BACKGROUND:Malaria remains a major public health problem, due largely to emergence and widespread P. falciparum drug resistance. WHO recommends artemisinine combination based therapy (ACT) to overcome P. falciparum drug resistance, but reports of declining ACT efficacy have been published. A thorough understanding of the molecular bases of P. falciparum resistance to existing drugs is therefore needed. The aims of this study were to analyze the in vitro sensitivity of P. falciparum field isolates from Franceville, Gabon, to chloroquine (CQ), mefloquine (MF), dihydroartemisinine (DHA) and monodesethylamodiaquine (MDAQ), and to investigate polymorphisms associated with drug resistance.
METHODS:We conducted a cross-sectional study of 53 field isolates. Field isolates sensitivity to CQ, MF, DHA and MDAQ was assessed using the colorimetric DELI test. The Pfmdr1 codons 86 and 1246, Pfcrt (haplotype codon 72 to 76) and the PfATPAse6 codons 110 and 2694 were analysed by PCR-RFLP. Associations between drug sensitivity and parasite gene polymorphisms were evaluated with the Chi square test, and routine hematological parameters were analyzed with Fisher's exact test implemented with Epinfo software. In all statistical tests, significance was assumed at p<0.05.
RESULTS:A total of 46 P. falciparum isolates were successfully cultured in vitro and their sensitivity was tested. The proportions of isolates resistant to CQ, MF and MDAQ were 43.5%, 23.4% and 56.5%, respectively. Some isolates (23.9%) had DHA IC50 values higher than 10 nM. The median IC50 values were 71.67 (interquartile range (IQR, 1-438.2), 6.59 (IQR, 0.08-96), 64.79 (IQR, 0.09-448) and 6.45 nM (IQR, 0.09-23) for CQ, MF, MDAQ and DHA, respectively. The strongest correlation between diminished DHA sensitivity and MF resistance was observed (r2=0.73), followed by correlation between diminished DHA sensitivity and CQ resistance. Cross-resistance between CQ and MF was also observed. The prevalence of the 86Y and 1246Y mutations in Pfmdr1, 76T in Pfcrt, and 110A and 2694T in PfATPase6 was respectively 42% and 17.1%, 97.8%, and 0% and 22.2%.
CONCLUSION:These high levels of antimalarial drug resistance in Franceville, Gabon, call for reinforced surveillance of drug efficacy.
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【In vitro antimalarial susceptibility and molecular markers of drug resistance in Franceville, Gabon.].
【加蓬弗朗斯维尔的体外抗疟药敏感性和耐药性分子标记。】
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DOI：10.1186/1471-2334-12-307文章类型：杂志文章
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背景：疟疾仍然是主要的公共卫生问题，这主要是由于恶性疟原虫耐药性的出现和广泛存在。世卫组织建议以青蒿素为基础的联合疗法（ACT）来克服恶性疟原虫的耐药性，但已发表了有关ACT疗效下降的报道。因此，需要彻底了解恶性疟原虫对现有药物的抗性的分子基础。这项研究的目的是分析来自法国弗朗斯维尔，加蓬的恶性疟原虫野外分离株对氯喹（CQ），甲氟喹（MF），双氢青蒿素（DHA）和单去甲二甲基喹（MDAQ）的体外敏感性，并研究与之相关的多态性。耐药性。
方法：我们对53个野外分离株进行了横断面研究。使用比色DELI测试评估了现场分离株对CQ，MF，DHA和MDAQ的敏感性。通过PCR-RFLP分析了Pfmdr1密码子86和1246，Pfcrt（单倍型密码子72至76）和PfATPAse6密码子110和2694。用卡方检验评估药物敏感性和寄生虫基因多态性之间的关联，并使用Epinfo软件实施的Fisher精确检验分析常规血液学参数。在所有统计检验中，显着性假设为p <0.05。
结果：共成功分离出46株恶性疟原虫分离株，并对其敏感性进行了测试。抗CQ，MF和MDAQ的分离株比例分别为43.5％，23.4％和56.5％。一些分离株（23.9％）的DHA IC50值高于10 nM。对于CQ，MF和MDAQ，IC50的中间值分别为71.67（四分位间距（IQR，1-438.2），6.59（IQR，0.08-96），64.79（IQR，0.09-448）和6.45 nM（IQR，0.09-23）分别观察到DHA和DHA灵敏度降低之间的最强相关性（r2 = 0.73），其次是DHA灵敏度降低与CQ电阻之间的相关性，还观察到CQ和MF之间的交叉抗性，86Y的患病率Pfmdr1，Pfcrt中的76T和PfATPase6中的110A和2694T的1246Y和1246Y突变分别为42％和17.1％，97.8％，0％和22.2％。
结论：在加蓬弗朗斯维尔，这些高水平的抗疟药耐药性要求加强对药物疗效的监测。
方法：我们对53个野外分离株进行了横断面研究。使用比色DELI测试评估了现场分离株对CQ，MF，DHA和MDAQ的敏感性。通过PCR-RFLP分析了Pfmdr1密码子86和1246，Pfcrt（单倍型密码子72至76）和PfATPAse6密码子110和2694。用卡方检验评估药物敏感性和寄生虫基因多态性之间的关联，并使用Epinfo软件实施的Fisher精确检验分析常规血液学参数。在所有统计检验中，显着性假设为p <0.05。
结果：共成功分离出46株恶性疟原虫分离株，并对其敏感性进行了测试。抗CQ，MF和MDAQ的分离株比例分别为43.5％，23.4％和56.5％。一些分离株（23.9％）的DHA IC50值高于10 nM。对于CQ，MF和MDAQ，IC50的中间值分别为71.67（四分位间距（IQR，1-438.2），6.59（IQR，0.08-96），64.79（IQR，0.09-448）和6.45 nM（IQR，0.09-23）分别观察到DHA和DHA灵敏度降低之间的最强相关性（r2 = 0.73），其次是DHA灵敏度降低与CQ电阻之间的相关性，还观察到CQ和MF之间的交叉抗性，86Y的患病率Pfmdr1，Pfcrt中的76T和PfATPase6中的110A和2694T的1246Y和1246Y突变分别为42％和17.1％，97.8％，0％和22.2％。
结论：在加蓬弗朗斯维尔，这些高水平的抗疟药耐药性要求加强对药物疗效的监测。
