2010 年塞内加尔达喀尔地区恶性疟原虫对抗疟药物的敏感性：一项离体和耐药分子标志物研究。
Plasmodium falciparum susceptibility to anti-malarial drugs in Dakar, Senegal, in 2010: an ex vivo and drug resistance molecular markers study.
机构信息
Laboratoire d'étude de la chimiosensibilité du paludisme, Fédération des laboratoires, Hôpital Principal de Dakar, Dakar, Sénégal.
出版信息
Malar J. 2013 Mar 20;12:107. doi: 10.1186/1475-2875-12-107.
BACKGROUND
In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, there have been very few reports on the level of resistance of P. falciparum to anti-malarial drugs. To determine whether parasite susceptibility has been affected by the new anti-malarial policies, an ex vivo susceptibility and drug resistance molecular marker study was conducted on local isolates obtained from the Centre de santé Elizabeth Diouf (Médina, Dakar, Senegal).
METHODS
The prevalence of genetic polymorphisms in genes associated with anti-malarial drug resistance, i.e., pfcrt, pfdhfr, pfdhps and pfmdr1, were evaluated for a panel of 165 isolates collected from patients recruited from 17 August 2010 to 6 January 2011. The malaria isolates were assessed for susceptibility to chloroquine (CQ); quinine (QN); monodesethylamodiaquine (MDAQ), the active metabolite of amodiaquine; mefloquine (MQ); lumefantrine (LMF); dihydroartemisinin (DHA), the active metabolite of artemisinin derivatives; and doxycycline (DOX) using the Plasmodium lactate dehydrogenase (pLDH) ELISA.
RESULTS
The prevalence of the in vitro resistant isolates, or isolates with reduced susceptibility, was 62.1% for MQ, 24.2% for CQ, 10.3% for DOX, 11.8% MDAQ, 9.7% for QN, 2.9% for LMF and 0% for DHA. The Pfcrt 76T mutation was identified in 43.6% of the samples. The pfmdr1 86Y, 184F and 1246Y mutations were found in 16.2%, 50.0% and 1.6% of the samples, respectively. The pfdhfr 108N, 51I and 59R mutations were identified in 81.9%, 77.4% and 79.4% of the samples, respectively. The double mutant (108N and 51I) was detected in 75.5% of the isolates, and the triple mutant (108N, 51I and 59R) was detected in 73.6% of the isolates. The pfdhps 437G, 436A and 613S mutations were found in 54.4%, 38.6% and 1.2% of the samples, respectively. There was only one double mutant, 437G and 540E, and one quintuple mutant, pfdhfr 108N, 51I and 59R and pfdhps 437G and 540E. The prevalence of the quadruple mutant (pfdhfr 108N, 51I and 59R and pfdhps 437G) was 36.7%.
CONCLUSIONS
The results of this study indicate that an intensive surveillance of the in vitro P. falciparum susceptibility to anti-malarial drugs must be conducted in Senegal.
背景
2006 年，塞内加尔国家疟疾控制规划推荐青蒿素为基础的联合疗法（ACT）作为治疗无并发症疟疾的一线药物。自 ACT 推出以来，关于恶性疟原虫对抗疟药物的耐药性水平的报告很少。为了确定新的抗疟政策是否影响寄生虫的敏感性，对从塞内加尔达喀尔伊丽莎白·迪乌夫医疗中心（ Medina ）招募的患者中获得的当地分离株进行了体外敏感性和耐药性分子标志物研究。
方法
评估了与抗疟药物耐药性相关的基因（即 pfcrt、pfdhfr、pfdhps 和 pfmdr1）的遗传多态性的流行率，用于从 2010 年 8 月 17 日至 2011 年 1 月 6 日招募的患者中收集的 165 个分离株。采用疟原乳酸脱氢酶（pLDH）ELISA 法评估氯喹（CQ）；奎宁（QN）；单去乙基阿莫地喹（MDAQ），阿莫地喹的活性代谢物；甲氟喹（MQ）；青蒿琥酯（LMF）；二氢青蒿素（DHA），青蒿素衍生物的活性代谢物；和强力霉素（DOX）对疟疾分离株的敏感性。
结果
体外耐药分离株或敏感性降低的分离株的流行率分别为 MQ 为 62.1%，CQ 为 24.2%，DOX 为 10.3%，MDAQ 为 11.8%，QN 为 9.7%，LMF 为 2.9%，DHA 为 0%。在 43.6%的样本中发现了 Pfcrt 76T 突变。pfmdr1 86Y、184F 和 1246Y 突变分别在 16.2%、50.0%和 1.6%的样本中发现。pfdhfr 108N、51I 和 59R 突变分别在 81.9%、77.4%和 79.4%的样本中发现。双突变（108N 和 51I）在 75.5%的分离株中检测到，三突变（108N、51I 和 59R）在 73.6%的分离株中检测到。pfdhps 437G、436A 和 613S 突变分别在 54.4%、38.6%和 1.2%的样本中发现。只有一个双突变，437G 和 540E，一个五重突变，pfdhfr 108N、51I 和 59R 和 pfdhps 437G 和 540E。四重突变（pfdhfr 108N、51I 和 59R 和 pfdhps 437G）的流行率为 36.7%。
结论
本研究结果表明，必须在塞内加尔对体外恶性疟原虫对抗疟药物的敏感性进行强化监测。
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