Mass drug administration of ivermectin and dihydroartemisinin-piperaquine as an additional intervention for malaria elimination

大规模施用伊维菌素和双氢青蒿素哌喹作为消除疟疾的额外干预措施

• 批准号: MC_EX_MR/R006075/1
• 负责人: Umberto D'Alessandro
• 金额: $ 262.18万
• 依托单位: MRC Unit the Gambia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_EX_MR%2FR006075%2F1
• 关键词: Mass; drug; administration; ivermectin; dihydroartemisinin

Since 2000, there has been a substantial decrease of the malaria burden in sub-Saharan Africa due to the scale up of vector control interventions such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), and better case management with artemisinin-based combination therapy (ACT). Though some African countries such as The Gambia and Senegal have achieved excellent coverage of standard control interventions, malaria transmission has not been interrupted. This is probably due to two major factors, namely (i) the large and hidden human reservoir of infection, meaning individuals without any symptom but infected with malaria and thus able to infect the mosquito vector, and (ii) vector-related factors, e.g. vector behaviour and insecticide resistance, allowing vectors to escape standard control interventions such as LLIN and IRS. These two factors maintaining transmission require additional interventions specifically targeting them. Mass Drug Administration (MDA) consists in administering at regular intervals a full antimalarial treatment to the whole population. This intervention has been identified as a potential tool to further reduce transmission where coverage of vector control activities is already high as it would clear malaria infection from asymptomatic carriers and thus reduce the human reservoir of infection. An ACT administered to the whole population should decrease the number of malaria-infected individuals and thus may have an effect on transmission. Ivermectin (IVM) is a mosquitocidal agent that is safe for humans but toxic to Anopheles mosquitoes when feeding on individuals recently treated with it. Combining an ACT with an IVM may have a synergistic effect because the former would reduce the human reservoir of infection while the latter would kill mosquitoes that have escaped standard vector control interventions. In addition, combining an ACT with IVM would also reduce the minimal coverage required by MDA to have an effect on transmission. Transmission models suggest that adding IVM to a MDA intervention may interrupt transmission where standard MDA would be insufficient. However, this has never been rigorously evaluated in a well-designed cluster-randomized trial. This community-based, cluster-randomized trial will be carried out in the Upper River Region of The Gambia. Thirty two villages (clusters) at least 3-4km apart and with 200-600 inhabitants will be randomized to either the intervention or the control arm. MDA with IVM and dihydroartemisinin-piperaquine (DP) will be implemented in 16 intervention villages and any other human settlement in the buffer zone around intervention villages (2km). MDA will consist of 3-monthly rounds per year during the malaria transmission season for two years. Malaria prevalence at the peak of each transmission season and the mosquito population age structure will be compared between intervention and control arms. We will also collect qualitative social science data on coverage, potential bottlenecks for the intervention, adherence and acceptability; a health economics study will determine the cost of the intervention in relation to malaria infections and malaria patients prevented.

自2000年以来，由于扩大了病媒控制干预措施，如长效驱虫蚊帐和室内滞留喷洒，以及使用青蒿素类复方疗法改善了病例管理，撒哈拉以南非洲的疟疾负担大幅减少。虽然冈比亚和塞内加尔等一些非洲国家的标准控制干预措施的覆盖率很高，但疟疾传播并未中断。这可能是由于两个主要因素造成的，即（一）巨大而隐蔽的人类感染库，即没有任何症状但感染了疟疾的个人，因此能够感染蚊子病媒，以及（二）与病媒有关的因素，例如病媒的行为和杀虫剂抗药性，使病媒能够逃脱长效杀虫剂和室内滞留喷洒等标准控制措施。这两个维持传播的因素需要专门针对它们的额外干预措施。大规模药物管理包括定期向全体人口提供全面的抗疟治疗。在病媒控制活动覆盖率已经很高的地方，这种干预措施被确定为进一步减少传播的潜在工具，因为它将清除无症状携带者中的疟疾感染，从而减少人类感染源。向全体人口施用青蒿素综合疗法应减少疟疾感染者的人数，从而可能对传播产生影响。伊维菌素（IVM）是一种杀蚊剂，对人类安全，但对刚用过的按蚊有毒性，ACT与IVM合用可能产生协同效应，因为前者可减少人类感染宿主，而后者可杀死逃脱标准病媒控制干预措施的蚊子。此外，将ACT与病媒综合防治相结合还将减少MDA对传播产生影响所需的最低覆盖范围。传播模型表明，在MDA干预措施中增加IVM可能会在标准MDA不足的情况下中断传播。然而，这从未在设计良好的随机分组试验中进行过严格的评估。这项以社区为基础的随机分组试验将在冈比亚上游地区进行。将32个相距至少3- 4公里、居民人数在200-600人之间的村庄（组）随机分配到干预组或对照组。将在16个干预村和干预村周围缓冲区（2公里）内的任何其他人类住区实施MDA，包括IVM和双氢青蒿素-哌喹（DP）。MDA将包括在疟疾传播季节每年3个月一轮，为期两年。将在干预组和控制组之间比较每个传播季节高峰期的疟疾流行率和蚊子种群年龄结构。我们还将收集关于覆盖率、干预措施的潜在瓶颈、坚持性和可接受性的定性社会科学数据;一项卫生经济学研究将确定与疟疾感染和预防疟疾患者有关的干预费用。

项目成果

Entomological impact of mass administration of ivermectin and dihydroartemisinin-piperaquine in The Gambia: a cluster-randomized controlled trial.

• DOI: 10.1186/s13071-022-05557-4
• 发表时间: 2022-11-17
• 期刊: Parasites & vectors
• 影响因子: 3.2

Costs and barriers faced by households seeking malaria treatment in the Upper River Region, The Gambia.

• DOI: 10.1186/s12936-021-03898-6
• 发表时间: 2021-09-16
• 期刊: Malaria journal
• 影响因子: 3
• 作者: Broekhuizen H;Fehr A;Nieto-Sanchez C;Muela J;Peeters-Grietens K;Smekens T;Kalleh M;Rijndertse E;Achan J;D'Alessandro U
• 通讯作者: D'Alessandro U

From informed consent to adherence: factors influencing involvement in mass drug administration with ivermectin for malaria elimination in The Gambia.

• DOI: 10.1186/s12936-021-03732-z
• 发表时间: 2021-04-26
• 期刊: Malaria journal
• 影响因子: 3
• 作者: Fehr A;Nieto-Sanchez C;Muela J;Jaiteh F;Ceesay O;Maneh E;Baldeh D;Achan J;Dabira E;Conteh B;Bunders-Aelen J;Smekens T;Broekhuizen H;D'Alessandro U;Peeters Grietens K
• 通讯作者: Peeters Grietens K

Ivermectin for malaria control in mass drug administration programmes - Authors' reply.

伊维菌素用于大规模药物管理计划中的疟疾控制 - 作者的答复。

• DOI: 10.1016/s1473-3099(22)00156-6
• 发表时间: 2022
• 期刊: The Lancet. Infectious diseases
• 作者: Dabira ED