Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment
Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment
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DOI：
10.1073/pnas.0901415106
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发表时间：
2009-06-02
影响因子：
11.1
通讯作者：
Duffy, P. E.
中科院分区：
文献类型：
--
作者：
Harrington, W. E.;Mutabingwa, T. K.;Duffy, P. E.
孕期间歇预防性治疗(IPTp)用于预防恶性疟疾。然而，对IPTp药物磺胺多辛-乙胺嘧啶(SP)产生抗药性的寄生虫已在全球范围内出现，乙胺嘧啶会加剧小鼠对混合抗药性和易感寄生虫的感染。在坦桑尼亚Muheza的一个前瞻性分娩队列中，我们检查了SP IPTp对寄生虫抗性等位基因、寄生虫多样性、寄生虫血症水平和胎盘炎症的影响。IPTp的使用与携带DHPS 581密码子耐药等位基因的寄生虫比例增加、寄生虫血症水平增加以及胎盘炎症加剧相关。最低的平均寄生虫多样性水平和最高的平均寄生虫血症水平出现在最近使用IPTp的妇女中。这些发现支持一种寄生虫释放和促进模型，即最高抗药性的寄生虫在药物压力下竞争不太适合的寄生虫种群并过度生长。对IPTp使用部分有效的抗疟疾药物可能会在普遍耐药的情况下加剧疟疾感染。
Intermittent preventive treatment in pregnancy (IPTp) is used to prevent Plasmodium falciparum malaria. However, parasites resistant to the IPTp drug sulfadoxine-pyrimethamine (SP) have emerged worldwide, and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice. In a prospective delivery cohort in Muheza, Tanzania, we examined the effects of SP IPTp on parasite resistance alleles, parasite diversity, level of parasitemia, and inflammation in the placenta. IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581, an increase in the level of parasitemia, and more intense placental inflammation. The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use. These findings support a model of parasite release and facilitation, whereby the most highly resistant parasites out-compete less fit parasite populations and overgrow under drug pressure. Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance.