分子标志物对磺胺多辛-乙胺嘧啶耐药性的影响：在马里实施婴儿间歇性预防治疗疟疾一年后。
Molecular markers of resistance to sulphadoxine-pyrimethamine one year after implementation of intermittent preventive treatment of malaria in infants in Mali.
机构信息
Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine Pharmacy and Dentistry, University of Bamako, PO Box 1805 Bamako, Mali.
出版信息
Malar J. 2010 Jan 10;9:9. doi: 10.1186/1475-2875-9-9.
BACKGROUND
Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations is efficacious in preventing malaria disease and shows no interaction with the vaccines. However, there is a fear that IPTi may result in a rapid increase of parasite resistance to SP.
METHODS
To evaluate the impact of IPTi on SP-resistance point mutations, the 22 health sub-districts in the district of Kolokani, Mali, were randomized in a 1:1 ratio and starting in December 2006, IPTi with SP was implemented in 11 health sub-districts (intervention zone), while the other 11 health sub-districts served as the control (non-intervention zone). Blood smears and blood dots on filter paper were obtained from children aged 0-5 years, randomly selected in each of heath sub-districts during two cross-sectional surveys. The first survey was conducted in May 2007 before the start of the transmission season to collect baseline prevalence of the molecular markers of resistance to SP and the second in December 2007 after the end of the transmission season and one year after implementation of IPTi. A total of 427 and 923 randomly selected blood samples from the first and second surveys respectively were analysed by PCR for dhfr and dhps mutations.
RESULTS
Each of the three dhfr mutations at codons 51, 59 and 108 was present in 35% and 57% of the samples during the two surveys with no significant differences between the two zones. Dhps mutations at codons 437 and 540 were present respectively in about 20% and 1% of the children during the two surveys in both zones at similar proportion. The prevalence of quadruple mutants (triple dhfr-mutants + dhps-437G) associated with in-vivo resistance to SP in Mali after one year implementation of IPTi was also similar between the two zones (11.6% versus 11.2%, p = 0.90) and to those obtained at baseline survey (10.3% versus 8.1%).
CONCLUSION
This study shows no increase in the frequency of molecular markers of SP resistance in areas where IPTi with SP was implemented for one year.
背景
在常规疫苗接种期间用磺胺多辛-乙胺嘧啶（SP）对婴儿进行间歇性预防治疗（IPTi）可有效预防疟疾，并且与疫苗之间没有相互作用。但是，人们担心 IPTi 可能导致寄生虫对 SP 的耐药性迅速增加。
方法
为了评估 IPTi 对 SP 耐药点突变的影响，在马里科洛卡尼区的 22 个卫生分区以 1：1 的比例进行了随机分组，从 2006 年 12 月开始，在 11 个卫生分区（干预区）实施了 IPTi 与 SP，而其他 11 个卫生分区作为对照（非干预区）。在两次横断面调查中，从每个卫生分区随机选择 0-5 岁儿童，采集血涂片和滤纸上的血点。第一次调查于 2007 年 5 月进行，在传播季节开始前进行，以收集 SP 耐药分子标志物的基线流行率，第二次调查于 2007 年 12 月进行，在传播季节结束后和实施 IPTi 一年后进行。共有 427 名和 923 名分别来自第一次和第二次调查的随机选择的血液样本，通过 PCR 分析 dhfr 和 dhps 突变。
结果
在两次调查中，每个 codon51、59 和 108 的三个 dhfr 突变都存在于 35%和 57%的样本中，两个区域之间没有显著差异。dhps 突变 codons437 和 540 分别存在于两次调查中约 20%和 1%的儿童中，在两个区域的比例相似。在实施 IPTi 一年后，与体内对 SP 耐药相关的四重突变（三重 dhfr-突变体+ dhps-437G）在两个区域的流行率也相似（11.6%对 11.2%，p=0.90），与基线调查时获得的流行率也相似（10.3%对 8.1%）。
结论
本研究表明，在实施 IPTi 与 SP 一年的地区，SP 耐药的分子标志物频率没有增加。
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