Sundar S, Rosenkaimer F, Makharia M K, Goyal A K, Mandal A K, Voss A, Hilgard P, Murray H W
Kala-Azar Medical Research Center, Banaras Hindu University Institute of Medical Sciences, Varanasi, India.
Lancet. 1998 Dec 5;352(9143):1821-3. doi: 10.1016/S0140-6736(98)04367-0.
There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kala-azar.
Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure--taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0--was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse.
21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1-2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7-10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3-6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed.
Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.
内脏利什曼病（黑热病）是一种在全球范围内传播的细胞内原生动物感染，目前尚无有效的口服治疗方法。米替福新是一种作为口服抗肿瘤药物开发的烷基磷脂，在动物模型中对内脏感染具有活性。我们测试了米替福新治疗黑热病的安全性、耐受性和疗效。
给六组每组五名印度男性口服米替福新28天：隔日50毫克（第1组）、隔日100毫克（第2组）、每日100毫克（第3组）、每日150毫克（第4组）、每日200毫克（第5组）和每日250毫克（第6组）。在第14天和第28天评估明显治愈情况，定义为无发热状态、脾脏大小减小且脾脏穿刺寄生虫密度评分为0。8个月时的彻底治愈要求骨髓穿刺无寄生虫且无复发的临床证据。
30名患者中有21名在第14天明显治愈。呕吐和腹泻的短暂发作在第1 - 2周很常见，22名患者出现此症状。第5组和第6组的另外4名患者因呕吐在7 - 10天后停用米替福新。第6组的1名患者出现肾功能不全和严重腹泻，于第21天死亡。在第28天，其余29名患者均明显治愈。到8个月时，第1组和第2组的10名患者中有7名复发；然而，每日接受治疗的19名患者（第3 - 6组）中有18名似乎已治愈。在21例彻底治愈的患者中，有4例治疗时间为10天或更短，12例之前使用五价锑治疗失败。
每日100 - 150毫克米替福新治疗4周有望成为内脏利什曼病包括锑耐药感染的有效口服治疗方法。
