Genetic mutations in pfcrt and pfmdr1 at the time of artemisinin combination therapy introduction in South Pacific islands of Vanuatu and Solomon Islands
Gresty, Karryn J., Gray, Karen-Ann, Bobogare, Albino, Taleo, George, Hii, Jeffrey, Wini, Lyndes, Cheng, Qin, and Waters, Norman C. (2014) 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, 13 (1). 406. pp. 1-9.
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Abstract
Background: Chloroquine (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.
Methods: Blood 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.
Results: Pfcrt 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 YYCND.
Conclusions: Prior 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.
| Item ID: | 37033 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1475-2875 |
| Keywords: | Plasmodium falciparum, chloroquine, pfcrt, microsatellite markers, surveillance, molecular markers, Vanuatu, Solomon Islands |
| Additional Information: | © 2014 Gresty et al.; licensee 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. |
| Funders: | AusAID, University of Queensland (UQ), Department of Defence (DoD), USA |
| Projects and Grants: | UQ Pacific Malaria Initiative Supporting Centre (PacMISC), DoD Global Emerging Infections Surveillance Program (DoD-GEIS) |
| Date Deposited: | 07 Jan 2015 07:56 |
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