Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and Solomon Islands prior to the introduction of artemisinin combination therapy

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 Programme, 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;    Plasmodium vivax;    Surveillance;    Molecular markers;    Sulphadoxine-pyrimethamine;    dhfr;    dhps;    Vanuatu;    Solomon Islands;   

DOI  :  10.1186/1475-2875-13-402

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

来源: Springer

【 摘 要 】

BackgroundPlasmodium falciparum and Plasmodium vivax are endemic in Vanuatu and the Solomon Islands. While both countries have introduced artemether-lumefantrine (AL) as first-line therapy for both P. falciparum and P. vivax since 2008, chloroquine and sulphadoxine-pyrimethamine (SP) were used as first-line therapy for many years prior to the introduction of AL. Limited data are available on the extent of SP resistance at the time of policy change.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 AL therapeutic efficacy study conducted in 2008. Plasmodium vivax and P. falciparum dhfr and dhps genes were sequenced to detect nucleotide polymorphisms.ResultsAll P. falciparum samples analysed (n =114) possessed a double mutant pfdhfr allele (C59R/S108N). Additionally, mutation A437G in pfhdps was detected in a small number of samples 2/13, 1/17 and 3/26 from Tanna Island, Vanuatu and Temotu and Malaita Provinces Solomon Islands respectively. Mutations were also common in pvdhfr from Tanna Island, Vanuatu, where 33/51 parasites carried the double amino acid substitution S58R/S117N, while in Temotu and Malaita Provinces, Solomon Islands 32/40 and 39/46 isolates carried the quadruple amino acid substitution F57L/S58R/T61M/S117T in DHFR respectively. No mutations in pvdhps (n =108) were detected in these three island groups.ConclusionPrior to the introduction of AL, there was a moderate level of SP resistance in the P. falciparum population that may cause SP treatment failure in young children. Of the P. vivax isolates, a majority of Solomon Islands isolates carried quadruple mutant pvdhfr alleles while a majority of Vanuatu isolates carried double mutant pvdhfr alleles. This suggests a higher level of SP resistance in the P. vivax population in Solomon Islands compared to the sympatric P. falciparum population and there is a higher level of SP resistance in P. vivax parasites from Solomon Islands than Vanuatu. This study demonstrates that the change of treatment policy in these countries from SP to ACT was timely. The information also provides a baseline for future monitoring.

【 授权许可】

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© 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.