A metapopulation approach to identify targets for Wolbachia-based dengue control.

Over the last decade, the release of Wolbachia-infected Aedes aegypti into the natural habitat of this mosquito species has become the most sustainable and long-lasting technique to prevent and control vector-borne diseases, such as dengue, zika, or chikungunya. However, the limited resources to generate such mosquitoes and their effective distribution in large areas dominated by the Aedes aegypti vector represent a challenge for policymakers. Here, we introduce a mathematical framework for the spread of dengue in which competition between wild and Wolbachia-infected mosquitoes, the cross-contagion patterns between humans and vectors, the heterogeneous distribution of the human population in different areas, and the mobility flows between them are combined. Our framework allows us to identify the most effective areas for the release of Wolbachia-infected mosquitoes to achieve a large decrease in the global dengue prevalence.

Prevention and control of dengue and chikungunya in Colombia: A cost-effectiveness analysis.

BACKGROUND: Chikungunya and dengue are emerging diseases that have caused large outbreaks in various regions of the world. Both are both spread by Aedes aegypti and Aedes albopictus mosquitos. We developed a dynamic transmission model of chikungunya and dengue, calibrated to data from Colombia (June 2014 -December 2017). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the health benefits and cost-effectiveness of residual insecticide treatment, long-lasting insecticide-treated nets, routine dengue vaccination for children aged 9, catchup vaccination for individuals aged 10-19 or 10-29, and portfolios of these interventions. Model calibration resulted in 300 realistic transmission parameters sets that produced close matches to disease-specific incidence and deaths. Insecticide was the preferred intervention and was cost-effective. Insecticide averted an estimated 95 chikungunya cases and 114 dengue cases per 100,000 people, 61 deaths, and 4,523 disability-adjusted life years (DALYs). In sensitivity analysis, strategies that included dengue vaccination were cost-effective only when the vaccine cost was 14% of the current price. CONCLUSIONS/SIGNIFICANCE: Insecticide to prevent chikungunya and dengue in Colombia could generate significant health benefits and be cost-effective. Because of limits on diagnostic accuracy and vaccine efficacy, the cost of dengue testing and vaccination must decrease dramatically for such vaccination to be cost-effective in Colombia. The vectors for chikungunya and dengue have recently spread to new regions, highlighting the importance of understanding the effectiveness and cost-effectiveness of policies aimed at preventing these diseases.

Cost of community-led larval source management and house improvement for malaria control: a cost analysis within a cluster-randomized trial in a rural district in Malawi.

BACKGROUND: House improvement (HI) to prevent mosquito house entry, and larval source management (LSM) targeting aquatic mosquito stages to prevent development into adult forms, are promising complementary interventions to current malaria vector control strategies. Lack of evidence on costs and cost-effectiveness of community-led implementation of HI and LSM has hindered wide-scale adoption. This study presents an incremental cost analysis of community-led implementation of HI and LSM, in a cluster-randomized, factorial design trial, in addition to standard national malaria control interventions in a rural area (25,000 people), in southern Malawi. METHODS: In the trial, LSM comprised draining, filling, and Bacillus thuringiensis israelensis-based larviciding, while house improvement (henceforth HI) involved closing of eaves and gaps on walls, screening windows/ventilation spaces with wire mesh, and doorway modifications. Communities implemented all interventions. Costs were estimated retrospectively using the 'ingredients approach', combining 'bottom-up' and 'top-down approaches', from the societal perspective. To estimate the cost of independently implementing each intervention arm, resources shared between trial arms (e.g. overheads) were allocated to each consuming arm using proxies developed based on share of resource input quantities consumed. Incremental implementation costs (in 2017 US$) are presented for HI-only, LSM-only and HI + LSM arms. In sensitivity analyses, the effect of varying costs of important inputs on estimated costs was explored. RESULTS: The total economic programme costs of community-led HI and LSM implementation was $626,152. Incremental economic implementation costs of HI, LSM and HI + LSM were estimated as $27.04, $25.06 and $33.44, per person per year, respectively. Project staff, transport and labour costs, but not larvicide or screening material, were the major cost drivers across all interventions. Costs were sensitive to changes in staff costs and population covered. CONCLUSIONS: In the trial, the incremental economic costs of community-led HI and LSM implementation were high compared to previous house improvement and LSM studies. Several factors, including intervention design, year-round LSM implementation and low human population density could explain the high costs. The factorial trial design necessitated use of proxies to allocate costs shared between trial arms, which limits generalizability where different designs are used. Nevertheless, costs may inform planners of similar intervention packages where cost-effectiveness is known. Trial registration Not applicable. The original trial was registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.

Cost and cost-effectiveness of indoor residual spraying with pirimiphos-methyl in a high malaria transmission district of Mozambique with high access to standard insecticide-treated nets.

BACKGROUND: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. METHODS: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. RESULTS: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. CONCLUSION: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1.

Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa.

BACKGROUND: Increasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy. METHODS: This cluster-randomised, open-label, non-inferiority trial compared reactive, targeted IRS with standard IRS practice in northeastern South Africa over two malaria seasons (2015-17). In standard IRS clusters, programme managers conducted annual mass spray campaigns prioritising areas using historical data, expert opinion, and other factors. In targeted IRS clusters, only houses of index cases (identified through passive surveillance) and their immediate neighbours were sprayed. The non-inferiority margin was 1 case per 1000 person-years. Health service costs of real-world implementation were modelled from primary and secondary data. Incremental costs per disability-adjusted life-year (DALY) were estimated and deterministic and probabilistic sensitivity analyses conducted. This study is registered with ClinicalTrials.gov, NCT02556242. FINDINGS: Malaria incidence was 0·95 per 1000 person-years (95% CI 0·58 to 1·32) in the standard IRS group and 1·05 per 1000 person-years (0·72 to 1·38) in the targeted IRS group, corresponding to a rate difference of 0·10 per 1000 person-years (-0·38 to 0·59), demonstrating non-inferiority for targeted IRS (p<0·0001). Per additional DALY incurred, targeted IRS saved US$7845 (2902 to 64 907), giving a 94-98% probability that switching to targeted IRS would be cost-effective relative to plausible cost-effectiveness thresholds for South Africa ($2637 to $3557 per DALY averted). Depending on the threshold used, targeted IRS would remain cost-effective at incidences of less than 2·0-2·7 per 1000 person-years. Findings were robust to plausible variation in other parameters. INTERPRETATION: Targeted IRS was non-inferior, safe, less costly, and cost-effective compared with standard IRS in this very-low-transmission setting. Saved resources could be reallocated to other malaria control and elimination activities. FUNDING: Joint Global Health Trials.

A cost analysis to address issues of budget constraints on the implementation of the indoor residual spray programme in two districts of Maputo Province, Mozambique.

BACKGROUND: It is frequently said that funding is essential to ensure optimal results from a malaria intervention control. However, in recent years, the capacity of the government of Mozambique to sustain the operational cost of indoor residual spraying (IRS) is facing numerous challenges due to restrictions of the Official Development Assistance. The purpose of the study was to estimate the cost of IRS operationalization in two districts of Maputo Province (Matutuíne and Namaacha) in Mozambique. The evidence produced in this study intends to provide decision-makers with insight into where they need to pay close attention in future planning in order to operationalize IRS with the existent budget in the actual context of budget restrictions. METHODS: Cost information was collected retrospectively from the provider perspective, and both economic and financial costs were calculated. A "one-way" deterministic sensitivity analysis was performed. RESULTS: The average economic costs totaled US$117,351.34, with an average economic cost per household sprayed of US$16.35, and an average economic cost per person protected of US$4.09. The average financial cost totaled US$69,174.83, with an average financial cost per household sprayed and per person protected of US$9.84 and US$2.46, respectively. Vehicle, salary, and insecticide costs were the greatest contributors to overall cost in the economic and financial analysis, corresponding to 52%, 17%, and 13% in the economic analysis and 21%, 27%, and 22% in the financial analysis, respectively. The sensitivity analysis was adapted to a range of ± (above and under) 25% change. There was an approximate change of 14% in the average economic cost when vehicle costs were decreased by 25%. In the financial analysis, the average financial cost was lowered by 7% when salary costs were decreased by 25%. CONCLUSIONS: Altogether, the current cost analysis provides an impetus for the consideration of targeted IRS operationalization within the available governmental budget, by using locally-available human resources as spray operators to decrease costs and having IRS rounds be correctly timed to coincide with the build-up of vector populations.

Addressing budget reduction and reallocation on health-related resources during COVID-19 pandemic in malaria-endemic countries.

The global COVID-19 pandemic has been affecting the maintenance of various disease control programmes, including malaria. In some malaria-endemic countries, funding and personnel reallocations were executed from malaria control programmes to support COVID-19 response efforts, resulting mainly in interruptions of disease control activities and reduced capabilities of health system. While it is principal to drive national budget rearrangements during the pandemic, the long-standing malaria control programmes should not be left behind in order to sustain the achievements from the previous years. With different levels of intensity, many countries have been struggling to improve the health system resilience and to mitigate the unavoidable stagnation of malaria control programmes. Current opinion emphasized the impacts of budget reprioritization on malaria-related resources during COVID-19 pandemic in malaria endemic countries in Africa and Southeast Asia, and feasible attempts that can be taken to lessen these impacts.

Long-lasting microbial larvicides for controlling insecticide resistant and outdoor transmitting vectors: a cost-effective supplement for malaria interventions.

The issues of pyrethroid resistance and outdoor malaria parasite transmission have prompted the WHO to call for the development and adoption of viable alternative vector control methods. Larval source management is one of the core malaria vector interventions recommended by the Ministry of Health in many African countries, but it is rarely implemented due to concerns on its cost-effectiveness. New long-lasting microbial larvicide can be a promising cost-effective supplement to current vector control and elimination methods because microbial larvicide uses killing mechanisms different from pyrethroids and other chemical insecticides. It has been shown to be effective in reducing the overall vector abundance and thus both indoor and outdoor transmission. In our opinion, the long-lasting formulation can potentially reduce the cost of larvicide field application, and should be evaluated for its cost-effectiveness, resistance development, and impact on non-target organisms when integrating with other malaria vector control measures. In this opinion, we highlight that long-lasting microbial larvicide can be a potential cost-effective product that complements current front-line long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) programs for malaria control and elimination. Microbial larviciding targets immature mosquitoes, reduces both indoor and outdoor transmission and is not affected by vector resistance to synthetic insecticides. This control method is a shift from the conventional LLINs and IRS programs that mainly target indoor-biting and resting adult mosquitoes.

Nextgen Vector Surveillance Tools: sensitive, specific, cost-effective and epidemiologically relevant.

BACKGROUND: Vector surveillance provides critical data for decision-making to ensure that malaria control programmes remain effective and responsive to any threats to a successful control and elimination programme. The quality and quantity of data collected is dependent on the sampling tools and laboratory techniques used which may lack the sensitivity required to collect relevant data for decision-making. Here, 40 vector control experts were interviewed to assess the benefits and limitations of the current vector surveillance tools and techniques. In addition, experts shared ideas on "blue sky" indicators which encompassed ideas for novel methods to monitor presently used indicators, or to measure novel vector behaviours not presently measured. Algorithms for deploying surveillance tools and priorities for understanding vector behaviours are also needed for collecting and interpreting vector data. RESULTS: The available tools for sampling and analysing vectors are often hampered by high labour and resource requirements (human and supplies) coupled with high outlay and operating costs and variable tool performance across species and geographic regions. The next generation of surveillance tools needs to address the limitations of present tools by being more sensitive, specific and less costly to deploy to enable the collection and use of epidemiologically relevant vector data to facilitate more proactive vector control guidance. Ideas and attributes for Target Product Profiles (TPPs) generated from this analysis provide targets for research and funding to develop next generation tools. CONCLUSIONS: More efficient surveillance tools and a more complete understanding of vector behaviours and populations will provide a basis for more cost effective and successful malaria control. Understanding the vectors' behaviours will allow interventions to be deployed that target vulnerabilities in vector behaviours and thus enable more effective control. Through defining the strengths and weaknesses of the current vector surveillance methods, a foundation and initial framework was provided to define the TPPs for the next generation of vector surveillance methods. The draft TTPs presented here aim to ensure that the next generation tools and technologies are not encumbered by the limitations of present surveillance methods and can be readily deployed in low resource settings.

The economic impact and cost-effectiveness of combined vector-control and dengue vaccination strategies in Thailand: results from a dynamic transmission model.

BACKGROUND AND AIMS: Dengue 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. METHODS: The 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. RESULTS: From 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. CONCLUSIONS: Our 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.

Design and development of porous terracotta disc: An eco-friendly novel control agent for mosquito larvae.

In the present work, we synthesized silver nanoparticles supported by rice husk by hydrothermal treatment, as-synthesized silver nanoparticles rice husk (AgNPs-RH) bio-composite mixed with potter clay thoroughly, molded, dried into a disc-shaped before firing and applying as a point of use larvicidal agent. As designed, porous terracotta disc (PTD) infused with AgNPs-RH-biocomposite were characterized by UV spectrophotometer, Fourier-transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction analysis and energy-dispersive X-ray spectroscopy. The amount of silver ions released from the PTD was also found to be within the prescribed limit of 0.1 ppm-level. Later we dropped the PTD and tested its larvicidal activity against the IVth instar larva stage of Aedes, Anopheles and Culex species. We found 100% larvicidal mortality in 24 h of exposure to the designed PTD and the amount of silver released from the porous disc was found to be 0.0343 ppm. Further from the histopathological studies of dead larvae revealed that the silver ions from the PTD have substantially damaged the exoskeleton of larvae.

Comparative functional survival and equivalent annual cost of 3 long-lasting insecticidal net (LLIN) products in Tanzania: A randomised trial with 3-year follow up.

BACKGROUND: Two billion long-lasting insecticidal nets (LLINs) have been procured for malaria control. A functional LLIN is one that is present, is in good physical condition, and remains insecticidal, thereby providing protection against vector-borne diseases through preventing bites and killing disease vectors. The World Health Organization (WHO) prequalifies LLINs that remain adequately insecticidal 3 years after deployment. Therefore, institutional buyers often assume that prequalified LLINs are functionally identical with a 3-year lifespan. We measured the lifespans of 3 LLIN products, and calculated their cost per year of functional life, to demonstrate the economic and public health importance of procuring the most cost-effective LLIN product based on its lifespan. METHODS AND FINDINGS: A randomised double-blinded trial of 3 pyrethroid LLIN products (10,571 nets in total) was conducted at 3 follow-up points: 10 months (August-October 2014), 22 months (August-October 2015), and 36 months (October-December 2016) among 3,393 households in Tanzania using WHO-recommended methods. Primary outcome was LLIN functional survival (LLIN present and in serviceable condition). Secondary outcomes were (1) bioefficacy and chemical content (residual insecticidal activity) and (2) protective efficacy for volunteers sleeping under the LLINs (bite reduction and mosquitoes killed). Median LLIN functional survival was significantly different between the 3 net products (p = 0.001): 2.0 years (95% CI 1.7-2.3) for Olyset, 2.5 years (95% CI 2.2-2.8) for PermaNet 2.0 (hazard ratio [HR] 0.73 [95% CI 0.64-0.85], p = 0.001), and 2.6 years (95% CI 2.3-2.8) for NetProtect (HR = 0.70 [95% CI 0.62-0.77], p < 0.001). Functional survival was affected by accumulation of holes, leading to users discarding nets. Protective efficacy also significantly differed between products as they aged. Equivalent annual cost varied between US$1.2 (95% CI $1.1-$1.4) and US$1.5 (95% CI $1.3-$1.7), assuming that each net was priced identically at US$3. The 2 longer-lived nets (PermaNet and NetProtect) were 20% cheaper than the shorter-lived product (Olyset). The trial was limited to only the most widely sold LLINs in Tanzania. Functional survival varies by country, so the single country setting is a limitation. CONCLUSIONS: These results suggest that LLIN functional survival is less than 3 years and differs substantially between products, and these differences strongly influence LLIN value for money. LLIN tendering processes should consider local expectations of cost per year of functional life and not unit price. As new LLIN products come on the market, especially those with new insecticides, it will be imperative to monitor their comparative durability to ensure that the most cost-effective products are procured for malaria control.

Cost-effectiveness analysis of VECTOS software for the control of diseases transmitted by Aedes aegypti in two Colombian municipalities / [Análisis de costo-efectividad del uso del programa VECTOS en el control rutinario de enfermedades transmitidas por Aedes aegypti en dos municipios de Santander, Colombia].

Introduction: Diseases transmitted by Aedes aegypti are considered a public health problem. VECTOS is a novel software for the integration of vector control strategies. Objective: To assess the cost-effectiveness of the use of VECTOS in the routine control programs of diseases transmitted by A. aegypti in the municipality of San Juan de Girón (Santander). Materials and methods: We conducted a cost-effectiveness analysis using a decision analysis model from the perspective of the local health authorities. We considered the use of the VECTOS software in the routine control activities in the municipality of San Juan de Girón during 2016 as the treatment group while the routine control in the municipality of Floridablanca, where VECTOS is not implemented, was considered as the comparator. We calculated the incremental cost-effectiveness ratio (ICER) taking as effectiveness measure the disability-adjusted life years (DALY). Results: VECTOS was cost-effective at a rate of USD$ 660,4 savings per each DALY avoided compared to the routine control in Floridablanca. The probabilistic model showed that the system was cost-effective in 70% of the 10.000 iterations for a threshold between 1 to 3 GDP per capita. Conclusions: VECTOS software as implemented in the municipality of San Juan de Girón is highly cost-effective and could be used in other municipalities in the country where diseases transmitted by A. aegypti are endemic.

Introducción. Las enfermedades transmitidas por Aedes aegypti son un problema de salud pública. VECTOS es un programa novedoso de integración de estrategias de control de vectores. Objetivo. Evaluar el costo-efectividad del uso del VECTOS en los programas de control rutinario de enfermedades transmitidas por el vector Aedes aegypti en el municipio de San Juan de Girón (Santander). Materiales y métodos. Se evaluó el costo-efectividad del programa empleando un modelo de análisis de decisiones desde la perspectiva de las autoridades locales de salud. Se estudió la integración de las estrategias de control de vectores mediante el programa VECTOS utilizado en el municipio de San Juan de Girón durante el 2016, con el control rutinario llevado a cabo sin VECTOS en el municipio de Floridablanca. Se calculó la razón incremental del costo-efectividad (RICE), usando como medida de efectividad los años de vida ajustados por discapacidad (AVAD). Resultados. El uso del programa VECTOS fue rentable a una tasa de ahorro de USD$660,4 por cada AVAD evitado en comparación con el control de rutina en Floridablanca. El modelo probabilístico indicó que el sistema fue costo-efectivo en el 70 % de las 10.000 iteraciones para un umbral entre 1 y 3 PIB per cápita. Conclusiones. El programa VECTOS fue muy costo-efectivo en el municipio de San Juan de Girón. Su uso puede adoptarse en otros municipios del país donde las enfermedades transmitidas por A. aegypti son endémicas.

Coordination among neighbors improves the efficacy of Zika control despite economic costs.

Emerging mosquito-borne viruses like Zika, dengue, and chikungunya pose a major threat to public health, especially in low-income regions of Central and South America, southeast Asia, and the Caribbean. Outbreaks of these diseases are likely to have long-term social and economic consequences due to Zika-induced congenital microcephaly and other complications. Larval control of the container-inhabiting mosquitoes that transmit these infections is an important tool for mitigating outbreaks. However, metapopulation theory suggests that spatiotemporally uneven larvicide treatment can impede control effectiveness, as recolonization compensates for mortality within patches. Coordinating the timing of treatment among patches could therefore substantially improve epidemic control, but we must also consider economic constraints, since coordination may have costs that divert resources from treatment. To inform practical disease management strategies, we ask how coordination among neighbors in the timing of mosquito control efforts influences the size of a mosquito-borne infectious disease outbreak under the realistic assumption that coordination has costs. Using an SIR (Susceptible-Infectious-Recovered)/metapopulation model of mosquito and disease dynamics, we examine whether sharing surveillance information and coordinating larvicide treatment among neighboring patches reduces human infections when incorporating coordination costs. We examine how different types of coordination costs and different surveillance methods jointly influence the effectiveness of larval control. We find that the effect of coordination depends on both costs and the type of surveillance used to inform treatment. With epidemiological surveillance, coordination improves disease outcomes, even when costly. With demographic surveillance, coordination either improves or hampers disease control, depending on the type of costs and surveillance sensitivity. Our results suggest coordination among neighbors can improve management of mosquito-borne epidemics under many, but not all, assumptions about costs. Therefore, estimating coordination costs is an important step for most effectively applying metapopulation theory to strategies for managing outbreaks of mosquito-borne viral infections.

Costs of insecticide-treated bed net distribution systems in sub-Saharan Africa.

BACKGROUND: Insecticide-treated nets (ITNs) are one of the most cost-effective measures for preventing malaria. The World Health Organization recommends both large-scale mass distribution campaigns and continuous distributions (CD) as part of a multifaceted strategy to achieve and sustain universal access to ITNs. A combination of these strategies has been effective for scaling up ITN access. For policy makers to make informed decisions on how to efficiently implement CD or combined strategies, information on the costs and cost-effectiveness of these delivery systems is necessary, but relatively few published studies of the cost continuous distribution systems exist. METHODS: To address the gap in continuous distribution cost data, four types of delivery systems-CD through antenatal care services (ANC) and the expanded programme on immunization (EPI) (Ghana, Mali, and mainland Tanzania), CD through schools (Ghana and mainland Tanzania), and a combined community/health facility-based distribution (Zanzibar, Tanzania), as well as mass distributions (Mali)-were costed. Data on costs were collected retrospectively from financial and operational records, stakeholder interviews, and resource use surveys. RESULTS: Overall, from a full provider perspective, mass distributions and continuous systems delivered ITNs at overlapping economic costs per net distributed (mass distributions: 4.37-4.61 USD, CD channels: 3.56-9.90 USD), with two of the school-based systems and the mass distributions at the lower end of this range. From the perspective of international donors, the costs of the CD systems were, for the most part, less costly than the mass distributions (mass distributions: 4.34-4.55 USD, Ghana and Tanzania 2017 school-based: 3.30-3.69 USD, health facility-based: 3.90-4.55 USD, combined community/health facility 4.55 USD). The 2015 school-based distribution (7.30 USD) and 2016 health facility-based distribution (6.52 USD) programmes in Tanzania were an exception. Mass distributions were more heavily financed by donors, while CD relied more extensively on domestic resource contributions. CONCLUSIONS: These results suggest that CD strategies can continue to deliver nets at a comparable cost to mass distributions, especially from the perspective of the donor.

Simulating the council-specific impact of anti-malaria interventions: A tool to support malaria strategic planning in Tanzania.

INTRODUCTION: The decision-making process for malaria control and elimination strategies has become more challenging. Interventions need to be targeted at council level to allow for changing malaria epidemiology and an increase in the number of possible interventions. Models of malaria dynamics can support this process by simulating potential impacts of multiple interventions in different settings and determining appropriate packages of interventions for meeting specific expected targets. METHODS: The OpenMalaria model of malaria dynamics was calibrated for all 184 councils in mainland Tanzania using data from malaria indicator surveys, school parasitaemia surveys, entomological surveillance, and vector control deployment data. The simulations were run for different transmission intensities per region and five interventions, currently or potentially included in the National Malaria Strategic Plan, individually and in combination. The simulated prevalences were fitted to council specific prevalences derived from geostatistical models to obtain council specific predictions of the prevalence and number of cases between 2017 and 2020. The predictions were used to evaluate in silico the feasibility of the national target of reaching a prevalence of below 1% by 2020, and to suggest alternative intervention stratifications for the country. RESULTS: The historical prevalence trend was fitted for each council with an agreement of 87% in 2016 (95%CI: 0.84-0.90) and an agreement of 90% for the historical trend (2003-2016) (95%CI: 0.87-0.93) The current national malaria strategy was expected to reduce the malaria prevalence between 2016 and 2020 on average by 23.8% (95% CI: 19.7%-27.9%) if current case management levels were maintained, and by 52.1% (95% CI: 48.8%-55.3%) if the case management were improved. Insecticide treated nets and case management were the most cost-effective interventions, expected to reduce the prevalence by 25.0% (95% CI: 19.7%-30.2) and to avert 37 million cases between 2017 and 2020. Mass drug administration was included in most councils in the stratification selected for meeting the national target at minimal costs, expected to reduce the prevalence by 77.5% (95%CI: 70.5%-84.5%) and to avert 102 million cases, with almost twice higher costs than those of the current national strategy. In summary, the model suggested that current interventions are not sufficient to reach the national aim of a prevalence of less than 1% by 2020 and a revised strategic plan needs to consider additional, more effective interventions, especially in high transmission areas and that the targets need to be revisited. CONCLUSION: The methodology reported here is based on intensive interactions with the NMCP and provides a helpful tool for assessing the feasibility of country specific targets and for determining which intervention stratifications at sub-national level will have most impact. This country-led application could support strategic planning of malaria control in many other malaria endemic countries.

A potential global surveillance tool for effective, low-cost sampling of invasive Aedes mosquito eggs from tyres using adhesive tape.

BACKGROUND: The international movement of used tyres is a major factor responsible for global introductions of Aedes invasive mosquitoes (AIMs) (Diptera: Culicidae) that are major disease vectors (e.g. dengue, Zika, chikungunya and yellow fever). Surveillance methods are restricted by expense, availability and efficiency to detect all life stages. Currently, no tested method exists to screen imported used tyres for eggs in diapause, the life stage most at risk from accidental introduction. Here we test the efficiency of adhesive tape as an affordable and readily available material to screen tyres for eggs, testing its effect on hatch rate, larval development, DNA amplification and structural damage on the egg surface. RESULTS: We demonstrated that the properties of adhesive tape can influence pick up of dormant eggs attached to dry surfaces. Tapes with high levels of adhesion, such as duct tape, removed eggs with high levels of efficiency (97% ± 3.14). Egg numbers collected from cleaned used tyres were found to explain larval hatch rate success well, particularly in subsequent larval to adult emergence experiments. The strength of this relationship decreased when we tested dirty tyres. Damage to the exochorion was observed following scanning electron microscopy (SEM), possibly resulting in the high variance in the observed model. We found that five days was the optimal time for eggs to remain on all tested tapes for maximum return on hatch rate success. Tape type did not inhibit amplification of DNA of eggs from three, five or ten days of exposure. Using this DNA, genotyping of AIMs was possible using species-specific markers. CONCLUSIONS: We demonstrated for the first time that adhesive tapes are effective at removing AIM eggs from tyres. We propose that this method could be a standardised tool for surveillance to provide public health authorities and researchers with an additional method to screen tyre cargo. We provide a screening protocol for this purpose. This method has a global applicability and in turn can lead to increased predictability of introductions and improve screening methods at high risk entry points.

A review of the economic evidence of Aedes-borne arboviruses and Aedes-borne arboviral disease prevention and control strategies.

Introduction:Aedes-borne arboviruses contributes substantially to the disease and cost burden.Areas covered: We performed a systematic review of the economic evidence surrounding aedes-borne arboviruses and strategies to prevent and control these diseases to inform disease control policy decisions and research directions. We searched four databases covering an 18-year period (2000-2018) to identify arboviral disease-related cost of illness studies, cost studies of vector control and prevention strategies, cost-effectiveness analyses and cost-benefit analyses. We identified 74 published studies that revealed substantial global total costs in yellow fever virus and dengue virus ranging from 2.1 to 57.3 billion USD. Cost studies of vector control and surveillance programs are limited, but a few studies found that costs of vector control programs ranged from 5.62 to 73.5 million USD. Cost-effectiveness evidence was limited across Aedes-borne diseases, but generally found targeted dengue vaccination programs cost-effective. This review revealed insufficient economic evidence for vaccine introduction and implementation of surveillance and vector control programs.Expert opinion: Evidence of the economic burden of aedes-borne arboviruses and the economic impact of strategies for arboviral disease prevention and control is critical to inform policy decisions and to secure continued financial support for these preventive and control measures.

A network analysis framework to improve the delivery of mosquito abatement services in Machala, Ecuador.

BACKGROUND: Vector-borne disease places a high health and economic burden in the American tropics. Comprehensive vector control programs remain the primary method of containing local outbreaks. With limited resources, many vector control operations struggle to serve all affected communities within their districts. In the coastal city of Machala, Ecuador, vector control services, such as application of larvicides and truck-mounted fogging, are delivered through two deployment facilities managed by the Ecuadorian Ministry of Health. Public health professionals in Machala face several logistical issues when delivering mosquito abatement services, namely applying limited resources in ways that will most effectively suppress vectors of malaria, dengue, and encephalitis viruses. METHODS: Using a transportation network analysis framework, we built models of service areas and optimized delivery routes based on distance costs associated with accessing neighborhoods throughout the city. Optimized routes were used to estimate the relative cost of accessing neighborhoods for mosquito control services in Machala, creating a visual tool to guide decision makers and maximize mosquito control program efficiency. Location-allocation analyses were performed to evaluate efficiency gains of moving service deployment to other available locations with respect to distance to service hub, neighborhood population, dengue incidence, and housing condition. RESULTS: Using this framework, we identified different locations for targeting mosquito control efforts, dependent upon management goals and specified risk factors of interest, including human population, housing condition, and reported dengue incidence. Our models indicate that neighborhoods on the periphery of Machala with the poorest housing conditions are the most costly to access. Optimal locations of facilities for deployment of control services change depending on pre-determined management priorities, increasing the population served via inexpensive routes up to 34.9%, and reducing overall cost of accessing neighborhoods up to 12.7%. CONCLUSIONS: Our transportation network models indicate that current locations of mosquito control facilities in Machala are not ideal for minimizing driving distances or maximizing populations served. Services may be optimized by moving vector control operations to other existing public health facilities in Machala. This work represents a first step in creating a spatial tool for planning and critically evaluating the systematic delivery of mosquito control services in Machala and elsewhere.