赞比亚东部卡特特地区停用氯喹后恶性疟原虫 PfCRT K76T 和 PfMDR1 N86Y 突变的流行率降低。
Decreased prevalence of the Plasmodium falciparum Pfcrt K76T and Pfmdr1 and N86Y mutations post-chloroquine treatment withdrawal in Katete District, Eastern Zambia.
机构信息
PATH Malaria Control and Elimination Partnership in Africa (MACEPA), National Malaria Elimination Centre, Ministry of Health, Chainama Grounds, Lusaka, Zambia.
School of Health Sciences, Biomedical Sciences Department, Ridgeway campus, Lusaka, Zambia.
出版信息
Malar J. 2021 Jul 28;20(1):329. doi: 10.1186/s12936-021-03859-z.
BACKGROUND
In 2002, Zambia withdrew chloroquine as first-line treatment for Plasmodium falciparum malaria due to increased treatment failure and worldwide spread of chloroquine resistance. The artemisinin combination regimen, artemether-lumefantrine, replaced chloroquine (CQ) as first choice malaria treatment. The present study determined the prevalence of CQ resistance molecular markers in the Pfcrt and Pfmdr1 genes in Eastern Zambia at 9 and 13 years after the removal of drug pressure.
METHODS
Samples collected from Katete District during the drug therapeutic efficacy assessments conducted in 2012 and 2016 were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) to determine the prevalence of genetic mutations, K76T on the Pfcrt gene and N86Y on the Pfmdr1 gene. A total of 204 P. falciparum-positive DBS samples collected at these two time points were further analysed.
RESULTS
Among the samples analysed for Pfcrt K76T and Pfmdr1 N86Y in the present study, 112 (82.4%) P. falciparum-infected samples collected in 2012 were successfully amplified for Pfcrt and 94 (69.1%) for Pfmdr1, while 69 (65.7%) and 72 (68.6%) samples from 2016 were successfully amplified for Pfcrt and Pfmdr1, respectively. In 2012, the prevalence of Pfcrt 76K (sensitive) was 97.3%, 76T (resistant) was 1.8%, and 0.8% had both 76K and 76T codons (mixed). Similarly in 2012, the prevalence of Pfmdr1 86N (sensitive) was 97.9% and 86Y (resistant) was 2.1%. In the 2016 samples, the prevalence of the respective samples was 100% Pfcrt 76K and Pfmdr1 86N.
CONCLUSION
This study shows that there was a complete recovery of chloroquine-sensitive parasites by 2016 in Katete District, Eastern Zambia, 13 years following the withdrawal of CQ in the country. These findings add to the body of evidence for a fitness cost in CQ-resistant P. falciparum in Zambia and elsewhere. Further studies are recommended to monitor resistance countrywide and explore the feasibility of integration of the former best anti-malarial in combination therapy in the future.
背景
2002 年，由于治疗失败率上升和氯喹抗药性在全球范围内的传播，赞比亚停止将氯喹作为治疗恶性疟原虫疟疾的一线药物。青蒿素联合疗法（青蒿琥酯-咯萘啶）取代氯喹（CQ）成为首选的疟疾治疗药物。本研究旨在确定在赞比亚东部地区停用药物压力 9 年和 13 年后，PfCRT 和 Pfmdr1 基因中 CQ 耐药分子标记的流行情况。
方法
在 2012 年和 2016 年进行的药物疗效评估期间，从 Katete 区采集样本，通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析，确定基因突变的流行情况，PfCRT 基因上的 K76T 和 Pfmdr1 基因上的 N86Y。对这两个时间点采集的 204 份疟原虫阳性 DBS 样本进行了进一步分析。
结果
在所分析的样本中，PfCRT K76T 和 Pfmdr1 N86Y 中，2012 年采集的 112 份（82.4%）感染恶性疟原虫的样本成功扩增了 PfCRT，94 份（69.1%）成功扩增了 Pfmdr1，而 2016 年采集的 69 份和 72 份样本分别成功扩增了 PfCRT 和 Pfmdr1。2012 年，PfCRT76K（敏感）的流行率为 97.3%，76T（耐药）的流行率为 1.8%，0.8%的样本同时存在 76K 和 76T 密码子（混合）。同样在 2012 年，Pfmdr186N（敏感）的流行率为 97.9%，86Y（耐药）的流行率为 2.1%。在 2016 年的样本中，各自样本的 PfCRT76K 和 Pfmdr186N 的流行率均为 100%。
结论
本研究表明，在赞比亚东部的 Katete 区，停用 CQ 13 年后，到 2016 年，已完全恢复对氯喹敏感的寄生虫。这些发现为赞比亚和其他地区 CQ 耐药恶性疟原虫存在适应性成本提供了更多证据。建议进一步开展研究，以监测全国的耐药情况，并探讨未来将以前最好的抗疟药物纳入联合治疗的可行性。
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