Genetic mutations in pfcrt and pfmdr1 at the time of artemisinin combination therapy introduction in South Pacific islands of Vanuatu and Solomon Islands

Malaria Journal

Research

Karryn J Gresty¹  Karen-Ann Gray¹  Qin Cheng¹  Norman C Waters²  Lyndes Wini³  Albino Bobogare³  Jeffrey Hii⁴  George Taleo⁵ 

[1] Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia;Walter Reed Army Institute of Research, Malaria Vaccine Branch, Military Malaria Research Program, Silver Spring, Maryland, USA;Malaria and Vector Borne Diseases Control Program, Ministry of Health, Honiara, Solomon Islands;School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland, Australia;Vector Borne Disease Control Program, Ministry of Health, Port Vila, Vanuatu;

关键词: Plasmodium falciparum;    Chloroquine;    pfcrt;    Microsatellite markers;    Surveillance;    Molecular markers;    Vanuatu;    Solomon Islands;   

DOI  :  10.1186/1475-2875-13-406

 received in 2014-07-18, accepted in 2014-10-07,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundChloroquine (CQ), alone or in combination with sulphadoxine-pyrimethamine, was widely used for the treatment of Plasmodium falciparum and Plasmodium vivax for several decades in both Vanuatu and Solomon Islands prior to the introduction of artemether-lumefantrine (AL) in 2008. However, the effect of chloroquine selection on parasite population, which may affect the efficacy of lumefantrine or other partner drugs of artemisinin, has not been well assessed. This study aims to provide baseline data on molecular markers (pfcrt and pfmdr1), along with the origins of pfcrt, prior to the introduction of AL.MethodsBlood spots were obtained from epidemiological surveys conducted on Tanna Island, Tafea Province, Vanuatu and Temotu Province, Solomon Islands in 2008. Additional samples from Malaita Province, Solomon Islands were collected as part of an artemether-lumefantrine efficacy study in 2008. Plasmodium falciparum pfcrt and pfmdr1 genes were examined for polymorphisms. Microsatellite markers flanking pfcrt were also examined to ascertain origins of CQ resistance.ResultsPfcrt analysis revealed 100% of parasites from Tafea Province, Vanuatu and Malaita Province, Solomon Islands and 98% of parasites from Temotu Province, Solomon Islands carried the K76T polymorphism that confers CQ resistance. Comparison of pfcrt allelic patterns and microsatellite markers flanking pfcrt revealed six haplotypes with more than 70% of isolates possessing haplotypes very similar to those observed in Papua New Guinea. The dominant (98.5%) pfmdr1 allele across all island groups was Y YC ND.ConclusionsPrior to the introduction of AL in the Solomon Islands and Vanuatu, P. falciparum isolates possessed point mutations known to confer CQ resistance and possibly associated with a decreased susceptibility to quinine and halofantrine, but an increased susceptibility to artemisinin and lumefantrine. Overall, pfcrt allelic types and the flanking microsatellite markers exhibited similarities to those of Papua New Guinea, suggesting these parasites share a common ancestry. The current use of AL for both P. falciparum and P. vivax infections will enable changes in these markers, in the absence of CQ pressure, to be monitored.

【 授权许可】

Unknown   
© Gresty et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.