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Poppy H L Lamberton - One of the best experts on this subject based on the ideXlab platform.
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the effects of subcurative Praziquantel treatment on life history traits and trade offs in drug resistant schistosoma mansoni
Evolutionary Applications, 2018Co-Authors: Mafalda Viana, Poppy H L Lamberton, Christina L Faust, Joanne P Webster, Daniel T HaydonAbstract:Natural selection acts on all organisms, including parasites, to maximize reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian state-space models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma mansoni may be limited by life-history costs not present in susceptible counterparts. S. mansoni parasites from a Praziquantel-susceptible (S), a Praziquantel-resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of Praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with Praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under Praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by Praziquantel treatment in the R line, could limit the spread of R parasites under Praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life-history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond.
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Praziquantel decreases fecundity in schistosoma mansoni adult worms that survive treatment evidence from a laboratory life history trade offs selection study
Infectious Diseases of Poverty, 2017Co-Authors: Poppy H L Lamberton, Christina L Faust, Joanne P WebsterAbstract:Mass drug administration of Praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although ‘hotspots’ remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols. We performed a four-generation Schistosoma mansoni Praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a Praziquantel-resistant isolate (R), a Praziquantel-susceptible isolate (S), and a co-infected line (RS), under three treatment regimens: untreated, 25 mg/kg Praziquantel, or 50 mg/kg Praziquantel. Life-history traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes. Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates. Our predicted cost of resistance was not supported by the traits we measured within the murine host. We did not find evidence for negative adult worm density-dependent effects on fecundity. In contrast, of the adult worms that survived treatment, even low doses of Praziquantel significantly reduced adult-worm fecundity. Such reductions in worm fecundity post treatment suggest that egg - based measures of drug efficacy, such as Kato-Katz, may overestimate the short-term effect of Praziquantel on adult - worm burdens. These findings have important implications for S. mansoni transmission control, diagnostic protocols, and the potential for undetected selection toward drug resistance.
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reduced efficacy of Praziquantel against schistosoma mansoni is associated with multiple rounds of mass drug administration
Clinical Infectious Diseases, 2016Co-Authors: Thomas Crellen, Poppy H L Lamberton, Martin Walker, N B Kabatereine, Edridah M Tukahebwa, James Cotton, Joanne P WebsterAbstract:Background. Mass drug administration (MDA) with Praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of Praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane. Methods. We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with Praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6–12 years before and 25–27 days after treatment with Praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds. Results. The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%–93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%–99.08%) or 1 round (95% BCI, 95.51%–98.96%) of MDA. We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8–9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal Praziquantel efficacy set by the World Health Organization. Conclusions. The reduced efficacy of Praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored.
Joanne P Webster - One of the best experts on this subject based on the ideXlab platform.
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the effects of subcurative Praziquantel treatment on life history traits and trade offs in drug resistant schistosoma mansoni
Evolutionary Applications, 2018Co-Authors: Mafalda Viana, Poppy H L Lamberton, Christina L Faust, Joanne P Webster, Daniel T HaydonAbstract:Natural selection acts on all organisms, including parasites, to maximize reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian state-space models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma mansoni may be limited by life-history costs not present in susceptible counterparts. S. mansoni parasites from a Praziquantel-susceptible (S), a Praziquantel-resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of Praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with Praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under Praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by Praziquantel treatment in the R line, could limit the spread of R parasites under Praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life-history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond.
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Praziquantel decreases fecundity in schistosoma mansoni adult worms that survive treatment evidence from a laboratory life history trade offs selection study
Infectious Diseases of Poverty, 2017Co-Authors: Poppy H L Lamberton, Christina L Faust, Joanne P WebsterAbstract:Mass drug administration of Praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although ‘hotspots’ remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols. We performed a four-generation Schistosoma mansoni Praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a Praziquantel-resistant isolate (R), a Praziquantel-susceptible isolate (S), and a co-infected line (RS), under three treatment regimens: untreated, 25 mg/kg Praziquantel, or 50 mg/kg Praziquantel. Life-history traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes. Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates. Our predicted cost of resistance was not supported by the traits we measured within the murine host. We did not find evidence for negative adult worm density-dependent effects on fecundity. In contrast, of the adult worms that survived treatment, even low doses of Praziquantel significantly reduced adult-worm fecundity. Such reductions in worm fecundity post treatment suggest that egg - based measures of drug efficacy, such as Kato-Katz, may overestimate the short-term effect of Praziquantel on adult - worm burdens. These findings have important implications for S. mansoni transmission control, diagnostic protocols, and the potential for undetected selection toward drug resistance.
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reduced efficacy of Praziquantel against schistosoma mansoni is associated with multiple rounds of mass drug administration
Clinical Infectious Diseases, 2016Co-Authors: Thomas Crellen, Poppy H L Lamberton, Martin Walker, N B Kabatereine, Edridah M Tukahebwa, James Cotton, Joanne P WebsterAbstract:Background. Mass drug administration (MDA) with Praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of Praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane. Methods. We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with Praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6–12 years before and 25–27 days after treatment with Praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds. Results. The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%–93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%–99.08%) or 1 round (95% BCI, 95.51%–98.96%) of MDA. We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8–9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal Praziquantel efficacy set by the World Health Organization. Conclusions. The reduced efficacy of Praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored.
K. J. Krieger - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of Emodepside plus Praziquantel Tablets (Profender® Tablets for Dogs) against Mature and Immature Adult Trichuris vulpis Infections in Dogs
Parasitology Research, 2009Co-Authors: Annette Schimmel, Iris Schroeder, Samuel Charles, L. Cruthers, Friederike Kraemer, K. J. KriegerAbstract:This paper reports on the efficacy of a novel flavoured tablet formulation of emodepside plus Praziquantel (Profender® tablets for dogs) against mature and immature adult whipworms ( Trichuris vulpis ) at the proposed minimum dose of 1 mg emodepside and 5 mg Praziquantel per kg body weight in dogs. Three randomised, blinded and controlled laboratory studies with naturally or experimentally infected dogs were performed. The first study was conducted as a dose determination study in experimentally infected dogs using three different dose levels, i.e., 0.5x, 1x and 2x the minimum therapeutic dose. Two further studies confirmed the efficacy of emodepside plus Praziquantel tablets against mature and immature adult T. vulpis at the recommended minimum dose. In all three studies, the efficacy against mature and immature adult T. vulpis was >99%. No side effects of the treatment were observed. It is concluded that the emodepside plus Praziquantel tablet is an effective and safe treatment against mature and immature adult stages of T. vulpis in dogs.
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Field Evaluation of the Efficacy and Safety of Emodepside plus Praziquantel Tablets (Profender® Tablets for Dogs) against Naturally Acquired Nematode and Cestode Infections in Dogs
Parasitology Research, 2009Co-Authors: Isabelle Radeloff, Annette Schimmel, Christophe Lesueur, K. J. KriegerAbstract:A controlled, blinded and randomised multicentre field study evaluated the efficacy and safety of a new anthelmintic tablet formulation containing emodepside plus Praziquantel (Profender® tablets for dogs) in the treatment of gastrointestinal nematode and cestode infections in dogs in France, Germany, Portugal and Slovakia. Dogs positive for nematodes and/or cestodes (demonstrated by faecal egg counts and/or the presence of proglottids) were treated with emodepside plus Praziquantel tablets (n = 239) or the reference product containing milbemycin oxime and Praziquantel (Milbemax® [n = 115]) at the recommended dose rate. Two faecal samples collected between 7 and 13 days after treatment were evaluated for proglottids, nematode and cestode eggs. No suspected adverse drug reactions were observed in the study. The following parasite species were identified: Trichuris vulpis , Toxocara canis , Toxascaris leonina , Uncinaria stenocephala , Ancylostoma caninum , Dipylidium caninum , Taeniidae and Mesocestoides spp. Geometric mean nematode egg counts in dogs treated with emodepside plus prazi quantel tablets were reduced by 99.9 % compared with a reduction of 99.6 % for the reference product. Statistical analysis demonstrated noninferiority of investigational versus reference product (p = 0.0342). None of the dogs treated with emodepside plus Praziquantel or reference product remained positive for cestodes after treatment. The study demonstrated that emodepside plus Praziquantel tablets are safe and highly efficacious against a broad spectrum of nematodes and cestodes under field conditions.
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Efficacy of Emodepside plus Praziquantel Tablets (Profender® Tablets for Dogs) against Mature and Immature Cestode Infections in Dogs
Parasitology Research, 2009Co-Authors: Iris Schroeder, Annette Schimmel, Manuela Schnyder, Peter Deplazes, K. J. KriegerAbstract:The efficacy of a novel flavoured tablet formulation of emodepside plus Praziquantel (Profender® tablets for dogs) against intestinal cestodes was investigated in four randomised, blinded placebocontrolled dose confirmation studies in dogs experimentally infected with Echinococcus granulosus or E. multilocularis and in dogs naturally infected with Dipylidium caninum or Taenia spp. The tablets were used at the minimum recommended dose of 1 mg emodepside and 5 mg Praziquantel per kg body weight. The studies demonstrated 100% efficacy against mature and immature E. granulosus and E. multilocularis and mature Taenia spp. and D. caninum . Additionally, one of the studies demonstrated non-interference of emodepside with the efficacy of Praziquantel against D. caninum . No side effects of the treatment were observed. It is concluded that emodepside plus Praziquantel tablets are safe and effective against mature and immature stages of E. granulosus and E. multilocularis and mature stages of Taenia spp. and D. caninum .
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Efficacy of a Combination of Emodepside plus Praziquantel against Larval and Adult Stages of Nematodes (Trichuris muris, Angiostrongylus cantonensis) in Rodents
Parasitology Research, 2007Co-Authors: G. Schmahl, A. Harder, H. Mehlhorn, S. Klimpel, K. J. KriegerAbstract:A combination of emodepside plus Praziquantel was tested in laboratory mice strain C57BL/10 experimentally infected with Trichuris muris . Under the conditions chosen, a single topical administration of 3.0 mg emodepside per kg of body weight (bw) and 12.0 mg Praziquantel per kg bw at day 52 led to a survival rate of 6.8% of mature T. muris at 54 day post infection (dpi). Using the same dose at 3 dpi, the survival rate of mature nematodes at 52 dpi was 84.7%. However, when single treatment with 3.0mg emodepside per kg bw plus 12.0 mg Praziquantel per kg bw was used at 20 dpi or 35 dpi, the survival rates of adult nematodes on day 52 were 15.7 or 18.8%, respectively. Following a single administration of 6 mg emodepside per kg bw and 24 mg Praziquantel per kg bw at 3, 20 and 35 dpi the survival rates of mature T. muris were 1.7, 0.6 or even 0%. In another series of experiments, emodepside plus Praziquantel were tested inWistar rats experimentally infected with Angiostrongylus cantonensis . Following a treatment at day 15 p.i. with either 3.0 or 6.0mg emodepside per kg bw and either 12.0mg or 24.0mg Praziquantel per kg bw, respectively, the survival rates of adult nematodes at 44 dpi were not significantly reduced in comparison to the untreated controls. Only when single treatment was done with the highest dose with 18 mg emodepside per kg bw and 72 mg Praziquantel per kg bw was the survival rate of larvae migrating in the CNS reduced to 32.4%at 20 dpi. A complete depression of the survival rate of adult A. cantonensis was observed following single treatment with 12.0 or 18.0 mg emodepside per kg bw and 48.0 or 72.0 mg Praziquantel per kg bw at 15 dpi when the control (killing and examination) was done at 44 dpi. The single standard dose of 3 mg emodepside per kg bw and 12 mg Praziquantel per kg bw, either administered at 15 or at 44 dpi, reduced the survival rate of adult A. cantonensis to 54.2 or 67.6% at 44 or 52 dpi, respectively. The present paper shows for the first time the efficacy of a combination containing emodepside plus Praziquantel against the nematodes T. muris and A. cantonensis .
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field evaluation of the efficacy and safety of emodepside Praziquantel spot on solution against naturally acquired nematode and cestode infections in domestic cats
Parasitology Research, 2005Co-Authors: J. Buch, S. D. Charles, K. J. Krieger, W L Davis, Isabelle RadeloffAbstract:Two controlled, blinded and randomized multi–site clinical field studies evaluated the efficacy and safety of emodepside/Praziquantel spot–on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/Praziquantel spot–on (Profender®, Bayer AG, Leverkusen, Germany). For a positivecontrol product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/Praziquantel spot–on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/Praziquantel spot–on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/Praziquantel spot–on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/Praziquantel spot–on is highly efficacious and safe under field conditions.
J. Buch - One of the best experts on this subject based on the ideXlab platform.
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field evaluation of the efficacy and safety of emodepside Praziquantel spot on solution against naturally acquired nematode and cestode infections in domestic cats
Parasitology Research, 2005Co-Authors: J. Buch, S. D. Charles, K. J. Krieger, W L Davis, Isabelle RadeloffAbstract:Two controlled, blinded and randomized multi–site clinical field studies evaluated the efficacy and safety of emodepside/Praziquantel spot–on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/Praziquantel spot–on (Profender®, Bayer AG, Leverkusen, Germany). For a positivecontrol product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/Praziquantel spot–on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/Praziquantel spot–on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/Praziquantel spot–on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/Praziquantel spot–on is highly efficacious and safe under field conditions.
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Efficacy of a topically administered combination of emodepside and Praziquantel against mature and immature Ancylostoma tubaeforme in domestic cats
Parasitology Research, 2005Co-Authors: F. H. M. Borgsteede, C Epe, J. Buch, S. D. Charles, L. Cruthers, K. J. KriegerAbstract:This paper reports the efficacy of emodepside/Praziquantel spot–on (Profender^®, Bayer AG, Leverkusen, Germany), a novel broadspectrum anthelmintic for dermal application, against L4 larvae and immature adult and adult stages of Ancylostoma tubaeforme in cats. The formulation contains 2.14% (w/w) emodepside and 8.58% (w/v) Praziquantel, with emodepside being active against gastrointestinal nematodes and Praziquantel against cestodes. Five randomized, blinded and controlled laboratory studies demonstrated 100% efficacy of emodepside/Praziquantel spot–on against mature A. tubaeforme and an efficacy of >95% and >97%, respectively, against L4 larvae and immature adults (based on worm counts after necropsy) at approximately the minimum proposed dose rate in cats of 3.0 mg emodepside and 12.0 mg Praziquantel/kg body weight. No adverse reactions to the treatment were observed. It is concluded that emodepside/Praziquantel spot–on is an effective and safe treatment against infections with mature and immature A. tubaeforme . Emodepside/Praziquantel spot–on will considerably facilitate the treatment of cats against nematodes and cestodes compared with orally administered preparations.
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Evaluation of the efficacy of emodepside+Praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats
Parasitology Research, 2005Co-Authors: S. D. Charles, Terry Settje, J. Buch, L. Cruthers, G. Altreuther, C. R. Reinemeyer, D. J. Kok, D. D. Bowman, K. R. Kazacos, D. J. JenkinsAbstract:Emodepside+Praziquantel topical solution was developed to provide broad–spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and Praziquantel (12 mg/kg) (Profender^®, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis , or experimental infections with Echinococcus multilocularis that were placebo–controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+Praziquantel topical solution was 100% against D. caninum and T. taeniaeformis , and 98.5– 100% against E. multilocularis . No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+Praziquantel topical solution was safe and highly effective against cestode infections.
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evaluation of the efficacy of emodepside Praziquantel topical solution against cestode dipylidium caninum taenia taeniaeformis and echinococcus multilocularis infections in cats
Parasitology Research, 2005Co-Authors: Samuel Charles, Terry Settje, J. Buch, L. Cruthers, G. Altreuther, C. R. Reinemeyer, D. J. Kok, D. D. Bowman, K. R. Kazacos, David JenkinsAbstract:Emodepside+Praziquantel topical solution was developed to provide broad–spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and Praziquantel (12 mg/kg) (Profender®, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis, or experimental infections with Echinococcus multilocularis that were placebo–controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+Praziquantel topical solution was 100% against D. caninum and T. taeniaeformis, and 98.5– 100% against E. multilocularis. No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+Praziquantel topical solution was safe and highly effective against cestode infections.
Jennifer Keiser - One of the best experts on this subject based on the ideXlab platform.
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Efficacy and Safety of Moxidectin, Synriam, Synriam-Praziquantel versus Praziquantel against Schistosoma haematobium and S. mansoni Infections: A Randomized, Exploratory Phase 2 Trial.
PLoS neglected tropical diseases, 2016Co-Authors: Beatrice Barda, Jean T Coulibaly, Maxim Puchkov, Jörg Huwyler, Jennifer KeiserAbstract:Schistosomiasis affects millions of people, yet treatment options are limited. The antimalarial Synriam (piperaquine 150 mg/arterolane 750 mg) and the anthelminthic moxidectin revealed promising antischistosomal properties in preclinical or clinical studies.; We conducted two single-blind, randomized exploratory Phase 2 trials in Schistosoma mansoni and S. haematobium-infected adolescents in northern and central Cote d'Ivoire. Our primary endpoints were cure rates (CRs) and egg reduction rates (ERRs) based on geometric mean and safety. Each subject was asked to provide two stool samples (S. mansoni trial) for Kato-Katz analysis or three urine samples (S. haematobium trial) for urine filtration and one finger prick for malaria screening at baseline and follow-up. Participants were randomly assigned to either moxidectin, Synriam, Synriam plus Praziquantel or Praziquantel.; 128 adolescents (age: 12-17 years) were included in each study. Against S. haematobium moxidectin and Synriam revealed low efficacy. On the other hand, Synriam plus Praziquantel and Praziquantel yielded CRs of 60.0% and 38.5% and ERRs of 96.0% and 93.5%, respectively. CRs observed in the treatment of S. mansoni were 13.0%, 6.7%, 27.0%, and 27.6% for moxidectin, Synriam, Synriam plus Praziquantel and Praziquantel, respectively. ERRs ranged from 64.9% (Synriam) to 87.5% (Praziquantel).; Synriam and moxidectin show low efficacy against S. haematobium, hence an ancillary benefit is not expected when these drugs are used for treating onchocerciasis and malaria in co-endemic settings. Further studies are needed to corroborate our findings that moxidectin and Synriam show moderate ERRs against S. mansoni.
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the little we know about the pharmacokinetics and pharmacodynamics of Praziquantel racemate and r enantiomer
Journal of Antimicrobial Chemotherapy, 2014Co-Authors: Jennifer Keiser, Piero Olliaro, Petra DelgadoromeroAbstract:Praziquantel has been the mainstay of schistosomiasis control since 1984 and widely distributed since 2006 through 'preventive chemotherapy' programmes to school-aged children or at-risk populations. In addition, preschool-aged children are now recognized as a vulnerable population and a group for targeted treatment, but they may be difficult to dose correctly with the available product--a racemate, based on the biologically active enantiomer (R-Praziquantel) and the inactive distomer (S-Praziquantel), which contributes the bitter taste and doubles the size of the tablets. Hence, a paediatric formulation is required, possibly enantiomerically pure. Developing such a product and extending its use to younger children should be pharmacologically guided, but limited data exist on pharmacokinetics and pharmacokinetic/pharmacodynamic correlations for Praziquantel. This article presents available data on the chemistry, pharmacokinetics and pharmacodynamics of Praziquantel, as well as R-Praziquantel, and points to gaps in our knowledge.
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interactions of mefloquine with Praziquantel in the schistosoma mansoni mouse model and in vitro
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Jennifer Keiser, Theresia Manneck, Mireille VargasAbstract:Objectives Mefloquine has interesting antischistosomal properties, hence it might be an attractive partner drug for combination treatment with Praziquantel. The aim of this study was to evaluate activities of mefloquine/Praziquantel combinations against Schistosoma mansoni in vitro and in vivo. Methods Dose-response relationships were established following exposure of adult S. mansoni to mefloquine, Praziquantel and fixed dose combinations of mefloquine/Praziquantel in vitro. S. mansoni-infected mice were treated orally with selected doses of single drugs and drug combinations 7 weeks post-infection. Results We calculated in vitro LC(50) values of 0.024 and 1.9 mug/mL for Praziquantel and mefloquine, respectively. Mefloquine/Praziquantel combinations showed synergistic effects, with combination index (CI) values >1 when adult S. mansoni were simultaneously incubated with both drugs in vitro. Reduced viabilities were also observed when schistosomes were first exposed to mefloquine followed by Praziquantel in vitro. ED(50)s of 62 mg/kg and 172 mg/kg were determined for mefloquine and Praziquantel against adult S. mansoni in vivo, respectively. Combinations of Praziquantel (50 or 100 mg/kg) followed the next day by mefloquine (50 or 100 mg/kg) treatment revealed only moderate total worm burden reductions of 47.8%-54.7%. On the other hand, when both drugs (100 mg/kg each) were either given simultaneously or mefloquine was given prior to Praziquantel, high total and female worm burden reductions of 86.0%-93.1% were observed. For the later treatment regimen, synergistic effects (CI > 1) were calculated when mefloquine and Praziquantel were combined using a fixed dose ratio based on their ED(50)s. Conclusions Combinations of mefloquine and Praziquantel may have clinical utility in the treatment of schistosomiasis
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2005Co-Authors: Jennifer Keiser, Bernard FriedAbstract:We examined the effects of Praziquantel and the artemisinins on adult Echinostoma caproni. In vitro, both Praziquantel and the artemisinins exhibited exposure-response relationships. In vivo, worm burden reductions of 100 % were achieved with single oral doses of Praziquantel, artesunate, and artemether at 50, 700, and 1,100 mg/kg of body weight, respectively. Food-borne trematodiasis is an emerging public health prob-lem (6). The current arsenal for treatment and morbidity con-trol of food-borne trematodiasis consists of only two drugs, namely, Praziquantel and triclabendazole (4, 5), and hence new drugs are urgently needed. We studied the trematocidal prop-erties of the artemisinins against adult Echinostoma caproni in vitro and in vivo. For comparison, the effect of Praziquantel was also examined. Approval of our animal studies was obtained according to local government regulations. Artesunate was obtained from Mepha (Aesch, Switzerland); artemether, arteether, and Praziquantel wer
