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

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 e...

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Published in:	The Lancet (British edition) Vol. 395; no. 10233; pp. 1361 - 1373
Main Authors:	Hsiang, Michelle S, Ntuku, Henry, Roberts, Kathryn W, Dufour, Mi-Suk Kang, Whittemore, Brooke, Tambo, Munyaradzi, McCreesh, Patrick, Medzihradsky, Oliver F, Prach, Lisa M, Siloka, Griffith, Siame, Noel, Gueye, Cara Smith, Schrubbe, Leah, Wu, Lindsey, Scott, Valerie, Tessema, Sofonias, Greenhouse, Bryan, Erlank, Erica, Koekemoer, Lizette L, Sturrock, Hugh J W, Mwilima, Agnes, Katokele, Stark, Uusiku, Petrina, Bennett, Adam, Smith, Jennifer L, Kleinschmidt, Immo, Mumbengegwi, Davis, Gosling, Roly
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 25-04-2020 Elsevier B.V Elsevier Limited Elsevier
Subjects:	Analysis Antimalarials - administration & dosage Antimalarials - therapeutic use Aquatic insects Artemether Artemether, Lumefantrine Drug Combination - administration & dosage Artemether, Lumefantrine Drug Combination - therapeutic use Case management Charities Clinical trials Cluster Analysis Clusters Community Control Culicidae Diagnostic systems Disease transmission Enumeration Factorial design Households Humans Infections Insecticides Intervention Malaria Malaria, Falciparum - epidemiology Malaria, Falciparum - prevention & control Mass Drug Administration - methods Mosquito Control - methods Mosquitoes Namibia - epidemiology Parasites Pesticides Pirimiphos-methyl Plasmodium falciparum Primaquine Randomization Seasons Seroepidemiologic Studies Spraying Surveillance Vector-borne diseases Namibia California Cambodia Africa
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Summary:	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.
Bibliography:	Joint first authors Contributed equally
ISSN:	0140-6736 1474-547X
DOI:	10.1016/S0140-6736(20)30470-0