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

Malaria Journal

Research

John C. Reeder¹  Peter A. Zimmerman²  Cristian Koepfli³  Elisheba Malau³  Harin Karunajeewa³  Ivo Mueller⁴  Timothy M. Davis⁵  Lincoln Timinao⁶  Benson Kiniboro⁶  Jonah Iga⁶  Peter M. Siba⁶  Lawrence Rare⁶  Sarah Javati⁶  Céline Barnadas⁷  Leanne J. Robinson⁷  Nicolas Senn⁸ 

[1] Burnet Institute, Melbourne, Australia;Center for Global Health and Diseases, Case Western Reserve University, Cleveland, USA;Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia;Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia;Centre de Recerca en Salut Internacional de Barcelona, Barcelona, Spain;School of Medicine and Pharmacology, University of Western Australia, Perth, Australia;Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea;Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea;Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia;Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia;Vector Borne Diseases Unit, Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea;Swiss Tropical and Public Health Institute, Basel, Switzerland;

关键词: Plasmodium vivax;    Plasmodium falciparum;    Malaria;    Drug resistance;    Molecular markers;    Papua New Guinea;   

DOI  :  10.1186/s12936-015-0879-9

 received in 2015-04-14, accepted in 2015-08-31,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundDrug 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.MethodsAn 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 in Plasmodium falciparum (n = 727) and Plasmodium 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.ResultsDespite some very low parasite densities, the assay successfully amplified all P. falciparum and P. vivax loci in 77 and 69 % of samples, respectively. In 2006, prevalences of pfdhfr (59R-108 N) double mutation/wild type pfdhps haplotype, pfcrt SVMNT haplotype (72S-76T double mutation), and 86Y pfmdr1 mutation all exceeded 90 %. For P. vivax, 65 % carried at least two pvdhfr mutations, 97 % the 647P pvdhps mutation and 54 % the 976F pvmdr1 mutation. Prevalence of mutant haplotypes was higher in Madang than East Sepik for pfcrt 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) and pvmdr1 976F (71.2 vs 26.2 %, p < 0.001). Data from a subsequent Madang survey in 2010 showed that the prevalence of pfdhps mutations increased significantly from <5 % to >30 % (p < 0.001) as did the prevalence of pvdhfr mutant haplotypes (from 75.8 to 97.4 %, p = 0.012).ConclusionsThis 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.

【 授权许可】

CC BY   
© Barnadas et al. 2015