{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T10:00:41Z","timestamp":1777111241457,"version":"3.51.4"},"reference-count":97,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["603240"],"award-info":[{"award-number":["603240"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite important advances in the reduction or disappearance of HAT cases, AAT represents a risky reservoir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.<\/jats:p>","DOI":"10.3390\/microorganisms10071298","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:07:02Z","timestamp":1656374822000},"page":"1298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Current Treatments to Control African Trypanosomiasis and One Health Perspective"],"prefix":"10.3390","volume":"10","author":[{"given":"Alberto","family":"Venturelli","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-7106","authenticated-orcid":false,"given":"Lorenzo","family":"Tagliazucchi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Doctorate School in Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, 41125 Modena, Italy"}]},{"given":"Clara","family":"Lima","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Group, Institute of Research and Innovation in Health, University of Porto, 4099-002 Porto, Portugal"},{"name":"Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3717-1420","authenticated-orcid":false,"given":"Federica","family":"Venuti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9093-2386","authenticated-orcid":false,"given":"Giulia","family":"Malpezzi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-1635","authenticated-orcid":false,"given":"George E.","family":"Magoulas","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece"}]},{"given":"Nuno","family":"Santarem","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Group, Institute of Research and Innovation in Health, University of Porto, 4099-002 Porto, Portugal"},{"name":"Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3369-5393","authenticated-orcid":false,"given":"Theodora","family":"Calogeropoulou","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 11635 Athens, Greece"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-6087","authenticated-orcid":false,"given":"Anabela","family":"Cordeiro-da-Silva","sequence":"additional","affiliation":[{"name":"Host-Parasite Interactions Group, Institute of Research and Innovation in Health, University of Porto, 4099-002 Porto, Portugal"},{"name":"Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-5402","authenticated-orcid":false,"given":"Maria Paola","family":"Costi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.brainresbull.2018.05.022","article-title":"Human African Trypanosomiasis: How Do the Parasites Enter and Cause Dysfunctions of the Nervous System in Murine Models?","volume":"145","author":"Masocha","year":"2019","journal-title":"Brain Res. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1645\/0022-3395(2001)087[0001:IAARTA]2.0.CO;2","article-title":"Innate and Acquired Resistance to African Trypanosomiasis","volume":"87","author":"Black","year":"2001","journal-title":"J. Parasitol."},{"key":"ref_3","unstructured":"WHO (2021). Elimination of Human African Trypanosomiasis as Public Health Problem. Wkly. Epidemiol. Rec., 96, 176."},{"key":"ref_4","unstructured":"WHO (2022, March 08). Human African Trypanosomiasis (Sleeping Sickness). Available online: https:\/\/www.who.int\/data\/gho\/data\/themes\/topics\/human-african-trypanosomiasis."},{"key":"ref_5","first-page":"100309","article-title":"Prevalence of hemoprotozoan parasites in small ruminants along a human-livestock-wildlife interface in western Uganda","volume":"17","author":"Kasozi","year":"2019","journal-title":"Vet. Parasitol. Reg. Stud. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.vetpar.2016.05.003","article-title":"Combatting African Animal Trypanosomiasis (AAT) in Livestock: The Potential Role of Trypanotolerance","volume":"225","author":"Yaro","year":"2016","journal-title":"Vet. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13071-022-05190-1","article-title":"A Review on the Diagnosis of Animal Trypanosomoses","volume":"15","author":"Desquesnes","year":"2022","journal-title":"Parasites Vectors"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.actatropica.2017.08.032","article-title":"Animal African Trypanosomiasis in Nigeria: A Long Way from Elimination\/Eradication","volume":"176","author":"Isaac","year":"2017","journal-title":"Acta Trop."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human African Trypanosomiasis","volume":"390","author":"Cecchi","year":"2017","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fimmu.2019.00039","article-title":"Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis","volume":"10","author":"Kennedy","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_11","unstructured":"WHO (2022, March 25). Number of New Reported Cases of Human African Trypanosomiasis (T. b. rhodesiense). Available online: https:\/\/www.who.int\/data\/gho\/data\/indicators\/indicator-details\/gho\/number-of-new-reported-cases-of-human-african-trypanosomiasis-(t-b-rhodesiense)."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.coi.2021.02.007","article-title":"Genetic and Immunological Basis of Human African Trypanosomiasis","volume":"72","author":"Pays","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4103\/0972-9062.213454","article-title":"Effect of Ivermectin on Trypanosoma brucei brucei in Experimentally Infected Mice","volume":"49","author":"Udensi","year":"2012","journal-title":"J. Vector Borne Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Checchi, F., Felipe, J.A.N., Haydon, D.T., Chandramohan, D., and Chappuis, F. (2008). Estimates of the Duration of the Early and Late Stage of Gambiense Sleeping Sickness. BMC Infect. Dis., 8.","DOI":"10.1186\/1471-2334-8-16"},{"key":"ref_15","unstructured":"CDC (2022, March 30). Diseases: Neglected Tropical Diseases, Available online: https:\/\/www.cdc.gov\/globalhealth\/ntd\/index.html."},{"key":"ref_16","unstructured":"European Medicine Agency (EMA), and Committee for Veterinary Medicinal Products (2022). Advice on the Designation of Antimicrobials or Groups of Antimicrobials Reserved for Treatment of Certain Infections in Humans."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chitanga, S., Marcotty, T., Namangala, B., Van Den Bossche, P., Van Den Abbeele, J., and Delespaux, V. (2011). High Prevalence of Drug Resistance in Animal Trypanosomes without a History of Drug Exposure. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001454"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dickie, E., Giordani, F., Gould, M.K., M\u00e4ser, P., Burri, C., Mottram, J.C., Rao, S.P.S., and Barrett, M.P. (2020). New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story. Trop. Med. Infect. Dis., 5.","DOI":"10.3390\/tropicalmed5010029"},{"key":"ref_19","first-page":"535","article-title":"Drugs for Protozoal Infections other than Malaria","volume":"42","author":"Bennett","year":"2020","journal-title":"Mandell, Douglas, and Bennett\u2019s Principles and Practice of Infectious Diseases"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Thomas, J.A., Baker, N., Hutchinson, S., Dominicus, C., Trenaman, A., Glover, L., Alsford, S., and Horn, D. (2018). Insights into Antitrypanosomal Drug Mode-of-Action from Cytology-Based Profiling. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006980"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.pt.2012.12.005","article-title":"Drug Resistance in African Trypanosomiasis: The Melarsoprol and Pentamidine Story","volume":"29","author":"Baker","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/200285a0","article-title":"Prophylactic Activity of Suramin Complexes in \u2018Surra\u2019 (Trypanosoma evansi)","volume":"200","author":"Gill","year":"1963","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8331","DOI":"10.1074\/jbc.RA120.012355","article-title":"Suramin Exposure Alters Cellular Metabolism and Mitochondrial Energy Production in African Trypanosomes","volume":"295","author":"Zoltner","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"737159","DOI":"10.3389\/fcell.2021.737159","article-title":"Novel Trypanocidal Inhibitors that Block Glycosome Biogenesis by Targeting PEX3\u2013PEX19 Interaction","volume":"9","author":"Li","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/ana.21429","article-title":"The Continuing Problem of Human African Trypanosomiasis (Sleeping Sickness)","volume":"64","author":"Kennedy","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1172\/JCI200421052","article-title":"Human African Trypanosomiasis of the CNS: Current Issues and Challenges","volume":"113","author":"Kennedy","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S1474-4422(12)70296-X","article-title":"Clinical Features, Diagnosis, and Treatment of Human African Trypanosomiasis (Sleeping Sickness)","volume":"12","author":"Kennedy","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_28","unstructured":"Davies, L.E., and Kennedy, P.G.E. (2000). Neurological Aspects of Human African Trypanosomiasis. Infectious Diseases of the Nervous System, Butterworth-Heinemann."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1179\/2047773213Y.0000000105","article-title":"A Current Analysis of Chemotherapy Strategies for the Treatment of Human African Trypanosomiasis","volume":"107","author":"Babokhov","year":"2013","journal-title":"Pathog. Glob. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.ijpara.2007.05.007","article-title":"Melarsoprol- and Pentamidine-Resistant Trypanosoma brucei rhodesiense Populations and Their Cross-Resistance","volume":"37","author":"Bernhard","year":"2007","journal-title":"Int. J. Parasitol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1093\/jac\/dkv376","article-title":"Nitroheterocyclic Drug Resistance Mechanisms in Trypanosoma brucei","volume":"71","author":"Wyllie","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vincent, I.M., Creek, D., Watson, D.G., Kamleh, M.A., Woods, D.J., Wong, P.E., Burchmore, R.J., and Barrett, M.P. (2010). A Molecular Mechanism for Eflornithine Resistance in African Trypanosomes. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001204"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1136\/bmj.39485.592674.BE","article-title":"Safety and Effectiveness of First Line Eflornithine for Trypanosoma brucei gambiense Sleeping Sickness in Sudan: Cohort Study","volume":"336","author":"Priotto","year":"2008","journal-title":"BMJ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"939","DOI":"10.2174\/1389557517666170315145410","article-title":"Trypanothione Reductase: A Target for the Development of Anti-Trypanosoma cruzi Drugs","volume":"17","author":"Vazquez","year":"2017","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S1473-3099(19)30612-7","article-title":"New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: Substantial changes for clinical practice","volume":"20","author":"Lindner","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0140-6736(17)32758-7","article-title":"Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: A pivotal multicentre, randomised, non-inferiority trial","volume":"391","author":"Mesu","year":"2018","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.pt.2017.12.002","article-title":"Fexinidazole: A New Drug for African Sleeping Sickness on the Horizon","volume":"34","author":"Pollastri","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_38","unstructured":"(2022, April 20). Efficacy and Safety of Fexinidazole in Patients with Stage 1 or Early Stage 2 Human African Trypanosomiasis (HAT) Due to T. b. gambiense: A Prospective, Multicentre, Open-Label Cohort Study, Plug-in to the Pivotal Study, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02169557."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s40265-019-1051-6","article-title":"Fexinidazole: First Global Approval","volume":"79","author":"Deeks","year":"2019","journal-title":"Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Torreele, E., Trunz, B.B., Tweats, D., Kaiser, M., Brun, R., Mazu\u00e9, G., Bray, M.A., and P\u00e9coul, B. (2010). Fexinidazole: A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000923"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/diseases2010003","article-title":"Trypanosomatid Aquaporins: Roles in Physiology and Drug Response","volume":"2","author":"Mandal","year":"2014","journal-title":"Diseases"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"De Koning, P.H. (2020). The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History. Trop. Med. Infect. Dis., 5.","DOI":"10.3390\/tropicalmed5010014"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.mib.2016.08.005","article-title":"Exploiting the Achilles\u2019 Heel of Membrane Trafficking in Trypanosomes","volume":"34","author":"Zoltner","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1124\/mol.59.3.586","article-title":"Uptake of Pentamidine in Trypanosoma brucei brucei Is Mediated by Three Distinct Transporters: Implications for Cross-Resistance with Arsenicals","volume":"59","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/jac\/dkt442","article-title":"Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs","volume":"69","author":"Munday","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kazibwe, A.J., Nerima, B., de Koning, H.P., M\u00e4ser, P., Barrett, M.P., and Matovu, E. (2009). Genotypic status of the TbAT1\/P2 adenosine transporter of Trypanosoma brucei gambiense isolates from Northwestern Uganda following melarsoprol withdrawal. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000523"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Franco, J.R., Cecchi, G., Priotto, G., Paone, M., Diarra, A., Grout, L., Simarro, P.P., Zhao, W., and Argaw, D. (2018). Monitoring the Elimination of Human African Trypanosomiasis: Update to 2016. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006890"},{"key":"ref_48","first-page":"257","article-title":"Epidemiology of Human African Trypanosomiasis","volume":"6","author":"Franco","year":"2014","journal-title":"Clin. Epidemiol."},{"key":"ref_49","unstructured":"FAO (2022, March 25). African Animal Trypanosomiasis. Available online: https:\/\/www.fao.org\/3\/ah809e\/ah809e02.htm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.pt.2021.04.007","article-title":"Pharma to Farmer: Field Challenges of Optimizing Trypanocide Use in African Animal Trypanosomiasis","volume":"37","author":"Richards","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4361","DOI":"10.1128\/AAC.02948-15","article-title":"Adaptation of the [3H]Hypoxanthine Uptake Assay for In Vitro-Cultured Plasmodium knowlesi Malaria Parasites","volume":"60","author":"Arnold","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1365-2885.1997.tb00092.x","article-title":"Concentrations of Isometamidium Chloride (Samorin) in Sera of Zebu Cattle which Showed Evidence of Hepatotoxicity Following Frequent Trypanocidal Treatments","volume":"20","author":"Eisler","year":"1997","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"380","DOI":"10.5897\/AJMR2017.8754","article-title":"Drug Resistance in African Animal Trypanosomes: A Review","volume":"12","author":"Assefa","year":"2018","journal-title":"Afr. J. Microbiol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"341","DOI":"10.3109\/10520290903297528","article-title":"Dyes, Trypanosomiasis and DNA: A Historical and Critical Review","volume":"85","author":"Wainwright","year":"2010","journal-title":"Biotech. Histochem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chowdhury, R.A., Bakshi, R., Wang, J., Yildirir, G., Liu, B., Pappas-Brown, V., Tolun, G., Griffith, J.D., Shapiro, T.A., and Jensen, R.E. (2010). The Killing of African Trypanosomes by Ethidium Bromide. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001226"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s13071-019-3484-x","article-title":"Equine Trypanosomosis: Enigmas and Diagnostic Challenges","volume":"12","author":"Gonzatti","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1017\/S0031182016001268","article-title":"The Animal Trypanosomiases and Their Chemotherapy: A Review","volume":"143","author":"Giordani","year":"2016","journal-title":"Parasitology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1177\/1753425913507488","article-title":"Diminazene Aceturate (Berenil) Modulates LPS Induced pro-Inflammatory Cytokine Production by Inhibiting Phosphorylation of MAPKs and STAT Proteins","volume":"20","author":"Kuriakose","year":"2014","journal-title":"Innate Immun."},{"key":"ref_59","first-page":"1","article-title":"Thiacetarsamide (Adulticide) versus Melarsomine (RM340) Developed as Macrofilaricide (Adulticide and Larvicide) to Cure Canine Heartworm Infection in Dogs","volume":"23","author":"Raynaud","year":"1992","journal-title":"Ann. Rech. Vet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"828111","DOI":"10.3389\/fvets.2022.828111","article-title":"An Update on African Trypanocide Pharmaceutics and Resistance","volume":"9","author":"Kazosi","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_61","unstructured":"Kasper, D., Fauci, A., Hauser, S., Longo, D., Jameson, J.L., and Loscalzo, J. (2014). 246e: Agents Used to Treat Parasitic Infections. Harrison\u2019s Principles of Internal Medicine, McGraw-Hill. [19th ed.]."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1124\/pr.58.3.3","article-title":"International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptor: From molecular mechanisms and pathophysiology to therapy","volume":"58","author":"Abbracchio","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1128\/AAC.48.5.1733-1738.2004","article-title":"Trypanocidal Activity of Melamine Based Nitroheterocycles","volume":"48","author":"Stewart","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.2217\/fmb.11.88","article-title":"Drug Resistance in Human African Trypanosomiasis","volume":"6","author":"Barrett","year":"2011","journal-title":"Future Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10771","article-title":"High-Throughput Decoding of Antitrypanosomal Drug Efficacy and Resistance","volume":"482","author":"Alsford","year":"2012","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"119re1","DOI":"10.1126\/scitranslmed.3003326","article-title":"The Anti-Trypanosome Drug Fexinidazole Shows Potential for Treating Visceral Leishmaniasis","volume":"4","author":"Wyllie","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1128\/AAC.00831-08","article-title":"Efficacy of the Novel Diamidine Compound 2,5-Bis(4-Amidinophenyl)- Furan-Bis-O-Methlylamidoxime (Pafuramidine, DB289) against Trypanosoma brucei rhodesiense infection in vervet monkeys after oral administration","volume":"53","author":"Mdachi","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Begolo, D., Vincent, I.M., Giordani, F., P\u00f6hner, I., Witty, M.J., Rowan, T.G., Bengaly, Z., Gillingwater, K., Freund, Y., and Wade, R.C. (2018). The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing. PLoS Pathog., 14.","DOI":"10.1101\/295550"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9616","DOI":"10.1073\/pnas.1807915115","article-title":"Clinical and Veterinary Trypanocidal Benzoxaboroles Target CPSF3","volume":"115","author":"Wall","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Steketee, P.C., Vincent, I.M., Achcar, F., Giordani, F., Kim, D.H., Creek, D.J., Freund, Y., Jacobs, R., Rattigan, K., and Horn, D. (2018). Benzoxaborole Treatment Perturbs S-Adenosyl-L-Methionine Metabolism in Trypanosoma brucei. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006450"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"621699","DOI":"10.3389\/fvets.2021.621699","article-title":"Epidemiology of Trypanosomiasis in Wildlife\u2014Implications for Humans at the Wildlife Interface in Africa","volume":"8","author":"Kasozi","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_72","unstructured":"(2022, April 04). Safety and Tolerability Study of Acoziborole in G-HAT Seropositive Subjects, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05256017."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0166-6851(84)90117-8","article-title":"Purine and Pyrimidine Metabolism in the Trypanosomatidae","volume":"13","author":"Hammond","year":"1984","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.pt.2012.05.005","article-title":"Purine Salvage in Leishmania: Complex or Simple by Design?","volume":"28","author":"Boitz","year":"2012","journal-title":"Trends Parasitol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Aoki, J.I., Coelho, A.C., Muxel, S.M., Zampieri, R.A., Ramos Sanchez, E.M., Nerland, A.H., Floeter-Winter, L.M., and Cotrim, P.C. (2016). Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004972"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/0035-9203(66)90146-5","article-title":"Cordycepin, an Antitumour Antibiotic with Trypanocidal Properties","volume":"60","author":"Williamson","year":"1966","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"9861","DOI":"10.1021\/jm401530a","article-title":"Structure\u2013Activity Relationships of Synthetic Cordycepin Analogues as Experimental Therapeutics for African trypanosomiasis","volume":"56","author":"Vodnala","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8771","DOI":"10.1038\/srep08771","article-title":"New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: An open resource","volume":"5","author":"Manzano","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ejmech.2018.12.050","article-title":"Revisiting Tubercidin against Kinetoplastid Parasites: Aromatic Substitutions at Position 7 Improve Activity and Reduce Toxicity","volume":"164","author":"Hulpia","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.1038\/s41467-019-13522-6","article-title":"Combining Tubercidin and Cordycepin Scaffolds Results in Highly Active Candidates to Treat Late-Stage Sleeping Sickness","volume":"10","author":"Hulpia","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1021\/acs.jmedchem.7b01670","article-title":"Targeting a subpocket in Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) enables the structure-based discovery of selective inhibitors with trypanocidal activity","volume":"61","author":"Blaazer","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Poehner, I., Quotadamo, A., Panecka-Hofman, J., Luciani, R., Santucci, M., Linciano, P., Landi, G., di Pisa, F., dello Iacono, L., and Pozzi, C. (2022). Multitarget, Selective Compound Design Yields Picomolar Inhibitors of a Kinetoplastid Pteridine Reductase 1. J. Med. Chem.","DOI":"10.26434\/chemrxiv-2021-9fpln-v5"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nature08893","article-title":"N-myristoyltransferase inhibitors as new leads to treat sleeping sickness","volume":"464","author":"Frearson","year":"2010","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1002\/cmdc.201500301","article-title":"Development of Small-Molecule Trypanosoma brucei N-Myristoyltransferase Inhibitors: Discovery and Optimisation of a Novel Binding Mode","volume":"10","author":"Spinks","year":"2015","journal-title":"ChemMedChem"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9404","DOI":"10.1021\/acs.jmedchem.1c00674","article-title":"Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis","volume":"64","author":"Klug","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9912","DOI":"10.1021\/acs.jmedchem.0c01017","article-title":"Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead for Trypanosoma brucei Inhibitors","volume":"63","author":"Singh","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Tassone, G., Landi, G., Linciano, P., Francesconi, V., Tonelli, M., Tagliazucchi, L., Costi, M.P., Mangani, S., and Pozzi, C. (2021). Evidence of Pyrimethamine and Cycloguanil Analogues as Dual Inhibitors of Trypanosoma brucei Pteridine Reductase and Dihydrofolate Reductase. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070636"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/0001-706X(94)90105-8","article-title":"The Persistence of Genetic Homogeneity among Trypanosoma brucei rhodesiense Isolates from Patients in North-West Tanzania","volume":"56","author":"Gashumba","year":"1994","journal-title":"Acta Trop."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.ijpddr.2017.10.002","article-title":"Genomic analysis of Isometamidium Chloride resistance in Trypanosoma congolense","volume":"7","author":"Tihon","year":"2017","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.pt.2008.04.006","article-title":"Ever-Increasing Complexities of Diamidine and Arsenical Crossresistance in African Trypanosomes","volume":"24","year":"2008","journal-title":"Trends Parasitol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1042\/bj3260755","article-title":"Modulation of Mitochondrial Electrical Potential: A Candidate Mechanism for Drug Resistance in African Trypanosomes","volume":"326","author":"Wilkes","year":"1997","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"14741","DOI":"10.1073\/pnas.1305404110","article-title":"Single Point Mutations in ATP Synthase Compensate for Mitochondrial Genome Loss in Trypanosomes","volume":"110","author":"Dean","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Okello, A.L., Bardosh, K., Smith, J., and Welburn, S.C. (2014). One Health: Past Successes and Future Challenges in Three African Contexts. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002884"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40249-016-0224-8","article-title":"Evaluating the impact of targeting livestock for the prevention of human and animal trypanosomiasis, at village level, in districts newly affected with T. b. rhodesiense in Uganda","volume":"6","author":"Hamill","year":"2017","journal-title":"Infect. Dis. Poverty"},{"key":"ref_95","unstructured":"WHO (2022, March 25). Elimination of Human African Trypanosomiasis as Public Health Problem. Wkly. Epidemiol. Rec, Available online: https:\/\/www.cdc.gov\/parasites\/sleepingsickness\/health_professionals\/index.html#dx."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e00185","DOI":"10.1016\/j.parepi.2020.e00185","article-title":"Experiences of the one-health approach by the Uganda Trypanosomiasis Control Council and its secretariat in the control of zoonotic sleeping sickness in Uganda","volume":"11","author":"Waiswa","year":"2020","journal-title":"Parasite Epidemiol. Control"},{"key":"ref_97","first-page":"E28","article-title":"Elimination of Sleeping Sickness in Uganda Could Be Jeopardised by Conflict in South Sudan","volume":"5","author":"Picado","year":"2017","journal-title":"Lancet"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/7\/1298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:02Z","timestamp":1760139542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/10\/7\/1298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":97,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["microorganisms10071298"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms10071298","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}