Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Malaria Elimination Initiative, Global Health Group, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Malaria Elimination Initiative, Global Health Group, University of California San Francisco, San Francisco, CA, USA.
Lancet. 2020 Apr 25;395(10233):1361-1373. doi: 10.1016/S0140-6736(20)30470-0.
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).
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.
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.
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.
Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.
在低疟疾流行地区，针对指数病例的密切接触者进行筛查和治疗（也称为反应性病例检测），是用于监测和应对疟疾的一种方法。然而，其他方法可能更有助于减少传播。我们旨在评估在赞比西（纳米比亚）低疟疾流行地区实施反应性局部群体药物管理（rfMDA）和反应性局部媒介控制（RAVC）的效果。
我们在赞比西（纳米比亚）的低疟疾流行地区进行了一项基于集群的、随机对照、开放性标签试验，采用二乘二析因设计，共包括 56 个计数区集群。我们使用限制随机化将这些集群随机分配到四个组：仅 RACD、仅 rfMDA、RAVC 加 RACD 或 rfMDA 加 RAVC。RACD 包括快速诊断测试和青蒿琥酯-咯萘啶治疗以及单剂量伯氨喹治疗，rfMDA 包括青蒿琥酯-咯萘啶的推定治疗，RAVC 包括使用吡虫啉进行室内滞留喷洒。干预措施在指数病例的 500 米范围内实施。为了评估针对人类寄生虫储存库（rfMDA 与 RACD）、蚊子（RAVC 与无 RAVC）以及人类和蚊子（rfMDA 加 RAVC 与仅 RACD）的干预措施的有效性，进行了意向治疗分析。对于这三种比较中的每一种，主要结局是局部获得性疟疾病例的累积发生率。这项试验在 ClinicalTrials.gov 注册，编号为 NCT02610400。
2017 年 1 月 1 日至 12 月 31 日期间，55 个计数区集群有 1118 名符合条件的指数病例，导致 342 次干预，覆盖了 8948 人。在接受 rfMDA 的集群中，局部获得性疟疾的累积发病率为每 1000 人年 30.8 例（95%CI 12.8-48.7），而在接受 RACD 的集群中为每 1000 人年 38.3 例（23.0-53.6）；在接受 RAVC 的集群中，每 1000 人年 30.2 例（15.0-45.5），而在未接受 RAVC 的集群中，每 1000 人年 38.9 例（20.7-57.1）；在接受 rfMDA 加 RAVC 的集群中，每 1000 人年 25.0 例（5.2-44.7），而在仅接受 RACD 的集群中，每 1000 人年 41.4 例（21.5-61.2）。在调整了基线和实施因素的不平衡后，接受 rfMDA 的集群中疟疾的发病率低于接受 RACD 的集群（调整后的发病率比 0.52[95%CI 0.16-0.88]，p=0.009），接受 RAVC 的集群中疟疾的发病率低于未接受 RAVC 的集群（0.48[0.16-0.80]，p=0.002），接受 rfMDA 加 RAVC 的集群中疟疾的发病率低于仅接受 RACD 的集群（0.26[0.10-0.68]，p=0.006）。没有报告严重不良事件。
在低疟疾流行地区，rfMDA 和 RAVC 单独和联合实施，可降低疟疾传播，应考虑作为 RACD 的替代方法，用于消除疟疾。
诺华基金会、比尔及梅琳达·盖茨基金会和霍奇家族基金。
