32 results found
Hancock PA, Lynd A, Wiebe A, et al., 2022, Modelling spatiotemporal trends in the frequency of genetic mutations conferring insecticide target-site resistance in African mosquito malaria vector species, BMC Biology, Vol: 20, Pages: 1-17, ISSN: 1741-7007
BackgroundResistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools. Target-site resistance is an important genetic resistance mechanism caused by mutations in the voltage-gated sodium channel (Vgsc) gene that encodes the pyrethroid target-site. Understanding the geographic distribution of target-site resistance, and temporal trends across different vector species, can inform strategic deployment of vector control tools.ResultsWe develop a Bayesian statistical spatiotemporal model to interpret species-specific trends in the frequency of the most common resistance mutations, Vgsc-995S and Vgsc-995F, in three major malaria vector species Anopheles gambiae, An. coluzzii, and An. arabiensis over the period 2005–2017. The models are informed by 2418 observations of the frequency of each mutation in field sampled mosquitoes collected from 27 countries spanning western and eastern regions of Africa. For nine selected countries, we develop annual predictive maps which reveal geographically structured patterns of spread of each mutation at regional and continental scales. The results show associations, as well as stark differences, in spread dynamics of the two mutations across the three vector species. The coverage of ITNs was an influential predictor of Vgsc allele frequencies, with modelled relationships between ITN coverage and allele frequencies varying across species and geographic regions. We found that our mapped Vgsc allele frequencies are a significant partial predictor of phenotypic resistance to the pyrethroid deltamethrin in An. gambiae complex populations.ConclusionsOur predictive maps show how spatiotemporal trends in insecticide target-site resistance mechanisms in African An. gambiae vary across individual vector species and geographic regions. Molecular surveillance of resistance mechanisms will help to predict resistance phenotypes and
Lucas TCD, Nandi AK, Keddie SH, et al., 2022, Improving disaggregation models of malaria incidence by ensembling non-linear models of prevalence, Spatial and Spatio-temporal Epidemiology, Vol: 41, Pages: 1-12, ISSN: 1877-5845
Maps of disease burden are a core tool needed for the control and elimination of malaria. Reliable routine surveillance data of malaria incidence, typically aggregated to administrative units, is becoming more widely available. Disaggregation regression is an important model framework for estimating high resolution risk maps from aggregated data. However, the aggregation of incidence over large, heterogeneous areas means that these data are underpowered for estimating complex, non-linear models. In contrast, prevalence point-surveys are directly linked to local environmental conditions but are not common in many areas of the world. Here, we train multiple non-linear, machine learning models on Plasmodium falciparum prevalence point-surveys. We then ensemble the predictions from these machine learning models with a disaggregation regression model that uses aggregated malaria incidences as response data. We find that using a disaggregation regression model to combine predictions from machine learning models improves model accuracy relative to a baseline model.
Moyes CL, Lees RS, Yunta C, et al., 2021, Assessing cross-resistance within the pyrethroids in terms of their interactions with key cytochrome P450 enzymes and resistance in vector populations, Parasites and Vectors, Vol: 14, Pages: 1-13, ISSN: 1756-3305
BackgroundIt is important to understand whether the potential impact of pyrethroid resistance on malaria control can be mitigated by switching between different pyrethroids or whether cross-resistance within this insecticide class precludes this approach.MethodsHere we assess the relationships among pyrethroids in terms of their binding affinity to, and depletion by, key cytochrome P450 enzymes (hereafter P450s) that are known to confer metabolic pyrethroid resistance in Anopheles gambiae (s.l.) and An. funestus, in order to identify which pyrethroids may diverge from the others in their vulnerability to resistance. We then investigate whether these same pyrethroids also diverge from the others in terms of resistance in vector populations.ResultsWe found that the type I and II pyrethroids permethrin and deltamethrin, respectively, are closely related in terms of binding affinity to key P450s, depletion by P450s and resistance within vector populations. Bifenthrin, which lacks the common structural moiety of most pyrethroids, diverged from the other pyrethroids tested in terms of both binding affinity to key P450s and depletion by P450s, but resistance to bifenthrin has rarely been tested in vector populations and was not analysed here. Etofenprox, which also lacks the common structural moiety of most pyrethroids, diverged from the more commonly deployed pyrethroids in terms of binding affinity to key P450s and resistance in vector populations, but did not diverge from these pyrethroids in terms of depletion by the P450s. The analysis of depletion by the P450s indicated that etofenprox may be more vulnerable to metabolic resistance mechanisms in vector populations. In addition, greater resistance to etofenprox was found across Aedes aegypti populations, but greater resistance to this compound was not found in any of the malaria vector species analysed. The results for pyrethroid depletion by anopheline P450s in the laboratory were largely not repeated in the findings
Lees RS, Lissenden N, Churcher T, et al., 2021, REVIEWING THE EVIDENCE FOR AND AGAINST SELECTION OF SPECIFIC PYRETHROIDS FOR PROGRAMMATIC PURPOSES, Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 432-432, ISSN: 0002-9637
Aguas R, Mahdi A, Shretta R, et al., 2021, Potential health and economic impacts of dexamethasone treatment for patients with COVID-19 (vol 12, 915, 2021), NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723
Adib K, Hancock PA, Rahimli A, et al., 2021, A participatory modelling approach for investigating the spread of COVID-19 in countries of the Eastern Mediterranean Region to support public health decision-making, BMJ Global Health, Vol: 6, Pages: 1-7, ISSN: 2059-7908
<jats:p>Early on in the COVID-19 pandemic, the WHO Eastern Mediterranean Regional Office recognised the importance of epidemiological modelling to forecast the progression of the COVID-19 pandemic to support decisions guiding the implementation of response measures. We established a modelling support team to facilitate the application of epidemiological modelling analyses in the Eastern Mediterranean Region (EMR) countries. Here, we present an innovative, stepwise approach to participatory modelling of the COVID-19 pandemic that engaged decision-makers and public health professionals from countries throughout all stages of the modelling process. Our approach consisted of first identifying the relevant policy questions, collecting country-specific data and interpreting model findings from a decision-maker’s perspective, as well as communicating model uncertainty. We used a simple modelling methodology that was adaptable to the shortage of epidemiological data, and the limited modelling capacity, in our region. We discuss the benefits of using models to produce rapid decision-making guidance for COVID-19 control in the WHO EMR, as well as challenges that we have experienced regarding conveying uncertainty associated with model results, synthesising and comparing results across multiple modelling approaches, and modelling fragile and conflict-affected states.</jats:p>
Aguas R, Mahdi A, Shretta R, et al., 2021, Potential health and economic impacts of dexamethasone treatment for patients with COVID-19, Nature Communications, Vol: 12, Pages: 1-8, ISSN: 2041-1723
Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries.
Aguas R, White L, Hupert N, et al., 2020, Modelling the COVID-19 pandemic in context: an international participatory approach, BMJ Global Health, Vol: 5, ISSN: 2059-7908
The SARS-CoV-2 pandemic has had an unprecedented impact on multiple levels of society. Not only has the pandemic completely overwhelmed some health systems but it has also changed how scientific evidence is shared and increased the pace at which such evidence is published and consumed, by scientists, policymakers and the wider public. More significantly, the pandemic has created tremendous challenges for decision-makers, who have had to implement highly disruptive containment measures with very little empirical scientific evidence to support their decision-making process. Given this lack of data, predictive mathematical models have played an increasingly prominent role. In high-income countries, there is a long-standing history of established research groups advising policymakers, whereas a general lack of translational capacity has meant that mathematical models frequently remain inaccessible to policymakers in low-income and middle-income countries. Here, we describe a participatory approach to modelling that aims to circumvent this gap. Our approach involved the creation of an international group of infectious disease modellers and other public health experts, which culminated in the establishment of the COVID-19 Modelling (CoMo) Consortium. Here, we describe how the consortium was formed, the way it functions, the mathematical model used and, crucially, the high degree of engagement fostered between CoMo Consortium members and their respective local policymakers and ministries of health.
Rathmes G, Rumisha SF, Lucas TCD, et al., 2020, Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated<i>Plasmodium falciparum</i>malaria 1991-2019, MALARIA JOURNAL, Vol: 19
Moyes CL, Athinya DK, Seethaler T, et al., 2020, Evaluating insecticide resistance across African districts to aid malaria control decisions, Proceedings of the National Academy of Sciences, Vol: 117, Pages: 22042-22050, ISSN: 0027-8424
Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps and consider the likelihood that resistance exceeds recommended thresholds. Our results show that this model provides more accurate next-year predictions than two simpler approaches. We have used the model to generate district-level maps for the probability that pyrethroid resistance in Anopheles gambiae s.l. exceeds the World Health Organization thresholds for susceptibility and confirmed resistance. In addition, we have mapped the three criteria for the deployment of piperonyl butoxide-treated nets that mitigate against the effects of metabolic resistance to pyrethroids. This includes a critical review of the evidence for presence of cytochrome P450-mediated metabolic resistance mechanisms across Africa. The maps for pyrethroid resistance are available on the IR Mapper website, where they can be viewed alongside the latest survey data.
Hancock PA, Hendriks CJM, Tangena J-A, et al., 2020, Mapping trends in insecticide resistance phenotypes in African malaria vectors, PLoS Biology, Vol: 18, Pages: 1-23, ISSN: 1544-9173
Mitigating the threat of insecticide resistance in African malaria vector populations requires comprehensive information about where resistance occurs, to what degree, and how this has changed over time. Estimating these trends is complicated by the sparse, heterogeneous distribution of observations of resistance phenotypes in field populations. We use 6,423 observations of the prevalence of resistance to the most important vector control insecticides to inform a Bayesian geostatistical ensemble modelling approach, generating fine-scale predictive maps of resistance phenotypes in mosquitoes from the Anopheles gambiae complex across Africa. Our models are informed by a suite of 111 predictor variables describing potential drivers of selection for resistance. Our maps show alarming increases in the prevalence of resistance to pyrethroids and DDT across sub-Saharan Africa from 2005 to 2017, with mean mortality following insecticide exposure declining from almost 100% to less than 30% in some areas, as well as substantial spatial variation in resistance trends.
Wu SL, Sánchez C HM, Henry JM, et al., 2020, Vector bionomics and vectorial capacity as emergent properties of mosquito behaviors and ecology, PLoS Computational Biology, Vol: 16, Pages: 1-32, ISSN: 1553-734X
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.
Hancock PA, Hendriks CJM, Tangena J-A, et al., 2020, Mapping Trends in Insecticide Resistance Phenotypes in African Malaria Vectors
<jats:title>ABSTRACT</jats:title><jats:p>Mitigating the threat of insecticide resistance in African malaria vector populations requires comprehensive information about where resistance occurs, to what degree, and how this has changed over time. Estimating these trends is complicated by the sparse, heterogeneous distribution of observations of resistance phenotypes in field populations. We use 6423 observations of the prevalence of resistance to the most important vector control insecticides to inform a Bayesian geostatistical ensemble modelling approach, generating fine-scale predictive maps of resistance phenotypes in mosquitoes from the<jats:italic>Anopheles gambiae</jats:italic>complex across Africa. Our models are informed by a suite of 111 predictor variables describing potential drivers of selection for resistance. Our maps show alarming increases in the prevalence of resistance to pyrethroids and DDT across Sub-Saharan Africa from 2005-2017 as well as substantial spatial variation in resistance trends.</jats:p>
Hendriks, Gibson, Trett, et al., 2019, Mapping geospatial processes affecting the environmental fate of agricultural pesticides in Africa, International Journal of Environmental Research and Public Health, Vol: 16, Pages: 3523-3523, ISSN: 1660-4601
The application of agricultural pesticides in Africa can have negative effects on human health and the environment. The aim of this study was to identify African environments that are vulnerable to the accumulation of pesticides by mapping geospatial processes affecting pesticide fate. The study modelled processes associated with the environmental fate of agricultural pesticides using publicly available geospatial datasets. Key geospatial processes affecting the environmental fate of agricultural pesticides were selected after a review of pesticide fate models and maps for leaching, surface runoff, sedimentation, soil storage and filtering capacity, and volatilization were created. The potential and limitations of these maps are discussed. We then compiled a database of studies that measured pesticide residues in Africa. The database contains 10,076 observations, but only a limited number of observations remained when a standard dataset for one compound was extracted for validation. Despite the need for more in-situ data on pesticide residues and application, this study provides a first spatial overview of key processes affecting pesticide fate that can be used to identify areas potentially vulnerable to pesticide accumulation.
Moyes CL, Wiebe A, Gleave K, et al., 2019, Analysis-ready datasets for insecticide resistance phenotype and genotype frequency in African malaria vectors, Scientific Data, Vol: 6, Pages: 1-11, ISSN: 2052-4463
The impact of insecticide resistance in malaria vectors is poorly understood and quantified. Here a series of geospatial datasets for insecticide resistance in malaria vectors are provided, so that trends in resistance in time and space can be quantified, and the impact of resistance found in wild populations on malaria transmission in Africa can be assessed. Specifically, data have been collated and geopositioned for the prevalence of insecticide resistance, as measured by standard bioassays, in representative samples of individual species or species complexes. Data are provided for the Anopheles gambiae species complex, the Anopheles funestus subgroup, and for nine individual vector species. Data are also given for common genetic markers of resistance to support analyses of whether these markers can improve the ability to monitor resistance in low resource settings. Allele frequencies for known resistance-associated markers in the Voltage-gated sodium channel (Vgsc) are provided. In total, eight analysis-ready, standardised, geopositioned datasets encompassing over 20,000 African mosquito collections between 1957 and 2017 are released.
Hancock PA, Ritchie SA, Koenraadt CJM, et al., 2019, Predicting the spatial dynamics of <i>Wolbachia</i> infections in <i>Aedes aegypti</i> arbovirus vector populations in heterogeneous landscapes, Journal of Applied Ecology, Vol: 56, Pages: 1674-1686, ISSN: 0021-8901
<jats:title>Abstract</jats:title><jats:p><jats:list><jats:list-item><jats:p>A promising strategy for reducing the transmission of dengue and other arboviral human diseases by <jats:italic>Aedes aegypti</jats:italic> mosquito vector populations involves field introductions of the endosymbiotic bacteria <jats:italic>Wolbachia</jats:italic>. <jats:italic>Wolbachia</jats:italic> infections inhibit viral transmission by the mosquito, and can spread between mosquito hosts to reach high frequencies in the vector population. <jats:italic>Wolbachia</jats:italic> spreads by maternal transmission, and spread dynamics can be variable and highly dependent on natural mosquito population dynamics, population structure and fitness components.</jats:p></jats:list-item><jats:list-item><jats:p>We develop a mathematical model of an <jats:italic>A. aegypti</jats:italic> metapopulation that incorporates empirically validated relationships describing density‐dependent mosquito fitness components. We assume that density dependent relationships differ across subpopulations, and construct heterogeneous landscapes for which model‐predicted patterns of variation in mosquito abundance and demography approximate those observed in field populations. We then simulate <jats:italic>Wolbachia</jats:italic> release strategies similar to that used in field trials.</jats:p></jats:list-item><jats:list-item><jats:p>We show that our model can produce rates of spatial spread of <jats:italic>Wolbachia</jats:italic> similar to those observed following field releases.</jats:p></jats:list-item><jats:list-item><jats:p>We then investigate how different types of spatio‐temporal variation in mosquito habitat, as well as different fitness costs incurred by <jats:italic>Wolbachia</jats:italic> on the mosquito host, i
Hancock PA, Wiebe A, Gleave KA, et al., 2018, Associated patterns of insecticide resistance in field populations of malaria vectors across Africa, Proceedings of the National Academy of Sciences of the United States of America, Vol: 115, Pages: 5938-5943, ISSN: 0027-8424
The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies.
Hancock PA, White VL, Ritchie SA, et al., 2016, Predicting Wolbachia invasion dynamics in Aedes aegypti populations using models of density-dependent demographic traits, BMC Biology, Vol: 14
Hancock PA, White VL, Callahan AG, et al., 2016, Density-dependent population dynamics in Aedes aegypti slow the spread of wMel Wolbachia, Journal of Applied Ecology, Vol: 53, Pages: 785-793, ISSN: 0021-8901
Field release of endosymbiotic Wolbachia bacteria into wild Aedes aegypti mosquito populations is a promising strategy for biocontrol of dengue. This strategy requires successful Wolbachia invasion through the mosquito vector population. Natural variation in mosquito fitness due to density-dependent competition for limited food resources may influence Wolbachia invasion. We know little about these effects, largely because our understanding of density-dependent dynamics in mosquito populations is limited.We developed an empirical model of A. aegypti–Wolbachia dynamics where food resources available to the developing larvae are limited. We assessed the extent of density-dependent regulation in our A. aegypti population using a Bayesian statistical model that estimates the temporal variation in mosquito fitness components. We monitored the spread of Wolbachia and assessed the effect of the bacteria on larval fitness components.We demonstrate that mosquito population growth is regulated by strong larval density-dependent variation in mosquito fitness components. Wolbachia spread was slowed by this heterogeneity in mosquito fitness, which reduces the capacity of the bacteria to invade. However, we found no evidence that Wolbachia affects larval fitness components.Synthesis and applications. We demonstrate that the extent and form of density-dependent dynamics in the host population can have a major influence on Wolbachia invasion. These findings help explain slow Wolbachia invasion rates and indicate that the success of field release strategies for dengue control can depend on attaining high Wolbachia frequencies in the mosquito population.
Heinig RL, Paaijmans KP, Hancock PA, et al., 2015, The potential for fungal biopesticides to reduce malaria transmission under diverse environmental conditions, Journal of Applied Ecology, Vol: 52, Pages: 1558-1566, ISSN: 0021-8901
The effectiveness of conventional malaria vector control is being threatened by the spread of insecticide resistance. One promising alternative to chemicals is the use of naturally occurring insect-killing fungi. Numerous laboratory studies have shown that isolates of fungal pathogens such as Beauveria bassiana can infect and kill adult mosquitoes, including those resistant to chemical insecticides.Unlike chemical insecticides, fungi may take up to a week or more to kill mosquitoes following exposure. This slow kill speed can still reduce malaria transmission because the malaria parasite itself takes at least eight days to complete its development within the mosquito. However, both fungal virulence and parasite development rate are strongly temperature-dependent, so it is possible that biopesticide efficacy could vary across different transmission environments.We examined the virulence of a candidate fungal isolate against two key malaria vectors at temperatures from 10 to 34 °C. Regardless of temperature, the fungus killed more than 90% of exposed mosquitoes within the predicted duration of the malarial extrinsic incubation period, a result that was robust to realistic diurnal temperature variation.We then incorporated temperature sensitivities of a suite of mosquito, parasite and fungus life-history traits that are important determinants of malaria transmission into a stage-structured malaria transmission model. The model predicted that, at achievable daily fungal infection rates, fungal biopesticides have the potential to deliver substantial reductions in the density of malaria-infectious mosquitoes across all temperatures representative of malaria transmission environments.Synthesis and applications. Our study combines empirical data and theoretical modelling to prospectively evaluate the potential of fungal biopesticides to control adult malaria vectors. Our results suggest that Beauveria bassiana could be a potent tool for malaria control and support furth
Hancock PA, Rehman Y, Hall IM, et al., 2014, Strategies for controlling non-transmissible infection outbreaks using a large human movement data set, PLoS Computational Biology, Vol: 10, Pages: 1-8, ISSN: 1553-734X
Prediction and control of the spread of infectious disease in human populations benefits greatly from our growing capacity to quantify human movement behavior. Here we develop a mathematical model for non-transmissible infections contracted from a localized environmental source, informed by a detailed description of movement patterns of the population of Great Britain. The model is applied to outbreaks of Legionnaires' disease, a potentially life-threatening form of pneumonia caused by the bacteria Legionella pneumophilia. We use case-report data from three recent outbreaks that have occurred in Great Britain where the source has already been identified by public health agencies. We first demonstrate that the amount of individual-level heterogeneity incorporated in the movement data greatly influences our ability to predict the source location. The most accurate predictions were obtained using reported travel histories to describe movements of infected individuals, but using detailed simulation models to estimate movement patterns offers an effective fast alternative. Secondly, once the source is identified, we show that our model can be used to accurately determine the population likely to have been exposed to the pathogen, and hence predict the residential locations of infected individuals. The results give rise to an effective control strategy that can be implemented rapidly in response to an outbreak.
Mnyone LL, Lyimo IN, Lwetoijera DW, et al., 2012, Exploiting the behaviour of wild malaria vectors to achieve high infection with fungal biocontrol agents, Malaria Journal, Vol: 11, Pages: 1-11, ISSN: 1475-2875
BackgroundControl of mosquitoes that transmit malaria has been the mainstay in the fight against the disease, but alternative methods are required in view of emerging insecticide resistance. Entomopathogenic fungi are candidate alternatives, but to date, few trials have translated the use of these agents to field-based evaluations of their actual impact on mosquito survival and malaria risk. Mineral oil-formulations of the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana were applied using five different techniques that each exploited the behaviour of malaria mosquitoes when entering, host-seeking or resting in experimental huts in a malaria endemic area of rural Tanzania.ResultsSurvival of mosquitoes was reduced by 39-57% relative to controls after forcing upward house-entry of mosquitoes through fungus treated baffles attached to the eaves or after application of fungus-treated surfaces around an occupied bed net (bed net strip design). Moreover, 68 to 76% of the treatment mosquitoes showed fungal growth and thus had sufficient contact with fungus treated surfaces. A population dynamic model of malaria-mosquito interactions shows that these infection rates reduce malaria transmission by 75-80% due to the effect of fungal infection on adult mortality alone. The model also demonstrated that even if a high proportion of the mosquitoes exhibits outdoor biting behaviour, malaria transmission was still significantly reduced.ConclusionsEntomopathogenic fungi strongly affect mosquito survival and have a high predicted impact on malaria transmission. These entomopathogens represent a viable alternative for malaria control, especially if they are used as part of an integrated vector management strategy.
Hancock PA, Godfray HCJ, 2012, Modelling the spread of Wolbachia in spatially heterogeneous environments, Journal of The Royal Society Interface, Vol: 9, Pages: 3045-3054, ISSN: 1742-5689
The endosymbiont Wolbachia infects a large number of insect species and is capable of rapid spread when introduced into a novel host population. The bacteria spread by manipulating their hosts' reproduction, and their dynamics are influenced by the demographic structure of the host population and patterns of contact between individuals. Reaction–diffusion models of the spatial spread of Wolbachia provide a simple analytical description of their spatial dynamics but do not account for significant details of host population dynamics. We develop a metapopulation model describing the spatial dynamics of Wolbachia in an age-structured host insect population regulated by juvenile density-dependent competition. The model produces similar dynamics to the reaction–diffusion model in the limiting case where the host's habitat quality is spatially homogeneous and Wolbachia has a small effect on host fitness. When habitat quality varies spatially, Wolbachia spread is usually much slower, and the conditions necessary for local invasion are strongly affected by immigration of insects from surrounding regions. Spread is most difficult when variation in habitat quality is spatially correlated. The results show that spatial variation in the density-dependent competition experienced by juvenile host insects can strongly affect the spread of Wolbachia infections, which is important to the use of Wolbachia to control insect vectors of human disease and other pests.
Hancock PA, Sinkins SP, Godfray HCJ, 2011, Strategies for introducing Wolbachia to reduce transmission of mosquito-borne diseases, PLoS Neglected Tropical Diseases, Vol: 5, Pages: 1-10, ISSN: 1935-2727
Certain strains of the endosymbiont Wolbachia have the potential to lower the vectorial capacity of mosquito populations and assist in controlling a number of mosquito-borne diseases. An important consideration when introducing Wolbachia-carrying mosquitoes into natural populations is the minimisation of any transient increase in disease risk or biting nuisance. This may be achieved by predominantly releasing male mosquitoes. To explore this, we use a sex-structured model of Wolbachia-mosquito interactions. We first show that Wolbachia spread can be initiated with very few infected females provided the infection frequency in males exceeds a threshold. We then consider realistic introduction scenarios involving the release of batches of infected mosquitoes, incorporating seasonal fluctuations in population size. For a range of assumptions about mosquito population dynamics we find that male-biased releases allow the infection to spread after the introduction of low numbers of females, many fewer than with equal sex-ratio releases. We extend the model to estimate the transmission rate of a mosquito-borne pathogen over the course of Wolbachia establishment. For a range of release strategies we demonstrate that male-biased release of Wolbachia-infected mosquitoes can cause substantial transmission reductions without transiently increasing disease risk. The results show the importance of including mosquito population dynamics in studying Wolbachia spread and that male-biased releases can be an effective and safe way of rapidly establishing the symbiont in mosquito populations.
Hancock PA, Brackley R, Palmer SCF, 2011, Modelling the effect of temperature variation on the seasonal dynamics of Ixodes ricinus tick populations, International Journal for Parasitology, Vol: 41, Pages: 513-522, ISSN: 0020-7519
Seasonal variation in temperature is known to drive annual patterns of tick activity and can influence the dynamics of tick-borne diseases. An age-structured model of the dynamics of Ixodes ricinus populations was developed to explore how changes in average temperature and different levels of temperature variability affect seasonal patterns of tick activity and the transmission of tick-borne diseases. The model produced seasonal patterns of tick emergence that are consistent with those observed throughout Great Britain. Varying average temperature across a continuous spectrum produced a systematic pattern in the times of peak emergence of questing ticks which depends on cumulative temperature over the year. Examination of the effects of between-year stochastic temperature variation on this pattern indicated that peak emergence times are more strongly affected by temperature stochasticity at certain levels of average temperature. Finally the model was extended to give a simple representation of the dynamics of a tick-borne disease. A threshold level of annual cumulative temperature was identified at which disease persistence is sensitive to stochastic temperature variation. In conclusion, the effect of changing patterns of temperature variation on the dynamics of I. ricinus ticks and the diseases they transmit may depend on the cumulative temperature over the year and will therefore vary across different locations. The results also indicate that diapause mechanisms have an important influence on seasonal patterns of tick activity and require further study.
Hancock PA, Sinkins SP, Godfray HCJ, 2011, Population dynamic models of the spread of Wolbachia, The American Naturalist, Vol: 177, Pages: 323-333, ISSN: 0003-0147
Wolbachia are endosymbionts that are found in many insect species and can spread rapidly when introduced into a naive host population. Most Wolbachia spread when their infection frequency exceeds a threshold normally calculated using purely population genetic models. However, spread may also depend on the population dynamics of the insect host. We develop models to explore interactions between host population dynamics and Wolbachia infection frequency for an age-structured insect population regulated by larval density dependence. We first derive a new expression for the threshold frequency that extends existing theory to incorporate important details of the insect’s life history. In the presence of immigration and emigration, the threshold also depends on the form of density-dependent regulation. We show how the type of immigration (constant or pulsed) and the temporal dynamics of the host population can strongly affect the spread of Wolbachia. The results help understand the natural dynamics of Wolbachia infections and aid the design of programs to introduce Wolbachia to control insects that are disease vectors or pests.
Hancock PA, 2009, Combining fungal biopesticides and insecticide-treated bednets to enhance malaria control, PLoS Computational Biology, Vol: 5, Pages: 1-11, ISSN: 1553-734X
In developing strategies to control malaria vectors, there is increased interest in biological methods that do not cause instant vector mortality, but have sublethal and lethal effects at different ages and stages in the mosquito life cycle. These techniques, particularly if integrated with other vector control interventions, may produce substantial reductions in malaria transmission due to the total effect of alterations to multiple life history parameters at relevant points in the life-cycle and transmission-cycle of the vector. To quantify this effect, an analytically tractable gonotrophic cycle model of mosquito-malaria interactions is developed that unites existing continuous and discrete feeding cycle approaches. As a case study, the combined use of fungal biopesticides and insecticide treated bednets (ITNs) is considered. Low values of the equilibrium EIR and human prevalence were obtained when fungal biopesticides and ITNs were combined, even for scenarios where each intervention acting alone had relatively little impact. The effect of the combined interventions on the equilibrium EIR was at least as strong as the multiplicative effect of both interventions. For scenarios representing difficult conditions for malaria control, due to high transmission intensity and widespread insecticide resistance, the effect of the combined interventions on the equilibrium EIR was greater than the multiplicative effect, as a result of synergistic interactions between the interventions. Fungal biopesticide application was found to be most effective when ITN coverage was high, producing significant reductions in equilibrium prevalence for low levels of biopesticide coverage. By incorporating biological mechanisms relevant to vectorial capacity, continuous-time vector population models can increase their applicability to integrated vector management.
Hancock PA, Thomas MB, Godfray HCJ, 2009, An age-structured model to evaluate the potential of novel malaria-control interventions: a case study of fungal biopesticide sprays, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 276, Pages: 71-80, ISSN: 0962-8452
Hancock PA, Godfray HCJ, 2007, Application of the lumped age-class technique to studying the dynamics of malaria-mosquito-human interactions, MALARIA JOURNAL, Vol: 6
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