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Deltamethrin (DLM) is a newer kind of insecticide that is used on pets, livestock, and crops, as well as to combat malaria vectors and household pests. It belongs to the synthetic pyrethroid group and is being promoted as an alternative to organophosphate chemicals due to its persistent and destructive effects. The current study aimed to evaluate the impact of sub-chronic oral exposure to DLM on autoimmune activity in rats. Three groups of male albino rats (15 rats/group) including the control group, the ethanol-treated group (1 ml/rat), and the DLM-treated group (5 mg/kg b.w). Samples of blood were taken from all groups at 4-, 8- and 12-week intervals for the determination of hematological, cytokines, and immunological parameters. T lymphocyte subsets and Treg lymphocytes were determined in serum using flow cytometric acquisition. The results revealed that DLM significantly increased TNF-α, IL-33, IL-6, IL-17, IgG, IgM, WBCs, differential count, and platelets while decreasing Hb concentration and RBCs. Additionally, DLM decreased the number of T-cell subsets (CD3, CD4, CD5, and CD8) and Treg lymphocytes. All of these impacts became more severe over time. It is possible to conclude that the sub-chronic oral exposure to DLM disturbed autoimmune activity through the disturbances in immunological indices, CDs subset Treg lymphocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The effectiveness of a visceral leishmaniasis (VL) control strategy based on the application of 4 % deltamethrin impregnated collars (DIC) exclusively in seropositive dogs was assessed between 2018 and 2019, through a prospective study. The effectiveness of DIC-collaring was evaluated by comparing the incidence rate of anti-leishmanial antibodies among dogs from two endemic districts in Brazil. In one of the areas, the conventional control measure which is based on the non-compulsory euthanasia of LV seropositive dogs, was practiced by the official healthy service as a regular procedure, whereas strategic collaring, conceived in this study, was carried out in the other. Results of serological tests applied to serum samples collected from all domiciled dogs were evaluated in three consecutive times, spaced by around 200 days. Incidence rates of VL seroreactivity were compared between districts in the same period of time as well as within the same district, in consecutive periods. Based on the results, the risk of infection in the population under conventional control measure was up to four times higher than the risk of infection where DIC-collaring was used. The strategic use of collar proposed here emerged as a promising measure for VL control in dogs from endemic areas. Strategic collaring does not rely on the euthanasia of infected animals, an extremely controversial procedure, and instead of being used in all dogs, as collaring is normally recommended; only seropositive dogs are intervened. Strategic use of DIC has the potential to drastically reduce costs, if compared to mass collaring canine population., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Believed to cause damage to the nervous system and possibly being associated with neurodegenerative diseases, deltamethrin (DM) is a type II pyrethroid used in pest control, public health, home environment, and vector control. The objective of this study was to evaluate the motor, cognitive and emotional changes associated with dopaminergic and BDNF imbalance after DM exposure in rats. Sixty Wistar rats (9-10 months-old) were used, under Ethics Committee on Animal Research license (ID 19/2017). The animals were randomly divided into four groups: control (CTL, 0.9% saline), DM2 (2 mg DM in 1.6 mL 0.9% saline), DM4 (4 mg of DM in 1.6 mL of 0.9% saline), and DM8 (8 mg of DM in 1.6 mL of 0.9% saline). DM groups were submitted to 9 or 15 inhalations, one every 48 h. Half of the animals from each group were randomly selected and perfused 24 h after the 9th or 15th inhalation. Throughout the experiment, the animal's behavior were evaluated using catalepsy test, open field, hole-board test, Modified Elevated Plus Maze, and social interaction. At the end of the experiments, the rats were perfused transcardially and their brains were processed for Tyrosine Hydroxylase (TH) and Brain derived neurotrophic factor (BDNF) immunohistochemistries. The animals submitted to 9 inhalations of DM showed a reduction in immunoreactivity for TH in the Substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and dorsal striatum (DS) areas, and an increase in BDNF in the DS and CA1, CA3 and dentate gyrus (DG) hippocampal areas. Conversely, the animals submitted to 15 inhalations of DM showed immunoreactivity reduced for TH in the SNpc and VTA, and an increase in BDNF in the hippocampal areas (CA3 and DG). Our results indicate that the DM inhalation at different periods induce motor and cognitive impairments in rats. Such alterations were accompanied by dopaminergic system damage and a possible dysfunction on synaptic plasticity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016., Methods: Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS., Results: Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019., Conclusion: Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets., Competing Interests: The authors have declared that no competing interests exist.

Exposure to chlorpyrifos-cypermethrin combination during early development resulted in defective looping and ventricular noncompaction of heart in domestic chicken. The study was extended to elucidate the molecular basis of this novel observation. The primary culture of chicken embryonic heart cells showed a concentration-dependent loss of viability when challenged with this combination of technical-grade insecticides. Comet assay, DNA ladder assay, and analyses of appropriate markers at transcript and protein levels, revealed that chlorpyrifos-cypermethrin combination induced cell death by activating apoptosis. Parallelly, the tissues derived from control and experimental group hearts were checked for apoptotic markers, and the result was much similar to that of the in-vitro study. Further analysis showed that chlorpyrifos-cypermethrin combination deranged the expression pattern of the transcriptional regulators of cardiogenesis, namely TBX20, GATA5, HAND2, and MYOCD. This, together with heightened apoptosis, could well be the reason behind the observed structural anomalies in the heart of chlorpyrifos-cypermethrin poisoned embryos., (© 2020 Wiley Periodicals LLC.)

Insecticide exposure has been identified as a contributing stressor to the decline in the North American monarch butterfly Danaus plexippus L. (Lepidoptera: Nymphalidae) population. Monarch toxicity data are currently limited and available data focuses on lethal endpoints. This study examined the 72-h toxicity of two pyrethroid insecticides, bifenthrin and β-cyfluthrin, and their effects on growth and diet consumption. The toxicity of bifenthrin to caterpillars was lower than β-cyfluthrin after 72 h. Survival was the most sensitive endpoint for bifenthrin, but diet consumption and caterpillar growth were significantly reduced at sublethal levels of β-cyfluthrin. Using AgDRIFT spray drift assessment, the aerial application of bifenthrin or β-cyfluthrin is predicted to pose the greatest risk to fifth-instar caterpillars, with lethal insecticide deposition up to 28 m for bifenthrin and up to 23 m for β-cyfluthrin from treated edges of fields. Low boom ground applications are predicted to reduce distances of lethal insecticide exposure to 2 m from the treated field edge for bifenthrin and β-cyfluthrin. Growth and survival of fifth-instar monarch caterpillars developing within the margins of a treated field may be significantly impacted following foliar applications of bifenthrin or β-cyfluthrin. These findings provide evidence that pyrethroid insecticides commonly used for soybean pest control are a potential risk to monarch caterpillars in agricultural landscapes., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America.)

The current study investigated the synergistic effect of combinations containing deltamethrin (D), Eucalyptus essential oil (E), and the thyme essential oil component thymol (T), against a field population of Rhipicephalus annulatus in Egypt that was characterized to be resistant to D. Solutions of T, E, or TE at concentrations of 1.25-5% were combined with 5% deltamethrin at different dilutions (0.25-2 mL/L). Results of the adult immersion test used to estimate the in vitro acaricidal activity of these combinations at 5% yielded LC 50 values for D, E-D, T-D, and TE-D of 3.87 mL/L, 3.89 mL/L, 0.14 mL/L, and 0.05 mL/L, respectively. Biochemical analyses using whole-body homogenate of ticks from the in vitro tests revealed that the lowest acetylcholinesterase and glutathione peroxidase activity, and the maximum lipid peroxidation were recorded in ticks treated with 5% TE-D. Glutathione content significantly decreased (p ≤ 0.05) in all treated ticks. Three groups, each containing five cross breed cattle naturally infested with R. annulatus from the same area where resistance to D was detected, were sprayed twice at two-week intervals using 1 mL/L of 5% solutions of D, T-D, or TE-D. Overall efficacy of the D, T-D, and TE-D sprays by day 30 post-treatment was 21.6, 88.3, and 95 %, respectively. Ticks collected from infested cattle three days after treatment with the D spray deposited egg masses that were able to hatch, deposited small masses of eggs unable to hatch when exposed to the T-D spray, and laid few eggs that didn't hatch when sprayed with the TE-D combination. Values for liver and kidney function parameters were comparable in cattle before and after treatment with the combination sprays tested. The TE-D spray overcame the insensitivity to D of this R. annulatus population in Egypt, which also highlighted the significant synergistic effect of thymol on the acaricidal activity of deltamethrin observed in vitro. Acaricidal activity of the TE-D combination apparently has deleterious effects on multiple tick systems involving inhibition of acetylcholinesterase, increased lipid peroxidation, and oxidative stress. These findings document that combinations of natural and synthetic products can be part of integrated management solutions to the problem with widespread resistance to pyrethroids like deltamethrin in populations of cattle ticks, including R. annulatus, around the world., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pyrethroids like permethrin have been used as topical formulations for their ectoparasiticidal effects since the 1970s. There are numerous efficacy studies in dogs and livestock animals that indicate a fast spread of pyrethroids after topical administration onto rather confined areas of the skin. Some studies correlate the efficacy against ticks, fleas or lice with concentrations of pyrethroids in hair and, less frequently, stratum corneum samples. It is often stated that lateral transport is responsible for the distribution of the pyrethroids over the body surface. With this review, we attempt to demonstrate evidence for lateral transport of pyrethroids after topical administration in dogs, cattle and sheep and to present data gaps that should be addressed in follow-up studies., (© 2020 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

The difficult experience of treating scabies in an elderly hospital reaffirmed my determination and responsibilities as a pharmacist. In 2000, there was no effective treatment for scabies in Japan. With the Japan Pharmaceutical Association as well as the Japanese Dermatological Association, the indication of ivermectin which is the intestinal fecal nematode was expanded for scabies. Since it was found that the administration of ivermectin through a tube to patients who could not take it orally had a dose loss of 50% depending on the injection method, an appropriate administration method was proposed. However, the oral administration of ivermectin has side effects including systemic liver damage, and external preparations require labor for systemic application, and recurrence from unapplied areas is also a problem. Therefore, we devised a whole-body bathing, in which patients are immersed in a fluid that contains ivermectin. The repeated ivermectin bathing three times a week cured scabies and has no problematic side effects in the clinical trial, suggesting that this method is a safer treatment. Next, in Okinawa, phenothrin-resistant head lice infestation was prevalent, and no medical drug for this infestation is available in Japan yet. Hence, to address this situation, we conducted a clinical trial to investigate the efficacy and safety of a combination regimen of 5% topical phenothrin and the unapproved 0.5% topical ivermectin. Consequently, 92% and 100% effectiveness were obtained in Okinawa and Tsukuba, respectively. As a result, we were able to conduct research aimed to maximize the safety and effectiveness of ivermectin in Japan.

Plague originated in Asia as a flea-borne zoonosis of mammalian hosts. Today, the disease is distributed nearly worldwide. In western United States of America, plague is maintained, transmitted, and amplified in diverse communities of rodents and fleas. We examined flea diversity on three species of prairie dogs ( Cynomys spp., PDs) and six species of sympatric small rodents in Montana and Utah, United States of America. Among 2896 fleas, 19 species were identified; 13 were found on PDs and 9 were found on small rodents. In Montana, three flea species were found on PDs; the three species parasitize PDs and mice. In Utah, 12 flea species were found on PDs; the 12 species parasitize PDs, mice, voles, chipmunks, ground squirrels, rock squirrels, and marmots. Diverse flea communities and their willingness to parasitize many types of hosts, across multiple seasons and habitats, may favor plague maintenance and transmission. Flea parasitism on Peromyscus deer mice varied directly with elevation. Fleas are prone to desiccation, and might prosper at higher, mesic elevations; in addition, Peromyscus nest characteristics may vary with elevation. Effective management of plague is critical. Plague management is probably most effective when encompassing communities of rodents and fleas. Treatment of PD burrows with 0.05% deltamethrin dust, which suppressed fleas on PDs for >365 days, suppressed fleas on small rodents for at least 58 days. At one site, deltamethrin suppressed fleas on small rodents for at least 383 days. By simultaneously suppressing fleas on PDs and small rodents, deltamethrin should promote ecosystem resilience and One Health objectives.

The present study was performed to determine the acaricidal activity of the cottonseed oil (CSO) against cattle tick Rhipicephalus microplus. CSO was analyzed using Gas Chromatograph with high-resolution Mass Spectrometer (GC-HRMS) to identify the presence of active compounds. In vitro bioassays were performed using larval packet test (LPT) and adult immersion test (AIT) by taking different concentrations of CSO (i.e. 0.1, 0.5, 1.5, 2.5, 5, 7.5, 10 and 12.5%). In vivo acaricidal activity of CSO was evaluated by its topical application on red Sahiwal calves for 144 h. Clinical safety of CSO was evaluated by performing skin irritancy test and examination of hematological profile of calves'. GC-HRMS analysis of CSO revealed the presence of many fatty acids including oleic acid, lauric acid, palmitic acid, stearic acid and other components. Results exhibited that all the concentrations of CSO were effective in reducing the number of ticks and their growth. However, CSO at concentrations of 10% (CSO7) and 12.5% (CSO8) exhibited 100% mortality of R. microplus larvae and adults in LPT and AIT, respectively. In vivo acaricidal assay revealed that CSO7 and CSO8 shown 85% and 89% inhibition of ticks, respectively on calves after 144 h as compared to the control group. CSO was clinically safe on calves' skin with mild erythema up to 20 min. Hematological profile of calves revealed no sign of toxicity after treatment with CSO. Thus, CSO can be used as an alternative and safe drug therapy against R. microplus., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The issues of pyrethroid resistance and outdoor malaria parasite transmission have prompted the WHO to call for the development and adoption of viable alternative vector control methods. Larval source management is one of the core malaria vector interventions recommended by the Ministry of Health in many African countries, but it is rarely implemented due to concerns on its cost-effectiveness. New long-lasting microbial larvicide can be a promising cost-effective supplement to current vector control and elimination methods because microbial larvicide uses killing mechanisms different from pyrethroids and other chemical insecticides. It has been shown to be effective in reducing the overall vector abundance and thus both indoor and outdoor transmission. In our opinion, the long-lasting formulation can potentially reduce the cost of larvicide field application, and should be evaluated for its cost-effectiveness, resistance development, and impact on non-target organisms when integrating with other malaria vector control measures. In this opinion, we highlight that long-lasting microbial larvicide can be a potential cost-effective product that complements current front-line long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) programs for malaria control and elimination. Microbial larviciding targets immature mosquitoes, reduces both indoor and outdoor transmission and is not affected by vector resistance to synthetic insecticides. This control method is a shift from the conventional LLINs and IRS programs that mainly target indoor-biting and resting adult mosquitoes.

Sarcoptic mange epidemics can have long-lasting impacts on susceptible wildlife populations, potentially contributing to local population declines and extirpation. Since 2013, there have been 460 reported cases of sarcoptic mange in an urban population of endangered San Joaquin kit foxes ( Vulpes macrotis mutica ) in Bakersfield, CA, with many of them resulting in fatality. As part of a multifaceted response to mitigate mange-caused mortalities and reduce this conservation threat, a 2-yr randomized field trial was conducted to assess the efficacy of long-acting flumethrin collars against sarcoptic mange in kit foxes. Thirty-five kit foxes living in a high-density population on a college campus were captured, examined, administered selamectin, and each fox randomly assigned to either receive a flumethrin collar placed within a VHF radio collar or a VHF radio collar without flumethrin. The survival and mange-infestation status of study animals was monitored via radio telemetry, remote cameras, and periodic recapture examinations and compared among treated and control kit foxes using a Cox proportional hazards model. The average time to onset of mange for treated kit foxes (176 days) was similar to controls (171 days) and treatment with flumethrin did not significantly reduce mange risk for all kit foxes. Kit foxes that had a mild mange infestation at the beginning of the study were four times more likely to develop mange again, regardless of flumethrin treatment, compared with kit foxes that had no signs at initial recruitment. This study demonstrates an approach to evaluating population-level protection and contributes to the limited literature on efficacy, safety, and practicality of acaricides in free-ranging wildlife.

Insecticide-impregnated traps and visual targets are used for tsetse (Diptera, Glossinidae) population control. Such devices are made with textiles and deltamethrin is frequently the insecticide of choice. However, persistence of an insecticide on textiles is affected by exposure to weather. Here we examine the effect of weathering on the capacity of four textiles with increasing proportions of polyester (0, 35, 65, and 100%) with cotton and viscose to retain deltamethrin. Textiles tested were those used to make visual targets in a pan-African program to maximize target efficiency for controlling tsetse vectors of African trypanosomiasis. Following impregnation in an aqueous suspension of deltamethrin at 1,000 mg/m2, textiles were weathered for 18 mo at Lambwe Valley, Kenya and sampled every 3 mo to make knockdown tests on the tsetse fly Glossina pallidipes Austen. Deltamethrin content of the textiles was established using gas chromatography mass-spectrometry at impregnation and after 9 mo of weathering. Textiles with higher proportions of polyester retained deltamethrin better: respectively, 100% polyester and 65:35 polyester/viscose textiles retained deltamethrin at 17 and 11 mg/m2 9-mo post-treatment that caused 100% knockdown in G. pallidipes after 1 h, and killed 67 and 47% of flies, respectively, after 24 h. Eighteen-month weathered 100% polyester treated textile still knocked down all tsetse exposed to it within 2 h. The LD50 for deltamethrin on filter paper for G. pallidipes was estimated at 28.8 mg/m2, indicating that deltamethrin is more available on polyester to kill tsetse., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pyrethroids are commonly used as insecticides in households, in agriculture or in veterinary and medicinal products. This study aimed to assess cumulative aggregate exposure to cyfluthrin, cypermethrin, deltamethrin and permethrin in adults in France and the associated health risk, and to identify major contributions of exposure sources and routes. External chronic exposures were estimated from dietary and several environmental sources for the oral, inhalation and dermal routes. Internal concentrations of five associated metabolites were simulated with a physiologically-based pharmacokinetic model. The predicted urinary concentrations were in same order of magnitude as those of the French ENNS biomonitoring survey. Dietary exposure, especially from cereals and animal products, was the major source of exposure. For the 1% of adults most highly exposed, dermal exposure to permethrin through medicinal and veterinary products was an important source of exposure. Considering alterations of motor, sensory and autonomic division, all individual margins of exposure were higher than 100, suggesting that no neurotoxic risk associated with the cumulative aggregate exposure to these four pyrethroids is expected for the French adult population., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Bed nets are the commonest malaria prevention tool and arguably the most cost-effective. Their efficacy is because they prevent mosquito bites (a function of physical durability and integrity), and kill mosquitoes (a function of chemical content and mosquito susceptibility). This essay follows the story of bed nets, insecticides and malaria control, and asks whether the nets must always have insecticides., Methods: Key attributes of untreated or pyrethroid-treated nets are examined alongside observations of their entomological and epidemiological impacts. Arguments for and against adding insecticides to nets are analysed in contexts of pyrethroid resistance, personal-versus-communal protection, outdoor-biting, need for local production and global health policies., Findings: Widespread resistance in African malaria vectors has greatly weakened the historical mass mosquitocidal effects of insecticide-treated nets (ITNs), which previously contributed communal benefits to users and non-users. Yet ITNs still achieve substantial epidemiological impact, suggesting that physical integrity, consistent use and population-level coverage are increasingly more important than mosquitocidal properties. Pyrethroid-treatment remains desirable where vectors are sufficiently susceptible, but is no longer universally necessary and should be re-examined alongside other attributes, e.g. durability, coverage, acceptability and access. New ITNs with multiple actives or synergists could provide temporary relief in some settings, but their performance, higher costs, and drawn-out innovation timelines do not justify singular emphasis on insecticides. Similarly, sub-lethal insecticides may remain marginally-impactful by reducing survival of older mosquitoes and disrupting parasite development inside the mosquitoes, but such effects vanish under strong resistance., Conclusions: The public health value of nets is increasingly driven by bite prevention, and decreasingly by lethality to mosquitoes. For context-appropriate solutions, it is necessary to acknowledge and evaluate the potential and cost-effectiveness of durable untreated nets across different settings. Though ~ 90% of malaria burden occurs in Africa, most World Health Organization-prequalified nets are manufactured outside Africa, since many local manufacturers lack capacity to produce the recommended insecticidal nets at competitive scale and pricing. By relaxing conditions for insecticides on nets, it is conceivable that non-insecticidal but durable, and possibly bio-degradable nets, could be readily manufactured locally. This essay aims not to discredit ITNs, but to illustrate how singular focus on insecticides can hinder innovation and sustainability.

The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), is a peridomestic, container-ovipositing mosquito commonly found throughout the southeastern United States. In the United States, Ae. albopictus is typically considered a nuisance pest; however, it is capable of transmitting multiple pathogens. Ae. albopictus is an important pest species and the target of numerous mosquito control efforts in the United States. Here, we evaluate the effectiveness and spatial extent of Ae. albopictus population reduction using a bifenthrin (AI Bifen IT, 7.9%) barrier spray and larval habitat management (LHM) in a temperate, suburban setting. Sixteen pairs of adjoining neighbors were randomly assigned to treatment groups with one neighbor receiving a treatment and the other monitored for evidence of a spillover effect of the treatments. Ae. albopictus populations in both yards were monitored for 33 d, with treatments occurring on the eighth day. Barrier sprays, both alone and combined with LHM, resulted in a significant reduction in Ae. albopictus abundance posttreatment. While LHM alone did not result in a significant reduction over the entire posttreatment period, Ae. albopictus populations were observed to be in decline during this period. No treatments were observed to have any reduction in efficacy 25 d posttreatment, with treatments involving LHM having a significantly increased efficacy. Yards neighboring treated yards were also observed to have reduced population sizes posttreatment, but these differences were rarely significant. These results provide insights into the population dynamics of Ae. albopictus following two common treatments and will be useful for integrated pest management plans., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hurricane Harvey has been recorded as the wettest cyclone in United States history, resulting in devastating and catastrophic flooding for the Texas Gulf Coast. The nature of the path of the hurricane, with multiple landfalls along the Texas Gulf Coast, resulted in the largest aerial mosquito control effort for one single storm. Two mosquito control contractors and the Air Force Aerial Spray Unit of the US Air Force Reserve were used to aerial treat 6,765,971 acres (3,075,441 ha) in 29 of the 60 disaster-declared counties in Texas. During the response, 101,253 liters of Dibrom® (active ingredient [AI]: naled) and 48,735 liters of Duet™ (AI: 1% prallethrin and 5% sumithrin) were used. In 23/29 counties requesting aerial spraying, mosquito control contractors were used to conduct pre- and postaerial application mosquito surveillance. The remaining 6 counties conducted their own surveillance during the response. A total of 105,153 mosquitoes in 7 genera and 35 species were collected during this response with the major floodwater nuisance mosquito being Psorophora columbiae. The most abundant vector mosquito collected was Culex nigripalpus. Duet at the 0.8% and 1% application rates resulted in 49% and 69% control of Ps. columbiae, respectively. Dibrom application resulted in 95% and 93% control of Ps. Columbia and Cx. nigripalpus populations, respectively., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

In the mouse carcinogenicity study, an apparent increase in lung adenocarcinoma was observed in male mice at 7000 ppm. Based on the overall evaluation of toxicology, oncology, pathology and statistics, we concluded that the apparent increase in lung tumors is not relevant for evaluation of carcinogenicity of imiprothrin (Regul Toxicol Pharmacol, 105, 1-14, 2019). To investigate whether imiprothrin has any mitogenic effect on mouse Club cells, the present study examined its effects on replicative DNA synthesis of Club cells and lung histopathology in male mice treated with imiprothrin for 7 days at 3500 and 7000 ppm in the diet. Isoniazid, a known mouse lung mitogen and tumor inducer, was also examined at 1000 ppm in the diet as a positive control of Club cell mitogenesis and morphological changes. Neither imiprothrin nor isoniazid caused any necrotic changes in lung by light or electron microscopy. There were no increases observed in the bromodeoxyuridine (BrdU) labeling index in the imiprothrin groups, while there was a statistically significant increase in the BrdU labeling index in the isoniazid group. These findings demonstrate that imiprothrin does not induce mouse Club cell proliferation or morphologic changes, supporting our previous conclusion described above. Thus, imiprothrin should not be classified as a carcinogen. Furthermore, this study indicates that short-term studies focusing on cell proliferation can be reliable for predicting a lack of carcinogenic potential of test chemicals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Samuel M. Cohen consults for Sumitomo Chemical Company, Ltd. The other authors are employed by Sumitomo Chemical Company, Ltd., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We assessed the efficacy of bifenthrin to suppress Ixodes scapularis Say and Amblyomma americanum (L.) nymphs when applied prior to the initiation of spring host-seeking activity versus when nymphs were already active. Treatment and control plots were sampled for host-seeking ticks every week from mid-April through June, and single occasion bifenthrin applications were done in different sets of treatment plots on 15 April, 29 April, 13 May, and 27 May. Ixodes scapularis nymphs and A. americanum nymphs and adults were effectively suppressed after each application, with at or near 100% suppression of all ticks being observed for up to 8-wk postapplication. Irrespective of the bifenthrin application date, the level of suppression of I. scapularis nymphs never declined below 70% during the study period. However, with the exception of the last application, the suppression of A. americanum nymphs decreased dramatically to below 25% by the conclusion of the trial. The results of this study demonstrated that preseason applications of bifenthrin can mitigate acarological risk of exposure to ticks throughout much of their spring peak activity period., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alpha-cypermethrin (ACy) is a synthetic pyrethroid insecticide commonly used in agricultural practices for controlling a broad range of insect pests particularly belonging to the order Lepidoptera and Coleoptera. The present study aims to evaluate the toxic effect of ACy on microalgae by studying its influence on Chlorella sp. According to our knowledge, this is the first detailed study of ACy toxicity on microalgae. Significant growth inhibition of Chlorella sp. was observed at high ACy concentration (6-48 mg L -1 ) during the entire 96 h bioassay. The 96 h median effective concentration (EC 50 ) of ACy was estimated to be 11.00 mg L -1 . Flow cytometry analysis showed an enhanced generation of reactive oxygen species (ROS) and intracellular lipid accumulation after 96 h exposure to 11.00 mg L -1 of ACy. Further, the same ACy concentration showed a significant decrease in photosynthetic pigment content and an increase in antioxidant enzyme activity and malondialdehyde (MDA) content in Chlorella sp., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Prevention of canine Leishmania infantum infection is critical to management of visceral leishmaniasis in people living in endemic areas of Brazil. A bill (PL 1738/11), currently under consideration, proposes to establish a national vaccination policy against canine leishmaniasis in Brazil. However, there is no solid scientific evidence supporting the idea that this could reduce transmission from infected vaccinated dogs to sand flies to a level that would significantly reduce the risk of L. infantum infection or visceral leishmaniasis in humans. Thus, we advocate that insecticide-impregnated collars should the first line protective measure for public health purposes and that vaccines are applied on a case-by-case, optional basis for individual dog protection., (Copyright © 2020 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Although ethanol withdrawal depression is one of the prominent reasons for ethanol consumption reinstatement and ethanol dependence, its neurochemical basis is not clearly understood. The present study investigated the role of the agmatinergic system in ethanol withdrawal-induced depression using the forced swim test (FST) in rats. Chronic exposure of animals to ethanol for 21 days and its abrupt withdrawal produced depression-like behavior, as evidenced by increased immobility time in the FST, compared to the pair-fed control animals. The ethanol withdrawal-induced depression was significantly attenuated by agmatine (20-40 μg/rat, i.c.v. [intracerebroventricularly]), moxonidine (50 μg/rat, i.c.v.), 2-BFI (20 μg/rat, i.c.v.), L-arginine (80 μg/rat, i.c.v.), amino-guanidine (25 μg/rat, i.c.v.), and arcaine (50 μg/rat, i.c.v.) by their once-daily administration during the withdrawal phase (Days 21, 22, and 23). The antidepressant effect of agmatine in ethanol-withdrawn rats was potentiated by the imidazoline receptor I 1 agonist moxonidine (25 μg/rat, i.c.v.) and the imidazoline receptor I 2 agonist, 2-BFI (10 μg/rat, i.c.v.) at their sub-effective doses. On the other hand, it was completely blocked by the imidazoline receptor I 1 antagonist, efaroxan (10 μg/rat, i.c.v.) and the imidazoline receptor I 2 antagonist, idazoxan (4 μg/rat, i.c.v.). In addition, agmatine levels were significantly reduced in brain samples of ethanol-withdrawn rats as compared to the pair-fed control animals. In conclusion, the present study suggests the importance of the endogenous agmatinergic system and the imidazoline receptors system in ethanol withdrawal-induced depression. The data project agmatine as a potential therapeutic target for the alcohol withdrawal-induced depression., Competing Interests: Conflicts of interest The authors declare that there are no conflicts to report., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In recent years, attractive toxic sugar bait has been used in the mosquito control in nature, and achieved good control effects. However, the current researches about toxic sugar bait did not focus on whether the wild mosquito population used for control is resistant or not. The purpose of this study was to evaluate the effectiveness of the toxic sugar bait against mosquito resistant populations to test the effects of bait on the control of mosquitoes with different levels of resistance. Boric acid, dinotefuran and deltamethrin were separately formulated into toxic sugar bait to test their anti-mosquito activity against Culex quinquefasciatus. Using the sugar baits formulated with boric acid and dinotefuran, the mortality of Cx. quinquefasciatus resistant populations was significantly higher than that of sensitive populations at the same concentration. Conversely, with the use of sugar baits formulated with deltamethrin, the mortality of Cx. quinquefasciatus resistant populations was significantly lower than that of sensitive populations at the same concentration. The results suggested that toxic sugar baits might have a good application prospect in high resistant mosquito management., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Malaria prevalence has significantly reduced since 2000, largely due to the scale-up of vector control interventions, mainly indoor residual spraying (IRS) and long-lasting insecticide-treated nets (LLINs). Given their success, these tools remain the frontline interventions in the fight against malaria. Their effectiveness relies on three key ingredients: the intervention, the mosquito vector and the end-user. Regarding the intervention, factors such as the insecticide active ingredient(s) used and the durability and/or bio-efficacy of the tool over time are critical. For the vectors, these factors include biting and resting behaviours and the susceptibility to insecticides. Finally, the end-users need to accept and properly use the intervention. Whilst human attitude and behaviour towards LLINs are well-documented both during and after distribution, only initial coverage is monitored for IRS and in a few geographic settings the residual efficacy of the used product. Here, the historical evidence on end-users modifying their wall surfaces post-spraying is presented, a behaviour that has the potential to reduce actual IRS coverage, effectiveness and impact, as fewer people are truly protected. Therefore, clear guidelines on how to monitor IRS acceptability and/or coverage, both before, during and after spraying, are urgently needed as part of the Monitoring and Evaluation of malaria programmes.

Background: We conducted a matched-pairs trial of three methods for detecting house infestation with triatominae bugs in a well-defined endemic rural area in the Argentine Chaco., Methods: The three methods included a simple double-sided adhesive tape (ST) installed near host resting sites; timed-manual collections with a dislodging aerosol (TMC, the reference method used by vector control programmes), and householders' bug notifications (HN). Triatomine infestations were evaluated in 103 sites of 54 houses, including domiciles, kitchens and storerooms., Results: In domiciles where Triatoma infestans was collected, sensitivity of each single method decreased from 79% by ST and 77% by HN, to 57% by TMC, and increased to 92% when ST was combined with HN. In peridomestic kitchens and storerooms, TMC was relatively as sensitive as ST and significantly more sensitive than HN. On average, the number of bugs recovered by ST was 0.94 times that collected by TMC. The ST mainly collected early-instar nymphs whereas TMC yielded late (larger) stages. Triatomines caught by ST had significantly lower mean weight-to-length ratios and lower blood-feeding rates than those caught by TMC, suggesting the ST intercepted and trapped vectors seeking a blood meal host., Conclusions: The ST may effectively replace TMC for detecting T. infestans in domiciles, and is especially apt for early detection of low-density domestic infestations in the frame of community-based surveillance or elimination programmes; decision making on whether an area should be targeted for full-coverage insecticide spraying, and to corroborate that extant conditions are compatible with the interruption of vector-borne transmission.

This study explored the camel milk (CM) efficacy to ameliorate the fenpropathrin (FNP) induced neurotoxic impacts in rats. Six groups were orally administered physiological saline, corn oil, CM (2ml/rat/day), FNP (15 mg/kg bw daily for 60 days), CM/FNP (protective) or FNP + CM (therapeutic). Sensorimotor functions, memory, exploratory, and locomotor activities were assessed. The levels of dopamine (DOPA) neurotransmitter, acetylcholinesterase (AChE) enzyme, oxidative stress, and inflammatory markers were determined. Brain histopathology and apoptotic markers immunohistochemical detection were performed. The results revealed that FNP exposure resulted in deficit sensorimotor functions, impaired memory, and less exploration. DOPA and AChE Levels were significantly reduced. FNP exposure increased nitric oxide, malondialdehyde, myeloperoxidase, Caspase-3, and tumor necrosis factor-alpha levels but interleukin 10, total antioxidant capacity, and Bcl-2 levels were declined. Also, FNP exposure induced obvious encephalopathy. Additionally, neurodegenerative changes were seen in the hippocampi of FNP-treated rats. FNP Exposure induced a significant decrease of Bcl-2 immunolabelling but Caspase-3 immunoexpression was increased in cerebral cortices and hippocampus tissues. CM significantly counteracted the FNP injurious impacts, especially when used as a prophylactic routine than a therapeutic one. Conclusively, these findings confirmed that CM could be a biologically effective protective agent against FNP induced neurobehavioral aberrations and neurotoxic impacts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lake Van fish is the only vertebrate species that lives in extreme condition (salinity of 2.2%, alkalinity of 151.2 meq/kg, and pH of 9.8) of largest soda lake of the world. This fish is an important source of protein for the people living in Van and surrounding provinces. . Cypermethrin (CYP) is used extensively against insects in agricultural, livestock, and domestic applications in Lake Van basin. CYP has toxic effects highly on non-target organisms as aquatic animals. The aim of this study was to evaluate the effect of commercial formulas of CYP (0.05 µg/L) on Van Lake fish ( Alburnus tarichi ) for 24, 48, 72, 96 h under semi-static conditions using oxidative damage biomarkers. In this study, antioxidant defense system enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and lipid peroxidation (LPO) product malondialdehyde (MDA) levels were determined in the liver, kidney, gills, and brain tissues. According to the results of this study, the decrease in SOD (at 48, 72, and 96 h) and CAT and GPx (at 24, 48, 72, and 96 h) enzyme activities were significant with exposure to CYP ( p  < 0.05). In addition, the increase in MDA levels, which is the indicator of LPO, was found to be significant ( p  < 0.05). However, in the 24 h period exposed to CYP, a significant increase in SOD activity was determined in kidney and brain compared to the control group ( p  < 0.05). In conclusion, sublethal concentrate application of CYP is thought to cause oxidative stress and disrupt the oxidant, antioxidant balance of Lake Van fish.

The use of toxic pesticides has become a world problem because they can contaminate streams and rivers, producing an adverse impact on non-target aquatic biota, including fishes. Cypermethrin is one of the most important insecticides to control ectoparasites in wide-scale. The aim of this study was to evaluate the effect of commercial formulations of cypermethrin, SHERPA O (0.0, 0.075, 0.15, and 0.3 µg/L of cypermethrin) in fish Prochilodus lineatus for 96 h in semi-static condition, using biomarkers of genotoxicity: micronucleus frequency (MNF) in erythrocytes and biomarkers of oxidative damage: lipid peroxidation (TBARS) and antioxidant defenses, catalase (CAT) and glutathione (GSH) in liver tissue. Our results showed a significant decrease ( p  < 0.05) of CAT at pesticide concentrations of 0.150 and 0.300 μg/L, but no significant difference was observed in TBARS or GSH in any exposed group ( p  > 0.05) in comparison to the control. A significant increase was observed in the MNF in the group exposed to 0.3 μg/L of cypermethrin compared to negative control ( p  < 0.05). Finally, P. lineatus proved to be a sensitive species to the commercial formulations of cypermethrin and that CAT and MNF are effective indicators of these toxic effects.

The capability of imidacloprid 10% + flumethrin 4.5% (Seresto®) collars to prevent transmission of Borrelia burgdorferi sensu lato (Bbsl) and Anaplasma phagocytophilum (Ap) by naturally infected ticks was evaluated in two studies with 44 dogs. In each study, one group served as non-treated control, whereas the other groups were treated with the Seresto® collar. All dogs were exposed to naturally Bbsl- and Ap-infected hard ticks (Ixodes ricinus, Ixodes scapularis). In study 1, tick infestation was performed on study day (SD) 63 (2 months post-treatment [p.t.]); in study 2, it was performed on SD 32 (one month p.t.) respectively SD 219 (seven months p.t.). In situ tick counts were performed 2 days after infestation. Tick counts and removals followed 6 (study 1) or 5 days (study 2) later. Blood sampling was performed for the detection of specific Bbsl and Ap antibodies and, in study 1, for the documentation of Ap DNA by PCR. Skin biopsies were examined for Bbsl by PCR and culture (only study 1). The efficacy against Ixodes spp. was 100% at all time points. In study 1, two of six non-treated dogs became infected with Bbsl, and four of six tested positive for Ap; none of the treated dogs tested positive for Bbsl or Ap. In study 2, ten of ten non-treated dogs became infected with Bbsl and Ap; none of the treated dogs tested positive for Bbsl or Ap; 100% acaricidal efficacy was shown in both studies. Transmission of Bbsl and Ap was successfully blocked for up to 7 months.

Terrestrial adult stages of freshwater insects may be exposed to pesticides by wind drift, over-spray, contact or feeding. However, studies addressing insecticide effects on freshwater invertebrates focus primarily on the impact of pesticides reaching the streams and potentially harming the aquatic juvenile stages. This is also reflected in the current risk assessment procedures, which do not include testing of adult freshwater insects. In order to assess the potential impact of insecticides on adult stages of freshwater insects, we exposed six common species to the insecticides Karate (lambda-cyhalothrin) and Confidor (imidacloprid). Dose-response relations were established, and LD 50 estimates were compared to those of the honey bee, Apis mellifera L. (Hymenoptera: Apidae), which is the standard terrestrial test insect when pesticides are evaluated prior to commercial release. Generally, the tested species were more sensitive to the studied insecticides than the honey bee. In order to examine whether the sensitivity of adult stages of freshwater insects corresponds with the sensitivity of the juvenile stages of the same species, the ranking of the two life stages with respect to the toxicity of Karate was compared, revealing some correspondence, but also some dissimilarities. Our results strongly indicate that terrestrial adult stages of aquatic insects are not adequately protected by current risk assessment procedures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Most pyrethroid insecticides (PYRs) share a similar primary target site in mammals. However, the potency estimates of the lethal and sublethal effects of these compounds differ up to 103-fold. The aim of this study was to evaluate the relationship between the dose administered, the target tissue dose, and the effect of 2 highly toxic PYRs, tefluthrin (TEF; 0.1-9 mg/kg) and bifenthrin (BIF; 0.5-12 mg/kg), by using the oral route, a corn oil vehicle (1 ml/kg) and subcutaneous temperature (Tsc) monitoring assays in adult rats. The Tsc was determined at 30-min intervals for 5 h (TEF) or 4.5 h (BIF) after dosing. Rats were sacrificed at 6 h after dosing, and BIF and TEF concentrations were determined in blood (Bd), liver (Lv), and cerebellum (Cb) by using a GC-ECD system. The minimal effective dose of BIF (3 mg/kg) affecting Tsc was similar to that found in prior studies using other testing paradigms. Regarding TEF, a very steep relationship between the dose administered and toxicity was observed, with a near-threshold to low-effective range for Tsc at 0.1-6 mg/kg, and a near lethal syndrome at ≥ 7.5 mg/kg. At 6-7.5 mg/kg TEF, the Cb/Bd and Cb/Lv concentration ratios were both > 1. Conversely, for BIF, the Cb concentration was barely over the Bd concentration and the Cb/Lv concentration ratio remained < 1. Our results and previous findings call for more comprehensive consideration to establish the relevance of the distribution into target tissues and the tissue dosimetry for health risks through the exposure to PYRs in humans., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Head lice infestation (Pediculosis) is one of the most important health challenges particularly in primary school-aged children. It is often present among 6-11-year-old students in various tropical and temperate regions of the world. The aim of this study was to examine epidemiologic indices and comparative analysis of two pyrethroid-based and one non-chemical pediculicide products on head lice treatment of primary school girls in a rural setting of Fars province, south Iran, as part of a randomized controlled assessor blind trial., Methods: Before treatment, infested students were screened using plastic detection combs to find live head lice. Three independent parallel groups, each with about 25 participants (#77) were eventually twice with a week apart treated with either 1% permethrin, 0.2% parasidose (d-phenothrin) or 4% dimeticone lotion preparations. In each case, a questionnaire form was completed on epidemiologic factors. Data were registered after a fortnight from primary scalp treatment and re-inspection on days 2, 6, 9 and 14. Data analyses were performed using Chi-square test with a P-value < 0.05 being taken as statistically significant., Results: From 3728 inspected students, 87 (2.33%) girls were infested with head lice, Pediculus humanus capitis De Geer, 1778. Ten students dropped out pertaining to exclusion criteria. No significant correlation was found between head lice infestation level and hair length, hair style, itching, nationality, age, settlement site and baths; but there was a significant relationship between age and hair style (P = 0.027). The efficacy values on each of the above re-inspection days from each of the three treatments were 81, 74, 70 and 63% for permethrin; 83, 92, 100 and 100% for dimeticone; and 96, 88, 96 and 92% for d-phenothrin; respectively. A quartile difference in efficacy of permethrin relative to dimeticone on day 14 represented the scale of head lice resistance to permethrin treatment. There were significant statistical differences in case re-inspection days 9 (P = 0.008) and 14 (P = 0.003) post treatment. Only two dropout cases, one non-compliant and the other lost before the second-week treatment, from permethrin trial were observed following two applications a week apart., Conclusions: Dimeticone lotion had the fullest efficacy (100%) among all treatments. This high cure rate was attributed to the low level of infestation and the extent of patients' involvement. Parasidose swiftly ameliorated the infested cases by the second day since initial treatment. Female third grade students were the most infested cohort., Trial Registration: Current Controlled Trials- IRCT2016041627408N1 , Dated: 21-08-2017.

Background: The purpose of this report is to provide information on Culicidae diversity; biting behavior and spatio-seasonal variation of abundance of Anopheles gambiae s.l. and Culex quinquefasciatus in rural and urban settings of the Alibori and Donga regions, Northern Benin, where an indoor residual spraying (IRS) campaign to control malaria is planned. Methods: Both human landing catches, associated with pyrethrum spray catches were used to monitor the mosquito populations in 12 sites with 1 urban and 1 rural located in each of the 6 districts randomly selected in the two targeted regions. After morphological identification of all mosquito specimens, biting behavior and density of An. gambiae s.l. and Cx quinquefasciatus were studied. PCR was also performed on An. gambiae s.l., to identify sibling species and its seasonal variation. Results: A total of 10,367 mosquitoes were captured, related to 14 species of the genera, Anopheles , Aedes , Culex and Mansonia . Of the total species collection, 40.39% were An. gambiae s.l. and 56.85% were Cx. quinquefasciatus. An. gambiae s.l. was more abundant in Donga (2521 specimens) compared with Alibori (1666 specimens). The opposite trend was observed with Cx. quinquefasciatus (2162 specimens in Donga against 4028 in Alibori). An. gambiae s.l. was predominant and displayed a higher blood feeding rate in rural areas, whereas Cx. quinquefasciatus was in majority in urban areas. An. gambiae s.l. was more endophagic, whereas Cx. quinquefasciatus showed similar indoor and outdoor biting behavior. An. gambiae s.l. was composed of An. coluzzii found in majority in the drought, and An. gambiae , which was predominant in the rainy season. Conclusion: The predominance of the malaria vector, An. gambiae s.l. and their higher blood feeding rate and their significantly high endophagy in rural areas indicate that these areas should be primarily targeted with the IRS operations to have a substantial impact on malaria transmission. Endophagy, characteristic of An. gambiae s.l. in our study area, suggests that IRS will have a positive impact on vector control if implemented 1 week before June that is the onset of the rainy season.

The combination of the organophosphate (OP) chlorpyrifos (CPF) and the pyrethroid cypermethrin (CPM) is commonly marketed as pour-on formulations for the control of sheep lice, ked, and blowflies. CPF irreversibly inhibits acetylcholinesterases (AChE), while pyrethroids are not AChE inhibitors. However, combinations of pyrethroids with OPs showed a highly synergistic effect on AChE inhibition. Thus, the aim of the current work was to evaluate in vitro and in vivo the inhibitory potency of both pesticides, alone and in combination with AChE and butyrylcholinesterase (BChE) activities in sheep blood. In vitro, IC50 values were similar after CPF or CPF plus CPM incubations. The pour-on coadministration of recommended doses of CPF and CPM did not cause a significant inhibition of AChE and BChE in sheep blood. Only slight percentages of inhibition of their catalytic activities were observed when both drugs were given at 4-fold higher dose rates. The lower systemic availability of topical administration of OPs in sheep may help to explain the lower degree of inhibition of blood AChE and BChE in vivo. The results emerged from this research are a further contribution to the knowledge of the risks of implementing higher dosage regimens of OPs-containing antiparasitic formulations., (© 2019 John Wiley & Sons Ltd.)

The majority of residents of the United States, Canada, and Europe are exposed to pyrethroids, the most commonly used class of insecticides. Surprisingly little is known about key aspects of their pharmacokinetics, including their mode of transport in the systemic circulation. This study tested the hypothesis that pyrethroids are transported by both plasma lipoproteins and proteins, similarly to other highly lipophilic environmental contaminants. Other aims were to characterize the binding of representative type I and II pyrethroids, and to compare their binding to rat versus human plasma. Binding of 14 C-labeled cis -permethrin (CIS), trans -permethrin (TRANS) and deltamethrin (DLM) to proteins and lipoproteins was measured by sequential extraction of spiked plasma with isooctane, 2-octanol, and acetonitrile. Binding of DLM, CIS, and TRANS to plasma proteins and lipoproteins was linear from 250 to 750 nM; concentrations present in the plasma of orally dosed rats. Binding of DLM to high-density lipoprotein was twice that to low-density lipoprotein. Binding of DLM, CIS, and TRANS was ∼2-fold greater to proteins than to lipoproteins of rat and human plasma; albumin was primarily responsible for protein binding. Higher total binding of each pyrethroid to human (∼90%) than to rat (∼80%) plasma resulted from higher protein binding in human plasma. This was attributable in part to the higher albumin/protein content of human plasma. Rat albumin exhibited lower pyrethroid binding capacity than did human albumin. The results of this investigation indicate that albumin and lipoproteins play a major role in binding and transport of pyrethroids in the systemic circulation of both rats and humans., (Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Indoor residual spraying (IRS) is the mainstay for vector control intervention of visceral leishmaniasis (VL) in India. Little is known on the control effects of IRS on different household types. Here, we assessed if IRS with insecticides has an equal residual and interventional effect on all household types in a village. We also developed a combined spatial-risk map and a sand fly, Phlebotomus argentipes density analytical model based on household characteristics, insecticide susceptibility and IRS-status to explore the spatio-temporal distributions of the vector at a micro-scale level., Methods: This study was carried out in two villages of Mahnar block in Vaishali district, Bihar. IRS using two insecticides [dichlorodiphenyltrichloroethane (DDT 50%) and synthetic pyrethroid (SP 5%)] was evaluated for VL-vector (P. argentipes) control. Temporal residual efficacy of the insecticides on different wall-surface types was evaluated using the cone-bioassay technique according to WHO guidelines. Insecticide susceptibility of local P. argentipes was explored using the tube-bioassay method. Pre- and post-IRS sand fly densities were monitored in human dwellings and animal shelters using Centers for Disease Control light-traps installed between 18:00-6:00 h. A best-fit model for sand fly density analysis was developed using multiple logistic regression analysis. Geographical information system based spatial analysis techniques were employed to map the household type distribution of insecticide susceptibility of the vector, and IRS-status of the households to interpret the spatio-temporal distributions of P. argentipes., Results: Phlebotomus argentipes was highly susceptible to SP (100%) but showed high resistance to DDT with a 49.1% mortality rate. SP-IRS has been reported as having better community acceptance than DDT-IRS in all household types. Residual efficacies were varied between wall-surfaces; both insecticides failed to achieve the duration of IRS effectiveness recommended by the WHO. Reduction in P. argentipes counts due to SP-IRS was higher than DDT-IRS between household groups (i.e. sprayed and sentinel), in all intervals post-IRS. Combined spatial risk-maps revealed a better control effect of SP-IRS on sand flies than DDT-IRS in all household types risk-zones. The multilevel logistic regression analysis explored five risk-factors that were strongly associated with the density of P. argentipes., Conclusions: The results contribute to furthering current understanding of IRS-practices for control of visceral leishmaniasis in endemic Bihar, which may help in future actions for improvements.

The impact of topical applications of deltamethrin and ivermectin to cattle on Culicoides spp. landing and blood-feeding was studied in this work using sticky traps mounted on Friesian heifers' backs. There was no effect of the insecticides on total numbers of Culicoides trapped or the proportion engorged. Deltamethrin and ivermectin treatment did not prevent blood-feeding on these animals. Deltamethrin did result in significant Culicoides mortality as evidenced by the numbers of dead midges combed from heifers' upper flanks. The proximity of engorged midges on traps to dead midges in the hair suggests that blood-feeding took place despite midges receiving an ultimately lethal dose of deltamethrin. Ivermectin application resulted in a smaller proportion of nulliparous than parous females caught. There was no significant effect of ivermectin on the numbers of Culicoides that emerged from dung samples (but p was small at 0.095 for the Obsoletus group Culicoides ). In cases of suspect animal imports, pour-on or spray applications of deltamethrin could reduce the risk of onward transmission of bluetongue virus.

Over the past decade, insecticide resistance to malaria vectors has been identified in 71 malaria endemic countries. This has posed a major global health challenge in the fight against malaria, with declining rates of indoor residual spraying coverage attributed to pyrethroid-resistance. As part of its vector control monitoring strategies, the Bioko Island Malaria Control Project (BIMCP) in Equatorial Guinea conducted routine insecticide resistance bioassays using the WHO's standard susceptibility tests from 2013 to 2018. During the same period, the frequency of the target-site knockdown resistance allele (kdr) in the local vector population was also determined via PCR for detection of the L1014 F mutation. Biochemical analysis for metabolic resistance was also conducted in 2015. From 2016-2017, Fludora™ fusion, a formulated combination of clothianidin (a neonicotinoid) and deltamethrin (a pyrethroid) was evaluated for 9 months on Bioko Island, using the WHO's standard test procedure for determining residual effectiveness of insecticides on sprayed surfaces. In 2016, the mortality rate of the vectors on 0.05% deltamethrin was as low as 38%. The frequency of the West African form of knockdown resistance allele, L1014 F, in the vector population was as high as 80%, and metabolic resistance analysis indicated high upregulated cytochrome P450 s. However, the residual effectiveness of Fludora™ fusion recorded mortalities above 80% after 72 h of exposure for 8 months. Although both target-site knockdown resistance and metabolic resistance to pyrethroids were implicated in the local malaria vector population, Fludora™ fusion was effective under field conditions in controlling the resistant vectors for a period of 8 months on wooden surfaces on Bioko Island and represents a valuable addition to IRS programs, especially in regions with high levels of pyrethroid resistance., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

A well-known strategy for managing pest resistance is application of mixture of pesticides. Conventionally formulated pesticides have several environmental incompatibilities. The use of biocompatible and biodegradable nanocarriers in formulating pesticides could improve environmental protection. In this study, a mixture of imidacloprid and lambda-cyhalothrin was co-encapsulated for the first time using liposomes as nanocarrier to simultaneously deliver these insecticides. Ethanol injection was used to produce self-assembled liposomes. The formed nanoliposomes were coated with different concentrations of chitosan. Nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscope (SEM) and FT-IR spectroscopy. The encapsulation efficiencies of lambda-cyhalothrin and imidacloprid were about 93% and 51%, respectively. The insecticide carrying liposomes had a size and surface charge of 57 nm and +0.6 mV, respectively. The size and surface charge of the particles produced were increased to 69 nm and +31 mV after being coated with chitosan (0.1%, W/V). In this study, residual activity of technical grade imidacloprid, lambda-cyhalothrin and their mixture and the effect of adjuvants used in commercial and nano formulations of these insecticides on Myzus persicae Sulzer was investigated. The insecticidal effects and duration of residual activity of nano-formulations was correlated with concentration of chitosan in final formulation. In accordance with the life cycle of M. persicae, using the mixture of imidacloprid and lambda-cyhalothrin improves the residual effect over their use alone. The use of lipid nanocarriers makes the improvement even further and can be a better alternative to conventional combination of these insecticides due to their more environmental friendliness., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The carcinogenic potential of a non-genotoxic pyrethroid imiprothrin was examined in rats and mice. There was no carcinogenicity in rats up to a maximum dose of 5000 ppm of the diet. There was a higher (p = 0.03) incidence of lung adenocarcinomas at 7000 ppm in males, and females showed an increasing (p < 0.01) trend in the incidence of lung adenomas and combined lung adenoma/adenocarcinomas. Additional step sections of lung demonstrated no significant increases in any tumor at p < 0.05, although an increasing trend with dose was observed among females. We argue that, the 7000 ppm dose exceeded the Maximum Tolerated Dose (MTD) for both sexes, based on systemic toxicity as evidenced by body weight gain reduction (both sexes) and high mortality (females). If the 7000 ppm dose is therefore removed from consideration, there are not significant (p < 0.05) increases in tumor formation. Moreover, a consideration of multiple comparisons reveals that the lung tumor increases observed are totally consistent with what would be expected by chance alone. Based on high susceptibility of this mouse strain for the appearance of lung tumors and the lack of a statistically significant increase in tumors by appropriate analysis, the mouse study does not indicate a carcinogenic effect of imiprothrin, and thus no classification for carcinogenicity is warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Plague is a flea-borne disease of mammalian hosts. On the grasslands of western North America, plague stifles populations of Cynomys spp. prairie dogs (PDs). To manage plague, PD burrows are treated with 0.05% deltamethrin dust that can suppress flea numbers and plague transmission. Here, we evaluate the degree and duration of deltamethrin flea control with three PD species at six sites across four U.S. states. Data were simultaneously collected at paired plots. Burrows from one randomly assigned member of each pair were treated with deltamethrin; non-treated plots served as experimental baselines. Flea control was strong ≤two months after treatment, remained moderate one year later, and was statistically detectable for up to two years at some sites. Flea abundance was lower in plots with higher rates of deltamethrin application. After burrow treatments, flea abundance increased over time, reaching >one per PD within 255 to 352 days. Nevertheless, annual treatments of burrows with deltamethrin provided PDs with substantial protection against plague. Even so, deltamethrin should be further evaluated and combined with other tools under an integrated approach to plague management. Integrated plague management should help to conserve PDs and species that associate with them, including the endangered black-footed ferret (Mustela nigripes)., (© 2019 The Society for Vector Ecology.)

In the present study, adult immersion test (AIT) was used for evaluation of resistance against synthetic pyrethroids (deltamethrin and cypermethrin) in Rhipicephalus (Boophilus) microplus ticks collected from nine districts of three agro-climatic zones of north-western Himalayan region of India. Resistance factors (RFs) were calculated between 0.94 to 50.71 for deltamethrin and 0.32 to 13.18 for cypermethrin. Resistance to deltamethrin was detected at level I in two, level II in four, level III and level IV in one isolate each while one isolate was susceptible. Against cypermethrin, resistance at levels I and II was detected in three isolates each while three isolates were found susceptible. The low altitude sub-tropical zone revealed higher density of resistant ticks where intensive animal husbandry practices were followed and the synthetic pyrethroid usage was common. Data generated on pyrethroid resistance status of ticks in north-western Himalayan region will provide new insights in acaricidal resistance particularly from remote areas of this region and will help in formulating suitable control measures.

Deltamethrin (DEL) and other synthetic repellents like N,N-diethyl benzamide (DEB), N,N-diethyl phenylacetamide (DEPA), and N,N-diethyl meta toluamide (DEET) are widely used due their high efficacy against mosquitoes. We evaluated the safe dose on exposure to insecticide and insect repellent individually and in combination in Wistar rats. Rats were administrated with individual chemicals DEL, DEB, DEPA, and DEET and in combination of DEL along DEB, DEPA, and DEET. The reduced glutathione and its detoxifying enzymes were significantly increased in DEL treated rats. Serotonin, dopamine, and noradrenaline were increased in DEL alone and its combination groups. Histopathology revealed that DEL and along with other insect repellants can cause lung toxicities. This study suggests that DEL in combination with other insect repellents showed antagonistic effect against oxidative stress, and there was no significant toxicological effect in the combination groups. The insect repellents with DEL cause less toxic effect and is safe for use., (© 2019 Wiley Periodicals, Inc.)

Background: Experimental pharmacology deals with effects of various test substances studied on different animal species which is aimed at finding out safe therapeutic agent suitable for public health as well as mechanism and site of action of a test substance. It is the basic step in the discovery of new drugs or studying the pharmacological actions of already developed one using both preclinical and clinical study designs in a stepwise phase of investigations. However, the investigations in the first phase of experimental pharmacology are usually concluded with assumption hypothesis without any adequate validation of the scientific evidence. Single dose acute toxicology had been conducted on Balb c mice with three different level of doses prepared from each of three different test chemicals (Dichlorvos, Chlorpyrifos and Cypermethrin) with known median lethal dose (LD 50 ) to define the fundamental principles, cause of toxicity and investigation timeframe in the first phase of experimental pharmacology., Methods: The methods used for data collection were: procurement of test chemicals, investigation of single dose acute toxicity on Balb c mice and quantitative immunoglobulins test. Data was thematically compiled for validation of the findings from each of the sources., Results: The result showed that the dose had never limited the toxic property of tested chemicals but the magnitude of adverse effect and length of time at which adverse effect was manifested on treated Balb c mice. The toxicity of tested chemicals was however limited by the toxic reaction rate of a dose in the biological process of exposed Balb c mice. The toxic effect of tested chemicals became magnified within a short period of time when large amount administered orally. It also remained after a long period of time when small amount administered in the same route., Conclusion: Adequate investigation time for acute toxicity study was therefore essential for comprehensive analysis of pharmacological property of tested chemicals at different level of doses.

The present study was planned to evaluate neurotoxic effects of β-cyfluthrin in female Swiss albino mice. Two doses of β-cyfluthrin, specifically, one-tenth of median lethal dose (LD 50 ) and one-twentieth of LD 50 , were selected for the study. Open-field behaviour, exploratory behaviour and emotional status were affected, and animals showed anxiety-like behaviour after β-cyfluthrin administration. Spatial learning was decreased using the Hebb-Wiliams maze. Acetylcholinesterase enzyme activity significantly decreased in the treated animals. The administration of β-cyfluthrin caused increased lipid peroxidation (malondialdehyde) and decreased superoxide dismutase, catalase and glutathione peroxidase activity in brain tissue. In conclusion, β-cyfluthrin caused neurotoxicity as well as oxidative damage in the brain of Swiss albino mice at the tested dose levels.

The western corn rootworm (Diabrotica virgifera virgifera LeConte) (WCR) is a major insect pest of corn (Zea mays L.) in the United States (US) and is highly adaptable to multiple management tactics. A low level of WCR field-evolved resistance to pyrethroid insecticides has been confirmed in the US western Corn Belt by laboratory dose-response bioassays. Further investigation has identified detoxification enzymes as a potential part of the WCR resistance mechanism, which could affect the performance of insecticides that are structurally related to pyrethroids, such as organophosphates. Thus, the responses of pyrethroid-resistant and -susceptible WCR populations to the commonly used pyrethroid bifenthrin and organophosphate dimethoate were compared in active ingredient bioassays. Results revealed a relatively low level of WCR resistance to both active ingredients. Therefore, a simulated aerial application bioassay technique was developed to evaluate how the estimated resistance levels would affect performance of registered rates of formulated products. The simulated aerial application technique confirmed pyrethroid resistance to formulated rates of bifenthrin whereas formulated dimethoate provided optimal control. Results suggest that the relationship between levels of resistance observed in dose-response bioassays and actual efficacy of formulated product needs to be further explored to understand the practical implications of resistance.

Pesticide self-poisoning is rare in developed countries. We report a suicide case after inhalation of a pyrethrins containing insecticide spray. The patient presented at the emergency department with respiratory failure. Despite mechanical ventilation, he developed severe pulmonary inflammation with a systemic inflammatory response syndrome and died 5 days later. Studies reporting on acute pyrethrins or pyrethroids insecticide poisoning in both occupational and non-occupational cases usually describe mild and self-limiting respiratory symptoms as the predominant symptom. Severe or fatal cases of pyrethrins or pyrethroids poisoning are very rare. Patients with asthma or allergies are apparently more at risk for severe symptoms. In these cases, early and aggressive treatment with bronchodilatators, steroids, antihistamines and epinephrine should be considered., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An imidacloprid/flumethrin collar (Seresto®) was previously shown to prevent infection with Babesia canis, transmitted by Dermacentor reticulatus, in dogs for up to 1 month after application. The present study evaluated the prevention of transmission throughout the claimed efficacy period of 8 months., Methods: Eight animals each were randomly included in groups 1 (negative control) and 2 (Seresto® collar), respectively. Animals in group 2 received the Seresto® collar on Day 0. Tick challenges were performed monthly from the 2nd to the 8th month. Assessment criteria included in situ tick counts 48 hours post-challenge, polymerase chain reaction (PCR) analyses and immunofluorescence assays (IFA). Whenever dogs were diagnosed with babesiosis they were "rescue-treated", excluded and replaced. Consequently, 24 replacement animals were introduced at various time points throughout the study in the control group; thus data for a total of 32 dogs were available in the latter group at study termination., Results: Acaricidal efficacy for in situ counts was 93% on Day 30, and ranged from 97 to 100% thereafter. No B. canis specific DNA or antibodies were detected in any Seresto®-treated dog at any time. Babesia canis-specific DNA and antibodies were detected in 2-6 of 8 control dogs after each challenge, confirming the validity of the challenge model., Conclusions: The Seresto® collar was highly effective against challenges with D. reticulatus ticks for up to 8 months. The high sustained acaricidal efficacy over this period prevented transmission of B. canis, thus fully protecting dogs against infection in this experimental infestation model.

Background: Bartonella henselae, Bartonella clarridgeiae and the rare Bartonella koehlerae are zoonotic pathogens, with cats being regarded as the main reservoir hosts. The spread of the infection among cats occurs mainly via fleas and specific preventive measures need to be implemented. The effectiveness of a 10% imidacloprid/4.5% flumethrin polymer matrix collar (Seresto®, Bayer Animal Health), registered to prevent flea and tick infestations, in reducing the risk of Bartonella spp. infection in privately owned cats, was assessed in a prospective longitudinal study., Methods: In March-May 2015 [Day 0 (D0)], 204 privately-owned cats from the Aeolian Islands (Sicily) were collared (G1, n = 104) or left as controls (G2, n = 100). The bacteraemia of Bartonella spp. was assessed at enrolment (D0) and study closure (D360) by PCR and DNA sequencing both prior to and after an enrichment step, using Bartonella alpha proteobacteria growth medium (BAPGM)., Results: A total of 152 cats completed the study with 3 in G1 and 10 in G2 being positive for Bartonella spp. Bartonella henselae genotype I ZF1 (1.35%) and genotype II Fizz/Cal-1 (6.76%) as well as B. clarridgeiae (5.41%) were detected in cats of G2. Bartonella clarridgeiae was the only species detected in G1. Based on the yearly crude incidence of Bartonella spp. infection (i.e. 3.85% in G1 and 13.51% in G2; P = 0.03) the Seresto® collar achieved a preventative efficacy of 71.54%. The incidence of Bartonella spp. infection was more frequent in flea-infested cats (6/33, 18.18%) than in uninfested ones (7/112, 5.88%) (P = 0.036)., Conclusions: Cats living in the Aeolian Islands are exposed to B. henselae and B. clarridgeiae. The Seresto® collar provided significant risk reduction against Bartonella spp. infection in outdoor cats under field conditions. Such a preventative tool could be a key contribution for decreasing the risk of Bartonella spp. infection in cats and thus ultimately to humans.