Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia

Abstract Background Malaria still poses one of the major threats to human health. Development of effective antimalarial drugs has decreased this threat; however, the emergence of drug-resistant Plasmodium falciparum, a cause of Malaria, is disconcerting. The antimalarial drug chloroquine has been ef...

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Main Authors:	Patrick Reteng, Visia Vrisca, Inka Sukarno, Ilham Habib Djarkoni, Jane Angela Kalangi, George Eduardo Jacobs, Lucky Ronald Runtuwene, Yuki Eshita, Ryuichiro Maeda, Yutaka Suzuki, Arthur Elia Mongan, Sarah Maria Warouw, Junya Yamagishi, Josef Tuda
Format:	Article
Language:	English
Published:	BioMed Central 2017-04-01
Series:	BMC Research Notes
Subjects:	Chloroquine Genetic polymorphism Indonesia Malaria Multiplex sequencing North Sulawesi
Online Access:	http://link.springer.com/article/10.1186/s13104-017-2468-1

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spelling	doaj-art-f19f729d2024422ea5f21ea4a1b237b02018-08-20T14:42:48ZengBioMed CentralBMC Research Notes1756-05002017-04-011011810.1186/s13104-017-2468-1Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, IndonesiaPatrick Reteng0Visia Vrisca1Inka Sukarno2Ilham Habib Djarkoni3Jane Angela Kalangi4George Eduardo Jacobs5Lucky Ronald Runtuwene6Yuki Eshita7Ryuichiro Maeda8Yutaka Suzuki9Arthur Elia Mongan10Sarah Maria Warouw11Junya Yamagishi12Josef Tuda13Department of Medicine, Sam Ratulangi UniversityDepartment of Medicine, Sam Ratulangi UniversityDepartment of Medicine, Sam Ratulangi UniversityDepartment of Medicine, Sam Ratulangi UniversityDepartment of Medicine, Sam Ratulangi UniversityDepartment of Medicine, Sam Ratulangi UniversityDepartment of Medical Genome Sciences, University of TokyoFaculty of Medicine, Oita UniversityDepartment of Human Sciences, Obihiro University of Agriculture and Veterinary MedicineDepartment of Medical Genome Sciences, University of TokyoDepartment of Medicine, Sam Ratulangi UniversityDepartment of Medicine, Sam Ratulangi UniversityResearch Center for Zoonosis Control, Hokkaido UniversityDepartment of Medicine, Sam Ratulangi UniversityAbstract Background Malaria still poses one of the major threats to human health. Development of effective antimalarial drugs has decreased this threat; however, the emergence of drug-resistant Plasmodium falciparum, a cause of Malaria, is disconcerting. The antimalarial drug chloroquine has been effectively used, but resistant parasites have spread worldwide. Interestingly, the withdrawal of the drug reportedly leads to an increased population of susceptible parasites in some cases. We examined the prevalence of genomic polymorphisms in a malaria parasite P. falciparum, associated with resistance to an antimalarial drug chloroquine, after the withdrawal of the drug from Indonesia. Results Blood samples were collected from 95 malaria patients in North Sulawesi, Indonesia, in 2010. Parasite DNA was extracted and analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) for pfcrt and pfmdr1. In parallel, multiplex amplicon sequencing for the same genes was carried out with Illumina MiSeq. Of the 59 cases diagnosed as P. falciparum infection by microscopy, PCR–RFLP analysis clearly identified the genotype 76T in pfcrt in 44 cases. Sequencing analysis validated the identified genotypes in the 44 cases and demonstrated that the haplotype in the surrounding genomic region was exclusively SVMNT. Results of pfmdr1 were successfully obtained for 51 samples, where the genotyping results obtained by the two methods were completely consistent. In pfmdr1, the 86Y mutant genotype was observed in 45 cases (88.2%). Conclusions Our results suggest that the prevalence of the mutated genotypes remained dominant even 6 years after the withdrawal of chloroquine from this region. Diversified haplotype of the resistance-related locus, potentially involved in fitness costs, unauthorized usage of chloroquine, and/or a short post-withdrawal period may account for the observed high persistence of prevalence.http://link.springer.com/article/10.1186/s13104-017-2468-1ChloroquineGenetic polymorphismIndonesiaMalariaMultiplex sequencingNorth Sulawesi
institution	Open Data Bank
collection	Open Access Journals
building	Directory of Open Access Journals
language	English
format	Article
author	Patrick Reteng Visia Vrisca Inka Sukarno Ilham Habib Djarkoni Jane Angela Kalangi George Eduardo Jacobs Lucky Ronald Runtuwene Yuki Eshita Ryuichiro Maeda Yutaka Suzuki Arthur Elia Mongan Sarah Maria Warouw Junya Yamagishi Josef Tuda
spellingShingle	Patrick Reteng Visia Vrisca Inka Sukarno Ilham Habib Djarkoni Jane Angela Kalangi George Eduardo Jacobs Lucky Ronald Runtuwene Yuki Eshita Ryuichiro Maeda Yutaka Suzuki Arthur Elia Mongan Sarah Maria Warouw Junya Yamagishi Josef Tuda Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia BMC Research Notes Chloroquine Genetic polymorphism Indonesia Malaria Multiplex sequencing North Sulawesi
author_facet	Patrick Reteng Visia Vrisca Inka Sukarno Ilham Habib Djarkoni Jane Angela Kalangi George Eduardo Jacobs Lucky Ronald Runtuwene Yuki Eshita Ryuichiro Maeda Yutaka Suzuki Arthur Elia Mongan Sarah Maria Warouw Junya Yamagishi Josef Tuda
author_sort	Patrick Reteng
title	Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia
title_short	Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia
title_full	Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia
title_fullStr	Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia
title_full_unstemmed	Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia
title_sort	genetic polymorphisms in plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in north sulawesi, indonesia
publisher	BioMed Central
series	BMC Research Notes
issn	1756-0500
publishDate	2017-04-01
description	Abstract Background Malaria still poses one of the major threats to human health. Development of effective antimalarial drugs has decreased this threat; however, the emergence of drug-resistant Plasmodium falciparum, a cause of Malaria, is disconcerting. The antimalarial drug chloroquine has been effectively used, but resistant parasites have spread worldwide. Interestingly, the withdrawal of the drug reportedly leads to an increased population of susceptible parasites in some cases. We examined the prevalence of genomic polymorphisms in a malaria parasite P. falciparum, associated with resistance to an antimalarial drug chloroquine, after the withdrawal of the drug from Indonesia. Results Blood samples were collected from 95 malaria patients in North Sulawesi, Indonesia, in 2010. Parasite DNA was extracted and analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) for pfcrt and pfmdr1. In parallel, multiplex amplicon sequencing for the same genes was carried out with Illumina MiSeq. Of the 59 cases diagnosed as P. falciparum infection by microscopy, PCR–RFLP analysis clearly identified the genotype 76T in pfcrt in 44 cases. Sequencing analysis validated the identified genotypes in the 44 cases and demonstrated that the haplotype in the surrounding genomic region was exclusively SVMNT. Results of pfmdr1 were successfully obtained for 51 samples, where the genotyping results obtained by the two methods were completely consistent. In pfmdr1, the 86Y mutant genotype was observed in 45 cases (88.2%). Conclusions Our results suggest that the prevalence of the mutated genotypes remained dominant even 6 years after the withdrawal of chloroquine from this region. Diversified haplotype of the resistance-related locus, potentially involved in fitness costs, unauthorized usage of chloroquine, and/or a short post-withdrawal period may account for the observed high persistence of prevalence.
topic	Chloroquine Genetic polymorphism Indonesia Malaria Multiplex sequencing North Sulawesi
url	http://link.springer.com/article/10.1186/s13104-017-2468-1
_version_	1612688739651289088

Genetic polymorphisms in Plasmodium falciparum chloroquine resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia

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