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

Abstract

Background: Plasmodium 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 an P. vivax since 2008, chloroquine and sulphadoxine-pyrimethamine (SP) were used as first-line therapy for many year prior to the introduction of AL. Limited data are available on the extent of SP resistance at the time of policy change 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 Island were collected as part of an AL therapeutic efficacy study conducted in 2008. Plasmodium vivax and P. falciparum dhf and dhps genes were sequenced to detect nucleotide polymorphisms Results: All 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, Vanuat and Temotu and Malaita Provinces Solomon Islands respectively. Mutations were also common in pvdhfr from Tann Island, Vanuatu, where 33/51 parasites carried the double amino acid substitution S58R/S117N, while in Temotu an 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 Conclusion: Prior to the introduction of AL, there was a moderate level of SP resistance in the P. falciparum populatio that may cause SP treatment failure in young children. Of the P. vivax isolates, a majority of Solomon Island isolates carried quadruple mutant pvdhfr alleles while a majority of Vanuatu isolates carried double mutant pvdhf alleles. This suggests a higher level of SP resistance in the P. vivax population in Solomon Islands compared t the sympatric P. falciparum population and there is a higher level of SP resistance in P. vivax parasites fro Solomon Islands than Vanuatu. This study demonstrates that the change of treatment policy in these countrie from SP to ACT was timely. The information also provides a baseline for future monitoring.