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

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 the...

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Autores: Barnadas, Céline, Timinao, Lincoln, Javati, Sarah, Iga, Jonah, Malau, Elisheba, Koepfli, Cristian, Robinson, Leanne J., Senn, Nicolas, Kiniboro, Benson, Rare, Lawrence, Reeder, John C., Siba, Peter, Zimmerman, Peter A., Karunajeewa, Harin, Davis, Timothy M., Mueller, Ivo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/69213
Acceso en línea:https://hdl.handle.net/2445/69213
Access Level:acceso abierto
Palabra clave:Plasmodium falciparum
Plasmodium vivax
Malària
Resistència als medicaments
Malaria
Drug resistance
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spelling Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New GuineaBarnadas, CélineTiminao, LincolnJavati, SarahIga, JonahMalau, ElishebaKoepfli, CristianRobinson, Leanne J.Senn, NicolasKiniboro, BensonRare, LawrenceReeder, John C.Siba, PeterZimmerman, Peter A.Karunajeewa, HarinDavis, Timothy M.Mueller, IvoPlasmodium falciparumPlasmodium vivaxMalàriaResistència als medicamentsPlasmodium falciparumPlasmodium vivaxMalariaDrug resistanceBACKGROUND: 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 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. RESULTS: Despite 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). 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.BioMed Central2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/69213Articles publicats en revistes (ISGlobal)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: http://dx.doi.org/10.1186/s12936-015-0879-9Malaria Journal, 2015, vol. 14, num. 399, 9 p.http://dx.doi.org/10.1186/s12936-015-0879-9cc by (c) Barnadas et al., 2015http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/692132026-05-27T06:46:51Z
dc.title.none.fl_str_mv Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
title Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
spellingShingle Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
Barnadas, Céline
Plasmodium falciparum
Plasmodium vivax
Malària
Resistència als medicaments
Plasmodium falciparum
Plasmodium vivax
Malaria
Drug resistance
title_short Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
title_full Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
title_fullStr Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
title_full_unstemmed Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
title_sort Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea
dc.creator.none.fl_str_mv Barnadas, Céline
Timinao, Lincoln
Javati, Sarah
Iga, Jonah
Malau, Elisheba
Koepfli, Cristian
Robinson, Leanne J.
Senn, Nicolas
Kiniboro, Benson
Rare, Lawrence
Reeder, John C.
Siba, Peter
Zimmerman, Peter A.
Karunajeewa, Harin
Davis, Timothy M.
Mueller, Ivo
author Barnadas, Céline
author_facet Barnadas, Céline
Timinao, Lincoln
Javati, Sarah
Iga, Jonah
Malau, Elisheba
Koepfli, Cristian
Robinson, Leanne J.
Senn, Nicolas
Kiniboro, Benson
Rare, Lawrence
Reeder, John C.
Siba, Peter
Zimmerman, Peter A.
Karunajeewa, Harin
Davis, Timothy M.
Mueller, Ivo
author_role author
author2 Timinao, Lincoln
Javati, Sarah
Iga, Jonah
Malau, Elisheba
Koepfli, Cristian
Robinson, Leanne J.
Senn, Nicolas
Kiniboro, Benson
Rare, Lawrence
Reeder, John C.
Siba, Peter
Zimmerman, Peter A.
Karunajeewa, Harin
Davis, Timothy M.
Mueller, Ivo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Plasmodium falciparum
Plasmodium vivax
Malària
Resistència als medicaments
Plasmodium falciparum
Plasmodium vivax
Malaria
Drug resistance
topic Plasmodium falciparum
Plasmodium vivax
Malària
Resistència als medicaments
Plasmodium falciparum
Plasmodium vivax
Malaria
Drug resistance
description 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 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. RESULTS: Despite 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). 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.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/69213
url https://hdl.handle.net/2445/69213
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1186/s12936-015-0879-9
Malaria Journal, 2015, vol. 14, num. 399, 9 p.
http://dx.doi.org/10.1186/s12936-015-0879-9
dc.rights.none.fl_str_mv cc by (c) Barnadas et al., 2015
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Barnadas et al., 2015
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (ISGlobal)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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