In vitro sensitivity of Plasmodium falciparum to conventional and novel antimalarial drugs in Papua New Guinea

In vitro sensitivity of Plasmodium falciparum to conventional and novel antimalarial drugs in Papua New Guinea
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DOI:
10.1111/j.1365-3156.2009.02463.x
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发表时间:
2010-03-01
影响因子:
3.3
通讯作者:
Davis, Timothy M. E.
Davis, Timothy M. E.
中科院分区:
医学4区
文献类型:
--
作者:
Wong, Rina P. M.;Lautu, Dulcie;Davis, Timothy M. E.

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目的近期临床研究表明,巴布亚新几内亚(PNG)流行区疟疾治疗失败率很高,需要从氯喹(CQ)或阿莫地喹(AQ)加磺胺乙胺改为青蒿素联合疗法(ACT)、蒿甲醚加鲁米芬(LM)。方法采用乳酸脱氢酶比色法测定恶性疟原虫分离株对9种常用或新型抗疟药物[CQ,AQ,DAQ,哌喹(PQ),萘喹(NQ),甲氟喹(MQ),LM,双氢青蒿素和阿奇霉素(AZ)]对恶性疟原虫生长抑制作用的几何平均浓度(95%可信区间)为167(141~197)nm。82%的菌株耐药(阈值100 nm),这与PNG中与CQ耐药相关的pfcrt等位基因接近固定一致。除AZ[8.351(5.418-12.871)nm]外,其余药物的几何平均IC_(50)为
OBJECTIVE Recent clinical studies have shown high rates of malaria treatment failure in endemic areas of Papua New Guinea (PNG), necessitating a change of treatment from chloroquine (CQ) or amodiaquine (AQ) plus sulphadoxine-pyrimethamine to the artemisinin combination therapy ( ACT) artemether plus lumefantrine (LM). To facilitate the monitoring of antimalarial drug resistance in this setting, we assessed the in vitro sensitivity of Plasmodium falciparum isolates from Madang Province.METHODS A validated colorimetric lactate dehydrogenase assay was used to assess growth inhibition of 64 P. falciparum isolates in the presence of nine conventional or novel antimalarial drugs [CQ, AQ, monodesethyl-amodiaquine (DAQ), piperaquine (PQ), naphthoquine (NQ), mefloquine (MQ), LM, dihydroartemisinin and azithromycin (AZ)].RESULTS The geometric mean (95% confidence interval) concentration required to inhibit parasite growth by 50% (IC50) was 167 (141-197) nm for CQ, and 82% of strains were resistant (threshold 100 nm), consistent with near-fixation of the CQ resistance-associated pfcrt allele in PNG. Except for AZ [8.351 (5.418-12.871) nm], the geometric mean IC50 for the other drugs was