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.,The Lancet

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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.
The Lancet ( IF 98.4 ) Pub Date : 2020-04-25 , DOI: 10.1016/s0140-6736(20)30470-0
Michelle S Hsiang ₁ , Henry Ntuku ₂ , Kathryn W Roberts ₂ , Mi-Suk Kang Dufour ₃ , Brooke Whittemore ₄ , Munyaradzi Tambo ₅ , Patrick McCreesh ₆ , Oliver F Medzihradsky ₇ , Lisa M Prach ₂ , Griffith Siloka ₈ , Noel Siame ₈ , Cara Smith Gueye ₂ , Leah Schrubbe ₂ , Lindsey Wu ₉ , Valerie Scott ₂ , Sofonias Tessema ₁₀ , Bryan Greenhouse ₁₀ , Erica Erlank ₁₁ , Lizette L Koekemoer ₁₁ , Hugh J W Sturrock ₂ , Agnes Mwilima ₈ , Stark Katokele ₁₂ , Petrina Uusiku ₁₂ , Adam Bennett ₂ , Jennifer L Smith ₂ , Immo Kleinschmidt ₁₃ , Davis Mumbengegwi ₅ , Roly Gosling ₁₄

Affiliation

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.
Division of Prevention Science, University of California San Francisco, San Francisco, CA, USA.
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Multidisciplinary Research Centre, University of Namibia, Windhoek, Namibia.
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.
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.
Zambezi Ministry of Health and Social Services, Katima, Namibia.
Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Wits Research Institute for Malaria, South African Medical Research Council Collaborating Centre for Multi-Disciplinary Research on Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
National Vector-Borne Diseases Control Programme, Namibia Ministry of Health and Social Services, Windhoek, Namibia.
Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Wits Research Institute for Malaria, South African Medical Research Council Collaborating Centre for Multi-Disciplinary Research on Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Southern African Development Community, Malaria Elimination Eight Secretariat, Windhoek, Namibia.
Malaria Elimination Initiative, Global Health Group, University of California San Francisco, San Francisco, CA, USA; Multidisciplinary Research Centre, University of Namibia, Windhoek, Namibia.

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. FUNDING Novartis Foundation, Bill & Melinda Gates Foundation, and Horchow Family Fund.

中文翻译：

在纳米比亚低疟疾流行地区，反应性局灶性大剂量药物管理和反应性病灶媒介物控制减少疟疾传播的有效性：一项集群随机对照，开放标签，二乘二因子设计试验。

背景技术在低疟疾流行的环境中，为监视和响应而实践了筛选和治疗紧邻索引病例的个体，也称为反应性病例检测（RACD）。但是，其他方法可能会更有效地减少传输。我们旨在评估在赞比西河（纳米比亚）低疟疾流行地区的反应性局灶性大规模药物管理（rfMDA）和反应性局灶性媒介物控制（RAVC）的有效性。方法我们在赞比西河（纳米比亚）低疟疾流行地区使用56个枚举区域集群的二乘二因子设计，进行了集群随机对照，开放标签试验。我们使用受限随机化将这些聚类随机分配给四个组：仅RACD，仅rfMDA，RAVC加RACD或rfMDA加RAVC。RACD涉及使用蒿甲醚-荧光粉和单剂量伯氨喹进行快速诊断测试和治疗，rfMDA涉及使用蒿甲醚-荧光粉进行推定性治疗，而RAVC涉及使用甲基吡咯烷磷进行室内残留喷雾。在指数病例的500 m内进行干预。为了评估针对人类（rfMDA与RACD），蚊子（RAVC与无RAVC）以及人类与蚊虫（仅rfMDA加RAVC与RACD）中的寄生虫库的干预措施的有效性，进行了意向性治疗分析完成。对于这三个比较中的每一个，主要结果是本地获得性疟疾病例的累积发生率。该试验已在ClinicalTrials.gov上注册，编号为NCT02610400。发现自2017年1月1日至2017年12月31日，55个枚举区域集群中有1118个符合条件的索引案例，导致342项干预措施，覆盖了8948个人。在接受rfMDA的人群中，本地获得性疟疾的累积发病率为每1000人年30·8（95％CI 12·8-48·7），而每千人年38.3（23·0-53· 6）在收到了RACD的集群中；在接受RAVC的集群中，每1000人年30·2（15·0-45·5），而在未接受RAVC的集群中，每1000人年38·9（20·7-57·1）；在接受rfMDA和RAVC的集群中，每1000人年25·0（5·2-44·7），而在接受RACD的集群中，每1000人年41·4（21·5-61·2）只要。在调整了基准和实施因素的不平衡之后，接受rfMDA的人群的疟疾发病率低于接受RACD的人群（调整发病率比0·52 [95％CI 0·16-0·88]，p = 0·009），接受RAVC的人群低于疟疾。那些没有接受（0·48 [0·16-0·80]，p = 0·002），并且在接受rfMDA加RAVC的集群中比那些仅接受RACD的集群更低（0·26 [0·10-0 ·68]，p = 0·006）。没有严重不良反应的报道。解释在低疟疾流行的情况下，rfMDA和RAVC单独或联合实施可减少疟疾的传播，应被视为替代RACD消除疟疾的替代方法。资金筹集诺华基金会，比尔和梅琳达·盖茨基金会以及霍肖家庭基金会。在接受rfMDA加RAVC的集群中，其发生率低于仅接受RACD的集群（0·26 [0·10-0·68]，p = 0·006）。没有严重不良反应的报道。解释在低疟疾流行的情况下，rfMDA和RAVC单独或联合实施可减少疟疾的传播，应被视为替代RACD消除疟疾的替代方法。资金筹集诺华基金会，比尔和梅琳达·盖茨基金会以及霍肖家庭基金会。在接受rfMDA加RAVC的集群中，其发生率低于仅接受RACD的集群（0·26 [0·10-0·68]，p = 0·006）。没有严重不良反应的报道。解释在低疟疾流行的情况下，rfMDA和RAVC单独或联合实施可减少疟疾的传播，应被视为替代RACD消除疟疾的替代方法。资金筹集诺华基金会，比尔和梅琳达·盖茨基金会以及霍肖家庭基金会。

更新日期：2020-04-24

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