Data from: Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection

The trypanosome Trypanosoma brucei gambiense (Tbg) is a cause of human African trypanosomiasis (HAT) endemic to many parts of sub-Saharan Africa. The disease is almost invariably fatal if untreated and there is no vaccine, which makes monitoring and managing drug resistance highly relevant. A recent study of HAT cases from the Democratic Republic of the Congo reported a high incidence of relapses in patients treated with melarsoprol. Of the 19 Tbg strains isolated from patients enrolled in this study, four pairs were obtained from the same patient before treatment and after relapse. We used whole genome sequencing to investigate whether these patients were infected with a new strain, or if the original strain had regrown to pathogenic levels. Clustering analysis of 5938 single nucleotide polymorphisms supports the hypothesis of regrowth of the original strain, as we found that strains isolated before and after treatment from the same patient were more similar to each other than to other isolates. We also identified 23 novel genes that could affect melarsoprol sensitivity, representing a promising new set of targets for future functional studies. This work exemplifies the utility of using evolutionary approaches to provide novel insights and tools for disease control.布氏冈比亚锥虫（Trypanosoma brucei gambiense, Tbg）是引发人类非洲锥虫病（human African trypanosomiasis, HAT）的病原体之一，该疾病流行于撒哈拉以南非洲诸多区域。若不经治疗，该病几乎无一例外会导致患者死亡，且目前尚无可用疫苗，这使得对药物抗性的监测与管理极具现实意义。近期一项针对刚果民主共和国HAT病例的研究显示，接受美拉胂醇（melarsoprol）治疗的患者复发率较高。在该研究纳入的患者体内分离得到的19株Tbg中，有4对菌株分别采自同一患者治疗前以及疾病复发后。我们采用全基因组测序技术，探究此类患者的复发感染究竟源于新菌株入侵，还是原始菌株重新增殖至致病水平。针对5938个单核苷酸多态性位点的聚类分析支持了原始菌株复燃的假说：我们发现，同一患者治疗前后分离得到的菌株，彼此间的遗传相似性显著高于其与其他分离株的相似性。我们还鉴定出23个可能影响美拉胂醇敏感性的新基因，为后续功能研究提供了一组极具前景的靶标。本研究彰显了利用进化分析方法为疾病防控提供全新认知与工具的实用价值。