Prevalence of Plasmodium falciparum Kelch 13 ( PfK13 ) and Ubiquitin-Specific Protease 1 ( pfubp1 ) Gene Polymorphisms in Returning Travelers from Africa Reported in Eastern China

Abstract

Delayed clearance of Plasmodium falciparum by artemisinin-based combination therapies (ACTs) has already been observed in African isolates. Here, we aimed to investigate the prevalence of polymorphisms in two genes correlated with delayed parasite clearance, P. falciparum Kelch 13 (PfK13) and ubiquitin-specific protease 1 (pfubp1), among returning travellers from African countries reported in eastern China and to provide baseline data for antimalarial drug resistance (ART) surveillance and evaluation. A total of 153 filter-paper blood spots collected in 2017-2019 from uncomplicated P. falciparum cases in Anhui and Shandong Provinces were included in this study. Among them, 3.3% (5/153) of the isolates carried PfK13 mutations, and 3 of them harboured the same synonymous mutation, C469C. A total of 13.1% (20/153) of the isolates were found to contain pfubp1 mutations, and all were non-synonymous. The pfubp1 genotypes associated with ART resistance that occurred in this study included E1528D (6.5%, 10/153) and D1525E (2.6%, 4/153). However, a high prevalence of the previously unreported mutation E1531D (5.9%, 9/153) was also detected. In addition, 2 types of deletions (encoding KID and KIE, respectively) and 2 types of insertions (encoding KYE and KYDKYD, respectively) were found in 16 isolates and 6 isolates, respectively. This study showed limited variation in PfK13 among returning travellers from African countries and suggested other potential molecular markers, such as pfubp1, for use in surveillance of African isolates in ACT susceptibility studies. Further clinical trials research is under way to investigate these PfK13 and pfubp1 mutations, as well as other candidate molecular markers, and their roles in delaying parasite clearance.