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Genomes and Genes | parasitic sensitivity testsSummarySummary: Tests that demonstrate the relative effectiveness of chemotherapeutic agents against specific parasites. Top Publications
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Publications
Spiroindolones, a potent compound class for the treatment of malaria
Matthias Rottmann
Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH 4002 Basel, Switzerland
Science 329:1175-80. 2010..The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model...Chloroquine-resistant Plasmodium vivax, Brazilian Amazon
Franklin Simoes de Santana Filho
Emerg Infect Dis 13:1125-6. 2007Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin
Amar bir Singh Sidhu
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, Bronx, NY 10461, USA
J Infect Dis 194:528-35. 2006..These results highlight the importance of pfmdr1 copy number in determining P. falciparum susceptibility to multiple agents currently being used to combat malaria caused by multidrug-resistant parasites...Determinants of in vitro drug susceptibility testing of Plasmodium vivax
B Russell
International Health Program, Infectious Diseases Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia
Antimicrob Agents Chemother 52:1040-5. 2008..vivax and suggest that susceptibility to chloroquine may be associated with variable growth rates. These findings have important implications for the phenotypic and downstream genetic characterization of P. vivax...Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations
Amar bir Singh Sidhu
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Science 298:210-3. 2002..pfcrt mutations increased susceptibility to artemisinin and quinine and minimally affected amodiaquine activity; hence, these antimalarials warrant further investigation as agents to control chloroquine-resistant falciparum malaria...Drug resistance in leishmaniasis
Simon L Croft
Drugs for Neglected Diseases Initiative, 1 place Saint Gervais, CH 1201 Geneva, Switzerland
Clin Microbiol Rev 19:111-26. 2006....In vitro sensitivities of Plasmodium falciparum to different antimalarial drugs in Uganda
Samuel L Nsobya
Department of Medicine, Makerere University, Kampala, Uganda
Antimicrob Agents Chemother 54:1200-6. 2010..In summary, we demonstrated in parasites from Kampala a range of sensitivities to older drugs; correlation of sensitivities to CQ, MDAQ, and QN; and good activity against nearly all strains for DHA, LM, and PQ...Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs
Bécaye Fall
1Laboratoire d étude de la chimiosensibilité du paludisme, Fédération deslaboratoires, Hôpital Principal de Dakar, Dakar, Senegal
Malar J 10:310. 2011..To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar...Monitoring of in vitro susceptibilities and molecular markers of resistance of Plasmodium falciparum isolates from Thai-Myanmar border to chloroquine, quinine, mefloquine and artesunate
Wanna Chaijaroenkul
Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani 12121, Thailand
Acta Trop 113:190-4. 2010..Moreover, the correlation between pfmdr1 gene amplification and susceptibility of the parasite to MQ, QN and AS was observed (decreased susceptibilities to MQ, QN and AS in isolates with increased pfmdr1 copy number)...Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria
Richard T Eastman
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, Hammer Health Sciences Center, Room 1502, 701 West 168th Street, New York 10032, New York, USA
Nat Rev Microbiol 7:864-74. 2009..This Review article discusses our current knowledge about the mode of action of ACTs, their pharmacological properties and the proposed mechanisms of drug resistance...Sterol methenyl transferase inhibitors alter the ultrastructure and function of the Leishmania amazonensis mitochondrion leading to potent growth inhibition
Juliany C F Rodrigues
Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS Bloco G, Ilha do Fundao, 21949 900 Rio de Janeiro RJ, Brazil
Protist 158:447-56. 2007..The present study confirms these findings, showing that in Leishmania amazonensis the mitochondrial complex appears to be the first organelle affected after treatment with different SMTI...Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia
Bruno Pradines
Unité de Recherche en Biologie et Epidémiologie Parasitaires Unité de Recherche pour les Maladies Infectieuses et Tropicales Emergentes UMR 6236, Institut de Medecine Tropicale du Service de Sante des Armees, Marseille, France
Malar J 10:268. 2011....Effect of elatol, isolated from red seaweed Laurencia dendroidea, on Leishmania amazonensis
Adriana Oliveira dos Santos
Programa de Pós Graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051 990, Campus Universitario, Londrina, Parana, Brazil
Mar Drugs 8:2733-43. 2010..Our studies indicated that elatol is a potent antiproliferative agent against promastigote and intracellular amastigote forms, and may have important advantages for the development of new anti-leishamanial chemotherapies...Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins
Michela Menegon
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanita, Rome, Italy
Parasitol Int 57:233-5. 2008Geographic structuring of the Plasmodium falciparum sarco(endo)plasmic reticulum Ca2+ ATPase (PfSERCA) gene diversity
Ronan Jambou
Institut Pasteur de Dakar, BP 220, Dakar, Senegal
PLoS ONE 5:e9424. 2010..One possible contributor could be the frequency of haemoglobinopathies that are associated with calcium dysregulation in the erythrocyte...Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory conc
Halima Kaddouri
Centre National de Référence du Paludisme, Laboratoire de Parasitologie, Hôpital Bichat Claude Bernard and Université René Descartes, Paris, France
Antimicrob Agents Chemother 50:3343-9. 2006..The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites...Simple histidine-rich protein 2 double-site sandwich enzyme-linked immunosorbent assay for use in malaria drug sensitivity testing
Harald Noedl
Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, A 1095 Vienna, Austria
Antimicrob Agents Chemother 49:3575-7. 2005..The sensitivity is comparable and the drug sensitivity results very closely match those obtained with the commercial ELISA kits (R(2) = 0.979; P < 0.001; mean log difference at the 50% inhibitory concentration = 0.07)...Urban malaria in Dakar, Senegal: chemosusceptibility and genetic diversity of Plasmodium falciparum isolates
Maud Henry
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Medecine Tropicale du Service de Sante des Armees, Marseille, France
Am J Trop Med Hyg 75:146-51. 2006..Areas with urban malaria should use vector control measures and efficient chemoprophylaxis for non-immune populations...Malaria drug-sensitivity testing: new assays, new perspectives
Harald Noedl
Dept of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology, University of Vienna, Kinderspitalgasse 15, A 1095, Vienna, Austria
Trends Parasitol 19:175-81. 2003..This review examines the various new approaches to the in vitro assessment of malaria drug sensitivity and their limitations...Comparison of a SYBR green I-based assay with a histidine-rich protein II enzyme-linked immunosorbent assay for in vitro antimalarial drug efficacy testing and application to clinical isolates
David J Bacon
Parasitology Program, Naval Medical Research Center Detachment, American Embassy, APO AA 34031, Lima, Peru
Antimicrob Agents Chemother 51:1172-8. 2007..falciparum with fresh or cultured parasites...Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening
Jacob D Johnson
Principal Investigator, Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA
Antimicrob Agents Chemother 51:1926-33. 2007..In conclusion, the MSF assay allows for reliable one-plate high-throughput, automated malaria in vitro susceptibility testing without the expense, time consumption, and hazard of other screening assays...Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border
Papichaya Phompradit
Thailand Center of Excellence on Drug Discovery and Development, Thammasat University, Rangsit Campus, Patumthani 12121, Thailand
Acta Trop 120:130-5. 2011..No association between mutation or amplification of pfatp6 gene and in vitro susceptibility of P. falciparum isolates was found...Polymorphisms of the pfmdr1 but not the pfnhe-1 gene is associated with in vitro quinine sensitivity in Thai isolates of Plasmodium falciparum
Teera Poyomtip
Department of Parasitology, Phramongkutklao College of Medicine, 315 Ratchawithi Rd, Ratchathewi, Bangkok, Thailand
Malar J 11:7. 2012..falciparum multidrug resistance 1 (pfmdr1), and P. falciparum Na+/H+ exchanger (pfnhe-1). This study was to investigate the role of the pfmdr1 and pfnhe-1 gene on in vitro QN sensitivity in Thai isolates of P. falciparum...Chloroquine resistance before and after its withdrawal in Kenya
Leah Mwai
Kenya Medical Research Institute Wellcome Trust Collaborative Research Programme, Kilifi, Kenya
Malar J 8:106. 2009..Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared...Evolution of the pfcrt T76 and pfmdr1 Y86 markers and chloroquine susceptibility 8 years after cessation of chloroquine use in Pikine, Senegal
Omar Ly
Laboratoire de Bactério Virologie, Hopital Aristide Le Dantec, 30 Avenue Pasteur, Dakar, Senegal
Parasitol Res 111:1541-6. 2012..The official discontinuation of CQ use is not completely followed by its total withdrawal from private drug sellers, and the molecule still exerts pressure on local P. falciparum populations...Bromopyrrole alkaloids as lead compounds against protozoan parasites
Fernando Scala
Dipartimento di Chimica delle Sostanze Naturali, Universita di Napoli Federico II, via D Montesano, 49, I 80131, Napoli, Italy
Mar Drugs 8:2162-74. 2010..Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids...A novel artemisinin-quinine hybrid with potent antimalarial activity
John J Walsh
School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin 2, Ireland
Bioorg Med Chem Lett 17:3599-602. 2007..The activity was superior to that of artemisinin alone, quinine alone, or a 1:1 mixture of artemisinin and quinine...Polymorphism of Plasmodium falciparum Na(+)/H(+) exchanger is indicative of a low in vitro quinine susceptibility in isolates from Viet Nam
Veronique Sinou
UMR MD3 Relations Hôte Parasite, pharmacologie et thérapeutique, Universite de la Mediterranee, Institut de Medecine Tropicale du Service de Sante des Armees, Antenne IRBA Marseille, Marseille, France
Malar J 10:164. 2011..However, its contribution to QN resistance seems to vary geographically depending on the genetic background of the parasites. Here, the role of this gene was investigated in in vitro QN susceptibility of isolates from Viet Nam...Improved assessment of plasmodium vivax response to antimalarial drugs by a colorimetric double-site plasmodium lactate dehydrogenase antigen capture enzyme-linked immunosorbent assay
Pierre Druilhe
Bio medical Parasitology Unit, Institut Pasteur, 25 rue du Dr Roux, Paris 75015, France
Antimicrob Agents Chemother 51:2112-6. 2007..falciparum, i.e., in the range of 100 nM for chloroquine and 15 nM for pyronaridine. However, further studies are required to precisely define the cutoff for resistance and the sensitivity to each drug...Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism
Benoit Witkowski
CNRS, Laboratoire de Chimie de Coordination, UPR8241, Toulouse, France
Antimicrob Agents Chemother 54:1872-7. 2010....Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria
T Nomura
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 0425, USA
J Infect Dis 183:1653-61. 2001..vivax gene. This is evidence that the molecular events underlying P. vivax CQR differ from those in P. falciparum...Reliability of antimalarial sensitivity tests depends on drug mechanisms of action
Sharon Wein
UMR 5235, Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS Universite Montpellier II, Case 107, Place Eugene Bataillon, 34095 Montpellier, Cedex 05, France
J Clin Microbiol 48:1651-60. 2010..Some of them might not detect the antimalarial potential of new classes of compounds with innovative modes of action, which subsequently could become promising new antimalarial drugs...A chemical genomic analysis of decoquinate, a Plasmodium falciparum cytochrome b inhibitor
Tae Gyu Nam
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
ACS Chem Biol 6:1214-22. 2011..The basis for this difference was revealed by molecular docking studies, in which both of these inhibitors were shown to have distinctly different modes of binding within the ubiquinol-binding site of cytochrome b...The patterns of mutation and amplification of Plasmodium falciparum pfcrt and pfmdr1 genes in Thailand during the year 1988 to 2003
Mathirut Mungthin
Department of Parasitology, Phramongkutklao College of Medicine, Ratchathewi, Bangkok, Thailand
Parasitol Res 107:539-45. 2010..The prominent pattern of pfmdr1 at codons 86/184/1034/1042/1246 was NFSND, with prevalence increasing from 40% to 95% during the 10-year period...Isothermal microcalorimetry to study drugs against Schistosoma mansoni
Theresia Manneck
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, P O Box, CH 4002 Basel, Switzerland
J Clin Microbiol 49:1217-25. 2011..IMC is a useful tool for antischistosomal drug discovery that should be further validated. In addition, our data support the use of NTS in in vitro antischistosomal drug assays...Leishmanicidal activity of a supercritical fluid fraction obtained from Tabernaemontana catharinensis
Deivid Costa Soares
Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941 590, Brazil
Parasitol Int 56:135-9. 2007..Importantly, this method preserved the alkaloid properties associated with inhibition of Leishmania growth in macrophages without toxicity to host cells...Limited ability of Plasmodium falciparum pfcrt, pfmdr1, and pfnhe1 polymorphisms to predict quinine in vitro sensitivity or clinical effectiveness in Uganda
Frederick N Baliraine
University of California, San Francisco, CA 94143 0811, USA
Antimicrob Agents Chemother 55:615-22. 2011..Our data suggest that quinine sensitivity is a complex trait and that known polymorphisms in pfcrt, pfmdr1, and pfnhe1, while associated with quinine sensitivity, are not robust markers for quinine resistance...Anti-Trichomonas vaginalis activity of saponins from Quillaja, Passiflora, and Ilex species
Tábitha Dahmer Rocha
Laboratório de Fitoquímica e Síntese Orgânica, Departamento de Produção de Matéria Prima, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, Av Ipiranga 2752, 90610 000, Porto Alegre, Rio Grande do Sul, Brazil
Parasitol Res 110:2551-6. 2012..vaginalis activity (MIC = 0.025%). In addition, all samples induced erythrocyte lysis and LDH release. As far as we know, this is the first report demonstrating the potential anti-T. vaginalis activity of these saponins...SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis
Robert T Jacobs
SCYNEXIS, Inc, Research Triangle Park, North Carolina, USA
PLoS Negl Trop Dis 5:e1151. 2011..We have discovered and optimized a novel class of small-molecule boron-containing compounds, benzoxaboroles, to identify SCYX-7158 as an effective, safe and orally active treatment for HAT...Anti-infective potential of natural products: how to develop a stronger in vitro 'proof-of-concept'
Paul Cos
Laboratory for Microbiology, Parasitology and Hygiene LMPH, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium
J Ethnopharmacol 106:290-302. 2006....Chloroquine resistant vivax malaria in a pregnant woman on the western border of Thailand
Marcus J Rijken
Shoklo Malaria Research Unit, PO Box 46 Mae Sot, Tak 63110, Thailand
Malar J 10:113. 2011..vivax. This is the first clinically and laboratory confirmed case of two high-grade CQ resistant vivax parasite strains from Thailand...Cost-effectiveness of malaria diagnostic methods in sub-Saharan Africa in an era of combination therapy
Samuel Shillcutt
Andean Health and Development Saludesa, Quito, Ecuador
Bull World Health Organ 86:101-10. 2008..To evaluate the relative cost-effectiveness in different sub-Saharan African settings of presumptive treatment, field-standard microscopy and rapid diagnostic tests (RDTs) to diagnose malaria...Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium
Tatiana Shioji Tiuman
Departamento de Analises Clinicas, Universidade Estadual de Maringa, Bloco I 90 Sala 123 CCS, Av Colombo 5790, BR 87020 900, Maringa, Parana, Brazil
Antimicrob Agents Chemother 49:176-82. 2005..These results provide new perspectives on the development of novel drugs with leishmanicidal activities obtained from natural products...Monitoring of clinical efficacy and in vitro sensitivity of Plasmodium vivax to chloroquine in area along Thai Myanmar border during 2009-2010
Poonuch Muhamad
Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Thailand
Malar J 10:44. 2011..vivax in other parts of the world, emphasize the need for closely and continuously monitoring clinical efficacy in conjunction with in vitro sensitivity of P. vivax isolates...Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness
Els Torreele
Drugs for Neglected Diseases Initiative DNDi, Geneva, Switzerland
PLoS Negl Trop Dis 4:e923. 2010..To complete the preclinical development and meet the regulatory requirements before initiating human trials, the anti-parasitic properties and the pharmacokinetic, metabolic and toxicological profile of fexinidazole have been assessed...In vitro sensitivity testing of Leishmania clinical field isolates: preconditioning of promastigotes enhances infectivity for macrophage host cells
Raquel Inocêncio da Luz
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Antwerp University, Antwerp, Belgium
Antimicrob Agents Chemother 53:5197-203. 2009..In conclusion, the proposed conditioning protocol further contributes toward a more standardized laboratory model for evaluation of the drug sensitivities of field isolates...Artesunate misuse and Plasmodium falciparum malaria in traveler returning from Africa
Dea Shahinas
University of Toronto, Toronto, Ontario, Canada
Emerg Infect Dis 16:1608-10. 2010..Isolates had an elevated 50% inhibitory concentration to artemisinin, artesunate, and artemether, compared with that of other African isolates. Inappropriate use of artemisinin derivatives can reduce P. falciparum susceptibility...Acridinediones: selective and potent inhibitors of the malaria parasite mitochondrial bc1 complex
Giancarlo A Biagini
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
Mol Pharmacol 73:1347-55. 2008..falciparum bc(1) Q(o). Dihydroacridinediones represent an entirely new class of bc(1) inhibitors and the potential of these compounds as novel antimalarial drugs is discussed...In vitro activities of quinine and other antimalarials and pfnhe polymorphisms in Plasmodium isolates from Kenya
John Okombo
Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108 Kilifi, Kenya
Antimicrob Agents Chemother 54:3302-7. 2010..Two DNNND repeats combined with the pfmdr1-86 mutation could be used as an indicator of reduced susceptibility to quinine...Dynamics of malaria drug resistance patterns in the Amazon basin region following changes in Peruvian national treatment policy for uncomplicated malaria
David J Bacon
Parasitology Program, Naval Medical Research Center Detachment, Lima, Peru
Antimicrob Agents Chemother 53:2042-51. 2009..Importantly, this study demonstrates that the Peruvian triple mutant Pfdhps genotypes are very similar to those found in other parts of South America...Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi
R F S Menna-Barreto
Laboratorio de Biologia Celular, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil
Parasitology 136:499-510. 2009..However, there are other pathways occurring concomitantly with variable intensities, justifying the need to detail the molecular features involved...An in vitro larval motility assay to determine anthelmintic sensitivity for human hookworm and Strongyloides species
A C Kotze
Commonwealth Scientific and Industrial Research Organisation Livestock Industries, St Lucia, Queensland 4067, Australia
Am J Trop Med Hyg 71:608-16. 2004....Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
Isabel D Ferreira
Centro de Malária e Outras Doenças Tropicais IHMT UEI Biologia Molecular UEI Malária, Lisbon, Portugal
Trop Med Int Health 13:199-207. 2008....Plasmodium falciparum drug resistance in Madagascar: facing the spread of unusual pfdhfr and pfmdr-1 haplotypes and the decrease of dihydroartemisinin susceptibility
Valérie Andriantsoanirina
Unité de Recherche sur le Paludisme, Institut Pasteur de Madagascar, Antananarivo, Madagascar
Antimicrob Agents Chemother 53:4588-97. 2009..In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required...In vitro susceptibilities of Leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific differences
Marieke Vermeersch
Laboratory for Microbiology, Parasitology, and Hygiene LMPH, Faculty of Pharmaceutical, Biomedical, and Veterinary Sciences, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium
Antimicrob Agents Chemother 53:3855-9. 2009..Axenic systems can be recommended only for compounds for which no cellular mechanisms are involved, for example, amphotericin B and miltefosine...Development of a modified MTT assay for screening antimonial resistant field isolates of Indian visceral leishmaniasis
Avijit Dutta
Dept of Immunobiology, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Kolkata 700 032, India
Parasitol Int 54:119-22. 2005..Considering the growing problem of antimonial unresponsiveness in the Indian subcontinent, this modified MTT assay is a useful tool for Leishmania research...Plasmodium vivax: isotopic, PicoGreen, and microscopic assays for measuring chloroquine sensitivity in fresh and cryopreserved isolates
Varakorn Kosaisavee
Faculty of Public Health, Mahidol University, Bangkok, Thailand
Exp Parasitol 114:34-9. 2006..Future efforts should focus on further development of high throughput assays such as the PicoGreen assay as described in this study...In vitro activity of chloroquine, quinine, mefloquine and halofantrine against Gabonese isolates of Plasmodium falciparum
Jérôme Mezui Me Ndong
Centre International de Recherches Medicales de Franceville, Gabon, Central Africa
Trop Med Int Health 8:25-9. 2003..To determine the in vitro activity of antimalarial drugs against isolates of Plasmodium falciparum in Gabon...Discovery of potent small-molecule inhibitors of multidrug-resistant Plasmodium falciparum using a novel miniaturized high-throughput luciferase-based assay
Edinson Lucumi
Department of Chemical and Biomolecular Engineering and Penn Center for Molecular Discovery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Antimicrob Agents Chemother 54:3597-604. 2010..Ultimately, this study may provide new probes to understand the molecular details of the malaria life cycle and to identify new antimalarials...Activity of novel nicotinic anthelmintics in cut preparations of Caenorhabditis elegans
Elizabeth Ruiz-Lancheros
Institute of Parasitology, McGill University, Macdonald Campus, 21111 Lakeshore Road, Ste Anne de Bellevue, Quebec, Canada H9X 3V9
Int J Parasitol 41:455-61. 2011..The permeability properties of the C. elegans cuticle may be more restrictive than those of adult parasites, calling into question primary anthelmintic screening strategies that rely on this model organism...Dynamics of pfcrt alleles CVMNK and CVIET in chloroquine-treated Sudanese patients infected with Plasmodium falciparum
Nahla B Gadalla
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK
Malar J 9:74. 2010....Plasmodium falciparum resistance to cytocidal versus cytostatic effects of chloroquine
Michelle F Paguio
Department of Chemistry, Georgetown University, Washington, DC 20057, United States
Mol Biochem Parasitol 178:1-6. 2011..falciparum. The results have important implications for development of new antimalarial drugs and for fully defining the genetic loci that confer clinically relevant antimalarial drug resistance phenomena...Synthesis and in vitro and in vivo evaluation of antimalarial polyamines
Lydia P P Liew
School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
Eur J Med Chem 69:22-31. 2013..3-9.5 nM, and selectivity indices (SI) of 42,300 to 4880. In vivo evaluation of three analogues against Plasmodium berghei was undertaken, with one demonstrating a modest 27.9% reduction in parasitaemia...Phenotypic changes in artemisinin-resistant Plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition
Franka Teuscher
Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia
Antimicrob Agents Chemother 56:428-31. 2012..Our results demonstrate that the AL resistance phenotype has (i) decreased sensitivity of mature-stage parasites, (ii) decreased sensitivity of the ring stage to the induction of dormancy, and (iii) a faster recovery from dormancy...Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum field isolates
Wiriya Rutvisuttinunt
Department of Immunology and Medicine, US Army Medical Corps, Armed Forces Research Institute of Medical Sciences USAMC AFRIMS, Bangkok, Thailand
Malar J 11:325. 2012..Although in vitro anti-malarial susceptibility tests are widely used, uncertainties remain regarding interpretation of P. falciparum field isolate values...Establishment of a panel of reference Trypanosoma evansi and Trypanosoma equiperdum strains for drug screening
K Gillingwater
Parasite Chemotherapy, Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel, Switzerland
Vet Parasitol 148:114-21. 2007..This panel of characterised strains with known drug sensitivities and resistances will be of great value for the screening of new active compounds, in comparison with the four standard drugs currently available...In vitro and in vivo interaction of synthetic peroxide RBx11160 (OZ277) with piperaquine in Plasmodium models
Christopher Snyder
Swiss Tropical Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
Exp Parasitol 115:296-300. 2007..1) was identified, suggesting that a RBx11160-piperaquine combination therapy in humans should allow each molecule to exert its full antimalarial effect...Antileishmanial activity of Eugenol-rich essential oil from Ocimum gratissimum
Tania Ueda-Nakamura
Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringa, Brazil
Parasitol Int 55:99-105. 2006..The essential oil showed no cytototoxic effects against mammalian cells. This set of results suggests that O. gratissimum essential oil and its compounds could be used as sources for new antileishmanial drugs...Ex vivo drug sensitivity profiles of Plasmodium falciparum field isolates from Cambodia and Thailand, 2005 to 2010, determined by a histidine-rich protein-2 assay
Stuart D Tyner
Department of Immunology and Medicine, US Army Medical Corps, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
Malar J 11:198. 2012....Differential association of Plasmodium falciparum Na+/H+ exchanger polymorphism and quinine responses in field- and culture-adapted isolates of Plasmodium falciparum
Stéphane Pelleau
Institut Pasteur de Dakar, BP 220 Dakar, Senegal
Antimicrob Agents Chemother 55:5834-41. 2011..However, we do not exclude the possibility that in particular settings, Pfnhe-1 polymorphism can be used as a molecular marker for surveillance of quinine resistance...A high-throughput assay for the identification of drugs against late-stage Plasmodium falciparum gametocytes
Christopher L Peatey
Malaria Biology Laboratory, Queensland Institute of Medical Research, 300 Herston Rd, Herston, Brisbane, Australia
Mol Biochem Parasitol 180:127-31. 2011..Here we describe the development of a robust and simple assay that is amenable to a high throughput format for the discovery of new antigametocyte drugs...Flow cytometry for the evaluation of anti-plasmodial activity of drugs on Plasmodium falciparum gametocytes
Severine Chevalley
Université de Toulouse 3, LPSNPR Laboratoire pharmacochimie des substances naturelles et pharmacophores redox, Toulouse, France
Malar J 9:49. 2010..Gametocytes were treated for 48 h with different drug concentrations and the gametocytaemia was then determined by flow cytometry and compared with visual estimation by microscopy...In vitro activity of ferroquine (SSR 97193) against Plasmodium falciparum isolates from the Thai-Burmese border
Marion Barends
Shoklo Malaria Research Unit, Mae Sot, Tak, Thailand
Malar J 6:81. 2007..The aim of the present study was to investigate the activity of ferroquine against P. falciparum isolates from an area with a known high multi-drug resistance rate...Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs
Aurélie Pascual
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Recherche Biomédicale des Armées Antenne de Marseille, Marseille, France
Malar J 10:8. 2011..The Genbag® system associated with the atmospheric generators for capnophilic bacteria Genbag CO2® was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions...Comparison of novel and existing tools for studying drug sensitivity against the hookworm Ancylostoma ceylanicum in vitro
Lucienne Tritten
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH 4002 Basel, Switzerland
Parasitology 139:348-57. 2012..Among all assays tested the xCELLigence System performed best on adult worms as the test was accurate, simple, required a minimal number of worms and offered the possibility for conducting a medium-throughput screening...Antimalarial bromotyrosine derivatives from the Australian marine sponge Hyattella sp
Xinzhou Yang
Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia
J Nat Prod 73:985-7. 2010..4 and 0.87 microM, respectively, while 1 showed 98% inhibition at 40 microM against the chloroquine-resistant (Dd2) strain of P. falciparum...In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene: the absence of association in clinical isolates from the Republic of Congo
Sebastien Briolant
Unite de Parasitologie, Unite Mixte de Recherche 6236, Institut de Recherche Biomédicale des Armées Antenne de Marseille, Marseille, France
Malar J 10:37. 2011..In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa...Dose-response assay templates for in vitro assessment of resistance to benzimidazole and nicotinic acetylcholine receptor agonist drugs in human hookworms
Andrew C Kotze
CSIRO Livestock Industries, St Lucia, Brisbane, Australia
Am J Trop Med Hyg 81:163-70. 2009..These assays will have immediate applicability in monitoring for the emergence of drug resistance in human hookworm populations...Evaluation of Turkish seaweeds for antiprotozoal, antimycobacterial and cytotoxic activities
Sevda Süzgeç-Selçuk
Department of Pharmacognosy, Faculty of Pharmacy, University of Istanbul, Istanbul, Turkey
Phytother Res 25:778-83. 2011..This is the second study investigating the antiprotozoal activities of Turkish marine algae and identifies Dasya pedicellata, an understudied algal species, as a candidate for further studies...Mining a cathepsin inhibitor library for new antiparasitic drug leads
Kenny K H Ang
The Small Molecule Discovery Center, University of California San Francisco, San Francisco, California, United States of America
PLoS Negl Trop Dis 5:e1023. 2011..The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts...Amplification of Plasmodium falciparum multidrug resistance gene 1 in isolates from Gabon
Anne Catrin Uhlemann
Department of Cellular and Molecular Medicine, Infectious Diseases Group, St George s Hospital Medical School, London, UK
J Infect Dis 192:1830-5. 2005..Nevertheless, the detection of multicopy pfmdr1 in African parasites suggests a high potential for rapid selection for resistance, implying that mefloquine use in Africa should be considered only as part of combination therapy...Antiretrovirals as antimalarial agents
Tina S Skinner-Adams
Malaria Biology Laboratory, Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and School of Population Health, University of Queensland, St Lucia, Queensland, Australia
J Infect Dis 190:1998-2000. 2004..These findings are particularly important in light of both the high rate of malaria and HIV-1 coinfection in sub-Saharan Africa and the effort to employ highly active antiretroviral therapy in these regions...A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue
Takeshi Q Tanaka
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, United States
Mol Biochem Parasitol 177:160-3. 2011..01). Six anti-malarials were also tested and at 10 μM only primaquine and dihydroartemisinin (DHA) had gametocytocidal activity. This new assay provides an important tool to efficiently screen compounds for gametocytocidal activity...Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches
Eric H Ekland
Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, 701 W 168th St, New York, NY 10032, USA
FASEB J 25:3583-93. 2011..These assays provide the foundation for high-throughput campaigns to identify novel chemotypes for combination therapies to treat multidrug-resistant malaria...Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents
David J Johnson
Molecular and Biochemical Parasitology Group, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom
Mol Cell 15:867-77. 2004..Evidence for the presence of this mutation in a Southeast Asian isolate supports the argument for a broad role for PfCRT in determining levels of susceptibility to structurally diverse antimalarials...Potent antimalarial 4-pyridones with improved physico-chemical properties
José M Bueno
Tres Cantos Medicines Development Campus, Diseases of the Developing World, GlaxoSmihKline, C Severo Ochoa, 2, 28760 Tres Cantos, Madrid, Spain
Bioorg Med Chem Lett 21:5214-8. 2011....Changes in susceptibility of Plasmodium falciparum to artesunate in vitro in Yunnan Province, China
Henglin Yang
Yunnan Institute of Parasitic Diseases, Simao, Yunnan Province 665000, P R China
Trans R Soc Trop Med Hyg 97:226-8. 2003..The results suggest that P. falciparum is generally susceptible to artemisinin derivatives but indicate a reduction in susceptibility during the study period in areas where the drugs have been used for a long time...Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax
R Suwanarusk
International Health Division, Menzies School of Health Research, Darwin, Australia
J Infect Dis 198:1558-64. 2008..Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia...Plasmodium falciparum Na+/H+ exchanger 1 transporter is involved in reduced susceptibility to quinine
Maud Henry
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Medecine Tropicale du Service de Sante des Armees, UMR 6236, Allée du Médecin Colonel Jamot, Parc le Pharo, BP 60109, 13262 Marseille cedex 07, Marseille, France
Antimicrob Agents Chemother 53:1926-30. 2009..falciparum susceptibility to QN. The validity of the markers should be further supported by analyzing more isolates...In vitro activity of pyrvinium pamoate against Entamoeba histolytica and Giardia intestinalis using radiolabelled thymidine incorporation and an SYBR Green I-based fluorescence assay
Autumn S Downey
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
J Antimicrob Chemother 64:751-4. 2009..To assess the in vitro activity of the FDA-approved antihelminthic drug pyrvinium pamoate against Entamoeba histolytica and Giardia intestinalis...In vivo antimalarial activity of essential oils from Cymbopogon citratus and Ocimum gratissimum on mice infected with Plasmodium berghei
F Tchoumbougnang
Department of Biochemistry, Faculty of Science, University of Douala, Douala, Cameroon
Planta Med 71:20-3. 2005..1 %, 81.7 % and 86.6 %. The corresponding values for the oil of O. gratissimum at the same concentrations were 55.0 %, 75.2 % and 77.8 %, respectively. Chloroquine (10 mg/kg of mouse, positive control) had a suppressive activity of 100 %...Clinical-parasitological response and in-vitro sensitivity of Plasmodium vivax to chloroquine and quinine on the western border of Thailand
Oumaporn Tasanor
Pharmacology and Toxicology Unit, Faculty of Allied Health Sciences, Thammasat University Rangsit Campus, Paholyothin Road, Pathumthani 12121, Thailand
Trans R Soc Trop Med Hyg 100:410-8. 2006....Quinine-resistant malaria in traveler returning from Senegal, 2007
Bruno Pradines
Institut de Medecine Tropicale du Service de Sante des Armees, Marseille, France
Emerg Infect Dis 16:546-8. 2010..Clinical quinine failure was associated with a 50% inhibitory concentration of 829 nmol/L. Increased vigilance is required during treatment follow-up...Molecular detection of benzimidazole resistance in Haemonchus contortus using real-time PCR and pyrosequencing
G von Samson-Himmelstjerna
Institute for Parasitology, University of Veterinary Medicine Hannover, Bunteweg 17, 30559 Hannover, Germany
Parasitology 136:349-58. 2009..Thus, they provide a realistic option for routine molecular resistance testing on farms...High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1
H A Babiker
Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh, EH9 3JT, Scotland, United Kingdom
J Infect Dis 183:1535-8. 2001..A significant association between pfmdr1-Y86 and pfcrt-T76 was apparent among resistant isolates, which suggests a joint action of the 2 genes in high-level chloroquine resistance...In vitro activity of artemisone compared with artesunate against Plasmodium falciparum
Michael Ramharter
Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon
Am J Trop Med Hyg 75:637-9. 2006..14 nmol/L, EC90 = 2.55 nmol/L) than artesunate against fresh Plasmodium falciparum isolates from Gabon and a high-activity correlation indicates a shared drug target...Turkish freshwater and marine macrophyte extracts show in vitro antiprotozoal activity and inhibit FabI, a key enzyme of Plasmodium falciparum fatty acid biosynthesis
I Orhan
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, TR 06330 Ankara, Turkey
Phytomedicine 13:388-93. 2006..falciparum FabI inhibitors from aquatic and marine macrophytes...A comparative study of a flow-cytometry-based assessment of in vitro Plasmodium falciparum drug sensitivity
Stephan Karl
School of Physics, M013, The University of Western Australia, 35 Stirling Highway, Crawley WA 6009, Australia
Malar J 8:294. 2009..falciparum lactate dehydrogenase assay, the tritiated hypoxanthine incorporation assay, a previously described Sybr Green based plate reader assay and light microscopy...In vitro assays for evaluation of drug activity against Leishmania spp
Luciana Fumarola
Department of Internal Medicine, Immunology and Infectious Diseases, Microbiology and Immunology Section, University of Bari, Medical School, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy
Res Microbiol 155:224-30. 2004..Reliable and simple in vitro models are required for large-scale initial screenings. In this review different methods for in vitro evaluation of drug activity against Leishmania spp. are summarized...Assessment of malaria in vitro drug combination screening and mixed-strain infections using the malaria Sybr green I-based fluorescence assay
Edgie Mark A Co
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Antimicrob Agents Chemother 53:2557-63. 2009..In conclusion, the MSF assay allows for reliable antimalarial drug combination screening and provides an important method to discern between homogenous and heterogeneous parasite populations...Recovery of chloroquine sensitivity and low prevalence of the Plasmodium falciparum chloroquine resistance transporter gene mutation K76T following the discontinuance of chloroquine use in Malawi
Toshihiro Mita
Department of International Affairs and Tropical Medicine, Tokyo Women s Medical University School of Medicine, Tokyo, Japan
Am J Trop Med Hyg 68:413-5. 2003..29). Withdrawal of the use of chloroquine appears to have resulted in the recovery of chloroquine efficacy and a reduction in the prevalence of K76T. However, other polymorphisms are also expected to contribute to resistance...
Research Grants
- TS PROPHYLAXIS AND DRUG-RESISTANT MALARIA IN MALAWICHRISTOPHER PLOWE; Fiscal Year: 2007..unreadable] [unreadable]..
- Pre-Clinical Development of Natural Product Analogues as Antimalarial AgentsShuren Zhu; Fiscal Year: 2007..Investigational new drug (IND) application will then be filed with FDA. Radix Pharmaceuticals has strategic alliance with commercial partners for Phase III development. [unreadable] [unreadable] [unreadable]..
- Development of Natural Product as Antimalarial AgentShuren Zhu; Fiscal Year: 2007..Investigational new drug (IND) application will then be filed with FDA. [unreadable] [unreadable] [unreadable]..
- Randomized, controlled trial of daily trimethoprim-sulfamethoxazole or weekly chlCHRISTOPHER PLOWE; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- TS PROPHYLAXIS AND DRUG-RESISTANT MALARIA IN MALAWICHRISTOPHER PLOWE; Fiscal Year: 2003....
- DRUG-RESISTANT MALARIA IN MALAWICHRISTOPHER PLOWE; Fiscal Year: 2002..abstract_text> ..
- Plasmodium Falciparum Metal MetabolismDavid Sullivan; Fiscal Year: 2009..Plasmodium parasitism provides a comparison of "simple" erythrocyte cell to more complex infected cell. ..
- TOTAL SYNTHESIS OF AZADIRACHTINK Nicolaou; Fiscal Year: 2008..The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology. ..
- TOTAL SYNTHESIS OF NATURAL PRODUCTSK Nicolaou; Fiscal Year: 2002..3] sigmatropic rearrangement and a radical based ring closure to form the bicyclic skeleton. ..
- Host Polymorphisms and Uncomplicated MalariaSunil Parikh; Fiscal Year: 2008..Parikh will be able to utilize modern molecular epidemiology techniques to investigate human genetic factors underlying susceptibility to malaria and he will be well equipped for a career in academic research. ..
- Role of iNOS and CAT-2 in defense against CP infectionJody Gookin; Fiscal Year: 2006..parvum infection. The PI is presently in the 3rd year of a 5-year K08 from NIDDK. These studies are anticipated to generate key preliminary data for the PI's first R01 application ..
- SYNTHESIS OF ANTICANCER AGENTSK C Nicolaou; Fiscal Year: 2010..abstract_text> ..
- TOTAL SYNTHESIS OF APOPTOLIDINK Nicolaou; Fiscal Year: 2004..The proposed work is expected to have significant impact in the area of cancer chemotherapy and should provide enabling technologies and tools for biology and medicine. ..
- Enabling Technologies for Combinatorial ChemistryK Nicolaou; Fiscal Year: 2005..abstract_text> ..
- Novel Tetracycyclines as Antimalarial DrugsMichael Draper; Fiscal Year: 2005..We anticipate that at the end of the Phase II period we will have identified several candidate molecules that are suitable for pre-clinical development. ..
- Sterol Biosynthesis in Trypanosomatid ParasitesFrederick Buckner; Fiscal Year: 2004..The drugs discovered in this research program will hopefully provide better future treatment for patients with these devastating diseases. ..
- IMMUNODOMINANT TARGETS OF CMI TO CRYPTOSPORIDIUMJan Mead; Fiscal Year: 2009..This will be accomplished by immunizing mice with a DNA construct of these antigens, assessing their ability to elicit immune responses, and challenging mice with C. parvum to determine the degree of protection achieved. ..
- THE PHYSIOLOGY OF DRUG RESISTANT MALARIAPAUL ROEPE; Fiscal Year: 2009..Knowledge gained during this research will significantly expand our understanding of malarial parasite physiology and antimalarial drug resistance. ..
- Chemoprevention/Therapy Using Non-Calcemic Vitamin DGary Posner; Fiscal Year: 2006..Collectively, these studies will provide important structure- activity insights into the cancer chemoprotective and chemotherapeutic actions and molecular biology of vitamin D3 analogs. ..
- SURFACE ANTIGENS OF TREPONEMA PALLIDUMWesley Van Voorhis; Fiscal Year: 2008..Finally, these studies will help define the protective immune response that results after immunization with Tp92 as well as the immune response to Tp92 that occurs during infection. [unreadable] [unreadable]..
- Molecular epidemiology of drug resistant malariaMIRIAM LAUFER; Fiscal Year: 2008..abstract_text> ..
- NO& Epithelial Repair in CryptosporidiosisJody Gookin; Fiscal Year: 2006..abstract_text> ..
- A randomized, controlled clinical trial of chloroquine as chemoprophylaxis versusMIRIAM LAUFER; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Inhibition of Alzheimer's Beta-Amyloid Fibril FormationDuy Hua; Fiscal Year: 2009..However, soluble oligomeric Abeta showed high neuronal toxicity. Inhibition of the formation of these toxic soluble Abeta oligomers would provide therapeutics for AD. ..
- TRIOXANES FOR CHEMOTHERAPY OF MALARIA AND CANCERGary Posner; Fiscal Year: 2005....
- Topoisomerases: Target for Antitrypanosomal TherapyTheresa Shapiro; Fiscal Year: 2006..Compounds that appear most promising will be evaluated in mice. These studies take a multi-faceted, rational, and tangible approach to the development of much-needed new anti-trypanosomal chemotherapy. ..