在马里，使用周效磺胺-乙胺嘧啶和阿莫地喹进行季节性疟疾化学预防会选择出Pfdhfr-dhps五重突变基因型。
Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali.
作者信息
Maiga Hamma, Lasry Estrella, Diarra Modibo, Sagara Issaka, Bamadio Amadou, Traore Aliou, Coumare Samba, Bahonan Soma, Sangare Boubou, Dicko Yeyia, Diallo Nouhoum, Tembely Aly, Traore Djibril, Niangaly Hamidou, Dao François, Haidara Aboubecrine, Dicko Alassane, Doumbo Ogobara K, Djimde Abdoulaye A
机构信息
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Odontostomatology and Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali.
Médecins Sans Frontières (MSF), New York, New York, United States of America.
出版信息
PLoS One. 2016 Sep 23;11(9):e0162718. doi: 10.1371/journal.pone.0162718. eCollection 2016.
BACKGROUND
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.
METHODS
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).
RESULTS
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.
CONCLUSION
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.
背景
在西非萨赫勒地区国家，正在扩大使用磺胺多辛 - 乙胺嘧啶（SP）加阿莫地喹（AQ）进行季节性疟疾化学预防（SMC）。然而，恶性疟原虫对各组分药物产生耐药性的潜在发展是一个主要问题。
方法
在马里库蒂亚拉进行了两次横断面调查，分别在SMC试点实施前（2012年8月）和实施后（2014年6月）。3至59个月大的儿童在两个疟疾季节接受了7轮治疗剂量的SP加AQ。通过对SMC前后收集的样本以及作为对照的非SMC患者群体（2014年11月）的DNA进行PCR分析，检测恶性疟原虫Pfdhfr密码子51、59和108；Pfdhps密码子437和540、Pfcrt密码子76以及Pfmdr1密码子86的基因型。
结果
在接受SMC的儿童群体中，通过显微镜检查，2012年（SMC实施前）和2014年（SMC实施后）分别有191/662（28.9%）和85/670（12.7%）的儿童恶性疟原虫呈阳性，并纳入分子分析。在非SMC患者群体中，220/310（71%）成功进行了PCR分析。在接受SMC的儿童中，SMC实施后所有SP耐药分子标记的患病率均显著增加，包括Pfdhfr - dhps五重突变基因型，该基因型在SMC实施前为1.6%，实施后为7.1%（p = 0.02）。Pfmdr1 - 86Y的患病率从26.7%显著降至15.3%（p = 0.04），而Pfcrt 76T未观察到显著变化。2014年，接受SMC的儿童中所有SP耐药分子标记的患病率显著高于非SMC患者群体（p < 0.01）。在基线和SMC实施后均未发现Pfdhfr - 164突变。
结论
SMC增加了接受治疗儿童中恶性疟原虫对SP耐药分子标记的患病率。然而，经过2年和7轮SMC后，这些耐药标记在总体寄生虫群体中并未显著增加。
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