Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia

Abstract Background While malaria incidence in Indonesia has decreased threefold in the last decade, more than 200,000 cases were reported in 2016. Different endemicity of Plasmodium falciparum malaria among several islands in Indonesia has been recognized and two unique mutations of P. falciparum d...

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Main Authors: Sukmawati Basuki, Fitriah, Petronella M. Risamasu, Kasmijati, Pancawati Ariami, Sugeng Riyanto, Ari Hidayat, Dewi Susilowati, Iskandar, Budi Armika, Budiono, Yoes P. Dachlan, Hiroji Kanbara, Haruki Uemura
Format: Article
Language:English
Published: BMC 2018-12-01
Series:Malaria Journal
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Online Access:http://link.springer.com/article/10.1186/s12936-018-2597-6
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author Sukmawati Basuki
Fitriah
Petronella M. Risamasu
Kasmijati
Pancawati Ariami
Sugeng Riyanto
Ari Hidayat
Dewi Susilowati
Iskandar
Budi Armika
Budiono
Yoes P. Dachlan
Hiroji Kanbara
Haruki Uemura
author_facet Sukmawati Basuki
Fitriah
Petronella M. Risamasu
Kasmijati
Pancawati Ariami
Sugeng Riyanto
Ari Hidayat
Dewi Susilowati
Iskandar
Budi Armika
Budiono
Yoes P. Dachlan
Hiroji Kanbara
Haruki Uemura
author_sort Sukmawati Basuki
collection DOAJ
description Abstract Background While malaria incidence in Indonesia has decreased threefold in the last decade, more than 200,000 cases were reported in 2016. Different endemicity of Plasmodium falciparum malaria among several islands in Indonesia has been recognized and two unique mutations of P. falciparum dihydropteroate synthase (pfdhps) affecting sulfadoxine–pyrimethamine (SP) resistance were detected from the research of SP efficiency and genotype analysis in South Kalimantan. In this study, geographical distribution and origin of these pfdhps K540T and I588F mutations were analysed. Methods Malaria parasites DNA from several endemic areas in Indonesia; Sumatera, Java, Kalimantan, Lombok, Sumbawa, Timor, Sulawesi, and Papua islands; in two periods, 2004–2006 and 2009–2012 were subjected for pfdhfr and pfdhps sequence analysis. Results Different genotype polymorphisms of pfdhfr and pfdhps were observed in the parasites from various regions in Indonesia and relatively more divergent genotypes were determined from Kalimantan isolates in both 2004–2006 and 2009–2012. The parasites containing K540T mutation were identified in 2004–2006 isolates from East Kalimantan, East Java and Sumbawa as an SGTGA haplotype. The other I588F mutation was also determined in 2004–2006 parasites, isolated from Lombok and Sumbawa islands as an SGEAA(588F) haplotype. The parasites with pfdhfr/pfdhps quintuple or sextuple mutation, a genotype marker of SP resistance, were determined mostly in Kalimantan in both 2004–2006 and 2009–2012. Conclusion Analysis of the prevalence and pfdhfr/pfdhps combined genotypes of K540T or I588F mutations suggested that K540T might be origin in Kalimantan Island and I588F in Sumbawa Island and then these were spread to other areas along with people movement. This research indicates regular monitoring of drug efficacy and parasite genotype analysis is important to keep efficiency and prevent the spread of resistance. It is also essential for the latest anti-malarial drug artemisinin-based combination therapy.
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spelling doaj.art-6109abf1ee78460dbf27f4b42fa7071a2022-12-22T01:13:59ZengBMCMalaria Journal1475-28752018-12-0117111410.1186/s12936-018-2597-6Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in IndonesiaSukmawati Basuki0Fitriah1Petronella M. Risamasu2Kasmijati3Pancawati Ariami4Sugeng Riyanto5Ari Hidayat6Dewi Susilowati7Iskandar8Budi Armika9Budiono10Yoes P. Dachlan11Hiroji Kanbara12Haruki Uemura13Department of Medical Parasitology, Faculty of Medicine, Universitas AirlanggaMalaria Study Group/Laboratory of Malaria, Institute of Tropical Disease, Universitas AirlanggaDisease Control of Jayapura District Department of HealthUPTD, Puskesmas Kuala PembuangPoltekkes MataramBanjar District Department of HealthArifin Achmad HospitalFaculty of Public Health, Universitas GorontaloPuskesmas Utan RheeWest Nusa Tenggara Provincial Department of HealthDepartment of Public Health and Preventive Medicine, Faculty of Medicine, Universitas AirlanggaDepartment of Medical Parasitology, Faculty of Medicine, Universitas AirlanggaDepartment of Protozoology, Institute of Tropical Medicine, Nagasaki UniversityDepartment of Protozoology, Institute of Tropical Medicine, Nagasaki UniversityAbstract Background While malaria incidence in Indonesia has decreased threefold in the last decade, more than 200,000 cases were reported in 2016. Different endemicity of Plasmodium falciparum malaria among several islands in Indonesia has been recognized and two unique mutations of P. falciparum dihydropteroate synthase (pfdhps) affecting sulfadoxine–pyrimethamine (SP) resistance were detected from the research of SP efficiency and genotype analysis in South Kalimantan. In this study, geographical distribution and origin of these pfdhps K540T and I588F mutations were analysed. Methods Malaria parasites DNA from several endemic areas in Indonesia; Sumatera, Java, Kalimantan, Lombok, Sumbawa, Timor, Sulawesi, and Papua islands; in two periods, 2004–2006 and 2009–2012 were subjected for pfdhfr and pfdhps sequence analysis. Results Different genotype polymorphisms of pfdhfr and pfdhps were observed in the parasites from various regions in Indonesia and relatively more divergent genotypes were determined from Kalimantan isolates in both 2004–2006 and 2009–2012. The parasites containing K540T mutation were identified in 2004–2006 isolates from East Kalimantan, East Java and Sumbawa as an SGTGA haplotype. The other I588F mutation was also determined in 2004–2006 parasites, isolated from Lombok and Sumbawa islands as an SGEAA(588F) haplotype. The parasites with pfdhfr/pfdhps quintuple or sextuple mutation, a genotype marker of SP resistance, were determined mostly in Kalimantan in both 2004–2006 and 2009–2012. Conclusion Analysis of the prevalence and pfdhfr/pfdhps combined genotypes of K540T or I588F mutations suggested that K540T might be origin in Kalimantan Island and I588F in Sumbawa Island and then these were spread to other areas along with people movement. This research indicates regular monitoring of drug efficacy and parasite genotype analysis is important to keep efficiency and prevent the spread of resistance. It is also essential for the latest anti-malarial drug artemisinin-based combination therapy.http://link.springer.com/article/10.1186/s12936-018-2597-6Plasmodium falciparumPfdhfrPfdhpsMutationPolymorphismIndonesia
spellingShingle Sukmawati Basuki
Fitriah
Petronella M. Risamasu
Kasmijati
Pancawati Ariami
Sugeng Riyanto
Ari Hidayat
Dewi Susilowati
Iskandar
Budi Armika
Budiono
Yoes P. Dachlan
Hiroji Kanbara
Haruki Uemura
Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia
Malaria Journal
Plasmodium falciparum
Pfdhfr
Pfdhps
Mutation
Polymorphism
Indonesia
title Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia
title_full Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia
title_fullStr Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia
title_full_unstemmed Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia
title_short Origins and spread of novel genetic variants of sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates in Indonesia
title_sort origins and spread of novel genetic variants of sulfadoxine pyrimethamine resistance in plasmodium falciparum isolates in indonesia
topic Plasmodium falciparum
Pfdhfr
Pfdhps
Mutation
Polymorphism
Indonesia
url http://link.springer.com/article/10.1186/s12936-018-2597-6
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