Wolbachia-infected mosquito to suppress the transmission chain of mosquito- borne virus: A systematic review and meta—analysis of community-based health intervention trials

Abstract

Objective: To identify the efficacy of Wolbachia-based intervention by reviewing community-based trials through meta-analysis and systematic review methods.

Methods: Studies about Wolbachia-infected mosquito intervention were collected through a screening process. Records underwent data extraction and quality assessment independently by the authors. The primary outcome of the study was protective efficacy. Quantitative analysis was conducted through meta-analysis and multivariate meta-regression using Rstudio Ver.2024.09.0-375. Qualitative analysis was done by summarizing records’ findings.

Results: 10 out of the 10 660 records met the criteria. The evidence was moderate in quality and highly heterogeneous. Intervention consisted of releasing Wolbachia-infected Aedes aegypti in densely populated settlements. The combined protective efficacy of Wolbachia intervention against dengue is highly heterogeneous (79%; 95% CI 70-88; I²=98%). wMel strain is significantly more efficacious compared to wAlbB (protective efficacy 84%; 95% CI 76-93; I²=95%) vs. 64% (95% CI 46-82; I²=85%); P<0.01) in preventing dengue cases. Wolbachia-infected mosquito populations were found to be unstable upon release cessation, which necessitated periodic release and monitoring to maintain desired concentration and protective efficacy.

Conclusions:Wolbachia-based intervention is effective in suppressing the transmission of mosquito-borne diseases, especially dengue, with an excellent safety profile. However, community acceptance and policy remain as significant barriers to implementation.

Keywords

Dengue / Mosquito-Borne Diseases / Mosquito / Primary prevention / Wolbachia

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The authors received no extramural funding for the study.

Authors’ contributions

NMA: Project leader, conceptualization, administrative, analysis, data collection, software. HH: Data collection, analysis, formatting, publication. GTD: Data collection, analysis, formatting, literature review validator. SR: Validation, advisor & supervision.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Edited by Pan Y, Lei Y, Zhang Q

Acknowledgements

We would like to acknowledge Prof. Adi Utarini for sharing her insight with us in the making of this review article.

References

[1] Indriani C, Tantowijoyo W, Rancès E, Andari B, Prabowo E, Yusdi D, et al. Reduced dengue incidence following deployments of Wolbachia-infected Aedes aegypti in Yogyakarta, Indonesia: A quasi-experimental trial using controlled interrupted time series analysis. Gates Open Res 2020; 4: 50.

[2] Utarini A, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Ansari MR, et al. Efficacy of Wolbachia-infected mosquito deployments for the control of dengue. N Engl J Med 2021; 384(23): 2177-2186.

[3] Rahayu A, Saraswati U, Supriyati E, Kumalawati DA, Hermantara R, Rovik A, et al. Prevalence and distribution of dengue virus in Aedes aegypti in Yogyakarta city before deployment of Wolbachia infected Aedes aegypti. Int J Environ Res Public Health 2019; 16(10): 1742.

[4] Pinto SB, Riback TIS, Sylvestre G, Costa G, Peixoto J, Dias FBS, et al. Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other aedes-borne diseases in Niterói, Crazil: A quasi-experimental study. PLoS Negl Trop Dis 2021; 15(7): e0009556.

[5] Ye YH, Carrasco AM, Frentiu FD, Chenoweth SF, Beebe NW, van den Hurk AF, et al. Wolbachia reduces the transmission potential of dengue-infected Aedes aegypti. PLoS Negl Trop Dis 2015; 9(6): e0003894.

[6] Brady OJ, Kharisma DD, Wilastonegoro NN, O’reilly KM, Hendrickx E, Bastos LS, et al. The cost-effectiveness of controlling dengue in Indonesia using wMel Wolbachia released at scale: A modelling study. BMC Med 2020; 18(1): 186.

[7] Tantowijoyo W, Andari B, Arguni E, Budiwati N, Nurhayati I, Fitriana I, et al. Stable establishment of wMel Wolbachia in Aedes aegypti populations in Yogyakarta, Indonesia . PLoS Negl Trop Dis 2020; 14(4): 1-13.

[8] Girard M, Nelson CB, Picot V, Gubler DJ. Arboviruses:A global public health threat. In: Vaccine. Amsterdam: Elsevier Ltd; 2020, p. 3989-3994.

[9] O'Neill SL, Ryan PA, Turley AP, Wilson G, Retzki K, Iturbe-Ormaetxe I, et al. Scaled deployment of Wolbachia to protect the community from dengue and other Aedes transmitted arboviruses. Gates Open Res 2019; 2: 36.

[10] Ryan PA, Turley AP, Wilson G, Hurst TP, Retzki K, Brown-Kenyon J, et al. Establishment of wMel Wolbachia in Aedes aegypti mosquitoes and reduction of local dengue transmission in Cairns and surrounding locations in northern Queensland, Australia. Gates Open Res 2020; 3: 1547.

[11] Hoffmann AA, Ahmad NW, Keong WM, Ling CY, Ahmad NA, Golding N, et al. Introduction of Aedes aegypti mosquitoes carrying wAlbB Wolbachia sharply decreases dengue incidence in disease hotspots. iScience 2024; 27(2): 108942.

[12] Velez ID, Uribe A, Barajas J, Uribe S, Ángel S, Suaza-Vasco JD, et al. Large-scale releases and establishment of wMel Wolbachia in Aedes aegypti mosquitoes throughout the Cities of Bello, Medellín and Itagüí Colombia. PLoS Negl Trop Dis 2023; 17(11): e0011642.

[13] Nazni WA, Hoffmann AA, NoorAfizah A, Cheong YL, Mancini MV, Golding N, et al. Establishment of Wolbachia strain wAlbB in Malaysian populations of Aedes aegypti for dengue control. Curr Biol 2019; 29(24): 4241-4248.e5.

[14] Dos Santos GR, Durovni B, Saraceni V, Souza RTI, Pinto SB, Anders KL, et al. Estimating the effect of the wMel release programme on the incidence of dengue and chikungunya in Rio de Janeiro, Brazil: A spatiotemporal modelling study. Lancet Infect Dis 2022; 22(11): 1587-1595.

[15] Lim JT, Bansal S, Chong CS, Dickens B, Ng Y, Deng L, et al. Efficacy of Wolbachia-mediated sterility to reduce the incidence of dengue: A synthetic control study in Singapore. Lancet Microbe 2024; 5(5): e422-e432.

[16] Orozco-Gonzales JL, Dos Santos AA, Cardona-Salgado D, Ferreira CP, de Oliveira FH, Sepulveda-Salcedo LS, et al. Comparing the long-term persistence of different Wolbachia strains after the release of bacteria-carrying mosquitoes. Math Biosci 2024; 372: 109190.

[17] Maciel-de-Freitas R, Sauer FG, Kliemke K, Garcia GA, Pavan MG, David MR, et al. Wolbachia strains wMel and wAlbB differentially affect Aedes aegypti traits related to fecundity. Microbiol Spectr 2024; 12(4): e0012824.

[18] Hien NT, Anh DD, Le NH, Yen NT, Phong TV, Nam VS, et al. Environmental factors influence the local establishment of Wolbachia in Aedes aegypti mosquitoes in two small communities in central Vietnam. Gates Open Res 2022; 5: 147.

[19] Pavan MG, Garcia GA, David MR, Maciel-de-Freitas R. The double-edged sword effect of expanding Wolbachia deployment in dengue endemic settings. Lancet Reg Health Am 2023; 27: 100610.

[20] Inácio da Silva LM, Dezordi FZ, Paiva MHS, Wallau GL. Systematic review of Wolbachia symbiont detection in mosquitoes: An entangled topic about methodological power and true symbiosis. Pathogens 2021; 10(1): 39.

[21] Johnson KN. The impact of Wolbachia on virus infection in mosquitoes. Viruses 2015; 7(11): 5705-5717.

[22] Buchori D, Mawan A, Nurhayati I, Aryati A, Kusnanto H, Hadi UK. Risk assessment on the release of Wolbachia-infected Aedes aegypti in Yogyakarta, Indonesia. Insects 2022; 13(10): 924.

[23] Flores HA, Taneja de Bruyne J, O'Donnell TB, Tuyet Nhu V, Thi Giang N, Thi Xuan Trang H, et al. Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti. PLoS Pathog 2020; 16(4): e1008433.

[24] Murray JV, Jansen CC, De Barro P. Risk associated with the release of Wolbachia-infected Aedes aegypti mosquitoes into the environment in an effort to control dengue. Front Public Health 2016; 4: 43.

[25] Sánchez-González L, Adams LE, Saavedra R, Little EM, Medina NA, Major CG, et al. Assessment of community support for Wolbachia-mediated population suppression as a control method for Aedes aegypti mosquitoes in a community cohort in Puerto Rico. PLoS Negl Trop Dis 2021; 15(12): e0009966.

[26] Indonesia Ministry of Communication and Information Technology. HOAKS:Penyebaran Nyamuk Wolbachia untuk Membentuk Genetik LGBT di Masyarakat. Jakarta (ID): Indonesia Ministry of Communication and Information Technology; 2023. [Online]. Available from: https://www.kominfo.go.id/content/detail/52994/hoaks-penyebaran-nyamuk-Wolbachia-untuk-membentuk-genetik-lgbt-di-masyarakat/0/laporan_isu_hoaks. [Accessed on 9 September 2024].

[27] Indonesia Ministry of Communication and Information Technology. HOAKS:Teknologi Nyamuk Wolbachia Dikendalikan sebagai Senjata Pembunuh Manusia. [Online]. Jakarta (ID): Indonesia Ministry of Communication and Information Technology; 2023. Available from: https://www.kominfo.go.id/content/detail/53271/hoaks-teknologi-nyamuk-Wolbachia-dikendalikan-sebagai-senjata-pembunuh-manusia/0/laporan_isu_hoaks.[Accessed on 9 September 2024].Accessed on 9 September 2024].

[28] Centers for Disease Control and Prevention. Why is dengue a global issue? Atlanta (US): Centers for Disease Control and Prevention; 2025. [Online]. Available from: https://www.cdc.gov/dengue/training/cme/ccm/page51440.html#:-:text=As%20many%20as%203.6%20billion,deaths%20are%20attributed%20to%20dengue. [Accessed on 9 September 2024].

[29] Chen S, Cao Z, Jiao L, Chen W, Prettner K, Kuhn M, et al. The global economic burden of dengue in 2020-2050:Estimates and projections for 141 countries and territories. [Online]. 2024. Available from: https://ssrn.com/abstract=4691773. [Accessed on 9 September 2024].