Thakur C P, Narayan S, Ranjan A
Balaji Utthan Sansthan & Rajendra Memorial Research Institute of Medical Sciences, Patna, India.
Indian J Med Res. 2004 Sep;120(3):166-72.
BACKGROUND & OBJECTIVES: Sodium antimony gluconate (SAG) is reported to be losing its efficacy in Bihar as a first line drug for treatment of visceral leishmaniasis (VL). Concerned with the increasing incidence of antimony-resistant VL patients in Bihar, we undertook an epidemiological, clinical and pharmacological study to formulate a scientific basis for choosing a suitable first line drug for VL.
Consecutive, fresh and parasitologically confirmed patients of VL from different geographical areas of Bihar were considered for inclusion in the study. Parasites isolated from patients were tested in vitro to assess their response to sodium antimony gluconate (SAG) to 20 microg/ml, response to 20 mg/kg of SAG for 5 days in experimentally induced VL in BALB/c mice from those isolates, and response to SAG in patients treated with SAG for 28 days. Similarly response in culture (1 microg/ml) to amphotericin B (AMB) of all 282 isolates, (1 mg/kg body wt for 20 days) in patients and infected BALB/c mice (1 mg/kg body wt for 5 days) was determined. Antimony levels of plasma were determined at 2, 8 and 24 h after intramuscular injection of SAG. Patients unwilling for SAG treatment or relapsed after SAG treatment and withdrawn from SAG group because of toxicity were treated with AMB. Plasma antimony levels were estimated by atomic absorption spectrometer.
Though antimony sensitive and resistant patient were distributed in all 14 districts of Bihar studied, there was a significant variation from district to district. Of the 123 patients included in the SAG treatment group, 19 were withdrawn due to development of toxicity and 2 died; 178 patients were treated with AMB. No patient in AMB group developed any toxicity or died. Only 47 (46%) of 102 patients, 106 (37.6%) of 282 infected macrophages, 90 (52.9%) of 170 experimental infections were cured with SAG. Mc Nemar's test on paired comparisons showed statistical significance difference (P<0.01) between infected macrophage and experimental infection. AMB cured all patients, infected mice and cleared parasites from all isolates.
INTERPRETATION & CONCLUSION: Antimony resistant strains of L. donovani were wide spread over different geographical areas in Bihar. SAG cured lesser percentage of VL cases clinically compared to AMB and should be replaced by AMB as a first line drug.
据报道，在比哈尔邦，葡萄糖酸锑钠（SAG）作为治疗内脏利什曼病（VL）的一线药物，其疗效正在丧失。鉴于比哈尔邦耐锑VL患者的发病率不断上升，我们开展了一项流行病学、临床和药理学研究，以便为选择合适的VL一线药物奠定科学基础。
来自比哈尔邦不同地理区域的连续、新发且经寄生虫学确诊的VL患者被纳入研究。对从患者分离出的寄生虫进行体外测试，以评估它们对20微克/毫升葡萄糖酸锑钠（SAG）的反应、对从这些分离株感染的BALB/c小鼠实验性诱导的VL中20毫克/千克SAG治疗5天的反应，以及对接受SAG治疗28天的患者中SAG的反应。同样，测定了所有282个分离株对两性霉素B（AMB）在培养物中（1微克/毫升）的反应、患者和感染的BALB/c小鼠中对AMB（1毫克/千克体重，共20天）的反应（1毫克/千克体重，共5天）。在肌肉注射SAG后2、8和24小时测定血浆锑水平。不愿接受SAG治疗或在SAG治疗后复发且因毒性退出SAG组的患者接受AMB治疗。通过原子吸收光谱仪估计血浆锑水平。
尽管锑敏感和耐药患者分布在比哈尔邦研究的所有14个区，但各区之间存在显著差异。在SAG治疗组纳入的123例患者中，19例因出现毒性反应退出，2例死亡；178例患者接受了AMB治疗。AMB组无患者出现任何毒性反应或死亡。102例患者中只有47例（46%）、282个感染巨噬细胞中有106个（37.6%）、170例实验性感染中有90例（52.9%）被SAG治愈。配对比较的Mc Nemar检验显示感染巨噬细胞与实验性感染之间存在统计学显著差异（P<0.01）。AMB治愈了所有患者、感染小鼠，并清除了所有分离株中的寄生虫。
杜氏利什曼原虫的耐锑菌株在比哈尔邦的不同地理区域广泛传播。与AMB相比，SAG临床治愈VL病例的比例较低，应将AMB作为一线药物取代SAG。
