Update to the AWED (Applying Wolbachia to Eliminate Dengue) trial study protocol: a cluster randomised controlled trial in Yogyakarta, Indonesia.

BACKGROUND: The AWED (Applying Wolbachia to Eliminate Dengue) trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Yogyakarta, Indonesia, with the aim of measuring the efficacy of Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting. Enrolment began in January 2018 and is ongoing. The original study protocol was published in April 2018. Here, we describe amendments that have been made to the study protocol since commencement of the trial. METHODS: The key protocol amendments are (1) a revised study duration with planned end of participant enrolment in August 2020, (2) the addition of new secondary objectives (i) to estimate serotype-specific efficacy of the Wolbachia intervention and (ii) to compare Ae. aegypti abundance in intervention versus untreated clusters, (3) an additional exposure classification for the per-protocol analysis where the Wolbachia exposure index is calculated using only the cluster-level Wolbachia prevalence in the participant's cluster of residence, (4) power re-estimation using a multinomial sampling method that better accounts for randomness in sampling, and (5) the addition of two trial stopping rules to address the potential for persistently low rates of virologically confirmed dengue case enrolment and Wolbachia contamination into untreated clusters. Additional minor changes to the protocol are also described. DISCUSSION: The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Enrolment in the trial will conclude this year (2020) and results will be reported shortly thereafter. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03055585. Registered on 14 February 2017. Last updated 22 March 2020

The AWED trial (Applying Wolbachia to Eliminate Dengue) to assess the efficacy of Wolbachia-infected mosquito deployments to reduce dengue incidence in Yogyakarta, Indonesia: study protocol for a cluster randomised controlled trial.

BACKGROUND: Dengue and other arboviruses transmitted by Aedes aegypti mosquitoes, including Zika and chikungunya, present an increasing public health challenge in tropical regions. Current vector control strategies have failed to curb disease transmission, but continue to be employed despite the absence of robust evidence for their effectiveness or optimal implementation. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with Wolbachia bacterium, with a significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Modelling predicts this will translate to local elimination of dengue in most epidemiological settings. This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field. METHODS/DESIGN: The study is a parallel, two-arm, non-blinded cluster randomised controlled trial conducted in a single site in Yogyakarta, Indonesia. The aim is to determine whether large-scale deployment of Wolbachia-infected Ae. aegypti mosquitoes leads to a measurable reduction in dengue incidence in treated versus untreated areas. The primary endpoint is symptomatic, virologically confirmed dengue virus infection of any severity. The 26 km2 study area was subdivided into 24 contiguous clusters, allocated randomly 1:1 to receive Wolbachia deployments or no intervention. We use a novel epidemiological study design, the cluster-randomised test-negative design trial, in which dengue cases and arbovirus-negative controls are sampled concurrently from among febrile patients presenting to a network of primary care clinics, with case or control status classified retrospectively based on the results of laboratory diagnostic testing. Efficacy is estimated from the odds ratio of Wolbachia exposure distribution (probability of living in a Wolbachia-treated area) among virologically confirmed dengue cases compared to test-negative controls. A secondary per-protocol analysis allows for individual Wolbachia exposure levels to be assessed to account for movements outside the cluster and the heterogeneity in local Wolbachia prevalence among treated clusters. DISCUSSION: The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Together with observational evidence that is accumulating from pragmatic deployments of Wolbachia in other field sites, this will provide valuable data to estimate the effectiveness of this novel approach to arbovirus control, inform future cost-effectiveness estimates, and guide plans for large-scale deployments in other endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03055585 . Registered on 14 February 2017

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.)

Aborsi dalam Perspektif Lintas Agama

xv.147 hal.;ill.;21 c

Enhancing community participation in dengue control through digital crowdsourcing: An analysis of a World Mosquito Program digital open call in Sri Lanka.

BACKGROUND: Two crowdsourcing open calls were created to enhance community engagement in dengue control in Sri Lanka. We analyzed the process and outcomes of these digital crowdsourcing open calls. METHODS: We used standard World Health Organization (WHO) methods to organize the open calls which used exclusively digital methods because of COVID-19. We collected and analyzed socio-demographic information and digital engagement metrics from each submission. Submissions in the form of textual data describing community-led strategies for mosquito release were coded using grounded theory. RESULTS: The open calls received 73 submissions. Most people who submitted ideas spoke English, lived in Sri Lanka, and were 18 to 34 years old. The total Facebook reach was initially limited (16,161 impressions), prompting expansion to a global campaign which reached 346,810 impressions over 14 days. Diverse strategies for the distribution of Wolbachia-infected mosquito boxes were identified, including leveraging traditional festivals, schools, and community networks. Fifteen submissions (21%) suggested the use of digital tools for monitoring and evaluation, sharing instructions, or creating networks. Thirteen submissions (18%) focused on social and economic incentives to prompt community engagement and catalyze community-led distribution. CONCLUSIONS: Our project demonstrates that digital crowdsourcing open calls are an effective way to solicit creative and innovative ideas in a resource-limited setting

Stable establishment of wMel Wolbachia in Aedes aegypti populations in Yogyakarta, Indonesia.

The successful establishment of the wMel strain of Wolbachia for the control of arbovirus transmission by Aedes aegypti has been proposed and is being implemented in a number of countries. Here we describe the successful establishment of the wMel strain of Wolbachia in four sites in Yogyakarta, Indonesia. We demonstrate that Wolbachia can be successfully introgressed after transient releases of wMel-infected eggs or adult mosquitoes. We demonstrate that the approach is acceptable to communities and that Wolbachia maintains itself in the mosquito population once deployed. Finally, our data show that spreading rates of Wolbachia in the Indonesian setting are slow which may reflect more limited dispersal of Aedes aegypti than seen in other sites such as Cairns, Australia

<i>Aedes aegypti</i> abundance and insecticide resistance profiles in the Applying <i>Wolbachia </i>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