First Detection in West Africa of a Mutation That May Contribute to Artemisinin Resistance Plasmodium falciparum

Abstract

<b>Background:</b> The spread of drug resistance has seriously impacted the effective treatment of infection with the malaria parasite, <i>Plasmodium falciparum</i>. Continuous monitoring of molecular marker polymorphisms associated with drug resistance in parasites is essential for malaria control and elimination efforts. Our study describes mutations observed in the resistance genes <i>Pfkelch13, Pfcrt</i>, and <i>Pfmdr1</i> in imported malaria and identifies additional potential drug resistance-associated molecular markers. <b>Methods:</b> Chinese patients infected in Africa with <i>P. falciparum</i> were treated with intravenous (IV) injections of artesunate 240-360 mg for 3-5 days while hospitalized and treated with oral dihydroartemisinin-piperaquine (DHP) for 3 days after hospital discharge. Blood samples were collected and PCR sequencing performed on genes <i>Pfkelch13, Pfcrt</i>, and <i>Pfmdr1</i> from all isolates. <b>Results:</b> We analyzed a total of 225 patients from Guangxi, China with <i>P. falciparum</i> malaria acquired in Africa between 2016 and 2018. All patients were cured completely after treatment. The F446I mutation of the <i>Pfkelch13</i> gene was detected for the first time from samples of West African <i>P. falciparum</i>, with a frequency of 1.0%. Five haplotypes of <i>Pfcrt</i> that encode residues 72-76 were found, with the wild-type CVMNK sequence predominating (80.8% of samples), suggesting that the parasites might be chloroquine sensitive. For <i>Pfmdr1</i>, N86<b>Y</b> (13.1%) and Y184<b>F</b> (58.8%) were the most prevalent, suggesting that artemether-lumefantrine may not, in general, be a suitable treatment for the group. <b>Conclusions:</b> For the first time, this study detected the F446I mutation of the <i>Pfkelch13</i> gene from Africa parasites that lacked clinical evidence of resistance. This study provides the latest data for molecular marker surveillance related to antimalarial drug resistance genes <i>Pfkelch13, Pfcrt</i>, and <i>Pfmdr1</i> imported from Africa, in Guangxi, China from Chinese migrate workers. <b>Clinical Trial Registration:</b> ChiCTROPC17013106.