Decreasing efficacy of antimalarial combination therapy in Uganda is explained by decreasing host immunity rather than increasing drug resistance.
Decreasing efficacy of antimalarial combination therapy in Uganda is explained by decreasing host immunity rather than increasing drug resistance.
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DOI：
10.1086/596741
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发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Dorsey G
中科院分区：
文献类型：
--
作者：
Greenhouse B;Slater M;Njama-Meya D;Nzarubara B;Maiteki-Sebuguzi C;Clark TD;Staedke SG;Kamya MR;Hubbard A;Rosenthal PJ;Dorsey G
控制工作的改善正在减轻非洲疟疾的负担，但可能导致抗疟免疫力下降。作为纵向临床试验的一部分，在乌干达坎帕拉的129名1 - 10岁的儿童队列中，在29个月期间用阿莫地喹+磺胺嘧啶-乙胺嘧啶治疗396次无并发症的疟疾发作。在研究过程中，治疗失败的风险从5%增加到21%（HR = 2.4/年，95%CI = 1.3 - 4.3）。寄生虫遗传多态性与失败风险增加相关，但其患病率并不随时间而变化。抗疟免疫的三个标志物与治疗失败的风险降低相关：年龄增加（HR = 0.5/5岁，95%CI = 0.2 - 1.2），生活在疟疾发病率较高的地区（HR = 0.26，95%CI = 0.11 - 0.64），近期无症状寄生虫血症（HR = 0.06，95%CI = 0.01 - 0.36）。在多变量分析中，调整近期无症状寄生虫血症，而不是寄生虫多态性，消除了日历时间和治疗失败风险之间的关联（HR = 1.5/yr，95%CI = 0.7 - 3.4），表明治疗效果恶化最好解释为宿主免疫力下降。在我们的研究人群中，免疫力下降似乎是阿莫地喹+磺胺嘧啶-乙胺嘧啶疗效下降的主要因素。随着疟疾控制工作的改进，免疫力下降可能会暴露对部分有效药物的耐药性。
Improved control efforts are reducing the burden of malaria in Africa, but may result in decreased antimalarial immunity. A cohort of 129 children aged 1–10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for 396 episodes of uncomplicated malaria over a 29 month period as part of a longitudinal clinical trial. The risk of treatment failure increased over the course of the study from 5% to 21% (HR=2.4/yr, 95%CI=1.3–4.3). Parasite genetic polymorphisms were associated with an increased risk of failure, but their prevalence did not change over time. Three markers of antimalarial immunity were associated with a decreased risk of treatment failure: increased age (HR=0.5/5yrs, 95%CI=0.2–1.2), living in an area of higher malaria incidence (HR=0.26, 95%CI=0.11–0.64), and recent asymptomatic parasitemia (HR=0.06, 95%CI=0.01–0.36). In multivariate analysis, adjustment for recent asymptomatic parasitemia, but not parasite polymorphisms, removed the association between calendar time and the risk of treatment failure (HR=1.5/yr, 95%CI=0.7–3.4), suggesting that worsening treatment efficacy was best explained by decreasing host immunity. Declining immunity in our study population appeared to be the primary factor underlying decreased efficacy of amodiaquine+sulfadoxine-pyrimethamine. With improved malaria control efforts, decreasing immunity may unmask resistance to partially efficacious drugs.
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临床免疫宿主是对药物敏感疟疾寄生虫的避难所。
影响因子：
3
作者：
Klein EY;Smith DL;Boni MF;Laxminarayan R
通讯作者：
Laxminarayan R
DOI：
10.4269/ajtmh.2000.62.686
发表时间：
2000-06-01
影响因子：
3.3
作者：
Dorsey, G;Kamya, MR;Rosenthal, PJ
通讯作者：
Rosenthal, PJ
影响因子：
6.4
作者：
Lynch, Caroline;Pearce, Richard;Roper, Cally
通讯作者：
Roper, Cally
DOI：
10.4269/ajtmh.2003.69.558
发表时间：
2003-11-01
影响因子：
3.3
作者：
Djimdé, AA;Doumbo, OK;Plowe, CV
通讯作者：
Plowe, CV
DOI：
10.4269/ajtmh.2004.71.758
发表时间：
2004-12-01
影响因子：
3.3
作者：
Dorsey, G;Dokomajilar, C;Rosenthal, PJ
通讯作者：
Rosenthal, PJ