Biotechnology Centre, University of Yaoundé I, Yaoundé, Cameroon.
Malar J. 2010 Jan 27;9:34. doi: 10.1186/1475-2875-9-34.
The efficacy of amodiaquine (AQ), sulphadoxine-pyrimethamine (SP) and the combination of SP+AQ in the treatment of Cameroonian children with clinical malaria was investigated. The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time.
Seven hundred and sixty children aged 6-59 months with uncomplicated falciparum malaria were studied in three ecologically different regions of Cameroon - Mutengene (littoral equatorial forest), Yaoundé (forest-savannah mosaic) and Garoua (guinea-savannah). Study children were randomized to receive either AQ, SP or the combination AQ+SP. Clinical outcome was classified according to WHO criteria, as either early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) or adequate clinical and parasitological response (ACPR). The occurrence of mutations in pfcrt, pfmdr1, dhfr and dhps genes was studied by either RFLP or dot blot techniques and the prevalence of these mutations related to parasitological and therapeutic failures.
After correction for the occurrence of re-infection by PCR, ACPRs on day 28 for AQ, SP and AQ+SP were 71.2%, 70.1% and 80.9%, in Garoua, 79.2%, 62.5%, and 81.9% in Mutengene, and 80.3%, 67.5% and 76.2% in Yaoundé respectively. High levels of Pfcrt 76T (87.11%) and Pfmdr1 86Y mutations (73.83%) were associated with quinoline resistance in the south compared to the north, 31.67% (76T) and 22.08% (86Y). There was a significant variation (p < 0.001) of the prevalence of the SGK haplotype between Garoua in the north (8.33%), Yaoundé (36.29%) in the savannah-forest mosaic and Mutengene (66.41%) in the South of Cameroon and a weak relation between SGK haplotype and SP failure. The 540E mutation on the dhps gene was extremely rare (0.3%) and occurred only in Mutengene while the pfmdr1 1034K and 1040D mutations were not detected in any of the three sites.
In this study the prevalence of molecular markers for quinoline and anti-folate resistances showed high levels and differed between the south and north of Cameroon. AQ, SP and AQ+SP treatments were well tolerated but with low levels of efficacy that suggested alternative treatments were needed in Cameroon since 2005.
研究了阿莫地喹（AQ）、磺胺多辛-乙胺嘧啶（SP）以及 SP+AQ 联合疗法在治疗喀麦隆儿童临床疟疾中的疗效。研究了这些药物耐药性的分子标志物的流行情况，为随时间推移进行耐药性监测奠定了基础。
在喀麦隆三个生态环境不同的地区——Mutengene（沿海赤道森林）、雅温得（森林-稀树草原镶嵌区）和加鲁阿（几内亚-稀树草原区），对 760 名 6-59 个月龄患有无并发症恶性疟的儿童进行了研究。研究儿童被随机分配接受 AQ、SP 或 AQ+SP 联合治疗。根据世界卫生组织的标准，临床疗效分为早期治疗失败（ETF）、晚期临床失败（LCF）、晚期寄生虫学失败（LPF）或适当的临床和寄生虫学反应（ACPR）。通过 RFLP 或斑点印迹技术研究了 pfcrt、pfmdr1、dhfr 和 dhps 基因的突变情况，并将这些突变的流行情况与寄生虫学和治疗失败相关联。
PCR 校正再感染后，28 天时 AQ、SP 和 AQ+SP 的 ACPR 分别为加鲁阿的 71.2%、70.1%和 80.9%，Mutengene 的 79.2%、62.5%和 81.9%，雅温得的 80.3%、67.5%和 76.2%。与北部相比，南部奎宁类药物耐药的 Pfcrt 76T（87.11%）和 Pfmdr1 86Y 突变（73.83%）水平较高，分别为 31.67%（76T）和 22.08%（86Y）。SGK 单倍型在北部加鲁阿（8.33%）、萨凡纳-森林镶嵌区雅温得（36.29%）和南部 Mutengene（66.41%）之间存在显著差异（p<0.001），与 SP 失败之间存在较弱的关系。dhps 基因的 540E 突变极为罕见（0.3%），仅发生在 Mutengene，而 pfmdr1 1034K 和 1040D 突变在这三个地点均未检测到。
在这项研究中，奎宁类药物和抗叶酸类药物耐药性的分子标志物流行率较高，且在喀麦隆南部和北部存在差异。AQ、SP 和 AQ+SP 治疗耐受性良好，但疗效较低，这表明 2005 年以来喀麦隆需要替代治疗方法。
