PDF(Pubmed)
Abstract：
Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle.
We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon.
We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island.
A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere.
Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa\'s Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421.
We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010 to 2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data, we inferred transmission chains and estimated case detection. Using a decision tree model, we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a 10-year time horizon.
We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island.
A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable, and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere.
Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa\'s Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 and SE0421.
摘要：
■狗介导的狂犬病在非洲流行，每年造成数千人死亡。提倡对狂犬病采取“一个健康”的方法，包括咬伤受害者的紧急暴露后疫苗接种和大规模狗疫苗接种，以打破传播周期。然而,这些组件的影响和成本效益很难理解。
■我们将接触者追踪与全基因组测序相结合，以追踪狂犬病在动物水库中的传播以及从2010年至2020年对人类的溢出风险，调查“一个健康”方法的组成部分如何减轻疾病负担并消除了奔巴岛的狂犬病，坦桑尼亚。通过所得的高分辨率时空和基因组数据，我们推断了传输链并估计了病例检测。使用决策树模型，我们量化了公共卫生负担，并评估了十年时间内干预措施的影响和成本效益。
■我们解决了从2010年起在奔巴上共同循环的五个传输链，到2014年5月全部淘汰。在此期间,疯狗,在开始和改进年度全岛犬疫苗接种后，人类狂犬病暴露和死亡人数都逐渐下降。我们在2016年底确定了两次引入Pemba的疫苗接种后重新出现。随后的疫情在2018年10月通过恢复全岛狗疫苗接种被消除。虽然暴露后疫苗预计具有很高的成本效益(避免每名死亡256美元)，只有狗接种疫苗会中断传播。一种联合健康的方法，即每年常规的狗疫苗接种以及为咬伤受害者免费的暴露后疫苗，迅速消灭狂犬病,具有很高的成本效益（避免每次死亡1657美元），并且通过保持狂犬病自由，可以防止30多个家庭每年在Pemba岛上遭受创伤性狂犬病狗咬伤。
■以狗接种疫苗为基础的“一个健康”方法是一种有效的方法，成本效益高,消除狂犬病的公平和可行的方法，但需要在互联人群中扩大规模，以维持消除的好处，正如在奔巴上看到的，并在其他地方取得类似进展。
■惠康[207569/Z/17/Z，095787/Z/11/Z,103270/Z/13/Z],瑞银擎天柱基金会,美国国立卫生研究院卫生与人类服务部[R01AI141712]和DELTAS非洲倡议[AfriqueOne-ASPIRE/DEL-15-008]，由非洲科学院（AAS）的捐助者联盟组成，促进非洲科学卓越联盟（AESA）非洲发展规划和协调新伙伴关系(新伙伴关系)机构，惠康[107753/A/15/Z],皇家热带医学和卫生学会2017年小额赠款[GR000892]和英国政府。2010-2015年消灭狂犬病示范项目得到了比尔和梅林达·盖茨基金会[OPP49679]的支持。全基因组测序得到了APHA的部分支持，得到了英国环境部的资助。食品和农村事务（Defra）苏格兰政府和威尔士政府根据项目SEV3500和SE0421。
■我们将接触者追踪与全基因组测序相结合，以追踪狂犬病在动物水库中的传播以及从2010年至2020年对人类的溢出风险，调查“一个健康”方法的组成部分如何减轻疾病负担并消除了奔巴岛的狂犬病，坦桑尼亚。通过所得的高分辨率时空和基因组数据，我们推断了传输链并估计了病例检测。使用决策树模型，我们量化了公共卫生负担，并评估了十年时间内干预措施的影响和成本效益。
■我们解决了从2010年起在奔巴上共同循环的五个传输链，到2014年5月全部淘汰。在此期间,疯狗,在开始和改进年度全岛犬疫苗接种后，人类狂犬病暴露和死亡人数都逐渐下降。我们在2016年底确定了两次引入Pemba的疫苗接种后重新出现。随后的疫情在2018年10月通过恢复全岛狗疫苗接种被消除。虽然暴露后疫苗预计具有很高的成本效益(避免每名死亡256美元)，只有狗接种疫苗会中断传播。一种联合健康的方法，即每年常规的狗疫苗接种以及为咬伤受害者免费的暴露后疫苗，迅速消灭狂犬病,具有很高的成本效益（避免每次死亡1657美元），并且通过保持狂犬病自由，可以防止30多个家庭每年在Pemba岛上遭受创伤性狂犬病狗咬伤。
■以狗接种疫苗为基础的“一个健康”方法是一种有效的方法，成本效益高,消除狂犬病的公平和可行的方法，但需要在互联人群中扩大规模，以维持消除的好处，正如在奔巴上看到的，并在其他地方取得类似进展。
■惠康[207569/Z/17/Z，095787/Z/11/Z,103270/Z/13/Z],瑞银擎天柱基金会,美国国立卫生研究院卫生与人类服务部[R01AI141712]和DELTAS非洲倡议[AfriqueOne-ASPIRE/DEL-15-008]，由非洲科学院（AAS）的捐助者联盟组成，促进非洲科学卓越联盟（AESA）非洲发展规划和协调新伙伴关系(新伙伴关系)机构，惠康[107753/A/15/Z],皇家热带医学和卫生学会2017年小额赠款[GR000892]和英国政府。2010-2015年消灭狂犬病示范项目得到了比尔和梅林达·盖茨基金会[OPP49679]的支持。全基因组测序得到了APHA的部分支持，得到了英国环境部的资助。食品和农村事务（Defra）苏格兰政府和威尔士政府根据项目SEV3500和SE0421。
