Sasi Philip, Abdulrahaman Abdi, Mwai Leah, Muriithi Steven, Straimer Judith, Schieck Elise, Rippert Anja, Bashraheil Mahfudh, Salim Amina, Peshu Judith, Awuondo Ken, Lowe Brett, Pirmohamed Munir, Winstanley Peter, Ward Steve, Nzila Alexis, Borrmann Steffen
Kenya Medical Research Institute, Center for Geographic Medicine Research-Coast, Kilifi, Kenya.
J Infect Dis. 2009 Jun 1;199(11):1575-82. doi: 10.1086/598862.
In light of reports of increasing resistance of parasites to amodiaquine in African countries in which Plasmodium falciparum is endemic as well as the paucity of recent in vitro sensitivity data, we assessed the in vivo and in vitro sensitivity to amodiaquine of P. falciparum isolates from 128 pediatric outpatients (0.5-10 years old) in Pingilikani, Kilifi District, Kenya, who were treated with amodiaquine (10 mg/kg/day for 3 days). The polymerase chain reaction-corrected parasitological cure rate on day 28 (by Kaplan-Meier analysis) was 82% (95% confidence interval [CI], 74%-88%). Twenty-six percent (17/66) of tested pretreatment P. falciparum field isolates had 50% in vitro growth inhibition at concentrations of N-desethyl-amodiaquine (DEAQ)-the major biologically active metabolite of amodiaquine-above the proposed resistance threshold of 60 nmol/L, but baseline median DEAQ 50% inhibitory concentration values were not associated with subsequent risk of asexual parasite recrudescence (29 nmol/L [95% CI, 23-170 nmol/L] and 34 nmol/L [95% CI, 30-46 nmol/L] for patients with and those without recrudescences, respectively). The median absolute neutrophil count dropped by 1.3 X 10(3) cells/microL (95% CI, -1.7 X 10(3) to -0.7 X 10(3) cells/microL) between days 0 and 28. The high prevalence of in vitro and in vivo resistance precludes the use of amodiaquine on its own as second-line treatment. These findings also suggest that the value of amodiaquine combinations as first- or second-line treatment in areas with similar patterns of 4-aminoquinoline resistance should be reassessed.
鉴于在恶性疟原虫流行的非洲国家有报告称寄生虫对阿莫地喹的耐药性不断增加，且近期体外敏感性数据匮乏，我们评估了来自肯尼亚基利菲区平吉利卡尼128名儿科门诊患者（0.5 - 10岁）的恶性疟原虫分离株对阿莫地喹的体内和体外敏感性，这些患者接受了阿莫地喹治疗（10 mg/kg/天，共3天）。第28天经聚合酶链反应校正的寄生虫学治愈率（通过Kaplan - Meier分析）为82%（95%置信区间[CI]，74% - 88%）。在测试的预处理恶性疟原虫野外分离株中，26%（17/66）在去乙基阿莫地喹（DEAQ，阿莫地喹的主要生物活性代谢物）浓度高于提议的60 nmol/L耐药阈值时，体外生长抑制率达50%，但基线DEAQ 50%抑制浓度值与无性寄生虫复发的后续风险无关（复发患者和未复发患者的基线DEAQ 50%抑制浓度值分别为29 nmol/L [95% CI，23 - 170 nmol/L]和34 nmol/L [95% CI，30 - 46 nmol/L]）。在第0天至第28天之间，绝对中性粒细胞计数中位数下降了1.3×10³个细胞/微升（95% CI， - 1.7×10³至 - 0.7×10³个细胞/微升）。体外和体内耐药的高流行率排除了单独使用阿莫地喹作为二线治疗的可能性。这些发现还表明，在具有类似4 - 氨基喹啉耐药模式的地区，作为一线或二线治疗的阿莫地喹联合用药的价值应重新评估。
