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The interplay of vaccination and vector control on small dengue networks.

ABSTRACT: Dengue fever is a major public health issue affecting billions of people in over 100 countries across the globe. This challenge is growing as the invasive mosquito vectors, Aedes aegypti and Aedes albopictus, expand their distributions and increase their population sizes. Hence there is an increasing need to devise effective control methods that can contain dengue outbreaks. Here we construct an epidemiological model for virus transmission between vectors and hosts on a network of host populations distributed among city and town patches, and investigate disease control through vaccination and vector control using variants of the sterile insect technique (SIT). Analysis of the basic reproductive number and simulations indicate that host movement across this small network influences the severity of epidemics. Both vaccination and vector control strategies are investigated as methods of disease containment and our results indicate that these controls can be made more effective with mixed strategy solutions. We predict that reduced lethality through poor SIT methods or imperfectly efficacious vaccines will impact efforts to control disease spread. In particular, weakly efficacious vaccination strategies against multiple virus serotype diversity may be counter productive to disease control efforts. Even so, failings of one method may be mitigated by supplementing it with an alternative control strategy. Generally, our network approach encourages decision making to consider connected populations, to emphasise that successful control methods must effectively suppress dengue epidemics at this landscape scale.

SUBMITTER: Hendron RS

PROVIDER: S-EPMC5016021 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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The interplay of vaccination and vector control on small dengue networks.

Hendron Ross-William S RS Bonsall Michael B MB

Journal of theoretical biology 20160722

Dengue fever is a major public health issue affecting billions of people in over 100 countries across the globe. This challenge is growing as the invasive mosquito vectors, Aedes aegypti and Aedes albopictus, expand their distributions and increase their population sizes. Hence there is an increasing need to devise effective control methods that can contain dengue outbreaks. Here we construct an epidemiological model for virus transmission between vectors and hosts on a network of host populatio ...[more]

PMID: 27457093

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Project description:BackgroundBecause no dengue vaccine or antiviral therapy is commercially available, controlling the primary mosquito vector, Aedes aegypti, is currently the only means to prevent dengue outbreaks. Traditional models of Ae. aegypti assume that population dynamics are regulated by density-dependent larval competition for food and little affected by oviposition behavior. Due to direct impacts on offspring survival and development, however, mosquito choice in oviposition site can have important consequences for population regulation that should be taken into account when designing vector control programs.Methodology/principal findingsWe examined oviposition patterns by Ae. aegypti among 591 naturally occurring containers and a set of experimental containers in Iquitos, Peru. Using larval starvation bioassays as an indirect measure of container food content, we assessed whether females select containers with the most food for their offspring. Our data indicate that choice of egg-laying site is influenced by conspecific larvae and pupae, container fill method, container size, lid, and sun exposure. Although larval food positively influenced oviposition, our results did not support the hypothesis that females act primarily to maximize food for larvae. Females were most strongly attracted to sites containing immature conspecifics, even when potential competitors for their progeny were present in abundance.Conclusion/significanceDue to strong conspecific attraction, egg-laying behavior may contribute more to regulating Ae. aegypti populations than previously thought. If highly infested containers are targeted for removal or larvicide application, females that would have preferentially oviposited in those sites may instead distribute their eggs among other suitable, previously unoccupied containers. Strategies that kill mosquitoes late in their development (i.e., insect growth regulators that kill pupae rather than larvae) will enhance vector control by creating "egg sinks," treated sites that exploit conspecific attraction of ovipositing females, but reduce emergence of adult mosquitoes via density-dependent larval competition and late acting insecticide.

Project description:Background and aimsDengue fever is a major public health problem in tropical/subtropical regions. Prior economic analyses have predominantly evaluated either vaccination or vector-control programmes in isolation and do not really consider the incremental benefits and cost-effectiveness of mixed strategies and combination control. We estimated the cost-effectiveness of single and combined approaches in Thailand.MethodsThe impacts of different control interventions were analysed using a previously published mathematical model of dengue epidemiology and control incorporating seasonality, age structure, consecutive infection, cross protection, immune enhancement and combined vector-host transmission. An economic model was applied to simulation results to estimate the cost-effectiveness of 4 interventions and their various combinations (6 strategies): i) routine vaccination of 1-year olds; ii) chemical vector control strategies targeting adult and larval stages separately; iii) environmental management/ public health education and awareness [EM/ PHEA]). Payer and societal perspectives were considered. The health burden of dengue fever was assessed using disability-adjusted life-years (DALYs) lost. Costs and effects were assessed for 10 years. Costs were discounted at 3% annually and updated to 2013 United States Dollars. Incremental cost-effectiveness analysis was carried out after strategies were rank-ordered by cost, with results presented in a table of incremental analysis. Sensitivity and scenario analyses were undertaken; and the impact and cost-effectiveness of Wolbachia was evaluated in exploratory scenario analyses.ResultsFrom the payer and societal perspectives, 2 combination strategies were considered optimal, as all other control strategies were dominated. Vaccination plus adulticide plus EM/ PHEA was deemed cost-effective according to multiple cost-effectiveness criteria. From the societal perspective, incremental differences vs. adulticide and EM/ PHEA resulted in costs of $157.6 million and DALYs lost of 12,599, giving an expected ICER of $12,508 per DALY averted. Exploratory scenario analyses showed Wolbachia to be highly cost-effective ($343 per DALY averted) vs. other single control measures.ConclusionsOur model shows that individual interventions can be cost-effective, but that important epidemiological reductions and economic impacts are demonstrated when interventions are combined as part of an integrated approach to combating dengue fever. Exploratory scenario analyses demonstrated the potential epidemiological and cost-effective impact of Wolbachia when deployed at scale on a nationwide basis. Our findings were robust in the face of sensitivity analyses.

Project description:BackgroundControl and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes. In Colombia, application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy. Resistance to temephos was recently detected in the dengue-endemic city of Cucuta, leading to questions about its efficacy as a control tool. Here, we characterize the underlying mechanisms and estimate the operational impact of this resistance.Methodology/principal findingsLarval bioassays of Ae. aegypti larvae from Cucuta determined the temephos LC50 to be 0.066 ppm (95% CI 0.06-0.074), approximately 15× higher than the value obtained from a susceptible laboratory colony. The efficacy of the field dose of temephos at killing this resistant Cucuta population was greatly reduced, with mortality rates <80% two weeks after application and <50% after 4 weeks. Neither biochemical assays nor partial sequencing of the ace-1 gene implicated target site resistance as the primary resistance mechanism. Synergism assays and microarray analysis suggested that metabolic mechanisms were most likely responsible for the temephos resistance. Interestingly, although the greatest synergism was observed with the carboxylesterase inhibitor, DEF, the primary candidate genes from the microarray analysis, and confirmed by quantitative PCR, were cytochrome P450 oxidases, notably CYP6N12, CYP6F3 and CYP6M11.Conclusions/significanceIn Colombia, resistance to temephos in Ae. aegypti compromises the duration of its effect as a vector control tool. Several candidate genes potentially responsible for metabolic resistance to temephos were identified. Given the limited number of insecticides that are approved for vector control, future chemical-based control strategies should take into account the mechanisms underlying the resistance to discern which insecticides would likely lead to the greatest control efficacy while minimizing further selection of resistant phenotypes.

Project description:BackgroundAn estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resource-constrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of different vector control strategies.MethodsWe developed a dynamic model of dengue transmission that assesses the evolution of insecticide resistance and immunity in the human population, thus allowing for long-term evolutionary and immunological effects of decreased dengue transmission. We measured the dengue health burden in terms of disability-adjusted life-years (DALYs) lost. We did a cost-effectiveness analysis of 43 insecticide-based vector control strategies, including strategies targeted at adult and larval stages, at varying efficacies (high-efficacy [90% mortality], medium-efficacy [60% mortality], and low-efficacy [30% mortality]) and yearly application frequencies (one to six applications). To assess the effect of parameter uncertainty on the results, we did a probabilistic sensitivity analysis and a threshold analysis.FindingsAll interventions caused the emergence of insecticide resistance, which, with the loss of herd immunity, will increase the magnitude of future dengue epidemics. In our model, one or more applications of high-efficacy larval control reduced dengue burden for up to 2 years, whereas three or more applications of adult vector control reduced dengue burden for up to 4 years. The incremental cost-effectiveness ratios of the strategies for two high-efficacy adult vector control applications per year was US$615 per DALY saved and for six high-efficacy adult vector control applications per year was $1267 per DALY saved. Sensitivity analysis showed that if the cost of adult control was more than 8·2 times the cost of larval control then all strategies based on adult control became dominated.InterpretationSix high-efficacy adult vector control applications per year has a cost-effectiveness ratio that will probably meet WHO's standard for a cost-effective or very cost-effective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only.FundingThe Fulbright Programme, CAPES (Brazilian federal agency for post-graduate education), the Miriam Burnett trust, and the Notsew Orm Sands Foundation.

Project description:BackgroundVector control remains the primary method to prevent dengue infections. Environmental interventions represent sustainable and safe methods as there are limited risks of environmental contamination and toxicity. The objective of this study is to perform a systematic review and meta-analysis of the effectiveness of the following environmental methods for dengue vector control.Methodology/principal findingsFollowing the PRISMA guidelines, a systematic literature search was conducted using the databases PubMed, EMBASE, LILACS, the Cochrane Library and Google Scholar. Quality assessment was done using the CONSORT 2010 checklist. For the meta-analysis the difference-in-differences (DID) and the difference-of-endlines (DOE) were calculated according to the Schmidt-Hunter method for the Breteau index (BI) and the pupae per person index (PPI). Nineteen studies were eligible for the systematic review, sixteen contributed data to the meta-analysis. The following methods were evaluated: (a) container covers with and without insecticides, (b) waste management and clean-up campaigns, and (c) elimination of breeding sites by rendering potential mosquito breeding sites unusable or by eliminating them. Study quality was highest for container covers with insecticides, followed by waste management without direct garbage collection and elimination of breeding places. Both, systematic review and meta-analysis, showed a weak effect of the interventions on larval populations, with no obvious differences between the results of each individual method. For the meta-analysis, both, container covers without insecticides (BI: DID -7.9, DOE -5) and waste management with direct garbage collection (BI: DID -8.83, DOE -6.2) achieved the strongest reductions for the BI, whereas for the PPI results were almost opposite, with container covers with insecticides (PPI: DID -0.83, DOE 0.09) and elimination of breeding places (PPI: DID -0.95, DOE -0.83) showing the strongest effects.ConclusionsEach of the investigated environmental methods showed some effectiveness in reducing larval and pupal densities of Aedes sp. mosquitoes. However, there is a need for more comparable high-quality studies at an adequate standard to strengthen this evidence.

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The interplay of vaccination and vector control on small dengue networks.

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The interplay of vaccination and vector control on small dengue networks.

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