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2017 年和 2019 年刚果民主共和国间日疟原虫抗疟药物耐药标志物的两年期监测

Biennial surveillance of Plasmodium falciparum anti-malarial drug resistance markers in Democratic Republic of Congo, 2017 and 2019.

机构信息

Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.

School of Public Health & Research Institute of Health and Society, Catholic University of Louvain, 1200, Brussels, Belgium.

出版信息

BMC Infect Dis. 2022 Feb 10;22(1):145. doi: 10.1186/s12879-022-07112-z.

Abstract

BACKGROUND

Because of the loss of chloroquine (CQ) effectiveness, the Democratic Republic of Congo (DRC)'s malaria treatment policy replaced CQ by sulfadoxine-pyrimethamine (SP) as first-line treatment of uncomplicated malaria in 2003, which in turn was replaced by artemisinin-based combination therapies (ACT) in 2005. The World Health Organization (WHO) recommends monitoring of anti-malarial drug resistance every 2 years. The study aimed to provide baseline data for biennial molecular surveillance of anti-malarial drug resistance by comparing data from a study conducted in 2019 to previously published data from a similar study conducted in 2017 in the DRC.

METHODS

From July to November 2019, a cross-sectional study was conducted in ten sites which were previously selected for a similar study conducted in 2017 across the DRC. P. falciparum malaria was diagnosed by a rapid diagnostic test (RDT) or by microscopy and dried blood samples (DBS) were taken from patients who had a positive test. Segments of interest in pfcrt and pfk13 genes were amplified by conventional PCR before sequencing.

RESULTS

Out of 1087 enrolled patients, 906 (83.3%) were PCR-confirmed for P. falciparum. Like in the 2017-study, none of the mutations known to be associated with Artemisinine (ART) resistance in Southeast Asia was detected. However, non-synonymous (NS) mutations with unknown functions were observed among which, A578S was detected in both 2017 and 2019-studies. The overall prevalence of pfcrt-K76T mutation that confers CQ-resistance was 22.7% in 2019-study compared to 28.5% in 2017-study (p-value = 0.069), but there was high variability between sites in the two studies. Like in 2017-study, the pfcrt 72-76 SVMNT haplotype associated with resistance to amodiaquine was not detected.

CONCLUSION

The study reported, within 2 years, the non-presence of molecular markers currently known to be associated with resistance to ART and to AQ in P. falciparum isolated in the DRC. However, the presence of polymorphisms with as-yet unknown functions was observed, requiring further characterization. Moreover, an overall decrease in the prevalence of CQ-resistance marker was observed in the DRC, but this prevalence remained highly variable from region to region.

摘要

背景

由于氯喹(CQ)效果丧失,刚果民主共和国(DRC)的疟疾治疗政策于 2003 年将 CQ 替换为磺胺多辛-乙胺嘧啶(SP),作为治疗无并发症疟疾的一线药物,而后者又于 2005 年被青蒿素为基础的联合疗法(ACT)所取代。世界卫生组织(WHO)建议每两年监测一次抗疟药物耐药性。本研究旨在通过比较 2019 年进行的研究数据和之前在 2017 年在 DRC 进行的类似研究中发表的数据,为每两年进行一次抗疟药物耐药性分子监测提供基线数据。

方法

2019 年 7 月至 11 月,在十个之前曾被选为在 DRC 进行类似研究的地点进行了一项横断面研究。通过快速诊断检测(RDT)或显微镜诊断疟原虫性疟疾,并从检测呈阳性的患者中采集干血样(DBS)。用常规 PCR 扩增 pfcrt 和 pfk13 基因的感兴趣片段,然后进行测序。

结果

在纳入的 1087 名患者中,906 名(83.3%)经 PCR 确认为恶性疟原虫。与 2017 年的研究一样,没有检测到与东南亚青蒿素(ART)耐药相关的已知突变。然而,观察到具有未知功能的非同义(NS)突变,其中 A578S 在 2017 年和 2019 年的研究中均有检测到。2019 年研究中,CQ 耐药性相关 pfcrt-K76T 突变的总体流行率为 22.7%,而 2017 年研究中为 28.5%(p 值=0.069),但在两项研究中,各地点之间的差异很大。与 2017 年的研究一样,没有检测到与阿莫地喹耐药相关的 pfcrt 72-76 SVMNT 单倍型。

结论

在 2 年内,本研究报告了在刚果民主共和国分离的恶性疟原虫中,目前与抗 ART 和 AQ 耐药相关的分子标记物不存在。然而,观察到具有未知功能的多态性,需要进一步表征。此外,在 DRC 中观察到 CQ 耐药性标记物的总体流行率下降,但该流行率在不同地区仍存在很大差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91e4/8832835/9672777dd6d7/12879_2022_7112_Fig1_HTML.jpg

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