Authors: Scott L. O’Neill, Peter A. Ryan, Andrew P. Turley, Geoff Wilson, Kate Retzki, Inaki Iturbe-Ormaetxe, Yi Dong, Nichola Kenny, Christopher J. Paton, Scott A. Ritchie, Jack Brown-Kenyon, Darren Stanford, Natalie Wittmeier, Katherine L. Anders, Cameron P. Simmons
The first successful citywide scaled deployment of Wolbachia in the northern Australian city of Townsville, across 66 km2 in four stages over 28 months with full community support. Wolbachia frequencies have remained stable since deployment and to date no local dengue transmission has been confirmed in any area of Townsville after Wolbachia has established, despite local transmission events every year for the prior 13 years and an epidemiological context of increasing imported cases.
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
Authors: 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 and Adi Utarini
This study protocol describes the first trial to measure the efficacy of Wolbachia in reducing dengue virus transmission in the field. 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.
Authors: Saijo Thomas, Jiyoti Verma, Megan Woolfit, Scott L. O’Neill
This study examines the various stages in the DENV infection process to better understand the mechanism of Wolbachia-mediated virus blocking (WMVB). The results suggest that infection with Wolbachia does not inhibit DENV binding or cell entry, but reduces virus replication. In contrast to a previous report, researchers observed a similar reduction in replication of West Nile virus (WNV). This reduced replication is associated with rapid viral RNA degradation in the cytoplasm.
Authors: Lauren B. Carrington, Truong Thanh Nguyen, Thanh Thanh Nguyen, Chau Van Vinh Nguyen, Huong Thi Cam Nguyenc, Trung Tuan, Long Thi Voa, Dui Thi Lea, Nguyen Diemd, Timothy P. Hurste, Scott L. O'Neill, Vi Thuy Trana, Duong Thi Hue Kiena, Nguyet Minh Nguyen, Marcel Wolbers, Bridget Willsa, and Cameron P Simmons
The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts.
The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.
Authors: Johanna E. Fraser , Jyotika Taneja De Bruyne , Iñaki Iturbe-Ormaetxe, Justin Stepnell, Rhiannon L. Burns, Heather A. Flores, Scott L. O’Neill
This study examines the generation of three new mosquito lines infected with the Wolbachia strains wMelCS, wRi and wPip. Each line induced cytoplasmic incompatibility and was effectively maternally transmitted, as required for rapid spread through uninfected mosquito populations. Each Wolbachia strain was also found to reside in the salivary glands; a key tissue involved in viral transmission.
Perhaps most importantly, wMelCS inhibited dengue virus replication and dissemination in mosquitoes following an infectious blood meal or intrathoracic injection, providing a similar level of protection as that described for wMel. wMelCS therefore warrants further investigation as a potential release strain in future field trials.
Authors: Tom L. Schmidt, Nicholas H. Barton, Gordana Rašić, Andrew P. Turley, Brian L. Montgomery, Inaki Iturbe-Ormaetxe, Peter E. Cook, Peter A. Ryan, Scott A. Ritchie, Ary A. Hoffmann, Scott L. O’Neill, Michael Turelli
This study examines the frequency of Wolbachia carrying Aedes aegypti mosquitoes, following releases in three locations in Cairns, Australia in 2013. The study found that Wolbachia-infected mosquitoes spread at about 100-200 metres per year in the two larger sites, but that there was little evidence of such spread in the smaller area, even after two years. This suggests that over time, strategic releases may be enough for mosquitoes infected with the dengue-suppressing bacteria to spread across large cities.
Authors: Joubert DA, O'Neill SL
This study examines the effect of stable and transient Wolbachia infection in Aedes aegypti mosquitoes exposed to dengue virus (DENV), West Nile virus (WNV) and Plasmodium. Both stable and transient Wolbachia infections were found to have a blocking effect on the tested pathogens, however the magnitude of the effect was greater for stably infected mosquitoes. The study found no evidence of any enhancement of either DENV or WNV pathogens in Wolbachia-infected Aedes aegypti.
Authors: Aliota MT, Peinado SA, Dario Velez I, Osorio JE
Zika virus (ZIKV) is causing an explosive outbreak of febrile disease in the Americas. There are no effective antiviral therapies or licensed vaccines for this virus, and mosquito control strategies have not been adequate to contain the virus. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against other arboviruses. At present, it is unknown whether or not ZIKV can infect, disseminate, and be transmitted by Wolbachia-infected Ae. aegypti. Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for ZIKV. These results support the use of Wolbachia biocontrol as a multivalent strategy against Ae. aegypti-transmitted viruses.
Authors: Dutra HLC, da Silva VL, Fernandes MDR, Logullo C, Maciel-de-Freitas R, Moreira LA
In this paper the authors examined whether the wMel strain of Wolbachia affects Aedes aegypti larval development under different rearing densities and how this in turn may alter morphology and energetic reserves in adult mosquitoes.
Authors: Dutra HLC, Rocha MN, Stehling Dias FB, Mansur SB, Caragata EP, Moreira LA
This paper found Aedes aegypti mosquitoes with Wolbachia are highly resistant to infection with two currently circulating Zika virus isolates from the recent Brazilian epidemic. Mosquitoes carrying Wolbachia displayed lower prevalence and intensity of Zika virus and did not carry infectious virus in the saliva, suggesting that transmission was blocked. The researchers conclude that use of mosquitoes with Wolbachia could represent an effective mechanism to reduce Zika virus transmission and should be included as part of Zika control strategies.
Authors: Aliota MT, Walker EC, Uribe Yepes A, Dario Velez I, Christensen BM, Osorio JE
This paper examines the effect of Wolbachia on the transmission of chikungunya virus by Aedes aegypti. The authors found that Aedes aegypti mosquitoes infected with Wolbachia had reduced chikungunya virus infection, dissemination and transmission rates, compared to wild mosquitoes without Wolbachia.
Cell (2016) 165: 510-511
Commentary from Professor Scott O'Neill on the need for novel vector control technologies to respond to Aedes-borne diseases including Zika virus.
Authors: Murray JV, Jansen CC and De Barro P
This paper explores the risk assessment process preceding the release of Wolbachia-infected mosquitoes as part of the Eliminate Dengue program in Australia. The authors describe the tools, process, and methodology used in the risk analysis and provide recommendations for developing future risk analyses for novel technologies.
Authors: Joubert DA, Walker T, Carrington LB, De Bruyne JT, Kien DHT, Hang NLT, Chau NVV, Iturbe-Ormaetxe I, Simmons CP, O’Neill SL
In this paper the authors describe the generation of an Aedes aegypti mosquito line simultaneously infected with two different Wolbachia strains, wMel andwAlbB. The deployment of mosquitoes containing two Wolbachia strains could represent an effective strategy to help manage potential resistance of dengue virus to a single strain of Wolbachia, should this be observed.
Authors: Skelton E, Rancès E, Frentiu FD, Kusmintarsih ES, Iturbe-Ormaetxe I, Caragata EP, Woolfit M, O’Neill SL
This paper examines the effect of a naturally occurring wNoto Wolbachia strain on the vector competence of Aedes notoscriptus mosquitoes for dengue-2 virus. Dengue-2 virus infection and dissemination rates and viral titres in wNoto infected Ae. notoscriptus were not significantly different compared to those in mosquitoes from which Wolbachia had been removed. The low density and restricted tissue distribution of the wNoto infection may underlie the absence of Wolbachia-mediated viral interference in this system.
Authors: Nguyen TH, Nguyen HL, Nguyen TY, Vu SN, Tran ND, Le TN, Vien QM, Bui TC, Le HT, Kutcher S, Hurst TP, Duong TT, Jeffery JA, Darbro JM, Kay BH, Iturbe-Ormaetxe I, Popovici J, Montgomery BL, Turley AP, Zigterman F, Cook H, Cook PE, Johnson PH, Ryan PA, Paton CJ, Ritchie SA, Simmons CP, O'Neill SL, Hoffmann AA
This paper evaluates the establishment of the wMelPop strain of Wolbachia in field sites in Australia and Vietnam. The authors describe an initial increase in Wolbachia frequency in all sites examined, followed by an eventual decline most likely due to deleterious fitness effects associated with this strain. The authors conclude that, for the wMelPop strain to successfully establish in wild mosquito populations, additional supplementary strategies would be required. In contrast, the wMel strain of Wolbachia has been shown to readily invade local areas under a range of conditions.
Authors: Ye YH, Carrasco AM, Beebe NW, van den Hurk AF, McGraw EA
This paper examines Wolbachia's efficacy for blocking dengue virus replication in the Aedes aegypti mosquito. The authors examine the saliva of mosquitoes to provide a more accurate assessment of Wolbachia's ability to limit disease transmission. Results suggest that the wMel strain of Wolbachia may have positive impacts on dengue transmission not only by reducing the number of infectious mosquitoes in a population but also delaying the arrival of virus in the saliva.
Authors: Lambrechts L, Ferguson NM, Harris E, Holmes EC, McGraw EA, O'Neill SL, Ooi EE, Ritchie SA, Ryan PA, Scott TW, Simmons CP and Weaver SC
This paper discusses strategies to assess the efficacy of Wolbachia in reducing dengue virus transmission. The authors present a multipronged approach that could provide valuable intermediate evidence of efficacy to justify a future cluster randomised trial.
Authors: Dutra HL, Dos Santos LM, Caragata EP, Silva JB, Villela DA, Maciel-de-Freitas R, Moreira LA
This paper examines key phenotypic effects of the wMel Wolbachia strain in laboratory Aedes aegypti mosquitoes with a Brazilian genetic background, and analyses the effects of different urban landscapes on the likelihood of mosquito survival. Through analysis of laboratory, field and mathematical data, the authors show that the wMel strain of Wolbachia possesses the characteristics required to spread effectively in different urban socio-demographic environments in Rio de Janeiro.
Authors: Kolopack PA, Parsons JA, Lavery JV
This paper examines the Eliminate Dengue program's approach to community engagement as part of initial trials in Queensland, Australia. The authors demonstrate how community engagement practices contributed to the willingness of stakeholders to support the trials, and provide a framework for developing an effective community engagement strategy.
Authors: Ferguson NM, Kien DTH, Clapham H, Aguas R, Trung VT, Chau TNB, Popovici J, Ryan PA, O’Neill SL, McGraw EA, Long VT, Dui LT, Nguyen HL, Chau NVV, Wills B, Simmons CP.
This paper assesses the vector competence of Aedes aegypti mosquitoes that carry the Wolbachia strains wMel and wMelPop. The authors use modelling to predict the impact of Wolbachia-infected Aedes aegypti establishment on dengue virus transmission.
Authors: Ritchie S
This review paper provides a comparative overview of insecticide-based mosquito control activities against dengue and recent trials involving releases of Wolbachia Aedes aegypti in northern Australia.
Authors: de Oliveira CD, Gonçalves DS, Baton LA, Shimabukuro PH, Carvalho FD, Moreira LA
This paper examines the incidence of Wolbachia in a broad range of insect species, collected from different regions of Brazil. The study included potential human disease vectors whose infection status has not previously been reported.
Authors: Mayoral JG, Hussain M, Joubert DA, Iturbe-Ormaetxe I, O’Neill SL, and Asgari S
This paper describes the first observation of Wolbachia small non-coding RNA’s influencing cross kingdom gene expression.
Authors: Hoffmann AA, Iturbe-Ormaetxe I, Callahan AG, Phillips BL, Billington K, et al
This paper reports on the persistence of wMel Wolbachia infection since its initial introduction into two natural populations of Aedes aegypti in North Queensland, Australia, and characterises factors that influence the ongoing dynamic of the infection.
Authors: Hoffmann AA, Goundar AA, Long SA, Johnson PH, Ritchie SA
This paper examines the relationships between various entomological and household characteristics in two field sites in northern Australia where releases of Wolbachia Aedes aegypti were undertaken.
Authors: Turley AP, Smallegange RC, Takken W, Zalucki MP, O’Neill SL and McGraw EA
This paper examines whether Wolbachia infection affects mosquito attraction to host odours at five and 15 days of age. No evidence was seen of reduced odour attraction of mosquitoes infected with the wMel or wMelPop strains of Wolbachia.
Authors: McNaughton D, Duong TTH
In this paper the authors demonstrate that social research is important to develop engagement frameworks that deliver ethical consultation processes; and explain how this approach was used to support releases of Wolbachia-infected mosquitoes in Australia and Vietnam.
Authors: Ross PA, Endersby NM, Yeap HL, Hoffmann AA
In this paper the authors assessed the effects of two Wolbachia infections (wMelPop and wMel) on intra-strain and inter-strain larval competition in Aedes aegypti.
Authors: Segoli M, Hoffmann AA, Lloyd J, Omodei GJ, Ritchie SA
This paper examines the effect of Wolbachia on the competitiveness of Aedes aegypti males under semi-field conditions. Results indicate that Wolbachiainfection does not reduce the competitiveness of Aedes aegypti males.
Authors: Frentiu FD, Zakir T, Walker T, Popovici J, Pyke AT, van den Hurk A, McGraw EA, O'Neill SL
This paper shows that virus-blocking is likely to persist in Wolbachia-infected mosquitoes after their release and establishment in wild populations, suggesting that Wolbachia may be a successful strategy for reducing dengue transmission in the field.
Authors: Hugo LE, Jeffery JAL, Trewin BJ, Wockner LF, Yen NT, Le NH, Nghia LT, Hine E, Ryan PA, Kay BH
In this paper the authors determined the seasonal survival characteristics of the adult Aedes aegypti populations on an island in Vietnam, prior to field releases of mosquitoes containing the life-shortening wMelPop Wolbachia strain.
Authors: Yeap HL, Axford JK, Popovici J, Endersby NM, Iturbe-Ormaetxe I, Ritchie SA, Hoffmann AA
This paper examines how infection with the life-shortening wMelPop strain ofWolbachia affects the fitness of field mosquitoes. Wing size and shape and oviposition success were measured as indicators of fitness. The results confirm the lower fitness of wMelPop-infected mosquitoes in the field, which helps to explain the challenges associated with establishing this strain of Wolbachia.
Authors: Ritchie SA, Buhagiar TS, Townsend M, Hoffmann A, van den Hurk AF, McMahon JL, Eiras AE
In this paper the authors report on field studies comparing Aedes aegypti capture rates using a non-powered, low-cost, Gravid Aedes Trap (GAT), to other trapping methods, and the potential utility of the GAT for monitoring of the Wolbachia infection frequency in mosquito populations.