Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani

Evidence that the high incidence of treatment failures in Indian kala-azar is due to the emergence of antimony-resistant strains of Leishmania donovani
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DOI:
10.1086/314896
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发表时间:
1999-08-01
影响因子:
6.4
通讯作者:
Sacks, D
Sacks, D
中科院分区:
医学2区
文献类型:
--
作者:
Lira, R;Sundar, S;Sacks, D

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印度黑热病治疗失败的高频率可能是由于感染了抗锑的多诺瓦利什曼原虫菌株,这一可能性尚未得到实验解决。从印度比哈尔邦24例对葡萄糖酸钠(SAG)治疗1个或多个疗程无反应(15例)或有反应(9例)的患者的脾涂片中分离到杜诺瓦尼乳杆菌。只有当菌株被检测为细胞内无鞭毛体时,临床反应与体外SAG敏感性之间才观察到强烈的相关性(P<.001):敏感菌株ED50=2.4+/-2.6,ED90=6.4+/-7.8 mU SAG/mL;无反应菌株ED50=7.4+/-3.7mUg SAG/mL,ED90=29.1+/-11.1SAG/mL。细胞外前鞭毛体的使用与临床疗效无相关性(ED50=48+/-22vs.52+/-29mUg/mL)。抗锑杜诺瓦尼乳杆菌菌株的出现似乎是印度治疗失败的一个原因。
The possibility that the high frequency of treatment failures in Indian kala-azar might be due to infection with antimony-resistant strains of Leishmania donovani has not been experimentally addressed. L. donovani isolates were obtained from splenic aspiration smears of 24 patients in Bihar, India, who either did not respond (15) or did respond (9) to 1 or more full courses of treatment with sodium antimony gluconate (SAG), A strong correlation (P < .001) between clinical response and SAG sensitivity in vitro was observed only when strains were assayed as intracellular amastigotes: responsive isolates ED50 = 2.4 +/- 2.6, ED90 = 6.4 +/- 7.8 mu g SAG/mL; unresponsive isolates ED50 = 7.4 +/- 3.7 mu g SAG/mL, ED90 = 29.1 +/- 11.1 SAG/mL. No correlation with clinical response was found by use of extracellular promastigotes (ED50 = 48 +/- 22 vs. 52 +/- 29 mu g/mL). The emergence of antimony-resistant L. donovani strains appears to be a cause of treatment failures in India.