Service de parasitologie-mycologie, faculté de médecine, université Cheikh-Anta-Diop, Dakar, Senegal.
C R Biol. 2013 May-Jun;336(5-6):295-300. doi: 10.1016/j.crvi.2013.04.016. Epub 2013 Jul 18.
Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positives samples (n=352) were collected from children under 5years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) was stable between years at<10% in the control group (P=0.69), while it rose significantly in the IPTi/c group from 2% in 2010 to 20% in 2011 (P=0.008). The prevalence of the Pfdhfr triple mutant haplotype (CIRN) increased in both groups, but only significantly in the IPTi/c group from 41% to 65% in 2011 (P=0.005). Conversely, the Pfdhps 437G mutation decreased in both groups from 44.6% to 28.6% (P=0.07) and from 66.7% to 47.5% (P=0.02) between 2010 and 2011 in the control and the IPTi/c groups, respectively. Combined with Pfdhfr, there was a weak trend for decreasing prevalence of quadruple mutants (triple Pfdhfr+Pfdhps 437G) in both groups (P=0.15 and P=0.34). During the two cross-sectional surveys, some significant changes were observed in the SP-resistance-related genes. However, since these changes were observed in the two groups, the IPTi/c strategy does only seem to have limited impact on resistance development and other factors as well. However, continuous monitoring will be needed, due to the up-scaling of the IPTi/c strategy in Senegal according to WHO recommendations.
自 2003 年以来，塞内加尔一直使用磺胺多辛-乙胺嘧啶（SP）对高危人群进行间歇性预防治疗（IPT）。然而，大规模的 IPT 策略可能会导致药物耐药性增加。我们的研究调查了在没有 IPTi/c 的地区和有 IPTi/c 的地区，给婴儿和儿童使用 SP-IPT 对恶性疟原虫基因 Pfdhfr 和 Pfdhps 中 SP 耐药单倍型流行率的可能影响。在 2010 年和 2011 年两次横断面调查中，从 5 岁以下儿童中采集了 352 个恶性疟原虫阳性样本，这些样本来自塞内加尔南部三个卫生区（两个有 IPTi/c，一个没有 IPTi/c 干预）。通过嵌套 PCR 随后进行序列特异性寡核苷酸探针（SSOP）-ELISA 确定 Pfdhfr 和 Pfdhps 中与 SP 耐药相关的单倍型的流行率。在对照组中，Pfdhfr 双突变体单倍型（CNRN 和 CICN）的流行率在两年间保持稳定，低于 10%（P=0.69），而在 IPTi/c 组中，该比例从 2010 年的 2%显著上升至 2011 年的 20%（P=0.008）。两组的 Pfdhfr 三突变体单倍型（CIRN）的流行率都有所增加，但仅在 IPTi/c 组中从 2011 年的 41%增加至 65%（P=0.005）。相反，Pfdhps 437G 突变在对照组和 IPTi/c 组中，分别从 2010 年的 44.6%下降至 28.6%（P=0.07）和从 2011 年的 66.7%下降至 47.5%（P=0.02）。如果与 Pfdhfr 结合，两组中四突变体（三突变体 Pfdhfr+Pfdhps 437G）的流行率有下降的趋势（P=0.15 和 P=0.34）。在两次横断面调查中，SP 耐药相关基因观察到一些显著变化。然而，由于这些变化在两组中都有观察到，因此 IPTi/c 策略似乎仅对耐药性发展产生了有限的影响，其他因素也有影响。然而，由于根据世卫组织的建议，塞内加尔正在扩大 IPTi/c 策略，因此仍需要持续监测。
