Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China-Myanmar border

• Published in: Malaria journal 2020-08, Vol.19 (1), p.281-281, Article 281
• Main Authors: Zhao, Yan, Wang, Lin, Soe, Myat Thu, Aung, Pyae Linn, Wei, Haichao, Liu, Ziling, Ma, Tongyu, Huang, Yuanyuan, Menezes, Lynette J, Wang, Qinghui, Kyaw, Myat Phone, Nyunt, Myat Htut, Cui, Liwang, Cao, Yaming
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antimalarials - administration & dosage; Asymptomatic; Asymptomatic infection; Asymptomatic Infections; Child; Codons; Deoxyribonucleic acid; Development and progression; Dihydrofolate reductase; Displaced persons; Divergence; DNA; Drug resistance; Drug Resistance - genetics; Drug resistance in microorganisms; Drug therapy; Drugs; Female; Gene amplification; Genetic aspects; Genetic Markers; Genotyping; Haplotypes; Health aspects; Human diseases; Humans; Identification and classification; Infections; Malaria; Malaria, Vivax - parasitology; Male; Membrane Transport Proteins - analysis; Molecular markers; Multidrug Resistance-Associated Proteins - analysis; Mutation; Myanmar; Northeast Myanmar; Nucleotide sequence; Parasite resistance; Parasites; PCR; Plasmodium vivax; Plasmodium vivax - drug effects; Plasmodium vivax - genetics; Polymerase chain reaction; Protozoan Proteins - analysis; Protozoan Proteins - genetics; rRNA 18S; Sequence Analysis, DNA; Surveillance; Symptomatic infection; Symptoms; Vector-borne diseases; Young Adult
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-020-03354-x

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. 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. 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. 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.