Ord Rosalynn, Alexander Neal, Dunyo Sam, Hallett Rachel, Jawara Musa, Targett Geoffrey, Drakeley Christopher J, Sutherland Colin J
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
J Infect Dis. 2007 Dec 1;196(11):1613-9. doi: 10.1086/522154. Epub 2007 Oct 25.
Observations in natural Plasmodium falciparum populations after removal of failing drugs suggest that there is a fitness cost of drug resistance.
To examine the effect of transient removal of drug pressure, we analyzed seasonal changes in the prevalence of chloroquine (CQ)-resistant parasite genotypes in The Gambia. Parasite isolates from 441 children presenting with uncomplicated falciparum malaria over 5 seasons (1998-2002) were linked to weekly rainfall data.
The prevalence of CQ-resistant parasites increased slightly over 5 years, with the 76T allele of pfcrt (odds ratio [OR] per year, 1.16; P=.03) and the 86Y allele of pfmdr1 (OR per year, 1.18; P=.02) becoming significantly more common. However, intraseasonal analysis showed that these alleles decreased in prevalence each dry season. Wild-type parasites with respect to both loci predominated as transmission began each year, with resistant parasites becoming more common as drug use increased. This pattern was seen for both pfcrt-76T (OR per week, 1.09; P=.001) and pfmdr1-86Y (OR per week, 1.07; P=.001) and could not be explained by seasonal changes in the clonal complexity of infections.
The fitness cost of CQ resistance works against the persistence of resistant parasites through the dry season.
在停用无效药物后对自然恶性疟原虫种群的观察表明，耐药存在适应性代价。
为了研究短暂去除药物压力的影响，我们分析了冈比亚氯喹（CQ）耐药寄生虫基因型流行率的季节性变化。将5个季节（1998 - 2002年）中441例患单纯性恶性疟的儿童的寄生虫分离株与每周降雨数据相关联。
5年期间，CQ耐药寄生虫的流行率略有上升，pfcrt基因的76T等位基因（每年优势比[OR]为1.16；P = 0.03）和pfmdr1基因的86Y等位基因（每年OR为1.18；P = 0.02）变得明显更为常见。然而，季节内分析表明，在每个旱季这些等位基因的流行率均下降。每年传播开始时，两个位点的野生型寄生虫占主导，随着药物使用增加，耐药寄生虫变得更为常见。pfcrt - 76T（每周OR为1.09；P = 0.001）和pfmdr1 - 86Y（每周OR为1.07；P = 0.001）均呈现这种模式，且无法用感染的克隆复杂性的季节性变化来解释。
CQ耐药的适应性代价在旱季对耐药寄生虫的持续存在起到抑制作用。
