Efficacy of a Spatial Repellent for Control of Malaria in Indonesia: A Cluster-Randomized Controlled Trial

Din Syafruddin, Puji B S Asih, Ismail Ekoprayitno Rozi, Dendi Hadi Permana, Anggi Puspa Nur Hidayati, Lepa Syahrani, Siti Zubaidah, Dian Sidik, Michael J Bangs, Claus Bøgh, Fang Liu, Evercita C Eugenio, Jared Hendrickson, Timothy Burton, J Kevin Baird, Frank Collins, John P Grieco, Neil F Lobo, Nicole L Achee, Din Syafruddin, Puji B S Asih, Ismail Ekoprayitno Rozi, Dendi Hadi Permana, Anggi Puspa Nur Hidayati, Lepa Syahrani, Siti Zubaidah, Dian Sidik, Michael J Bangs, Claus Bøgh, Fang Liu, Evercita C Eugenio, Jared Hendrickson, Timothy Burton, J Kevin Baird, Frank Collins, John P Grieco, Neil F Lobo, Nicole L Achee

Abstract

A cluster-randomized, double-blinded, placebo-controlled trial was conducted to estimate the protective efficacy (PE) of a spatial repellent (SR) against malaria infection in Sumba, Indonesia. Following radical cure in 1,341 children aged ≥ 6 months to ≤ 5 years in 24 clusters, households were given transfluthrin or placebo passive emanators (devices designed to release vaporized chemical). Monthly blood screening and biweekly human-landing mosquito catches were performed during a 10-month baseline (June 2015-March 2016) and a 24-month intervention period (April 2016-April 2018). Screening detected 164 first-time infections and an accumulative total of 459 infections in 667 subjects in placebo-control households, and 134 first-time and 253 accumulative total infections among 665 subjects in active intervention households. The 24-cluster protective effect of 27.7% and 31.3%, for time to first-event and overall (total new) infections, respectively, was not statistically significant. Purportedly, this was due in part to zero to low incidence in some clusters, undermining the ability to detect a protective effect. Subgroup analysis of 19 clusters where at least one infection occurred during baseline showed 33.3% (P-value = 0.083) and 40.9% (P-value = 0.0236, statistically significant at the one-sided 5% significance level) protective effect to first infection and overall infections, respectively. Among 12 moderate- to high-risk clusters, a statistically significant decrease in infection by intervention was detected (60% PE). Primary entomological analysis of impact was inconclusive. Although this study suggests SRs prevent malaria, additional evidence is required to demonstrate the product class provides an operationally feasible and effective means of reducing malaria transmission.

Conflict of interest statement

Disclaimer: The contents are the responsibility of the authors.

Figures

Figure 1.
Figure 1.
Study site areas in Southwest and West Sumba districts located in Kodi, Kodi Bangedo, and Lamboya subdistricts of Sumba Island, Nusa Tenggara Timur Province (eastern Lesser Sunda Islands), Indonesia (map not to scale).
Figure 2.
Figure 2.
Traditional Sumba house structure (A) raised ∼1 m aboveground and averaging ∼70 m3 in size with thatch roof, bamboo floors, and walls (B), which offer minimal protection from mosquito entry.
Figure 3.
Figure 3.
Location of 24 study clusters in West and Southwest districts, Sumba. Clusters were selected for enrolling the incidence cohort, each consisting of ca. 100 households with an average distance of 500 m between clusters. A total of 48 sentinel houses from 12 clusters were selected for routine entomological human-landing catch.
Figure 4.
Figure 4.
Flowchart of enrollment of study volunteers.
Figure 5.
Figure 5.
Kaplan-Meier curves by treatment (all clusters [A]; subset analysis [B and C]) and by cluster (D).
Figure 6.
Figure 6.
Mean (+SD) cumulative biweekly indoor (A) and outdoor (B) anopheline human-landing catch averaged over 20–24 households per treatment arm—spatial repellent intervention and placebo, respectively.

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