@article {96347, title = {Human lice: Past, present and future control}, volume = {106}, year = {2013}, month = {Jul-01-2013}, pages = {162-171}, abstract = {

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.

}, issn = {0048-3575}, doi = {10.1016/j.pestbp.2013.03.008}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0048357513000527}, author = {Clark,J. Marshall and Kyong Sup Yoon and Si Hyeock Lee and Barry R. Pittendrigh} } @article {94764, title = {Detoxification of ivermectin by ATP binding cassette transporter C4 and cytochrome P450 monooxygenase 6CJ1 in the human body louse, Pediculus humanus humanus}, journal = {Insect Molecular Biology}, volume = {27}, year = {2018}, month = {07-2017}, pages = {73 - 82}, abstract = {

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.

}, doi = {10.1111/imb.12348}, url = {http://doi.wiley.com/10.1111/imb.12348}, author = {J. H. Kim and K. J. Gellatly and B. Lueke and M. Kohler and Ralf Nauen and Edwin Murenzi and Kyong Sup Yoon and Clark,J. Marshall} } @article {94707, title = {Brief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance}, journal = {Insect Molecular Biology}, volume = {20}, year = {2011}, month = {Sept 2011}, pages = {687 - 699}, abstract = {

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.

}, doi = {https://doi.org/10.1111/j.1365-2583.2011.01097.x}, url = {https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2583.2011.01097.x}, author = {Kyong Sup Yoon and Strycharz,Joseph P. and J. H. Baek and Sun, Weilin and J. H. Kim and J. S. Kang and Barry R. Pittendrigh and Si Hyeock Lee and Clark,J. Marshall} } @article {94705, title = {A New Ivermectin Formulation Topically Kills Permethrin-Resistant Human Head Lice (Anoplura: Pediculidae)}, journal = {Journal of Medical Entomology}, volume = {45}, year = {2008}, month = {Jan 2008}, pages = {75 - 81}, abstract = {

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 ef\Þcacy of pediculicide formulations in a reproducible format that mimics the exposure scenario that occurs on the human scalp.

}, keywords = {human head louse, in vitro rearing system, ivermectin formulation}, issn = {0022-2585}, doi = {10.1093/jmedent/45.1.75}, url = {https://academic.oup.com/jme/article/45/1/75/874003}, author = {Strycharz,Joseph P. and Kyong Sup Yoon and Clark,J. Marshall} } @article {94422, title = {Ovicidal Efficacy of Abametapir Against Eggs of Human Head and Body Lice (Anoplura: Pediculidae)}, journal = {Journal of Medical Entomology}, volume = {54}, year = {2017}, pages = {167 - 172}, abstract = {

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.

}, keywords = {abametapir, body louse, Head louse, voiced}, issn = {0022-2585}, doi = {10.1093/jme/tjw132}, url = {https://academic.oup.com/jme/article-lookup/doi/10.1093/jme/tjw132}, author = {Bowles,V. M. and Kyong Sup Yoon and Stephen C. Barker and Christopher Tran and Christopher Rhodes and Clark,J. Marshall} } @article {47769, title = {Increased 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 Texas}, journal = {Pesticide Biochemistry and Physiology}, volume = {77}, year = {2003}, month = {2003}, pages = {115 - 124}, doi = {https://doi.org/10.1016/j.pestbp.2003.08.003}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0048357503001160}, author = {Gao,Jian-Rong and Kyong Sup Yoon and Si Hyeock Lee and Takano-Lee,Miwa and Edman,John D. and Meinking,Terri Lynn and Taplin,David and Clark,J. Marshall} } @article {47492, title = {Esterase-mediated malathion resistance in the human head louse, Pediculus capitis (Anoplura: Pediculidae)}, journal = {Pesticide Biochemistry and Physiology}, volume = {85}, year = {2006}, month = {2006}, pages = {28 - 37}, abstract = {

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.

}, url = {https://www.researchgate.net/publication/222825684}, author = {Gao,Jian-Rong and Kyong Sup Yoon and Frisbie,Richard K. and G. C. Coles and Clark,J. Marshall} } @article {47490, title = {An improved in vitro rearing system for the human head louse allows the determination of resistance to formulated pediculicides}, journal = {Pesticide Biochemistry and Physiology}, volume = {86}, year = {2006}, month = {2006}, pages = {195 - 202}, abstract = {

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.

}, keywords = {capitis, In Vitro, Pediculicide, Pediculus, Permethrin, Pyrethrins, rearing system, resistance}, doi = {https://doi.org/10.1016/j.pestbp.2006.04.001}, url = {https://www.sciencedirect.com/science/article/abs/pii/S0048357506000654}, author = {Kyong Sup Yoon and Strycharz,Joseph P. and Gao,Jian-Rong and Takano-Lee,Miwa and Edman,John D. and Clark,J. Marshall} } @article {45983, title = {Permethrin-resistant human head lice, Pediculus capitis, and their treatment}, journal = {Archives of Dermatology}, volume = {139}, year = {2003}, month = {2003}, pages = {994 - 1000}, abstract = {

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.

}, keywords = {animals, child, Comparative Study, Genotype, humans, In Vitro, insecticide, Insecticide resistance, Lice Infestations/drug therapy/genetics, Malathion, Pediculus, Permethrin, Research Support, Non-U.S. Gov{\textquoteright}t, Research Support, U.S. Gov{\textquoteright}t, P.H.S., scalp dermatoses, Time Factors}, url = {https://www.researchgate.net/publication/10609106_Permethrin-Resistant_Human_Head_Lice_Pediculus_capitis_and_Their_Treatment}, author = {Kyong Sup Yoon and Gao,Jian-Rong and Si Hyeock Lee and Clark,J. Marshall and Brown,Leon and Taplin,David} } @article {45966, title = {In vivo and in vitro rearing of Pediculus humanus capitis (Anoplura: Pediculidae)}, journal = {Journal of Medical Entomology}, volume = {40}, year = {2003}, month = {2003}, pages = {628 - 635}, abstract = {

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.

}, keywords = {animals, Anti-Bacterial Agents/pharmacology, Feeding Behavior, geography, humans, Lice Infestations/parasitology/physiopathology, Molting/physiology, Pediculus, Research Support, U.S. Gov{\textquoteright}t, P.H.S.}, doi = {https://doi.org/10.1603/0022-2585-40.5.628}, url = {https://academic.oup.com/jme/article/40/5/628/863031}, author = {Takano-Lee,Miwa and Kyong Sup Yoon and Edman,John D. and Mullens,B. A. and Clark,J. Marshall} } @article {45827, title = {Sodium channel mutations associated with knockdown resistance in the human head louse, Pediculus capitis (DeGeer)}, journal = {Pesticide Biochemistry and Physiology}, volume = {75}, year = {2003}, month = {2003}, pages = {79 - 91}, keywords = {humanus, mechanism, Pediculus, resistance}, url = {http://www.phthiraptera.info/sites/phthiraptera.info/files/44566.pdf}, author = {Si Hyeock Lee and Gao,Jian-Rong and Kyong Sup Yoon and Kosta Y. Mumcuoglu and Taplin,David and Edman,John D. and Takano-Lee,Miwa and Clark,J. Marshall} } @article {39775, title = {Pesticide molecular analysis of KDR-like resistance in permethrin resistant strains of head lice, Pediculus capitis}, journal = {Pesticide Biochemistry and Physiology}, volume = {66}, year = {2000}, month = {2000}, pages = {130 - 143}, abstract = {The 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.}, keywords = {Blattella, cockroaches, genes, housefly, identification, insecticide, knockdown resistance, linkage, locus, musca domestica, mutations, Pyrethrum, sodium channel}, author = {Si Hyeock Lee and Kyong Sup Yoon and Williamson,M. S. and Goodson,S. J. and Takano-Lee,Miwa and Edman,John D. and Devonshire,A. L. and Clark,J. Marshall} }