Surveillance of Antimalarial Resistance Molecular Markers in Imported Plasmodium falciparum Malaria Cases in Anhui, China, 2012–2016

Zhang, Tao; Xu, Xiaoqin; Jiang, Jingjing; Chen, Yu; Tian, Cuicui; Li, Weidong

doi:10.4269/ajtmh.17-0864

Cited by 18 publications

(16 citation statements)

References 29 publications

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“…The predominant mutation of Y184F had prevalence of 24.7% (107/434). The single mutant haplotype of pfmdr1 N86Y was at low prevalence of 5.3% (23/434), lower than another study with the prevalence of 31.0% in 2012 and 8.2% in 2016 [34]. The single mutant type NYY was not detected in this study, suggesting that NYY was rare in Africa compared with previous data [35].…”

Section: Discussioncontrasting

confidence: 87%

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China

Huang

Xue

et al. 2021

Malar J

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Background The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. Methods Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. Results A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. Conclusion This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.

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Section: Discussioncontrasting

confidence: 87%

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China

Huang

Xue

et al. 2021

Malar J

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“…The k13 and Pfcrt genes were amplified by nested PCR, as previously described [17,18]. The primers for PCR were described in previous study and they are listed in Additional file 1: Table S1 [17,18]. Proof-reading polymerase was used in each reaction to prevent amplification errors.…”

Section: Dna Amplification and Sequencingmentioning

confidence: 99%

Molecular surveillance of Pfcrt and k13 propeller polymorphisms of imported Plasmodium falciparum cases to Zhejiang Province, China between 2016 and 2018

Wang

Ruan

Zhou³

et al. 2020

Malar J

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Background: Resistance to anti-malarial drugs hinders malaria elimination. Monitoring the molecular markers of drug resistance helps improve malaria treatment policies. This study aimed to assess the distribution of molecular markers of imported Plasmodium falciparum infections. Methods: In total, 485 P. falciparum cases imported from Africa, Southeast Asia, and Oceania into Zhejiang province, China, from 2016 to 2018 were investigated. Most were imported from Africa, and only a few cases originated in Asia and Oceania. Blood samples were collected from each patient. Plasmodium falciparum chloroquine resistance transporter (Pfcrt) at residues 72-76 and Kelch13-propeller (k13) were determined by nested PCR and DNA sequence. Results: Wild-type Pfcrt at residues 72-76 was predominant (72.61%), but mutant and mixed alleles were also detected, of which CVIET (22.72%) was the most common. Mutant Pfcrt haplotypes were more frequent in patients from West Africa (26.92%), North Africa (25%), and Central Africa (21.93%). The number of cases of P. falciparum infections was small in Southeast Asia and Oceania, and these cases involved Pfcrt mutant type. For the k13 propeller gene, 26 samples presented 19 different point mutations, including eight nonsynonymous mutations (P441S, D464E, K503E, R561H, A578S, R622I, V650F, N694K). In addition, R561H, one of the validated SNPs in k13, was detected in one patient from Myanmar and one patient from Rwanda. A578S, although common in Africa, was found in only one patient from Cameroon. R622I was detected in one sample from Mozambique and one sample from Somalia. The genetic diversity of k13 was low in most regions of Africa and purifying selection was suggested by Tajima's D test. Conclusions: The frequency and spatial distributions of Pfcrt and k13 mutations associated with drug resistance were determined. Wild-type Pfcrt was dominant in Africa. Among k13 mutations correlated with delayed parasite clearance, only the R561H mutation was found in one case from Rwanda in Africa. Both Pfcrt and k13 mutations were detected in patients from Southeast Asia and Oceania. These findings provide insights into the molecular epidemiological profile of drug resistance markers in the study region.

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“…Furthermore, delayed clearance following ART treatment has been detected around the China–Myanmar border, with F446I identified as the predominant K13 mutant allele (7, 12). In central China, no K13 resistance alleles have been validated, except in Henan Province where R539T and P574L have been identified as the main alleles found among migrant workers returning from African countries (13, 14). Recently, a patient who returned from Equatorial Guinea to Jiangsu Province was identified as harboring M579I, which has been linked to ART resistance with a 2.29% in vitro survival rate by ring-stage survival assay (15).…”

Section: Introductionmentioning

confidence: 99%

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

Feng

Kong

et al. 2019

Front. Public Health

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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.

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Surveillance of Antimalarial Resistance Molecular Markers in Imported Plasmodium falciparum Malaria Cases in Anhui, China, 2012–2016

Cited by 18 publications

References 29 publications

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China

Molecular surveillance of Pfcrt and k13 propeller polymorphisms of imported Plasmodium falciparum cases to Zhejiang Province, China between 2016 and 2018

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

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