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BACKGROUND: The resurgence of Anopheles funestus, a dominant vector of human malaria in western Kenya was partly attributed to insecticide resistance. However, evidence on the molecular basis of pyrethroid resistance in western Kenya is limited. Here, we reported metabolic resistance mechanisms and demonstrated that multiple non-coding Ribonucleic Acids (ncRNAs) could play a potential role in An. funestus resistance to pyrethroid in western Kenya. Anopheles funestus mosquitoes were sampled using aspiration methods in Bungoma, Teso, Siaya, Port Victoria and Kombewa in western Kenya. The F1 progenies were exposed to deltamethrin (0.05%), permethrin (0.75%), DDT (4%) and pirimiphos-methyl (0.25%) following WHO test guidelines. A synergist assay using piperonyl butoxide (PBO) (4%) was conducted to determine cytochrome P450s role in pyrethroid resistance. RNA-seq was conducted on a combined pool of specimens that were resistant and unexposed, and the results were compared with those of the FANG susceptible reference strain. This approach aimed to uncover the molecular mechanisms underlying the observed phenotypic pyrethroid resistance. RESULTS: Pyrethroid resistance was observed in all sites with an average mortality rate (MR) of 57.6%. Port Victoria had the highest level of pyrethroid resistance to permethrin (MR = 53%) and deltamethrin (MR = 11%. Teso had the lowest level of resistance to permethrin (MR = 70%) and deltamethrin (MR = 87%). Resistance to DDT was observed only in Kombewa (MR = 89%) and Port Victoria (MR = 85%). A full susceptibility to P-methyl (0.25%) was observed in all sites. PBO synergist assay revealed high susceptibility (> 98%) to pyrethroids in all the sites except for Port Victoria (MR = 96%). Whole transcriptomic analysis showed that most gene families associated with pyrethroid resistance comprised non-coding RNAs (67%), followed by immunity proteins (10%), cytochrome P450s (6%), cuticular proteins (5%), olfactory proteins (4%), glutathione S-transferases (3%), UDP-glycosyltransferases (2%), ATP-binding cassettes (2%) and carboxylesterases (1%). CONCLUSION: This study unveils the molecular basis of insecticide resistance in An. funestus in western Kenya, highlighting for the first time the potential role of non-coding RNAs alongside metabolic detoxification in pyrethroid resistance. Targeting non-coding RNAs for intervention development could help in insecticide resistance management.

BACKGROUND: The swift expansion of the invasive malaria vector Anopheles stephensi throughout Africa presents a major challenge to malaria control initiatives. Unlike the native African vectors, An. stephensi thrives in urban settings and has developed resistance to multiple classes of insecticides, including pyrethroids, organophosphates, and carbamates. METHODS: Insecticide susceptibility tests were performed on field-collected An. stephensi mosquitoes from Awash Sebac Kilo, Ethiopia, to assess insecticide resistance levels. Illumina RNA-seq analysis was then employed to compare the transcriptomes of field-resistant populations and susceptible laboratory strains (STE2). RESULTS: An. stephensi populations exhibited high levels of resistance to both deltamethrin (mortality, 39.4 ± 6.0%) and permethrin (mortality, 59.3 ± 26.3%) in WHO tube bioassays. RNA-seq analysis revealed that both field-resistant and field-unexposed populations exhibited increased expressions of genes associated with pyrethroid resistance, including esterases, P450s, and GSTs, compared to the susceptible STE2 strain. Notably, esterase E4 and venom carboxylesterase-6 were significantly overexpressed, up to 70-fold, compared to the laboratory strain. Functional enrichment analysis revealed a significant overrepresentation of genes associated with catalytic activity under molecular functions and metabolic process under biological process. Using weighted gene co-expression network analysis (WGCNA), we identified two co-expression modules (green and blue) that included 48 genes strongly linked to pyrethroid insecticide resistance. A co-expression network was subsequently built based on the weight values within these modules. CONCLUSIONS: This study highlights the role of esterases in the pyrethroid resistance of an An. stephensi population. The identification of candidate genes associated with insecticide resistance will facilitate the development of rapid diagnostic tools to monitor resistance trends.

The recent emergence of Oropouche virus (OROV) highlights the importance of understanding insecticide susceptibility in the genus Culicoides (Diptera: Ceratopogonidae). In addition to the vector of OROV, this genus contains many other species that are biting nuisances and vectors of pathogens that affect humans, livestock, and wildlife. With adulticides as the primary method of Culicoides control, there is growing concern about insecticide resistance, compounded by the lack of tools to monitor Culicoides susceptibility. We adapted the Centers for Disease Control and Prevention (CDC) bottle bioassay and field cage trial methods, typically used to monitor insecticide susceptibility in mosquitoes and formulated adulticide efficacy, to evaluate permethrin susceptibility in the widely distributed coastal nuisance species, Culicoides furens. Permethrin caused 100% mortality in C. furens in field and laboratory assays. We identified a diagnostic dose (10.75 µg) and time (30 min) that resulted in 100% mortality in CDC bottle bioassays. Additionally, we determined that no-see-um netting is an effective mesh for field cage trials, allowing for the accurate assessment of Culicoides susceptibility to ultra-low volume applications of formulated adulticides like Permanone 30–30, a widely used adulticide. These methodologies offer essential tools for assessing Culicoides susceptibility, which is crucial for managing populations of Culicoides and preventing the spread of OROV and other pathogens. [ABSTRACT FROM AUTHOR]

This article explores the effects of acute permethrin exposure on sinonasal epithelia in a murine model. The study found that mice exposed to permethrin showed signs of inflammation, including increased mucinous cells, neutrophilic infiltration, and lymphocytic infiltration in sinus tissues. The research suggests that short-term intranasal exposure to permethrin has a proinflammatory impact on sinonasal epithelia. [Extracted from the article]

Background: Scabies is a contagious skin conditions that exclusively infect humans and spread through direct skin-to-skin contact. Aim: This study aimed to compare the effectiveness and adverse effects of 5% topical permethrin and oral ivermectin versus 5% topical permethrin alone for the treatment of scabies. Methods: This prospective observational comparative study included 150 diagnosed patients with scabies aged > 5 years who were divided into two groups. Group A received 5% permethrin cream and 12-mg of ivermectin, and group B received 5% permethrin cream. The patients were followed up at the first, second, and fourth weeks. The effectiveness of the treatment was assessed according to the reduction in the number and severity of lesions. The severity of itching was assessed by using a Visual Analog Scale (VAS). The adverse effects were also monitored. Statistical analysis was performed using Statistical Package for Social Sciences version 20. Student "t" test, the chisquare test, and the Friedman test were used. Results: There were 71 males (47.3%) and 79 females (52.6%). Group A exhibited mean and standard deviation (m ± SD) values of 40.3 ± 9.4 and 2.8 ± 3.4 for no. of lesions at baseline and at week 4, respectively. In contrast, Group B had 40.1 ± 10.7 and 2.7 ±3.2 for no. of lesions at these time points. For VAS score, Group A recorded 2.89 ± 0.31 and 0.79 ± 0.68 at baseline and at week 4, while Group B showed 2.81 ± 0.39 and 0.71 ± 0.63 for these respective measures. The groups were compared, and the p value was > 0.05. The incidence of adverse effects was higher in Group A than in Group B. Conclusion: Both groups showed equal effectiveness in the treatment of scabies. [ABSTRACT FROM AUTHOR]

Background: Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists. Methods: Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts. Results: Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC50s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC50 of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD50s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants' secondary metabolites. Conclusion: This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC50 < 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors. [ABSTRACT FROM AUTHOR]

Abstract Background Tanzania has experienced outbreaks of dengue fever in major cities. The main vectors of the dengue virus in Tanzania are Aedes aegypti mosquitoes. The control of this mosquito vector is based on insecticide, and yet, the insecticide susceptibility of this species is not well known in many places in Tanzania. Conversely, the breeding habitats mostly preferred by this species are not well documented in the study area. Therefore, the present study aimed to determine the pyrethroid insecticide susceptibility status and breeding habitats preference of Ae. aegypti mosquito in the three sites from three districts in Mwanza, Tanzania. The assessment of Ae. aegypti mosquito 24-h percentage mortality was based on WHO criteria. Results A total of 850 Ae. aegypti were exposed to three pyrethroid insecticides. In Bwiru site, 100% mortality was observed for all three pyrethroids, indicating full susceptibility. At Igekemaja and Mwagagala villages, Ae. aegypti were resistant to all the three pyrethroid insecticides tested. In Igekemaja, there were variations in Ae. aegypti mortality rates induced by different insecticides, with mortality rates ranging from 72% for alphacypermethrin to 86% for deltamethrin. Although the mortality rates were lower than in Bwiru site, they were still substantial and statistically significant. The mortality rates in Mwagagala were lowest across the three insecticides, with mortality rates ranging from 60% for deltamethrin to 86% for alphacypermethrin. In Mwagagala, the Ae. aegypti mosquitoes were less susceptible to the insecticides tested. Aedes aegypti mosquito prefer breeding in abandoned old tires in urban area and in small containers and uncovered water storage containers in rural settings. Conclusion The study has revealed pyrethroid insecticide susceptibility status and breeding habitats of Ae. aegypti in the rural and urban settings in Mwanza, Tanzania. The study findings imply the need for public health interventions with focus on community education on mosquito control.

Permethrin (PMT) is a synthetic pyrethroid insecticide widely applied in the agriculture and animal husbandry industry. The current study focused on the evaluation of the oxidative damage and apoptosis induced by PMT, as well as the protective role of coenzyme Q10 and N-acetylcysteine (NAC) against PMT toxicity in the liver of male rats. In this study, rats were divided in four groups, including G1 (control), G2 (PMT), G3 (NAC + PMT), and G4 (Q10 + PMT). Levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. RT-PCR was adopted to study the expression of Bax, Bcl2, p53, Caspases-3 and -9 genes. PMT exposure significantly decreased FRAP value, whereas increased MDA content in the liver tissue (p < 0.001). While Bcl2 was downregulated (5.31-fold), permethrin increased the expression of Bax (4.84-fold), p53 (4.67-fold), Caspases-3 (6.21-fold) and Caspases -9 (6.36-fold) genes in exposed group (p

One of the important causes of Parkinson's disease is the permethrin pesticide. Therefore, the objective of the present study was to synthesise new catalyst based on TiO2 immobilised in steel slag (SS) for photocatalytic degradation of permethrin in aqueous solutions. The experiments were designed by response surface methodology (RSM) using design expert software. The parameters such as pH, dose (g), concentration of permethrin (mgL−1) and agitation time were variables of the process, and their optimal conditions were taken by conducting 30 experiment runs. The characterisation of the resulting catalyst shows that coating Ni-TiO2 onto the modified SS has improved its photocatalytic properties. DRS and PL results showed not only well-doping TiO2 by Ni but also coating Ni-TiO2 onto the modified SS makes a reduction in the band gap, from 2.78 to 2.61 eV, and electron recombination. Additionally, the saturated magnetisation value, VSM, for SS@Ni-TiO2 was found to be 54 emu/g. The catalyst dosage was the most influent parameter which achieved an F-value of 42.18 followed by agitation time (33.58), pH (11.69) and concentration of permethrin (4.97) with the high R2 value of 0.9952.Overall, the performance of the process in optimum conditions, such as pH 7, dose 0.7 g, concentration of permethrin 50 mgL−1 and agitation time 30 min, was 72.11%, and the effect of the parameters studied on the process was significant (p-value <0.5). In addition, it resulted that $$H{O^\circ }$$ HO ° plays a crucial role in the photocatalytic degradation of permethrin by SS@Ni-TiO2 composite. The SS@Ni-TiO2 exhibited excellent photocatalytic reactivity for permethrin over five cycles. During the five cycles, only 4% reduction was observed in the photocatalytic degradation of permethrin. In conclusion, the SS@Ni-TiO2 would be a promising catalyst for photocatalytic degradation of permethrin from aqueous solution. [ABSTRACT FROM AUTHOR]

Background: Tanzania has experienced outbreaks of dengue fever in major cities. The main vectors of the dengue virus in Tanzania are Aedes aegypti mosquitoes. The control of this mosquito vector is based on insecticide, and yet, the insecticide susceptibility of this species is not well known in many places in Tanzania. Conversely, the breeding habitats mostly preferred by this species are not well documented in the study area. Therefore, the present study aimed to determine the pyrethroid insecticide susceptibility status and breeding habitats preference of Ae. aegypti mosquito in the three sites from three districts in Mwanza, Tanzania. The assessment of Ae. aegypti mosquito 24-h percentage mortality was based on WHO criteria. Results: A total of 850 Ae. aegypti were exposed to three pyrethroid insecticides. In Bwiru site, 100% mortality was observed for all three pyrethroids, indicating full susceptibility. At Igekemaja and Mwagagala villages, Ae. aegypti were resistant to all the three pyrethroid insecticides tested. In Igekemaja, there were variations in Ae. aegypti mortality rates induced by different insecticides, with mortality rates ranging from 72% for alphacypermethrin to 86% for deltamethrin. Although the mortality rates were lower than in Bwiru site, they were still substantial and statistically significant. The mortality rates in Mwagagala were lowest across the three insecticides, with mortality rates ranging from 60% for deltamethrin to 86% for alphacypermethrin. In Mwagagala, the Ae. aegypti mosquitoes were less susceptible to the insecticides tested. Aedes aegypti mosquito prefer breeding in abandoned old tires in urban area and in small containers and uncovered water storage containers in rural settings. Conclusion: The study has revealed pyrethroid insecticide susceptibility status and breeding habitats of Ae. aegypti in the rural and urban settings in Mwanza, Tanzania. The study findings imply the need for public health interventions with focus on community education on mosquito control. [ABSTRACT FROM AUTHOR]

Quantifying the consequences of winter ticks (Dermacentor albipictus) on the body condition and life‐history traits of moose (Alces alces) is a challenge due to several confounding factors. We experimentally reduced tick load on moose calves by testing the effectiveness of 2 acaricide treatments: one using topical permethrin (5%) alone and the other a combination of a more concentrated topical permethrin (44%) and orally administered fluralaner (25 mg/kg). We evaluated changes in tick load, body mass, hematocrit, and hair loss severity and occurrence, from recaptured or resighted moose calves over winter in Québec and New Brunswick, Canada. Nearly all untreated moose (94%, n = 41) experienced hair loss compared to calves that received the combination of permethrin (44%) and fluralaner (41%, n = 37). Of treated moose that exhibited hair loss, only 22% had more than 5% damage and some already had hair loss at capture. Capturing moose later likely increased the probability of observing hair loss when resighting treated moose, although hair loss essentially remained lower for treated calves than for untreated calves. In untreated moose, tick load at capture tended to drive hair loss, but calendar date mostly drove hair loss severity, especially during April. There was no clear effect of topical permethrin (5%) on tick load, body mass, and hematocrit. Body condition simply decreased from January captures to spring recaptures, regardless of treatment. Our results suggested that combining permethrin (44%) and fluralaner effectively reduced tick load based on hair loss severity and occurrence. We cannot, however, disentangle the individual effects of permethrin (44%) and fluralaner. We discuss research implications and considerations of using such a treatment for reducing winter tick load. [ABSTRACT FROM AUTHOR]

Head lice infestations significantly impact schoolchildren, with permethrin being the primary treatment. The escalation in the prevalence of the knockdown resistance (kdr) mutation, potentially affecting treatment efficacy, is highly concerning. This study examined head lice infestation prevalence, the efficacy of 1% permethrin lotion, kdr mutation frequency, and the association between kdr genotype and permethrin treatment outcomes in schoolchildren in Nonthaburi province, Thailand. Participants and lice samples were collected from six primary schools using cluster sampling. Clinical outcomes and adverse events were assessed on days 7 and 14 post-treatment. Kdr mutations (T917I) in head lice samples were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Head lice infestation prevalence was 6.1%, with a kdr mutation frequency of 63.2% and a permethrin cure rate of approximately 50%. Multivariate regression analysis revealed the association between kdr genotype and clinical response to permethrin treatment (Odds Ratio (OR) = 13.15, p = 0.005). The presence of resistance genes hinders the cure rate (presence 35.9% versus absence 85.7%). These findings highlight the importance of the kdr genotype in predicting permethrin treatment responses in head lice infestations. Furthermore, in regions with documented reduced permethrin efficacy and a high prevalence of kdr mutations, alternative non-pyrethroid-based pediculicides should be considered. This research could help improve the control of head lice infestations, especially in problematic areas of Thailand. [ABSTRACT FROM AUTHOR]

Head lice infestation (HLI), caused by Pediculus humanus capitis De Geer, 1767, has long been a common global problem of school children. Permethrin is an old pyrethroid derivative that has been used commonly for its treatment, and it exerts its activity over the voltage-sensitive calcium channels (VSCC) of the lice. There has been a growing list of persistent HLI cases lately in the world among patients using permethrin, and knockdown resistance (kdr)-related point mutations on VSCC have been identified and reported from those resistant lice samples. The aim of this study was to investigate the gene mutations associated with permethrin resistance in head lice collected from primary school children in Istanbul (Türkiye) and Nagarkot (Nepal) for the first time. A total of 192 P. h. capitis adults were collected from school children aged 6–12 years in two cities (96 lice each). Following DNA isolation, the fragment of the VSCC a-subunit gene, which contained the possible mutation sites ((kdr-like M815I (ATG > ATT), kdr T917I (ACA > ATA), and kdr-like L920F (CTT > TTT)), was amplified in each louse by PCR, and the PCR products were sequenced and aligned, followed by frequency calculations for alleles, genotypes, and haplotypes. Using nucleic acid sequence analysis, it was revealed that M815I, T917I, or L920F mutations were present on the VSCC genes in the lice samples from both Türkiye and Nepal. In addition, genotypic analyses indicated the presence of all three mutations in the lice samples from Türkiye, while the T917I mutation was detected in none of the lice collected in Nepal. This is the first report of gene mutations associated with permethrin resistance in head lice collected from a group of primary school children in the largest city of Türkiye (Istanbul) and Nagarkot. High mutation rates were identified in the lice, especially those from Istanbul, which is concordant with our previous unpublished study, in which almost 60% of the examined lice of the school children (in the same school selected in this study) remained alive despite long-term exposure to permethrin in the laboratory. These initial results show that gene mutations associated with permethrin resistance are common in lice samples in Istanbul and Nagarkot, which may suggest the current need for the selection of new pediculicidal agents in HLI treatment. [ABSTRACT FROM AUTHOR]

Developmental exposure to carbamates, organophosphates, and pyrethroids has been associated with impaired neurodevelopmental outcomes. Sex-specific differences following chronic insecticide exposure are rather common in vivo. Therefore, we assessed the chronic effects of in vitro exposure to different carbamates (carbaryl, methomyl and aldicarb), organophosphates [chlorpyrifos (CPF), chlorpyrifos-oxon (CPO), and 3,5,6,trichloropyridinol (TCP)], and pyrethroids [permethrin, alpha-cypermethrin and 3-phenoxy benzoic acid (3-PBA)] on neuronal network development in sex-separated rat primary cortical cultures using micro-electrode array (MEA) recordings. Our results indicate that exposure for 1 week to carbaryl inhibited neurodevelopment in male cultures, while a hyperexcitation was observed in female cultures. Methomyl and aldicarb evoked a hyperexcitation after 2 weeks of exposure, which was more pronounced in female cultures. In contrast to acute MEA results, exposure to ≥ 10 µM CPF caused hyperexcitation in both sexes after 10 days. Interestingly, exposure to 10 µM CPO induced a clear hyperexcitation after 10 days of exposure in male but not female cultures. Exposure to 100 µM CPO strongly inhibited neuronal development. Exposure to the type I pyrethroid permethrin resulted in a hyperexcitation at 10 µM and a decrease in neuronal development at 100 µM. In comparison, exposure to ≥ 10 µM of the type II pyrethroid alpha-cypermethrin decreased neuronal development. In female but not in male cultures, exposure to 1 and 10 µM permethrin changed (network) burst patterns, with female cultures having shorter (network) bursts with fewer spikes per (network) burst. Together, these results show that MEA recordings are suitable for measuring sex-specific developmental neurotoxicity in vitro. Additionally, pyrethroid exposure induced effects on neuronal network development at human-relevant concentrations. Finally, chronic exposure has different effects on neuronal functioning compared to acute exposure, highlighting the value of both exposure paradigms. [ABSTRACT FROM AUTHOR]

Demodex species are associated with many dermatological diseases, so an acaricidal agent that is effective against them and safe for skin applications may benefit many diseases. This study aims to investigate the anti-demodex potential of spilanthol, a product obtained from the Spilanthes Acmella plant, by determining the minimal effective dose for the first time in the literature. Demodex mites were obtained from 70 patients with standard superficial skin biopsy. Spilanthol extract was used at 1%, 2%, 3%, 4%, and 5%. Standard immersion oil was used for the negative control, and permethrin 5% was used for the positive control group. The dependent variable is the survival time of the mite. Comparisons with the negative control group, the anti-demodex effect demonstrated itself in all groups, creating a statistically significant difference (p < 0.001). The positive control group, had 3%, 4%, and 5% spilanthol rates which were very similar to the results with 5% permethrin (p > 0.05). Higher concentrations than 3% did not make any additional contribution to survival times. This is the first attempt to show the dose-dependent acaricidal effect of spilanthol on demodex mites. Even the 3% dose shows similar results to 5% permethrin, and no additional effect increase was observed at higher doses. Therefore, in vivo, studies may be planned with a 3% spilanthol dose for further studies. [ABSTRACT FROM AUTHOR]

The octanol/water partition coefficient, P (logP), is a hydrophobicity index and is one of the determining factors of the pharmacokinetics of chemical compounds. LogP values obtained from in silico software, open chemistry databases, and in vitro liquid chromatography retention factors may vary. Some chemicals (boscalid, etoxazole, and permethrin) have up to four-order-magnitude differences in in silico/in vitro P values. This study aimed to evaluate the effects of logP values of these three compounds, along with bisphenol A, 1,2-dibromobenzene, tetrabromobisphenol A, trazodone, and triazolam, on the input parameters and output plasma/hepatic concentration–time profiles of simple physiologically based pharmacokinetic (PBPK) models. Although the blood-to-plasma concentration ratios (~0.9–0.6) were slightly affected by variations in logP values, logarithmic plasma unbound fraction values and liver-to-plasma partition coefficients (Kp,h) were, respectively, inversely and linearly correlated with logP values (Kp,h was stable at ~6.7 for logP > 4). LogP was among the input parameters for previously established machine learning systems; consequently, the resulting logarithmic intrinsic clearance values were correlated with logP values in the range 2–8. However, the bioavailability, absorption rate constants, and volumes of distribution were not affected. PBPK-modeled plasma and hepatic maximum concentrations and areas under the concentration–time curves after virtual oral doses were mostly within ~0.5- to ~2-fold ranges, except for substances with low in vitro logP values, e.g., etoxazole and permethrin. These results suggest that in silico logP values are generally suitable for pharmacokinetic modeling; nevertheless, caution is needed for compounds with low in vitro logP values of ~2. [ABSTRACT FROM AUTHOR]

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Pyrethroids are the most widely used insecticides for controlling insect vectors carrying medically and economically significant pathogens. In Colombia, studies on triatomine insecticide resistance are limited. Due to the increasing challenge of insecticide resistance, this work focuses on determining resistance to different pyrethroid insecticides in populations of Triatoma dimidiata from Colombia. To define the possible causes of resistance, three potential molecular mechanisms were explored: 1) mutations in the coding region of the voltage-gated sodium channel gene (vgsc), the insecticide target site; 2) modulation of enzymatic activity associated with metabolic resistance; and 3) changes in the mRNA profiles using RNA-seq. The results showed that the field population of T. dimidiata was resistant to lambda-cyhalothrin and deltamethrin insecticides. Insects surviving sublethal doses of insecticides did not exhibit the classical mutations in the vgsc gene. Transcriptomic profile analyses of T. dimidiata revealed differentially regulated genes in field and laboratory populations under selective pressure with lambda-cyhalothrin. Gene enrichment analysis showed the positive regulation of transcripts related to detoxifying enzymes and mitochondrial proteins, which could play a significant role in insecticide resistance. This comprehensive investigation is crucial for providing insights into resistance mechanisms and generating strategies to manage these critical vector species.

On October 2, 2022, a 60-year-old male hobbyist outdoor photographer in southern Manitoba, Canada, noticed a black-legged tick (Ixodes scapularis) attached to his neck (Figure). The patient sought treatment for [...]

Gulf War Illness (GWI) affects nearly 30% of veterans from the 1990-1991 Gulf War (GW) and is a multi-symptom illness with many neurological effects attributed to in-theater wartime chemical overexposures. Brain-focused studies have revealed persistent structural and functional alterations in veterans with GWI, including reduced volumes, connectivity, and signaling that correlate with poor cognitive and motor performance. GWI symptomology components have been recapitulated in rodent models as behavioral, neurochemical, and neuroinflammatory aberrations. However, preclinical structural imaging studies remain limited. This study aimed to characterize the progression of brain structural alterations over the course of 12 months in two established preclinical models of GWI. In the PB/PM model, male C57BL/6 J mice (8-9 weeks) received daily exposure to the nerve agent prophylactic pyridostigmine bromide (PB) and the pyrethroid insecticide permethrin (PM) for 10 days. In the PB/DEET/CORT/DFP model, mice received daily exposure to PB and the insect repellent DEET (days 1-14) and corticosterone (CORT; days 7-14). On day 15, mice received a single injection of the sarin surrogate diisopropylfluorophosphate (DFP). Using a Varian 7 T Bore MRI System, structural (sagittal T2-weighted) scans were performed at 6-, 9-, and 12-months post GWI exposures. Regions of interest, including total brain, ventricles, cortex, hippocampus, cerebellum, and brainstem were delineated in the open source Aedes Toolbox in MATLAB, followed by brain volumetric and cortical thickness analyses in ImageJ. Limited behavioral testing 1 month after the last MRI was also performed. The results of this study compare similarities and distinctions between these exposure paradigms and aid in the understanding of GWI pathogenesis. Major similarities among the models include relative ventricular enlargement and reductions in hippocampal volumes with age. Key differences in the PB/DEET/CORT/DFP model included reduced brainstem volumes and an early and persistent loss of total brain volume, while the PB/PM model produced reductions in cortical thickness with age. Behaviorally, at 13 months, motor function was largely preserved in both models. However, the GWI mice in the PB/DEET/CORT/DFP model exhibited an elevation in anxiety-like behavior. [ABSTRACT FROM AUTHOR]

Background: Scabies is a prevalent dermatological condition with significant public health implications. The recent rise in drug-resistant scabies presents new challenges for effective disease management and control. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, and Web of Science. Studies published from 2000 to August 2024 were considered, focusing on those reporting drug-resistant scabies and advancements in treatment approaches. Results: Clinical studies, in vitro investigations, and case reports show significant resistance of human scabies to permethrin. Main resistance mechanisms involve genetic mutations in the mites' voltage-gated sodium channels (VGSCs) and enhanced activity or expression of the detoxifying enzyme glutathione S-transferase (GST). Resistance to ivermectin and benzyle benzoate, although suggested by some authors, seems less obvious. The clinical evidence of widespread ivermectin resistance in human scabies infestations is lacking, despite indications of increased tolerance in laboratory settings and anecdotal reports of resistance in patients with crusted scabies. Benzyl benzoate resistance in scabies mites remains unconfirmed. Conclusions: Permethrin-resistant scabies is an escalating threat requiring new management strategies and updated guidelines. Infection control measures, alternative treatments, and ongoing research into new therapeutics are crucial to mitigate the impact of drug-resistant scabies. [ABSTRACT FROM AUTHOR]

Gulf War Illness (GWI) is a chronic multisymptom disorder that affects approximately 25–32% of Gulf War veterans and is characterized by a number of symptoms such as cognitive impairment, psychiatric disturbances, chronic fatigue and gastrointestinal distress, among others. While the exact etiology of GWI is unknown, it is believed to have been caused by toxic exposures encountered during deployment in combination with other factors such as stress. In the present study we sought to evaluate the hypothesis that exposure to the toxin permethrin could prime neuroinflammatory stress response and elicit psychiatric symptoms associated with GWI. Specifically, we developed a mouse model of GWI, to evaluate the effects of chronic permethrin exposure followed by unpredictable stress. We found that subjecting mice to 14 days of chronic permethrin exposure followed by 7 days of unpredictable stress resulted in the development of depression-like behavior. This behavioral change coincided with distinct alterations in the microglia phenotype, indicating microglial activation in the hippocampus. We revealed that blocking microglial activation through Gi inhibitory DREADD receptors in microglia effectively prevented the behavioral change associated with permethrin and stress exposure. To elucidate the transcriptional networks impacted within distinct microglia populations linked to depression-like behavior in mice exposed to both permethrin and stress, we conducted a single-cell RNA sequencing analysis using 21,566 single nuclei collected from the hippocampus of mice. For bioinformatics, UniCell Deconvolve was a pre-trained, interpretable, deep learning model used to deconvolve cell type fractions and predict cell identity across spatial datasets. Our bioinformatics analysis identified significant alterations in permethrin exposure followed by stress-associated microglia population, notably pathways related to neuronal development, neuronal communication, and neuronal morphogenesis, all of which are associated with neural synaptic plasticity. Additionally, we observed permethrin exposure followed by stress-mediated changes in signal transduction, including modulation of chemical synaptic transmission, regulation of neurotransmitter receptors, and regulation of postsynaptic neurotransmitter receptor activity, a known contributor to the pathophysiology of depression in a subset of the hippocampal pyramidal neurons in CA3 subregions. Our findings tentatively suggest that permethrin may prime microglia towards a state of inflammatory activation that can be triggered by psychological stressors, resulting in depression-like behavior and alterations of neural plasticity. These findings underscore the significance of synergistic interactions between multi-causal factors associated with GWI. [ABSTRACT FROM AUTHOR]

Pesticide residue levels in water bodies have increased due to the extensive use of pesticides in agriculture. To address this challenge, this study considered the possibility of using biogenic silver nanoparticles (Ag-NPs) embedded in chitosan beads to remove the pesticide. A simple, efficient method was used: Ag-NPs (diameter range: 8.02 to 27.2nm) were biosynthesized by Fredinandcohnia onubensis and then immobilized on chitosan to remove the permethrin from aqueous solutions. At 90%, the resultant chitosan silver nanoparticles composite (CS-Ag-NPs composite) showed a remarkable adsorption capacity. To be more precise, 1g of CS-Ag-NPs composite efficiently eliminated 90% of permethrin from a 25mL pesticide solution (0.1mg/ L) under controlled circumstances (35°C, pH 7-, and 60-minutes shaking). These results demonstrate the potential of Fredinandcohnia onubensis-biosynthesized CS-Ag-NPs composites as a novel, biocompatible, and eco-friendly method for the removal of pesticide in water treatment applications. [ABSTRACT FROM AUTHOR]

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides, such as Roundup, Malathion, and Permethrin, have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other non-target organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of Permethrin, Malathion, and Roundup. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid Permethrin was the most toxic pesticide tested, with a median lethal concentration (LC50) value for 96 h of 3.96 × 10−6 µg·L−1, followed by organophosphate Malathion (8.87 µg·L−1) and Roundup (748.92 µg·L−1). Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti (L.) is the main vector of dengue, yellow fever, Zika, and chikungunya viruses in many parts of the world, impacting millions of people worldwide each year. Insecticide-based interventions have been effective in controlling Aedes mosquito populations for several years, but in recent times, resistance to these compounds has developed, posing a global threat to the control of this mosquito. Methods: Ovitraps were used to collect A. aegypti eggs in the cities of Tartagal and San Ramón de la Nueva Orán (Salta), Puerto Iguazú (Misiones), and Clorinda (Formosa). World Health Organization (WHO)-impregnated papers with the discriminating concentration (DC) of permethrin, 5X, 10X and pirimiphos methyl were used for the toxicological bioassays. We also genotyped each sample for the three kdr single nucleotide polymorphisms (SNP): V410L, V1016I, and F1534C in individual TaqMan quantitative PCR (qPCR) reactions. Results: All investigated A. aegypti populations were highly resistant to permethrin, as the mortality percentage with the permethrin 10×DC remained below 98%. However, all populations were 100% susceptible to pirimiphos-methyl. Kdr genotyping demonstrated the presence of the V410L mutation for the first time in Argentina in all the populations studied. A prevalence of the triple mutant genotype (LL + II + CC) was observed in the northeastern cities of Clorinda (83.3%) and Puerto Iguazú (55.6%). Conclusions: This study demonstrates for the first time the presence and intensity of resistance to permethrin in different populations from Argentina, and correlates the observed phenotype with the presence of kdr mutations (genotype). [ABSTRACT FROM AUTHOR]

Aquatic toxicity tests with benthic organisms are used to predict the toxicity of hydrophobic organic chemicals (HOCs) in sediments, assuming that the freely dissolved concentration (Cfree) is a good surrogate of bioavailability in the exposure system. However, Cfree of HOCs is difficult to control in water‐only setups. Moreover, the role of dissolved organic carbon (DOC) in the occurrence of toxicity needs clarification because DOC concentrations in sediment porewater can be substantially higher than in typical test water. We introduced biocompatible polyethylene meshes with high sorptive capacities and fast release kinetics as a novel passive dosing phase, which maintained Cfree and Cwater (i.e., free + DOC‐bound) in Hyalella azteca water‐only tests. Adding the supernatant fraction of peat to test water as a DOC source increased Cwater to an extent comparable to sediment porewater and significantly increased and decreased the observed toxicity of permethrin and benzo[a]pyrene, respectively, to H. azteca. This result indicates that DOC can both benefit and harm test species likely due to the increased health after ingestion of DOC and to the uptake of DOC‐bound HOCs, respectively. Passive dosing in combination with the addition of sediment DOC surrogates may better reflect exposure and habitat conditions in sediment porewater than conventional aquatic tests. Environ Toxicol Chem 2024;43:1747–1756. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

The widespread use of pyrethroid and organophosphate pesticides necessitates accurate toxicity predictions for regulatory compliance. In this study QSAR and SSD models for six pyrethroid and four organophosphate compounds using QSAR Toolbox and SSD Toolbox have been developed. The QSAR models, described by the formula 48 h-EC50 or 96 h-LC50 = x + y * log Kow, were validated for predicting 48 h-EC50 values for acute Daphnia toxicity and 96 h-LC50 values for acute fish toxicity, meeting criteria of n ≥10, r2 ≥0.7, and Q2 >0.5. Predicted 48 h-EC50 values for pyrethroids ranged from 3.95 × 10−5 mg/L (permethrin) to 8.21 × 10−3 mg/L (fenpropathrin), and 96 h-LC50 values from 3.89 × 10−5 mg/L (permethrin) to 1.68 × 10−2 mg/L (metofluthrin). For organophosphates, 48 h-EC50 values ranged from 2.00 × 10−5 mg/L (carbophenothion) to 3.76 × 10−2 mg/L (crufomate) and 96 h-LC50 values from 3.81 × 10−3 mg/L (carbophenothion) to 12.3 mg/L (crufomate). These values show a good agreement with experimental data, though some, like Carbophenothion, overestimated toxicity. HC05 values, indicating hazardous concentrations for 5% of species, range from 0.029 to 0.061 µg/L for pyrethroids and 0.030 to 0.072 µg/L for organophosphates. These values aid in establishing environmental quality standards (EQS). Compared to existing EQS, HC05 values for pyrethroids were less conservative, while those for organophosphates were comparable. [ABSTRACT FROM AUTHOR]

Mosquitoes are prime examples of vectors for various diseases such as malaria, the West Nile virus, elephantiasis, dengue fever, and yellow fever. The repeated use of chemical pesticides has created numerous obstacles and environmental risks including mosquito resistance to insecticides. This work aimed at assessing the larvicidal effect of chlorophyllin (a water-soluble substance obtained after removing the phytol tail from chlorophyll) and coumarin as photosensitizers, compared to the microbial insecticide Bacillus thuringiensis israelensis (Bti) and permethrin, a chemical insecticide, against the third larval instar of Culex pipiens larvae monitoring its mode of action and its genotoxic effect. Photosensitizers exposed to sunlight generate reactive oxygen species (ROS), with singlet oxygen (¹O2) capable of killing parasitic organisms primarily in aquatic systems. Our experiments demonstrated a high potential activity of Na-Cu chlorophyllin against mosquito larvae after at least 8 hours of incubation in the dark. The LC50 values were 0.22x10-3, 0.96x10-2, 13.7x10-2, and 4.59x10-1 mg/ l after 24 hours of exposure to chlorophyllin, Bti, permethrin, and coumarin, respectively. The molecular changes after treatment with chlorophyllin were tracked using RAPD-PCR with six arbitrary DNA primers. Results confirmed no significant changes or genetic damage after treatment with chlorophyll derivatives. [ABSTRACT FROM AUTHOR]

Background: Resistance to insecticides is one of the major problems in successfully controlling of mosquito-borne diseases. The present study explores the role of Voltage-Gated Sodium Channel (VGSC) and their mutation in the development of insecticide resistance in Anopheles mosquito. Materials and Methods: Homology protein modelling of wild-type and mutated VGSC protein was performed using the Swiss-Model server. Model proteins were analyzed using different bioinformatic tools, such as Procheck, Anolea, Errat, to study the overall quality. The binding affinity of insecticide permethrin with VGSC was analyzed using Autodock Tools software. Results and Discussion: The study observed that the model proteins have slight structural deviation between wild-type and mutant proteins. Model proteins docked with permethrin insecticide showed a higher binding affinity with wild-type than mutant channel protein. The present studies suggest that the point mutation in codon 1014 (Leucine→Cysteine) affects the complex stability, plausibly resisting the effect of the insecticide permethrin. Conclusion: The present study proposes the molecular interaction of permethrin with the ion channel leading to the development of insecticide resistance capacity in mosquito vectors. [ABSTRACT FROM AUTHOR]