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Master's Dissertation
DOI
10.11606/D.42.2012.tde-31012013-081821
Document
Author
Full name
Rosa Del Carmen Miluska Vargas Rodriguez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Ferreira, Marcelo Urbano (President)
Marinho, Claudio Romero Farias
Soares, Irene da Silva
Title in Portuguese
Resistência à cloroquina em Plasmodium vivax: avaliação fenotípica e molecular na Amazônia Ocidental Brasileira.
Keywords in Portuguese
Amazônia brasileira
Antimaláricos
Malária
Polimorfismo
Resistência a drogas
Resistência microbiana às drogas
Abstract in Portuguese
No presente trabalho avaliamos fenotípica e molecularmente isolados de P. vivax da Amazônia Ocidental Brasileira. A avaliação fenotípica de sensibilidade à cloroquina (CQ) foi realizada por meio do ensaio de maturação de esquizonte. A avaliação molecular efetuou-se por tipagem de cinco polimorfismos de nucleotídeo único (SNPs) não-sinônimos do gene pvmdr-1 (A266G, A1498G, A2722C, A2927T e T3226C) e variações no número de cópias deste gene. Em decorrência, o fenótipo de susceptibilidade à CQ nos 36 isolados analisados não foi estabelecido devido ao escasso desenvolvimento ex-vivo dos parasitos. Mutações na posição Y976F, potencialmente associada à resistência à CQ, não foram observadas nos 80 isolados testados. Além disso, 10% das amostras apresentaram a mutação F1076L, que frequentemente acompanha a mutação Y976F. Finalmente, apenas dois isolados (0,9%) dos 215 analisados apresentaram duas cópias do gene pvmdr-1, sugerindo que a duplicação gênica, potencial mecanismo de resistência à mefloquina, ainda não está disseminada nas populações de parasitos desta região.
Title in English
Chloroquine resistance in Plasmodium vivax: molecular and phenotypic evaluation in the Brazilian Western Amazon.
Keywords in English
Antimalarials
Brazilian Amazon
Drug resistance
Malaria
Microbial drug resistance
Polymorphism
Abstract in English
In this study, we performed a molecular and phenotypic evaluation of isolates of P. vivax from Brazilian Western Amazon. The phenotypic evaluation of chloroquine (CQ) sensitivity was performed using the schizont maturation assay. The molecular evaluation was made by typing of five non-synonymous single nucleotide polymorphisms (SNPs) of the pvmdr-1 gene (A266G, A1498G, A2722C, T3226C and A2927T) and variations of the copy number of this gene. As a result, the CQ susceptibility phenotype in 36 isolates of P. vivax analyzed was not established, due to the scarce ex-vivo development of the parasites. Mutations at position Y976F, potentially associated with CQ resistance, were not observed in 80 isolates tested. In addition, 10% of the isolates had the mutation F1076L, which often accompanies the mutation Y976F. Finally, two isolates (0,9%), from a total of 215 had two copies of the pvmdr-1 gene, suggesting that the gene duplication, a potential mechanism of mefloquine resistance, is not spread in the parasites populations of this region.
 
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Publishing Date
2013-03-21
 
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