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简短报告:刚果民主共和国与恶性疟原虫对磺胺多辛-乙胺嘧啶耐药性相关的分子标志物

Short report: molecular markers associated with Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in the Democratic Republic of Congo.

作者信息

Cohuet Sandra, Bonnet Maryline, Van Herp Michel, Van Overmeir Chantal, D'Alessandro Umberto, Guthmann Jean-Paul

机构信息

Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium.

出版信息

Am J Trop Med Hyg. 2006 Jul;75(1):152-4.

Abstract

Sulfadoxine-pyrimethamine (SP) is the first line antimalarial treatment in the Democratic Republic of Congo. Using polymerase chain reaction, we assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulfadoxine, respectively. Four hundred seventy-four patients were sampled in Kilwa (N = 138), Kisangani (N = 112), Boende (N = 106), and Basankusu (N = 118). The proportion of triple mutations dhfr varied between sites but was always > 50%. The proportion of dhps double mutations was < 20%, with some sites as low as 0.9%. A quintuple mutation was present in 12.8% (16/125) samples in Kilwa; 11.9% (13/109) in Kisangani, 2.9% (3/102) in Boende, and 0.9% (1/112) in Basankusu. These results suggest high resistance to pyrimethamine alone or combined with sulfadoxine. Adding artesunate to SP does not seem a valid alternative to the current monotherapy.

摘要

周效磺胺-乙胺嘧啶(SP)是刚果民主共和国的一线抗疟治疗药物。我们使用聚合酶链反应评估了恶性疟原虫二氢叶酸还原酶(dhfr)(密码子108、51、59)和二氢蝶酸合酶(dhps)(密码子437、540)基因中的突变流行情况,这些突变分别与对乙胺嘧啶和周效磺胺的耐药性有关。在基尔瓦(N = 138)、基桑加尼(N = 112)、博恩德(N = 106)和巴萨库苏(N = 118)对474名患者进行了采样。dhfr三重突变的比例在各地点之间有所不同,但始终>50%。dhps双重突变的比例<20%,有些地点低至0.9%。基尔瓦12.8%(16/125)的样本中存在五重突变;基桑加尼为11.9%(13/109),博恩德为2.9%(3/102),巴萨库苏为0.9%(1/112)。这些结果表明对单独使用乙胺嘧啶或与周效磺胺联合使用具有高度耐药性。在SP中添加青蒿琥酯似乎不是当前单一疗法的有效替代方案。

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