Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border
Abstract Background In the Greater Mekong sub-region, Plasmodium vivax has become the predominant species and imposes a major challenge for regional malaria elimination. This study aimed to investigate the variations in genes potentially related to drug resistance in P. vivax populations from the Ch...
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2020-08-01
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Series: | Malaria Journal |
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Online Access: | http://link.springer.com/article/10.1186/s12936-020-03354-x |
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doaj-8aca4943f2c94014b7ddcf28c1b84751 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yan Zhao Lin Wang Myat Thu Soe Pyae Linn Aung Haichao Wei Ziling Liu Tongyu Ma Yuanyuan Huang Lynette J. Menezes Qinghui Wang Myat Phone Kyaw Myat Htut Nyunt Liwang Cui Yaming Cao |
spellingShingle |
Yan Zhao Lin Wang Myat Thu Soe Pyae Linn Aung Haichao Wei Ziling Liu Tongyu Ma Yuanyuan Huang Lynette J. Menezes Qinghui Wang Myat Phone Kyaw Myat Htut Nyunt Liwang Cui Yaming Cao Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border Malaria Journal Plasmodium vivax Asymptomatic infection Symptomatic infection Drug resistance Molecular markers Northeast Myanmar |
author_facet |
Yan Zhao Lin Wang Myat Thu Soe Pyae Linn Aung Haichao Wei Ziling Liu Tongyu Ma Yuanyuan Huang Lynette J. Menezes Qinghui Wang Myat Phone Kyaw Myat Htut Nyunt Liwang Cui Yaming Cao |
author_sort |
Yan Zhao |
title |
Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border |
title_short |
Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border |
title_full |
Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border |
title_fullStr |
Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border |
title_full_unstemmed |
Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border |
title_sort |
molecular surveillance for drug resistance markers in plasmodium vivax isolates from symptomatic and asymptomatic infections at the china–myanmar border |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2020-08-01 |
description |
Abstract Background In the Greater Mekong sub-region, Plasmodium vivax has become the predominant species and imposes a major challenge for regional malaria elimination. This study aimed to investigate the variations in genes potentially related to drug resistance in P. vivax populations from the China–Myanmar border area. In addition, this study also wanted to determine whether divergence existed between parasite populations associated with asymptomatic and acute infections. Methods A total of 66 P. vivax isolates were obtained from patients with acute malaria who attended clinics at the Laiza area, Kachin State, Myanmar in 2015. In addition, 102 P. vivax isolates associated with asymptomatic infections were identified by screening of volunteers without signs or symptoms from surrounding villages. Slide-positive samples were verified with nested PCR detecting the 18S rRNA gene. Multiclonal infections were further excluded by genotyping at msp-3α and msp-3β genes. Parasite DNA from 60 symptomatic cases and 81 asymptomatic infections was used to amplify and sequence genes potentially associated with drug resistance, including pvmdr1, pvcrt-o, pvdhfr, pvdhps, and pvk12. Results The pvmdr1 Y976F and F1076L mutations were present in 3/113 (2.7%) and 97/113 (85.5%) P. vivax isolates, respectively. The K10 insertion in pvcrt-o gene was found in 28.2% of the parasites. Four mutations in the two antifolate resistance genes reached relatively high levels of prevalence: pvdhfr S58R (53.4%), S117N/T (50.8%), pvdhps A383G (75.0%), and A553G (36.3%). Haplotypes with wild-type pvmdr1 (976Y/997K/1076F) and quadruple mutations in pvdhfr (13I/57L/58R/61M/99H/117T/173I) were significantly more prevalent in symptomatic than asymptomatic infections, whereas the pvmdr1 mutant haplotype 976Y/997K/1076L was significantly more prevalent in asymptomatic than symptomatic infections. In addition, quadruple mutations at codons 57, 58, 61 and 117 of pvdhfr and double mutations at codons 383 and 553 of pvdhps were found both in asymptomatic and symptomatic infections with similar frequencies. No mutations were found in the pvk12 gene. Conclusions Mutations in pvdhfr and pvdhps were prevalent in both symptomatic and asymptomatic P. vivax infections, suggestive of resistance to antifolate drugs. Asymptomatic carriers may act as a silent reservoir sustaining drug-resistant parasite transmission necessitating a rational strategy for malaria elimination in this region. |
topic |
Plasmodium vivax Asymptomatic infection Symptomatic infection Drug resistance Molecular markers Northeast Myanmar |
url |
http://link.springer.com/article/10.1186/s12936-020-03354-x |
work_keys_str_mv |
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doaj-8aca4943f2c94014b7ddcf28c1b847512020-11-25T03:04:29ZengBMCMalaria Journal1475-28752020-08-0119111210.1186/s12936-020-03354-xMolecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar borderYan Zhao0Lin Wang1Myat Thu Soe2Pyae Linn Aung3Haichao Wei4Ziling Liu5Tongyu Ma6Yuanyuan Huang7Lynette J. Menezes8Qinghui Wang9Myat Phone Kyaw10Myat Htut Nyunt11Liwang Cui12Yaming Cao13Department of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityMyanmar Health Network OrganizationMyanmar Health Network OrganizationDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityMyanmar Health Network OrganizationDepartment of Medical ResearchDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityAbstract Background In the Greater Mekong sub-region, Plasmodium vivax has become the predominant species and imposes a major challenge for regional malaria elimination. This study aimed to investigate the variations in genes potentially related to drug resistance in P. vivax populations from the China–Myanmar border area. In addition, this study also wanted to determine whether divergence existed between parasite populations associated with asymptomatic and acute infections. Methods A total of 66 P. vivax isolates were obtained from patients with acute malaria who attended clinics at the Laiza area, Kachin State, Myanmar in 2015. In addition, 102 P. vivax isolates associated with asymptomatic infections were identified by screening of volunteers without signs or symptoms from surrounding villages. Slide-positive samples were verified with nested PCR detecting the 18S rRNA gene. Multiclonal infections were further excluded by genotyping at msp-3α and msp-3β genes. Parasite DNA from 60 symptomatic cases and 81 asymptomatic infections was used to amplify and sequence genes potentially associated with drug resistance, including pvmdr1, pvcrt-o, pvdhfr, pvdhps, and pvk12. Results The pvmdr1 Y976F and F1076L mutations were present in 3/113 (2.7%) and 97/113 (85.5%) P. vivax isolates, respectively. The K10 insertion in pvcrt-o gene was found in 28.2% of the parasites. Four mutations in the two antifolate resistance genes reached relatively high levels of prevalence: pvdhfr S58R (53.4%), S117N/T (50.8%), pvdhps A383G (75.0%), and A553G (36.3%). Haplotypes with wild-type pvmdr1 (976Y/997K/1076F) and quadruple mutations in pvdhfr (13I/57L/58R/61M/99H/117T/173I) were significantly more prevalent in symptomatic than asymptomatic infections, whereas the pvmdr1 mutant haplotype 976Y/997K/1076L was significantly more prevalent in asymptomatic than symptomatic infections. In addition, quadruple mutations at codons 57, 58, 61 and 117 of pvdhfr and double mutations at codons 383 and 553 of pvdhps were found both in asymptomatic and symptomatic infections with similar frequencies. No mutations were found in the pvk12 gene. Conclusions Mutations in pvdhfr and pvdhps were prevalent in both symptomatic and asymptomatic P. vivax infections, suggestive of resistance to antifolate drugs. Asymptomatic carriers may act as a silent reservoir sustaining drug-resistant parasite transmission necessitating a rational strategy for malaria elimination in this region.http://link.springer.com/article/10.1186/s12936-020-03354-xPlasmodium vivaxAsymptomatic infectionSymptomatic infectionDrug resistanceMolecular markersNortheast Myanmar |