Letter | Published:

Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission

Nature volume 476, pages 454457 (25 August 2011) | Download Citation


Genetic manipulations of insect populations for pest control have been advocated for some time, but there are few cases where manipulated individuals have been released in the field and no cases where they have successfully invaded target populations1. Population transformation using the intracellular bacterium Wolbachia is particularly attractive because this maternally-inherited agent provides a powerful mechanism to invade natural populations through cytoplasmic incompatibility2. When Wolbachia are introduced into mosquitoes, they interfere with pathogen transmission and influence key life history traits such as lifespan3,4,5,6. Here we describe how the wMel Wolbachia infection, introduced into the dengue vector Aedes aegypti from Drosophila melanogaster7, successfully invaded two natural A. aegypti populations in Australia, reaching near-fixation in a few months following releases of wMel-infected A. aegypti adults. Models with plausible parameter values indicate that Wolbachia-infected mosquitoes suffered relatively small fitness costs, leading to an unstable equilibrium frequency <30% that must be exceeded for invasion. These findings demonstrate that Wolbachia-based strategies can be deployed as a practical approach to dengue suppression with potential for area-wide implementation.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    & Population genetics of autocidal control and strain replacement. Annu. Rev. Entomol. 49, 193–217 (2004)

  2. 2.

    & Cytoplasmic incompatibility in Drosophila simulans: dynamics and parameter estimates from natural populations. Genetics 140, 1319–1338 (1995)

  3. 3.

    et al. A Wolbachia symbiont in Aedes aegypti limits infection with dengue, chikungunya, and Plasmodium. Cell 139, 1268–1278 (2009)

  4. 4.

    et al. Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti. Science 323, 141–144 (2009)

  5. 5.

    , , & Immune activation by life-shortening Wolbachia and reduced filarial competence in mosquitoes. Science 326, 134–136 (2009)

  6. 6.

    , , , & The endosymbiotic bacterium Wolbachia induces resistance to dengue virus in Aedes aegypti. PLoS Pathog. 6, e1000833 (2010)

  7. 7.

    et al. A non-virulent Wolbachia infection blocks dengue transmission and rapidly invades Aedes aegypti populations. Nature 10.1038/nature10355 (this issue).

  8. 8.

    & Global spread and persistence of dengue. Annu. Rev. Microbiol. 62, 71–92 (2008)

  9. 9.

    et al. Dengue: a continuing global threat. Nature Rev. Microbiol. 8. S7–S16 (2010)

  10. 10.

    & Rapid spread of an inherited incompatibility factor in California Drosophila. Nature 353, 440–442 (1991)

  11. 11.

    , , & Evidence for a global Wolbachia replacement in Drosophila melanogaster. Curr. Biol. 15, 1428–1433 (2005)

  12. 12.

    Cytoplasmic incompatibility in population with overlapping generations. Evolution 64, 232–241 (2010)

  13. 13.

    et al. Dynamics of the ‘popcorn’ Wolbachia infection in Aedes aegypti in an outbred background. Genetics 187, 583–595 (2011)

  14. 14.

    & On the evolutionary importance of cytoplasmic sterility in mosquitos. Evolution 13, 568–570 (1959)

  15. 15.

    & A virulent Wolbachia infection decreases the viability of the dengue vector Aedes aegypti during periods of embryonic quiescence. PloS Neglect. Trop. Dis. 4, e748 (2010)

  16. 16.

    , , & Variation in antiviral protection mediated by different Wolbachia strains in Drosophila simulans. PLoS Pathog. 5, e1000656 (2009)

  17. 17.

    et al. Changes in the genetic structure of Aedes aegypti (Diptera: Culicidae) populations in Queensland, Australia, across two seasons: implications for potential mosquito releases. J. Med. Entomol. (in the press)

  18. 18.

    & Spatial waves of advance with bistable dynamics: cytoplasmic and genetic analogs of Allee effects. Am. Nat. 10.1086/661246 (2011)

  19. 19.

    , , & Influence of urban landscapes on population dynamics in a short-distance migrant mosquito: evidence for the dengue vector Aedes aegypti. PLoS Negl. Trop. Dis. 4, e634 (2010)

  20. 20.

    , , & Dispersal of Aedes aegypti in an urban area after blood feeding as desmonstrated by rubidium-marked eggs. Am. J. Trop. Med. Hyg. 52, 177–179 (1995)

  21. 21.

    et al. Dispersal of the dengue vector Aedes aegypti within and between rural communities. Am. J. Trop. Med. Hyg. 72, 209–220 (2005)

  22. 22.

    , & Container productivity, daily survival rates and dispersal of Aedes aegypti mosquitoes in a high income dengue epidemic neighbourhood of Rio de Janeiro: presumed influence of differential urban structure on mosquito biology. Mem. Inst. Oswaldo Cruz 104, 927–932 (2009)

  23. 23.

    Eradication of Culex pipiens fatigans through cytoplasmic incompatibility. Nature 216, 383–384 (1967)

  24. 24.

    Genetic control of insect pests: growth industry or lead balloon? Biol. J. Linn. Soc. 26, 359–374 (1985)

  25. 25.

    Genetic control of sheep blowfly (Lucilia cuprina) and the logistics of the CSIRO control program. Wool Technol. Sheep Breed. 28, 5–10 (1980)

  26. 26.

    , , & The proposed release of the yellow fever mosquito, Aedes aegypti containing a naturally occurring strain of Wolbachia pipientis, a question of regulatory responsibility. J. Cons. Protect. Food Safety 6, (suppl. 1)33–40 (2011)

  27. 27.

    et al. Assessing key safety concerns of a Wolbachia-based strategy to control dengue transmission by Aedes mosquitoes. Mem. Inst. Oswaldo Cruz 105, 957–964 (2010)

  28. 28.

    , , , & Beyond the ‘back yard’: lay knowledge about Aedes aegypti in northern Australia and its implications for policy and practice. Acta Trop. 116, 74–80 (2010)

  29. 29.

    et al. Genetic structure of Aedes aegypti in Australia and Vietnam revealed by microsatellite and exon primed intron crossing markers suggests feasibility of local control options. J. Med. Entomol. 46, 1074–1083 (2009)

  30. 30.

    et al. A secure semi-field cage for the study of Aedes aegypti. PLoS Negl. Trop. Dis. 5, e988 (2011)

  31. 31.

    et al. Field efficacy of the BG-Sentinel compared with CDC backpack aspirators and CO2-baited EVS traps for collection of adult Aedes aegypti in Cairns, Queensland, Australia. J. Am. Mosq. Control Assoc. 22, 296–300 (2006)

  32. 32.

    & Sampling biases of the BG-sentinel trap with respect to physiology, age, and body size of adult Aedes aegypti (Diptera: Culicidae). J. Med. Entomol. 47, 649–656 (2010)

  33. 33.

    Effect of some animal feeds and oviposition substrates on Aedes oviposition in ovitraps in Cairns, Australia. J. Am. Mosq. Control Assoc. 17, 206–208 (2001)

  34. 34.

    & Discrimination of all members of the Anopheles punctulatus complex by polymerase chain reaction restriction-fragment-polymorphism analysis. Am. J. Trop. Med. Hyg. 53, 478–481 (1995)

Download references


We are grateful to J. Sutton, C. Paton, G. Omodei, S. Long, A. Gofton, V. White, A. Weeks, A. James, J. Dick, R. Bagita, P. Gibson, J. Jeffery, E. Rances, D. Rossi and J. Gough for technical and mapping support. We thank B. Kay for ongoing advice. We acknowledge and thank both D. McNaughton and D. Eastop for the early community engagement work preceding the trial. We thank all of our volunteers who helped blood-feed the mosquito colonies and we are particularly grateful to the residents of Gordonvale and Yorkeys Knob for their strong support and participation. This research was supported by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation, The National Health and Medical Research Council, Australia, the National and International Research Alliances Program of the Queensland Government, the RAPIDD program of the NIH, the Climate Health Cluster of the CSIRO Flagship Collaboration Fund, the National Science Foundation and Fellowships from the Australian Research Council.

Author information


  1. Bio21 Institute, Department of Genetics, The University of Melbourne, Victoria 3010, Australia

    • A. A. Hoffmann
    • , J. Axford
    •  & A. G. Callahan
  2. School of Biological Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia

    • B. L. Montgomery
    • , J. Popovici
    • , I. Iturbe-Ormaetxe
    • , F. Muzzi
    • , M. Greenfield
    • , M. Durkan
    • , Y. S. Leong
    • , Y. Dong
    • , H. Cook
    • , N. Kenny
    • , E. A. McGraw
    • , P. A. Ryan
    •  & S. L. O’Neill
  3. School of Biological Sciences, Monash University, Victoria 3800, Australia

    • J. Popovici
    • , I. Iturbe-Ormaetxe
    • , Y. Dong
    • , N. Kenny
    • , E. A. McGraw
    • , P. A. Ryan
    •  & S. L. O’Neill
  4. School of Public Health and Tropical Medicine and Rehabilitative Sciences, James Cook University, Cairns, Queensland 4870, Australia

    • P. H. Johnson
    • , C. Omodei
    •  & S. A. Ritchie
  5. Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia

    • P. A. Ryan
  6. Department of Evolution and Ecology, University of California, Davis, California 95616, USA

    • M. Turelli


  1. Search for A. A. Hoffmann in:

  2. Search for B. L. Montgomery in:

  3. Search for J. Popovici in:

  4. Search for I. Iturbe-Ormaetxe in:

  5. Search for P. H. Johnson in:

  6. Search for F. Muzzi in:

  7. Search for M. Greenfield in:

  8. Search for M. Durkan in:

  9. Search for Y. S. Leong in:

  10. Search for Y. Dong in:

  11. Search for H. Cook in:

  12. Search for J. Axford in:

  13. Search for A. G. Callahan in:

  14. Search for N. Kenny in:

  15. Search for C. Omodei in:

  16. Search for E. A. McGraw in:

  17. Search for P. A. Ryan in:

  18. Search for S. A. Ritchie in:

  19. Search for M. Turelli in:

  20. Search for S. L. O’Neill in:


A.A.H. and S.L.O. provided oversight of the releases and drafted most of the paper. S.A.R. and B.L.M. provided knowledge of local mosquito populations and liaison with authorities. J.P., I.I.-O., Y.D. and Y.S.L. carried out the Wolbachia screening. P.H.J., C.O., J.A., N.K., E.A.M. and A.G.C. were responsible for mosquito culture and backcrossing. Field releases and monitoring collections were undertaken by F.M., M.G., M.D. and B.L.M. and coordinated by B.L.M. and P.A.R. M.T. developed models to interpret the results and A.A.H. interpreted data during the release. H.C., S.L.O., S.A.R., M.D. and P.A.R. were involved in community engagement and mapping. S.L.O. and I.I.-O. were responsible for gaining regulatory approvals for the releases.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to S. L. O’Neill.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    The file contains Supplementary Figures 1-5 with legends, Supplementary Text and Data and additional references.

About this article

Publication history







By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.