National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, People's Republic of China.
Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, People's Republic of China.
Malar J. 2022 Dec 4;21(1):369. doi: 10.1186/s12936-022-04398-x.
Artemisinin-based combination therapy (ACT) has been recommended as the first-line treatment by the World Health Organization to treat uncomplicated Plasmodium falciparum malaria. However, the emergence and spread of P. falciparum resistant to artemisinins and their partner drugs is a significant risk for the global effort to reduce disease burden facing the world. Currently, dihydroartemisinin-piperaquine (DHA-PPQ) is the most common drug used to treat P. falciparum, but little evidence about the resistance status targeting DHA (ACT drug) and its partner drug (PPQ) has been reported in Shandong Province, China.
A retrospective study was conducted to explore the prevalence and spatial distribution of Pfk13 and Pfcrt polymorphisms (sites of 72-76, and 93-356) among imported P. falciparum isolates between years 2015-2019 in Shandong Province in eastern China. Individual epidemiological information was collected from a web-based reporting system were reviewed and analysed.
A total of 425 P. falciparum blood samples in 2015-2019 were included and 7.3% (31/425) carried Pfk13 mutations. Out of the isolates that carried Pfk13 mutations, 54.8% (17/31) were nonsynonymous polymorphisms. The mutant alleles A578S, Q613H, C469C, and S549S in Pfk13 were the more frequently detected allele, the mutation rate was the same as 9.7% (3/31). Another allele Pfk13 C580Y, closely associated with artemisinin (ART) resistance, was found as 3.2% (2/31), which was found in Cambodia. A total of 14 mutant isolates were identified in Western Africa countries (45.2%, 14/31). For the Pfcrt gene, the mutation rate was 18.1% (77/425). TT and T were more frequent in all 13 different haplotypes with 26.0% (20/77) and 23.4% (18/77). The CVIET and CVIKT mutant at loci 72-76 have exhibited a prevalence of 19.5% (15/77) and 3.9% (3/77), respectively. The CVIET was mainly observed in samples from Congo (26.7%, 4/15) and Mozambique (26.7%, 4/15). No mutations were found at loci 97, 101 and 145. For polymorphisms at locus 356, a total of 24 isolates were identified and mainly from Congo (29.2%, 7/24).
These findings indicate a low prevalence of Pfk13 in the African isolates. However, the emergence and increase in the new alleles Pfcrt I356T, reveals a potential risk of drug pressure in PPQ among migrant workers returned from Africa. Therefore, continuous molecular surveillance of Pfcrt mutations and in vitro susceptibility tests related to PPQ are necessary.
世界卫生组织推荐青蒿素类复方疗法（ACT）作为治疗无并发症恶性疟原虫疟疾的一线治疗方法。然而，恶性疟原虫对青蒿素及其联合用药的耐药性的出现和传播，对全球减少疟疾负担的努力构成了重大风险。目前，双氢青蒿素-哌喹（DHA-PPQ）是治疗恶性疟原虫最常用的药物，但在中国山东省，针对 DHA（ACT 药物）及其联合用药（PPQ）的耐药性状况的证据很少。
对 2015-2019 年期间山东省通过网络报告系统收集的输入性恶性疟原虫分离株进行了回顾性研究，分析了 Pfk13 和 Pfcrt 基因（72-76 位和 93-356 位）多态性的流行情况和空间分布。
共纳入 2015-2019 年 425 例恶性疟原虫血样，7.3%（31/425）携带 Pfk13 突变。在携带 Pfk13 突变的分离株中，54.8%（17/31）为非同义突变。Pfk13 中更频繁检测到的突变等位基因为 A578S、Q613H、C469C 和 S549S，突变率均为 9.7%（3/31）。另一个与青蒿素（ART）耐药性密切相关的等位基因 Pfk13 C580Y，在柬埔寨发现了 3.2%（2/31）。在 14 个突变分离株中鉴定出 14 个来自西非国家（45.2%，14/31）。对于 Pfcrt 基因，突变率为 18.1%（77/425）。在所有 13 种不同单倍型中，TT 和 T 更为常见，分别占 26.0%（20/77）和 23.4%（18/77）。72-76 位的 CVIET 和 CVIKT 突变的流行率分别为 19.5%（15/77）和 3.9%（3/77）。CVIET 主要存在于来自刚果（26.7%，4/15）和莫桑比克（26.7%，4/15）的样本中。在 97、101 和 145 位未发现突变。在 356 位的多态性中，共鉴定出 24 个分离株，主要来自刚果（29.2%，7/24）。
这些发现表明非洲分离株中 Pfk13 的流行率较低。然而，新等位基因 Pfcrt I356T 的出现和增加，揭示了来自非洲的移民工人返回后，PPQ 药物压力下存在潜在的耐药风险。因此，有必要对 Pfcrt 突变和与 PPQ 相关的体外药敏试验进行持续的分子监测。
