Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial
Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: a cluster-randomised controlled, open-label, two-by-two factorial design trial
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DOI：
10.1016/s0140-6736(20)30470-0
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发表时间：
2020-04-25
期刊：
影响因子：
168.9
通讯作者：
Gosling, Roly
中科院分区：
文献类型：
--
作者：
Hsiang, Michelle S.;Ntuku, Henry;Gosling, Roly
背景在低疟疾流行环境中，筛查和治疗与指示病例密切相关的个体，也称为反应性病例检测（RACD），用于监测和应对。然而，其他方法可能对减少传播更有效。我们的目的是评估反应性局灶性药物管理（rfMDA）和反应性局灶性病媒控制（RAVC）在低疟疾流行的设置赞比西河（纳米比亚）的有效性。方法我们做了一个集群随机对照，开放标签试验，使用两个两个析因设计的56个枚举区集群在低疟疾流行的设置赞比西河（纳米比亚）。我们使用限制性随机化将这些集群随机分配到四组：仅RACD组、仅rfMDA组、RAVC + RACD组或rfMDA + RAVC组。RACD涉及快速诊断检测和蒿甲醚-本芴醇和单剂量伯氨喹治疗，rfMDA涉及蒿甲醚-本芴醇的推定治疗，RAVC涉及甲基吡咪酮的室内残留喷洒。在索引病例的500米范围内进行干预。为了评价针对人类（rfMDA vs RACD）、蚊子（RAVC vs无RAVC）以及人类和蚊子（rfMDA + RAVC vs仅RACD）中寄生虫宿主的干预措施的有效性，进行了意向治疗分析。对于三项比较中的每一项，主要结果是当地获得的疟疾病例的累积发病率。该试验注册于ClinicalTrials.gov，编号NCT 02610400。结果在2017年1月1日至2017年12月31日期间，55个枚举区域集群有1118个合格的索引病例，导致342项干预措施，覆盖8948人。当地获得性疟疾的累积发病率为30.8/1000人年（95% CI 12.8-48.7），接受rfMDA的组群中为38.3/1000人-年（23.0-53.6）在接受RACD的集群中; 30.2/1000人-年（15.0-45.5），而接受RAVC的人群为38.9/1000人-年（20.7-57.1）;在接受rfMDA + RAVC的组中为25.0/1000人-年（5.2-44.7），而在仅接受RACD的组中为41.4/1000人-年（21.5-61.2）。在调整基线和实施因素的不平衡后，接受rfMDA的群组的疟疾发病率低于接受RACD的群组（校正后的发病率比为0.52 [95% CI 0.16-0.88]，p=0.009），接受RAVC的人群低于未接受RAVC的人群（0.48 [0.16-0.80]，p=0.002），并且在接受rfMDA + RAVC的组中低于仅接受RACD的组（0.26 [0.10-0.68]，p=0.006）。在低疟疾流行的环境中，rfMDA和RAVC，单独和联合实施，减少疟疾传播，应被视为替代RACD消除疟疾。
Background In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia).Methods We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400.Findings Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30.8 per 1000 person-years (95% CI 12.8-48.7) in the clusters that received rfMDA versus 38.3 per 1000 person-years (23.0-53.6) in the clusters that received RACD; 30.2 per 1000 person-years (15.0-45.5) in the clusters that received RAVC versus 38.9 per 1000 person-years (20.7-57.1) in the clusters that did not receive RAVC; and 25.0 per 1000 person-years (5.2-44.7) in the clusters that received rfMDA plus RAVC versus 41.4 per 1000 person-years (21.5-61.2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0.52 [95% CI 0.16-0.88], p=0.009), lower in clusters receiving RAVC than in those that did not (0.48 [0.16-0.80], p=0.002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0.26 [0.10-0.68], p=0.006). No serious adverse events were reported.Interpretation In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria.