Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia
Drug resistant Plasmodium parasites are a major threat to malaria control and elimination. After reports of high levels of multidrug resistant P. falciparum and P. vivax in Indonesia, in 2005, the national first-line treatment policy for uncomplicated malaria was changed in March 2006, to dihydroart...
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Elsevier
2021-12-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320721000294 |
| _version_ | 1819320178608963584 |
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| author | Jutta Marfurt Grennady Wirjanata Pak Prayoga Ferryanto Chalfein Leo Leonardo Boni F. Sebayang Dwi Apriyanti Maic A.E.M. Sihombing Leily Trianty Rossarin Suwanarusk Alan Brockman Kim A. Piera Irene Luo Angela Rumaseb Barbara MacHunter Sarah Auburn Nicholas M. Anstey Enny Kenangalem Rintis Noviyanti Bruce Russell Jeanne R. Poespoprodjo Ric N. Price |
| author_facet | Jutta Marfurt Grennady Wirjanata Pak Prayoga Ferryanto Chalfein Leo Leonardo Boni F. Sebayang Dwi Apriyanti Maic A.E.M. Sihombing Leily Trianty Rossarin Suwanarusk Alan Brockman Kim A. Piera Irene Luo Angela Rumaseb Barbara MacHunter Sarah Auburn Nicholas M. Anstey Enny Kenangalem Rintis Noviyanti Bruce Russell Jeanne R. Poespoprodjo Ric N. Price |
| author_sort | Jutta Marfurt |
| collection | DOAJ |
| description | Drug resistant Plasmodium parasites are a major threat to malaria control and elimination. After reports of high levels of multidrug resistant P. falciparum and P. vivax in Indonesia, in 2005, the national first-line treatment policy for uncomplicated malaria was changed in March 2006, to dihydroartemisinin-piperaquine against all species.This study assessed the temporal trends in ex vivo drug susceptibility to chloroquine (CQ) and piperaquine (PIP) for both P. falciparum and P. vivax clinical isolates collected between 2004 and 2018, by using schizont maturation assays, and genotyped a subset of isolates for known and putative molecular markers of CQ and PIP resistance by using Sanger and next generation whole genome sequencing.The median CQ IC50 values varied significantly between years in both Plasmodium species, but there was no significant trend over time. In contrast, there was a significant trend for increasing PIP IC50s in both Plasmodium species from 2010 onwards. Whereas the South American CQ resistant 7G8 pfcrt SVMNT isoform has been fixed since 2005 in the study area, the pfmdr1 86Y allele frequencies decreased and became fixed at the wild-type allele in 2015. In P. vivax isolates, putative markers of CQ resistance (no pvcrt-o AAG (K10) insertion and pvmdr1 Y967F and F1076L) were fixed at the mutant alleles since 2005. None of the putative PIP resistance markers were detected in P. falciparum.The ex vivo drug susceptibility and molecular analysis of CQ and PIP efficacy for P. falciparum and P. vivax after 12 years of intense drug pressure with DHP suggests that whilst the degree of CQ resistance appears to have been sustained, there has been a slight decline in PIP susceptibility, although this does not appear to have reached clinically significant levels. The observed decreasing trend in ex vivo PIP susceptibility highlights the importance of ongoing surveillance. |
| first_indexed | 2024-12-24T11:15:27Z |
| format | Article |
| id | doaj.art-101f0af0b8c24723b71393e8a4ab93c8 |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-12-24T11:15:27Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
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| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-101f0af0b8c24723b71393e8a4ab93c82022-12-21T16:58:23ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072021-12-01174656Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, IndonesiaJutta Marfurt0Grennady Wirjanata1Pak Prayoga2Ferryanto Chalfein3Leo Leonardo4Boni F. Sebayang5Dwi Apriyanti6Maic A.E.M. Sihombing7Leily Trianty8Rossarin Suwanarusk9Alan Brockman10Kim A. Piera11Irene Luo12Angela Rumaseb13Barbara MacHunter14Sarah Auburn15Nicholas M. Anstey16Enny Kenangalem17Rintis Noviyanti18Bruce Russell19Jeanne R. Poespoprodjo20Ric N. Price21Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, Australia; Corresponding author. Menzies School of Health Research, PO Box 41096, Casuarina, NT, 0811, Darwin, Australia.Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaPapuan Health and Community Development Foundation (PHCDF), Jl. Caritas No. 1, 99961, Timika, Papua, IndonesiaPapuan Health and Community Development Foundation (PHCDF), Jl. Caritas No. 1, 99961, Timika, Papua, IndonesiaPapuan Health and Community Development Foundation (PHCDF), Jl. Caritas No. 1, 99961, Timika, Papua, IndonesiaEijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Jakarta, IndonesiaEijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Jakarta, IndonesiaEijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Jakarta, IndonesiaEijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Jakarta, IndonesiaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, Australia; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK; Mahidol‐Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, ThailandGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaPapuan Health and Community Development Foundation (PHCDF), Jl. Caritas No. 1, 99961, Timika, Papua, Indonesia; District Health Authority, Timika, Papua, IndonesiaEijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Jakarta, IndonesiaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, AustraliaPapuan Health and Community Development Foundation (PHCDF), Jl. Caritas No. 1, 99961, Timika, Papua, Indonesia; Paediatric Research Office, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, IndonesiaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, NT, 0811, Darwin, Australia; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, UK; Mahidol‐Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, ThailandDrug resistant Plasmodium parasites are a major threat to malaria control and elimination. After reports of high levels of multidrug resistant P. falciparum and P. vivax in Indonesia, in 2005, the national first-line treatment policy for uncomplicated malaria was changed in March 2006, to dihydroartemisinin-piperaquine against all species.This study assessed the temporal trends in ex vivo drug susceptibility to chloroquine (CQ) and piperaquine (PIP) for both P. falciparum and P. vivax clinical isolates collected between 2004 and 2018, by using schizont maturation assays, and genotyped a subset of isolates for known and putative molecular markers of CQ and PIP resistance by using Sanger and next generation whole genome sequencing.The median CQ IC50 values varied significantly between years in both Plasmodium species, but there was no significant trend over time. In contrast, there was a significant trend for increasing PIP IC50s in both Plasmodium species from 2010 onwards. Whereas the South American CQ resistant 7G8 pfcrt SVMNT isoform has been fixed since 2005 in the study area, the pfmdr1 86Y allele frequencies decreased and became fixed at the wild-type allele in 2015. In P. vivax isolates, putative markers of CQ resistance (no pvcrt-o AAG (K10) insertion and pvmdr1 Y967F and F1076L) were fixed at the mutant alleles since 2005. None of the putative PIP resistance markers were detected in P. falciparum.The ex vivo drug susceptibility and molecular analysis of CQ and PIP efficacy for P. falciparum and P. vivax after 12 years of intense drug pressure with DHP suggests that whilst the degree of CQ resistance appears to have been sustained, there has been a slight decline in PIP susceptibility, although this does not appear to have reached clinically significant levels. The observed decreasing trend in ex vivo PIP susceptibility highlights the importance of ongoing surveillance.http://www.sciencedirect.com/science/article/pii/S2211320721000294MalariaPlasmodium falciparumPlasmodium vivaxChloroquinePiperaquineDrug resistance |
| spellingShingle | Jutta Marfurt Grennady Wirjanata Pak Prayoga Ferryanto Chalfein Leo Leonardo Boni F. Sebayang Dwi Apriyanti Maic A.E.M. Sihombing Leily Trianty Rossarin Suwanarusk Alan Brockman Kim A. Piera Irene Luo Angela Rumaseb Barbara MacHunter Sarah Auburn Nicholas M. Anstey Enny Kenangalem Rintis Noviyanti Bruce Russell Jeanne R. Poespoprodjo Ric N. Price Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia International Journal for Parasitology: Drugs and Drug Resistance Malaria Plasmodium falciparum Plasmodium vivax Chloroquine Piperaquine Drug resistance |
| title | Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia |
| title_full | Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia |
| title_fullStr | Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia |
| title_full_unstemmed | Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia |
| title_short | Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia |
| title_sort | longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against plasmodium falciparum and p vivax before and after introduction of artemisinin based combination therapy in papua indonesia |
| topic | Malaria Plasmodium falciparum Plasmodium vivax Chloroquine Piperaquine Drug resistance |
| url | http://www.sciencedirect.com/science/article/pii/S2211320721000294 |
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