Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali.
Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali.
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DOI：
10.1371/journal.pone.0162718
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Djimde AA
中科院分区：
文献类型：
--
作者：
Maiga H;Lasry E;Diarra M;Sagara I;Bamadio A;Traore A;Coumare S;Bahonan S;Sangare B;Dicko Y;Diallo N;Tembely A;Traore D;Niangaly H;Dao F;Haidara A;Dicko A;Doumbo OK;Djimde AA
西非萨赫勒国家正在推广使用磺胺二甲基乙胺(SP)加阿莫地喹(AQ)进行季节性疟疾化学预防(SMC)。然而，恶性疟原虫对各自成分药物的潜在耐药性的发展是一个主要问题。在马里库蒂亚拉试行SMC之前(2012年8月)和之后(2014年6月)进行了两次横断面调查。3-59个月的儿童在两个疟疾季节接受了7轮SP加AQ的治疗。采用聚合酶链式反应(PCR)对恶性疟原虫Pfdhfr密码子51、59和108、Pfdhps密码子437和540、Pfcrt密码子76和Pfmdr1密码子86进行基因分型，并以2014年11月非恶性疟患者为对照。在SMC人群中，镜检恶性疟原虫阳性者191/662(28.9%)和85/670(12.7%)，分别在实施SMC前(2012)和实施SMC后(2014)纳入分子分析。在非SMC患者中，220/310人(71%)成功地进行了聚合酶链式反应分析。在SMC儿童中，包括Pfdhfr-DHPS五重突变型在内的所有SP耐药分子标志物的患病率在SMC后均显著增加，SMC前为1.6%，SMC后为7.1%(p=0.02)。Pfmdr1-86Y的患病率从26.7%降至15.3%(p=0.04)，而Pfcrt 76T的患病率无明显变化。2014年，SMC儿童中SP耐药的所有分子标志物的患病率显著高于非SMC人群患者(P<；0.01)。SMC前和SMC后均未发现Pfdhfr-164突变。SMC增加了治疗儿童恶性疟原虫对SP耐药的分子标志物的发生率。然而，经过2年和7轮SMC后，这些抗性标记物在普通寄生虫种群中没有显著增加。
Seasonal malaria chemoprevention (SMC) with sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ) is being scaled up in Sahelian countries of West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern. Two cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP plus AQ over two malaria seasons. Genotypes of P. falciparum Pfdhfr codons 51, 59 and 108; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1codon 86 were analyzed by PCR on DNA from samples collected before and after SMC, and in non-SMC patient population as controls (November 2014). In the SMC population 191/662 (28.9%) and 85/670 (12.7%) of children were P. falciparum positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the non-SMC patient population 220/310 (71%) were successfully PCR analyzed. In the SMC children, the prevalence of all molecular markers of SP resistance increased significantly after SMC including the Pfdhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p = 0.02). The prevalence of Pfmdr1-86Y significantly decreased from 26.7% to 15.3% (p = 0.04) while no significant change was seen for Pfcrt 76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC population patient (p < 0.01). No Pfdhfr-164 mutation was found neither at baseline nor post SMC. SMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant increase of these markers of resistance in the general parasite population after 2 years and 7 rounds of SMC.
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DOI：
10.1086/647988
发表时间：
2009-12-01
期刊：
The Journal of infectious diseases
影响因子：
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作者：
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影响因子：
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影响因子：
3.3
作者：
Mockenhaupt, FP;Bousema, JT;Bienzle, U
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Bienzle, U
DOI：
10.4269/ajtmh.2003.69.558
发表时间：
2003-11-01
影响因子：
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