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Plasmodium falciparum del estado de Pará (Brasil) muestra una respuesta satisfactoria in vitro frente a derivados de artemisinina y ausencia de la mutación S769N en el gen PfATPase6 tipo SERCA
Author(s) -
Ferreira Isabel D.,
Martinelli Axel,
Rodrigues Louise A.,
Do Carmo Ediclei L.,
Do Rosário Virgílio E.,
Póvoa Marinete M.,
Cravo Pedro
Publication year - 2008
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/j.1365-3156.2007.01991.x
Subject(s) - plasmodium falciparum , biology , artemisinin , single nucleotide polymorphism , haplotype , microbiology and biotechnology , genetics , mutation , gene , genotype , silent mutation , virology , malaria , missense mutation , immunology
Summary Objective To evaluate the in vitro efficacy of artesunate (ATN) and artemether (ATH) against Plasmodium falciparum isolates from the Brazilian Amazon state of Pará and to search for mutations and/or altered copy numbers in the putative resistance‐associated pfcrt , pfmdr1 and pfATPase6 genes. Methods In vitro efficacy of ATN and ATH was successfully measured in 56 freshly collected P. falciparum isolates, using a conventional WHO microtest with minor modifications. Single nucleotide polymorphisms (SNPs) in the same isolates were inspected using DNA sequencing and/or PCR‐RFLP. We used real‐time quantitative PCR to assess gene copy numbers. Results ATN and ATH geometric mean IC 50 s were 0.85 n m , 95% CI (0.55–1.15) and 3.0 n m , 95% CI (1.5–4.5), respectively. There was extremely limited diversity of pfcrt and pfmdr1 genotypes and three SNPs were identified in the pfATPase6 gene: one T to A synonymous mutation at nucleotide 2694 and two non‐synonymous (both G to A) mutations at nucleotides 110 and 1916, causing predicted aminoacid shifts of arginine to lysine and of glycine to aspartate, respectively. The previously reported S769N mutation was not detected in any of the isolates inspected. In addition, no gene amplifications were detected in a subset of eight isolates. Conclusion Artemisinin derivatives display satisfactory in vitro activity locally and the pfATPase6 gene is distinct from that reported in French Guiana, suggesting that those haplotypes have not been introduced regionally.