Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue.

BACKGROUND: Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection. METHODS: We conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype. RESULTS: After successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P = 0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3). CONCLUSIONS: Introgression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants. (Funded by the Tahija Foundation and others; AWED ClinicalTrials.gov number, NCT03055585; Indonesia Registry number, INA-A7OB6TW.).

Aedes aegypti abundance and insecticide resistance profiles in the Applying Wolbachia to Eliminate Dengue trial.

The Applying Wolbachia to Eliminate Dengue (AWED) trial was a parallel cluster randomised trial that demonstrated Wolbachia (wMel) introgression into Ae. aegypti populations reduced dengue incidence. In this predefined substudy, we compared between treatment arms, the relative abundance of Ae. aegypti and Ae. albopictus before, during and after wMel-introgression. Between March 2015 and March 2020, 60,084 BG trap collections yielded 478,254 Ae. aegypti and 17,623 Ae. albopictus. Between treatment arms there was no measurable difference in Ae. aegypti relative abundance before or after wMel-deployments, with a count ratio of 0.96 (95% CI 0.76, 1.21) and 1.00 (95% CI 0.85, 1.17) respectively. More Ae. aegypti were caught per trap per week in the wMel-intervention arm compared to the control arm during wMel deployments (count ratio 1.23 (95% CI 1.03, 1.46)). Between treatment arms there was no measurable difference in the Ae. albopictus population size before, during or after wMel-deployment (overall count ratio 1.10 (95% CI 0.89, 1.35)). We also compared insecticide resistance phenotypes of Ae. aegypti in the first and second years after wMel-deployments. Ae. aegypti field populations from wMel-treated and untreated arms were similarly resistant to malathion (0.8%), permethrin (1.25%) and cyfluthrin (0.15%) in year 1 and year 2 of the trial. In summary, we found no between-arm differences in the relative abundance of Ae. aegypti or Ae. albopictus prior to or after wMel introgression, and no between-arm difference in Ae. aegypti insecticide resistance phenotypes. These data suggest neither Aedes abundance, nor insecticide resistance, confounded the epidemiological outcomes of the AWED trial.

Voluntary Medical Male Circumcision to Prevent HIV in Tanah Papua, Indonesia: Field Trial to Assess Acceptability and Feasibility.

BACKGROUND: Relatively little attention has been paid to the significant HIV prevention role that voluntary medical male circumcision (VMMC) can play in populations with moderate levels of HIV prevalence. One such location is Tanah Papua, Indonesia, which in 2013 had a general population having HIV prevalence of 2.3% concentrated among indigenous Papuans (2.9% prevalence), very few of whom are circumcised. This article reports the findings of an implementation research study assessing the acceptability and feasibility of introducing VMMC for HIV prevention. METHODS: Following a situational assessment and socialization of targeted groups of men and key stakeholders, a single-arm, open-label, prospective cohort trial using the non-surgical PrePex® device was undertaken in four cities. Study participants were recruited via study-associated socialization events. Data were collected from clients prior to and following device insertion, and at several "check-up" points (2-, 21- and 42-days) using standardized case report forms. A random sample of circumcision clients from one city was surveyed six months' post-removal to assess the prevalence of compensatory sexual risk behaviours. RESULTS: Demand for circumcision was weak in three of the cities, reflecting insufficient prior socialization and lingering concerns over religious appropriateness and safety issues. Despite no prior experience with PrePex ®, the pilot implementation yielded side-effect and adverse event rates that were unremarkable in comparison with sub-Saharan African countries, where PrePex ® is widely used. No evidence of increased post-procedure sexual risk-taking was found. CONCLUSION: The study findings point to both opportunity and significant challenges in introducing VMMC on a large scale in Tanah Papua, Indonesia. Although there were enough promising signs in the qualitative research and in the limited-scale implementation trial undertaken to remain optimistic as to the potential for VMMC to help contain HIV in Tanah Papua, much remains to be done to promote the benefits of VMMC and address lingering concerns as to safety and religious appropriateness. An acceleration of the pace of task-shifting from physicians to nurses will be needed in order for VMMC to be feasible for implementation on a large scale.