Randomized Trial of Targeted Indoor Spraying to Prevent Aedes-Borne Diseases

Submitted by the MVCAC VVBD Committee

Dean et al. N Engl J Med 2025;393:1387-98. DOI: 10.1056/NEJMoa2501069

ABSTRACT:

BACKGROUND Targeted indoor residual spraying focuses insecticide applications on common resting surfaces of Aedes aegypti mosquitoes (an arboviral disease vector) in houses, such as exposed lower sections of walls and under furniture.

METHODS We conducted a two-group, parallel, unblinded, cluster-randomized trial in Merida, Mexico, to quantify the efficacy of targeted indoor residual spraying for preventing Aedes-borne diseases (chikungunya, dengue, or Zika). Children 2 to 15 years of age were enrolled from households in 50 clusters of five-by-five city blocks. Households in 25 clusters received an annual application of targeted indoor residual spraying (intervention) before each season of Aedes-borne disease (July through December). All clusters received routine Ministry of Health vector control. The primary end point was laboratory-confirmed, symptomatic Aedes-borne disease. Community effects were assessed with the use of geolocated national surveillance data.

RESULTS A total of 4461 children were monitored for up to three seasons (2021, 2022, and 2023). The indoor density of A. aegypti mosquitoes was 59% (95% confidence interval [CI], 51 to 65) lower with the intervention than with control. A total of 422 cases of aedes-borne disease were confirmed, primarily dengue in 2023. In the per-protocol analysis of cluster centers, 91 cases occurred among 1038 participants in the intervention group and 89 cases among 1037 participants in the control group (efficacy, −12.8%; 95% CI, −60.7 to 23.0). In an intention-to-treat analysis of entire clusters, 198 cases occurred among 2239 participants in the intervention group and 199 cases among 2222 participants in the control group (efficacy, 3.9%; 95% CI, −28.1 to 26.7). Adjustment of analyses for mobility or demographic characteristics did not change results. On the basis of 150 cases in the intervention clusters and 202 in the control clusters that were geolocated, the estimated community effect of the intervention was 24.0% (95% CI, 6.0 to 38.6). Two cases of multisymptom adverse events (e.g., nausea, watery eyes, diarrhea, and vomiting) were associated with the intervention.

CONCLUSIONS Despite lower entomologic indexes with targeted indoor residual spraying than with routine vector control, the cumulative incidence of Aedes-borne diseases was not significantly lower with targeted indoor residual spraying.

Note: Indoor residual insecticide treatments are not new and were the primary approach to Anopheles control during malaria eradication efforts when all indoor surfaces of all houses were sprayed. The results herein show that mosquito population reduction >60% is necessary to prevent disease and that targeted control may be inadequate.