Pyana Patient Pati, Sere Modou, Kaboré Jacques, De Meeûs Thierry, MacLeod Annette, Bucheton Bruno, Van Reet Nick, Büscher Philippe, Belem Adrien Marie Gaston, Jamonneau Vincent
Département de Parasitologie, Institut National de Recherche Biomédicale, Av. de la Démocratie, BP 1197, Kinshasa Gombe, Congo.
Centre International de Recherche-Développement sur l'Élevage en zones Subhumides (CIRDES), Unité de recherches sur les bases biologiques de la lutte intégrée, Institut de Recherche pour le Développement, Unité Mixte de Recherche IRD-CIRAD 177 INTERTRYP, 01 BP 454 Bobo-Dioulasso 01, Burkina Faso.
Infect Genet Evol. 2015 Mar;30:128-133. doi: 10.1016/j.meegid.2014.12.017. Epub 2014 Dec 20.
Human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) is caused by the protozoan Trypanosoma brucei gambiense. Until recently, all patients in the second or neurological stage of the disease were treated with melarsoprol. At the end of the past and the beginning of the present century, alarmingly high relapse rates in patients treated with melarsoprol were reported in isolated HAT foci. In the Mbuji-Mayi focus of DRC, a particular mutation that confers cross resistance for pentamidine and melarsoprol was recently found for all strains studied. Nevertheless, treatment successfully cured a significant proportion of patients. To check for the existence of other possible genetic factors of the parasites, we genotyped trypanosomes isolated from patients before and after treatment (relapsing patients) with eight microsatellite markers. We found no evidence of any genetic correlation between parasite genotype and treatment outcome and we concluded that relapse or cure probably depend more on patients' factors such as disease progression, nutritional or immunological status or co-infections with other pathogens. The existence of a melarsoprol and pentamidine resistance associated mutation at such high rates highlights an increasing problem, even for other drugs, especially those using the same transporters as melarsoprol and pentamidine.
刚果民主共和国的人类非洲锥虫病（HAT）由原生动物布氏冈比亚锥虫引起。直到最近，所有处于疾病第二阶段或神经阶段的患者都用美拉胂醇进行治疗。在过去世纪末和本世纪初，在个别HAT疫源地报告了接受美拉胂醇治疗的患者中令人担忧的高复发率。在刚果民主共和国的姆布吉马伊疫源地，最近在所研究的所有菌株中发现了一种赋予对喷他脒和美拉胂醇交叉耐药性的特定突变。尽管如此，治疗还是成功治愈了相当比例的患者。为了检查寄生虫其他可能的遗传因素的存在情况，我们用八个微卫星标记对治疗前后（复发患者）从患者分离出的锥虫进行了基因分型。我们没有发现寄生虫基因型与治疗结果之间存在任何遗传相关性的证据，并且我们得出结论，复发或治愈可能更多地取决于患者因素，如疾病进展、营养或免疫状况或与其他病原体的合并感染。如此高比例存在与美拉胂醇和喷他脒耐药相关的突变凸显了一个日益严重的问题，即使对于其他药物，尤其是那些与美拉胂醇和喷他脒使用相同转运蛋白的药物也是如此。
