Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodiumvivax drug resistance in two regions from Papua New Guinea. (December 2015)

• Record Type: Journal Article
• Authors: Barnadas, Céline; Timinao, Lincoln; Javati, Sarah; Iga, Jonah; Malau, Elisheba; Koepfli, Cristian; Robinson, Leanne; Senn, Nicolas; Kiniboro, Benson; Rare, Lawrence; Reeder, John; Siba, Peter; Zimmerman, Peter; Karunajeewa, Harin; Davis, Timothy; Mueller, Ivo
• Is Part Of: Malaria journal. Volume 14:Number 1(2015)
• Page Start: 1
• Page End: 9
• Publication Date: 2015-12
• Subjects: Plasmodium vivax -- Plasmodium falciparum -- Malaria -- Drug resistance -- Molecular markers -- Papua New Guinea; Malaria -- Periodicals; 616.9362
• DOI: 10.1186/s12936-015-0879-9
• Languages: English
• ISSNs: 1475-2875

Abstract

Abstract Background Drug resistance remains a major obstacle to malaria treatment and control. It can arise and spread rapidly, and vary substantially even at sub-national level. National malaria programmes require cost-effective and timely ways of characterizing drug-resistance at multiple sites within their countries. Methods An improved multiplexed post-PCR ligase detection reaction—fluorescent microsphere assay (LDR-FMA) was used to simultaneously determine the presence of mutations in chloroquine resistance transporter (crt ), multidrug resistance 1 (mdr1 ), dihydrofolate reductase (dhfr ) and dihydropteroate synthase (dhps ) genes inPlasmodium falciparum (n = 727) andPlasmodium vivax (n = 574) isolates collected in 2006 from cross-sectional community population surveys in two geographically distinct regions (Madang and East Sepik) of Papua New Guinea (PNG) where strong regional differences in in vivo aminoquinoline and antifolate therapeutic efficacy had previously been observed. Data were compared to those of a follow-up survey conducted in 2010. Results Despite some very low parasite densities, the assay successfully amplified allP. falciparum andP. vivax loci in 77 and 69 % of samples, respectively. In 2006, prevalences ofpfdhfr (59R-108 N) double mutation/wild typepfdhps haplotype, pfcrt SVMNT haplotype (72S-76T double mutation), and 86Ypfmdr1 mutation all exceeded 90 %. ForP. vivax, 65 % carried at least twopvdhfr mutations, 97 % the 647Ppvdhps mutation and 54 % the 976Fpvmdr1 mutation. Prevalence of mutant haplotypes was higher in Madang than East Sepik forpfcrt SVMNT (97.4 vs 83.3 %, p = 0.001), pfdhfr (59R-108 N) (100 vs 90.6 %, p = 0.001), pvdhfr haplotypes (75.8 vs 47.6 %, p = 0.001) andpvmdr1 976F (71.2 vs 26.2 %, p < 0.001). Data from a subsequent Madang survey in 2010 showed that the prevalence ofpfdhps mutations increased significantly from <5 % to >30 % (p < 0.001) as did the prevalence ofpvdhfr mutant haplotypes (from 75.8 to 97.4 %, p = 0.012). Conclusions This LDR-FMA multiplex platform shows feasibility for low-cost, high-throughput, rapid characterization of a broad range of drug-resistance markers in low parasitaemia infections. Significant geographical differences in mutation prevalence correlate with previous genotyping surveys and in vivo trials and may reflect variable drug pressure and differences in health-care access in these two PNG populations.