Affiliation: University of Basel
- Duthaler U, Keiser J, Huwyler J. LC-MS/MS method for the determination of two metabolites of tribendimidine, deacylated amidantel and its acetylated metabolite in plasma, blood and dried blood spots. J Pharm Biomed Anal. 2015;105:163-73 pubmed publisher..DBS samples should be stored at -20Â°C. The validation results demonstrated that the LC-MS/MS method is precise, accurate and selective and can be applied for pharmacokinetic studies with tribendimidine. ..
- Keiser J, Shu Hua X, Tanner M, Utzinger J. Artesunate and artemether are effective fasciolicides in the rat model and in vitro. J Antimicrob Chemother. 2006;57:1139-45 pubmed..hepatica displayed very poor mobility and there was focal swelling of the tegument and spines. Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the hosts. ..
- VejzagiÄ‡ N, Adelfio R, Keiser J, Kringel H, Thamsborg S, Kapel C. Bacteria-induced egg hatching differs for Trichuris muris and Trichuris suis. Parasit Vectors. 2015;8:371 pubmed publisher..The observed difference in hatching of T. muris and T. suis eggs incubated with selected bacteria, indicate significant biological differences which may reflect specific adaptation to different host-specific gut microbiota. ..
- Speich B, Ali S, Ame S, Albonico M, Utzinger J, Keiser J. Quality control in the diagnosis of Trichuris trichiura and Ascaris lumbricoides using the Kato-Katz technique: experience from three randomised controlled trials. Parasit Vectors. 2015;8:82 pubmed publisher..Existing WHO guidelines for quality control might be overambitious and might have to be revised, specifically with regard to handling disagreements in FECs. ..
- Keiser J, Manneck T, Kirchhofer C, Braissant O. Isothermal microcalorimetry to study the activity of triclabendazole and its metabolites on juvenile and adult Fasciola hepatica. Exp Parasitol. 2013;133:265-8 pubmed publisher..05)h. In conclusion, IMC is useful to document drug effects on juvenile F. hepatica and since rapid technological developments in this field are occurring IMC might also hold promise to study adult F. hepatica in the near future. ..
- Keiser J, Xiao S, Smith T, Utzinger J. Combination chemotherapy against Clonorchis sinensis: experiments with artemether, artesunate, OZ78, praziquantel, and tribendimidine in a rat model. Antimicrob Agents Chemother. 2009;53:3770-6 pubmed publisher..sinensis is confirmed, and combination chemotherapy with praziquantel produces synergistic and antagonistic effects depending on the doses administered. Further preclinical investigations are warranted. ..
- Cowan N, DÃ¤twyler P, Ernst B, Wang C, Vennerstrom J, Spangenberg T, et al. Activities of N,N'-Diarylurea MMV665852 analogs against Schistosoma mansoni. Antimicrob Agents Chemother. 2015;59:1935-41 pubmed publisher..To counteract the low efficacy observed in the mouse model, further investigations should focus on identifying compounds with improved solubility and pharmacokinetic properties. ..
- Keiser J, Ingram K, Vargas M, Chollet J, Wang X, Dong Y, et al. In vivo activity of aryl ozonides against Schistosoma species. Antimicrob Agents Chemother. 2012;56:1090-2 pubmed publisher..05), respectively. Furthermore, treatment of S. haematobium-infected mice with OZ418 reduced the total worm burden by 86%. In conclusion, OZ418 is a promising antischistosomal lead compound. ..
- Keiser J. Is Caenorhabditis elegans the Magic Bullet for Anthelminthic Drug Discovery?. Trends Parasitol. 2015;31:455-6 pubmed publisher..A new study demonstrates that C. elegans is a useful tool in high-throughput anthelminthic drug discovery. Despite challenges, drug discovery using C. elegans offers opportunities that might lead the way to novel anthelminthic drugs. ..
- Meister I, Leonidova A, KovaÄ J, Duthaler U, Keiser J, Huwyler J. Development and validation of an enantioselective LC-MS/MS method for the analysis of the anthelmintic drug praziquantel and its main metabolite in human plasma, blood and dried blood spots. J Pharm Biomed Anal. 2016;118:81-88 pubmed publisher..Moreover, the enantioselective separation was achieved with a run time of 11.5 min and a simple sample processing method. ..
- Panić G, Flores D, Ingram Sieber K, Keiser J. Fluorescence/luminescence-based markers for the assessment of Schistosoma mansoni schistosomula drug assays. Parasit Vectors. 2015;8:624 pubmed publisher..mansoni. CellTiter-GloÂ® can likely be used for endpoint go/no go screens and potentially for drug dose-response studies. ..
- Cowan N, Yaremenko I, Krylov I, Terent ev A, Keiser J. Elucidation of the in vitro and in vivo activities of bridged 1,2,4-trioxolanes, bridged 1,2,4,5-tetraoxanes, tricyclic monoperoxides, silyl peroxides, and hydroxylamine derivatives against Schistosoma mansoni. Bioorg Med Chem. 2015;23:5175-81 pubmed publisher..The high in vitro antischistosomal activity of trioxolanes and tricyclic monoperoxides is a promising basis for future investigations, with the focus on improving in vivo efficacy. ..
- Keiser J, Xiao S, Dong Y, Utzinger J, Vennerstrom J. Clonorchicidal properties of the synthetic trioxolane OZ78. J Parasitol. 2007;93:1208-13 pubmed publisher..sinensis, respectively. SEM observations revealed tegumental surface alterations, including blebbing and sloughing. OZ78 emerges as a new compound with a broad spectrum of activity against major foodborne trematode infections. ..
- Keiser J, Utzinger J. Food-borne trematodiasis: current chemotherapy and advances with artemisinins and synthetic trioxolanes. Trends Parasitol. 2007;23:555-62 pubmed..Lastly, prospects for the development of a safe, efficacious, inexpensive and broad-spectrum trematocidal drug are considered. ..
- Sayasone S, Odermatt P, Vonghachack Y, Xayavong S, Senggnam K, Duthaler U, et al. Efficacy and safety of tribendimidine against Opisthorchis viverrini: two randomised, parallel-group, single-blind, dose-ranging, phase 2 trials. Lancet Infect Dis. 2016;16:1145-1153 pubmed publisher..Department for International Development, Medical Research Council, Wellcome Trust Joint Global Health Trials Scheme. ..
- Moser W, Labhardt N, Cheleboi M, Muhairwe J, Keiser J. Unexpected low soil-transmitted helminth prevalence in the Butha-Buthe district in Lesotho, results from a cross-sectional survey. Parasit Vectors. 2017;10:72 pubmed publisher..Additional parasitological surveys on the prevalence and the spatial distributions of STH infections across the entire country of Lesotho are needed. ..
- Cowan N, Vargas M, Keiser J. In Vitro and In Vivo Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis. Antimicrob Agents Chemother. 2016;60:6127-33 pubmed publisher..Even though this study indicates that it is safe to coadminister albendazole-oxantel pamoate and albendazole-mebendazole, human pharmacokinetic studies are recommended. ..
- Keiser J, Utzinger J. Chemotherapy for major food-borne trematodes: a review. Expert Opin Pharmacother. 2004;5:1711-26 pubmed
- Keiser J, Panić G, Adelfio R, Cowan N, Vargas M, Scandale I. Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections. Parasit Vectors. 2016;9:376 pubmed publisher..Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a starting point for drug discovery for STH. ..
- Keiser J, Tritten L, Adelfio R, Vargas M. Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo. Parasit Vectors. 2012;5:292 pubmed publisher..Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies. ..
- Cowan N, Raimondo A, Keiser J. Approved oncology drugs lack in vivo activity against Trichuris muris despite in vitro activity. Parasitol Res. 2016;115:4443-4446 pubmed..Drug discovery against STH should be strengthened including the definition of compound progression criteria. Follow-up structure-activity relationship studies with modified compounds might be considered. ..
- Duthaler U, Sayasone S, Vanobbergen F, Penny M, Odermatt P, Huwyler J, et al. Single-Ascending-Dose Pharmacokinetic Study of Tribendimidine in Opisthorchis viverrini-Infected Patients. Antimicrob Agents Chemother. 2016;60:5705-15 pubmed publisher..Further studies are warranted to assess the large differences between individuals in the rate of metabolic turnover of dADT to adADT. (This study has been registered with the ISRCTN Registry under no. ISRCTN96948551.). ..
- Speich B, Moser W, Ali S, Ame S, Albonico M, Hattendorf J, et al. Efficacy and reinfection with soil-transmitted helminths 18-weeks post-treatment with albendazole-ivermectin, albendazole-mebendazole, albendazole-oxantel pamoate and mebendazole. Parasit Vectors. 2016;9:123 pubmed publisher..e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections. Current Controlled Trials ISRCTN80245406. ..
- Leonidova A, Vargas M, Huwyler J, Keiser J. Pharmacokinetics of the Antischistosomal Lead Ozonide OZ418 in Uninfected Mice Determined by Liquid Chromatography-Tandem Mass Spectrometry. Antimicrob Agents Chemother. 2016;60:7364-7371 pubmed..Our results provide a first insight into the disposition of OZ418, paving the way for further studies of its biological fate and effect. ..
- Keiser J, Utzinger J. Emerging foodborne trematodiasis. Emerg Infect Dis. 2005;11:1507-14 pubmed..This is supported by reviewing aquaculture development in countries endemic for foodborne trematodiasis over the past 10-50 years. Future and sustainable control of foodborne trematodiasis is discussed. ..
- Speich B, Croll D, FÃ¼rst T, Utzinger J, Keiser J. Effect of sanitation and water treatment on intestinal protozoa infection: a systematic review and meta-analysis. Lancet Infect Dis. 2016;16:87-99 pubmed publisher..Swiss National Science Foundation (project numbers PBBSP3-146869 and P300P3-154634), Medicor Foundation, European Research Council (614739-A_HERO). ..
- Clède S, Cowan N, Lambert F, Bertrand H, Rubbiani R, Patra M, et al. Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni. Chembiochem. 2016;17:1004-7 pubmed publisher..Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm. ..
- Cowan N, Meier C, Neodo A, Keiser J. Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate inÂ vitro and inÂ vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes. Int J Parasitol Drugs Drug Resist. 2017;7:159-173 pubmed publisher..muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied. ..
- Bergquist R, Utzinger J, Keiser J. Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?. Infect Dis Poverty. 2017;6:74 pubmed publisher..Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis. ..
- Bogoch I, Coulibaly J, Rajchgot J, Andrews J, Kovač J, Utzinger J, et al. Poor Validity of Noninvasive Hemoglobin Measurements by Pulse Oximetry Compared with Conventional Absorptiometry in Children in Côte d'Ivoire. Am J Trop Med Hyg. 2017;96:217-220 pubmed publisher..50 for children 4-9 years of age, and 0.33 for children 10-15 years of age. Further study and development of noninvasive Hb devices is necessary prior to implementation in African pediatric populations. ..
- Keiser J, Chollet J, Xiao S, Mei J, Jiao P, Utzinger J, et al. Mefloquine--an aminoalcohol with promising antischistosomal properties in mice. PLoS Negl Trop Dis. 2009;3:e350 pubmed publisher..It will be interesting to investigate whether mefloquine, which is widely and effectively used for the treatment of malaria, has an impact on schistosomiasis in areas where both malaria and schistosomiasis co-exist. ..
- Coulibaly J, Panić G, SiluÃ© K, KovaÄ J, Hattendorf J, Keiser J. Efficacy and safety of praziquantel in preschool-aged and school-aged children infected with Schistosoma mansoni: a randomised controlled, parallel-group, dose-ranging, phase 2 trial. Lancet Glob Health. 2017;5:e688-e698 pubmed publisher..In the absence of treatment alternatives, a single dose of praziquantel of 40 mg/kg, recommended by the WHO for S mansoni infections in SAC can be endorsed for PSAC in preventive chemotherapy programmes. European Research Council. ..
- Keiser J, Vargas M, Winter R. Anthelminthic properties of mangostin and mangostin diacetate. Parasitol Int. 2012;61:369-71 pubmed publisher..mansoni and E. caproni in vivo, respectively. Pharmacokinetic studies would be helpful to understand the differences observed between in vitro and in vivo activities and lacking dose-response relationships. ..
- Keiser J, Utzinger J. Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA. 2008;299:1937-48 pubmed publisher..Preventive chemotherapy is the mainstay of control, but only 4 drugs are available: albendazole, mebendazole, levamisole, and pyrantel pamoate...
- Keiser J, Brun R, Fried B, Utzinger J. Trematocidal activity of praziquantel and artemisinin derivatives: in vitro and in vivo investigations with adult Echinostoma caproni. Antimicrob Agents Chemother. 2006;50:803-5 pubmed..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...
- Keiser J, Utzinger J. Antimalarials in the treatment of schistosomiasis. Curr Pharm Des. 2012;18:3531-8 pubmed
- Moser W, Coulibaly J, Ali S, Ame S, Amour A, Yapi R, et al. Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d'Ivoire: a ra. Lancet Infect Dis. 2017;17:1162-1171 pubmed publisher..Swiss National Science Foundation. ..
- ..Current research needs are emphasized...
- Moser W, Schindler C, Keiser J. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis. BMJ. 2017;358:j4307 pubmed publisher..The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against T trichiura. ..
- Keiser J, Vargas M. Effect of artemether, artesunate, OZ78, praziquantel, and tribendimidine alone or in combination chemotherapy on the tegument of Clonorchis sinensis. Parasitol Int. 2010;59:472-6 pubmed publisher..The effect of drug combinations against C. sinensis requires further scientific inquiry, e.g. in transmission electron microscopy studies and in the C. sinensis-rabbit model...
- Keiser J, Shu Hua X, Chollet J, Tanner M, Utzinger J. Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni, Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini. Antimicrob Agents Chemother. 2007;51:1096-8 pubmed..1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica...
- Keiser J, Engels D, Büscher G, Utzinger J. Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opin Investig Drugs. 2005;14:1513-26 pubmed
- Keiser J, Tritten L, Silbereisen A, Speich B, Adelfio R, Vargas M. Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug. PLoS Negl Trop Dis. 2013;7:e2119 pubmed publisher..The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations...
- Keiser J, Shu Hua X, Utzinger J. Effect of tribendimidine on adult Echinostoma caproni harbored in mice, including scanning electron microscopic observations. J Parasitol. 2006;92:858-62 pubmed..Our findings call for further investigations using tribendimidine in other trematode-animal models, because this compound shows promising trematocidal activity...
- Keiser J, Utzinger J, Xiao S, Odermatt P, Tesana S. Opisthorchis viverrini: efficacy and tegumental alterations following administration of tribendimidine in vivo and in vitro. Parasitol Res. 2008;102:771-6 pubmed publisher..0%. In conclusion, our experiments confirm that tribendimidine possesses interesting trematocidal properties, which warrant additional investigations and provide further data for subsequent clinical trials...
- Keiser J, Thiemann K, Endriss Y, Utzinger J. Strongyloides ratti: in vitro and in vivo activity of tribendimidine. PLoS Negl Trop Dis. 2008;2:e136 pubmed publisher..Strongyloidiasis is a truly neglected tropical disease, but its public health significance is far from being negligible. At present, only a few drugs are available for the treatment and control of strongyloidiasis...
- Keiser J, Rinaldi L, Veneziano V, Mezzino L, Tanner M, Utzinger J, et al. Efficacy and safety of artemether against a natural Fasciola hepatica infection in sheep. Parasitol Res. 2008;103:517-22 pubmed publisher..Further studies are warranted to assess the potential of additional artemisinin derivatives and other peroxidic compounds for the treatment of Fasciola spp. infections in different ruminants...
- Keiser J, Veneziano V, Rinaldi L, Mezzino L, Duthaler U, Cringoli G. Anthelmintic activity of artesunate against Fasciola hepatica in naturally infected sheep. Res Vet Sci. 2010;88:107-10 pubmed publisher..3% and 83.9%, respectively, were calculated in the three surviving sheep. In conclusion, the interesting fasciocidal properties of artesunate in sheep warrant further investigations with an emphasis on toxicity studies...
- Keiser J, N Guessan N, Adoubryn K, Silué K, Vounatsou P, Hatz C, et al. Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. Clin Infect Dis. 2010;50:1205-13 pubmed publisher..Morbidity control of schistosomiasis relies on a single drug, praziquantel. The antimalarial drug mefloquine possesses interesting antischistosomal properties, yet no clinical studies have been performed...
- Keiser J, Duthaler U, Utzinger J. Update on the diagnosis and treatment of food-borne trematode infections. Curr Opin Infect Dis. 2010;23:513-20 pubmed publisher..This review provides an update on recent developments in the diagnosis and treatment of food-borne trematodiases...