体内对阿莫地喹耐药的恶性疟原虫疟疾与pfcrt 76T和pfmdr1 86Y的选择有关。
Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y.
作者信息
Holmgren Gabrielle, Gil José P, Ferreira Pedro M, Veiga Maria I, Obonyo Charles O, Björkman Anders
机构信息
Malaria Research Laboratory, Unit of Infectious diseases, Department of Medicine, Karolinska Institute, Karolinska University Hospital, M9:02, 17176 Stockholm, Sweden.
出版信息
Infect Genet Evol. 2006 Jul;6(4):309-14. doi: 10.1016/j.meegid.2005.09.001. Epub 2005 Nov 2.
The choice of partner drug is critical for artemisinine-based combination therapy (ACT) to remain effective and amodiaquine (AQ) is one important candidate to evaluate. We treated 81 children <5 years with uncomplicated Plasmodium falciparum malaria with AQ alone and related the treatment outcome to the possible selection of pfcrt 76T, 152T, 163S, 326S, pfmdr1 86Y and pfmrp 191H, 437S in recurrent infections (recrudescenses and re-infections) and to the blood concentration of desethylamodiaquine (DEAQ). During 21 days follow-up 28 children had a recurrent infection (9 recrudescenses, 13 re-infections and 6 mixed). Neither genotyping of the polymorphisms before treatment nor DEAQ blood concentrations could predict treatment outcome. pfcrt 76T was however significantly selected for in recurrent infections (p=0.020). pfmdr1 86Y was also selected for, but only in recrudescent infections (p=0.048). The study showed high prevalence of AQ resistant parasites in vivo, which appeared to be associated to pfcrt 76T and pfmdr1 86Y.
对于以青蒿素为基础的联合疗法（ACT）而言，选择联合用药对于维持其有效性至关重要，而阿莫地喹（AQ）是一个值得评估的重要候选药物。我们单用AQ治疗了81名5岁以下患单纯性恶性疟原虫疟疾的儿童，并将治疗结果与复发性感染（复发和再感染）中可能出现的pfcrt 76T、152T、163S、326S、pfmdr1 86Y以及pfmrp 191H、437S的选择情况，以及去乙基阿莫地喹（DEAQ）的血药浓度进行关联分析。在21天的随访期间，28名儿童出现了复发性感染（9例复发、13例再感染和6例混合感染）。治疗前的多态性基因分型和DEAQ血药浓度均无法预测治疗结果。然而，pfcrt 76T在复发性感染中被显著选择（p=0.020）。pfmdr1 86Y也被选择，但仅在复发感染中（p=0.048）。该研究表明，体内AQ耐药寄生虫的患病率很高，这似乎与pfcrt 76T和pfmdr1 86Y有关。
Zotero 插件