Efficacy of Wolbachia-infected mosquito deployments for the control of dengue

Utarini, Adi; Indriani, Citra; Ahmad, Riris Andono; Tantowijoyo, Warsito; Arguni, Eggi; Ansari, M. Ridwan; Supriyati, Endah; Wardana, Dwi Satria; Metika, Yeti; Ernesia, Inggrid; Nurhayati, Indah; Prabowo, Equatori; Andari, Bekti; Green, Benjamin R.; Hodgson, Lauren; Cutcher, Zoe; Rancès, Edwige; Ryan, Peter A.; O’Neill, Scott L.; Dufault, Suzanne M.; Tanamas, Stephanie K.; Jewell, Nicholas P.; Anders, Katherine L.; Simmons, Cameron P.

BACKGROUND: Aedes aegypti mosquitoes infected with Wolbachia pipientis (wMel strain) have reduced potential to transmit dengue viruses. METHODS: We conducted a cluster randomised trial of deployments of wMel-infected Ae. aegypti for control of dengue in Yogyakarta City, Indonesia. Twenty-four geographic clusters were randomly allocated to receive wMel deployments as an adjunct to local mosquito control measures; or to continue with local mosquito control measures only. A test-negative design was used to measure efficacy. Study participants were persons 3–45 years old attending primary care clinics with acute undifferentiated fever. Laboratory testing identified virologically-confirmed dengue cases and test-negative controls. The primary endpoint was efficacy of wMel in reducing the incidence of symptomatic, virologically-confirmed dengue, caused by any dengue virus serotype. RESULTS: Following successful introgression of wMel in intervention clusters, 8144 participants were enrolled; 3721 from wMel-treated clusters and 4423 from untreated clusters. In the ITT analysis virologically-confirmed dengue occurred in 67 of 2905 (2.3%) participants in the wMel-treated and 318 of 3401 (9.4%) in the untreated arm (OR 0.23, 95% CI, 0.15 to 0.35; P=0.004): protective efficacy of 77.1% (95% CI, 65.3 to 84.9). Protective efficacy was similar for the four serotypes. Hospitalisation for virologically-confirmed dengue was less frequent for participants resident in the wMel-treated (13/2905, 2.8%) compared to the untreated arm (102/3401, 6.3%): protective efficacy 86.2% (95% CI, 66.2 to 94.3) CONCLUSIONS: wMel introgression into Ae. aegypti populations was efficacious in reducing the incidence of symptomatic dengue, and also led to fewer dengue hospitalisations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03055585 and INA-A7OB6TW