| Texto completo | |
| Autor(es): |
Inoue, Juliana
[1]
;
Lopes, Dinora
[2]
;
do Rosario, Virgilio
[2]
;
Machado, Marta
[2]
;
Hristov, Angelica D.
[1]
;
Lima, Giselle F. M. C.
[1]
;
Costa-Nascimento, Maria J.
[3]
;
Segurado, Aluisio C.
[1]
;
Di Santi, Silvia M.
[1, 3]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias, BR-05403000 Sao Paulo - Brazil
[2] Univ Nova Lisboa, Inst Higiene & Med Trop, P-1349008 Lisbon - Portugal
[3] Univ Sao Paulo, Inst Med Trop Sao Paulo, Nucleo Estudos Malaria Superintendencia Controle, BR-05403000 Sao Paulo - Brazil
Número total de Afiliações: 3
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Malaria Journal; v. 13, SEP 19 2014. |
| Citações Web of Science: | 5 |
| Resumo | |
Background: Anti-malarial resistance in Plasmodium falciparum remains an obstacle for malaria control. Resistance-associated genes were analysed in Brazilian samples over four decades to evaluate the impact of different treatment regimens on the parasite genetic profile. Methods: Samples were collected on filter paper from patients infected in the Amazon region from 1984 to 2011. DNA was extracted with Chelex (R) 100 and monoinfection confirmed by PCR. SNPs in the pfcrt, pfmdr1, pfdhfr and pfdhps genes were assessed by PCR-RFLP. The pfmdr1 copy number was estimated using real time quantitative PCR with SYBR (R) Green. Parasite response was assessed ex vivo with seven concentrations of each anti-malarial. Patients were treated according to Brazilian guidelines: quinine plus tetracycline or mefloquine in period 1 and ACT in period 2. Results: All 96 samples presented the pfcrt 76T mutant throughout the assessed periods. In addition, all isolates showed ex vivo chloroquine resistance. The pfmdr1 86Y was detected in 1.5% of samples in period 1, and in 25% in period 2. All samples presented the pfmdr1 1246Y. The analysis of pfmdr1 copy number showed amplification in 37.3% in period 1 and in 42% in period 2. Mutations in pfdhfr were shown as follows: 51l in all samples in period 1 and in 81.2% in period 2; 59R in 6.4% in period 2. The pfdhfr 108N and the pfdhps 437G were seen in all samples along time; the pfdhps 540E in 93.7% in period 1 and in 75% in period 2. Conclusions: The 76T mutation associated to chloroquine resistance is still present in the parasite population, although this anti-malarial was withdrawn from the chemotherapy of P. falciparum in Brazil in the mid-1980s. All isolates assayed ex vivo for chloroquine showed resistant phenotype and 76T. No association was observed between pfmdr1 mutations and resistance to quinine, mefloquine and artemisinin derivatives. Additionally, the pfdhfr 108N mutation was detected in all samples throughout the evaluated periods, demonstrating fixation of the mutant allele in the parasite population. Changes in Brazilian national guidelines for the malaria chemotherapy in the last 27 years yielded a discreet genetic impact in the parasite population. (AU) | |
| Processo FAPESP: | 11/07380-8 - Marcadores moleculares para análise do polimorfismo genético relacionado à resposta de Plasmodium falciparum aos antimaláricos |
| Beneficiário: | Silvia Maria Fátima Di Santi |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |