scholarly journals Vector genetics, insecticide resistance and gene drives: an agent-based modeling approach to evaluate malaria transmission and elimination

2020 ◽  
Author(s):  
Prashanth Selvaraj ◽  
Edward A. Wenger ◽  
Daniel Bridenbecker ◽  
Nikolai Windbichler ◽  
Jonathan R. Russell ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Malaria Transmission ◽  
Control Measures ◽  
Phenotypic Traits ◽  
Gene Drive ◽  
Agent Based ◽  
Transmission Setting ◽  
In The Wild ◽  
Gene Drives

AbstractVector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations, which is the transfer of genetic information from one population to another through migration, can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and a many-to-many mapping cardinality of genotypes to phenotypes to investigate gene flow, and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed.Author summaryVector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi-locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.

scholarly journals Vector genetics, insecticide resistance and gene drives: An agent-based modeling approach to evaluate malaria transmission and elimination

2020 ◽  
Vol 16 (8) ◽  
pp. e1008121
Author(s):  
Prashanth Selvaraj ◽  
Edward A. Wenger ◽  
Daniel Bridenbecker ◽  
Nikolai Windbichler ◽  
Jonathan R. Russell ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Malaria Transmission ◽  
Agent Based Modeling ◽  
Agent Based ◽  
Modeling Approach ◽  
Gene Drives

scholarly journals High insecticide resistance mediated by different mechanisms in Culex quinquefasciatus populations from the city of Yaoundé, Cameroon

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abdou Talipouo ◽  
Konstantinos Mavridis ◽  
Elysée Nchoutpouen ◽  
Borel Djiappi-Tchamen ◽  
Emmanouil Alexandros Fotakis ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
High Resistance ◽  
Culex Quinquefasciatus ◽  
Control Strategies ◽  
Cuticular Hydrocarbon ◽  
Control Measures ◽  
High Frequencies ◽  
The City ◽  
Integrated Vector Control

AbstractCulex mosquitoes particularly Culex quinquefasciatus are important arboviral and filariasis vectors, however despite this important epidemiological role, there is still a paucity of data on their bionomics. The present study was undertaken to assess the insecticide resistance status of Cx. quinquefasciatus populations from four districts of Yaoundé (Cameroon). All Culex quinquefasciatus populations except one displayed high resistance to bendiocarb and malathion with mortalities ranging from 0 to 89% while high resistance intensity against both permethrin and deltamethrin was recorded. Molecular analyses revealed high frequencies of the ACE-1 G119S mutation (ranging from 0 to 33%) and kdr L1014F allele (ranging from 55 to 74%) in all Cx. quinquefasciatus populations. Significant overexpression was detected for cytochrome P450s genes CYP6AA7 and CYP6Z10, as well as for Esterase A and Esterase B genes. The total cuticular hydrocarbon content, a proxy of cuticular resistance, was significantly increased (compared to the S-lab strain) in one population. The study confirms strong insecticide resistance mediated by different mechanisms in Cx. quinquefasciatus populations from the city of Yaoundé. The expansion of insecticide resistance in Culex populations could affect the effectiveness of current vector control measures and stress the need for the implementation of integrated vector control strategies in urban settings.

scholarly journals Anopheles metabolic proteins in malaria transmission, prevention and control: a review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Eunice Oluwatobiloba Adedeji ◽  
Olubanke Olujoke Ogunlana ◽  
Segun Fatumo ◽  
Thomas Beder ◽  
Yvonne Ajamma ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Malaria Transmission ◽  
Control Strategies ◽  
Parasite Development ◽  
Potential Contribution ◽  
Population Replacement ◽  
Blood Digestion ◽  
Significant Toxicity ◽  
And Control

Abstract The increasing resistance to currently available insecticides in the malaria vector, Anopheles mosquitoes, hampers their use as an effective vector control strategy for the prevention of malaria transmission. Therefore, there is need for new insecticides and/or alternative vector control strategies, the development of which relies on the identification of possible targets in Anopheles. Some known and promising targets for the prevention or control of malaria transmission exist among Anopheles metabolic proteins. This review aims to elucidate the current and potential contribution of Anopheles metabolic proteins to malaria transmission and control. Highlighted are the roles of metabolic proteins as insecticide targets, in blood digestion and immune response as well as their contribution to insecticide resistance and Plasmodium parasite development. Furthermore, strategies by which these metabolic proteins can be utilized for vector control are described. Inhibitors of Anopheles metabolic proteins that are designed based on target specificity can yield insecticides with no significant toxicity to non-target species. These metabolic modulators combined with each other or with synergists, sterilants, and transmission-blocking agents in a single product, can yield potent malaria intervention strategies. These combinations can provide multiple means of controlling the vector. Also, they can help to slow down the development of insecticide resistance. Moreover, some metabolic proteins can be modulated for mosquito population replacement or suppression strategies, which will significantly help to curb malaria transmission.

scholarly journals Resting behaviour of malaria vectors in a highland and a lowland site of western Kenya: Implication on malaria vector control measures

2019 ◽  
Author(s):  
Maxwell G. Machani ◽  
Eric Ochomo ◽  
Fred Amimo ◽  
Jackline Kosgei ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Malaria Vector ◽  
Control Measures ◽  
Malaria Vectors ◽  
Western Kenya ◽  
Sporozoite Rate ◽  
Resting Behaviour ◽  
Outdoor Resting ◽  
Indoor And Outdoor

AbstractBackgroundUnderstanding the interactions between increased insecticide resistance in field malaria vector populations and the subsequent resting behaviour patterns is important for planning adequate vector control measures in a specific context and sustaining the current vector interventions. The aim of this study was to investigate the resting behavior, host preference and infection with Plasmodium falciparum sporozoites by malaria vectors in different ecological settings of western Kenya with different levels of insecticide resistance.MethodsIndoor and outdoor resting Anopheline mosquitoes were sampled during the dry and rainy seasons in Kisian (lowland site) and Bungoma (highland site), both in western Kenya. WHO tube bioassay was used to determine levels of phenotypic resistance of first generation offspring (F1 progeny) of malaria vectors resting indoors and outdoors to deltamethrin. PCR-based molecular diagnostics were used for mosquito speciation, genotype for resistance mutations and to determine specific host blood meal origins. Enzyme-linked Immunosorbent Assay (ELISA) was used to determine mosquito sporozoite infections.ResultsOverall, 3,566 female Anopheles mosquitoes were collected with Anopheles gambiae s.l [In Bungoma, An. gambiae s.s (90.9%), An arabiensis (7.6%) and in Kisian, An. gambiae s.s (38.9%), An. arabiensis (60.2%)] being the most abundant species (74.7%) followed by An. funestus s.l (25.3%). The majority of An. gambiae s.l (85.4 and 58%) and An. funestus (96.6 and 91.1%) were caught resting indoors in Bungoma and Kisian respectively.Vgsc-1014S was observed at a slightly higher frequency in An. gambiae s.s hereafter(An. gambiae) resting indoor than outdoor (89.7 vs 84.6% and 71.5 vs 61.1%) in Bungoma and Kisian respectively. For An. arabiensis, Vgsc-1014S was 18.2% indoor and outdoor (17.9%) in Kisian. In Bungoma, the Vgsc-1014S was only detected in An. arabiensis resting indoors with a frequency of 10%. The Vgsc-1014F mutation was only present in An. gambiae resting indoors from both sites, but at very low frequencies in Kisian compared to Bungoma (0.8 and 9.2% respectively. In Bungoma, the sporozoite rates for An. funestus, An. gambiae, and An. arabiensis resting indoors were 10.9, 7.6 and 3.4 % respectively. For outdoor resting, An. gambiae and An. arabiensis in Bungoma, the sporozoite rates were 4.7 and 2.9 % respectively.Overall, in Bungoma, the sporozoite rate for indoor resting mosquitoes was 8.6% and 4.2% for outdoors. In Kisian the sporozoite rate was 0.9% for indoor resting An. gambiae. None of the outdoor collected mosquitoes in Kisian tested positive for sporozoite infections.ConclusionThe study reports high densities of insecticide-resistant An. gambiae and An. funestus resting indoors and the persistence of malaria transmission indoors with high entomological inoculation rates (EIR) regardless of the use of Long-lasting insecticidal nets (LLINs). These findings underline the difficulties of controlling malaria vectors resting and biting indoors using the current interventions. Supplemental vector control tools and implementation of sustainable insecticide resistance management strategies are needed in western Kenya.

scholarly journals Monitoring of Insecticide Resistance in Anopheles culicifacies in Twelve Districts of Madhya Pradesh, Central India (2017–2019)

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Ashok K. Mishra ◽  
Praveen K Bharti ◽  
Gyan Chand ◽  
Aparup Das ◽  
Himanshu Jayswar ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Vector Control ◽  
Indoor Residual Spraying ◽  
Central India ◽  
Control Programme ◽  
Madhya Pradesh ◽  
Control Measures ◽  
Malaria Vectors ◽  
Malaria Vector Control ◽  
The Impact

Background. Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are malaria vector control measures used in India, but the development of insecticide resistance poses major impediments for effective vector control strategies. As per the guidelines of the National Vector Borne Disease Control Programme (NVBDCP), the study was conducted in 12 districts of Madhya Pradesh to generate data on insecticide resistance in malaria vectors. Methods. The susceptibility tests were conducted on adult An. culicifacies as per the WHO standard technique with wild-caught mosquitoes. The blood-fed female mosquitoes were exposed in 3 to 4 replicates on each occasion to the impregnated papers with specified discriminating dosages of the insecticides (DDT: 4%, malathion: 5%, deltamethrin: 0.05%, and alphacypermethrin: 0.05%), for one hour, and mortality was recorded after 24-hour holding. Results. An. culicifacies was found resistant to DDT 4% in all the 12 districts and malathion in 11 districts. The resistance to alphacypermethrin was also observed in two districts, and possible resistance was found to alphacypermethrin in seven districts and to deltamethrin in eight districts, while the vector was found susceptible to both deltamethrin and alphacypermethrin in only 3 districts. Conclusion. An. culicifacies is resistant to DDT and malathion and has emerging resistance to pyrethroids, alphacypermethrin, and deltamethrin. Therefore, regular monitoring of insecticide susceptibility in malaria vectors is needed for implementing effective vector management strategies. However, studies to verify the impact of IRS with good coverage on the transmission of disease are required before deciding on the change of insecticide in conjunction with epidemiological data.

scholarly journals Threshold-Dependent Gene Drives in the Wild: Spread, Controllability, and Ecological Uncertainty

BioScience ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 900-907 ◽  
Author(s):  
Gregory A Backus ◽  
Jason A Delborne
Keyword(s):  
Critical Frequency ◽  
Wild Population ◽  
Detailed Knowledge ◽  
Gene Drive ◽  
Potential Solution ◽  
Spreading Behavior ◽  
The Face ◽  
In The Wild ◽  
Ecological Uncertainty ◽  
Gene Drives

Abstract Gene drive technology could allow the intentional spread of a desired gene throughout an entire wild population in relatively few generations. However, there are major concerns that gene drives could either fail to spread or spread without restraint beyond the targeted population. One potential solution is to use more localized threshold-dependent drives, which only spread when they are released in a population above a critical frequency. However, under certain conditions, small changes in gene drive fitness could lead to divergent outcomes in spreading behavior. In the face of ecological uncertainty, the inability to estimate gene drive fitness in a real-world context could prove problematic because gene drives designed to be localized could spread to fixation in neighboring populations if ecological conditions unexpectedly favor the gene drive. This perspective offers guidance to developers and managers because navigating gene drive spread and controllability could be risky without detailed knowledge of ecological contexts.

scholarly journals Agent-based modelling of complex factors impacting malaria prevalence

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Miracle Amadi ◽  
Anna Shcherbacheva ◽  
Heikki Haario
Keyword(s):  
Malaria Transmission ◽  
Field Data ◽  
Control Measures ◽  
Model Parameters ◽  
Economic Factors ◽  
Agent Based ◽  
Wide Range ◽  
The Impact ◽  
Socio Economic Factors

Abstract Background Increasingly complex models have been developed to characterize the transmission dynamics of malaria. The multiplicity of malaria transmission factors calls for a realistic modelling approach that incorporates various complex factors such as the effect of control measures, behavioural impacts of the parasites to the vector, or socio-economic variables. Indeed, the crucial impact of household size in eliminating malaria has been emphasized in previous studies. However, increasing complexity also increases the difficulty of calibrating model parameters. Moreover, despite the availability of much field data, a common pitfall in malaria transmission modelling is to obtain data that could be directly used for model calibration. Methods In this work, an approach that provides a way to combine in situ field data with the parameters of malaria transmission models is presented. This is achieved by agent-based stochastic simulations, initially calibrated with hut-level experimental data. The simulation results provide synthetic data for regression analysis that enable the calibration of key parameters of classical models, such as biting rates and vector mortality. In lieu of developing complex dynamical models, the approach is demonstrated using most classical malaria models, but with the model parameters calibrated to account for such complex factors. The performance of the approach is tested against a wide range of field data for Entomological Inoculation Rate (EIR) values. Results The overall transmission characteristics can be estimated by including various features that impact EIR and malaria incidence, for instance by reducing the mosquito–human contact rates and increasing the mortality through control measures or socio-economic factors. Conclusion Complex phenomena such as the impact of the coverage of the population with long-lasting insecticidal nets (LLINs), changes in behaviour of the infected vector and the impact of socio-economic factors can be included in continuous level modelling. Though the present work should be interpreted as a proof of concept, based on one set of field data only, certain interesting conclusions can already be drawn. While the present work focuses on malaria, the computational approach is generic, and can be applied to other cases where suitable in situ data is available.

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