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Monitoring resistance of Plasmdium vivax: point mutations in dihydrofolate reductase gene in isolates from Central China.

Huang F, Zhou S, Zhang S, Li W, Zhang H - Parasit Vectors (2011)

Bottom Line: Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps).Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively.And it also highlights genotyping in the pvdhfr genes remains a useful tool to monitor the emergence and spread of P. vivax pyrimethamine resistance.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, PR China.

ABSTRACT

Background: Malaria still represents a significant public health problem in China, and the cases dramatically increased in Central China after 2001. Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps). In this study, we used direct sequencing to investigate genetic variation in pvdhfr of malaria patients' samples from Central China.

Results: Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.6%) and double mutants (43.8%). The most prevalent mutant allele was the one with double mutation at codons 58 and 117 (24.6%). Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively. The four P. vivax parasite populations in Central China also differed in pvdhfr allele frequencies.

Conclusions: This study suggested that P. vivax in Central China may be relatively susceptible to pyrimethamine. And it also highlights genotyping in the pvdhfr genes remains a useful tool to monitor the emergence and spread of P. vivax pyrimethamine resistance.

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The Pie charts show the proportions of wild type and mutant pvdhfr alleles.
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Figure 3: The Pie charts show the proportions of wild type and mutant pvdhfr alleles.

Mentions: Total of 187 samples were collected and all the samples were confirmed to be P. vivax by PCR (data not shown). Pvdhfr gene sequences from a total of 187 P. vivax samples were amplified by primary and nested PCR. Sequence polymorphism was assessed in pvdhfr genes from 187 P. vivax samples. Compared with the wild-type sequence (GenBank accession nos.98123), pvdhfr genes from the 187 samples had point mutations, among which three resulted in amino acid substitutions. No synonymous mutations were detected at positions 58, 61 and 117, and the point mutation at codons 57 and 173 was not observed in the samples. The S117T mutation was the most prevalent (20.9%), followed by the T61M mutation. Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.8%) and double mutants (43.8%) without triple mutations. The proportions of wild type and mutant pvdhfr alleles were different in different provinces (showed in Figure 3).


Monitoring resistance of Plasmdium vivax: point mutations in dihydrofolate reductase gene in isolates from Central China.

Huang F, Zhou S, Zhang S, Li W, Zhang H - Parasit Vectors (2011)

The Pie charts show the proportions of wild type and mutant pvdhfr alleles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108914&req=5

Figure 3: The Pie charts show the proportions of wild type and mutant pvdhfr alleles.
Mentions: Total of 187 samples were collected and all the samples were confirmed to be P. vivax by PCR (data not shown). Pvdhfr gene sequences from a total of 187 P. vivax samples were amplified by primary and nested PCR. Sequence polymorphism was assessed in pvdhfr genes from 187 P. vivax samples. Compared with the wild-type sequence (GenBank accession nos.98123), pvdhfr genes from the 187 samples had point mutations, among which three resulted in amino acid substitutions. No synonymous mutations were detected at positions 58, 61 and 117, and the point mutation at codons 57 and 173 was not observed in the samples. The S117T mutation was the most prevalent (20.9%), followed by the T61M mutation. Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.8%) and double mutants (43.8%) without triple mutations. The proportions of wild type and mutant pvdhfr alleles were different in different provinces (showed in Figure 3).

Bottom Line: Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps).Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively.And it also highlights genotyping in the pvdhfr genes remains a useful tool to monitor the emergence and spread of P. vivax pyrimethamine resistance.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, PR China.

ABSTRACT

Background: Malaria still represents a significant public health problem in China, and the cases dramatically increased in Central China after 2001. Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps). In this study, we used direct sequencing to investigate genetic variation in pvdhfr of malaria patients' samples from Central China.

Results: Among all the samples, 21.4% were wild-type, whereas mutations were detected at three codons (58, 61 and 117) including single mutant (34.6%) and double mutants (43.8%). The most prevalent mutant allele was the one with double mutation at codons 58 and 117 (24.6%). Three types of single mutation (S58R, T61M and S117N) were found in 2.1%, 11.8% and 20.9% of parasite isolates, respectively. The four P. vivax parasite populations in Central China also differed in pvdhfr allele frequencies.

Conclusions: This study suggested that P. vivax in Central China may be relatively susceptible to pyrimethamine. And it also highlights genotyping in the pvdhfr genes remains a useful tool to monitor the emergence and spread of P. vivax pyrimethamine resistance.

Show MeSH
Related in: MedlinePlus