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
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-018-2670-z |
| _version_ | 1811325535989530624 |
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| author | Katherine L. Anders Citra Indriani Riris Andono Ahmad Warsito Tantowijoyo Eggi Arguni Bekti Andari Nicholas P. Jewell Edwige Rances Scott L. O’Neill Cameron P. Simmons Adi Utarini |
| author_facet | Katherine L. Anders Citra Indriani Riris Andono Ahmad Warsito Tantowijoyo Eggi Arguni Bekti Andari Nicholas P. Jewell Edwige Rances Scott L. O’Neill Cameron P. Simmons Adi Utarini |
| author_sort | Katherine L. Anders |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T14:36:05Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-13T14:36:05Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
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| series | Trials |
| spelling | doaj.art-6fe8d970efdd4511be794cb08dbf47bc2022-12-22T02:43:03ZengBMCTrials1745-62152018-05-0119111610.1186/s13063-018-2670-zThe 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 trialKatherine L. Anders0Citra Indriani1Riris Andono Ahmad2Warsito Tantowijoyo3Eggi Arguni4Bekti Andari5Nicholas P. Jewell6Edwige Rances7Scott L. O’Neill8Cameron P. Simmons9Adi Utarini10World Mosquito Program, Institute of Vector Borne Disease, Monash UniversityDepartment of Biostatistics, Epidemiology and Population Health, Faculty of Medicine, Universitas Gadjah MadaDepartment of Biostatistics, Epidemiology and Population Health, Faculty of Medicine, Universitas Gadjah MadaEliminate Dengue Project, Centre for Tropical Medicine, Faculty of Medicine, Universitas Gadjah MadaEliminate Dengue Project, Centre for Tropical Medicine, Faculty of Medicine, Universitas Gadjah MadaEliminate Dengue Project, Centre for Tropical Medicine, Faculty of Medicine, Universitas Gadjah MadaSchool of Public Health, University of CaliforniaWorld Mosquito Program, Institute of Vector Borne Disease, Monash UniversityWorld Mosquito Program, Institute of Vector Borne Disease, Monash UniversityWorld Mosquito Program, Institute of Vector Borne Disease, Monash UniversityEliminate Dengue Project, Centre for Tropical Medicine, Faculty of Medicine, Universitas Gadjah MadaAbstract 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.http://link.springer.com/article/10.1186/s13063-018-2670-zWolbachiadenguechikungunyaZikavector-borne diseasecluster randomised trial |
| spellingShingle | Katherine L. Anders Citra Indriani Riris Andono Ahmad Warsito Tantowijoyo Eggi Arguni Bekti Andari Nicholas P. Jewell Edwige Rances Scott L. O’Neill Cameron P. Simmons Adi Utarini 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 Trials Wolbachia dengue chikungunya Zika vector-borne disease cluster randomised trial |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Wolbachia dengue chikungunya Zika vector-borne disease cluster randomised trial |
| url | http://link.springer.com/article/10.1186/s13063-018-2670-z |
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