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Mosquitoes are important vectors for pathogens that infect humans and other vertebrate animals. Some aspects of adult mosquito behavior and mosquito ecology play an important role in determining the capacity of vector populations to transmit pathogens. Here, we re-examine factors affecting the transmission of pathogens by mosquitoes using a new approach. Unlike most previous models, this framework considers the behavioral states and state transitions of adult mosquitoes through a sequence of activity bouts. We developed a new framework for individual-based simulation models called MBITES (Mosquito Bout-based and Individual-based Transmission Ecology Simulator). In MBITES, it is possible to build models that simulate the behavior and ecology of adult mosquitoes in exquisite detail on complex resource landscapes generated by spatial point processes. We also developed an ordinary differential equation model which is the Kolmogorov forward equations for models developed in MBITES under a specific set of simplifying assumptions. While mosquito infection and pathogen development are one possible part of a mosquito's state, that is not our main focus. Using extensive simulation using some models developed in MBITES, we show that vectorial capacity can be understood as an emergent property of simple behavioral algorithms interacting with complex resource landscapes, and that relative density or sparsity of resources and the need to search can have profound consequences for mosquito populations' capacity to transmit pathogens.

Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 "Pareto" rule has been proposed to describe this heterogeneity whereby 80% of transmission is accounted for by 20% of individuals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain individuals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders.

Background: Heterogeneity in malaria transmission has household, temporal, and spatial components. These factors are relevant for improving the efficiency of malaria control by targeting heterogeneity. To quantify variation, we analyzed mosquito counts from entomological surveillance conducted at three study sites in Uganda that varied in malaria transmission intensity. Mosquito biting or exposure is a risk factor for malaria transmission. Methods: Using a Bayesian zero-inflated negative binomial model, validated via a comprehensive simulation study, we quantified household differences in malaria vector density and examined its spatial distribution. We introduced a novel approach for identifying changes in vector abundance hotspots over time by computing the Getis-Ord statistic on ratios of household biting propensities for different scenarios. We also explored the association of household biting propensities with housing and environmental covariates. Results: In each site, there was evidence for hot and cold spots of vector abundance, and spatial patterns associated with urbanicity, elevation, or other environmental covariates. We found some differences in the hotspots in rainy vs. dry seasons or before vs. after the application of control interventions. Housing quality explained a portion of the variation among households in mosquito counts. Conclusion: This work provided an improved understanding of heterogeneity in malaria vector density at the three study sites in Uganda and offered a valuable opportunity for assessing whether interventions could be spatially targeted to be aimed at abundance hotspots which may increase malaria risk. Indoor residual spraying was shown to be a successful measure of vector control interventions in Tororo, Uganda.  Cement walls, brick floors, closed eaves, screened airbricks, and tiled roofs were features of a house that had shown reduction of household biting propensity. Improvements in house quality should be recommended as a supplementary measure for malaria control reducing risk of infection.

BackgroundMajor gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.Methods and resultsUsing analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.ConclusionsReaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.

BackgroundStandard advice regarding vector control is to prefer interventions that reduce the lifespan of adult mosquitoes. The basis for this advice is a decades-old sensitivity analysis of 'vectorial capacity', a concept relevant for most malaria transmission models and based solely on adult mosquito population dynamics. Recent advances in micro-simulation models offer an opportunity to expand the theory of vectorial capacity to include both adult and juvenile mosquito stages in the model.MethodsIn this study we revisit arguments about transmission and its sensitivity to mosquito bionomic parameters using an elasticity analysis of developed formulations of vectorial capacity.ResultsWe show that reducing adult survival has effects on both adult and juvenile population size, which are significant for transmission and not accounted for in traditional formulations of vectorial capacity. The elasticity of these effects is dependent on various mosquito population parameters, which we explore. Overall, control is most sensitive to methods that affect adult mosquito mortality rates, followed by blood feeding frequency, human blood feeding habit, and lastly, to adult mosquito population density.ConclusionsThese results emphasise more strongly than ever the sensitivity of transmission to adult mosquito mortality, but also suggest the high potential of combinations of interventions including larval source management. This must be done with caution, however, as policy requires a more careful consideration of costs, operational difficulties and policy goals in relation to baseline transmission.

IntroductionInsecticide-treated nets (ITNs) are one of the main interventions used for malaria control. However, these nets may also be effective against other vector borne diseases (VBDs). We conducted a systematic review and meta-analysis to estimate the efficacy of ITNs, insecticide-treated curtains (ITCs) and insecticide-treated house screening (ITS) against Chagas disease, cutaneous and visceral leishmaniasis, dengue, human African trypanosomiasis, Japanese encephalitis, lymphatic filariasis and onchocerciasis.MethodsMEDLINE, EMBASE, LILACS and Tropical Disease Bulletin databases were searched using intervention, vector- and disease-specific search terms. Cluster or individually randomised controlled trials, non-randomised trials with pre- and post-intervention data and rotational design studies were included. Analysis assessed the efficacy of ITNs, ITCs or ITS versus no intervention. Meta-analysis of clinical data was performed and percentage reduction in vector density calculated.ResultsTwenty-one studies were identified which met the inclusion criteria. Meta-analysis of clinical data could only be performed for four cutaneous leishmaniasis studies which together showed a protective efficacy of ITNs of 77% (95%CI: 39%-91%). Studies of ITC and ITS against cutaneous leishmaniasis also reported significant reductions in disease incidence. Single studies reported a high protective efficacy of ITS against dengue and ITNs against Japanese encephalitis. No studies of Chagas disease, human African trypanosomiasis or onchocerciasis were identified.ConclusionThere are likely to be considerable collateral benefits of ITN roll out on cutaneous leishmaniasis where this disease is co-endemic with malaria. Due to the low number of studies identified, issues with reporting of entomological outcomes, and few studies reporting clinical outcomes, it is difficult to make strong conclusions on the effect of ITNs, ITCs or ITS on other VBDs and therefore further studies be conducted. Nonetheless, it is clear that insecticide-treated materials such as ITNs have the potential to reduce pathogen transmission and morbidity from VBDs where vectors enter houses.

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross-Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross-Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross-Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

An important question for mosquito population dynamics, mosquito-borne pathogen transmission and vector control is how mosquito populations are regulated. Here we develop simple models with heterogeneity in egg laying patterns and in the responses of larval populations to crowding in aquatic habitats. We use the models to evaluate how such heterogeneity affects mosquito population regulation and the effects of larval source management (LSM). We revisit the notion of a carrying capacity and show how heterogeneity changes our understanding of density dependence and the outcome of LSM. Crowding in and productivity of aquatic habitats is highly uneven unless egg-laying distributions are fine-tuned to match the distribution of habitats' carrying capacities. LSM reduces mosquito population density linearly with coverage if adult mosquitoes avoid laying eggs in treated habitats, but quadratically if eggs are laid in treated habitats and the effort is therefore wasted (i.e., treating 50% of habitat reduces mosquito density by approximately 75%). Unsurprisingly, targeting (i.e. treating a subset of the most productive pools) gives much larger reductions for similar coverage, but with poor targeting, increasing coverage could increase adult mosquito population densities if eggs are laid in higher capacity habitats. Our analysis suggests that, in some contexts, LSM models that accounts for heterogeneity in production of adult mosquitoes provide theoretical support for pursuing mosquito-borne disease prevention through strategic and repeated application of modern larvicides.

BackgroundWith a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. ObjectiveThe study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. MethodsThe study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. ResultsThe MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. ConclusionsThis is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. Trial RegistrationClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 International Registered Report Identifier (IRRID)DERR1-10.2196/20904

Millions of affordable healthy homes are needed for the rapidly expanding population of sub-Saharan Africa. This enormous challenge is an opportunity to address pervasive health issues linked to housing, where diseases that most impact children—malaria, diarrhoea and respiratory tract infections—are often acquired. A pilot project in northern Tanzania demonstrated the potential of novel house designs to reduce infectious disease transmission in homes. To conduct a randomized controlled trial of one novel-design house, the research team moved to the southeast of the country. This article describes the challenges experienced during the construction and initial evaluation of the novel house. [ABSTRACT FROM AUTHOR]

Objective To assess the contributions of both microbial larvicides and insecticide-treated nets (ITNs) in terms of reducing malaria incidence in an integrated vector management programme in an area moderately endemic for malaria in the western Kenyan highlands. Methods A pre-post, control group design was used. Larval and adult vector populations were surveyed weekly in six separate valley communities. The incidence of Plasmodium infections in children 6 months to 13 years of age was measured during the long and short rainy seasons each year. Baseline data were collected for 17 months, after which Bacillus-based larvicides were applied weekly to aquatic habitats in three of the valleys for another 19 months. At around the same time the larviciding was initiated, ITNs were introduced gradually into all study communities by the National Malaria Control Programme. The effect of larviciding, ITNs and other determinants of malaria risk was assessed by means of generalized estimating equations. Findings The risk of acquiring new parasite infections in children was substantially and independently reduced by ITN use (odds ratio, OR: 0.69; 95% confidence interval, Ch 0.48-0.99) and larvicide application (OR: 0.44; 95% CI: 0.23-0.82), after adjusting for confounders. Conclusion Vector control with microbial larvicides enhanced the malaria control achieved with ITNs alone. Anti-larval measures are a promising complement to ITN distribution in the economically important highland areas and similar transmission settings in Africa. Objectif Evaluer les contributions des larvicides microbiens et des moustiquaires impregnees d'insecticide (Mil) a la reduction de l'incidence du paludisme dans le cadre d'un programme de lutte antivectorielle integree, applique a une zone d'endemie moderee de cette maladie, dans les hauts plateaux du Kenya occidental. Methodes On a fait appel a une etude de type avant-apres avec groupe temoin. On a surveille chaque semaine les populations de larves et de vecteurs adultes menacant les communautes vivant dans six vallees separees. On a mesure chaque annee l'incidence des infections a Plasmodium chez les enfants de 6 mois a 13 ans au cours des deux saisons des pluies (Iongue et courte). On a collecte des donnee de reference pendant 17 mois, apres quoi on applique chaque semaine des larvicides a base de Bacillus sur les habitats aquatiques de trois des vallees pendant 19 autres mois. En meme temps a peu pres que debutait la destruction des larves, le Programme kenyan de lutte contre le paludisme a commence a introduire progressivement des Mil dans toutes los communautes etudiees. Les effets de la destruction larvaire, des Mil et d'autres determinants du risque de paludisme ont ete evalues a l'aide d'equations d'estimation generalisee. Resultats Apres ajustement pour les facteurs de confusion, le risque de contracter une nouvelle infestation parasitaire chez l'enfant etait substantiellement et independamment reduit par l'utilisation de Mil (Odds ratio, OR : 0,69, intervalle de confiance a 95%, IC : 0,48-0,99) et par l'application de larvicide (OR : 0,44 ; IC a 95% : 0,23-0,82). Conclusion La lutte antivectorielle par application de larvicides microbiens a permis de renforcer les resultats obtenus contre le paludisme avec les Mil seules. Les mesures de lutte antilarvaire representent un complement prometteur a la distribution de Mil dans les zones importantes sur le plan economique des hauts plateaux et dans d'autres contextes similaires en Afrique ou se transmet actuellement le paludisme. Objetivo Determinar la contribucion de los larvicidas microbianos y los mosquiteros tratados con insecticida (MTI) a la reduccion de la incidencia de malaria en un programa de lucha antivectorial integrada emprendido en una zona con malaria moderadamente endemica de las tierras altas dei oeste de Kenya. Metodos Se Ilevo a cabo un estudio pre-post con un grupo de control en el que se procedio a vigilar las poblaciones de larvas y vectores adultos en las comunidades de seis valles. Anualmente se midio la incidencia de infeccion por Plasmodium en los ninos de 6 meses a 13 anos durante cada estacion de las Iluvias cortas y largas. Se reunieron datos de referencia por espacio de 17 meses, tras lo cual se procedio a aplicar todas las semanas larvicidas basados en Bacillus en habitats acuaticos entres de los valles durante otros 19 meses. Aproximadamente al mismo tiempo que se iniciaba la aplicacion de larvicidas, el Programa Nacional de Control de la Malaria comenzo tambien a introducir gradualmente los MTI en todas las comunidades estudiadas. El efecto de los larvicidas, los MTI y otros determinantes dei riesgo de malaria se evaluo mediante ecuaciones de estimacion generalizadas. Resultados El riesgo de los nifios de contraer nuevas infecciones por el parasito se vio reducido de forma sustancial e independiente por el uso de MTI (razon de posibilidades, OR: 0,69; intervalo de confianza [IC] del 95%: 0,48-0,99) y por la aplicacion de larvicidas (OR: 0,44; IC 95%: 0,23-0,82), despues de ajustar por los factores de confusion. Conclusion La lucha antivectorial con larvicidas microbianos potencio el control de la malaria logrado solo con MTI. Las medidas antilarvarias son un complemento prometedor de la distribucion de MTI en las zonas montanosas economicamente importantes y otros entornos de transmision similares en Africa., Introduction A marked increase in malaria has recently been noted in the African highlands, largely due to the rise of drug-resistant strains of Plasmodium falciparum parasites. (1-4) The ecological features [...]

Abstract Background Little is known about how malaria mosquitoes locate oviposition sites in nature. Such knowledge is important to help devise monitoring and control measures that could be used to target gravid females. This study set out to develop a suite of tools that can be used to study the attraction of gravid Anopheles gambiae s.s. towards visual or olfactory cues associated with aquatic habitats. Methods Firstly, the study developed and assessed methods for using electrocuting nets to analyse the orientation of gravid females towards an aquatic habitat. Electric nets (1m high × 0.5m wide) were powered by a 12V battery via a spark box. High and low energy settings were compared for mosquito electrocution and a collection device developed to retain electrocuted mosquitoes when falling to the ground. Secondly, a range of sticky materials and a detergent were tested to quantify if and where gravid females land to lay their eggs, by treating the edge of the ponds and the water surface. A randomized complete block design was used for all experiments with 200 mosquitoes released each day. Experiments were conducted in screened semi-field systems using insectary-reared An. gambiae s.s. Data were analysed by generalized estimating equations. Results An electric net operated at the highest spark box energy of a 400 volt direct current made the net spark, creating a crackling sound, a burst of light and a burning smell. This setting caught 64% less mosquitoes than a net powered by reduced voltage output that could neither be heard nor seen (odds ratio (OR) 0.46; 95% confidence interval (CI) 0.40-0.53, p < 0.001). Three sticky boards (transparent film, glue coated black fly-screen and yellow film) were evaluated as catching devices under electric nets and the transparent and shiny black surfaces were found highly attractive (OR 41.6, 95% CI 19.8 – 87.3, p < 0.001 and OR 28.8, 95% CI 14.5 – 56.8, p < 0.001, respectively) for gravid mosquitoes to land on compared to a yellow sticky film board and therefore unsuitable as collection device under the e-nets. With a square of four e-nets around a pond combined with yellow sticky boards on average 33% (95% CI 28-38%) of mosquitoes released were collected. Sticky materials and detergent in the water worked well in collecting mosquitoes when landing on the edge of the pond or on the water surface. Over 80% of collected females were found on the water surface (mean 103, 95% CI 93–115) as compared to the edge of the artificial pond (mean 24, 95% CI 20–28). Conclusion A square of four e-nets with yellow sticky boards as a collection device can be used for quantifying the numbers of mosquitoes approaching a small oviposition site. Shiny sticky surfaces attract gravid females possibly because they are visually mistaken as aquatic habitats. These materials might be developed further as gravid traps. Anopheles gambiae s.s. primarily land on the water surface for oviposition. This behaviour can be exploited for the development of new trapping and control strategies.