Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China
Abstract Background The problem of anti-malarial drug resistance is a long-term challenge faced by malaria control in Yunnan Province. Recently, the detection rates of chloroquine-resistant molecular markers (Plasmodium falciparum chloroquine resistant transporter, Pfcrt) and artemisinin-resistant m...
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| Format: | Article |
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BMC
2018-12-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-018-2619-4 |
| _version_ | 1819264362714497024 |
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| author | Ying Dong Jian Wang Aiming Sun Yan Deng Mengni Chen Yanchun Xu Jingpo Xue |
| author_facet | Ying Dong Jian Wang Aiming Sun Yan Deng Mengni Chen Yanchun Xu Jingpo Xue |
| author_sort | Ying Dong |
| collection | DOAJ |
| description | Abstract Background The problem of anti-malarial drug resistance is a long-term challenge faced by malaria control in Yunnan Province. Recently, the detection rates of chloroquine-resistant molecular markers (Plasmodium falciparum chloroquine resistant transporter, Pfcrt) and artemisinin-resistant molecular markers (P. falciparum kelch13 gene, ork13) were 85% and 35%, respectively. To understand the association of k13 gene mutation with artemisinin resistance in falciparum malaria cases, the difference in k13 gene differentiation between two populations and artemisinin resistance phenotype on falciparum malaria cases in Myanmar were analysed in this study. Methods This research involved all of falciparum malaria cases diagnosed continuously in Yunnan Province from 2013 to 2015 and some of falciparum malaria cases found in Lazar, Myanmar. Blood samples were taken from the former group for molecular epidemiological analysis of k13 gene mutations, and artemisinin resistance phenotypes of P. falciparum were observed in the latter group using the in vivo testing method recommended by the World Health Organization. Nested PCR was used to amplify the propeller domain of the k13 gene in P. falciparum, followed by sequencing. Results A total of 202 blood samples were collected from Yunnan Province and 382 blood samples were collected from falciparum malaria cases in Myanmar. 49 of 382 Myanmar cases were in vivo tested for artesunate resistance phenotype through full treatment course observation. At the same time, all the blood samples were screened for k13 gene mutation of P. falciparum. The genetic diversity of k13 was higher in the Plasmodium isolates from Yunnan Province than those from Myanmar cases. The genetic differentiation index of the two populations was 0.0410, where the intra- and inter-group variations were 95.9% and 4.1%, respectively. The odds ratio of artemisinin resistance phenotype and mutation at the locus 446 in k13 gene in Myanmar cases was 1.640, while the value was 1.840 based on the estimations of the mutations in the 12 loci. Conclusion Although the Plasmodium isolates from Yunnan Province and those from Myanmar were collected from different sites, they still belong to the same geographical population. It is, therefore, reasonable to contrast the artemisinin resistance status of the Plasmodium population from Myanmar with the Plasmodium population from Yunnan Province. As a result, based on the molecular epidemiological investigation on k13 mutations of Plasmodium isolates in Yunnan Province and the determination of the artemisinin resistance on falciparum malaria cases in Myanmar, the positively genetic correlated was found between the k13 locus mutations with artemisinin resistance phenotype. This provides a basis for further monitoring the artemisinin resistance by detection some molecular markers in k13 gene of Plasmodium in Yunnan Province. |
| first_indexed | 2024-12-23T20:28:17Z |
| format | Article |
| id | doaj.art-47143741abd448e4a975c0d9c2fcdc88 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-23T20:28:17Z |
| publishDate | 2018-12-01 |
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| spelling | doaj.art-47143741abd448e4a975c0d9c2fcdc882022-12-21T17:32:18ZengBMCMalaria Journal1475-28752018-12-0117111210.1186/s12936-018-2619-4Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, ChinaYing Dong0Jian Wang1Aiming Sun2Yan Deng3Mengni Chen4Yanchun Xu5Jingpo Xue6Yunnan Institute of Parasitic Diseases Control, Yunnan Provincial Key Laboratory, Yunnan Centre of Malaria ResearchYunnan Institute of Parasitic Diseases Control, Yunnan Provincial Key Laboratory, Yunnan Centre of Malaria ResearchHubei International Travel Healthcare CentreYunnan Institute of Parasitic Diseases Control, Yunnan Provincial Key Laboratory, Yunnan Centre of Malaria ResearchYunnan Institute of Parasitic Diseases Control, Yunnan Provincial Key Laboratory, Yunnan Centre of Malaria ResearchYunnan Institute of Parasitic Diseases Control, Yunnan Provincial Key Laboratory, Yunnan Centre of Malaria ResearchNational Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionAbstract Background The problem of anti-malarial drug resistance is a long-term challenge faced by malaria control in Yunnan Province. Recently, the detection rates of chloroquine-resistant molecular markers (Plasmodium falciparum chloroquine resistant transporter, Pfcrt) and artemisinin-resistant molecular markers (P. falciparum kelch13 gene, ork13) were 85% and 35%, respectively. To understand the association of k13 gene mutation with artemisinin resistance in falciparum malaria cases, the difference in k13 gene differentiation between two populations and artemisinin resistance phenotype on falciparum malaria cases in Myanmar were analysed in this study. Methods This research involved all of falciparum malaria cases diagnosed continuously in Yunnan Province from 2013 to 2015 and some of falciparum malaria cases found in Lazar, Myanmar. Blood samples were taken from the former group for molecular epidemiological analysis of k13 gene mutations, and artemisinin resistance phenotypes of P. falciparum were observed in the latter group using the in vivo testing method recommended by the World Health Organization. Nested PCR was used to amplify the propeller domain of the k13 gene in P. falciparum, followed by sequencing. Results A total of 202 blood samples were collected from Yunnan Province and 382 blood samples were collected from falciparum malaria cases in Myanmar. 49 of 382 Myanmar cases were in vivo tested for artesunate resistance phenotype through full treatment course observation. At the same time, all the blood samples were screened for k13 gene mutation of P. falciparum. The genetic diversity of k13 was higher in the Plasmodium isolates from Yunnan Province than those from Myanmar cases. The genetic differentiation index of the two populations was 0.0410, where the intra- and inter-group variations were 95.9% and 4.1%, respectively. The odds ratio of artemisinin resistance phenotype and mutation at the locus 446 in k13 gene in Myanmar cases was 1.640, while the value was 1.840 based on the estimations of the mutations in the 12 loci. Conclusion Although the Plasmodium isolates from Yunnan Province and those from Myanmar were collected from different sites, they still belong to the same geographical population. It is, therefore, reasonable to contrast the artemisinin resistance status of the Plasmodium population from Myanmar with the Plasmodium population from Yunnan Province. As a result, based on the molecular epidemiological investigation on k13 mutations of Plasmodium isolates in Yunnan Province and the determination of the artemisinin resistance on falciparum malaria cases in Myanmar, the positively genetic correlated was found between the k13 locus mutations with artemisinin resistance phenotype. This provides a basis for further monitoring the artemisinin resistance by detection some molecular markers in k13 gene of Plasmodium in Yunnan Province.http://link.springer.com/article/10.1186/s12936-018-2619-4YunnanMyanmarFalciparum malaria casesPfK13 geneArtemisinin resistanceAssociative analysis |
| spellingShingle | Ying Dong Jian Wang Aiming Sun Yan Deng Mengni Chen Yanchun Xu Jingpo Xue Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China Malaria Journal Yunnan Myanmar Falciparum malaria cases PfK13 gene Artemisinin resistance Associative analysis |
| title | Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China |
| title_full | Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China |
| title_fullStr | Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China |
| title_full_unstemmed | Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China |
| title_short | Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China |
| title_sort | genetic association between the pfk13 gene mutation and artemisinin resistance phenotype in plasmodium falciparum isolates from yunnan province china |
| topic | Yunnan Myanmar Falciparum malaria cases PfK13 gene Artemisinin resistance Associative analysis |
| url | http://link.springer.com/article/10.1186/s12936-018-2619-4 |
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