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Background: In the Greater Mekong Subregion (GMS), new vector-control tools are needed to target mosquitoes that bite outside during the daytime and night-time to advance malaria elimination. Methods: We conducted systematic literature searches to generate a bionomic dataset of the main malaria vectors in the GMS, including human blood index (HBI), parity proportion, sac proportion (proportion with uncontracted ovary sacs, indicating the amount of time until they returned to host seeking after oviposition) and the resting period duration. We then performed global sensitivity analyses to assess the influence of bionomics and intervention characteristics on vectorial capacity. Results: Our review showed that Anopheles minimus, An. sinensis, An. maculatus and An. sundaicus display opportunistic blood-feeding behaviour, while An. dirus is more anthropophilic. Multivariate regression analysis indicated that environmental, climatic and sampling factors influence the proportion of parous mosquitoes, and resting duration varies seasonally. Sensitivity analysis highlighted HBI and parity proportion as the most influential bionomic parameters, followed by resting duration. Killing before feeding is always a desirable characteristic across all settings in the GMS. Disarming is also a desirable characteristic in settings with a low HBI. Repelling is only an effective strategy in settings with a low HBI and low parity proportion. Killing after feeding is only a desirable characteristic if the HBI and parity proportions in the setting are high. Conclusions: Although in general adopting tools that kill before feeding would have the largest community-level effect on reducing outdoor transmission, other modes of action can be effective. Current tools in development which target outdoor biting mosquitoes should be implemented in different settings dependent on their characteristics. [ABSTRACT FROM AUTHOR]

Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as 'attract-and-kill' or 'push-and-pull', have been suggested as complementary tools to indoor residual spraying and long-lasting insecticidal nets. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions. A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a 'push' intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a 'pull' intervention placing an odour-baited mosquito trap at a 5 m distance from a house; the combined 'push–pull' package; and the control where houses contained all elements but without active ingredients. Treatments were rotated through 12 houses in a randomized-block design. Outdoor biting was estimated using human landing catches, and indoor mosquito densities using light-traps. None of the interventions provided any protection from outdoor biting malaria vectors. The 'push' reduced indoor vector densities dominated by Anopheles funestus by around two thirds. The 'pull' device did not add any benefit. In the light of the high Anopheles arabiensis biting densities outdoors in the study location, the search for efficient outdoor protection and effective pull components needs to continue. [ABSTRACT FROM AUTHOR]

Background: Semi-field experiments with human landing catch (HLC) measure as the outcome are an important step in the development of novel vector control interventions against outdoor transmission of malaria since they provide good estimates of personal protection. However, it is often infeasible to determine whether the reduction in HLC counts is due to mosquito mortality or repellency, especially considering that spatial repellents based on volatile pyrethroids might induce both. Due to the vastly different impact of repellency and mortality on transmission, the community-level impact of spatial repellents can not be estimated from such semi-field experiments. Methods: We present a new stochastic model that is able to estimate for any product inhibiting outdoor biting, its repelling effect versus its killing and disarming (preventing host-seeking until the next night) effects, based only on time-stratified HLC data from controlled semi-field experiments. For parameter inference, a Bayesian hierarchical model is used to account for nightly variation of semi-field experimental conditions. We estimate the impact of the products on the vectorial capacity of the given Anopheles species using an existing mathematical model. With this methodology, we analysed data from recent semi-field studies in Kenya and Tanzania on the impact of transfluthrin-treated eave ribbons, the odour-baited Suna trap and their combination (push–pull system) on HLC of Anopheles arabiensis in the peridomestic area. Results: Complementing previous analyses of personal protection, we found that the transfluthrin-treated eave ribbons act mainly by killing or disarming mosquitoes. Depending on the actual ratio of disarming versus killing, the vectorial capacity of An. arabiensis is reduced by 41 to 96% at 70% coverage with the transfluthrin-treated eave ribbons and by 38 to 82% at the same coverage with the push–pull system, under the assumption of a similar impact on biting indoors compared to outdoors. Conclusions: The results of this analysis of semi-field data suggest that transfluthrin-treated eave ribbons are a promising tool against malaria transmission by An. arabiensis in the peridomestic area, since they provide both personal and community protection. Our modelling framework can estimate the community-level impact of any tool intervening during the mosquito host-seeking state using data from only semi-field experiments with time-stratified HLC. [ABSTRACT FROM AUTHOR]

Background: Larviciding against malaria vectors in Africa has been limited compared to indoor residual spraying and insecticide treated nets but is increasingly being considered by some countries as a complementary strategy. However, despite progress towards improved larvicides and new tools for mapping or treating mosquito-breeding sites, little is known about the optimal deployment strategies for larviciding in different transmission and seasonality settings. Methods: A malaria transmission model, OpenMalaria, was used to simulate varying larviciding strategies and their impact on host-seeking mosquito densities, entomological inoculation rate (EIR) and malaria prevalence. Variations in coverage, duration, frequency, and timing of larviciding were simulated for three transmission intensities and four transmission seasonality profiles. Malaria transmission was assumed to follow rainfall with a lag of one month. Theoretical sub-Saharan African settings with Anopheles gambiae as the dominant vector were chosen to explore impact. Relative reduction compared to no larviciding was predicted for each indicator during the simulated larviciding period. Results: Larviciding immediately reduced the predicted host-seeking mosquito densities and EIRs to a maximum that approached or exceeded the simulated coverage. Reduction in prevalence was delayed by approximately one month. The relative reduction in prevalence was up to four times higher at low than high transmission. Reducing larviciding frequency (i.e., from every 5 to 10 days) resulted in substantial loss in effectiveness (54, 45 and 53% loss of impact for host-seeking mosquito densities, EIR and prevalence, respectively). In seasonal settings the most effective timing of larviciding was during or at the beginning of the rainy season and least impactful during the dry season, assuming larviciding deployment for four months. Conclusion: The results highlight the critical role of deployment strategies on the impact of larviciding. Overall, larviciding would be more effective in settings with low and seasonal transmission, and at the beginning and during the peak densities of the target species populations. For maximum impact, implementers should consider the practical ranges of coverage, duration, frequency, and timing of larviciding in their respective contexts. More operational data and improved calibration would enable models to become a practical tool to support malaria control programmes in developing larviciding strategies that account for the diversity of contexts. [ABSTRACT FROM AUTHOR]

Malaria and some other tropical diseases are currently targeted for elimination and eventually eradication. Since resources are limited, prioritisation of countries or areas for elimination is often necessary. However, this prioritisation is frequently conducted in an ad hoc manner. Lower transmission areas are usually targeted for elimination first, but for some areas this necessitates long and potentially expensive surveillance programs while transmission is eliminated from neighbouring higher transmission areas. We use a mathematical model to compare the implications of prioritisation choices in reducing overall burden and costs. We show that when the duration of the elimination program is independent of the transmission potential, burden is always reduced most by targeting high transmission areas first, but to reduce costs the optimal ordering depends on the actual transmission levels. In general, when overall transmission potential is low and the surveillance cost per secondary case compared to the cost per imported case is low, targeting the higher transmission area for elimination first is favoured. [ABSTRACT FROM AUTHOR]

Background: Despite great achievements by insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, it is unlikely these tools will be sufficient to eliminate malaria transmission on their own in many settings today. Fortunately, field experiments indicate that there are many promising vector control interventions that can be used to complement ITNs and/or IRS by targeting a wide range of biological and environmental mosquito resources. The majority of these experiments were performed to test a single vector control intervention in isolation; however, there is growing evidence and consensus that effective vector control with the goal of malaria elimination will require a combination of interventions. Method and findings: We have developed a model of mosquito population dynamic to describe the mosquito life and feeding cycles and to optimize the impact of vector control intervention combinations at suppressing mosquito populations. The model simulations were performed for the main three malaria vectors in sub-Saharan Africa, Anopheles gambiae s.s, An. arabiensis and An. funestus. We considered areas having low, moderate and high malaria transmission, corresponding to entomological inoculation rates of 10, 50 and 100 infective bites per person per year, respectively. In all settings, we considered baseline ITN coverage of 50% or 80% in addition to a range of other vector control tools to interrupt malaria transmission. The model was used to sweep through parameters space to select the best optimal intervention packages. Sample model simulations indicate that, starting with ITNs at a coverage of 50% (An. gambiae s.s. and An. funestus) or 80% (An. arabiensis) and adding interventions that do not require human participation (e.g. larviciding at 80% coverage, endectocide treated cattle at 50% coverage and attractive toxic sugar baits at 50% coverage) may be sufficient to suppress all the three species to an extent required to achieve local malaria elimination. Conclusion: The Vector Control Optimization Model (VCOM) is a computational tool to predict the impact of combined vector control interventions at the mosquito population level in a range of eco-epidemiological settings. The model predicts specific combinations of vector control tools to achieve local malaria elimination in a range of eco-epidemiological settings and can assist researchers and program decision-makers on the design of experimental or operational research to test vector control interventions. A corresponding graphical user interface is available for national malaria control programs and other end users. [ABSTRACT FROM AUTHOR]

Background: Increasing coverage of malaria vector control interventions globally has led to significant reductions in disease burden. However due to its high recurrent cost, there is a need to determine if and when vector control can be safely scaled back after transmission has been reduced. Methods and findings: A mathematical model of Plasmodium falciparum malaria epidemiology was simulated to determine the impact of scaling back vector control on transmission and disease. A regression analysis of simulation results was conducted to derive predicted probabilities of resurgence, severity of resurgence and time to resurgence under various settings. Results indicate that, in the absence of secular changes in transmission, there are few scenarios where vector control can be removed without high expectation of resurgence. These, potentially safe, scenarios are characterized by low historic entomological inoculation rates, successful vector control programmes that achieve elimination or near elimination, and effective surveillance systems with high coverage and effective treatment of malaria cases. Conclusions: Programmes and funding agencies considering scaling back or withdrawing vector control from previously malaria endemic areas need to first carefully consider current receptivity and other available interventions in a risk assessment. Surveillance for resurgence needs to be continuously conducted over a long period of time in order to ensure a rapid response should vector control be withdrawn. [ABSTRACT FROM AUTHOR]

Background: Mass drug administration (MDA) has been proposed as an intervention to achieve local extinction of malaria. Although its effect on the reproduction number is short lived, extinction may subsequently occur in a small population due to stochastic fluctuations. This paper examines how the probability of stochastic extinction depends on population size, MDA coverage and the reproduction number under control, Rc. A simple compartmental model is developed which is used to compute the probability of extinction using probability generating functions. The expected time to extinction in small populations after MDA for various scenarios in this model is calculated analytically. The results indicate that mass drug administration (Firstly, Rc must be sustained at Rc < 1.2 to avoid the rapid re-establishment of infections in the population. Secondly, the MDA must produce effective cure rates of >95% to have a non-negligible probability of successful elimination. Stochastic fluctuations only significantly affect the probability of extinction in populations of about 1000 individuals or less. The expected time to extinction via stochastic fluctuation is less than 10 years only in populations less than about 150 individuals. Clustering of secondary infections and of MDA distribution both contribute positively to the potential probability of success, indicating that MDA would most effectively be administered at the household level. Conclusions: There are very limited circumstances in which MDA will lead to local malaria elimination with a substantial probability. [ABSTRACT FROM AUTHOR]

Background and methods: In areas where malaria transmission has been suppressed by vector control interventions many malaria control and elimination programmes are actively seeking new interventions to further reduce malaria prevalence, incidence and transmission. Malaria infection prevalence and incidence has been shown to cluster geographically, especially at lower transmission levels, and as such a reactive strategy is frequently used, by which index cases presenting to a passive surveillance system are used to target small areas for testing and treatment, reactive case detection (RCD), or focal drug administration (fDA). This study utilizes geo-located data from a census with parasitological testing with rapid diagnostic tests (RDTs) and treatment-seeking data collection conducted in southern Zambia to estimate the coverage of RCD or fDA in terms of the population and parasite reservoir as well as the operational requirements of such strategies, using a re-sampling algorithm developed exclusively for this purpose. This re-sampling algorithm allows for the specification of several parameters, such that different operational variants of these reactive strategies can be examined, including varying the search radius, screening for fever, or presumptive treatment (fDA). Results: Results indicate that RCD, fDA and active fever screening followed by RCD, even with search radii over several hundered meters will only yield limited coverage of the RDT positive parasite reservoir during a short period. Long-term use of these strategies may increase this proportion. Reactive strategies detect a higher proportion of the reservoir of infections than random searches, but this effect appears to be greater in areas of low, but not moderate malaria prevalence in southern Zambia. Discussion: Increases in the sensitivity of RDTs could also affect these results. The number of individuals and households that need to be searched increase rapidly, but approximately linearly with search radius. Conclusions: Reactive strategies in southern Zambia yield improved identification of the parasite reservoir when targeted to areas with prevalence less than 10%. The operational requirements of delivering reactive strategies routinely are likely to prevent their uptake until prevalence falls far below this level. [ABSTRACT FROM AUTHOR]

Along with the scaled-up distribution of long-lasting insecticidal nets for malaria control has become concern about insecticide resistance. A related concern regards the evolution of host-seeking periodicity from the nocturnal to the crepuscular periods of the day. Why we observe such shifts in some areas but not others and which methods could prove useful in managing such behavioral resistance remain open questions. We developed a foraging model to explore whether environmental conditions affect the evolution of behavioral resistance. We looked at the role of the abundance of blood hosts and nectar sources and investigated the potential of attractive toxic sugar baits for integrated control. Higher encounter rates with hosts and nectar sources allowed behaviorally resistant populations to persist at higher levels of bed net coverage. Whereas higher encounter rates with nectar increased the threshold where resistance emerged, higher encounter rates of hosts lowered this threshold. Adding sugar baits lowered the coverage level of bed nets required to eliminate the vector population. In certain environments, using lower bed net coverage levels together with toxic sugar baits may delay or prevent the evolution of behavioral resistance. Designing sustainable control strategies will depend on an understanding of vector behavior expressed in local environmental conditions. [ABSTRACT FROM AUTHOR]

Background: The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between the two diseases into account. Methodology/Principal Findings: We developed a general model of malaria and LF transmission and derived expressions for the basic reproductive number (R0) for each disease. Transmission of both diseases was most sensitive to vector mortality and biting rate. Simulating different levels of coverage of long lasting-insecticidal nets (LLINs) and larval control confirms the effectiveness of these interventions for the control of both diseases. When LF was maintained near the critical density of mosquitoes, minor levels of vector control (8% coverage of LLINs or treatment of 20% of larval sites) were sufficient to eliminate the disease. Malaria had a far greater R0 and required a 90% population coverage of LLINs in order to eliminate it. When the mosquito density was doubled, 36% and 58% coverage of LLINs and larval control, respectively, were required for LF elimination; and malaria elimination was possible with a combined coverage of 78% of LLINs and larval control. Conclusions/Significance: Despite the low level of vector control required to eliminate LF, simulations suggest that prevalence of LF will decrease at a slower rate than malaria, even at high levels of coverage. If representative of field situations, integrated management should take into account not only how malaria control can facilitate filariasis elimination, but strike a balance between the high levels of coverage of (multiple) interventions required for malaria with the long duration predicted to be required for filariasis elimination. Author Summary: Integrated vector management aims to optimize efficacy and make better use of available funds, including targeting multiple diseases, using one or more interventions. However, we have relatively poor understanding of the programmatic demands that arise when controlling two diseases. For instance, does the intensity, duration of deployment, or type of intervention most suitable for each disease overlap or clash? We developed a mathematical model to explore these issues for the example of the vector-borne diseases malaria and lymphatic filariasis. Since the causative agents of these diseases are transmitted by the same mosquito species in certain areas, there is clear potential for an integrated approach using long-lasting insecticidal nets (LLINs) or larval source management. We found that the transmission potential of both malaria and LF is most sensitive to changes in mosquito survivorship and the duration of the feeding cycle, supporting the usefulness of LLINs. In areas where both diseases occur, malaria elimination was predicted to require high levels of both LLINs and larval source management, whereas either intervention at a low intensity was sufficient to eliminate LF, if maintained for a longer period. This highlights that integrated control programs should be flexible and dynamic in order to accommodate these demands. [ABSTRACT FROM AUTHOR]

Introduction: Tools that allow for in silico optimization of available malaria control strategies can assist the decision-making process for prioritizing interventions. The OpenMalaria stochastic simulation modeling platform can be applied to simulate the impact of interventions singly and in combination as implemented in Rachuonyo South District, western Kenya, to support this goal. Methods: Combinations of malaria interventions were simulated using a previously-published, validated model of malaria epidemiology and control in the study area. An economic model of the costs of case management and malaria control interventions in Kenya was applied to simulation results and cost-effectiveness of each intervention combination compared to the corresponding simulated outputs of a scenario without interventions. Uncertainty was evaluated by varying health system and intervention delivery parameters. Results: The intervention strategy with the greatest simulated health impact employed long lasting insecticide treated net (LLIN) use by 80% of the population, 90% of households covered by indoor residual spraying (IRS) with deployment starting in April, and intermittent screen and treat (IST) of school children using Artemether lumefantrine (AL) with 80% coverage twice per term. However, the current malaria control strategy in the study area including LLIN use of 56% and IRS coverage of 70% was the most cost effective at reducing disability-adjusted life years (DALYs) over a five year period. Conclusions: All the simulated intervention combinations can be considered cost effective in the context of available resources for health in Kenya. Increasing coverage of vector control interventions has a larger simulated impact compared to adding IST to the current implementation strategy, suggesting that transmission in the study area is not at a level to warrant replacing vector control to a school-based screen and treat program. These results have the potential to assist malaria control program managers in the study area in adding new or changing implementation of current interventions. [ABSTRACT FROM AUTHOR]

Background: Eliminating malaria requires vector control interventions that dramatically reduce adult mosquito population densities and survival rates. Indoor applications of insecticidal nets and sprays are effective against an important minority of mosquito species that rely heavily upon human blood and habitations for survival. However, complementary approaches are needed to tackle a broader diversity of less human-specialized vectors by killing them at other resource targets. Methods: Impacts of strategies that target insecticides to humans or animals can be rationalized in terms of biological coverage of blood resources, quantified as proportional coverage of all blood resources mosquito vectors utilize. Here, this concept is adapted to enable impact prediction for diverse vector control strategies based on measurements of utilization rates for any definable, targetable resource subset, even if that overall resource is not quantifiable. Results: The usefulness of this approach is illustrated by deriving utilization rate estimates for various blood, resting site, and sugar resource subsets from existing entomological survey data. Reported impacts of insecticidal nets upon human-feeding vectors, and insecticide-treated livestock upon animal-feeding vectors, are approximately consistent with model predictions based on measured utilization rates for those human and animal blood resource subsets. Utilization rates for artificial sugar baits compare well with blood resources, and are consistent with observed impact when insecticide is added. While existing data was used to indirectly measure utilization rates for a variety of resting site subsets, by comparison with measured rates of blood resource utilization in the same settings, current techniques for capturing resting mosquitoes underestimate this quantity, and reliance upon complex models with numerous input parameters may limit the applicability of this approach. Conclusions: While blood and sugar consumption can be readily quantified using existing methods for detecting natural markers or artificial tracers, improved techniques for labelling mosquitoes, or other arthropod pathogen vectors, will be required to assess vector control measures which target them when they utilize non-nutritional resources such as resting, oviposition, and mating sites. [ABSTRACT FROM AUTHOR]

Background: Traps baited with synthetic human odors have been proposed as suitable technologies for controlling malaria and other mosquito-borne diseases. We investigated the potential benefits of such traps for preventing malaria transmission in Africa and the essential characteristics that they should possess so as to be effective. Methods and Principal Findings: An existing mathematical model was reformulated to distinguish availability of hosts for attack by mosquitoes from availability of blood per se. This adaptation allowed the effects of pseudo-hosts such as odor-baited mosquito traps, which do not yield blood but which can nonetheless be attacked by the mosquitoes, to be simulated considering communities consisting of users and non-users of insecticide-treated nets (ITNs), currently the primary malaria prevention method. We determined that malaria transmission declines as trap coverage (proportion of total availability of all hosts and pseudo hosts that traps constitute) increases. If the traps are more attractive than humans and are located in areas where mosquitoes are most abundant, 20-130 traps per 1000 people would be sufficient to match the impact of 50% community-wide ITN coverage. If such traps are used to complement ITNs, malaria transmission can be reduced by 99% or more in most scenarios representative of Africa. However, to match cost-effectiveness of ITNs, the traps delivery, operation and maintenance would have to cost a maximum of US$4.25 to 27.61 per unit per year. Conclusions and Significance: Odor-baited mosquito traps might potentially be effective and affordable tools for malaria control in Africa, particularly if they are used to complement, rather than replace, existing methods. We recommend that developers should focus on super-attractive baits and cheaper traps to enhance cost-effectiveness, and that the most appropriate way to deploy such technologies is through vertical delivery mechanisms. [ABSTRACT FROM AUTHOR]

This first sentence used to read "Larviciding against malaria vectors in Africa has been limited to indoor residual spraying and insecticide treated nets but is increasingly being considered by some countries as a complementary strategy". Correction to: Evaluation of different deployment strategies for larviciding to control malaria: a simulation study However, the sentence should read as "Larviciding against malaria vectors in Africa has been limited compared to indoor residual spraying and insecticide treated nets but is increasingly being considered by some countries as a complementary strategy.". [Extracted from the article]