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An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV)-associated acute lower respiratory infections in children

机译:对新兴的针对儿童呼吸道合胞病毒(RSV)相关的急性下呼吸道感染的干预措施的评估

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BackgroundRespiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization.MethodsWe used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%.ResultsIn the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost; moderate levels of optimism for likelihood of efficacy, deliverability, sustainability and impact on equity; high levels of optimism regarding acceptance to end users and health workers. The group also evaluated immunoprophylaxis against RSV using monoclonal antibodies and expressed no optimism towards low product cost; very low levels of optimism regarding deliverability, affordability, sustainability, low implementation cost and impact on equity; moderate levels of optimism against the criteria of answerability, likelihood of efficacy, acceptance to end-users and health workers; and high levels of optimism regarding low development cost. They felt that either of these vaccines would have a high impact on reducing burden of childhood ALRI due to RSV and reduce the overall childhood ALRI burden by a maximum of about 10%.ConclusionAlthough monoclonal antibodies have proven to be effective in providing protection to high-risk infants, their introduction in resource poor settings might be limited by high cost associated with them. Candidate vaccines for active immunization of infants against RSV hold greatest promise. Introduction of a low cost vaccine against RSV would reduce the inequitable distribution of burden due to childhood ALRI and will most likely have a high impact on morbidity and mortality due to severe ALRI.
机译:背景呼吸道合胞病毒(RSV)是儿童急性下呼吸道感染(ALRI)的主要原因。据估计,每年在儿童中引起约3380万新的ALRI发作,其中96%发生在发展中国家。据估计每年还导致幼儿死亡约53,000至199,000。目前,在针对主动和被动免疫的发展阶段,有几种针对RSV的疫苗和免疫预防候选物。方法我们使用改良的CHNRI方法确定健康研究投资的重点。这是分两个阶段完成的。在第一阶段,我们系统地回顾了与针对RSV的新兴疫苗相关的文献,涉及12个相关标准。在第二阶段,我们邀请了20位专家(领先的基础科学家,国际公共卫生研究人员,国际政策制定者和制药公司代表)进行了专家意见调查。决策者和行业代表在匿名的情况下接受了我们的邀请,因为他们参与此类活动具有敏感性。他们回答了来自CHNRI框架的问题,并记录了他们对每个标准的“集体乐观”程度,范围为0%到100%。产品成本低,可负担性和开发成本低;在回答标准,功效可能性,可传递性,可持续性和对最终用户接受干预措施的标准方面,有中等程度的乐观;对公平和对卫生工作者的接受程度的乐观程度很高。在考虑针对孕妇的候选疫苗时,专家组表示对产品成本低,负担能力强,负责任且开发成本低的乐观程度较低;对效力,可交付性,可持续性和对公平的影响的可能性持中等程度的乐观;对最终用户和卫生工作者的接受程度高度乐观。该小组还评估了使用单克隆抗体对RSV的免疫预防效果,并对低廉的产品成本表示不乐观。对可交付性,可负担性,可持续性,较低的实施成本以及对公平的影响的乐观程度很低;针对责任感,功效的可能性,最终用户和卫生工作者的接受程度等标准的乐观程度;以及对低开发成本的高度乐观。他们认为,这两种疫苗都将对减轻由于RSV引起的儿童ALRI负担产生最大的影响,并将儿童ALRI的总体负担减少最多约10%。结论尽管已证明单克隆抗体可有效保护高危儿童,危险的婴儿,他们在资源贫乏地区的介绍可能会受到与之相关的高昂费用的限制。对RSV进行婴儿主动免疫的候选疫苗具有最大的前景。引入针对RSV的低成本疫苗将减少由于儿童ALRI引起的负担的不公平分配,并且最有可能对由于严重ALRI引起的发病率和死亡率产生重大影响。

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