoglobulin, as per 2010 WHO recommendations.Findings All individuals had rabies virus neutralising antibody titres considered protective (>= 0.5 IU/mL) and plasmablast activation on day 28 before the last injection. The median rabies virus neutralising antibody concentration in the group of individuals bitten by rabies virus-positive dogs was 1.08 IU/mL (IQR 0.37-3.09) on day 7, 26.86 (22.68-49.50) on day 28, and 26.74 (11.78-49.06) on day 42. No significant differences were observed in titres between days 28 and 42, after titres reached a plateau. These titres were reached notwithstanding equine rabies immunoglobulin use, age, sex, nutrition status as indicated by upper-arm circumference in children or BMI in adults, or dog infection status. Titres or plasmablast percentages did not increase between the day of the last injection and 2 weeks later. All patients were alive 1 year after post-exposure prophylaxis.Interpretation The fourth vaccine session on day 28 provides no additional benefit. Rabies post-exposure prophylaxis can be abridged to a two-dose, three-session, 1 week regimen to improve post-exposure prophylaxis coverage and equity at no risk to patients.Funding Institut Pasteur. Copyright (c) 2019 Elsevier Ltd. All rights reserved.