乌干达各地潜在的氨基喹啉、抗叶酸和青蒿素耐药性中介体的流行率变化。
Changing Prevalence of Potential Mediators of Aminoquinoline, Antifolate, and Artemisinin Resistance Across Uganda.
机构信息
Infectious Diseases Research Collaboration, Kampala, Uganda.
University of California, San Francisco, San Francisco, California, USA.
出版信息
J Infect Dis. 2021 Mar 29;223(6):985-994. doi: 10.1093/infdis/jiaa687.
BACKGROUND
In Uganda, artemether-lumefantrine is recommended for malaria treatment and sulfadoxine-pyrimethamine for chemoprevention during pregnancy, but drug resistance may limit efficacies.
METHODS
Genetic polymorphisms associated with sensitivities to key drugs were characterized in samples collected from 16 sites across Uganda in 2018 and 2019 by ligase detection reaction fluorescent microsphere, molecular inversion probe, dideoxy sequencing, and quantitative polymerase chain reaction assays.
RESULTS
Considering transporter polymorphisms associated with resistance to aminoquinolines, the prevalence of Plasmodium falciparum chloroquine resistance transporter (PfCRT) 76T decreased, but varied markedly between sites (0-46% in 2018; 0-23% in 2019); additional PfCRT polymorphisms and plasmepsin-2/3 amplifications associated elsewhere with resistance to piperaquine were not seen. For P. falciparum multidrug resistance protein 1, in 2019 the 86Y mutation was absent at all sites, the 1246Y mutation had prevalence ≤20% at 14 of 16 sites, and gene amplification was not seen. Considering mutations associated with high-level sulfadoxine-pyrimethamine resistance, prevalences of P. falciparum dihydrofolate reductase 164L (up to 80%) and dihydropteroate synthase 581G (up to 67%) were high at multiple sites. Considering P. falciparum kelch protein propeller domain mutations associated with artemisinin delayed clearance, prevalence of the 469Y and 675V mutations has increased at multiple sites in northern Uganda (up to 23% and 41%, respectively).
CONCLUSIONS
We demonstrate concerning spread of mutations that may limit efficacies of key antimalarial drugs.
背景
在乌干达，青蒿琥酯-咯萘啶被推荐用于疟疾治疗，磺胺多辛-乙胺嘧啶用于妊娠期间的化学预防，但药物耐药性可能会限制疗效。
方法
通过连接酶检测反应荧光微球、分子反转探针、双脱氧测序和定量聚合酶链反应检测，对 2018 年至 2019 年在乌干达 16 个地点采集的样本中与关键药物敏感性相关的遗传多态性进行了特征描述。
结果
考虑到与抗氨基喹啉耐药性相关的转运体多态性，恶性疟原虫氯喹耐药转运体（PfCRT）76T 的流行率下降，但在不同地点之间差异显著（2018 年为 0-46%；2019 年为 0-23%）；在其他地方与哌喹耐药性相关的其他 PfCRT 多态性和质体蛋白酶 2/3 扩增未被发现。对于恶性疟原虫多药耐药蛋白 1，在 2019 年，所有地点均未出现 86Y 突变，14 个地点中有 1246Y 突变的流行率≤20%，且未出现基因扩增。考虑到与高水平磺胺多辛-乙胺嘧啶耐药性相关的突变，恶性疟原虫二氢叶酸还原酶 164L（高达 80%）和二氢蝶酸合成酶 581G（高达 67%）的流行率在多个地点较高。考虑到与青蒿素清除延迟相关的恶性疟原虫 kelch 蛋白螺旋桨结构域突变，在乌干达北部的多个地点，469Y 和 675V 突变的流行率有所增加（分别高达 23%和 41%）。
结论
我们证明了可能限制关键抗疟药物疗效的令人担忧的突变的传播。
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