01585nas a2200181 4500008004100000022001400041245004900055210004700104260001600151300001200167490000800179520105200187100002001239700002101259700002001280700002701300856007601327 2013 eng d a0048-357500aHuman lice: Past, present and future control0 aHuman lice Past present and future control cJul-01-2013 a162-1710 v1063 a

Human lice represent one of the longest ectoparasitic relationships associated with mankind. Whereas the body louse vectors bacterial diseases that have killed millions, the head louse does not but represents an economic and social concern worldwide. A crisis exists in the control of lice due to the availability of only a few new pediculicides and the occurrence of resistance. In this review, we summarize data that validates the knockdown resistance mechanism (kdr) as the main cause of control failures to the pyrethrin/pyrethroid-based pediculicides and the molecular diagnostics used to determine kdr worldwide. New commercially-available pediculicide are discussed in terms of their use in sustainable resistance management approaches. Lastly, the optimization of dose, the timing of exposure, and the assessment of transcript levels during tolerance is used to identify detoxification genes that metabolize ivermectin as a proof of principle experiment, indicating that such an approach may allow proactive resistance management.

1 aClark, Marshall1 aYoon, Kyong, Sup1 aLee, Si, Hyeock1 aPittendrigh, Barry, R. uhttps://www.sciencedirect.com/science/article/abs/pii/S004835751300052702288nas a2200217 4500008004100000245016900041210006900210260001200279300001200291490000700303520157500310100001601885700002101901700001401922700001501936700001601951700001901967700002101986700002002007856004302027 2018 eng d00aDetoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus0 aDetoxification of ivermectin by ATP binding cassette transporter c07-2017 a73 - 820 v273 a

We previously observed that ivermectin‐induced detoxification genes, including ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) were identified from body lice following a brief exposure to a sublethal dose of ivermectin using a non‐invasive induction assay. In this current study, the functional properties of PhABCC4 and CYP6CJ1 were investigated after expression in either X. laevis oocytes or using a baculovirus expression system, respectively. Efflux of [3H]‐9‐(2‐phosphonomethoxyethyl) adenine ([3H]‐PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA‐injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors. Efflux was also determined to be ATP‐dependent. Using a variety of insecticides in a competition assay, only co‐injection of ivermectin and dichlorodiphenyltrichloroethane led to decreased efflux of [3H]‐PMEA. PhABCC4‐expressing oocytes also directly effluxed [3H]‐ivermectin, which increased over time. In addition, ivermectin appeared to be oxidatively metabolized and/or sequestered, although at low levels, following functional expression of CYP6CJ1 along with cytochrome P450 reductase in Sf9 cells. Our study suggests that PhABCC4 and perhaps CYP6CJ1 are involved in the Phase III and Phase I xenobiotic metabolism of ivermectin, respectively, and may play an important role in the evolution of ivermectin resistance in lice and other insects as field selection occurs.

1 aKim, J., H.1 aGellatly, K., J.1 aLueke, B.1 aKohler, M.1 aNauen, Ralf1 aMurenzi, Edwin1 aYoon, Kyong, Sup1 aClark, Marshall uhttp://doi.wiley.com/10.1111/imb.1234801897nas a2200229 4500008004100000245013400041210006900175260001400244300001400258490000700272520113000279100002101409700002601430700001701456700001601473700001601489700001701505700002701522700002001549700002001569856007801589 2011 eng d00aBrief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance0 aBrief exposures of human body lice to sublethal amounts of iverm cSept 2011 a687 - 6990 v203 a

Transcriptional profiling results, using our non-invasive induction assay [short exposure intervals (2–5 h) to sub-lethal amounts of insecticides (<LD3 at 24 h) administered by stress reducing means (contact vs. immersion screen) and with induction assessed in a time frame when tolerance is still present (~LC90 in 2–4 h)], show that ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses.
Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin.
Injection of dsRNAs against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increase sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance.

1 aYoon, Kyong, Sup1 aStrycharz, Joseph, P.1 aBaek, J., H.1 aSun, Weilin1 aKim, J., H.1 aKang, J., S.1 aPittendrigh, Barry, R.1 aLee, Si, Hyeock1 aClark, Marshall uhttps://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2583.2011.01097.x01729nas a2200205 4500008004100000022001400041245011000055210006900165260001300234300001200247490000700259520105800266653002101324653002801345653002701373100002601400700002101426700002001447856005601467 2008 eng d a0022-258500aA New Ivermectin Formulation Topically Kills Permethrin-Resistant Human Head Lice (Anoplura: Pediculidae)0 aNew Ivermectin Formulation Topically Kills PermethrinResistant H cJan 2008 a75 - 810 v453 a

This study examines the effectiveness of a new ivermectin formulation for the topical treatment of the human head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae). Permethrin-resistant lice originally obtained from south Florida and maintained on an in vitro rearing system were 100% susceptible to ivermectin formulations by using a semiclinical hair tuft bioassay. The formulation was 100% effective at killing lice using 1, 0.5, and 0.25% ivermectin concentrations after 10-min exposures. As judged by the lethal time (LT)50 and LT95 values, 0.5% formulated ivermectin was 3.8 and 3.2 times faster at killing lice, respectively, than 0.5% nonformulated ivermectin, indicating that the formulation may facilitate the penetration of ivermectin into the louse. The hair tuft-based bioassay in conjunction with the in vitro rearing system provides a standardized method to assess the comparative efÞcacy of pediculicide formulations in a reproducible format that mimics the exposure scenario that occurs on the human scalp.

10ahuman head louse10ain vitro rearing system10aivermectin formulation1 aStrycharz, Joseph, P.1 aYoon, Kyong, Sup1 aClark, Marshall uhttps://academic.oup.com/jme/article/45/1/75/87400302267nas a2200241 4500008004100000022001400041245010100055210006900156300001400225490000700239520152200246653001501768653001501783653001501798653001101813100001901824700002101843700002401864700002201888700002401910700002001934856007101954 2017 eng d a0022-258500aOvicidal Efficacy of Abametapir Against Eggs of Human Head and Body Lice (Anoplura: Pediculidae)0 aOvicidal Efficacy of Abametapir Against Eggs of Human Head and B a167 - 1720 v543 a

Studies were undertaken to determine the ovicidal efficacy of 5,50-dimethyl-2,20-bipyridyl (abametapir) against eggs of both human head and body lice. Head lice eggs of different ages (0–2, 3–5, and 6–8-d-old eggs) were exposed to varying concentrations of abametapir in isopropanol and concentration-dependent response rela- tionships established based on egg hatch. One hundred percent of all abametapir-treated eggs failed to hatch at the 0.74 and 0.55% concentrations, whereas 100% of 6–8-d-old head louse eggs failed to hatch only at the 0.74% concentration. The LC50 value for abametapir varied, depending on the age of the head lice eggs, from ?0.10% recorded for 0–2-d-old eggs and increasing to ?0.15% for 6–8-d-old eggs. Abametapir was also evaluated once formulated into a lotion referred to as Xeglyze (0.74% abametapir) and serial dilutions made. Ovicidal efficacies were determined against head lice eggs 0–8-d-old. Results indicated 100% ovicidal activity at the 0.74, 0.55, 0.37, and 0.18% concentrations. Additional studies undertaken using body lice eggs also demonstrated that aba- metapir was 100% ovicidal against eggs of all ages when evaluated at a concentration of 0.37 and 0.55%. Given that ovicidal activity is a critical component of any effective treatment regime for louse control, the data pre- sented in this study clearly demonstrate the ability of abametapir to inhibit hatching of both head and body louse eggs as assessed in vitro.

10aabametapir10abody louse10aHead louse10avoiced1 aBowles, V., M.1 aYoon, Kyong, Sup1 aBarker, Stephen, C.1 aTran, Christopher1 aRhodes, Christopher1 aClark, Marshall uhttps://academic.oup.com/jme/article-lookup/doi/10.1093/jme/tjw13200793nas a2200205 4500008004100000245020600041210006900247260000900316300001400325490000700339100001900346700002100365700002000386700002100406700002000427700002600447700001800473700002000491856007600511 2003 eng d00aIncreased frequency of the T929I and L932F mutations associated with knockdown resistance in permethrin-resistant populations of human head louse, Pediculus capitus, from California, Florida, and Texas0 aIncreased frequency of the T929I and L932F mutations associated  c2003 a115 - 1240 v771 aGao, Jian-Rong1 aYoon, Kyong, Sup1 aLee, Si, Hyeock1 aTakano-Lee, Miwa1 aEdman, John, D.1 aMeinking, Terri, Lynn1 aTaplin, David1 aClark, Marshall uhttps://www.sciencedirect.com/science/article/abs/pii/S004835750300116001836nas a2200181 4500008004100000245011000041210006900151260000900220300001200229490000700241520124800248100001901496700002101515700002501536700001801561700002001579856005501599 2006 eng d00aEsterase-mediated malathion resistance in the human head louse, Pediculus capitis (Anoplura: Pediculidae)0 aEsterasemediated malathion resistance in the human head louse Pe c2006 a28 - 370 v853 a

Resistance in a dual malathion- and permethrin-resistant head louse strain (BR-HL) was studied. BR-HL was 3.6- and 3.7-fold more resistant to malathion and permethrin, respectively, compared to insecticide-susceptible EC-HL. S,S,S - Tributylphosphorotrithioate synergized malathion toxicity by 2.1-fold but not permethrin toxicity in BR-HL. Piperonyl butoxide did not synergize malathion or permethrin toxicity. Malathion carboxylesterase (MCE) activity was 13.3-fold and general esterase activity was 3.9-fold higher in BR-HL versus EC-HL. There were no significant differences in phosphotriesterase, glutathione S-transferase, and acetylcholinesterase activities between strains. There was no differential sensitivity in acetylcholinesterase inhibition by malaoxon. Esterases from BR-HL had higher affinities and hydrolysis efficiencies versus EC-HL using various naphthyl-substituted esters. Protein content of BR-HL females and males was 1.6- and 1.3-fold higher, respectively, versus EC-HL adults. Electrophoresis revealed two esterases with increased intensity and a unique esterase associated with BR-HL. Thus, increased MCE activity and over-expressed esterases appear to be involved in malathion resistance in the head louse.

1 aGao, Jian-Rong1 aYoon, Kyong, Sup1 aFrisbie, Richard, K.1 aColes, G., C.1 aClark, Marshall uhttps://www.researchgate.net/publication/22282568402407nas a2200289 4500008004100000245013200041210006900173260000900242300001400251490000700265520152200272653001201794653001301806653001701819653001401836653001501850653001501865653001901880653001501899100002101914700002601935700001901961700002101980700002002001700002002021856007602041 2006 eng d00aAn improved in vitro rearing system for the human head louse allows the determination of resistance to formulated pediculicides0 aimproved in vitro rearing system for the human head louse allows c2006 a195 - 2020 v863 a

An improved in vitro rearing system, based on a silicone-reinforced Parafilm® M membrane, human hair tufts and reconstituted human blood, enabled the large-scale rearing of pediculicide-susceptible (EC-HL) and resistant (SF-HL and BR-HL) strains of human head lice. Developmental time differed for early instars but differences became synchronized as lice matured. Mean survivorship amongst the three strains reared in vitro were not significantly different when compared to EC-HL and SF-HL reared in vivo. The efficacies of three pediculicidal products were assessed under semi-clinical conditions using a modified version of the in vitro rearing system. Treatments of 1% permethrin in acetone, Nix®, Rid® or Pronto® Plus to hair tufts following manufacturer’s instructions were highly efficacious (100% mortality) on EC-HL but differentially efficacious (62.2–84.4% mortality) on SF-HL examined eight days post-treatment. SF-HL that survived the first treatment received an identical second treatment eight days following the first treatment. Survivors (13.3–30.0%) developed to adults (10th–11th day following first treatment) and females successfully laid fertile eggs that developed to first instars. These results confirm resistance to permethrin- and pyrethrin-based pediculicide formulations in SF-HL when assessed under semi-clinical conditions and validates resistance previously determined using filter-paper contact bioassays and unformulated insecticides.

10acapitis10aIn Vitro10aPediculicide10aPediculus10aPermethrin10aPyrethrins10arearing system10aresistance1 aYoon, Kyong, Sup1 aStrycharz, Joseph, P.1 aGao, Jian-Rong1 aTakano-Lee, Miwa1 aEdman, John, D.1 aClark, Marshall uhttps://www.sciencedirect.com/science/article/abs/pii/S004835750600065403077nas a2200385 4500008004100000245008100041210006900122260000900191300001500200490000800215520189800223653001202121653001002133653002202143653001302165653001102178653001302189653001602202653002702218653004402245653001402289653001402303653001502317653003702332653004102369653002102410653001702431100002102448700001902469700002002488700002002508700001602528700001802544856012902562 2003 eng d00aPermethrin-resistant human head lice, Pediculus capitis, and their treatment0 aPermethrinresistant human head lice Pediculus capitis and their  c2003 a994 - 10000 v1393 a

OBJECTIVE: To compare the pediculicidal activity of Ovide lotion and its active ingredient, 0.5% malathion, with Nix and its active ingredient, 1% permethrin, in permethrin-resistant head lice. DESIGN: In vitro pediculicidal product and active ingredient comparison. The presence of knockdown resistance-type mutations (T929I and L932F) was validated by DNA sequencing. SETTING: University of Massachusetts-Amherst; University of Miami School of Medicine, Miami, Fla; Plantation and Homestead, Fla; and Mathis, Tex.Other PARTICIPANTS: Lice were collected in 3 geographical regions within the United States and in Yamburara, Ecuador, from healthy but infested individuals.Intervention Within 3 to 6 hours of collection, lice were given a blood meal, exposed to products or active ingredients, and observed at regular intervals. MAIN OUTCOME MEASURES: Percent mortality of lice at regular intervals after exposure to products or active ingredients and presence of T929I and L932F mutations. RESULTS: South Florida lice exhibited a significantly slower mortality response to permethrin compared with susceptible Ecuadorian lice. Ovide and malathion killed permethrin-resistant lice faster than Nix or permethrin. The presence of T929I and L932F in permethrin-resistant south Florida lice was confirmed by DNA sequencing. The population of Texas lice from Mathis was slightly resistant to permethrin and included 13% with resistant genotypes. CONCLUSIONS: The presence of the T929I and L932F mutations was confirmed by DNA sequencing in lice collected from children in south Florida that were resistant to the pediculicidal effects of permethrin and the leading permethrin-based head lice product, Nix. Malathion resistance was not observed in this study. The data also show that Ovide killed these same permethrin-resistant head lice approximately 10 times faster than permethrin or Nix.

10aanimals10achild10aComparative Study10aGenotype10ahumans10aIn Vitro10ainsecticide10aInsecticide resistance10aLice Infestations/drug therapy/genetics10aMalathion10aPediculus10aPermethrin10aResearch Support, Non-U.S. Gov't10aResearch Support, U.S. Gov't, P.H.S.10ascalp dermatoses10aTime Factors1 aYoon, Kyong, Sup1 aGao, Jian-Rong1 aLee, Si, Hyeock1 aClark, Marshall1 aBrown, Leon1 aTaplin, David uhttps://www.researchgate.net/publication/10609106_Permethrin-Resistant_Human_Head_Lice_Pediculus_capitis_and_Their_Treatment02490nas a2200289 4500008004100000245008600041210006900127260000900196300001400205490000700219520158900226653001201815653003901827653002101866653001401887653001101901653005101912653002301963653001401986653004102000100002102041700002102062700002002083700002002103700002002123856005702143 2003 eng d00aIn vivo and in vitro rearing of Pediculus humanus capitis (Anoplura: Pediculidae)0 aIn vivo and in vitro rearing of Pediculus humanus capitis Anoplu c2003 a628 - 6350 v403 a

Four geographically distinct colonies of the human head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae) were reared on a live host and exhibited significantly different life history patterns. Florida head lice exhibited approximately 10% slower development and approximately 15% reduced longevity relative to California or Ecuador head lice. Fecundity (4.9 +/- 0.2 eggs/female/d) and fertility (76.4 +/- 2.9% mean hatching rate) declined over the lifetime of female lice, especially when separated from males (i.e., unmated recently). All four colonies (above plus one from Panama) were similar in their ability to tolerate starvation, although older stages tended to die sooner. An in vitro feeding apparatus was developed to rear head lice. Teneral first instar lice were placed on human hair tufts on the upper side of membrane-covered feeders, which were immersed bottom-side down within a vessel containing warmed human blood. Relative to lice reared on a human host, in vitro-reared lice required a significantly longer time (10-20%) to molt and survived a significantly shorter time as adults (30-50%); the addition of antibiotics did not adversely affect louse development. Teneral first instars were more likely than any other stage to feed through the membrane. Lice spent a significantly greater proportion of time searching in the in vitro apparatus than on a host, but the proportion of time spent feeding did not differ. This research is the first to demonstrate that head lice can be reared successfully in vitro through a complete life cycle.

10aanimals10aAnti-Bacterial Agents/pharmacology10aFeeding Behavior10ageography10ahumans10aLice Infestations/parasitology/physiopathology10aMolting/physiology10aPediculus10aResearch Support, U.S. Gov't, P.H.S.1 aTakano-Lee, Miwa1 aYoon, Kyong, Sup1 aEdman, John, D.1 aMullens, B., A.1 aClark, Marshall uhttps://academic.oup.com/jme/article/40/5/628/86303100802nas a2200253 4500008004100000245011800041210006900159260000900228300001200237490000700249653001200256653001400268653001400282653001500296100002000311700001900331700002100350700002500371700001800396700002000414700002100434700002000455856007300475 2003 eng d00aSodium channel mutations associated with knockdown resistance in the human head louse, Pediculus capitis (DeGeer)0 aSodium channel mutations associated with knockdown resistance in c2003 a79 - 910 v7510ahumanus10amechanism10aPediculus10aresistance1 aLee, Si, Hyeock1 aGao, Jian-Rong1 aYoon, Kyong, Sup1 aMumcuoglu, Kosta, Y.1 aTaplin, David1 aEdman, John, D.1 aTakano-Lee, Miwa1 aClark, Marshall uhttp://www.phthiraptera.info/sites/phthiraptera.info/files/44566.pdf03896nas a2200373 4500008004100000245012000041210006900161260000900230300001400239490000700253520275100260653001403011653001603025653001003041653001303051653001903064653001603083653002503099653001203124653001003136653002003146653001403166653001403180653001903194100002003213700002103233700002303254700002003277700002103297700002003318700002303338700002003361856014103381 2000 eng d00aPesticide molecular analysis of KDR-like resistance in permethrin resistant strains of head lice, Pediculus capitis0 aPesticide molecular analysis of KDRlike resistance in permethrin c2000 a130 - 1430 v663 aThe present study examines the level of permethrin and malathion resistance in human head (Pediculosis capitis) and body (Pediculosis humanus L.) louse populations. Putatively insecticide-susceptible body and head louse populations were obtained from Israel (IS-BL) and Panama (PA-HL), respectively. Putatively insecticide-resistant populations of head lice were obtained from Florida (FL-HL) and Massachusetts (MA- HL), in the United States, and from Bristul (BR-HL), in the United Kingdom. Using knockdown and mortality bioassays, we confirmed permethrin resistance in the FL-HL and MA-I-IL populations. Resistance levels of the FL-HL and MA-HL populations were 132 and 223 times higher than that of the IS-BL population and 41 and 68 times higher than that, of the PA-HL population when determined by knockdown resistance ratios. Resistance levels of the FL-HL and MA-HL populations were 4.3 and 4.9 times that of the IS-BL population and 3.8 and 4.3 times that of the PA-HL population when determined by mortality resistance ratios. The significantly higher levels of resistance determined using the knockdown ratios compared to the mortality ratios suggest that nerve insensitivity, most likely mediated by mutations within sodium channel genes, ia a principal mechanism associated with resistance. None of these populations were resistant to malathion. The mortality response was significantly synergized by piperonyl butoxide in the PA-I-IL and MA-I-IL populations, indicating a possible role of oxidative metabolism in these strains. This apparent increase in oxidative metabolism is likely responsible for the lower permethrin sensitivity of the PA-HL versus the IS-BL and the MA-HL versus the FL-HL populations, respectively. Using a homology probing strategy, we have amplified para-orthologous louse sodium channel alpha- subunit cDNA fragments that span the similar to IIS4-IIS6 region, where most of the sodium channel gene mutations that are known to be associated with knockdown resistance are located. Through molecular cloning and sequencing, we have identified two pi,int mutations, T929I and L932F, located in the IISS transmembrane segment of cDNAs from only the permethrin-resistant FL-HL and BR-HL populations. Using homologous primers from our initial sequencing analysis of the cDNA fragments, we obtained a 568-bp genomic DNA fragment and confirmed the presence of the two mutations associated with permethrin resistance. The availability of PCR primers that directly amplify the genomic DNA fragment containing the mutation sites that are widely found associated with knockdown resistance will greatly facilitate the development of DNA-based diagnostic protocols For use in monitoring programs. (C) 2000 Academic Press.10aBlattella10acockroaches10agenes10ahousefly10aidentification10ainsecticide10aknockdown resistance10alinkage10alocus10amusca domestica10amutations10aPyrethrum10asodium channel1 aLee, Si, Hyeock1 aYoon, Kyong, Sup1 aWilliamson, M., S.1 aGoodson, S., J.1 aTakano-Lee, Miwa1 aEdman, John, D.1 aDevonshire, A., L.1 aClark, Marshall uhttps://phthiraptera.myspecies.info/content/pesticide-molecular-analysis-kdr-resistance-permethrin-resistant-strains-head-lice-pediculus