Investigation and Evaluation of Genetic Diversity of Plasmodium falciparum Kelch 13 Polymorphisms Imported From Southeast Asia and Africa in Southern China

Abstract

Objectives: In this study, we aimed to analyse the genetic diversity Kelch 13 (K13) propeller allele of the Plasmodium falciparum isolates mainly imported from Southeast Asia and Africa in southern China, including the provinces of Yunnan and Guangxi. Methods: At enrolment, we collected blood samples from patients with confirmed cases of malaria infection between January 2012 and December 2017, for analysis. Individual patient information was obtained via a malaria surveillance system. The malaria infections and P. falciparum K13 mutations were diagnosed by using a nested polymerase chain reaction (PCR) method. Results: The K13 mutations were identified in 283 P. falciparum isolates from 18 counties in Yunnan and 22 counties in Guangxi. Of Forty-six isolates (46/283, 16.3%) that harbored K13 mutant alleles were detected: 26.8% in Yunnan (33/123) and 8.1% in Guangxi (13/160). A total of 18 different K13 mutations were detected. Only the F446I mutation was detected in Yunnan isolates, and F446I was more frequent (20/46, 43.5%) than other alleles. Further, the temporal distribution of the F446I mutation ratio from 2012 to 2015 exhibited no significant difference in Yunnan Province (2012, 2/13, 15.4%; 2013, 7/40, 17.5%; 2014, 7/33, 21.2%; 2015, 4/37, 10.8%, p = 0.121). A578S allele was the main K13 mutation (5/283, 1.8%) from Africa. The K13 mutants were present in 33.3% of indigenous isolates, 27.4% of isolates from Southeast Asia, and 7.9% of isolates from Africa. The analysis of 10 neutral microsatellite loci of 60 isolates showed that at the TAA109 locus, the expected heterozygosity of F446I ( H e = 0.112 ± 0.007) was much lower than that of wild type and other mutation types in Myanmar isolates. With respect to geographic distribution, TAA109 also exhibited a significant difference between isolates from Southeast Asia ( H e = 0.139 ± 0.012) and those from Africa ( H e = 0.603 ± 0.044). Conclusions: The present findings on the geographic diversity of K13 mutant alleles in P. falciparum may provide a basis for routine molecular surveillance and risk assessment, to monitor artemisinin resistance (ART) in China. Our results will be helpful for enriching the artemisinin resistance database in China during the elimination and post-elimination phases.

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998–2020)

“…A number of mutations have also been reported outside the K13 propeller region notably, K189T and E252Q [ 25 , 28 – 30 ]. In Africa, the Pfk13 mutation with the highest geographical distribution is A578S [ 25 , 26 , 31 ] and the presence of R561H mutation has recently been reported in Tanzania [ 32 ] and Rwanda [ 33 ]. Hence, there are fears that ACT resistance may spread to other regions including sub-Saharan Africa where malaria is still a major burden, similar to what happened in the past with the chloroquine, amodiaquine, and sulfadoxine–pyrimethamine.…”

Malaria Knowledge and Infection Among Migrant Population in the China-vietnam Border: A Questionnaire-based Survey

“…The risk of anti-malarial drug-resistance spread to the border, is likely due to importation of multi-drug resistant malaria caused by migrant population [24]. However, the emergence of Kelch 13 mutations associated with increased ring survival rates and parasite clearance delay were found in the China-Myanmar border [25][26][27][28], though there is no evidence showing the emergence of resistance P. falciparum strain against ACT along the China-Vietnam border, more attention should be paid to the pathogen population to monitor and evaluate the potential emergence of ACT resistance. Third, the malaria knowledge rate was low in our study among the migrant population.…”

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis protocol

“…A number of mutations have also been reported outside the K13 propeller region notably, K189T and E252Q [19,[21][22][23]. In Africa, the highest geographical distribution is A578S [18,19,24] and the presence of R561H mutation has recently been reported in Tanzania [25] and Rwanda [26]. Hence, there are fears that ACT resistance may spread to other regions including sub-Saharan Africa where malaria is still a major burden, similar to what happened in the past with the chloroquine, amodiaquine, and sulphadoxine-pyrimethamine.…”