Increasing prevalence of a novel triple-mutant dihydropteroate synthase genotype in Plasmodium falciparum in western Kenya.
Antimicrob Agents Chemother
; 59(7): 3995-4002, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25896703
ABSTRACT
The molecular basis of sulfadoxine-pyrimethamine (SP) resistance lies in a combination of single-nucleotide polymorphisms (SNPs) in two genes coding for Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. The continued use of SP for intermittent preventive treatment in pregnant women in many African countries, despite SP's discontinuation as a first-line antimalarial treatment option due to high levels of drug resistance, may further increase the prevalence of SP-resistant parasites and/or lead to the selection of new mutations. An antimalarial drug resistance surveillance study was conducted in western Kenya between 2010 and 2013. A total of 203 clinical samples from children with uncomplicated malaria were genotyped for SNPs associated with SP resistance. The prevalence of the triple-mutant Pfdhfr C50 I51R59N108 I164 genotype and the double-mutant Pfdhps S436 G437E540 A581A613 genotype was high. Two triple-mutant Pfdhps genotypes, S436 G437E540G581 A613 and H436G437E540 A581A613, were found, with the latter thus far being uniquely found in western Kenya. The prevalence of the S436 G437E540G581 A613 genotype was low. However, a steady increase in the prevalence of the Pfdhps triple-mutant H436G437E540 A581A613 genotype has been observed since its appearance in early 2000. Isolates with these genotypes shared substantial microsatellite haplotypes with the most common double-mutant allele, suggesting that this triple-mutant allele may have evolved locally. Overall, these findings show that the prevalence of the H436G437E540 A581A613 triple mutant may be increasing in this population and could compromise the efficacy of SP for intermittent preventive treatment in pregnant women if it increases the resistance threshold further.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Pirimetamina
/
Sulfadoxina
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Resistência a Medicamentos
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Malária Falciparum
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Di-Hidropteroato Sintase
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Antimaláricos
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Adult
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Child
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Child, preschool
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Female
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Humans
/
Pregnancy
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article