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Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids.

Ranson H, Jensen B, Vulule JM, Wang X, Hemingway J, Collins FH.

Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA. RansonHA cardiff.ac.uk

A field trial of permethrin-impregnated bednets and curtains was initiated in Western Kenya in 1990, and a strain of Anopheles gambiae showing reduced susceptibility to permethrin was colonized from this site in 1992. A leucine-phenylalanine substitution at position 1014 of the voltage-gated sodium channel is associated with resistance to permethrin and DDT in many insect species, including Anopheles gambiae from West Africa. We cloned and sequenced a partial sodium channel cDNA from the Kenyan permethrin-resistant strain and we identified an alternative substitution (leucine to serine) at the same position, which is linked to the inheritance of permethrin resistance in the F(2) progeny of genetic crosses between susceptible and resistant individuals. The diagnostic polymerase chain reaction (PCR) developed by Martinez-Torres et al. [(1998) Insect Mol Biol 7: 179-184] to detect kdr alleles in field populations of An. gambiae will not detect the Kenyan allele and hence reliance on this assay may lead to an underestimate of the prevalence of pyrethroid resistance in this species. We adapted the diagnostic PCR to detect the leucine-serine mutation and with this diagnostic we were able to demonstrate that this kdr allele was present in individuals collected from the Kenyan trial site in 1986, prior to the introduction of pyrethroid-impregnated bednets. The An. gambiae sodium channel was physically mapped to chromosome 2L, division 20C. This position corresponds to the location of a major quantitative trait locus determining resistance to permethrin in the Kenyan strain of An. gambiae.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11029667&dopt=Abstract permethrin Elimite



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Potential Estrogenic and Antiandrogenic Effects of Permethrin in Rats.

Kim SS, Lee RD, Lim KJ, Kwack SJ, Rhee GS, Seok JH, Lee GS, An BS, Jeung EB, Park KL.

National Institute of Toxicological Research, Korea Food and Drug Administration.

Many environmental chemicals including pesticides have been reported to possess hormonal activities, and thus are classified as endocrine disruptors. Permethrin, a synthetic pyrethroid insecticide, is used worldwide, which provides potential environmental exposure. However, relatively few studies have reported on hormonal activities, particularly estrogenic and androgenic activities of permethrin, and the results of these studies are in some respects contradictory. Therefore, this study investigated the potential estrogenic and androgenic activities of permethrin in vitro and in vivo. We conducted an uterine Calbindin-D9k (CaBP-9k) gene expression assay and an uterotrophic assay for estrogenic activity, and a Hershberger assay for androgenic activity. The CaBP-9k gene, one of the intracellular calcium binding proteins, is estrogen-responsive in the uterus. The rat uterotrophic and Hershberger assays are generally used as in vivo short-term screening assays for detecting the estrogenic and androgenic activities of chemicals, although these assays are still being validated by the Organization for Economic Cooperation and Development (OECD). Northern blot analysis showed the induction of uterine CaBP-9k mRNA level in response to permethrin as well as co-administration of permethrin with E2. In the uterotrophic assay using 18-day-old female rats, subcutaneous treatments with permethrin (10 to 800 mg/kg) for three days increased relative uterine wet weights, and E2-induced uterine weights. These effects were statistically significant at 800 and 200 mg/kg, respectively. Moreover, permethrin-induced uterine weights were inhibited by the co-administration of ICI 182,780, an antiestrogen. In the Hershberger assay, the administration of permethrin orally to testosterone propionate-treated castrated male rats led to statistically significant reductions in androgen-dependent sex accessory tissue (ventral prostate, seminal vesicles, levator ani and bulbocavernosus muscles, Cowper's gland and glans penis) weights at all doses tested (10, 50 and 100 mg/kg). These results suggest that permethrin might have estrogen-like effects on female rats, but antiandrogen-like effects on males.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15599112&dopt=Abstract permethrin Elimite



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Combined dermal exposure to permethrin and cis-urocanic acid suppresses the contact hypersensitivity response in C57BL/6N mice in an additive manner.

Prater MR, Blaylock BL, Holladay SD.

Department of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, 2265 Kraft Drive, Blacksburg, VA 24060, USA. mrprater vt.edu

Cutaneous exposure to the pyrethroid insecticide permethrin significantly suppresses contact hypersensitivity (CH) response to oxazolone in C57BL/6N mice. Additionally, cis-urocanic acid (cUCA), an endogenous cutaneous chromophore isomerized to its active form following exposure to ultraviolet radiation, modulates cell-mediated cutaneous immune responses. This study describes cutaneous immune alterations following combined topical permethrin and intradermal cUCA exposure. Female C57BL/6N mice were administered 5, 50 or 100 microg cUCA daily for 5 consecutive days. CH was then evaluated by the mouse ear swelling test (MEST) response to oxazolone. Decreased responses of 52.3%, 76.3% and 76.3%, respectively, as compared to controls were observed. Then, mice were co-exposed to 5 microg cUCA daily for 5 days and 1.5, 5, 15, or 25 microL permethrin, on either day 1, 3 or 5 of the cUCA treatment to evaluate combined immunomodulatory effects of the two chemicals, or cUCA daily for 5 days followed by permethrin on day 3, 5, or 7 after the last cUCA injection to demonstrate prolonged immunosuppressive effects. Two days after final treatment, mice were sensitized with oxazolone and MEST was performed. Mice receiving five cUCA injections and permethrin topically on cUCA injection day 1 showed up to 93.3% suppression of MEST compared to vehicle control. CH was suppressed by 87.5%, 86.6% and 74.2% in mice treated with 25 muL permethrin on days 3, 5 and 7 after cUCA, respectively, compared to vehicle control. Taken together, these data indicate co-exposure to cUCA and permethrin profoundly suppresses cell-mediated cutaneous immunity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15629246&dopt=Abstract permethrin Elimite



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Repellency of permethrin-treated battle-dress uniforms during Operation Tandem Thrust 2001.

Miller RJ, Wing J, Cope SE, Klavons JA, Kline DL.

Cattle Fever Tick Research Laboratory, Agricultural Research Service, United States Department of Agriculture, Moore Air Base, Building 6419, 22675 North Moorefield Road, Edinburg, TX 78541, USA.

Successful feeding by mosquitoes through permethrin-treated battle-dress uniforms (BDUs) was observed in the Shoalwater Bay Training Area (SWBTA), Queensland, Australia, during Operation Tandem Thrust 1997 (TT97). Therefore, during Operation Tandem Thrust 2001, the repellency of permethrin-treated BDUs was evaluated. Washing permethrin-treated BDUs 1 time reduced the permethrin concentration by 60%, but permethrin concentration was not reduced further after subsequent washings (up to 20 times). The probing time of Ochlerotatus vigilax landing on permethrin-treated BDUs was reduced to the greatest extent on the treated, unwashed uniform (7.5-fold reduction). Treated, washed uniforms also reduced probing time (2.5 times) compared to the untreated control uniform containing no permethrin. Reduced probing time should reduce feeding success and protect operational forces from bothersome mosquitoes and the associated risk of mosquito-borne disease in SWBTA. Observations of successful mosquito feeding made during TT97 could be attributed to the use of old and well-worn BDUs and seasonal differences in mosquito population density.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15669394&dopt=Abstract permethrin Elimite



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[Recent observations on the sensitivity to pyrethroids and DDT of Anopheles arabiensis and Anopheles funestus in the central Highlands of Madagascar; preliminary results on the absence of the kdr mutation in An. arabiensis]

[Article in French]

Ratovonjato J, Le Goff G, Rajaonarivelo E, Rakotondraibe EM, Robert V.

Groupe de Recherche sur le Paludisme, Institut Pasteur de Madagascar, BP 1274, 101 Antananarivo, Madagascar.

Anopheles arabiensis and Anopheles funestus are the principal vectors of malaria on the central highlands of Madagascar. These two species of mosquito are directly or indirectly the targets of indoor insecticide spread. The survey of the susceptibility of these two vectors to insecticides is essential specifying for the anti-vectorial current directives and for the future programs. This paper describes: --the recent tests of susceptibility and the study of the knock-down effect of four pyrethroids (deltamethrin 0.50%, permethrin 0.250%, alpha-cypermethrin 0.025%, cyfluthrin 0.150%) and DDT 4% on An. arabiensis collected from December 2002 to May 2003 in three villages on the district of Tsiroanomandidy and in Alasora, a rural area near the capital, Antananarivo. --the susceptibility tests of An. funestus realised in Morafeno, against cyfluthrin 0.150%, deltamethrin 0.050%, lambda-cyhalothrin 0.050% and DDT 4%. --the preliminary study of the kdr gene mutation, which might account for the pyrethrinoid and DDT resistance, of An. arabiensis in Alasora. The data indicate a decrease in the efficiency of alpha-cypermethrin 0.025% (Tkd99 = 21 mn) and of DDT 4% (Tkd99 = 191.5 mn) on An. arabiensis in Analamiranga. Nevertheless, the effectiveness of permethrin 0.250% has been notified. In Soanierana, alpha-cypermethrin 0.025% was effective against An. arabiensis, whilst the ineffectiveness of the DDT 4% (Tkd99 = 116 mn) in Andranonahoatra was observed. In Alasora, a fall in the effectiveness of alpha-cypermethrin 0.025% (Tkd99 = 21 mn) and the resistance to DDT 4% (Tkd99 = 6894 mn) was noted. No kdr mutation was detected on the kd gene of An. arabiensis resistant to the alpha-cypermethrin 0.025% and to DDT 4%, collected in Alasora. An. funestus collected in the district of Miandrivazo is susceptible to pyrethroids and to DDT. To conclude, in the Malagasy Central Highlands, An. arabiensis is ordinary sensitive to pyrethroid and poorly sensitive, or even resistant to DDT (as observed in Antananarivo plain). However, An. funestus remains sensitive to all tested insecticides; this observation is crucial because this anopheles vector is the first target of the campaigns of indoor spraying insecticides.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15678819&dopt=Abstract permethrin Elimite