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BMC Medicine
Published in: BMC Medicine 1/2020

Open Access 01-12-2020 | Research article

The cost-effectiveness of controlling dengue in Indonesia using wMel Wolbachia released at scale: a modelling study

Authors: Oliver J. Brady, Dinar D. Kharisma, Nandyan N. Wilastonegoro, Kathleen M. O’Reilly, Emilie Hendrickx, Leonardo S. Bastos, Laith Yakob, Donald S. Shepard

Published in: BMC Medicine | Issue 1/2020

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Abstract

Background

Release of virus-blocking Wolbachia-infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes, and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform government, donor, or philanthropist decisions on scale-up beyond single city releases, we assessed this technology’s cost-effectiveness under alternative programmatic options.

Methods

Using costing data from existing Wolbachia releases, previous dynamic model-based estimates of Wolbachia effectiveness, and a spatially explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the ongoing programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta, and Bali.

Results

We predicted Wolbachia to be a highly cost-effective intervention when deployed in high-density urban areas with gross cost-effectiveness below $1500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over 10 years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost-saving intervention.

Conclusions

Wolbachia releases in high-density urban areas are expected to be highly cost-effective and could potentially be the first cost-saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritised.
Appendix
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Literature
1.
Bowman LR, Donegan S, McCall PJ. Is dengue vector control deficient in effectiveness or evidence?: systematic review and meta-analysis. PLoS Negl Trop Dis. 2016;10:e0004551.CrossRef
2.
Ritchie SA, Staunton KM. Reflections from an old Queenslander: can rear and release strategies be the next great era of vector control? Proc R Soc B Biol Sci. 2019;286:20190973.CrossRef
3.
Walker T, Johnson PH, Moreira LA, Iturbe-Ormaetxe I, Frentiu FD, McMeniman CJ, et al. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature. 2011;476:450–3.CrossRef
4.
Aliota MT, Peinado SA, Velez ID, Osorio JE. The wMel strain of Wolbachia reduces transmission of Zika virus by Aedes aegypti. Sci Rep. 2016;6:28792.CrossRef
5.
van den Hurk AF, Hall-Mendelin S, Pyke AT, Frentiu FD, McElroy K, Day A, et al. Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti. PLoS Negl Trop Dis. 2012;6:e1892.CrossRef
6.
7.
Nazni WA, Hoffmann AA, Afizah AN, 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;29:1–8.CrossRef
8.
Zheng X, Zhang D, Li Y, Yang C, Wu Y, Liang X, et al. Incompatible and sterile insect techniques combined eliminate mosquitoes. Nature. 2019;572:56–61.CrossRef
9.
10.
Mains JW, Kelly PH, Dobson KL, Petrie WD, Dobson SL. Localized control of Aedes aegypti (Diptera: Culicidae) in Miami, FL, via inundative releases of Wolbachia-infected male mosquitoes. J Med Entomol. 2019;56:1296–303.CrossRef
11.
Flores HA, O’Neill SL. Controlling vector-borne diseases by releasing modified mosquitoes. Nat Rev Microbiol. 2018;16:508–18.CrossRef
12.
Schmidt TL, Barton NH, Rašić G, Turley AP, Montgomery BL, Iturbe-Ormaetxe I, et al. Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti. PLoS Biol. 2017;15:e2001894.CrossRef
13.
Garcia G de A, Sylvestre G, Aguiar R, da Costa GB, Martins AJ, Lima JBP, et al. Matching the genetics of released and local Aedes aegypti populations is critical to assure Wolbachia invasion. PLoS Negl Trop Dis. 2019;13:e0007023.
14.
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. 2018;2:36.CrossRef
15.
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.
16.
Anders KL. Growing evidence that the World Mosquito Program’s Wolbachia method reduces dengue transmission. In: 68th Annual Meeting of the American Society of Tropical Medicine and Hygiene. National Harbour, MD; 2019.
17.
Anders KL, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Andari B, et al. 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. 2018;19:302.
18.
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:e0008157.
19.
O’Reilly KM, Hendrickx E, Kharisma DD, Wilastonegoro NN, Carrington LB, Elyazar IRF, et al. Estimating the burden of dengue and the impact of release of wMel Wolbachia-infected mosquitoes in Indonesia: a modelling study. BMC Med. 2019;17:172.CrossRef
20.
Ferguson NM, Kien DTH, Clapham H, Aguas R, Trung VT, Chau TNB, et al. Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti. Sci Transl Med. 2015;7:279ra37.CrossRef
21.
General Secretary of the Ministry of Health of Indonesia. Guidelines for Indonesian health program with family approach (Pedoman umum program Indonesia sehat dengan pendekatan keluarga). Jakarta: Kementerian Kesehatan Republik Indonesia; 2016.
22.
World Mosquito Program Indonesia. Research as the evidence of deployment impact of Aedes aegypti with Wolbachia to reduce the dengue transmission in Yogyakarta City (Riset untuk membuktikan dampak Pelepasan Aedes aegypti ber-Wolbachia berskala luas pada penurun. Yogyakarta, Indonesia; 2016.
23.
Fitzpatrick C, Haines A, Bangert M, Farlow A, Hemingway J, Velayudhan R. An economic evaluation of vector control in the age of a dengue vaccine. PLoS Negl Trop Dis. 2017;11:e0005785.CrossRef
24.
Flasche S, Jit M, Rodríguez-Barraquer I, Coudeville L, Recker M, Koelle K, et al. The long-term safety, public health impact, and cost-effectiveness of routine vaccination with a recombinant, live-attenuated dengue vaccine (Dengvaxia): a model comparison study. PLoS Med. 2016;13:e1002181.CrossRef
25.
Coudeville L, Baurin N, Shepard DS. The potential impact of dengue vaccination with, and without, pre-vaccination screening. Vaccine. 2020;38:1363–9.
26.
Ross PA, Endersby NM, Hoffmann AA. Costs of three Wolbachia infections on the survival of Aedes aegypti larvae under starvation conditions. PLoS Negl Trop Dis. 2016;10:e0004320.
27.
Alphey L, McKemey A, Nimmo D, Neira Oviedo M, Lacroix R, Matzen K, et al. Genetic control of Aedes mosquitoes. Pathog Glob Health. 2013;107:170–9.
28.
Marshall JM. The impact of dissociation on transposon-mediated disease control strategies. Genetics. 2008;178:1673–82.CrossRef
29.
Carrington LB, Tran BCN, Le NTH, Luong TTH, Nguyen TT, Nguyen PT, et al. Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes. Proc Natl Acad Sci U S A. 2018;115:361–6.CrossRef
30.
Joubert DA, Walker T, Carrington LB, De Bruyne JT, Kien DHT, Hoang NLT, et al. Establishment of a Wolbachia superinfection in Aedes aegypti mosquitoes as a potential approach for future resistance management. PLoS Pathog. 2016;12:e1005434.
31.
32.
33.
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 Aedes transmitted arboviruses. Gates Open Res. 2018;2:36.CrossRef
34.
Wilastonegoro NN, Kharisma DD, Laksanawati I, Halasa-Rappel YA, Brady OJ, Shepard DS. Cost of dengue illness in Indonesia: from hospital to nonmedical settings. Am J Trop Med Hyg. 2020. in press.
35.
Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, et al. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature. 2011;476:454–7.CrossRef
36.
Neumann PJ, Russell LB, Siegel JE, Prosser LA, Krahn M, Gold MR. Using cost-effectiveness analysis in health and medicine: experiences since the original panel. In: Neumann PJ, Sanders GD, Russell LB, Siegel JE, Ganiats TG, editors. Cost-effectiveness in health and medicine. 2nd editio. Oxford University Press; 2017. p. 1–37.
37.
38.
Hoffmann AA, Ross PA, Rašić G. Wolbachia strains for disease control: ecological and evolutionary considerations. Evol Appl. 2015;8:751–68.CrossRef
39.
Huber K, Le Loan L, Hoang TH, Ravel S, Rodhain F, Failloux AB. Genetic differentiation of the dengue vector, Aedes aegypti (Ho Chi Minh City, Vietnam) using microsatellite markers. Mol Ecol. 2002;11:1629–35.CrossRef
40.
Suaya JA, Shepard DS, Chang M-S, Caram M, Hoyer S, Socheat D, et al. Cost-effectiveness of annual targeted larviciding campaigns in Cambodia against the dengue vector Aedes aegypti. Tropical Med Int Health. 2007;12:1026–36.CrossRef
41.
Luz PM, Vanni T, Medlock J, Paltiel AD, Galvani AP. Dengue vector control strategies in an urban setting: an economic modelling assessment. Lancet. 2011;377:1673–80.CrossRef
42.
Mendoza-Cano O, Hernandez-Suarez CM, Trujillo X, Ochoa Diaz-Lopez H, Lugo-Radillo A, Espinoza-Gomez F, et al. Cost-effectiveness of the strategies to reduce the incidence of dengue in Colima, México. Int J Environ Res Public Health. 2017;14:890.CrossRef
43.
Liyanage P, Rocklöv J, Tissera H, Palihawadana P, Wilder-Smith A, Tozan Y. Evaluation of intensified dengue control measures with interrupted time series analysis in the Panadura Medical Officer of Health division in Sri Lanka: a case study and cost-effectiveness analysis. Lancet Planet Heal. 2019;3:e211–8.CrossRef
44.
de Soárez PC, Silva AB, Randi BA, Azevedo LM, Novaes HMD, Sartori AMC. Systematic review of health economic evaluation studies of dengue vaccines. Vaccine. 2019;37:2298–310.CrossRef
45.
Brady OJ, Slater HC, Pemberton-Ross P, Wenger E, Maude RJ, Ghani AC, et al. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study. Lancet Glob Heal. 2017;5:e680–7.
46.
47.
48.
Harapan H, Michie A, Mudatsir M, Nusa R, Yohan B, Wagner AL, et al. Chikungunya virus infection in Indonesia: a systematic review and evolutionary analysis. BMC Infect Dis. 2019;19:243.CrossRef
49.
Drummond M, Barbieri M, Cook J, Glick HA, Lis J, Malik F, et al. Transferability of economic evaluations across jurisdictions: ISPOR good research practices task force report. Value Heal. 2009;12:409–18.CrossRef
50.
Kolopack PA, Parsons JA, Lavery JV. What makes community engagement effective?: lessons from the eliminate dengue program in Queensland Australia. PLoS Negl Trop Dis. 2015;9:e0003713.CrossRef
Metadata
Title
The cost-effectiveness of controlling dengue in Indonesia using wMel Wolbachia released at scale: a modelling study
Authors
Oliver J. Brady
Dinar D. Kharisma
Nandyan N. Wilastonegoro
Kathleen M. O’Reilly
Emilie Hendrickx
Leonardo S. Bastos
Laith Yakob
Donald S. Shepard
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2020
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-020-01638-2

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