Méndez Fabián, Herrera Sócrates, Murrain Bermans, Gutiérrez Andrés, Moreno Luz A, Manzano María, Muñoz Alvaro, Plowe Christopher V
Escuela de Salud Pública, Universidad del Valle, Cali, Colombia.
Am J Trop Med Hyg. 2007 Sep;77(3):438-43.
Resistance-conferring mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Plasmodium falciparum are selected by treatment with sulfadoxine pyrimethamine (SP). We assessed the association between these mutations and transmission capacity of parasites to Anopheles mosquitoes on the Pacific coast of Colombia. Patients with uncomplicated P. falciparum malaria received SP treatment and were followed-up to compare the prevalence of DHFR and DHPS mutations before and after SP treatment. Membrane feeding assays were used to measure infectivity to mosquitoes of post-treatment gametocytes with and without these mutations. Per-protocol treatment efficacy was 95.0% (132 of 139). Gametocytes carrying resistance-conferring mutations were selected after SP treatment and were infective to mosquitoes. Seven days after treatment, infections with two DHFR mutations had a 10-fold higher probability of infecting mosquitoes than infections with no DHFR mutations (odds ratio = 10.23, P < 0.05). Low-level drug resistance mutations have the potential to enhance transmission of P. falciparum and spread resistant parasites.
恶性疟原虫中二氢叶酸还原酶（DHFR）和二氢蝶酸合酶（DHPS）的耐药性突变是通过使用磺胺多辛-乙胺嘧啶（SP）治疗而产生的。我们评估了这些突变与哥伦比亚太平洋沿岸地区疟原虫向按蚊传播能力之间的关联。患有非复杂性恶性疟原虫疟疾的患者接受了SP治疗，并进行随访以比较SP治疗前后DHFR和DHPS突变的发生率。采用膜饲法测定有或无这些突变的治疗后配子体对蚊子的感染性。符合方案的治疗有效率为95.0%（139例中的132例）。携带耐药性突变的配子体在SP治疗后被筛选出来，并对蚊子具有感染性。治疗7天后，具有两种DHFR突变的感染感染蚊子的概率比没有DHFR突变的感染高10倍（优势比 = 10.23，P < 0.05）。低水平耐药性突变有可能增强恶性疟原虫的传播并扩散耐药寄生虫。
