Jha T K, Sundar S, Thakur C P, Bachmann P, Karbwang J, Fischer C, Voss A, Berman J
Kala-azar Research Center, Brahmpura, Muzaffarpur, India.
N Engl J Med. 1999 Dec 9;341(24):1795-800. doi: 10.1056/NEJM199912093412403.
There is no effective orally administered medication for any leishmania infection. We investigated miltefosine, which can be taken orally, for the treatment of Indian visceral leishmaniasis. Miltefosine is a phosphocholine analogue that affects cell-signaling pathways and membrane synthesis.
The study was an open-label, multicenter, phase 2 trial in which four 30-person cohorts received 50, 100, or 150 mg of miltefosine per day for four or six weeks. The 120 patients, who ranged in age from 12 to 50 years, had anorexia, fever, and splenomegaly with at least moderate (2+) leishmania in a splenic aspirate. A parasitologic cure was defined by the absence of parasites in a splenic aspirate obtained two weeks after completion of treatment. The clinical response was assessed at six months.
In all 120 patients there was an initial parasitologic cure. Six patients had clinical and parasitologic relapses; the remaining 114 patients had not relapsed by six months after treatment, for a cure rate of 95 percent (95 percent confidence interval, 89 to 98 percent). With the regimen of 100 mg of miltefosine per day (approximately 2.5 mg per kilogram of body weight per day) for four weeks, 29 of 30 patients (97 percent) were cured. Gastrointestinal side effects were frequent (occurring in 62 percent of patients) but mild to moderate in severity, and no patient discontinued therapy because of gastrointestinal side effects. In two patients, treatment was discontinued because of elevated levels of aspartate aminotransferase or creatinine; in both patients the levels rapidly returned to normal. In 12 other patients, the level of aspartate aminotransferase increased to 100 to 150 U per liter during treatment.
Orally administered miltefosine appears to be an effective treatment for Indian visceral leishmaniasis.
对于任何利什曼原虫感染，目前尚无有效的口服药物。我们对可口服的米替福新进行了研究，用于治疗印度内脏利什曼病。米替福新是一种磷胆碱类似物，可影响细胞信号通路和膜合成。
本研究为开放标签、多中心、2期试验，四个30人队列分别接受每日50、100或150毫克米替福新治疗，为期四周或六周。这120名患者年龄在12至50岁之间，有厌食、发热和脾肿大，脾穿刺液中利什曼原虫至少为中度（2+）。寄生虫学治愈的定义为治疗结束两周后脾穿刺液中无寄生虫。在六个月时评估临床反应。
所有120名患者最初均实现寄生虫学治愈。6名患者出现临床和寄生虫学复发；其余114名患者在治疗后六个月未复发，治愈率为95%（95%置信区间，89%至98%）。采用每日100毫克米替福新（约每日每公斤体重2.5毫克）治疗四周的方案，30名患者中有29名（97%）治愈。胃肠道副作用常见（62%的患者出现），但严重程度为轻至中度，没有患者因胃肠道副作用而停药。两名患者因天冬氨酸转氨酶或肌酐水平升高而停药；两名患者的水平均迅速恢复正常。另外12名患者在治疗期间天冬氨酸转氨酶水平升至每升100至150单位。
口服米替福新似乎是治疗印度内脏利什曼病的有效方法。
