Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017
Abstract Background Plasmodium vivax remains the predominant species at the China–Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correla...
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BMC
2022-04-01
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| Series: | Infectious Diseases of Poverty |
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| Online Access: | https://doi.org/10.1186/s40249-022-00964-2 |
| _version_ | 1811289214164140032 |
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| author | Zhensheng Wang Chunyan Wei Yunchun Pan Zhihua Wang Xin Ji Qianqian Chen Lianhui Zhang Zenglei Wang Heng Wang |
| author_facet | Zhensheng Wang Chunyan Wei Yunchun Pan Zhihua Wang Xin Ji Qianqian Chen Lianhui Zhang Zenglei Wang Heng Wang |
| author_sort | Zhensheng Wang |
| collection | DOAJ |
| description | Abstract Background Plasmodium vivax remains the predominant species at the China–Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time. Methods A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza sub-township in Myanmar, from 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. The Pearson’s Chi-squared test or Fisher’s exact test were applied to determine the statistical frequency differences of mutations between categorical data. Results The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.6%, 56.7%, 40.1%, and 56.0% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated in Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.6%) dominated in Laiza and increased with time. In pvdhps, the A383G prevailed in 69.2% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.4% and 30.8% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.2%), while T958M was fixed and F1076L was approaching fixed (72.4%). The K10 insertion was detected at an occurrence of 33.2% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12. Conclusions Mutations related with resistance to antifolate drugs are prevalent in this area, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to chloroquine (CQ) is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance. Graphical abstract |
| first_indexed | 2024-04-13T03:52:01Z |
| format | Article |
| id | doaj.art-2f1634d673174e11bd1cd27771a9f8e1 |
| institution | Directory Open Access Journal |
| issn | 2049-9957 |
| language | English |
| last_indexed | 2024-04-13T03:52:01Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-2f1634d673174e11bd1cd27771a9f8e12022-12-22T03:03:48ZengBMCInfectious Diseases of Poverty2049-99572022-04-0111111210.1186/s40249-022-00964-2Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017Zhensheng Wang0Chunyan Wei1Yunchun Pan2Zhihua Wang3Xin Ji4Qianqian Chen5Lianhui Zhang6Zenglei Wang7Heng Wang8Department of Microbiology and Parasitology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeDepartment of Microbiology and Parasitology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeNo. II Department of Orthopedics, Pingdu People’s HospitalDepartment of Immunology, Guilin Medical UniversityInstitute of Chinese Materia Medica, China Academy of Chinese Medical SciencesNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Microbiology and Parasitology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeNHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Microbiology and Parasitology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeAbstract Background Plasmodium vivax remains the predominant species at the China–Myanmar border, imposing a major challenge to the recent gains in regional malaria elimination. To closely supervise the emerging of drug resistance in this area, we surveyed the variations in genes potentially correlated with drug resistance in P. vivax parasite and the possible drug selection with time. Methods A total of 235 P. vivax samples were collected from patients suffering uncomplicated malaria at Yingjiang, Tengchong, and Longling counties, and Nabang port in China, Yunnan province, and Laiza sub-township in Myanmar, from 2008 to 2017. Five potential drug resistance genes were amplified utilizing nested-PCR and analyzed, including pvdhfr, pvdhps, pvmdr1, pvcrt-o, and pvk12. The Pearson’s Chi-squared test or Fisher’s exact test were applied to determine the statistical frequency differences of mutations between categorical data. Results The pvdhfr F57I/L, S58R, T61M and S117T/N presented in 40.6%, 56.7%, 40.1%, and 56.0% of the sequenced P. vivax isolates, and these mutations significantly decreased with years. The haplotype formed by these quadruple mutations predominated in Yingjiang, Tengchong, Longling and Nabang. While a mutation H99S/R (56.6%) dominated in Laiza and increased with time. In pvdhps, the A383G prevailed in 69.2% of the samples, which remained the most prevalent haplotype. However, a significant decrease of its occurrence was also noticed over the time. The S382A/C and A553G existed in 8.4% and 30.8% of the isolates, respectively. In pvmdr1, the mutation Y976F occurred at a low frequency in 5/232 (2.2%), while T958M was fixed and F1076L was approaching fixed (72.4%). The K10 insertion was detected at an occurrence of 33.2% in pvcrt-o, whereas there was no significant difference among the sites or over the time. No mutation was identified in pvk12. Conclusions Mutations related with resistance to antifolate drugs are prevalent in this area, while their frequencies decrease significantly with time, suggestive of increased susceptibility of P. vivax parasite to antifolate drugs. Resistance to chloroquine (CQ) is possibly emerging. However, since the molecular mechanisms underneath CQ resistance is yet to be better understood, close supervision of clinical drug efficiency and continuous function investigation is urgently needed to alarm drug resistance. Graphical abstracthttps://doi.org/10.1186/s40249-022-00964-2Plasmodium vivaxAntimalarial drugDrug resistanceMolecular markerChina–Myanmar border |
| spellingShingle | Zhensheng Wang Chunyan Wei Yunchun Pan Zhihua Wang Xin Ji Qianqian Chen Lianhui Zhang Zenglei Wang Heng Wang Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017 Infectious Diseases of Poverty Plasmodium vivax Antimalarial drug Drug resistance Molecular marker China–Myanmar border |
| title | Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017 |
| title_full | Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017 |
| title_fullStr | Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017 |
| title_full_unstemmed | Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017 |
| title_short | Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China–Myanmar border during 2008‒2017 |
| title_sort | polymorphisms of potential drug resistant molecular markers in plasmodium vivax from china myanmar border during 2008 2017 |
| topic | Plasmodium vivax Antimalarial drug Drug resistance Molecular marker China–Myanmar border |
| url | https://doi.org/10.1186/s40249-022-00964-2 |
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