Characterization of the Plasmodium falciparum Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase Gene in Samples from Equatorial Guinea before Implementation of Artemisinin-Based Combination Therapy

Amalia Fernández-Martínez,Pedro Berzosa,Policarpo Ncogo,Patricia Mula,Pedro Cravo,Pilar Charle,Aranzazu Amor,Agustín Benito

doi:10.4269/ajtmh.2012.12-0364

Abstract

Plasmodium falciparum resistance to the primary drugs used for treatment of malaria has become the main obstacle to malaria control. Artemisinin combination therapies are the current treatment strategy, and it has been suggested that resistance to artemisinin derivatives may be related to mutations in the Plasmodium falciparum sarcoplasmic-endoplasmic reticulum Ca2+-ATPase ortholog of the mammalian sarco-endoplasmic reticulum Ca2+ ATPase gene, known as the pfatp6 gene. Thus, the purpose of this study was to determine the prevalence of single-nucleotide polymorphisms (SNPs) in pfatp6. The presence of different SNPs was detected by polymerase chain reaction amplification of the pfatp6 gene, and then sequencing to identify all possible alleles of the gene. A total of 20 SNPs were detected, including eight SNPs that have not been previously described: K481R in Malabo; R801H on Annobon Island; and the synonymous SNPs a141t, c1788t, a2211g, t2739g, a2760c, and g2836a. The genotypic profile of pfatp6 in samples from Equatorial Guinea, may be a useful epidemiologic tool for monitoring local efficacy of artemisinin combination therapies.

Highlights

Half the world’s population is at risk for malaria
Artemisinin combination therapies are the current treatment strategy, and it has been suggested that resistance to artemisinin derivatives may be related to mutations in the Plasmodium falciparum sarcoplasmicendoplasmic reticulum Ca2+-ATPase ortholog of the mammalian sarco-endoplasmic reticulum Ca2+ ATPase gene, known as the pfatp[6] gene
The purpose of this study was to determine the prevalence of single-nucleotide polymorphisms (SNPs) in pfatp[6]

Summary

Introduction

Half the world’s population is at risk for malaria. The region most affected by this disease is Africa, accounting for 78% of the estimated 225 million malaria episodes and 91% of all malaria-related deaths worldwide in 2009.1 Children less than five years of age in stable transmission areas, who have not yet developed protective immunity against the most severe forms of the disease, constitute a special risk group and have the most malaria deaths worldwide.[2]. There has been a lag in the implementation of these treatment policies because of various factors, such as high costs.[4] Despite observed changes in parasite sensitivity to artemisinins (ARTs) in western Cambodia and along the Thailand-Myanmar border,[5,6,7,8] the clinical and parasitologic efficacy of ACTs has not been compromised. Both components of the drug combination are currently at risk for resistance, and using an ART with an ineffective partner medicine can increase the risk of development and spread of artemisinin resistance.[1]

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Conclusion