Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon Region of Brazil
Mem. Inst. Oswaldo Cruz
; 95(5): 721-8, Sept.-Oct. 2000. ilus, tab
Article
in En
| LILACS
| ID: lil-267902
Responsible library:
BR1.1
RESUMO
Since the late 1970s pyrimethamine-sulfadoxine (PS; FansidarTM Hoffman-LaRoche, Basel) has been used as first line therapy for uncomplicated malaria in the Amazon basin. Unfortunately, resistance has developed over the last ten years in many regions of the Amazon and PS is no longer recommended for use in Brazil. In vitro resistance to pyrimethamine and cycloguanil (the active metabolite of proguanil) is caused by specific point mutations in Plasmodium falciparum dihydrofolate reductase (DHFR), and in vitro resistance to sulfadoxine has been associated with mutations in dihydropteroate synthase (DHPS). In association with a proguanil-sulfamethoxazole clinical trial in Brazil, we performed a nested mutation-specific polymerase chain reaction to measure the prevalence of DHFR mutations at codons 50, 51, 59, 108 and 164 and DHPS mutations at codons 436, 437, 540, 581 and 613 at three sites in the Brazilian Amazon. Samples from two isolated towns showed a high degree of homogeneity, with the DHFR Arg-50/Ile-51/Asn-108 and DHPS Gly-437/Glu-540/Gly-581 mutant genotype accounting for all infections in Peixoto de Azevedo (n = 15) and 60 percent of infections in Apiacás (n = 10), State of Mato Grosso. The remaining infections in Apiacás differed from this predominant genotype only by the addition of the Bolivia repeat at codon 30 and the Leu-164 mutation in DHFR. By contrast, 17 samples from Porto Velho, capital city of the State of Rondônia, with much in- and out-migration, showed a wide variety of DHFR and DHPS genotypes.
Full text:
1
Collection:
01-internacional
Database:
LILACS
Main subject:
Plasmodium falciparum
/
Tetrahydrofolate Dehydrogenase
/
Dihydropteroate Synthase
/
Mutation
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
Mem Inst Oswaldo Cruz
/
Mem. Inst. Oswaldo Cruz
/
Mem. Inst. Oswaldo Cruz (Online)
/
Memórias do Instituto Oswaldo Cruz (Impresso)
/
Proceedings of the Instituto Oswaldo Cruz
Journal subject:
MEDICINA TROPICAL
/
PARASITOLOGIA
Year:
2000
Document type:
Article
Affiliation country:
Brazil
/
United States
Country of publication:
Brazil