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Scientific Reports Dec 2022To control pyrethroid-resistant malaria vectors, Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal Nets (LLINs) that include additional ingredients to...
To control pyrethroid-resistant malaria vectors, Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal Nets (LLINs) that include additional ingredients to pyrethroid are being developed. Same progress needs to be made to the pyrethroid-treated blankets, which are more compatible with shelter structures found in emergency settings such as displaced populations. In the current study, efficacy of blankets treated with permethrin and piperonyl butoxide (PBO) was evaluated against pyrethroid-resistant Anopheles gambiae sensu stricto. Efficacy was compared with that of Olyset LLIN, Olyset Plus LLIN and untreated blanket in terms of mortality and blood-feeding inhibition against pyrethroid-resistant Anopheles gambiae mosquitoes. The current study indicates that, in emergency shelters such as migrant and refugee camps where LLINs cannot be used, PBO-permethrin blankets may provide protection against resistant mosquitoes if widely used. No side effects related to the use of the treated blankets were reported from the participants. These results need validation in a large-scale field trial to assess the epidemiological impact of the intervention, durability and acceptability of this new vector control strategy for malaria vector control.
Topics: Animals; Humans; Pyrethrins; Permethrin; Piperonyl Butoxide; Anopheles; Insecticide Resistance; Malaria; Insecticide-Treated Bednets; Mosquito Vectors; Insecticides; Mosquito Control
PubMed: 36550139
DOI: 10.1038/s41598-022-26804-9 -
Toxicology Reports Dec 2023Piperonyl butoxide (PBO) is a popular insecticide synergist present in thousands of commercial, agricultural, and household products. PBO inhibits cytochrome P450...
Piperonyl butoxide (PBO) is a popular insecticide synergist present in thousands of commercial, agricultural, and household products. PBO inhibits cytochrome P450 activity, impairing the ability of insects to detoxify insecticides. PBO was recently discovered to also inhibit Sonic hedgehog signaling, a pathway required for embryonic development, and rodent studies have demonstrated the potential for PBO exposure to cause structural malformations of the brain, face, and limbs, or more subtle neurodevelopmental abnormalities. The current understanding of the pharmacokinetics of PBO in mice is limited, particularly with respect to dosing paradigms associated with developmental toxicity. To establish a pharmacokinetic (PK) model for oral exposure, PBO was administered to female C57BL/6J mice acutely by oral gavage (22-1800 mg/kg) or via diet (0.09 % PBO in chow). Serum and adipose samples were collected, and PBO concentrations were determined by HPLC-MS/MS. The serum concentrations of PBO were best fit by a linear one-compartment model. PBO concentrations in visceral adipose tissue greatly exceeded those in serum. PBO concentrations in both serum and adipose tissue decreased quickly after cessation of dietary exposure. The elimination half-life of PBO in the mouse after gavage dosing was 6.5 h (90 % CI 4.7-9.5 h), and systemic oral clearance was 83.3 ± 20.5 mL/h. The bioavailability of PBO in chow was 41 % that of PBO delivered in olive oil by gavage. Establishment of this PK model provides a foundation for relating PBO concentrations that cause developmental toxicity in the rodent models to Sonic hedgehog signaling pathway inhibition.
PubMed: 37789951
DOI: 10.1016/j.toxrep.2023.09.017 -
The American Journal of Tropical... Oct 2022Despite the scale-up of interventions against malaria over the past decade, this disease remains a leading threat to health in Malawi. To evaluate the epidemiology of...
Despite the scale-up of interventions against malaria over the past decade, this disease remains a leading threat to health in Malawi. To evaluate the epidemiology of both Plasmodium falciparum infection and malaria disease, the Malawi International Center of Excellence for Malaria Research (ICEMR) has developed and implemented diverse and robust surveillance and research projects. Descriptive studies in ICEMR Phase 1 increased our understanding of the declining effectiveness of long-lasting insecticidal nets (LLINs), the role of school-age children in malaria parasite transmission, and the complexity of host-parasite interactions leading to disease. These findings informed the design of ICEMR Phase 2 to test hypotheses about LLIN use and effectiveness, vector resistance to insecticides, demographic targets of malaria control, patterns and causes of asymptomatic to life-threatening disease, and the impacts of RTS,S vaccination plus piperonyl butoxide-treated LLINs on infection and disease in young children. These investigations are helping us to understand mosquito-to-human and human-to-mosquito transmission in the context of Malawi's intransigent malaria problem.
Topics: Animals; Child; Child, Preschool; Humans; Insecticide Resistance; Insecticide-Treated Bednets; Insecticides; Malaria; Malawi; Mosquito Control; Mosquito Vectors; Piperonyl Butoxide
PubMed: 36228915
DOI: 10.4269/ajtmh.21-1263 -
Malaria Journal Jan 2022Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance....
BACKGROUND
Long-lasting insecticidal nets (LLINs) are the main vector control tool for pregnant women, but their efficacy may be compromised, in part, due to pyrethroid resistance. In 2017, the Ugandan Ministry of Health embedded a cluster randomized controlled trial into the national LLIN campaign, where a random subset of health subdistricts (HSDs) received LLINs treated with piperonyl butoxide (PBO), a chemical synergist known to partially restore pyrethroid sensitivity. Using data from a small, non-randomly selected subset of HSDs, this secondary analysis used quasi-experimental methods to quantify the overall impact of the LLIN campaign on pregnancy outcomes. In an exploratory analysis, differences between PBO and conventional (non-PBO) LLINs on pregnancy outcomes were assessed.
METHODS
Birth registry data (n = 39,085) were retrospectively collected from 21 health facilities across 12 HSDs, 29 months before and 9 months after the LLIN campaign (from 2015 to 2018). Of the 12 HSDs, six received conventional LLINs, five received PBO LLINs, and one received a mix of conventional and PBO LLINs. Interrupted time-series analyses (ITSAs) were used to estimate changes in monthly incidence of stillbirth and low birthweight (LBW; <2500 g) before-and-after the campaign. Poisson regression with robust standard errors modeled campaign effects, adjusting for health facility-level differences, seasonal variation, and time-varying maternal characteristics. Comparisons between PBO and conventional LLINs were estimated using difference-in-differences estimators.
RESULTS
ITSAs estimated the campaign was associated with a 26% [95% CI: 7-41] reduction in stillbirth incidence (incidence rate ratio (IRR) = 0.74 [0.59-0.93]) and a 15% [-7, 33] reduction in LBW incidence (IRR=0.85 [0.67-1.07]) over a 9-month period. The effect on stillbirth incidence was greatest for women delivering 7-9 months after the campaign (IRR=0.60 [0.41-0.87]) for whom the LLINs would have covered most of their pregnancy. The IRRs estimated from difference-in-differences analyses comparing PBO to conventional LLINs was 0.78 [95% CI: 0.52, 1.16] for stillbirth incidence and 1.15 [95% CI: 0.87, 1.52] for LBW incidence.
CONCLUSIONS
In this region of Uganda, where pyrethroid resistance is high, this study found that a mass LLIN campaign was associated with reduced stillbirth incidence. Effects of the campaign were greatest for women who would have received LLINs early in pregnancy, suggesting malaria protection early in pregnancy can have important benefits that are not necessarily realized through antenatal malaria services. Results from the exploratory analyses comparing PBO and conventional LLINs on pregnancy outcomes were inconclusive, largely due to the wide confidence intervals that crossed the null. Thus, future studies with larger sample sizes are needed.
Topics: Adult; Female; Humans; Insecticide-Treated Bednets; Insecticides; Interrupted Time Series Analysis; Malaria; Mosquito Vectors; Piperonyl Butoxide; Pregnancy; Pregnancy Outcome; Retrospective Studies; Uganda; Young Adult
PubMed: 34983550
DOI: 10.1186/s12936-021-04034-0 -
Current Research in Parasitology &... 2022Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however,...
LLIN evaluation in Uganda project (LLINEUP): The fabric integrity, chemical content and bioefficacy of long-lasting insecticidal nets treated with and without piperonyl butoxide across two years of operational use in Uganda.
Long-lasting insecticidal nets (LLINs) supplemented with the synergist piperonyl butoxide have been developed in response to growing pyrethroid resistance; however, their durability in the field remains poorly described. A pragmatic cluster-randomised trial was embedded into Uganda's 2017-2018 LLIN distribution to compare the durability of LLINs with and without PBO. A total of 104 clusters (health sub-districts) were included with each receiving one of four LLIN products, two with pyrethroid + PBO (Olyset Plus and PermaNet 3.0) and two pyrethroid-only (Olyset Net and PermaNet 2.0). Nets were sampled at baseline, 12 and 25 months post-distribution to assess physical condition, chemical content, and bioefficacy. Physical condition was quantified using proportionate Hole Index and chemical content measured using high-performance liquid chromatography. Bioefficacy was assessed with three-minute World Health Organisation (WHO) Cone and Wireball assays using pyrethroid-resistant , with 1-h knockdown and 24-h mortality recorded. There was no difference in physical durability between LLIN products assessed ( = 0.644). The pyrethroid content of all products remained relatively stable across time-points but PBO content declined by 55% ( < 0.001) and 58% ( < 0.001) for Olyset Plus and PermaNet 3.0 respectively. Both PBO LLINs were highly effective against pyrethroid-resistant mosquitoes when new, knocking down all mosquitoes. However, bioefficacy declined over time with Olyset Plus knocking down 45.72% (95% CI: 22.84-68.62%, = 0.021) and Permanent 3.0 knocking down 78.57% (95% CI: 63.57-93.58%, < 0.001) after 25 months. Here we demonstrate that both Olyset Plus and PermaNet 3.0 are as durable as their pyrethroid-only equivalents and had superior bioefficacy against pyrethroid-resistant . However, the superiority of PBO-LLINs decreased with operational use, correlating with a reduction in total PBO content. This decline in bioefficacy after just two years is concerning and there is an urgent need to assess the durability of PBO LLINs in other settings.
PubMed: 35734077
DOI: 10.1016/j.crpvbd.2022.100092 -
Pediatrics Mar 2011Recent pesticide-monitoring results suggest that a shift in residential pesticide exposure from organophosphorus insecticides to pyrethroid insecticides has occurred.... (Comparative Study)
Comparative Study
OBJECTIVE
Recent pesticide-monitoring results suggest that a shift in residential pesticide exposure from organophosphorus insecticides to pyrethroid insecticides has occurred. Pyrethroid insecticides are potential neurodevelopmental toxicants and have not been evaluated for developmental toxicity. Our objective was to explore the association between prenatal exposure to permethrin (a common pyrethroid) and piperonyl butoxide (a pyrethroid synergist) and 36-month neurodevelopment.
METHODS
Participants is this study were part of a prospective cohort of black and Dominican mothers and newborns living in low-income neighborhoods in New York City. We examined 36-month cognitive and motor development (using the Bayley Scales of Infant Development, second edition) as a function of permethrin levels measured in maternal and umbilical cord plasma collected on delivery and permethrin and piperonyl butoxide levels measured in personal air collected during pregnancy. All models were controlled for gender, gestational age, ethnicity, maternal education, maternal intelligence, quality of the home environment, and prenatal exposure to environmental tobacco smoke and chlorpyrifos.
RESULTS
Prenatal exposure to permethrin in personal air and/or plasma was not associated with performance scores for the Bayley Mental Developmental Index or the Psychomotor Developmental Index. After data adjustment, children more highly exposed to piperonyl butoxide in personal air samples (>4.34 ng/m(3)) scored 3.9 points lower on the Mental Developmental Index than those with lower exposures (95% confidence interval: -0.25 to -7.49).
CONCLUSIONS
Prenatal exposure to piperonyl butoxide was negatively associated with 36-month neurodevelopment.
Topics: Adolescent; Adult; Child Development; Cognition; Developmental Disabilities; Female; Follow-Up Studies; Humans; Infant, Newborn; Motor Activity; Nervous System; Pesticide Synergists; Piperonyl Butoxide; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Young Adult
PubMed: 21300677
DOI: 10.1542/peds.2010-0133 -
Parasitology Research Dec 2023Numerous biting and nuisance insects are a noted cause of discomfort and stress to horses. Pyrethrins and pyrethroids have been used for many years in numerous...
Efficacy of topical administration of prallethrin-permethrin-piperonyl butoxide (Bronco® Equine Fly Spray) for the treatment and control of flies and other nuisance insects of horses.
Numerous biting and nuisance insects are a noted cause of discomfort and stress to horses. Pyrethrins and pyrethroids have been used for many years in numerous formulations for the control of insect pests in animals, humans and environment. There are, however, few studies reporting their field efficacy in horses. The aim of the present study was to evaluate the repellent activity of a spray formulation based on prallethrin and permethrin synergized with piperonyl butoxide (BRONCO® Equine Fly Spray, Farnam Companies, Inc., USA) against annoying and harmful insects for horses in field conditions. Nine horses of mixed breed were divided into 2 groups (treatment and control). Pre-treatment insect counts were compared to daily counts for 4 days post-treatment (pt). One minute after the administration of the product (day 0), all the horses were negative for the presence of insects. All counts up to the 6-h pt check remained negative for Hippobosca equina, tabanid flies and Simulium spp., showing 100% efficacy. This remained above 90% throughout the study. For the H. equina, the repellent efficacy remained > 99.7% for all 4 days pt, for tabanid flies > 93.3% and for Simulium spp. > 97.4%. The efficacy against Musca spp. decreased from 82.2% at day 0 to 62.2% at day 3. Treatment was well-tolerated. In conclusion, despite the low number of tested horses, Bronco® has demonstrated high insecticide and repellent efficacy and a good persistence, maintained for up to 4 days post-treatment, against the most common species of insects harmful for horses.
Topics: Humans; Horses; Animals; Permethrin; Piperonyl Butoxide; Pyrethrins; Insecticides; Muscidae; Insect Repellents; Simuliidae; Administration, Topical
PubMed: 37921904
DOI: 10.1007/s00436-023-08004-0 -
PLoS Neglected Tropical Diseases Jun 2022Information on the insecticide resistance profiles of Aedes aegypti in Indonesia is fragmentary because of the lack of wide-area insecticide resistance surveillance. We...
Information on the insecticide resistance profiles of Aedes aegypti in Indonesia is fragmentary because of the lack of wide-area insecticide resistance surveillance. We collected Ae. aegypti from 32 districts and regencies in 27 Indonesian provinces and used WHO bioassays to evaluate their resistance to deltamethrin, permethrin, bendiocarb, and pirimiphos-methyl. To determine the possible resistance mechanisms of Ae. aegypti, synergism tests were conducted using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioates (DEF). The Ae. aegypti from all locations exhibited various levels of resistance to pyrethroids. Their resistance ratio (RR50) to permethrin and deltamethrin ranged from 4.08× to 127× and from 4.37× to 72.20×, respectively. In contrast with the findings of other studies, most strains from the highly urbanized cities on the island of Java (i.e., Banten, Jakarta, Bandung, Semarang, Yogyakarta, and Surabaya) exhibited low to moderate resistance to pyrethroids. By contrast, the strains collected from the less populated Kalimantan region exhibited very high resistance to pyrethroids. The possible reasons are discussed herein. Low levels of resistance to bendiocarb (RR50, 1.24-6.46×) and pirimiphos-methyl (RR50, 1.01-2.70×) were observed in all tested strains, regardless of locality. PBO and DEF synergists significantly increased the susceptibility of Ae. aegypti to permethrin and deltamethrin and reduced their resistance ratio to less than 16×. The synergism tests suggested the major involvement of cytochrome P450 monooxygenases and esterases in conferring pyrethroid resistance. On the basis of our results, we proposed a 6-month rotation of insecticides (deltamethrin + synergists ➝ bendiocarb ➝ permethrin + synergists ➝ pirimiphos-methyl) and the use of an insecticide mixture containing pyrethroid and pyrimiphos-methyl to control Ae. aegypti populations and overcome the challenge of widespread Ae. aegypti resistance to pyrethroid in Indonesia.
Topics: Aedes; Animals; Indonesia; Insecticide Resistance; Insecticides; Permethrin; Pyrethrins
PubMed: 35666774
DOI: 10.1371/journal.pntd.0010501 -
Molecules (Basel, Switzerland) Jan 2023In this work, we have studied the benzofurans of (aerial parts and transformed roots), (aerial parts and transformed roots), (aerial parts), and (aerial parts and...
In this work, we have studied the benzofurans of (aerial parts and transformed roots), (aerial parts and transformed roots), (aerial parts), and (aerial parts and roots). This work has permitted the isolation of the new benzofurans 10-ethoxy-11-hydroxy-10,11-dihydroeuparin (), (-)-eupachinin A ethyl ether (), 11,15-didehydro-eupachinin A (), 10,12-dihydroxy-11-angelyloxy-10,11-dihydroeuparin (), 2,4-dihydroxy-5-formyl-acetophenone () isolated for the first time as a natural product, 11-angelyloxy-10,11-dihydroeuparin (), and 12-angelyloxyeuparone (), along with several known ones (-). In addition, the incubation of the abundant component, 6-hydroxytremetone (), with the fungus has been studied. Benzofurans in the tremetone series (, , -, , ), the euparin series (, , , -, , ), and the eupachinin-type (, ) were tested for antifeedant effects against the insect . The antifeedant compounds (, , , , ) were further tested for postingestive effects on larvae. The most antifeedant compounds were among the tremetone series, with 3-ethoxy-hydroxy-tremetone () being the strongest antifeedant. Glucosylation of by its biotransformation with gave inactive products. Among the euparin series, the dihydroxyangelate was the most active, followed by euparin (). The eupachinin-type compounds (, ) were both antifeedants. Compounds and showed antifeedant effects without postingestive toxicity to orally dosed larvae. Euparin ( had postingestive toxicity that was enhanced by the synergist piperonyl butoxide.
Topics: Animals; Insecta; Mucor; Larva; Benzofurans; Spodoptera; Insecticides
PubMed: 36770655
DOI: 10.3390/molecules28030975 -
Malaria Journal Dec 2020Pyrethroid-treated mosquito nets are currently the mainstay of vector control in Côte d'Ivoire. However, resistance to pyrethroids has been reported across the country,...
Susceptibility of Anopheles gambiae from Côte d'Ivoire to insecticides used on insecticide-treated nets: evaluating the additional entomological impact of piperonyl butoxide and chlorfenapyr.
BACKGROUND
Pyrethroid-treated mosquito nets are currently the mainstay of vector control in Côte d'Ivoire. However, resistance to pyrethroids has been reported across the country, limiting options for insecticide resistance management due to the paucity of alternative insecticides. Two types of insecticide-treated nets (ITNs), ITNs with pyrethroids and the synergist piperonyl butoxide (PBO), and Interceptor®G2 nets, a net treated with a combination of chlorfenapyr and alpha-cypermethrin, are believed to help in the control of pyrethroid-resistant mosquitoes.
METHODS
The susceptibility of Anopheles gambiae sensu lato (s.l.) to pyrethroid insecticides with and without pre-exposure to PBO as well as to chlorfenapyr was investigated in fifteen sites across the country. Susceptibility tests were conducted on 2- to 4-day old adult female An. gambiae s.l. reared from larval collections. The resistance status, intensity, and effects of PBO on mortality after exposure to different concentrations of deltamethrin, permethrin and alpha-cypermethrin were determined using WHO susceptibility test kits. In the absence of a WHO-recommended standard protocol for chlorfenapyr, two interim doses (100 and 200 µg/bottle) were used to test the susceptibility of mosquitoes using the CDC bottle assay method.
RESULTS
Pre-exposure to PBO did not result in full restoration of susceptibility to any of the three pyrethroids for the An. gambiae s.l. populations from any of the sites surveyed. However, PBO pre-exposure did increase mortality for all three pyrethroids, particularly deltamethrin (from 4.4 to 48.9%). Anopheles gambiae s.l. from only one site (Bettie) were susceptible to chlorfenapyr at the dose of 100 µg active ingredient (a.i.)/bottle. At the dose of 200 µg (a.i.)/bottle, susceptibility was only recorded in 10 of the 15 sites.
CONCLUSION
Low mosquito mortality was found for pyrethroids alone, and while PBO increased mortality, it did not restore full susceptibility. The vector was not fully susceptible to chlorfenapyr in one third of the sites tested. However, vector susceptibility to chlorfenapyr seems to be considerably higher than for pyrethroids alone or with PBO. These data should be used cautiously when making ITN procurement decisions, noting that bioassays are conducted in controlled conditions and may not fully represent field efficacy where the host-seeking behaviours, which include free-flying activity are known to enhance pro-insecticide chlorfenapyr intoxication to mosquitoes.
Topics: Animals; Anopheles; Cote d'Ivoire; Drug Synergism; Female; Insecticide Resistance; Insecticide-Treated Bednets; Insecticides; Mosquito Control; Mosquito Vectors; Pesticide Synergists; Piperonyl Butoxide; Pyrethrins
PubMed: 33298071
DOI: 10.1186/s12936-020-03523-y