Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
PLoS One. 2011;6(11):e26746. doi: 10.1371/journal.pone.0026746. Epub 2011 Nov 11.
Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance.
尽管经杀虫剂处理的蚊帐（ITN）具有明显的公共卫生效益，但通过病媒控制减少疟疾传播对耐药性传播的影响尚不清楚。在本研究中，在肯尼亚西部 Asembo 地区进行的 ITN 试验中，研究了持续减少传播对五岁以下儿童中与抗疟药物磺胺多辛-乙胺嘧啶（SP）和氯喹（CQ）耐药相关的恶性疟原虫基因突变流行率的影响。在 ITN 试验期间，国家一线抗疟治疗从 CQ 改为 SP。在 ITN 引入之前（基线，n=250）和五年后（第 5 年调查，n=242）进行的横断面调查中，从涂片阳性样本中采集样本，用于 dhfr-51、59、108、164 和 dhps-437、540（SP 耐药性）和 pfcrt-76 和 pfmdr1-86（CQ 耐药性）的单核苷酸多态性（SNP）基因分型。评估了耐药突变与流行病学变量之间的关联。SP dhps 突变和 dhfr/dhps 五重突变的流行率显著增加，而 dhfr-51、59 和 dhps-437、540 SNP 检测到的混合感染比例从基线到第 5 年调查显著降低。pfcrt-76 和 pfmdr1-86 突变的高流行率没有变化。多变量回归分析进一步表明，目前抗叶酸药物的使用和调查年份与更多的 SP 耐药突变显著相关。这些结果表明，由于药物政策的改变，抗叶酸药物的使用增加可能导致 ITN 干预五年后 SP 突变的高流行率，而传播减少对现有 CQ 突变的高流行率没有明显影响。目前的研究没有证据表明 ITN 的持续传播减少会降低与疟疾药物耐药性相关的基因的流行率。
