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A deltamethrin crystal polymorph for more effective malaria control.

ABSTRACT: Pyrethroid contact insecticides are mainstays of malaria control, but their efficacies are declining due to widespread insecticide resistance in Anopheles mosquito populations, a major public health challenge. Several strategies have been proposed to overcome this challenge, including insecticides with new modes of action. New insecticides, however, can be expensive to implement in low-income countries. Here, we report a simple and inexpensive method to improve the efficacy of deltamethrin, the most active and most commonly used pyrethroid, by more than 10 times against Anopheles mosquitoes. Upon heating for only a few minutes, the commercially available deltamethrin crystals, form I, melt and crystallize upon cooling into a polymorph, form II, which is much faster acting against fruit flies and mosquitoes. Epidemiological modeling suggests that the use of form II in indoor residual spraying in place of form I would significantly suppress malaria transmission, even in the presence of high levels of resistance. The simple preparation of form II, coupled with its kinetic stability and markedly higher efficacy, argues that form II can provide a powerful, timely, and affordable malaria control solution for low-income countries that are losing protection in the face of worldwide pyrethroid resistance.

SUBMITTER: Yang J

PROVIDER: S-EPMC7604418 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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A deltamethrin crystal polymorph for more effective malaria control.

Yang Jingxiang J Erriah Bryan B Hu Chunhua T CT Reiter Ethan E Zhu Xiaolong X López-Mejías Vilmalí V Carmona-Sepúlveda Isis Paola IP Ward Michael D MD Kahr Bart B

Proceedings of the National Academy of Sciences of the United States of America 20201012 43

Pyrethroid contact insecticides are mainstays of malaria control, but their efficacies are declining due to widespread insecticide resistance in <i>Anopheles</i> mosquito populations, a major public health challenge. Several strategies have been proposed to overcome this challenge, including insecticides with new modes of action. New insecticides, however, can be expensive to implement in low-income countries. Here, we report a simple and inexpensive method to improve the efficacy of deltamethri ...[more]

PMID: 33046642

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Project description:Malaria vectors in sub-Saharan Africa have proven themselves very difficult adversaries in the global struggle against malaria. Decades of anti-vector interventions have yielded mixed results--with successful reductions in transmission in some areas and limited impacts in others. These varying successes can be ascribed to a lack of universally effective vector control tools, as well as the development of insecticide resistance in mosquito populations. Understanding the impact of vector control on mosquito populations is crucial for planning new interventions and evaluating existing ones. However, estimates of population size changes in response to control efforts are often inaccurate because of limitations and biases in collection methods. Attempts to evaluate the impact of vector control on mosquito effective population size (N(e)) have produced inconclusive results thus far. Therefore, we obtained data for 13-15 microsatellite markers for more than 1,500 mosquitoes representing multiple time points for seven populations of three important vector species--Anopheles gambiae, An. melas, and An. moucheti--in Equatorial Guinea. These populations were exposed to indoor residual spraying or long-lasting insecticidal nets in recent years. For comparison, we also analyzed data from two populations that have no history of organized vector control. We used Approximate Bayesian Computation to reconstruct their demographic history, allowing us to evaluate the impact of these interventions on the effective population size. In six of the seven study populations, vector control had a dramatic impact on the effective population size, reducing N(e) between 55%-87%, the exception being a single An. melas population. In contrast, the two negative control populations did not experience a reduction in effective population size. This study is the first to conclusively link anti-vector intervention programs in Africa to sharply reduced effective population sizes of malaria vectors.

Project description:BackgroundThe widespread use of pyrethroid insecticides in Africa has led to the development of strong resistance in Anopheles mosquitoes. Introducing new active ingredients can contribute to overcome this phenomenon and ensure the effectiveness of vector control strategies. Transfluthrin is a polyfluorinated pyrethroid whose structural conformation was thought to prevent its metabolism by cytochrome P450 monooxygenases in malaria vectors, thus representing a potential alternative for managing P450-mediated resistance occurring in the field. In this study, a controlled selection was used to compare the dynamics of resistance between transfluthrin and the widely used pyrethroid deltamethrin in the mosquito Anopheles gambiae. Then, the associated molecular mechanisms were investigated using target-site mutation genotyping and RNA-seq.MethodsA field-derived line of An. gambiae carrying resistance alleles at low frequencies was used as starting material for a controlled selection experiment. Adult females were selected across 33 generations with deltamethrin or transfluthrin, resulting in three distinct lines: the Delta-R line (selected with deltamethrin), the Transflu-R line (selected with transfluthrin) and the Tiassale-S line (maintained without selection). Deltamethrin and transfluthrin resistance levels were monitored in each selected line throughout the selection process, as well as the frequency of the L1014F kdr mutation. At generation 17, cross-resistance to other public health insecticides was investigated and transcriptomes were sequenced to compare gene transcription variations and polymorphisms associated with adaptation to each insecticide.ResultsA rapid increase in resistance to deltamethrin and transfluthrin was observed throughout the selection process in each selected line in association with an increased frequency of the L1014F kdr mutation. Transcriptomic data support a broader response to transfluthrin selection as compared to deltamethrin selection. For instance, multiple detoxification enzymes and cuticle proteins were specifically over-transcribed in the Transflu-R line including the known pyrethroid metabolizers CYP6M2, CYP9K1 and CYP6AA1 together with other genes previously associated with resistance in An. gambiae.ConclusionThis study confirms that recurrent exposure of adult mosquitoes to pyrethroids in a public health context can rapidly select for various resistance mechanisms. In particular, it indicates that in addition to target site mutations, the polyfluorinated pyrethroid transfluthrin can select for a broad metabolic response, which includes some P450s previously associated to resistance to classical pyrethroids. This unexpected finding highlights the need for an in-depth study on the adaptive response of mosquitoes to newly introduced active ingredients in order to effectively guide and support decision-making programmes in malaria control.

Project description:BackgroundAfter three years with no local transmission of malaria, an outbreak occurred in Iran in 2022. Key malaria control methods in Iran are including indoor residual spraying (IRS), long-lasting insecticide-treated nets (LLINs), and prompt diagnosis and treatment of malaria cases. Anopheles sacharovi is one of the main malaria vectors in Iran. This study aimed to determine the insecticides resistance status of An. sacharovi in northwestern Iran, to inform effective vector control programs in this region.MethodsLarval stages of An. sacharovi were collected from various larval habitats located in the villages along the Aras River. Adult susceptibility tests were performed on An. sacharovi using diagnostic doses of insecticides accordance to World Health Organization (WHO) guidelines. The study also evaluated agricultural insecticide and fertilizer usage alongside the presence of natural mosquito predators in breeding sites in the study area.ResultsAlongside various chemicals such as silica, humic acid, superphosphate, sulfur, urea, and solupotasse at different dose levels, organophosphorus and pyrethroid insecticides are commonly used in rice fields and orchards. Anopheles sacharovi displayed diverse reactions to insecticides, demonstrating resistance to DDT but sensitivity to malathion, and showing similar reactions to carbamate and pyrethroid insecticides.ConclusionsThese results provide significant insights into agricultural practices and the presence of mosquito larvae in the study area. The extensive use of a specific herbicide illustrates its popularity among farmers for weed control, while other agricultural products focus on enhancing soil fertility and productivity. The absence of mosquito larvae in habitats with predators indicates the usefulness of these predators in controlling the population of mosquitoes. The resistance of mosquitoes to certain insecticides highlights the need for careful selection and intermittent use of insecticides in vector control programs. These findings can inform the development of targeted strategies to reduce malaria transmission risks. Further research is essential for assessing the effectiveness of these interventions.

Dataset Information

A deltamethrin crystal polymorph for more effective malaria control.

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A deltamethrin crystal polymorph for more effective malaria control.

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