{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:47:54Z","timestamp":1761929274781},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> To determine the drug resistance of <jats:italic>Trypanosoma brucei rhodesiense<\/jats:italic> strains isolated from sleeping sickness patients in Tanzania.<\/jats:p><jats:p><jats:bold>Method\u2002<\/jats:bold> We first screened 35 <jats:italic>T. b. rhodesiense strains<\/jats:italic> in the mouse model, for sensitivity to melarsoprol (1.8, 3.6 and 7.2\u2003mg\/kg), diminazene aceturate (3.5, 7 and 14\u2003mg\/kg), suramin (5, 10 and 20\u2003mg\/kg) and isometamidium (0.1, 1.0 and 2\u2003mg\/kg). A 13 isolates suspected to be resistant were selected for further testing <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. From the <jats:italic>in vitro<\/jats:italic> testing, IC<jats:sub>50<\/jats:sub> values were determined by short\u2010term viability assay, and MIC values were calculated by long\u2010term viability assay. For <jats:italic>in vivo<\/jats:italic> testing, doses higher than those in the initial screening test were used.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Two <jats:italic>T. b rhodesiense<\/jats:italic> stocks expressed resistance <jats:italic>in vivo<\/jats:italic> to melarsoprol at 5\u2003mg\/kg and at 10\u2003mg\/kg. These strains had high IC<jats:sub>50<\/jats:sub> and MIC values consistent with those of the melarsoprol\u2010resistant reference strain. Another isolate relapsed after treatment with 5\u2003mg\/kg of melarsoprol although it did not appear resistant <jats:italic>in vitro<\/jats:italic>. One isolate was resistant to diminazene at 14\u2003mg\/kg and another was resistant at both 14 and 28\u2003mg\/kg of diminazene. These two isolates had high IC<jats:sub>50<\/jats:sub> values consistent with the diminazene\u2010resistant reference strain. Two isolates relapsed at a dose of 5\u2003mg\/kg of suramin, although no isolate appeared resistant in the <jats:italic>in vitro<\/jats:italic> tests. Two isolates were resistant to isometamidium at 1.0\u2003mg\/kg and had higher IC<jats:sub>50<\/jats:sub> values. Two isolates were cross\u2010resistant to melarsoprol and diminazene and one isolate was cross\u2010resistant to suramin and isometamidium.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> The reduced susceptibility of <jats:italic>T. b. rhodesiense<\/jats:italic> isolates to these drugs strongly indicates that drug resistance may be emerging in north\u2013western Tanzania.<\/jats:p>","DOI":"10.1111\/j.1365-3156.2005.01545.x","type":"journal-article","created":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T14:41:34Z","timestamp":1138804894000},"page":"144-155","source":"Crossref","is-referenced-by-count":37,"title":["Drug\u2010resistance of <i>Trypanosoma b. rhodesiense<\/i> isolates from Tanzania"],"prefix":"10.1111","volume":"11","author":[{"given":"S. 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