Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment
Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment
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DOI：
10.1111/j.1365-3165.2007.01813.x
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发表时间：
2007-02-01
影响因子：
3.3
通讯作者：
Taylor, Walter R. J.
中科院分区：
文献类型：
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作者：
Mugittu, Kefas;Priotto, Gerardo;Taylor, Walter R. J.
药效试验中疟原虫的聚合酶链反应 (PCR) 基因分型有助于区分再感染和复发。在乌干达西部中流行区姆巴拉拉进行了一项联合治疗试验，试验为青蒿琥酯（1AS、3AS 4 mg/kg/天）加磺胺多辛-乙胺嘧啶 (SP) 与单独 SP (n = 153) 的联合治疗试验。通过 PCR 扩增和分析富含谷氨酸蛋白 (glurp) 和裂殖子表面蛋白 (msp) 1 和 2 基因，对治疗后第 7、14、21 和 28 天的所有配对复发恶性疟原虫寄生虫病进行基因分型，以区分复发感染和新感染。成功分析了 199 个配对复发样本中的总共 156 个（1AS = 61、3AS = 35、单独 SP = 60），并解析为 79 个复发样本（1AS = 32、3AS = 8、SP = 39）和 77 个新感染（1AS = 29、3AS = 27、SP = 21）。第7、14、21和28天新发感染与复发感染的比例之比分别为0.2、0.9、1.4和1.9（P < 0.001，线性趋势χ(2)检验）。在随访第 7 天 [5/26 (19.2%)] 和第 14 天 [24/51 (47.1%)] 早期观察到意外的高新感染率。这些结果对耐药性监测有显着影响，并指出了抗疟试验中对所有复发感染进行基因分型的价值。
Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.