Sundar Shyam, Jha T K, Sindermann Herbert, Junge Klaus, Bachmann Peter, Berman Jonathan
Institutes of Medical Sciences, Banaras Hindu University, 6 SK Gupta Nagar, Varanasi 221005, India.
Pediatr Infect Dis J. 2003 May;22(5):434-8. doi: 10.1097/01.inf.0000066877.72624.cb.
Miltefosine is the first oral drug with demonstrable success in treating visceral leishmaniasis in adults. Because approximately one-half of the visceral leishmaniasis patients worldwide are children, we performed a Phase I/II dose ranging study in the pediatric population in India.
Thirty-nine (39) children (defined as < 12 years of age) with visceral leishmaniasis demonstrated by parasites in splenic aspirates, were treated with oral miltefosine daily for 28 days: 21 patients received 1.5 mg/kg/day (Group A); and 18 patients received 2.5 mg/kg/day (Group B). About one-half of these children had failed prior antileishmanial treatment.
All patients were parasitologically negative and symptomatically improved by the end of therapy on Day 28 of therapy; the initial parasitologic cure rate was 100%. Two patients in each treatment group relapsed with fever, splenomegaly and parasite-positive splenic aspirates by the end of the 6-month follow-up. The per protocol final clinical cure rate was 19 of 21 = 90% in Group A and 15 of 17 = 88% in Group B. Miltefosine was well-tolerated. As per the adult experience, gastrointestinal adverse events were seen: 33 and 39% of children experienced vomiting and 5 and 17% experienced diarrhea in Groups A and B, respectively, but all episodes were mild to moderate in severity and commonly lasted <1 day without symptomatic treatment.
Oral miltefosine was safe and approximately 90% effective in this initial clinical trial of childhood visceral leishmaniasis.
米替福新是首个在治疗成人内脏利什曼病方面取得显著成功的口服药物。由于全球约一半的内脏利什曼病患者是儿童，我们在印度的儿科人群中开展了一项I/II期剂量范围研究。
39名（定义为年龄<12岁）经脾穿刺抽吸物中发现寄生虫确诊为内脏利什曼病的儿童，每天口服米替福新，持续28天：21名患者接受1.5mg/kg/天（A组）；18名患者接受2.5mg/kg/天（B组）。这些儿童中约一半先前的抗利什曼病治疗失败。
所有患者在治疗第28天疗程结束时寄生虫学检查均为阴性且症状改善；初始寄生虫学治愈率为100%。在6个月随访结束时，每个治疗组各有2名患者出现发热、脾肿大且脾穿刺抽吸物寄生虫阳性复发。符合方案的最终临床治愈率在A组为21例中的19例=90%，在B组为17例中的15例=88%。米替福新耐受性良好。根据成人经验，观察到胃肠道不良事件：A组和B组分别有33%和39%的儿童出现呕吐，5%和17%的儿童出现腹泻，但所有发作均为轻度至中度，通常无需对症治疗持续时间<1天。
在这项儿童内脏利什曼病的初步临床试验中，口服米替福新安全且有效性约为90%。
