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PubMed1996

Neurotoxicity resulting from coexposure to pyridostigmine bromide, deet, and permethrin: implications of Gulf War chemical exposures.

Of the three-quarters of a million service personnel involved in the Persian Gulf War, approximately 30,000 have complained of neurological symptoms of unknown etiology. One contributing factor to the emergence of such symptoms may be the simultaneous exposure to multiple agents used to protect the health of service personnel, in particular, the anti-nerve agent pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methylpyridinium bromide), the insect repellent DEET (N,N-diethyl-m-toluamide), and the insecticide permethrin (3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3-phenoxyphenyl)methyl ester). This study investigated neurotoxicity produced in hens by individual or simultaneous exposure to these agents (5 d/wk for 2 months to 5 mg/kg/d PB in water, po; 500 mg/kg/d DEET, neat, sc; and 500 mg/kg/d permethrin in corn oil, sc). At these dosages, exposure to single compounds resulted in minimal toxicity. Combinations of two agents produced greater neurotoxicity than that caused by individual agents. Neurotoxicity was further enhanced following concurrent administration of all three agents. We hypothesize that competition for liver and plasma esterases by these compounds leads to their decreased breakdown and increased transport of the parent compound to nervous tissues. Thus, carbamylation of peripheral esterases by PB reduces the hydrolysis of DEET and permethrin and increases their availability to the nervous system. In effect, PB "pumps" more DEET and permethrin into the central nervous system. Consistent with this hypothesis, hens exposed to the combination of the three agents exhibited neuropathological lesions with several characteristics similar to those previously reported in studies of near-lethal doses of DEET and permethrin. If this hypothesis is correct, then blood and liver esterases play an important "buffering" role in protecting against neurotoxicity in the population at large. It also suggests that individuals with low plasma esterase activity may be predisposed to neurologic deficits produced by exposure to certain chemical mixtures.

Administration, Oral↗

PubMed1982

Control of blueberry thrips, Frankliniella vaccinii Morgan, with permethrin and effect on yield and residue in fruit.

Permethrin at 0.4 kg a.i./ha controlled blueberry thrips Frankliniella vaccinii Morgan. There was no plant damage and crop yield was notably increased. Permethrin was extracted from berries with acetone, partitioned in hexane, cleaned-up on Florisil column and analysed by the electron capture gas chromatography using a 3% OV-210 column. No permethrin residues were found in the berries. The relative retention times of cis-, and trans-permethrins to aldrin were 10.3 and 12.1, respectively. The absence of permethrin from berries was further confirmed by TLC.

Animals↗

PubMed1994

Stimulation of attachment in a camel tick, Hyalomma dromedarii (Acari: Ixodidae): the unintended result of sublethal exposure to permethrin-impregnated fabric.

The susceptibility of a camel tick, Hyalomma dromedarii (Koch), to permethrin-impregnated military uniform fabric was studied to determine the effects of laundering and contact time. Separate contact toxicity tests were conducted with laboratory-colonized male and female ticks of uniform age. Unfed, unmated ticks were exposed for periods of 5, 10, 30, and 60 min to each of five fabrics: unwashed-untreated, unwashed-treated, and 1, 2, or 3 times washed after treatment (1-, 2-, 3-wash-treated). Treated fabric was impregnated with permethrin at 0.125 mg (AI)/cm2. Laundering was by machine washing with detergent followed by hot air machine drying. Intoxication immediately after exposure was assessed by activity response: the proportion of ticks attaching to a host (rabbit) within 60 min and the average time elapsed between contact and insertion of mouthparts. Unexpectedly, permethrin exposure activated an attachment response in both sexes. At all contact times, and in each wash-treated group, a greater proportion of ticks attached, and did so more rapidly, than in controls. Mortality assessment 24 h after exposure showed that females were more tolerant than males and experienced light mortality even after 60 min of contact. Both natural and acquired factors may account for permethrin tolerance in this species. Consistent with pyrethroid mode of action and pheromone function in ticks, it is hypothesized that sublethal levels of permethrin may act on H. dromedarii to induce premature or excess release of a neurosecretory substance that elicits attachment.

Animals↗

PubMed1992

Cytogenetic effects of permethrin in cultured human lymphocytes.

The pyrethroid insecticide permethrin was tested for its ability to induce sister chromatid exchanges (SCE), micronuclei (MN) and structural chromosome aberrations (CA) in cultured human peripheral blood lymphocytes. Permethrin was tested in the range of 5-500 micrograms/ml in the absence and in the presence of a rat liver activation system (S9 mix). Small elevations in the SCE frequencies were found and even though statistically significant may have no biological meaning, the more so since there was no dose-effect relationship. Permethrin induced both MN and CA when it was evaluated in the absence of a metabolic activation system. Nevertheless, it cannot be said that S9 mix suppressed the activity in itself. The effect of permethrin seemed to be time of exposure dependent. Permethrin could be characterized as a S-phase independent agent with greater potential for inducing chromosomal damage than sister chromatid exchanges.

Animals↗

PubMed1989

Impact of permethrin-treated bednets on malaria transmission by the Anopheles gambiae complex in The Gambia.

Malaria vector mosquitoes belonging to the Anopheles gambiae complex were studied in four hamlets in The Gambia. All inhabitants were given bednets treated either with a placebo (milk) in two hamlets or with the pyrethroid insecticide permethrin (500 mg/m2) in two other hamlets. Malaria transmission occurred mainly during a few weeks of the rainy season, in September and October 1987. The indoor resting densities of mosquitoes in permethrin-treated hamlets were reduced, and we estimated over 90% reduction in biting on man by An. gambiae Giles sensu stricto in these hamlets. No mosquitoes were found under permethrin-treated bednets compared with eighty-one recovered from placebo-treated bednets. Mosquitoes exited more readily from rooms where permethrin-treated bednets were used than from rooms with placebo-treated nets. The annual mean probability that a child would receive an infective bite was estimated to be 0.09 in hamlets with insecticide-treated bednets, compared with 1.9 where placebo-treated bednets were used. Permethrin-treated bednets are therefore recommended as a means of effectively reducing the risk of exposure to malaria transmission, particularly in areas of low seasonal transmission.

Animals↗

PubMed1989

Evaluations of permethrin-impregnated clothing and three topical repellent formulations of deet against tsetse flies in Zambia.

Permethrin-impregnated clothing and three topical repellent formulations of deet (diethyltoluamide) were field tested against natural populations of tsetse flies, mostly Glossina morsitans centralis Machado, in central Zambia. Volunteers wore different combinations of clothing impregnated with permethrin 0.125 mg ai/cm2 and repellents while riding in a vehicle that was driven slowly (4-6 km/h), with the windows and rear door open, through fly-infested areas. The mean rate of tsetse bites was about twenty per 75 min for unprotected people. The treatment combination of permethrin-impregnated clothing (blue cotton coveralls) and either of two controlled-release deet formulations on exposed skin of face and arms provided 91% mean protection, but this was not significantly better (P greater than 0.05) than wearing deet repellent alone (76-87% protection). No significant differences of protection were observed between the three repellent treatments, although the two controlled-release formulations (intended to be more persistent) were applied at approximately half the dosage of the standard 75% deet. Wearing permethrin-impregnated coveralls alone provided relatively poor protection (34%) for the untreated and exposed skin of head and hands. However, olive drab mesh jackets treated with permethrin reduced the tsetse biting rate by 75%.

Animals↗

PubMed1995

Permethrin resistance in the head louse Pediculus capitis from Israel.

Head lice, Pediculus capitis, were collected from children aged 3-12 years in Maale Adumin, a town near Jerusalem, after reports of control failure with the pyrethroid insecticide permethrin. A total of 1516 children were examined: living lice and eggs were found on 12.1% of the children; or another 22.8% of the children only nits were found. Twice as many girls as boys (8.1% v 4%) were infested with lice and or nits. Head lice collected from infested children were exposed to permethrin impregnated filter-papers. Log time probit mortality (ltp) regression lines were calculated for mortality data and compared to ltp lines for a similar collection of head lice made in 1989. The regression lines for the two years were significantly different, with a 4-fold decrease in susceptibility at the LT50 level between 1989 and 1994. The slopes of the lines also suggested that the 1994 population was more heterogenous in its response to permethrin than the 1989 population. In contrast, a laboratory population of body lice (Pediculus humanus) tested with the same batch of permethrin-impregnated papers showed a slight but non-significant increase in susceptibility between 1989 and 1994. The results suggest that resistance to pyrethroids has developed rapidly among head lice since permethrin was introduced in 1991 as a pediculicide in Israel.

Animals↗

PubMed1995

Village trial of bednets impregnated with wash-resistant permethrin compared with other pyrethroid formulations.

A village-scale field trial of pyrethroid-impregnated mosquito nets was undertaken in The Gambia, West Africa, in the Mandinka village of Saruja (13 degrees 13'N, 14 degrees 55'W) during July-November 1989. Nearly all the villagers possessed and used their own bednets. Anopheles gambiae is the main vector of human malaria in the area. An experimental wash-resistant formulation of permethrin was compared with standard emulsifiable concentrate (EC) formulations of permethrin and lambda-cyhalothrin, versus placebo-treated bednets. Target concentrations of pyrethroids on bednets were permethrin 500 mg/m2 and lambda-cyhalothrin 25 mg/m2. The experimental design involved random allocation of a treatment to one net per family. Whereas 68% of people questioned said they washed their nets fortnightly, observations during the 16-week trial period showed that only 4/130 (3%) of nets involved in the trial had been washed as frequently as once per month. Early morning searches for mosquitoes under bednets (1 day/week for 16 weeks) found significantly more mosquitoes (60% An.gambiae) in placebo-treated nets than in pyrethroid-treated nets. The numbers found with each of the three pyrethroid treatments did not differ significantly from each other. Insecticidal efficacy of the treatments was tested by bioassays using wild-caught unfed mosquitoes exposed to netting for 3 min. Linear regression analysis of bioassay mortality against number of times that a net had been washed by villagers showed that nets impregnated with the wash-resistant permethrin retained their insecticidal properties better than nets impregnated with lambda-cyhalothrin or with the standard permethrin formulation.

Animals↗

PubMedDate not supplied

Albendazole: single or combination therapy with permethrin against pediculosis capitis.

Pediculosis capitis is a worldwide problem and a growing concern because of resistance to pediculicides. In the present study, we investigated whether albendazole could be used in the treatment of pediculosis capitis in combination with 1% permethrin or alone. A total of 150 children were randomly divided to five groups of 30 each. Group 1 got albendazole in a single dose (400 mg), group 2 got albendazole at 400 mg for 3 days, group 3 was given 1% permethrin, group 4 took 1% permethrin and albendazole in a single dose (400 mg), and group 5 got 1% permethrin and albendazole in a dose of 400 mg for 3 days. Groups given albendazole were also given another 400 mg dose of albendazole after 1 week. The success rate of treatment at the 2-week follow-up for all groups was 61.5%, 66.6%, 80.0%, 84.6%, and 82.1%, respectively. No statistically significant difference was found between the groups. The results of this study suggest that albendazole is effective against pediculosis capitis and there is no synergistic effect between albendazole and 1% permethrin.

Adolescent↗

PubMed2006

Treatment of scabies with 5% permethrin cream: results of a German multicenter study.

BACKGROUND: Until recently, no prescription drug containing permethrin for the therapy of scabies was available on the German market.Therefore, a 5% permethrin cream formulation (InfectoScab 5%) was tested in a single-arm multi-center study including adults and children from 3 months of age with proven scabies. PATIENTS AND METHODS: On day 0, patients were treated once with permethrin cream in the study center. Control examinations including dermatoscopy were performed on day 14+/-2 and on day 28+/-3. Patients who were not considered cured or who had contact to individuals with untreated scabies received one further treatment with permethrin cream on day 14+/-2. Itching and local tolerability of the cream were documented in patients' diaries. Side effects were assessed by history, skin inspection and evaluation of patients' notes. RESULTS: 106 patients in 13 centers were enrolled in the study. Their mean age was 29.2 years (range, 141 days to 71.9 years); 34% of them were children or adolescents. 78.3% of patients were either severely (3 body sites) or very severely (4-5 sites) affected. The cure rate on day 28+/-3 was 95.1% (95% confidence interval, 91.0-99.3%). Pruritus declined markedly and continuously. In general, the cream was well tolerated; side effects were almost invariably mild. CONCLUSIONS: Our results support the efficacy and safety of 5% permethrin cream in adults, children and infants suffering from scabies. These results have contributed to the approval of InfectoScab 5% in Germany for the treatment of scabies in October 2004.

Administration, Topical↗

PubMedDate not supplied

Immunohistochemical changes in the mouse striatum induced by the pyrethroid insecticide permethrin.

Epidemiological studies have linked insecticide exposure and Parkinson's disease. In addition, some insecticides produce damage or physiological disruption within the dopaminergic nigrostriatal pathway of non-humans. This study employed immunohistochemical analysis in striatum of the C57BL/6 mouse to clarify tissue changes suggested by previous pharmacological studies of the pyrethroid insecticide permethrin. Dopamine transporter, tyrosine hydroxylase, and glial fibrillary acidic protein immunoreactivities were examined in caudate-putamen to distinguish changes in amount of dopamine transporter immunoreactive protein from degeneration or other damage to dopaminergic neuropil. Weight-matched pairs of pesticide-treated and vehicle-control mice were dosed and sacrificed on the same days. Permethrin at 0.8, 1.5 and 3.0 mg/kg were the low doses and at 200 mg/kg the high dose. Brains from matched pairs of mice were processed on the same slides using the avidin-biotin technique. Four fields were morphometrically located in each of the serial sections of caudate-putamen, digitally photographed, and immunopositive image pixels were counted and compared between members of matched pairs of permethrin-treated and vehicle-control mice. For low doses, only 3.0 mg/kg produced a significant decrease in dopamine transporter immunostaining. The high dose of permethrin did not produce a significant change in dopamine transporter or tyrosine hydroxylase immunostaining, but resulted in a significant increase in glial fibrillary acidic protein immunostaining. These data suggest that a low dose of permethrin can reduce the amount of dopamine transporter immunoreactive protein in the caudate-putamen. They also suggest that previously reported reductions in dopamine uptake of striatal synaptosomes of high-dose mice may be due to nondegenerative tissue damage within this region as opposed to reductions of dopamine transporter protein or death of nigrostriatal terminals. These data provide further evidence that insecticides can affect the primary neurodegenerative substrate of Parkinson's disease.

Animals↗

PubMed2005

Effect of sub-lethal concentrations of permethrin on ovary activation in the predator Supputius cincticeps (Heteroptera: Pentatomidae).

Insecticides may cause mortality and deleterious effects on predatory stinkbugs. For this reason, the effect of five concentrations of permethrin applied on third instar nymphs of Supputius cincticeps (Stål) (Heteroptera: Pentatomidae) was investigated on ovary activation in this predator. The nymphs received topical application of permethrin in the following concentrations (mg a.i./ml): 10(-7), 10(-6), 10(-5), 10(-4), and 10(-3). Ovary lengths and oocyte numbers were quantified following first egg mass. Ovary length of S. cincticeps varied from 5.7 mm with 10(-4) mg a.i./ml, to 6.4 mm with 10(-7) mg a.i./ml, with similar values for the other permethrin concentrations and for the control. The number of oocytes per female varied from 13.5 with 10(-3) mg a.i./ml, to 29.2 for the control, with significant differences. The number of oocytes per female of nymphs exposed to a permethrin concentration of 10(-5) mg a.i./ml was similar to that of the control. However, the lower number of oocytes per female from nymphs exposed to other concentrations of permethrin suggests that this insecticide may affect the reproductive capacity of this predator. The results obtained are discussed in relation to tolerance of Heteroptera predators to insecticides and possible hormesis occurrence.

Animals↗

PubMed2006

Quantitative genetics of adult behavioral response and larval physiological tolerance to permethrin in diamondback moth (Lepidoptera: Plutellidae).

We investigated the genetic basis of adult behavioral response and larval physiological tolerance to permethrin within two diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), populations from Wooster and Celeryville, OH, with different average levels of larval tolerance. The adult behavioral response was measured as oviposition site preference and was investigated using full-sib design and parent-offspring regression. Additive genetic variance (0.134 +/- 0.02) and the heritability (h2 = 0.31 +/- 0.08) for the behavioral response was significant for the Celeryville population, suggesting that in this population, a high proportion of phenotypic variation for adult behavioral response to permethrin was heritable genetic variation. The larval physiological response was measured with a topical application bioassay and was investigated using a half-sib design. Significant additive genetic variances and heritabilities for physiological tolerance to permethrin were detected in both populations. The genetic correlation between adult behavioral response and larval physiological tolerance to permethrin were negative, but significant only in the Celeryville population; indicating that adults from this population that are more behaviorally responsive produced offspring that are more susceptible to permethrin. Our findings have implications for the evolution and management of insecticide resistance in the diamondback moth. The adult behavioral response can lower the exposure of larvae to the insecticide, lowering selection pressure for physiological resistance in larvae. Furthermore, to the extent that the adult behavioral response increases fitness, it can indirectly select for larval susceptibility because of the negative correlation between the two traits.

Animals↗

PubMed2000

Resistance to insecticides and effect of synergists on permethrin toxicity in Pediculus capitis (Anoplura: Pediculidae) from Buenos Aires.

Permethrin-resistant colonies of Pediculus capitis (De Geer) from Buenos Aires were used to establish a resistance profile and to examine resistance mechanisms. All permethrin-resistant head lice (resistance ratio from 52.8 to > 88.7) were also resistant to d-phenothrin (resistance ratio from 40.86 to > 48.39) and deltamethrin (resistance ratio from 16.24 to 38.06). No cross-resistance to carbaryl was found in any of the pyrethroid-resistant P. capitis tested. Otherwise, all resistant colonies showed low to high levels of resistance to beta-cypermethrin. This pyrethroid had never been applied as a pediculicide in Argentina; however, the high level of resistance found in these permethrin-resistant colonies (resistance ratio from 9.74 to 50.97) demonstrated that pyrethroid cross-resistance occurred to this novel insecticide. Treatment with piperonyl butoxide (PBO) or triphenylphosphate (TPP) significantly decreased the toxicity of permethrin in the four colonies tested. The esterase inhibitor TPP produced lower enhancement of toxicity than the multifunction oxidase inhibitor PBO in the colonies having the highest resistance levels. Results presented here concerning the cross-resistance profile and synergism by enzyme inhibitors in permethrin-resistant head lice demonstrated that enhanced metabolism was involved in the pyrethroid resistance. However, the substantial degree of resistance that remained after synergism suggested the presence of another resistance mechanism. Cross-resistance to pyrethroid and susceptibility to the carbamate carbaryl suggested a common action mechanism.

Animals↗

PubMed2002

Toxic effect of aliphatic alcohols against susceptible and permethrin-resistant Pediculus humanus capitis (Anoplura: Pediculidae).

The effectiveness of 1-octanol, 1-nonanol, 1-decanol, 1-undecanol, and 1-dodecanol was evaluated by immersion method against susceptible and permethrin-resistant head lice, Pediculus humanus capitis De Geer, from Buenos Aires, Argentina. All the tested alcohols showed knockdown effect at 10 min and mortality 18 h after treatment. The highest activity was found for the 1-dodecanol (KC50 2.55%, LC50 2.28%) and the lowest for 1-octanol (KC50 8%, LC50 4.46%). The toxicity to the head lice systematically increased with the increase in carbon atoms in the n-aliphatic alcohol moiety, and with the octanol:water coefficient (r2 = 0.94). The pediculicidal activity of 1-dodecanol was not correlated with resistance to permethrin, because no significant difference was observed between toxicity parameters in the susceptible (MAR) and the permethrin-resistant populations which had different resistant levels (RR 5.77 x for E49 population, RR 9.5 x for HL population and RR > 35.3 x for GH population). The pediculicidal effect of aliphatic alcohols demonstrated in this study and the lack of correlation with the permethrin resistance may prove to have a practical value for use in susceptible and permethrin-resistant head lice control.

Alcohols↗

PubMed1992

Postmarketing surveillance study of permethrin creme rinse.

BACKGROUND: An observational, epidemiological study was undertaken to evaluate the safety of permethrin 1% creme rinse (Nix) for treatment of head lice infestations. METHODS: Thirty-seven local public health departments enrolled a total of 38,160 patients for 47,578 treatments with permethrin or other pediculicides from September 1, 1986, through January 31, 1988. Follow-up safety information was collected between 7 and 14 days following treatment via return visit or telephone contact. RESULTS: One hundred three adverse events were reported among 41,955 evaluable treatments. The rates of reported adverse events were 2.2 per 1000 treatments among permethrin treatments, 3.4 per 1000 treatments among lindane treatments, and 1.5 per 1000 treatments among other over-the-counter treatments. No serious, unexpected adverse events were detected in the 18,950 patients treated with permethrin. CONCLUSIONS: This study confirmed the safety profile of permethrin in conditions of general use, as seen in clinical trials. Postmarketing safety monitoring in public health departments of drugs used to treat public health conditions was shown to be feasible.

Adolescent↗

PubMed1982

Comparisons of permethrin formulations and application methods for northern fowl mite control on caged laying hens.

Formulations of permethrin (Ectiban), a synthetic pyrethroid, as an emulsifiable concentrate (EC), wettable powder (WP), and dust were nearly equally effective for 9 or more weeks for control of the northern fowl mite, Ornithonyssus sylviarum (Canestrini and Fanzago), on caged laying hens under environmentally controlled conditions. The permethrin was applied to the vent area as .05% active ingredient (AI) spray of the diluted EC or WP at 40 ml per bird, .1% AI mist of the diluted EC at 20 ml per bird, and 4.5 g per bird of the .25% AI dust. Dilute sprays of .05% permethrin prepared from the EC and WP and applied at 40 ml per bird were more effective in a commercial caged-laying hen house for northern fowl mite control than were .5% sprays of tetrachlorvinphos (Rabon), Ravap, and carbaryl (Sevin). Satisfactory mite control was obtained with .6% permethrin prepared from the EC and misted at the rate of 2.5 ml per bird. Low volume, high concentration misting of permethrin was a promising method for mite control with satisfactory control achieved with .2% AI at 5 ml per bird and .6% AI at 2.5 ml per bird.

Aerosols↗

PubMed1997

Inheritance of larval resistance to permethrin in Aedes aegypti and association with sex ratio distortion and life history variation.

The genetic mechanisms that confer larval permethrin resistance were investigated in two strains of Aedes aegypti, vectors of yellow fever and dengue hemorrhagic fever. Larval resistance to permethrin in an Ae. aegypti field-collected resistant Couva (R) strain was associated with the sex-determining locus by analysis of backcrosses to the susceptible Rockefeller (S) strain. The median lethal concentrations (LC50s) of these strains were 23.1 (95% confidence interval = 22.0-24.3) and 2.2 (2.0-2.3) parts/billion of permethrin, respectively. The estimated resistance ratio (RR) for the R strain was 10.8 (10.3-11.4) compared with the S strain. Resistance was inherited as partly recessive (dominance [D] = -0.31) with an estimated RR of 2.3 (2.1-2.4) in the F1 hybrids when the R parent was male. There were also significantly male-biased sex ratios for this cross. In contrast, inheritance was slightly dominant (D = 0.19) with an estimated RR of 4.1 (3.8-4.4) when the R parent was female, and no significant sex ratio bias of progeny was observed. Analysis revealed a strong paternal-strain effect in bioassay mortality, sex ratio, egg hatch, and fecundity. A maternal-strain effect was also evident for bioassay mortality. Similarly, a strong maternal by paternal strain interaction was also evident for sex ratio. Progeny of single-family backcrosses of F1 hybrids to R were statistically homogeneous for sex ratio, duration of oviposition, fecundity, and hatch rate. A significant increase in male bias was found for only one backcross to R, after treatment with permethrin. In contrast, complex patterns of inheritance of life histories were observed among backcrosses to S. Backcrosses to S had greater mean fecundities, shorter mean times to the start of oviposition, and shorter mean oviposition periods than did backcrosses to R. Hatch rates were statistically homogeneous among backcrosses, but all strikingly reduced relative to the parental generation. Times of start and duration of oviposition were highly negatively correlated with fecundity (first gonotropic cycle only) and rate of egg hatch. Females with lower fecundities had lower hatch rates, and there was a threshold of approximately 80 eggs per female, below which no eggs hatched. Generally all backcrosses had higher LC50s than expected from single-locus inheritance. Association between sex bias and inheritance of resistance was apparent, but no single genetic linkage model based on current understanding of sex chromosome genetics was consistent with these observations. These results may have epidemiologic importance considering that permethrin-soaked bed nets are being used in many countries to control the biting activity of disease vectors.

Aedes↗