Legros D, Evans S, Maiso F, Enyaru J C, Mbulamberi D
Epicentre, Kampala, Uganda.
Trans R Soc Trop Med Hyg. 1999 Jul-Aug;93(4):439-42. doi: 10.1016/s0035-9203(99)90151-7.
We evaluated the treatment failure rate among late-stage human African trypanosomiasis (HAT) patients treated with melarsoprol in Arua, northern Uganda, between September 1995 and August 1996, and identified the risk factors for treatment failure. We conducted a retrospective cohort study in October 1998, and performed a survival analysis. A treatment failure was defined as a late-stage HAT patient fully treated with melarsoprol and classified as an HAT case at any follow-up visit within 2 years after treatment. Among 428 patients treated in the study period, 130 (30.4%) were identified as treatment failure within 2 years after discharge. The multivariate analysis showed that patients who experienced treatment failure after melarsoprol were more likely to have been admitted as a relapsing case (relative hazard, RH = 11.15 [6.34-19.61]), and to have been diagnosed with trypanosomes in the lymph nodes (RH = 3.19 [2.10-4.83]) or in the cerebrospinal fluid (CSF) (RH = 1.66 [1.09-2.53]). The risk of treatment failure also increased with the number of cells in the CSF. The treatment failure rate after melarsoprol observed in Arua is greatly above the expected figures of 3-9%. More research is needed to confirm whether it is related to the variation of melarsoprol pharmacokinetics between individuals, or if it is associated with a reduced susceptibility of the trypanosomes to melarsoprol. The study emphasizes the need for second-line drugs to treat patients that have already received one or several full course(s) of melarsoprol.
1995年9月至1996年8月期间，我们对乌干达北部阿鲁阿接受美拉胂醇治疗的晚期人类非洲锥虫病（HAT）患者的治疗失败率进行了评估，并确定了治疗失败的风险因素。1998年10月，我们进行了一项回顾性队列研究，并进行了生存分析。治疗失败定义为接受美拉胂醇全程治疗的晚期HAT患者，且在治疗后2年内的任何随访中被归类为HAT病例。在研究期间接受治疗的428名患者中，130名（30.4%）在出院后2年内被确定为治疗失败。多变量分析显示，接受美拉胂醇治疗后出现治疗失败的患者更有可能作为复发病例入院（相对风险，RH = 11.15 [6.34 - 19.61]），并且更有可能在淋巴结（RH = 3.19 [2.10 - 4.83]）或脑脊液（CSF）（RH = 1.66 [1.09 - 2.53]）中检测到锥虫。治疗失败的风险也随着脑脊液中细胞数量的增加而增加。在阿鲁阿观察到的美拉胂醇治疗后的失败率大大高于预期的3 - 9%。需要更多的研究来确认这是否与个体间美拉胂醇药代动力学的差异有关，或者是否与锥虫对美拉胂醇的敏感性降低有关。该研究强调需要二线药物来治疗已经接受过一个或几个美拉胂醇完整疗程的患者。
