恶性疟原虫对复方新抗疟药双氢青蒿素/哌喹敏感性现场体外微量测定方法研究(英文)

STUDY OF ON-SITE METHODS OF IN VITRO DETERMINATION OF THE SENSITIVITY OF PLASMODIUM FALCIPARUM TO A NEW ANTIMALARIAL COMPOUND OF DIHYDROARTEMISININ AND PIPERAQUINE

目的探索恶性疟原虫对复方新抗疟药双氢青蒿素/哌喹的敏感性现场体外监测方法 ,以指导药物敏感性监测。方法参照WHO推荐的Rieckmann体外微量测定法,在自制双氢青蒿素/哌喹涂药板中测定2种药物单方以及复方的敏感性。结果单一药物板测定成功率分别为76.92%和75.00%,复方涂药板测定成功率为76.92%;两药联用疟原虫抑制率明显高于单方,单方和复方各井疟原虫抑制率均随药物浓度的增高而依次上升。两药联用可明显减少药物用量,且两药协同降低哌喹使用比例。结论自制药物测定板稳定、灵敏、重复性好、简便易行,可现场推广使用;单方青蒿素类药物以及哌喹耐药性有上升趋势,两药联用时明显减少药物用量,可能延缓抗药性的产生;双氢青蒿素与哌喹两药组方最佳摩尔浓度比例为1∶3.5～4.4。

Objective To explore on-site methods for in vitro determination of the sensitivity of Plasmodium falciparum to a new compound of the antimalarials dihydroartemisinin and piperaquine in order to guide drug sensitivity monitoring. Methods Referring to the Rieckmann micro in vitro assay recommended by the WHO, the sensitivity of P. falciparum to each drug was measured in combination and alone in plates coated with dihydroartemisinin and piperaquine. Results Sensitivity was determined at a success rate of 76.92% and 75.00% in single-drug plates and at a success rate of 76.92% in compound-coated plates. The drug compound had a markedly higher rate of inhibiting P. falciparum than single drugs. The inhibition rates of both single drugs and a compound of both increased in succession as their concentration increased. The compound significantly reduced drug dosage, and the synergy of the two drugs reduced the proportion of piperaquine. Conclusion Results suggested that these plates coated with dihydroartemisinin and piperaquine are sta- ble, sensitive, provide good reproducibility, are simple and easy to use, and can encourage increased use on-site. P. falciparum has become increasingly resistant to single artemisinin derivatives and piperaquine. Drug dosage was significantly reduced when the two drugs were combined and may delay the emergence of drug resistance, so using the two in combina- tion is vital. The optimal molar concentration ratio for concomitant use of dihydroartemisinin and piperaquine was 1 ： 3.5-4.4.