Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti
Science Translational Medicine • 18 Mar 2015 • Vol 7, Issue 279 • p. 279ra37 • DOI: 10.1126/scitranslmed.3010370
Use a bug to fight a bug
Dengue is the most common mosquito-borne viral infection in humans. In this new work, Ferguson et al. have assessed the extent to which infecting mosquitoes with a bacterium called Wolbachia was able to prevent those mosquitoes from being infected with dengue virus after they were fed with blood collected from dengue patients. One Wolbachia strain (wMelPop) almost completely prevented dengue infection. A second strain (wMel) partially blocked dengue infection. A mathematical model fitted to the data collected on the wMel strain suggested that wMel could reduce the transmissibility of dengue by 66 to 75%, enough to eliminate dengue in low or moderate transmission settings.
Abstract
Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75%. Our results suggest that establishment of wMelPop-infected A. aegypti at a high frequency in a dengue-endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel-infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.
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Supplementary Material
Summary
Table S1. Study population characteristics.
Table S2. List of primers and probes used.
Fig. S1. Human DENV viremia kinetics.
Supplementary data: Mosquito biting study data.
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REFERENCES AND NOTES
1
Simmons C. P., Farrar J. J., Nguyen v. V., Wills B., Dengue. N. Engl. J. Med. 366, 1423–1432 (2012).
2
Bhatt S., Gething P. W., Brady O. J., Messina J. P., Farlow A. W., Moyes C. L., Drake J. M., Brownstein J. S., Hoen A. G., Sankoh O., Myers M. F., George D. B., Jaenisch T., Wint G. R., Simmons C. P., Scott T. W., Farrar J. J., Hay S. I., The global distribution and burden of dengue. Nature 496, 504–507 (2013).
3
McMeniman C. J., Lane R. V., Cass B. N., Fong A. W., Sidhu M., Wang Y. F., O’Neill S. L., Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti. Science 323, 141–144 (2009).
4
Walker T., Johnson P. H., Moreira L. A., Iturbe-Ormaetxe I., Frentiu F. D., McMeniman C. J., Leong Y. S., Dong Y., Axford J., Kriesner P., Lloyd A. L., Ritchie S. A., O’Neill S. L., Hoffmann A. A., The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature 476, 450–453 (2011).
5
Moreira L. A., Iturbe-Ormaetxe I., Jeffery J. A., Lu G., Pyke A. T., Hedges L. M., Rocha B. C., Hall-Mendelin S., Day A., Riegler M., Hugo L. E., Johnson K. N., Kay B. H., McGraw E. A., van den Hurk A. F., Ryan P. A., O’Neill S. L., A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium. Cell 139, 1268–1278 (2009).
6
McMeniman C. J., O’Neill S. L., A virulent Wolbachia infection decreases the viability of the dengue vector Aedes aegypti during periods of embryonic quiescence. PLOS Negl. Trop. Dis. 4, e748 (2010).
7
Turley A. P., Moreira L. A., O’Neill S. L., McGraw E. A., Wolbachia infection reduces blood-feeding success in the dengue fever mosquito, Aedes aegypti. PLOS Negl. Trop. Dis. 3, e516 (2009).
8
Zhang G., Hussain M., O’Neill S. L., Asgari S., Wolbachia uses a host microRNA to regulate transcripts of a methyltransferase, contributing to dengue virus inhibition in Aedes aegypti. Proc. Natl. Acad. Sci. U.S.A. 110, 10276–10281 (2013).
9
Caragata E. P., Rances E., Hedges L. M., Gofton A. W., Johnson K. N., O’Neill S. L., McGraw E. A., Dietary cholesterol modulates pathogen blocking by Wolbachia. PLOS Pathog. 9, e1003459 (2013).
10
Pan X., Zhou G., Wu J., Bian G., Lu P., Raikhel A. S., Xi Z., Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti. Proc. Natl. Acad. Sci. U.S.A. 109, E23–E31 (2012).
11
Hoffmann A. A., Montgomery B. L., Popovici J., Iturbe-Ormaetxe I., Johnson P. H., Muzzi F., Greenfield M., Durkan M., Leong Y. S., Dong Y., Cook H., Axford J., Callahan A. G., Kenny N., Omodei C., McGraw E. A., Ryan P. A., Ritchie S. A., Turelli M., O’Neill S. L., Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature 476, 454–457 (2011).
12
Johansson M. A., Hombach J., Cummings D. A., Models of the impact of dengue vaccines: A review of current research and potential approaches. Vaccine 29, 5860–5868 (2011).
13
Nguyet M. N., Duong T. H., Trung V. T., Nguyen T. H., Tran C. N., Long V. T., Dui le T., Nguyen H. L., Farrar J. J., Holmes E. C., Rabaa M. A., Bryant J. E., Nguyen T. T., Nguyen H. T., Nguyen L. T., Pham M. P., Nguyen H. T., Luong T. T., Wills B., Nguyen C. V., Wolbers M., Simmons C. P., Host and viral features of human dengue cases shape the population of infected and infectious Aedes aegypti mosquitoes. Proc. Natl. Acad. Sci. U.S.A. 110, 9072–9077 (2013).
14
Sabchareon A., Wallace D., Sirivichayakul C., Limkittikul K., Chanthavanich P., Suvannadabba S., Jiwariyavej V., Dulyachai W., Pengsaa K., Wartel T. A., Moureau A., Saville M., Bouckenooghe A., Viviani S., Tornieporth N. G., Lang J., Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: A randomised, controlled phase 2b trial. Lancet 380, 1559–1567 (2012).
15
Xi Z., Khoo C. C., Dobson S. L., Wolbachia establishment and invasion in an Aedes aegypti laboratory population. Science 310, 326–328 (2005).
16
Hue K. D., Tuan T. V., Thi H. T., Bich C. T., Anh H. H., Wills B. A., Simmons C. P., Validation of an internally controlled one-step real-time multiplex RT-PCR assay for the detection and quantitation of dengue virus RNA in plasma. J. Virol. Methods 177, 168–173 (2011).
17
Harrington L. C., Buonaccorsi J. P., Edman J. D., Costero A., Kittayapong P., Clark G. G., Scott T. W., Analysis of survival of young and old Aedes aegypti (Diptera: Culicidae) from Puerto Rico and Thailand. J. Med. Entomol. 38, 537–547 (2001).
18
Maciel-de-Freitas R., Codeço C. T., Lourenço-de-Oliveira R., Daily survival rates and dispersal of Aedes aegypti females in Rio de Janeiro, Brazil. Am. J. Trop. Med. Hyg. 76, 659–665 (2007).
19
Sheppard P. M., Macdonald W. W., Tonn R. J., Grab B., The dynamics of an adult population of Aedes aegypti in relation to dengue haemorrhagic fever in Bangkok. J. Anim. Ecol. 38, 661–702 (1969).
20
W. R. Gilks, S. Richardson, D. Spiegelhalter, Markov Chain Monte Carlo in Practice (Chapman & Hall, London, 1996).
Information & Authors
Information
Published In
Science Translational Medicine
Volume 7 | Issue 279
March 2015
March 2015
Copyright
Copyright © 2015, American Association for the Advancement of Science.
Submission history
Received: 15 August 2014
Accepted: 26 February 2015
Acknowledgments
Supported by the Wellcome Trust; the Bill and Melinda Gates Foundation (BMGF); the Foundation for the NIH, as part of the Grand Challenges in Global Health Initiative of BMGF; the National Health and Medical Research Council, Australia; the U.K. Medical Research Council; the National Institute of General Medical Sciences Models of Infectious Disease Agent Study initiative; and the European Union Seventh Framework Programme European Management Platform for Emerging and Re-emerging Infectious Disease Entities consortium. Author contributions: C.P.S., N.M.F., and S.L.O. designed the study; B.W., D.T.H.K., V.T.T., T.N.B.C., V.T.L., L.T.D., H.L.N., and N.V.V.C. performed the mosquito biting experiments; J.P., P.A.R., S.L.O., and E.A.M. developed the Wolbachia-infected A. aegypti; N.M.F., H.C., and R.A. performed the analysis; and N.M.F. and C.P.S. drafted the manuscript. Competing interests: N.F. is an informal and unpaid advisor on dengue control measures (including Wolbachia and vaccines) and dengue modeling for BMGF and Sanofi Pasteur Inc. C.S. has a paid consulting position with Sanofi Pasteur Inc., which has a business interest in developing dengue vaccines. S.L.O., P.A.R., and E.A.M. are named as coinventors on a patent for Wolbachia mosquito strains: Modified Arthropod and Method of Use; Filing # 14/304,919; Filing date: 06/14/2014. The other authors declare that they have no competing interests. Data and materials availability: The data collected in this study are provided in Supplementary Materials.
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