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

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

doi:10.1186/s12916-020-01638-2

Cited by 27 publications

(19 citation statements)

References 42 publications

(74 reference statements)

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“… 30 An attractive aspect of this strategy is that it maintains itself in the mosquito population and does not need re-application. 31 Future trials should explore the multivalency of the intervention, since laboratory studies 12 , 32 – 35 suggest w Mel should also attenuate transmission of Zika, chikungunya, Yellow Fever and Mayaro viruses by Ae. aegypti .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue

Utarini¹,

Indriani²,

Ahmad³

et al. 2021

N Engl J Med

315

235

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Background: Aedes aegypti mosquitoes infected with Wolbachia pipientis ( w Mel strain) have reduced potential to transmit dengue viruses. Methods: We conducted a cluster randomised trial of deployments of w Mel-infected Ae. aegypti for control of dengue in Yogyakarta City, Indonesia. Twenty-four geographic clusters were randomly allocated to receive w Mel deployments as an adjunct to local mosquito control measures; or to continue with local mosquito control measures only. A test-negative design was used to measure efficacy. Study participants were persons 3–45 years old attending primary care clinics with acute undifferentiated fever. Laboratory testing identified virologically-confirmed dengue cases and test-negative controls. The primary endpoint was efficacy of w Mel in reducing the incidence of symptomatic, virologically-confirmed dengue, caused by any dengue virus serotype. Results: Following successful introgression of w Mel in intervention clusters, 8144 participants were enrolled; 3721 from w Mel-treated clusters and 4423 from untreated clusters. In the ITT analysis virologically-confirmed dengue occurred in 67 of 2905 (2.3%) participants in the w Mel-treated and 318 of 3401 (9.4%) in the untreated arm (OR 0.23, 95% CI, 0.15 to 0.35; P=0.004): protective efficacy of 77.1% (95% CI, 65.3 to 84.9). Protective efficacy was similar for the four serotypes. Hospitalisation for virologically-confirmed dengue was less frequent for participants resident in the w Mel-treated (13/2905, 2.8%) compared to the untreated arm (102/3401, 6.3%): protective efficacy 86.2% (95% CI, 66.2 to 94.3) Conclusions: w Mel introgression into Ae. aegypti populations was efficacious in reducing the incidence of symptomatic dengue, and also led to fewer dengue hospitalisations. Trial registration number: ClinicalTrials.gov Identifier: NCT03055585 and INA-A7OB6TW

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Section: Discussionmentioning

confidence: 99%

Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue

Utarini¹,

Indriani²,

Ahmad³

et al. 2021

N Engl J Med

315

235

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“…However, costs are far higher compared to the currently available estimate of $1500 per DALYs averted under the replacement programme in Yogyakarta [14]. There are several competing factors driving the disparities in the cost-effectiveness of the Wolbachia programme: (1) labour and equipment costs in Singapore are far higher than Indonesia, (2) the replacement approach includes a large number of one off costs mostly related to releases that occur in the initial year of intervention, whereas the suppression approach relies on the assumption that constant release is necessary to maintain low wild-type mosquito populations, (3) our estimates of Wolbachia effectiveness, and by extension its cost-effectiveness come from field data/trials rather than model-based extrapolations of effectiveness based on laboratory data (4) Singapore presents an overall different epidemiological situation, with a drastically higher population density at 7,810 persons per square kilometre [61] compared to urban areas included in [14]. In comparison, the densest release area was the Jakarta metropolitan area [14] with only 4,383 persons per square kilometre in 2021.…”

Section: Plos Global Public Healthmentioning

confidence: 81%

“…China [11], the USA [12] and Singapore [13] have suppression-based programmes, which have been implemented due to its perceived compatibility with existing vector control programmes, and greater social acceptability compared to the former approach. A previous study in Yogyarkata, Indonesia has since explored the cost-effectiveness of introgression programmes, taking into account spatio-temporal heterogeneity of the impact of Wolbachia through a modelling approach [14]. However, to the best of the authors' knowledge, the cost-effectiveness of suppression-based programmes is not yet known.…”

Section: Introductionmentioning

confidence: 99%

Economic impact of dengue in Singapore from 2010 to 2020 and the cost-effectiveness of Wolbachia interventions

Soh

Seah

Ong

et al. 2021

PLOS Glob Public Health

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The release of Wolbachia-infected mosquitoes is a promising disease intervention strategy that aims to control dengue and other arboviral infections. While early field trials and modelling studies suggest promising epidemiological and entomological outcomes, the overall cost effectiveness of the technology is not well studied in a resource rich setting nor under the suppression approach that aims to suppress the wild-type mosquito population through the release of Wolbachia-infected males. We used economical and epidemiological data from 2010 to 2020 to first ascertain the economic and health costs of dengue in Singapore, a high income nation where dengue is hyper-endemic. The hypothetical cost effectiveness of a national Wolbachia suppression program was then evaluated historically from 2010 to 2020. We estimated that the average economic impact of dengue in Singapore from 2010 to 2020 in constant 2010US$ ranged from $1.014 to $2.265 Billion. Using empirically derived disability weights, we estimated a disease burden of 7,645–21,262 DALYs from 2010–2020. Under an assumed steady-state running cost of a national Wolbachia suppression program in Singapore, we conservatively estimate that Wolbachia would cost an estimated $50,453–$100,907 per DALYs averted and would lead to an estimated $329.40 Million saved in economic costs over 2010 to 2020 under 40% intervention efficacy. Wolbachia releases in Singapore are expected to be highly cost-effective and its rollout must be prioritised to reduce the onward spread of dengue.

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“…As an additional scenario analysis, we also use a cost per person covered of $15.05 (the mean of the accelerated costs in Brady et al [ 78 ]) adjusted to 2013 prices (for consistency). This is the average of the cost per person for an accelerated Wolbachia programme ranging from approximately $12 to $21 per person.…”

Section: Methodsmentioning

confidence: 99%

Reducing dengue fever cases at the lowest budget: a constrained optimization approach applied to Thailand

2021

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Background With the challenges that dengue fever (DF) presents to healthcare systems and societies, public health officials must determine where best to allocate scarce resources and restricted budgets. Constrained optimization (CO) helps to address some of the acknowledged limitations of conventional health economic analyses and has typically been used to identify the optimal allocation of resources across interventions subject to a variety of constraints. Methods A dynamic transmission model was developed to predict the number of dengue cases in Thailand at steady state. A CO was then applied to identify the optimal combination of interventions (release of Wolbachia-infected mosquitoes and paediatric vaccination) within the constraints of a fixed budget, set no higher than cost estimates of the current vector control programme, to minimize the number of dengue cases and disability-adjusted life years (DALYs) lost. Epidemiological, cost, and effectiveness data were informed by national data and the research literature. The time horizon was 10 years. Scenario analyses examined different disease management and intervention costs, budget constraints, vaccine efficacy, and optimization time horizon. Results Under base-case budget constraints, the optimal coverage of the two interventions to minimize dengue incidence was predicted to be nearly equal (Wolbachia 50%; paediatric vaccination 49%) with corresponding coverages under lower bound (Wolbachia 54%; paediatric vaccination 10%) and upper bound (Wolbachia 67%; paediatric vaccination 100%) budget ceilings. Scenario analyses indicated that the most impactful situations related to the costs of Wolbachia and paediatric vaccination with decreases/ increases in costs of interventions demonstrating a direct correlation with coverage (increases/ decreases) of the respective control strategies under examination. Conclusions Determining the best investment strategy for dengue control requires the identification of the optimal mix of interventions to implement in order to maximize public health outcomes, often under fixed budget constraints. A CO model was developed with the objective of minimizing dengue cases (and DALYs lost) over a 10-year time horizon, within the constraints of the estimated budgets for vector control in the absence of vaccination and Wolbachia. The model provides a tool for developing estimates of optimal coverage of combined dengue control strategies that minimize dengue burden at the lowest budget.

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

Cited by 27 publications

References 42 publications

Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue

Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue

Economic impact of dengue in Singapore from 2010 to 2020 and the cost-effectiveness of Wolbachia interventions

Reducing dengue fever cases at the lowest budget: a constrained optimization approach applied to Thailand

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