Aubouy Agnès, Bakary Mohamed, Keundjian Annick, Mbomat Bernard, Makita Jean Ruffin, Migot-Nabias Florence, Cot Michel, Le Bras Jacques, Deloron Philippe
Centre International de Recherches Médicales de Franceville, Unité de Parasitologie Médicale, Franceville, Gabon.
Antimicrob Agents Chemother. 2003 Jan;47(1):231-7. doi: 10.1128/AAC.47.1.231-237.2003.
Many African countries currently use a sulfadoxine-pyrimethamine combination (SP) or amodiaquine (AQ) to treat uncomplicated Plasmodium falciparum malaria. Both drugs represent the last inexpensive alternatives to chloroquine. However, resistant P. falciparum populations are largely reported in Africa, and it is compulsory to know the present situation of resistance. The in vivo World Health Organization standard 28-day test was used to assess the efficacy of AQ and SP to treat uncomplicated falciparum malaria in Gabonese children under 10 years of age. To document treatment failures, molecular genotyping to distinguish therapeutic failures from reinfections and drug dosages were undertaken. A total of 118 and 114 children were given AQ or SP, respectively, and were monitored. SP was more effective than AQ, with 14.0 and 34.7% of therapeutic failures, respectively. Three days after initiation of treatment, the mean level of monodesethylamodiaquine (MdAQ) in plasma was 149 ng/ml in children treated with amodiaquine. In those treated with SP, mean levels of sulfadoxine and pyrimethamine in plasma were 100 microg/ml and 212 ng/ml, respectively. Levels of the three drugs were higher in patients successfully treated with AQ (MdAQ plasma levels) or SP (sulfadoxine and pyrimethamine plasma levels). Blood concentration higher than breakpoints of 135 ng/ml for MdAQ, 100 micro g/ml for sulfadoxine, and 175 ng/ml for pyrimethamine were associated with treatment success (odds ratio: 4.5, 9.8, and 11.8, respectively; all P values were <0.009). Genotyping of merozoite surface proteins 1 and 2 demonstrated a mean of 4.0 genotypes per person before treatment. At reappearance of parasitemia, both recrudescent parasites (represented by common bands in both samples) and newly inoculated parasites (represented by bands that were absent before treatment) were present in the blood of most (51.1%) children. Only 3 (6.4%) therapeutic failures were the result not of treatment inefficacy but of new infection. In areas where levels of drug resistance and complexity of infections are high, drug dosage and parasite genotyping may be of limited interest in improving the precision of drug efficacy measurement. Their use should be weighted according to logistical constraints.
目前，许多非洲国家使用磺胺多辛-乙胺嘧啶合剂（SP）或阿莫地喹（AQ）治疗非复杂性恶性疟原虫疟疾。这两种药物是氯喹最后的廉价替代药物。然而，非洲大量报告了恶性疟原虫抗药群体，因此必须了解抗药现状。采用世界卫生组织的体内28天标准试验，评估AQ和SP治疗加蓬10岁以下儿童非复杂性恶性疟的疗效。为记录治疗失败情况，进行了分子基因分型以区分治疗失败与再感染，并记录了药物剂量。分别有118名和114名儿童接受了AQ或SP治疗并接受监测。SP比AQ更有效，治疗失败率分别为14.0%和34.7%。治疗开始三天后，接受阿莫地喹治疗的儿童血浆中单去乙基阿莫地喹（MdAQ）的平均水平为149纳克/毫升。接受SP治疗的儿童血浆中磺胺多辛和乙胺嘧啶的平均水平分别为100微克/毫升和212纳克/毫升。成功接受AQ治疗（MdAQ血浆水平）或SP治疗（磺胺多辛和乙胺嘧啶血浆水平）的患者中，这三种药物的水平更高。MdAQ血药浓度高于135纳克/毫升、磺胺多辛高于100微克/毫升、乙胺嘧啶高于175纳克/毫升的血药浓度与治疗成功相关（优势比分别为4.5、9.8和11.8；所有P值均<0.009）。裂殖子表面蛋白1和2的基因分型显示，治疗前每人平均有4.0种基因型。在再次出现寄生虫血症时，大多数（51.1%）儿童血液中既有复发的寄生虫（以两个样本中的共同条带表示），也有新感染的寄生虫（以治疗前不存在的条带表示）。只有3例（6.4%）治疗失败不是治疗无效所致，而是新感染所致。在耐药水平和感染复杂性较高的地区，药物剂量和寄生虫基因分型对于提高药物疗效测量的准确性可能作用有限。应根据后勤限制权衡其使用。
