No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border
Abstract Background The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China’s plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-020-03410-6 |
| _version_ | 1818048286404116480 |
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| author | Fang Huang Biraj Shrestha Hui Liu Lin-Hua Tang Shui-Sen Zhou Xiao-Nong Zhou Shannon Takala-Harrison Pascal Ringwald Myaing M. Nyunt Christopher V. Plowe |
| author_facet | Fang Huang Biraj Shrestha Hui Liu Lin-Hua Tang Shui-Sen Zhou Xiao-Nong Zhou Shannon Takala-Harrison Pascal Ringwald Myaing M. Nyunt Christopher V. Plowe |
| author_sort | Fang Huang |
| collection | DOAJ |
| description | Abstract Background The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China’s plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China–Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance. Methods The therapeutic efficacy of DHA-PPQ for the treatment of uncomplicated P. falciparum was evaluated along the China–Myanmar border from 2010 to 2014. The dry blood spots samples collected in the efficacy study prior DHA-PPQ treatment and from the local hospital by passive detection were used to amplify k13 and pm2. Polymorphisms within k13 were genotyped by capillary sequencing and pm2 copy number was quantified by relative-quantitative real-time polymerase chain reaction. Treatment outcome was evaluated with the World Health Organization protocol. A linear regression model was used to estimate the association between the day 3 positive rate and k13 mutation and the relationship of the pm2 copy number variants and k13 mutations. Results DHA-PPQ was effective for uncomplicated P. falciparum infection in Yunnan Province with cure rates > 95%. Twelve non synonymous mutations in the k13 domain were observed among the 268 samples with the prevalence of 44.0% and the predominant mutation was F446I with a prevalence of 32.8%. Only one sample was observed with multi-copies of pm2, including parasites with and without k13 mutations. The therapeutic efficacy of DHA-PPQ was > 95% along the China–Myanmar border, consistent with the lack of amplification of pm2. Conclusion DHA-PPQ for uncomplicated P. falciparum infection still showed efficacy in an area with artemisinin-resistant malaria along the China–Myanmar border. There was no evidence to show PPQ resistance by clinical study and molecular markers survey. Continued monitoring of the parasite population using molecular markers will be important to track emergence and spread of resistance in this region. |
| first_indexed | 2024-12-10T10:19:16Z |
| format | Article |
| id | doaj.art-79bfe86e4ae7400e8836e00276a1895f |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-10T10:19:16Z |
| publishDate | 2020-09-01 |
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| series | Malaria Journal |
| spelling | doaj.art-79bfe86e4ae7400e8836e00276a1895f2022-12-22T01:52:55ZengBMCMalaria Journal1475-28752020-09-011911910.1186/s12936-020-03410-6No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar borderFang Huang0Biraj Shrestha1Hui Liu2Lin-Hua Tang3Shui-Sen Zhou4Xiao-Nong Zhou5Shannon Takala-Harrison6Pascal Ringwald7Myaing M. Nyunt8Christopher V. Plowe9National Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionCenter for Vaccine Development and Global Health, University of Maryland School of MedicineYunnan Institute of Parasitic DiseasesNational Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionNational Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionNational Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionCenter for Vaccine Development and Global Health, University of Maryland School of MedicineGlobal Malaria Programme, World Health OrganizationDuke Global Health Institute, Duke UniversityDuke Global Health Institute, Duke UniversityAbstract Background The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China’s plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China–Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance. Methods The therapeutic efficacy of DHA-PPQ for the treatment of uncomplicated P. falciparum was evaluated along the China–Myanmar border from 2010 to 2014. The dry blood spots samples collected in the efficacy study prior DHA-PPQ treatment and from the local hospital by passive detection were used to amplify k13 and pm2. Polymorphisms within k13 were genotyped by capillary sequencing and pm2 copy number was quantified by relative-quantitative real-time polymerase chain reaction. Treatment outcome was evaluated with the World Health Organization protocol. A linear regression model was used to estimate the association between the day 3 positive rate and k13 mutation and the relationship of the pm2 copy number variants and k13 mutations. Results DHA-PPQ was effective for uncomplicated P. falciparum infection in Yunnan Province with cure rates > 95%. Twelve non synonymous mutations in the k13 domain were observed among the 268 samples with the prevalence of 44.0% and the predominant mutation was F446I with a prevalence of 32.8%. Only one sample was observed with multi-copies of pm2, including parasites with and without k13 mutations. The therapeutic efficacy of DHA-PPQ was > 95% along the China–Myanmar border, consistent with the lack of amplification of pm2. Conclusion DHA-PPQ for uncomplicated P. falciparum infection still showed efficacy in an area with artemisinin-resistant malaria along the China–Myanmar border. There was no evidence to show PPQ resistance by clinical study and molecular markers survey. Continued monitoring of the parasite population using molecular markers will be important to track emergence and spread of resistance in this region.http://link.springer.com/article/10.1186/s12936-020-03410-6Plasmodium falciparumArtemisinin resistancePiperaquinePlasmepsin IIChina–Myanmar border |
| spellingShingle | Fang Huang Biraj Shrestha Hui Liu Lin-Hua Tang Shui-Sen Zhou Xiao-Nong Zhou Shannon Takala-Harrison Pascal Ringwald Myaing M. Nyunt Christopher V. Plowe No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border Malaria Journal Plasmodium falciparum Artemisinin resistance Piperaquine Plasmepsin II China–Myanmar border |
| title | No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border |
| title_full | No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border |
| title_fullStr | No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border |
| title_full_unstemmed | No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border |
| title_short | No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China–Myanmar border |
| title_sort | no evidence of amplified plasmodium falciparum plasmepsin ii gene copy number in an area with artemisinin resistant malaria along the china myanmar border |
| topic | Plasmodium falciparum Artemisinin resistance Piperaquine Plasmepsin II China–Myanmar border |
| url | http://link.springer.com/article/10.1186/s12936-020-03410-6 |
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