GPR39-mediated ERK1/2 signaling reduces permethrin-induced proliferation of estrogen receptor α-negative cells.

Certain insecticides are known to have estrogenic effects by activating estrogen receptors through genomic transcription. This has led researchers to associate specific insecticide use with an increased breast cancer risk. However, it is unclear if estrogen receptor-dependent pathways are the only way in which these compounds induce carcinogenic effects. The objective of this study was to determine the impact of the pyrethroid insecticide permethrin on the growth of estrogen receptor negative breast cancer cells MDA-MB-231. Using tandem mass spectrometric techniques, the effect of permethrin on cellular protein expression was investigated, and gene ontology and pathway function enrichment analyses were performed on the deregulated proteins. Finally, molecular docking simulations of permethrin with the candidate target protein was performed and the functionality of the protein was confirmed through gene knockdown experiments. Our findings demonstrate that exposure to 10-40 µM permethrin for 48 h enhanced cell proliferation and cell cycle progression in MDA-MB-231. We observed deregulated expression in 83 upregulated proteins and 34 downregulated proteins due to permethrin exposure. These deregulated proteins are primarily linked to transmembrane signaling and chemical carcinogenesis. Molecular docking simulations revealed that the overexpressed transmembrane signaling protein, G protein-coupled receptor 39 (GPR39), has the potential to bind to permethrin. Knockdown of GPR39 partially impeded permethrin-induced cellular proliferation and altered the expression of proliferation marker protein PCNA and cell cycle-associated protein cyclin D1 via the ERK1/2 signaling pathway. These findings offer novel evidence for permethrin as an environmental breast cancer risk factor, displaying its potential to impact breast cancer cell proliferation via an estrogen receptor-independent pathway.

Long-term trends in housefly (Musca domestica L.) insecticide resistance in China.

Controlling housefly populations relies on the use of insecticides, which inevitably leads to the development of resistance. A better and more comprehensive understanding of the spatial and temporal distribution of resistance could guide the control of houseflies. However, most studies on housefly resistance in China are scattered and poorly coordinated. We collected resistance data from houseflies in the published literature and from the vector biomonitoring system of the Chinese Center for Disease Control and Prevention. A 5- or 10-year resolution was used to study the temporal dynamics of resistance to five commonly used insecticides: deltamethrin, permethrin, beta-cypermethrin, dichlorvos, and propoxur. ArcGIS was used to visualize their spatial distributions. The correlation between year and resistance coefficient was determined using SPSS 26.0 and RStudio to explore the changes in resistance over the years. A total of 2128 data were included in this study, ranging from 1982 to 2022, based on which we found significant increases in resistance over the past forty years for the five studied insecticides. Among them, pyrethroids had the most strikingly elevated resistance level and were mainly distributed in the northern and southeastern coastal areas. Dichlorvos and propoxur had intermediate increases in resistance, and most of these increases were identified in North China and the Yangtze River. Housefly resistance to commonly used insecticides in China is increasing and spatially heterogeneous. This finding also highlights the necessity of continuous routine surveillance of housefly resistance, which could guide future housefly control operations and slow the development of resistance.

A proposal to reduce the amount of permethrin entering wastewater resultant from topical use to treat scabies.

The incidence of scabies is rising in the last years. Subsequently, the use of pharmaceuticals to treat the disease has also increased. Treatment with topical permethrin is usually recommended as a first line agent. This substance is also an aquatic contaminant that is toxic for many non-target organisms, and has been included as a priority substance in the recently published proposal of the European Water Framework Directive. Current guidelines neglect the potential environmental impact of this drug, recommending that the cream should be applied head to toe and "washed off after 8-12 h". Recently, a wiping procedure before hand washing after application of the topical treatment resulted in a 66 % reduction of the amount of diclofenac released in wastewater. The authors suggested that this method could be explored for other topical treatments. In the case of scabiosis, a protocol implicating the whole body needs to be designed. The absorption of topical permethrin is low. Considering the growing incidence of scabies, the amount of the pyrethroid reaching the environment may also be increasing. Therefore, we believe that applying the wiping procedure to the case of topical permethrin deserves consideration. Other measures to minimize the amount of permethrin residues reaching wastewater by washing clothes and bed linen such as wearing single-use pijamas should also be explored. In conclusion, we need to apply a One Health approach in the treatment with scabies, without neglecting the environmental impact of pharmaceuticals. It is not rational to forget drugs once they go down the drain.

Monitoring Aedes populations for arboviruses, Wolbachia, insecticide resistance and its mechanisms in various agroecosystems in Benin.

Aedes mosquitoes are the main vectors of arboviruses in Benin. Cases of dengue have been reported in Benin with all four serotypes of the virus actively circulating in this region. Some agricultural settings are known to harbor Aedes vectors responsible for the transmission of arboviruses. The massive use of certain insecticides in agricultural settings has probably contributed to insecticide resistance in these vectors. In Benin, the susceptibility of arbovirus vectors to insecticides is poorly studied. In addition, the distribution of Wolbachia spp., which is used against some arboviruses is unknown. Moreover, there is limited information regarding the vectors responsible for the transmission of arboviruses in Benin. This present study monitored the species composition, arboviruses, and Wolbachia symbiont status, as well as the phenotypic and molecular insecticide resistance profile of Aedes populations from three agroecosystems in Benin. Aedes species identification was performed morphologically and confirmed using qPCR. (RT)-qPCR assay was applied for monitoring the presence of DENV, CHIKV, ZIKV, and WNV pathogens as well as for naturally occurring Wolbachia symbionts. Insecticide resistance was assessed phenotypically, by permethrin (0.75%) exposure of Adults (F0) using World Health Organization (WHO) bioassay protocols, and at the molecular level, using TaqMan (RT)-qPCR assays for assessing knock-down resistance (kdr) mutations (F1534C, V1016G/I, and S989P) and the expression levels of eight detoxification genes (P450s from the CYP9 and CYP6 families, carboxylesterases and glutathione-S-transferases). Aedes aegypti (Ae. aegypti) mosquitoes were the most abundant (93.9%) in the three agroecosystems studied, followed by Aedes albopictus (Ae. albopictus) mosquitoes (6.1%). No arboviruses were detected in the study's mosquito populations. Naturally occurring Wolbachia symbionts were present in 7 pools out of 15 pools tested. This could influence the effectiveness of vector control strategies based on exogenously introduced Wolbachia, all present in the three agroecosystems. Full susceptibility to permethrin was observed in all tested populations of Ae. albopictus. On the contrary, Ae. aegypti were found to be resistant in all three agroecosystem sites except for banana plantation sites, where full susceptibility was observed. Molecular analysis revealed that individual target site resistance kdr mutations F1534C and V1016G/I were detected in most Ae. aegypti populations. Additionally, double mutant (F1534C + V1016G/I) mosquitoes were found in some populations, and in one case, triple mutant (F1534C + V1016G/I + S989P) mosquitoes were detected. Metabolic resistance, as reflected by overexpression of three P450 genes (CYP6BB2, CYP9J26, and CYP9J32), was also detected in Ae. aegypti mosquitoes. Our study provides information that could be used to strategize future vector control strategies and highlights the importance of continuing vector surveillance. Future studies should assess the effect of piperonyl butoxide (PBO) on metabolic resistance and identify the different strains of Wolbachia spp., to choose the best vector control strategies in Benin.

Pyrethroid resistance status and co-occurrence of V1016G, F1534C and S989P mutations in the Aedes aegypti population from two dengue outbreak counties along the China-Myanmar border.

BACKGROUND: Over the past two decades, dengue fever (DF) has emerged as a significant arboviral disease in Yunnan province, China, particularly in the China-Myanmar border area. Aedes aegypti, an invasive mosquito species, plays a crucial role in transmitting the dengue virus to the local population. Insecticide-based vector control has been the primary tool employed to combat DF, but the current susceptibility status of Ae. aegypti to commonly used insecticides is unknown. Assessment of Ae. aegypti resistance to pyrethroid insecticides and an understanding of the underlying mechanisms of this resistance in the China-Myanmar border region is of significant strategic importance for effectively controlling the DF epidemic in the area. METHODS: Aedes aegypti larvae collected from Ruili and Gengma counties in Yunnan Province were reared to adults in the laboratory and tested for susceptibility to three pyrethroid insecticides (3.20% permethrin, 0.08% lambda-cyhalothrin and 0.20% deltamethrin) by the standard WHO susceptibility bioassay. Genotyping of mutations in the knockdown gene (kdr), namely S989P, V1016G and F1534C, that are responsible for resistance to pyrethroid insecticides was performed using allele-specific PCR methods. A possible association between the observed resistant phenotype and mutations in the voltage-gated sodium channel gene (VGSC) was also studied. RESULTS: Aedes aegypti mosquitoes collected from the two counties and reared in the laboratory were resistant to all of the pyrethroids tested, with the exception of Ae. aegypti from Gengma County, which showed sensitivity to 0.20% deltamethrin. The mortality rate of Ae. aegypti from Ruili county exposed to 3.20% permethrin did not differ significantly from that of Ae. aegypti from Gengma County (χ2 = 0.311, P = 0.577). By contrast, the mortality rate of Ae. aegypti from Ruili County exposed to 0.08% lambda-cyhalothrin and 0.20% deltamethrin, respectively, was significantly different from that of Ae. aegypti from Gengma. There was no significant difference in the observed KDT50 of Ae. aegypti from the two counties to various insecticides. Four mutation types and 12 genotypes were detected at three kdr mutation sites. Based on results from all tested Ae. aegypti, the V1016G mutation was the most prevalent kdr mutation (100% prevalence), followed by the S989P mutation (81.6%) and the F1534C mutation (78.9%). The constituent ratio of VGSC gene mutation types was significantly different in Ae. aegypti mosquitoes from Ruili and those Gengma. The triple mutant S989P + V1016G + F1534C was observed in 274 Ae. aegypti mosquitoes (60.8%), with the most common genotype being SP + GG + FC (31.4%). The prevalence of the F1534C mutation was significantly higher in resistant Ae. aegypti from Ruili (odds ratio [OR] 7.43; 95% confidence interval [CI] 1.71-32.29; P = 0.01) and Gengma (OR 9.29; 95% CI 3.38-25.50; P = 0.00) counties than in susceptible Ae. aegypti when exposed to 3.20% permethrin and 0.08% lambda-cyhalothrin, respectively. No significant association was observed in the triple mutation genotypes with the Ae. aegypti population exposed to 3.20% permethrin and 0.20% deltamethrin resistance (P > 0.05), except for Ae. aegypti from Gengma County when exposed to 0.08% lambda-cyhalothrin (OR 2.86; 95% CI 1.20-6.81; P = 0.02). CONCLUSIONS: Aedes aegypti from Ruili and Gengma counties have developed resistance to various pyrethroid insecticides. The occurrence of multiple mutant sites in VGSC strongly correlated with the high levels of resistance to pyrethroids in the Ae. aegypti populations, highlighting the need for alternative strategies to manage the spread of resistance. A region-specific control strategy for dengue vectors needs to be implemented in the future based on the status of insecticide resistance and kdr mutations.

Resistance risk assessment, cross-resistance potential and realized heritability of resistance to methomyl in Musca domestica Linnaeus.

The use of insecticides in agricultural settings often exerts negative effects on nontarget species. Methomyl, a broad-spectrum carbamate insecticide, is recommended to manage a number of insect pests of the cotton crop. Recently, Musca domestica, which is a nontarget insect species in cotton fields, has shown resistance to methomyl in Pakistan. The present study tried to assess resistance-risk assessment, rapidity of resistance development to methomyl, cross-resistance potential to other insecticides, resistance heritability and to forecast the projected rate of resistance development under field conditions. For this purpose, a field strain of M. domestica with 186 fold resistance to methomyl was re-selected in the laboratory for eight consecutive generations. Consequently, LD50 values increased rapidly (126.64 ng/fly to 3112.79 ng/fly) compared to those before selection experiments. Similarly, RR values increased from 186 to 3113 fold as a result of the selection process. However, resistance to methomyl did not remain stable when the selected strain (Meth-SEL) reared for the next five generations in a pesticide free environment. The Meth-SEL strain also developed cross-resistance to permethrin. The realized heritability (h2) value for the Meth-SEL strain was 0.39 with 27% average mortality of M. domestica. Assuming the standard deviation (σp) value 0.27 and the h2 value 0.39 for eight generations of continuous exposure to methomyl, then five, seven, eight, ten and twelve generations at 90, 80, 70, 60 and 50% selection intensity, respectively, would be required for a tenfold increase in the LD50 value of methomyl. In conclusion, the Meth-SEL strain of M. domestica exhibited a high risk of resistance development to methomyl under continuous selection pressure. Resistance increased rapidly during selection experiments that reflect the probability of resistance development under field conditions if M. domestica receive exposures to methomyl during its applications for the management of target pest species.

FRET-Based Host-Guest Supramolecular Probe for On-Site and Broad-Spectrum Detection of Pyrethroids in the Environment.

The massive use of pyrethroid pesticides in agriculture has brought growing concerns about food safety due to their several harmful effects on human health, especially through the accumulation of the food chain. To date, most of the available analytical methods for pyrethroids still suffer from insufficient detection universality, complicated sample pretreatment, and detection processes, which severely limit their practical applications. Herein, a novel Förster resonance energy transfer (FRET)-assisted host-guest supramolecular nanoassembly is reported, for the first time, successfully realizing ratiometric fluorescent detection of pyrethroids in real samples through the indicator displacement assay (IDA) mechanism. This method is capable of detecting a broad spectrum of pyrethroids, including bifenthrin, cyfluthrin, cypermethrin, deltamethrin, etofenprox, fenvalerate, and permethrin, with ultrahigh detection sensitivity, great selectivity, high anti-interference ability, and, in particular, distinct emission color response from red to green. Such a large chromatic response makes this method available for fast and on-site detection of pyrethroids in real samples with the aid of several simple portable analytical apparatuses.

Insecticide resistance status of Aedes aegypti in border areas of Yunnan Province.

BACKGROUND: Aedes aegypti is a main vector of arboviral diseases, principally dengue, chikungunya, and Zika. Insecticides remain the most effective vector control method. Pyrethroid is the main insecticide currently used, and the long-term use of insecticides can cause mosquitoes to develop knockdown resistance. Studying the mutation sites and genotypes of Ae. aegypti can reveal the mutation characteristics and regional distribution of the kdr gene in an Ae. aegypti population. Testing for a correlation between the mutation rate in various populations and pyrethrin resistance can clarify the resistance mechanism. RESULTS: The bioassay results showed that all 15 populations are resistant. In the study of the kdr gene, three non-synonymous mutations were identified in the DNA of first generation females from the wild Ae. aegypti population: S989P (TCC-CCC), V1016G (GTA-GGA), and F1534C (TTC-TGC). The mortality rate of the various populations was correlated with the mutation rate at the V1016G + F1534C locus, but not the S989P + V1016G locus. CONCLUSION: Aedes aegypti populations in border regions of Yunnan Province are resistant to permethrin and beta-cyfluthrin. The insecticidal effect of beta-cyfluthrin is stronger than that of permethrin. The mutation rate at sites V1016G + F1534C is negatively correlated with the mortality of Ae. aegypti based on bioassays. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fine-scale monitoring of insecticide resistance in Aedes aegypti (Diptera: Culicidae) from Sri Lanka and modeling the phenotypic resistance using rational approximation.

BACKGROUND: The unplanned and intensified use of insecticides to control mosquito-borne diseases has led to an upsurge of resistance to commonly used insecticides. Aedes aegypti, the main vector of dengue, chikungunya, and Zika virus, is primarily controlled through the application of adulticides (pyrethroid insecticides) and larvicides (temephos). Fine spatial-scale analysis of resistance may reveal important resistance-related patterns, and the application of mathematical models to determine the phenotypic resistance status lessens the cost and usage of resources, thus resulting in an enhanced and successful control program. METHODS: The phenotypic resistance for permethrin, deltamethrin, and malathion was monitored in the Ae. aegypti populations using the World Health Organization (WHO) adult bioassay method. Mosquitoes' resistance to permethrin and deltamethrin was evaluated for the commonly occurring base substitutions in the voltage-gated sodium channel (vgsc) gene. Rational functions were used to determine the relationship between the kdr alleles and the phenotypic resistant percentage of Ae. aegypti in Sri Lanka. RESULTS: The results of the bioassays revealed highly resistant Ae. aegypti populations for the two pyrethroid insecticides (permethrin and deltamethrin) tested. All populations were susceptible to 5% malathion insecticide. The study also revealed high frequencies of C1534 and G1016 in all the populations studied. The highest haplotype frequency was detected for the haplotype CC/VV, followed by FC/VV and CC/VG. Of the seven models obtained, this study suggests the prediction models using rational approximation considering the C allele frequencies and the total of C, G, and P allele frequencies and phenotypic resistance as the best fits for the area concerned. CONCLUSIONS: This is the first study to our knowledge to provide a model to predict phenotypic resistance using rational functions considering kdr alleles. The flexible nature of the rational functions has revealed the most suitable association among them. Thus, a general evaluation of kdr alleles prior to insecticide applications would unveil the phenotypic resistance percentage of the wild mosquito population. A site-specific strategy is recommended for monitoring resistance with a mathematical approach and management of insecticide applications for the vector population.

Lack of fitness costs associated with resistance to permethrin in Musca domestica.

Resistance to permethrin has been reported in Pakistani strains of Musca domestica. The present study explored the performance of biological traits and analyzed life tables to determine whether there is any detrimental effect of permethrin resistance on the fitness of permethrin-resistant strains [an isogenic resistant strain (Perm-R) and a field strain (Perm-F)] compared to a susceptible strain (Perm-S). Perm-R and Perm-F exhibited 233.93- and 6.87-fold resistance to permethrin, respectively. Life table analyses revealed that the Perm-R strain had a significantly shorter preadult duration, longer longevity, shorter preoviposition period, higher fecundity, finite rate of increase, intrinsic rate of increase, net reproductive rate and a shorter mean generation time, followed by the Perm-F strain when compared to the Perm-S strain. Data of the performance of biological traits reveled that permethrin resistance strains had a better fit than that of the Perm-S strain. The enhanced fitness of resistant strains of M. domestica may accelerate resistance development to permethrin and other pyrethroids in Pakistan. Some possible measures to manage M. domestica and permethrin resistance in situations of fitness advantage are discussed.

Impact of a spatial repellent intervention on Anopheles kdr insecticide resistance allele in Sumba, Indonesia.

BACKGROUND: The emergence of insecticide resistance and outdoor transmission in malaria-endemic areas underlines the urgent need to develop innovative tools, such as spatial repellents (SR), that may circumvent this residual transmission. With limited options for effective insecticides, regular resistance monitoring is warranted for selecting and using appropriate tools. This study evaluates the pyrethroid knockdown resistance (kdr) allele before and after implementing a transfluthrin-based spatial repellent (SR) intervention in placebo-treated clusters. METHODS: This study looks at the frequency distribution of the kdr allele in Sumba Island from June 2015 to August 2018. Insecticide susceptibility tests were carried out on female Anopheles sp. aged 3-5 days against permethrin 21.5 µg/ml, deltamethrin 12.5 µg/ml, and transfluthrin 10 µg/ml using CDC bottle assay. PCR sequencing of representative samples from adult mosquito collections and insecticide tests revealed the presence of kdr mutations (L1014F and L1014S) in the VGSC gene. RESULTS: A total of 12 Anopheles species, Anopheles tesselatus, Anopheles. aconitus, Anopheles barbirostris, Anopheles kochi, Anopheles annularis, Anopheles maculatus, Anopheles sundaicus, Anopheles flavirostris, Anopheles balabacensis, Anopheles indefinitus, Anopheles subpictus, and Anopheles vagus were analysed. Anopheles vagus and An. sundaicus predominated in the larval populations. Susceptibility assays for all insecticides identified fully susceptible phenotypes in all species examined. Anopheles increasing frequency of kdr mutant alleles during the 3 year SR deployment was observed in both SR-treated and placebo areas, a statistically significant increase occurred in each arm. However, it is unclear how significant SR is in causing the increase in mutant alleles. The L1014S, knockdown resistance east type (kdr-e) allele was detected for the first time among the mosquito samples in this study. The L1014F, knockdown resistance west type (kdr-w) allele and heteroduplex form (wild-type-mutant) were found in almost all Anopheles species examined, including An. vagus, An. aconitus, An. subpictus, An. tesselatus, An. annularis, An. flavirostris and An. sundaicus. CONCLUSION: The presence of fully susceptible phenotypes over time, along with an increase in the frequency distribution of the L1014F/S mutations post-intervention, suggest drivers of resistance external to the study, including pyrethroid use in agriculture and long-lasting insecticidal nets (LLINs). However, this does not negate possible SR impacts that support resistance. More studies that enable the comprehension of possible SR-based drivers of resistance in mosquitoes need to be conducted.

Correlation between pyrethroid knockdown resistance and mutation frequency of voltage-gated sodium channel and its application in Aedes aegypti management.

Aedes aegypti, the primary vector responsible for transmitting dengue fever in southern Taiwan, has developed a relatively high resistance to synthetic pyrethroids. It has evolved four amino acid substitutions in the voltage-gated sodium channel (VGSC), namely S996P, V1023G, F1565C, and D1794Y. To unveil the distribution and correlation of VGSC mutations and pyrethroid resistance among different field populations, Ae. aegypti collected from various districts in Kaohsiung and Tainan Cities underwent tests for resistance development against different pyrethroids and frequency of S996P, V1023G, F1565C, and D1794Y substitutions. The adult knockdown assay revealed a relatively high knockdown resistance in the Ae. aegypti populations from Kaohsiung and Tainan against permethrin, cypermethrin, and fenvalerate (averaging >50-fold). Conversely, less resistance was observed against α-cypermethrin, deltamethrin, λ-cyhalothrin, cyfluthrin, and etofenprox (averaging <35-fold). Using Polymerase Chain Reaction/restriction fragment length polymorphism analysis, four mutant haplotypes were identified in these field populations. Notably, the SIAVFD and SIBVFD wild haplotypes were absent. Analysis utilizing IBM SPSS Statistics 20.0 and Spearman's rank correlation coefficient indicated that Haplotype C (PIAGFD), especially P allele, frequency displayed a significant positive correlation with five Type II pyrethroid resistance, while 1023G and 1023G/G exhibited a significant association with permethrin and fevalerate resistance. Conversely, Haplotype E (SIBVCD) negatively correlated with pyrethroid resistance, particularly fenvalerate resistance (-0.776). Haplotype C and E were the most prevalent and widely distributed among the investigated field populations. This prevalence of haplotype C is likely tied to the extensive and excessive use of Type II pyrethroids for dengue control over the past three decades. Given the significant positive correlation, the best-fit lines and R2 values were established to facilitate the swift prediction of knockdown resistance levels to various pyrethroids based on VGSC mutation frequency. This predictive approach aims to guide insecticide usage and the management of pyrethroid resistance in the field populations of Ae. aegypti in Taiwan.

Genetics, genomics and mechanisms responsible for high levels of pyrethroid resistance in Musca domestica.

Insecticide resistance is both economically important and evolutionarily interesting phenomenon. Identification of the mutations responsible for resistance allows for highly sensitive resistance monitoring and allows tools to study the forces (population genetics, fitness costs, etc.) that shape the evolution of resistance. Genes coding for insecticide targets have many well-characterized mutations, but the mutations responsible for enhanced detoxification have proven difficult to identify. We employed multiple strategies to identify the mutations responsible for the extraordinarily high permethrin resistance in the KS17-R strain of house fly (Musca domestica): insecticide synergist assays, linkage analysis, bulk segregant analyses (BSA), transcriptomics and long read DNA (Nanopore) sequencing. The >85,100-fold resistance in KS17-R was partially suppressed by the insecticide synergists piperonyl butoxide and S,S,S-tributylphosphorothionate, but not by diethyl maleate nor by injection. This suggests the involvement of target site insensitivity, CYP-mediated resistance, possibly hydrolase mediated resistance and potentially other unknown factors. Linkage analysis identified chromosomes 1, 2, 3 and 5 as having a role in resistance. BSA mapped resistance loci on chromosomes 3 and 5. The locus on chromosome 3 was centered on the voltage sensitive sodium channel. The locus on chromosome 5 was associated with a duplication of multiple detoxification genes. Transcriptomic analyses and long read DNA sequencing revealed overexpressed CYPs and esterases and identified a complex set of structural variants at the chromosome 5 locus.

Pyrethroid susceptibility reversal in Aedes aegypti: A longitudinal study in Tapachula, Mexico.

Pyrethroid resistance in Aedes aegypti has become widespread after almost two decades of frequent applications to reduce the transmission of mosquito-borne diseases. Because few insecticide classes are available for public health use, insecticide resistance management (IRM) is proposed as a strategy to retain their use. A key hypothesis of IRM assumes that negative fitness is associated with resistance, and when insecticides are removed from use, susceptibility is restored. In Tapachula, Mexico, pyrethroids (PYRs) were used exclusively by dengue control programs for 15 years, thereby contributing to selection for high PYR resistance in mosquitoes and failure in dengue control. In 2013, PYRs were replaced by organophosphates-insecticides from a class with a different mode of action. To test the hypothesis that PYR resistance is reversed in the absence of PYRs, we monitored Ae. aegypti's PYR resistance from 2016 to 2021 in Tapachula. We observed significant declining rates in the lethal concentration 50 (LC50), for permethrin and deltamethrin. For each month following the discontinuation of PYR use by vector control programs, we observed increases in the odds of mosquitoes dying by 1.5% and 8.4% for permethrin and deltamethrin, respectively. Also, knockdown-resistance mutations (kdr) in the voltage-gated sodium channel explained the variation in the permethrin LC50s, whereas variation in the deltamethrin LC50s was only explained by time. This trend was rapidly offset by application of a mixture of neonicotinoid and PYRs by vector control programs. Our results suggest that IRM strategies can be used to reverse PYR resistance in Ae. aegypti; however, long-term commitment by operational and community programs will be required for success.

In-vivo and in-silico studies to identify toxicity mechanisms of permethrin with the toxicity-reducing role of ginger.

In this study, the toxic effects of permethrin on Allium cepa L. and the protective role of Zingiber officinale rhizome extract (Zoex) were investigated. In this context, 6 different groups were formed. While the control group was treated with tap water, the groups II and III were treated with 10 µg/mL and 20 µg/mL Zoex, respectively, and the group IV was treated with 100 µg/L permethrin. The protective effect of Zoex against permethrin toxicity was studied as a function of dose, and groups V and VI formed for this purpose were treated with 10 µg/mL Zoex + 100 µg/L permethrin and 20 µg/mL Zoex + 100 µg/L permethrin, respectively. After 72 h of germination, cytogenetic, biochemical, physiological, and anatomical changes in meristematic cells of A. cepa were studied. As a result, permethrin application decreased the mitotic index (MI) and increased the frequency of micronuclei (MN), and chromosomal abnormalities. The increase in malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) and the decrease in glutathione (GSH) indicate that permethrin causes oxidative damage. Compared to the control group, a 68.5% decrease in root elongation (p < 0.05) and an 81.8% decrease (p < 0.05) in weight gain were observed in the permethrin-treated group. It was found that the application of Zoex together with permethrin resulted in regression of all detected abnormalities, reduction in the incidence of anatomical damage, MN and chromosomal aberrations, and improvement in MI rates. The most significant improvement was observed in group VI treated with 20 µg/mL Zoex, and Zoex was also found to provide dose-dependent protection. The toxicity mechanism of permethrin was also elucidated by molecular docking and spectral studies. From the data obtained during the study, it was found that permethrin has toxic effects on A. cepa, a non-target organism, while Zoex plays a protective role by reducing these effects.

The effect of educational intervention on efficacy of 1% permethrin shampoo and 4% dimeticone lotion to treat head lice infestation using propensity score matching (PSM).

BACKGROUND: Head lice are a main public health problem and the most important human ectoparasites and the use of pediculicides is the most common way to control it. One of the possible causes of treatment failure is the lack of improper application of pediculicide. The aim of this study was to assess the effect of education on efficacy of 1% permethrin or 4% dimeticone lotion to treat head lice infestation. METHODS: This quasi-experimental study included 100 individuals with head lice infestation from comprehensive urban health centers in Ardabil as the intervention group, and 400 individuals from East Azerbaijan and West Azerbaijan provinces as the control group, from April to March 2019. The data collection tools included a demographic questionnaire and an examination recording sheet, which documented the presence of adult lice or nits. Due to the inability to perform random assignment and control for numerous observed covariates, propensity score matching (PSM) was used. RESULTS: The outcome of treatment included elimination of head lice infestation on is 7, and in the case of recurrence, it was considered on days 14 and 30 after treatment. The results showed that the educational intervention program had a significant positive effect on the efficacy of both treatments. The likelihood of improvement was approximately three times greater in the intervention group compared to the control group. CONCLUSION: Participants who received the training intervention (OR = 3.29; CI 95%: 2.21-4.88) were more likely to have a successful treatment than control group. In the case of providing proper training on the use of pediculicides and observing hygiene tips to patients with pediculosis, could help to successful treatment of pediculosis.