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Pfatp6 molecular profile of Plasmodium falciparum isolates in the western Brazilian Amazon

Larissa W Brasil1, André LL Areas1, Gisely C Melo3, Cintia MC Oliveira2, Maria G C Alecrim23, Marcus V G Lacerda23, Connor O'Brien4, Walter MR Oelemann1 and Mariano G Zalis1*

Author Affiliations

1 Universidade Federal do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil

2 Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Avenida Pedro Teixeira, 25, Dom Pedro, Manaus, AM, Brazil

3 Universidade do Estado do Amazonas, Avenida Pedro Teixeira, 25, Dom Pedro, Manaus, AM, Brazil

4 Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, USA

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Malaria Journal 2012, 11:111  doi:10.1186/1475-2875-11-111

Published: 10 April 2012

Abstract

Background

Anti-malarial drug resistance has emerged as one of the biggest challenges confronting the worldwide effort to control malaria. The appearance of chloroquine and multi-drug resistance had devastating effects on therapeutic efficacy of former first-line agents. Artemisinin has proven to be an excellent therapeutic alternative to fill the void in chemotherapeutic options left by resistance mechanisms. At the time of introduction, no resistance to artemisinins had been recorded, and artemisinins demonstrated excellent parasite reduction rates. In an attempt to protect artemisinin efficacy, the World Health Organization (WHO) made artemisinin-based combination therapy (ACT) its official first-line treatment recommendation for uncomplicated Plasmodium falciparum in 2006. In Brazil, artemether/lumefantrine became the Brazilian Malaria Control Programme's official treatment recommendation in 2007. The sarco/endoplasmic reticulum Ca2+ - ATPase ortholog of P. falciparum (pfatp6) has been suggested as one of the targets of artemisinins. Consequently, pfatp6 gene polymorphisms are being investigated as markers of artemisinin resistance elsewhere. The goal of this work was to describe the molecular profile of pfatp6 in P. falciparum isolates from different localities in the Amazonas State.

Methods

DNA polymorphisms of the pfatp6 gene in 80 P. falciparum isolates from 11 municipalities of the Amazonas State (Western Brazilian Amazon), before and after the introduction of ACT in the Brazilian anti-malarial guidelines, were analysed by automatic sequencing. Mutations in the pfatp6 gene were searched using Mutation Surveyor v3.25 software.

Results

The P. falciparum pfatp6 gene presented polymorphisms at codons 37, 630 and 898. The R37K mutation was found in 16% of the samples, A630S in 32% and I898I in 52%. No S769N mutation, however, was detected in the analysed samples.

Conclusion

Despite the small number of samples, data presented here provide baseline information about polymorphisms of pfatp6 gene before and after exposure to ACT in a low transmission area, which will help to infer drug selection pressure in this area in the future.

Keywords:
Malaria; Plasmodium falciparum; Artemisinin; Molecular marker; pfatp6; Polymorphisms; Amazon