Plasmodium falciparum is the main cause of human malaria and is one of the important pathogens causing high rates of morbidity and mortality. The total number of malaria patients in Vietnam has gradually decreased over the last decade. However, the spread of pathogens with drug resistance remains a significant problem. Defining the trend in genotypes related to drug resistance is essential for the control of malaria in Plasmodium falciparum has long been one of the most important pathogens, causing severe illness and large numbers of deaths worldwide. In the 1990s, more than 1 million people living in Vietnam suffered from P. falciparum infections, resulting in thousands of deaths per year. Since then, the National Institute of Malariology, Parasitology, and Entomology (NIMPE) and the government of Vietnam have focused a great deal of time and effort on a malaria control program. As a result,
From March to December 2021, this prospective, open-label, single-armobservational clinical trial, conducted in Binh Phuoc, Gia Lai and Phu Yen provinces,evaluated the safety and efficacy of oral Pyronaridine tetraphosphate-Artesunate oncedaily for three consecutive days in adults and children with microscopically confirmedP. falciparum malaria. Patients were treated as in-patients for Days 0–3, with followup visits on Days 7, 14, 21, 28, 35 and 42. The primary outcome was PCR-adjustedadequate clinical and parasitological response (ACPR) at Day 42. The results from 54P. falciparum patients has shown that: The efficacy of Pyronaridine tetraphosphate -Artesunate to P. falciparum has still high, with the rate of ACPR is 100%, the rate ofpositive parasitemia at day 3 is 50%, 54.5% and 54.8% in Binh Phuoc, Phu Yen andGia Lai, respectively. Pyronaridine-Artesunate is safety for the patients. None seriousadverd event are recorded.
Background
Plasmodium falciparum has acquired resistance to artemisinin in Southeast Asia, with mutations in the P. falciparum Kelch-13 (Pfk13) gene associated with the resistance phenotype. The widespread use of Artemisinin-based combination therapy (ACT)s in Southeast Asia has led to the selection and spread of parasites carrying mutations in Pfk13. We characterised the allele diversity of Pfk13 and pfg377, an artemisinin-resistance neutral polymorphic gene, in parasite DNA extracted human blood from in southern Vietnam in 2003, 2012, 2015 and 2018.
Method
This study was conducted in Bu Gia Map commune, Binh Phuoc province, Vietnam, from May 2018 to January 2019. Twenty-four samples from 2018 to 2019, 30 from 2003, 24 from 2012 and 32 from 2015 were analysed. Malaria-infected human blood was collected by finger-prick and used for molecular analysis. A nested-PCR targeting the small subunit ribosomal RNA gene was used for Plasmodium species identification, followed by amplification and nucleotide sequencing of Pfk13 and region 3 of pfg377. Archived blood samples collected in the same region in 2012 and 2015 were also analysed as above for comparison.
Results
The genetic diversity of Pfk13 and pfg377 was lower in 2018–2019 compared to 2012 and 2015. The number of distinct Pfk13 mutants decreased from three in 2012 and 2015, P553L, V568G and C580Y, to one, C580Y in 2018–2019. In 2018–2019, the frequency of C580Y mutant strains was 71% (17/24 isolates). All samples were wild type in 2003. In 2012 and 2015, there were single-strain infections as well as co-infections with two mutant strains or with mutant and wild strains, whereas there were no co-infections in 2018. pfg377 allele diversity decreased from five alleles in 2012 to two alleles in 2018–2019.
Conclusion
The genetic diversity of P. falciparum was reduced at the two genetic loci surveyed in this study, Pfk13 and pfg377. In the case of the former gene, we observed an increase in the prevalence of parasites carrying the C580Y gene, known to confer reduced susceptibility to ACTs. The reduction in the diversity of pfg377 may be linked to the clonal expansion of parasite strains carrying the C580Y mutation, leading to an overall reduction in parasite genetic diversity across the population.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.