Department of Infectious Diseases, Istituto Superiore di Sanità, viale Regina Elena 299, 00161, Rome, Italy.
National Institute for Infectious Diseases, IRCCS "Lazzaro Spallanzani", Via Portuense 292, 00149 Rome, Italy.
J Travel Med. 2021 Jul 7;28(5). doi: 10.1093/jtm/taaa231.
Plasmodium falciparum (P. falciparum) malaria is a significant public health problem in returning travellers, and artemisinin combination therapy (ACT) remains the first choice for treatment. Several single nucleotide polymorphisms (SNPs) in the P. falciparum kelch 13 (Pfk13) gene have been associated with artemisinin (ART) resistance. Moreover, the increase in the P. falciparum plasmepsin 2 (Pfpm2) gene copy number was shown to be linked with reduced susceptibility of P. falciparum to piperaquine (PPQ), a partner drug in an ACT regimen. Active molecular surveillance for imported drug-resistant malaria parasites is a pivotal activity to provide adequate chemoprophylaxis and treatment guidelines.
A retrospective study to review imported P. falciparum malaria in patients admitted to Spallanzani Institute between 2014 and 2015 was conducted. Information collected included clinic and epidemiological characteristics such as age, gender, country of origin, time since arrival to our country, travel history. All P.falciparum isolates were analysed for SNPs in the Pfk13 gene and for copy number variations in the Pfpm2 gene.
P. falciparum malaria was identified in 54 travellers. The mean age was 37 years, 44 were males. All cases were imported from non-EU countries. In the Pfk13 gene two mutations (R561R and F673L) were detected. Six P. falciparum isolates carried two copies of Pfpm2 gene, and one three copies, representing ≈16% of the analysed isolates.
None of the SNPs known to be associated with ART resistance were detected in the examined parasites. Our results provide evidence that Pfpm2 duplications (associated with piperaquine resistance) occur in Africa, emphasizing the necessity to better decode the genetic background associated with PPQ resistance. Further epidemiological investigations in Pfpm2 amplification along with mutations in the Pfk13 gene will be useful for developing and updating anti-malarial guidance in travellers.
恶性疟原虫(P. falciparum)疟疾是返回旅行者面临的重大公共卫生问题,青蒿素联合疗法(ACT)仍然是治疗的首选。P. falciparum 中的kelch 13(Pfk13)基因的几个单核苷酸多态性(SNP)与青蒿素(ART)耐药性有关。此外,P. falciparum plasmepsin 2(Pfpm2)基因拷贝数的增加与青蒿琥酯(PPQ)敏感性降低有关,PPQ 是 ACT 方案中的一种联合用药。对输入性耐药疟原虫进行主动分子监测是提供充分的化学预防和治疗指南的关键活动。
对 2014 年至 2015 年期间入住 Spallanzani 研究所的输入性恶性疟原虫疟疾病例进行回顾性研究。收集的信息包括年龄、性别、原籍国、到达我国的时间、旅行史等临床和流行病学特征。对所有 P. falciparum 分离株进行 Pfk13 基因的 SNP 分析和 Pfpm2 基因的拷贝数变异分析。
共发现 54 例输入性恶性疟原虫疟疾病例。平均年龄为 37 岁,男性 44 例。所有病例均来自非欧盟国家。在 Pfk13 基因中检测到两种突变(R561R 和 F673L)。6 株 P. falciparum 分离株携带 2 个 Pfpm2 基因拷贝,1 株携带 3 个拷贝,占分析分离株的约 16%。
在检测的寄生虫中未发现与 ART 耐药性相关的 SNP。我们的研究结果表明 Pfpm2 基因的重复(与哌喹耐药性相关)发生在非洲,这强调了更好地解码与 PPQ 耐药性相关的遗传背景的必要性。进一步对 Pfpm2 扩增和 Pfk13 基因突变的流行病学调查将有助于制定和更新旅行者的抗疟指南。