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

自2000年以来，撒哈拉以南非洲的疟疾负担大幅减少，这是因为扩大了病媒控制干预措施，如长效杀虫蚊帐和室内滞留喷洒，以及青蒿素综合疗法更好的病例管理。虽然冈比亚和塞内加尔等一些非洲国家实现了标准控制干预措施的良好覆盖，但疟疾传播并未中断。这可能是由于两个主要因素，即(I)巨大和隐蔽的人类感染宿主，这意味着没有任何症状但感染了疟疾的人能够感染蚊子媒介，以及(Ii)与媒介有关的因素，例如媒介行为和杀虫剂抗药性，使媒介能够逃脱标准的控制干预，如LLIN和IRS。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。大众药物管理局(MDA)包括定期对全体人口进行全面的抗疟疾治疗。这一干预措施已被确定为进一步减少媒介控制活动复盖率已经很高的传播的潜在工具，因为它将清除无症状携带者的疟疾感染，从而减少人类感染的宿主。对全体人口实施ACT应该会减少感染疟疾的个人数量，从而可能对传播产生影响。伊维菌素(IVM)是一种对人类安全的灭蚊剂，但在以最近处理过的个体为食时，对按蚊有毒。将ACT和IVM结合起来可能具有协同效应，因为前者将减少人类感染的宿主，而后者将杀死逃脱标准媒介控制干预的蚊子。此外，将ACT与IVM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，在丙二醛干预中加入IVM可能会在标准丙二醛不足的情况下中断传播。然而，在设计良好的整群随机试验中，这从未得到过严格的评估。这项以社区为基础的整群随机试验将在冈比亚上游地区进行。相距至少3-4公里、居民200-600人的32个村庄(群)将被随机分为干预组或控制组。将在16个干预村庄和干预村庄周围缓冲区(2公里)的任何其他人类住区实施丙二醛和IVM和双氢青蒿素-哌喹(DP)。在为期两年的疟疾传播季节，丙型肝炎将由每年3个月轮次组成。将比较干预和控制部门在每个传播季节高峰期的疟疾流行率和蚊子种群年龄结构。我们还将收集有关覆盖面、干预的潜在瓶颈、依从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成本。

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.