Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.
Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.
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DOI：
10.1371/journal.pntd.0000709
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发表时间：
2010-10-26
影响因子：
3.8
通讯作者：
Leishmaniasis East Africa Platform (LEAP) group
中科院分区：
文献类型：
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作者：
Hailu A;Musa A;Wasunna M;Balasegaram M;Yifru S;Mengistu G;Hurissa Z;Hailu W;Weldegebreal T;Tesfaye S;Makonnen E;Khalil E;Ahmed O;Fadlalla A;El-Hassan A;Raheem M;Mueller M;Koummuki Y;Rashid J;Mbui J;Mucee G;Njoroge S;Manduku V;Musibi A;Mutuma G;Kirui F;Lodenyo H;Mutea D;Kirigi G;Edwards T;Smith P;Muthami L;Royce C;Ellis S;Alobo M;Omollo R;Kesusu J;Owiti R;Kinuthia J;Leishmaniasis East Africa Platform (LEAP) group
内脏利什曼病（VL）是发展中国家的一个主要健康问题。未经治疗的疾病是致命的，现有的治疗是昂贵的，往往有毒，耐药性正在增加。需要改进治疗方案。巴龙霉素在印度被证明是一种有效的低毒性一线治疗药物。这是一项3组、多中心、开放标签、随机、对照临床试验，旨在比较东非VL的3种治疗方案：硫酸巴龙霉素（PM）15 mg/kg/天持续21天与葡萄糖酸锑钠（SSG）20 mg/kg/天持续30天;以及两种剂量方案联合治疗17天。主要疗效终点是基于治疗后6个月的无寄生虫组织抽吸物的治愈。总体而言，在苏丹（2家研究中心）、肯尼亚（1家）和埃塞俄比亚（2家）的5家研究中心，每组入组了135例患者，PM组因疗效不佳而不得不停药。该试验继续使用较高剂量的PM以及PM和SSG组的组合。这些结果将在稍后报告。各治疗组的基线患者特征相似。PM的总体治愈率显著低于SSG（63.8%对92.2%;差异28.5%，95%CI 18.8%至38.8%，p<0.001）。PM的有效性因中心而异，苏丹（14.3%和46.7%）显著低于肯尼亚（80.0%）和埃塞俄比亚（75.0%和96.6%）。未发现PM的重大安全性问题。PM以15 mg/kg/天剂量给药21天的疗效不充分，尤其是在苏丹。更高剂量和联合治疗的疗效需要进一步研究。内脏利什曼病（VL）是一种致命的寄生虫病，据世卫组织估计，每年有50万新病例。在疾病流行地区，由于病程长、毒性和对目前治疗的耐药性，迫切需要新的和更好的治疗选择。最近，抗生素巴龙霉素在印度进行了测试和注册，以治疗这种疾病。目前的研究描述了一项临床试验，以测试注射巴龙霉素的有效性，单独或与标准药物葡萄糖酸锑钠在三个东非国家-苏丹，肯尼亚和埃塞俄比亚。该研究表明，在印度成功使用和注册的相同巴龙霉素剂量下，获得的结果要差得多，特别是在苏丹，这表明与印度相比，东非患者对药物的反应能力或寄生虫的易感性存在差异。然而，治疗中未发现重大安全性问题。进一步的研究开始，看看更高剂量的巴龙霉素是否会表现得更好，特别是在苏丹。其结果和组合组的性能将在稍后报告。我们的研究强调了考虑地理差异对治疗反应的重要性。
Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India. This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment. Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified. The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies. Visceral leishmaniasis (VL) is a fatal parasitic disease with 500,000 new cases each year according to WHO estimates. New and better treatment options are urgently needed in disease endemic areas due to the long courses, toxicity and development of resistance to current treatments. Recently, the antibiotic paromomycin was tested and registered in India to treat this disease. The current study describes a clinical trial to test the effectiveness of injectable paromomycin, either alone or in combination with the standard drug sodium stibogluconate in three East African countries—Sudan, Kenya and Ethiopia. The study showed that at the same paromomycin dose that was successfully used and registered in India, a far poorer outcome was obtained, particularly in Sudan, suggesting that there are either differences in the patients ability to respond to the drug or in the susceptibility of parasites in East Africa compared with those in India. However, no major safety concerns were noted with the treatment. Further research was initiated to see if a higher dose of paromomycin would perform better, especially in Sudan. The results of this and the performance of the combination arm will be reported later. Our study highlights the importance of considering geographical differences to treatment responses.
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影响因子：
--
作者：
Thakur, CP;Sinha, GP;Roy, RK
通讯作者：
Roy, RK
影响因子：
2.7
作者：
Desjeux, P
通讯作者：
Desjeux, P
影响因子：
--
作者：
Jha, TK;Olliaro, P;Jha, S
通讯作者：
Jha, S
DOI：
10.1016/s0035-9203(00)90130-5
发表时间：
2000-07-01
影响因子：
2.2
作者：
Thakur, CP;Kanyok, TP;Olliaro, P
通讯作者：
Olliaro, P
影响因子：
158.5
作者：
Sundar, Shyam;Jha, T. K.;Li, X.
通讯作者：
Li, X.