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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]

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care. Author summary: Sleeping sickness is a parasitic disease present in parts of Central and West Africa that is fatal if left untreated. Current case management requires unpleasant procedures such as a lumbar puncture and intravenous drug administration, but has high compliance rates as the treatment is given by hospital staff to patients. In this study, we explore the impact of a new oral treatment on compliance rates for treatment using a mathematical model fitted to data on sleeping sickness cases and screening activities. We also look at the possibility of patients being more likely to seek and access treatment since the new treatment can be used without a lumbar puncture if the patient does not display clinically severe symptoms. We find that reduced compliance, especially from patients suffering from the first less severe stage of the disease, will lead to more sleeping sickness cases and delay elimination, but increases in the number of patients seeking treatment will likely counter effects of reduced compliance. [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]

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]

The gambiense form of sleeping sickness is a neglected tropical disease, which is presumed to be anthroponotic. However, the parasite persists in human populations at levels of considerable rarity and as such the existence of animal reservoirs has been posited. Clarifying the impact of animal host reservoirs on the feasibility of interrupting sleeping sickness transmission through interventions is a matter of urgency. We developed a mathematical model allowing for heterogeneous exposure of humans to tsetse, with animal populations that differed in their ability to transmit infections, to investigate the effectiveness of two established techniques, screening and treatment of at-risk populations, and vector control. Importantly, under both assumptions, an integrated approach of human screening and vector control was supported in high transmission areas. However, increasing the intensity of vector control was more likely to eliminate transmission, while increasing the intensity of human screening reduced the time to elimination. Non-human animal hosts played important, but different roles in HAT transmission, depending on whether or not they contributed as reservoirs. If they did not serve as reservoirs, sensitivity analyses suggested their attractiveness may instead function as a sink for tsetse bites. These outcomes highlight the importance of understanding the ecological and environmental context of sleeping sickness in optimizing integrated interventions, particularly for moderate and low transmission intensity settings. [ABSTRACT FROM AUTHOR]

Background: The ability of mosquitoes to evade fatal exposure to insecticidal nets and sprays represents the primary obstacle to eliminating malaria. However, it remains unclear which behaviours are most important for buffering mosquito and parasite populations against vector control. Methods: Simulated life histories were used to compare the impact of alternative feeding behaviour strategies upon overall lifetime feeding success, and upon temporal distributions of successful feeds and biting rates experienced by unprotected humans, in the presence and absence of insecticidal nets. Strictly nocturnal preferred feeding times were contrasted with 1) a wider preference window extending to dawn and dusk, and 2) crepuscular preferences wherein foraging is suppressed when humans sleep and can use nets but is maximal immediately before and after. Simulations with diversion and mortality parameters typical of endophagic, endophilic African vectors, such as Anopheles gambiae and Anopheles funestus, were compared with those for endophagic but exophilic species, such as Anopheles arabiensis, that also enter houses but leave earlier before lethal exposure to insecticide-treated surfaces occurs. Results: Insecticidal nets were predicted to redistribute successful feeding events to dawn and dusk where these were included in the profile of innately preferred feeding times. However, predicted distributions of biting unprotected humans were unaffected because extended host-seeking activity was redistributed to innately preferred feeding times. Recently observed alterations of biting activity distributions therefore reflect processes not captured in this model, such as evolutionary selection of heritably modified feeding time preferences or phenotypically plastic expression of feeding time preference caused by associative learning. Surprisingly, endophagy combined with exophily, among mosquitoes that enter houses but then feed and/or rest briefly before rapidly exiting, consistently attenuated predicted insecticide impact more than any feeding time preference trait. Conclusions: Regardless of underlying cause, recent redistributions of host-biting activity to dawn and dusk necessitate new outdoor control strategies. However, persistently indoor-feeding vectors, that evade intradomiciliary insecticide exposure, are at least equally important. Fortunately, recent evaluations of occupied houses or odour-baited stations, with baffled entrances that retain An. arabiensis within insecticide-treated structures, illustrate how endophagic but exophilic vectors may be more effectively tackled using existing insecticides. [ABSTRACT FROM AUTHOR]

Vector control interventions have resulted in considerable reductions in malaria morbidity and mortality. When universal coverage cannot be achieved for financial or logistical reasons, the spatial arrangement of vector control is potentially important for optimizing benefits. This study investigated the effect of spatial clustering of vector control interventions on reducing the population of biting mosquitoes. A discrete-space continuous-time mathematical model of mosquito population dynamics and dispersal was extended to incorporate vector control interventions of insecticide treated bednets (ITNs), Indoor residual Spraying (IRS), and larviciding. Simulations were run at varying levels of coverage and degree of spatial clustering. At medium to high coverage levels of each of the interventions or in combination was more effective to spatially spread these interventions than to cluster them. Suggesting that when financial resources are limited, unclustered distribution of these interventions is more effective. Although it is often stated that locally high coverage is needed to achieve a community effect of ITNs or IRS, our results suggest that if the coverage of ITNs or IRS are insufficient to achieve universal coverage, and there is no targeting of high risk areas, the overall effects on mosquito densities are much greater if they are distributed in an unclustered way, rather than clustered in specific localities. Also, given that interventions are often delivered preferentially to accessible areas, and are therefore clustered, our model results show this may be inefficient. This study provides evidence that the effectiveness of an intervention can be highly dependent on its spatial distribution. Vector control plans should consider the spatial arrangement of any intervention package to ensure effectiveness is maximized. [ABSTRACT FROM AUTHOR]

We present two ordinary differential equation models for Rift Valley fever (RVF) transmission in cattle and mosquitoes. We extend existing models for vector-borne diseases to include an asymptomatic host class and vertical transmission in vectors. We define the basic reproductive number,0, and analyse the existence and stability of equilibrium points. We compute sensitivity indices of0and a reactivity index (that measures epidemicity) to parameters for baseline wet and dry season values.0is most sensitive to the mosquito biting and death rates. The reactivity index is most sensitive to the mosquito biting rate and the infectivity of hosts to vectors. Numerical simulations show that even with low equilibrium prevalence, increases in mosquito densities through higher rainfall, in the presence of vertical transmission, can result in large epidemics. This suggests that vertical transmission is an important factor in the size and persistence of RVF epidemics. [ABSTRACT FROM AUTHOR]

Abstract: Subsistence livestock herding is an important component of livestock production in Mongolia. However, pasture degradation, extreme weather, desertification, livestock overpopulation, infectious diseases and limited government support increasingly threaten this livelihood. To better assess these afflictions, understanding the population dynamics of livestock is critical. Towards this goal, we developed a model of Mongolian livestock populations. Using the Leslie–Gower difference equation competition model, a discrete analog of the continuous Lotka–Volterra 2-species model, Mongolian livestock population dynamics were simulated in MATLAB. The model encompasses four species and is stratified by age and sex. Calibration of parameters is accomplished using official population data from 1970 to 2010; a turbulent time period that includes the socialist to capitalist market transition and two growth periods both followed by two dzuds (severe winter storms). Herders were surveyed and herd structures were sampled for parameter and model initial value estimation. The current model simulates the Töv aimag (province) goat, sheep, cattle and horse populations. However, with more data collection, the intention would be to simulate all species populations in any aimag or soum (province subdivision). A ten-year simulation of future livestock populations predicts a more than two-fold increase in goat and sheep populations, a slight increase in cattle populations and a slight decline in horse populations. Preliminary validation with 2011 population data shows accurate estimation. Furthermore, a stable future livestock population was attained with the implementation of more than double the current culling rate. The model can be integrated in infectious disease transmission modeling, used as a tool for predicting the economic potential and support requirements of the livestock sector and used to illustrate the urgency of fostering sustainable management of livestock populations in Mongolia. This story of Mongolian pastoral life presents an excellent opportunity to study a social-ecological system as well as to contribute in creating a sustainable, healthy and efficient Mongolian livelihood. [Copyright &y& Elsevier]

Background: The effectiveness of long-lasting, insecticidal nets (LLINs) in preventing malaria is threatened by the changing biting behaviour of mosquitoes, from nocturnal and endophagic to crepuscular and exophagic, and by their increasing resistance to insecticides. Methods: Using epidemiological stochastic simulation models, we studied the impact of a mass LLIN distribution on Plasmodium falciparum malaria. Specifically, we looked at impact in terms of episodes prevented during the effective life of the batch and in terms of net health benefits (NHB) expressed in disability adjusted life years (DALYs) averted, depending on biting behaviour, resistance (as measured in experimental hut studies), and on pre-intervention transmission levels. Results: Results were very sensitive to assumptions about the probabilistic nature of host searching behaviour. With a shift towards crepuscular biting, under the assumption that individual mosquitoes repeat their behaviour each gonotrophic cycle, LLIN effectiveness was far less than when individual mosquitoes were assumed to vary their behaviour between gonotrophic cycles. LLIN effectiveness was equally sensitive to variations in host-searching behaviour (if repeated) and to variations in resistance. LLIN effectiveness was most sensitive to pre-intervention transmission level, with LLINs being least effective at both very low and very high transmission levels, and most effective at around four infectious bites per adult per year. A single LLIN distribution round remained cost effective, except in transmission settings with a pre-intervention inoculation rate of over 128 bites per year and with resistant mosquitoes that displayed a high proportion (over 40%) of determined crepuscular host searching, where some model variants showed negative NHB. Conclusions: Shifts towards crepuscular host searching behaviour can be as important in reducing LLIN effectiveness and cost effectiveness as resistance to pyrethroids. As resistance to insecticides is likely to slow down the development of behavioural resistance and vice versa, the two types of resistance are unlikely to occur within the same mosquito population. LLINs are likely cost effective interventions against malaria, even in areas with strong resistance to pyrethroids or where a large proportion of host-mosquito contact occurs during times when LLIN users are not under their nets. [ABSTRACT FROM AUTHOR]

Over the past decade the use of long-lasting insecticidal nets (LLINs), in combination with improved drug therapies, indoor residual spraying (IRS), and better health infrastructure, has helped reduce malaria in many African countries for the first time in a generation. However, insecticide resistance in the vector is an evolving threat to these gains. We review emerging and historical data on behavioral resistance in response to LLINs and IRS. Overall the current literature suggests behavioral and species changes may be emerging, but the data are sparse and, at times unconvincing. However, preliminary modeling has demonstrated that behavioral resistance could have significant impacts on the effectiveness of malaria control. We propose seven recommendations to improve understanding of resistance in malaria vectors. Determining the public health impact of physiological and behavioral insecticide resistance is an urgent priority if we are to maintain the significant gains made in reducing malaria morbidity and mortality. [ABSTRACT FROM AUTHOR]

We describe and analyze a periodically-forced difference equation model for malaria in mosquitoes that captures the effects of seasonality and allows the mosquitoes to feed on a heterogeneous population of hosts. We numerically show the existence of a unique globally asymptotically stable periodic orbit and calculate periodic orbits of field-measurable quantities that measure malaria transmission. We integrate this model with an individual-based stochastic simulation model for malaria in humans to compare the effects of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) in reducing malaria transmission, prevalence, and incidence. We show that ITNs are more effective than IRS in reducing transmission and prevalence though IRS would achieve its maximal effects within 2 years while ITNs would need two mass distribution campaigns over several years to do so. Furthermore, the combination of both interventions is more effective than either intervention alone. However, although these interventions reduce transmission and prevalence, they can lead to increased clinical malaria; and all three malaria indicators return to preintervention levels within 3 years after the interventions are withdrawn. [ABSTRACT FROM AUTHOR]

Background: High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as "very zoophagic,'' meaning they feed occasionally (<10% of blood meals) upon humans, so personal protection interventions have negligible impact upon their survival. Methods and Findings: We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with and without assuming reduced human infectivity, respectively) impacts of personal protection measures upon transmission. (3) Illustrate how appreciable indirect communallevel protection for non-users can be accrued through direct personal protection of users. (4) Suggest the coverage and efficacy thresholds required to attain epidemiological impact. The findings suggest that immediate, indirect, communitywide protection of users and non-users alike may linearly relate to the efficacy of a user's direct personal protection, regardless of whether that is achieved by killing or repelling mosquitoes. High protective coverage and efficacy ($80%) are important to achieve epidemiologically meaningful impact. Non-users are indirectly protected because the two most common species of human malaria are strict anthroponoses. Therefore, the small proportion of mosquitoes that are killed or diverted while attacking humans can represent a large proportion of those actually transmitting malaria. Conclusions: Simplified models of malaria transmission by very zoophagic vectors may be used by control practitioners to predict intervention impact interventions using three field-measurable parameters; the proportion of human exposure to mosquitoes occurring when an intervention can be practically used, its protective efficacy when used, and the proportion of people using it. [ABSTRACT FROM AUTHOR]

A quantitative framework is used to explore the potential applications and probable effects of sexual stage or mosquito stage transmission blocking vaccines (TBVs) against malaria. The combination of TBVs with biocides or other malaria vaccines will increase chances of interrupting transmission, whereas the value of TBVs for morbidity control will be limited. Vaccine combination will also protect against selection of insensitive parasites. Simulations indicate that TBVs will reduce risks of reestablishment of transmission when vector control is withdrawn. Simple mathematical analysis shows that efficacy and coverage are equally important, implying that a vaccine that requires a small number of doses (ideally one) is preferable to one that is difficult to deliver, even if this entails accepting a lower efficacy. [Copyright &y& Elsevier]

We perform sensitivity analyses on a mathematical model of malaria transmission to determine the relative importance of model parameters to disease transmission and prevalence. We compile two sets of baseline parameter values: one for areas of high transmission and one for low transmission. We compute sensitivity indices of the reproductive number (which measures initial disease transmission) and the endemic equilibrium point (which measures disease prevalence) to the parameters at the baseline values. We find that in areas of low transmission, the reproductive number and the equilibrium proportion of infectious humans are most sensitive to the mosquito biting rate. In areas of high transmission, the reproductive number is again most sensitive to the mosquito biting rate, but the equilibrium proportion of infectious humans is most sensitive to the human recovery rate. This suggests strategies that target the mosquito biting rate (such as the use of insecticide-treated bed nets and indoor residual spraying) and those that target the human recovery rate (such as the prompt diagnosis and treatment of infectious individuals) can be successful in controlling malaria. [ABSTRACT FROM AUTHOR]

We describe and develop a difference equation model for the dynamics of malaria in a mosquito population feeding on, infecting and getting infected from a heterogeneous population of hosts. Using the force of infection from different classes of humans to mosquitoes as parameters, we evaluate a number of entomological parameters, indicating malaria transmission levels, which can be compared to field data. By assigning different types of vector control interventions to different classes of humans and by evaluating the corresponding levels of malaria transmission, we can compare the effectiveness of these interventions. We show a numerical example of the effects of increasing coverage of insecticide-treated bed nets in a human population where the predominant malaria vector is Anopheles gambiae. [ABSTRACT FROM AUTHOR]

We present an ordinary differential equation mathematical model for the spread of malaria in human and mosquito populations. Susceptible humans can be infected when they are bitten by an infectious mosquito. They then progress through the exposed, infectious, and recovered classes, before reentering the susceptible class. Susceptible mosquitoes can become infected when they bite infectious or recovered humans, and once infected they move through the exposed and infectious classes. Both species follow a logistic population model, with humans having immigration and disease-induced death. We define a reproductive number, R0, for the number of secondary cases that one infected individual will cause through the duration of the infectious period. We find that the disease-free equilibrium is locally asymptotically stable when R0 < 1 and unstable when R0 > 1. We prove the existence of at least one endemic equilibrium point for all R0 > 1. In the absence of disease-induced death, we prove that the transcritical bifurcation at R0 = 1 is supercritical (forward). Numerical simulations show that for larger values of the disease-induced death rate, a subcritical (backward) bifurcation is possible at R0 = 1. [ABSTRACT FROM AUTHOR]

Cambodia’s goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence. [ABSTRACT FROM AUTHOR]

Entomological evaluations of vector control tools often use human landing catches (HLCs) as a standard measure of a direct human-vector contact. However, some tools have additional characteristics, such as mortality, and HLCS are not sensitive for measuring other effects beyond landing inhibition. Therefore, additional measures may need to be considered when evaluating these tools for public health use. This study has two main aims (1) the evaluate the accuracy of HLCs as a proxy for feeding and (2) to compare the predicted reduction in vectorial capacity when we do and do not consider these additional characteristics. To achieve this, we analyse previously published semi-field data from an experiment which used HLCs and another where mosquitoes were allowed to feed in the presence of different dosages of the volatile pyrethroid spatial repellent, transfluthrin. We compare results for two mathematical models: one which only considers the reduction in feeding effect and one which also considers mortality before and after feeding (using data gathered by the aspiration of mosquitoes after the semi-field feeding/landing period and 24 h survival monitoring). These Bayesian hierarchical models are parameterised using Bayesian inference. We observe that, for susceptible mosquitoes, reduction in landing is underestimated by HLCs. For knockdown resistant mosquitoes the relationship is less clear; with HLCs sometimes appearing to overestimate this characteristic. We find HLCs tend to under-predict the relative reduction in vectorial capacity in susceptible mosquitoes while over-predicting this impact in knockdown-resistant mosquitoes. Models without secondary effects have lower predicted relative reductions in vectorial capacities. Overall, this study highlights the importance of considering additional characteristics to reduction in biting of volatile pyrethroid spatial repellents. We recommend that these are considered when evaluating novel vector control tools. [ABSTRACT FROM AUTHOR]

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021–2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets. [ABSTRACT FROM AUTHOR]

Background: Reactive case detection (RCD) is an integral part of many malaria control and elimination programmes and can be conceived of as a way of gradually decreasing transmission. However, it is unclear under what circumstances RCD may have a substantial impact on prevalence, how likely it is to lead to local elimination, or how effective it needs to be to prevent reintroduction after transmission has been interrupted. Methods: Analyses and simulations of a discrete time compartmental susceptible-infectious-susceptible (SIS) model were used to understand the mechanisms of how RCD changes transmission dynamics and estimate the impact of RCD programmes in a range of settings with varying patterns of transmission potential and programme characteristics. Prevalence survey data from recent studies in Zambia were used to capture the effects of spatial clustering of patent infections. Results: RCD proved most effective at low prevalence. Increasing the number of index cases followed was more important than increasing the number of neighbours tested per index case. Elimination was achieved only in simulations of situations with very low transmission intensity and following many index cases. However, RCD appears to be helpful in maintaining the disease-free state after achieving malaria elimination (through other interventions). Conclusion: RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low, and improving the coverage of RCD has little effect on this range. In other settings, it is likely to reduce disease burden. RCD may also help maintain the disease-free state in the face of imported infections. Prevalence survey data can be used to estimate a targeting ratio (the ratio of prevalence found through RCD to that in the general population) which is an important determinant of the effect of RCD. [ABSTRACT FROM AUTHOR]

Background: As areas move closer to malaria elimination, a combination of limited resources and increasing heterogeneity in case distribution and transmission favour a shift to targeted reactive interventions. Reactive case detection (RCD), the following up of additional individuals surrounding an index case, has the potential to target transmission pockets and identify asymptomatic cases in them. Current RCD implementation strategies vary, and it is unclear which are most effective in achieving elimination. Methods: OpenMalaria, an established individual-based stochastic model, was used to simulate RCD in a Zambia-like setting. The capacity to follow up index cases, the search radius, the initial transmission and the case management coverage were varied. Suitable settings were identified and probabilities of elimination and time to elimination estimated. The value of routinely collected prevalence and incidence data for predicting the success of RCD was assessed. Results: The results indicate that RCD with the aim of transmission interruption is only appropriate in settings where initial transmission is very low (annual entomological inoculation rate (EIR) 1–2 or prevalence approx. < 7–19% depending on case management levels). Every index case needs to be followed up, up to a maximum case-incidence threshold which defines the suitability threshold of settings for elimination using RCD. Increasing the search radius around index cases is always beneficial. Conclusions: RCD is highly resource intensive, requiring testing and treating of 400–500 people every week for 5–10 years for a reasonable chance of elimination in a Zambia-like setting. [ABSTRACT FROM AUTHOR]

Opisthorchis viverrini is a parasitic liver fluke contracted by consumption of raw fish, which affects over 10 million people in Southeast Asia despite sustained control efforts. Chronic infections are a risk factor for the often fatal bile duct cancer, cholangiocarcinoma. Previous modeling predicted rapid elimination of O. viverrini following yearly mass drug administration (MDA) campaigns. However, field data collected in affected populations shows persistence of infection, including heavy worm burden, after many years of repeated interventions. A plausible explanation for this observation is systematic adherence of individuals in health campaigns, such as MDA and education, with some individuals consistently missing treatment. We developed an agent-based model of O. viverrini which allows us to introduce various heterogeneities including systematic adherence to MDA and education campaigns at the individual level. We validate the agent-based model by comparing it to a previously published population-based model. We estimate the degree of systematic adherence to MDA and education campaigns indirectly, using epidemiological data collected in Lao PDR before and after 5 years of repeated MDA, education and sanitation improvement campaigns. We predict the impact of interventions deployed singly and in combination, with and without the estimated systematic adherence. We show how systematic adherence can substantially increase the time required to achieve reductions in worm burden. However, we predict that yearly MDA campaigns alone can result in a strong reduction of moderate and heavy worm burden, even under systematic adherence. We predict latrines and education campaigns to be particularly important for the reduction in overall prevalence, and therefore, ultimately, elimination. Our findings show how systematic adherence can explain the observed persistence of worm burden; while emphasizing the benefit of interventions for the entire population, even under systematic adherence. At the same time, the results highlight the substantial opportunity to further reduce worm burden if patterns of systematic adherence can be overcome. Author summary: Opisthorchis viverrini is a liver parasite contracted by consumption of raw fish which affects over 10 million people in Southeast Asia despite sustained control efforts, with heavy infections being a major risk factor for often fatal bile duct cancer. Efforts to reduce the worm burden in populations include education of individuals on the safe consumption of fish meals, improvement of sanitation to interrupt the parasitic life cycle and mass drug administration campaigns, where ideally all targeted individuals of a population receive a drug against the parasite without a prior test of whether they are infected. We present a new agent-based mathematical model of Opisthorchis viverrini transmission and control. This model allows us to include systematic adherence to interventions, which describes the pattern of some individuals consistently being missed by interventions aimed at an entire (sub-)population. Our findings show how systematic adherence can explain the observed persistence of worm burden, but how interventions can be greatly beneficial even for individuals that systematically miss treatment. At the same time, we show the substantial opportunity to further reduce worm burden if patterns of systematic adherence can be overcome. [ABSTRACT FROM AUTHOR]

Background: A clear understanding of mosquito biology is fundamental to the control efforts of mosquito-borne diseases such as malaria. Mosquito mark-release-recapture (MMRR) experiments are a popular method of measuring the survival and dispersal of disease vectors; however, examples with African malaria vectors are limited. Ethical and technical difficulties involved in carrying out MMRR studies may have held back research in this area and, therefore, a device that marks mosquitoes as they emerge from breeding sites was developed and evaluated to overcome the problems of MMRR. Methods: A modified self-marking unit that marks mosquitoes with fluorescent pigment as they emerge from their breeding site was developed based on a previous design for Culex mosquitoes. The self-marking unit was first evaluated under semi-field conditions with laboratory-reared Anopheles arabiensis to determine the marking success and impact on mosquito survival. Subsequently, a field evaluation of MMRR was conducted in Yombo village, Tanzania, to examine the feasibility of the system. Results: During the semi-field evaluation the self-marking units successfully marked 86% of emerging mosquitoes and there was no effect of fluorescent marker on mosquito survival. The unit successfully marked wild male and female Anopheles gambiae sensu lato (s.l.) in sufficiently large numbers to justify its use in MMRR studies. The estimated daily survival probability of An. gambiae s.l. was 0.87 (95% CI 0.69–1.10) and mean dispersal distance was 579 m (95% CI 521–636 m). Conclusions: This study demonstrates the successful use of a self-marking device in an MMRR study with African malaria vectors. This method may be useful in investigating population structure and dispersal of mosquitoes for deployment and evaluation of future vector control tools, such as gene drive, and to better parameterize mathematical models. [ABSTRACT FROM AUTHOR]

Free-roaming domestic dogs (FRDD), as vectors of zoonotic diseases, are of high relevance for public health. Understanding roaming patterns of dogs can help to design disease control programs and disease transmission simulation models. Studies on GPS tracking of dogs report stark differences in recording periods. So far, there is no accepted number of days required to capture a representative home range (HR) of FRDD. The objective of this study was to evaluate changes in HR size and shape over time of FRDD living in Chad, Guatemala, Indonesia and Uganda and identify the period required to capture stable HR values. Dogs were collared with GPS units, leading to a total of 46 datasets with, at least, 19 recorded days. For each animal and recorded day, HR sizes were estimated using the Biased Random Bridge method and percentages of daily change in size and shape calculated and taken as metrics. The analysis revealed that the required number of days differed substantially between individuals, isopleths, and countries, with the extended HR (95% isopleth value) requiring a longer recording period. To reach a stable HR size and shape values for 75% of the dogs, 26 and 21 days, respectively, were sufficient. However, certain dogs required more extended observational periods. [ABSTRACT FROM AUTHOR]

We consider a Darwinian (evolutionary game theoretic) version of a standard susceptible-infectious SI model in which the resistance of the disease causing pathogen to a treatment that prevents death to infected individuals is subject to evolutionary adaptation. We determine the existence and stability of all equilibria, both disease-free and endemic, and use the results to determine conditions under which the treatment will succeed or fail. Of particular interest are conditions under which a successful treatment in the absence of resistance adaptation (i.e. one that leads to a stable disease-free equilibrium) will succeed or fail when pathogen resistance is adaptive. These conditions are determined by the relative breadths of treatment effectiveness and infection transmission rate distributions as functions of pathogen resistance. [ABSTRACT FROM AUTHOR]

An abstract of the article "Does mosquito mortality in WHO insecticide susceptibility tests relate to mosquito mortality in LLIN experimental hut studies?," by Olivier J. T. Briët, Nakul Chitnis, and Melissa Penny is presented.

An abstract of the article "Modeling the effects of vector control interventions in reducing malaria transmission, morbidity and mortality" that was presented at a conference titled "From Parasite to Prevention: Advances in the understanding of malaria" held in Edinburgh, Great Britain on October 20-22, 2010, is presented.

Background: Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. Methods: A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission. Results: A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively. Conclusion: Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting. [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]

An abstract of the article "Modelling the requirements and benefits of mosquito control interventions in the presence of mosquito dispersal," by Angelina M Lutambi, Nakul Chitnis, Tom Smith, and Melissa Penny is presented.

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]

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. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Testing and treatment for malaria elimination: a systematic review" published in the Malaria Journal. The authors have identified two errors in the Results section and one clarification in the caption of Figure 4. The first error was due to an inconsistency between the updated figure and the accompanying text, while the second error occurred during the transfer of information between documents. The clarification was made to prevent misinterpretation of the relative ratios presented in Figure 4. The corrected text and table have been provided in the notice. The authors apologize for any inconvenience caused. [Extracted from the article]

Background: Substantial research is underway to develop next-generation interventions that address current malaria control challenges. As there is limited testing in their early development, it is difficult to predefine intervention properties such as efficacy that achieve target health goals, and therefore challenging to prioritize selection of novel candidate interventions. Here, we present a quantitative approach to guide intervention development using mathematical models of malaria dynamics coupled with machine learning. Our analysis identifies requirements of efficacy, coverage, and duration of effect for five novel malaria interventions to achieve targeted reductions in malaria prevalence. Methods: A mathematical model of malaria transmission dynamics is used to simulate deployment and predict potential impact of new malaria interventions by considering operational, health-system, population, and disease characteristics. Our method relies on consultation with product development stakeholders to define the putative space of novel intervention specifications. We couple the disease model with machine learning to search this multi-dimensional space and efficiently identify optimal intervention properties that achieve specified health goals. Results: We apply our approach to five malaria interventions under development. Aiming for malaria prevalence reduction, we identify and quantify key determinants of intervention impact along with their minimal properties required to achieve the desired health goals. While coverage is generally identified as the largest driver of impact, higher efficacy, longer protection duration or multiple deployments per year are needed to increase prevalence reduction. We show that interventions on multiple parasite or vector targets, as well as combinations the new interventions with drug treatment, lead to significant burden reductions and lower efficacy or duration requirements. Conclusions: Our approach uses disease dynamic models and machine learning to support decision-making and resource investment, facilitating development of new malaria interventions. By evaluating the intervention capabilities in relation to the targeted health goal, our analysis allows prioritization of interventions and of their specifications from an early stage in development, and subsequent investments to be channeled cost-effectively towards impact maximization. This study highlights the role of mathematical models to support intervention development. Although we focus on five malaria interventions, the analysis is generalizable to other new malaria interventions. [ABSTRACT FROM AUTHOR]

Evaluating the effectiveness of malaria control interventions on the basis of their impact on transmission as well as impact on morbidity and mortality is becoming increasingly important as countries consider pre-elimination and elimination as well as disease control. Data on prevalence and transmission are traditionally obtained through resource-intensive epidemiological and entomological surveys that become difficult as transmission decreases. This work employs mathematical modeling to examine the relationships between malaria indicators allowing more easily measured data, such as routine health systems data on case incidence, to be translated into measures of transmission and other malaria indicators. Simulations of scenarios with different levels of malaria transmission, patterns of seasonality and access to treatment were run with an ensemble of models of malaria epidemiology and within-host dynamics, as part of the OpenMalaria modeling platform. For a given seasonality profile, regression analysis mapped simulation results of malaria indicators, such as annual average entomological inoculation rate, prevalence, incidence of uncomplicated and severe episodes, and mortality, to an expected range of values of any of the other indicators. Results were validated by comparing simulated relationships between indicators with previously published data on these same indicators as observed in malaria endemic areas. These results allow for direct comparisons of malaria transmission intensity estimates made using data collected with different methods on different indicators. They also address key concerns with traditional methods of quantifying transmission in areas of differing transmission intensity and sparse data. Although seasonality of transmission is often ignored in data compilations, the models suggest it can be critically important in determining the relationship between transmission and disease. Application of these models could help public health officials detect changes of disease dynamics in a population and plan and assess the impact of malaria control interventions. [ABSTRACT FROM AUTHOR]

Highlights: [•] Accurate measures of transmission are necessary for malaria elimination. [•] Different settings are conducive to different measures of transmission. [•] Mathematical models provide a means to translate between different measures of transmission and disease burden. [•] The effect of seasonality on the relationship between malaria measures is crucial. [ABSTRACT FROM AUTHOR]

Background: The 'overall insecticidal effect' is a key measure used to evaluate public health pesticides for indoor use in experimental hut trials. It depends on the proportion of mosquitoes that are killed out of those that enter the treated hut, intrinsic mortality in the control hut, and the ratio of mosquitoes entering the treatment hut to those entering the control hut. This paper critically examines the way the effect is defined, and discusses how it can be used to infer effectiveness of intervention programmes. Findings: The overall insecticidal effect, as defined by the World Health Organization in 2006, can be negative when deterrence from entering the treated hut is high, even if all mosquitoes that enter are killed, wrongly suggesting that the insecticide enhances mosquito survival. Also in the absence of deterrence, even if the insecticide kills all mosquitoes in the treatment hut, the insecticidal effect is less than 100%, unless intrinsic mortality is nil. A proposed alternative definition for the measurement of the overall insecticidal effect has the desirable range of 0 to 1 (100%), provided mortality among non-repelled mosquitoes in the treated hut is less than the corresponding mortality in the control hut. This definition can be built upon to formulate the coverage-dependent insecticidal effectiveness of an intervention programme. Coverage-dependent population protection against feeding can be formulated similarly. Conclusions: This paper shows that the 2006 recommended quantity for measuring the overall insecticidal effect is problematic, and proposes an alternative quantity with more desirable properties. [ABSTRACT FROM AUTHOR]

A difference equation model, called that Leslie/Gower model, played a key historical role in laboratory, experiments that helped establish the ‘competitive exclusion principle’ in ecology. We show that this model has the mine dynamic scenarios as the famous Lotka/Volterra (differential equation) competition model. It is less well known that some anomalous results from the experiments seem to contradict the exclusion principle and Lotka/Volterra dynamics. We give an example of a competition model that has non-Lotka/Volterra dynamics that are consistent with the anomalous case. [ABSTRACT FROM AUTHOR]

Background: Efforts to improve the impact of long-lasting insecticidal nets (LLINs) should be informed by understanding of the causes of decay in effect. Holes in LLINs have been estimated to account for 7–11% of loss in effect on vectorial capacity for Plasmodium falciparum malaria in an analysis of repeated cross-sectional surveys of LLINs in Kenya. This does not account for the effect of holes as a cause of net attrition or non-use, which cannot be measured using only cross-sectional data. There is a need for estimates of how much these indirect effects of physical damage on use and attrition contribute to decay in effectiveness of LLINs. Methods: Use, physical integrity, and survival were assessed in a cohort of 4514 LLINs followed for up to 4 years in Kenya. Flow diagrams were used to illustrate how the status of nets, in terms of categories of use, physical integrity, and attrition, changed between surveys carried out at 6-month intervals. A compartment model defined in terms of ordinary differential equations (ODEs) was used to estimate the transition rates between the categories. Effects of physical damage to LLINs on use and attrition were quantified by simulating counterfactuals in which there was no damage. Results: Allowing for the direct effect of holes, the effect on use, and the effect on attrition, 18% of the impact on vectorial capacity was estimated to be lost because of damage. The estimated median lifetime of the LLINs was 2.9 years, but this was extended to 5.7 years in the counterfactual without physical damage. Nets that were in use were more likely to be in a damaged state than unused nets but use made little direct difference to LLIN lifetimes. Damage was reported as the reason for attrition for almost half of attrited nets, but the model estimated that almost all attrited nets had suffered some damage before attrition. Conclusions: Full quantification of the effects of damage will require measurement of the supply of new nets and of household stocks of unused nets, and also of their impacts on both net use and retention. The timing of mass distribution campaigns is less important than ensuring sufficient supply. In the Kenyan setting, nets acquired damage rapidly once use began and the damage led to rapid attrition. Increasing the robustness of nets could substantially increase their lifetime and impact but the impact of LLIN programmes on malaria transmission is ultimately limited by levels of use. Longitudinal analyses of net integrity data from different settings are needed to determine the importance of physical damage to nets as a driver of attrition and non-use, and the importance of frequent use as a cause of physical damage in different contexts. [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]

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]

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 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]