Antimalarial drug resistance molecular makers of Plasmodium falciparum isolates from Sudan during 2015-2017
Current malaria control and elimination strategies rely mainly on efficacious antimalarial drugs. However, drug resistance is a major threat facing malaria control programs. Determination of drug resistance molecular markers is useful in the monitoring and surveillance of malaria drug efficacy. This...
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| creator | Hussien, Maazza Abdel Hamid, Muzamil Mahdi Elamin, Elamin Abdelkarim Hassan, Abdalla O Elaagip, Arwa H Salama, Abusofyan Hamattallah A Abdelraheem, Mohammed H Mohamed, Abdelrahim O |
| description | Current malaria control and elimination strategies rely mainly on efficacious antimalarial drugs. However, drug resistance is a major threat facing malaria control programs. Determination of drug resistance molecular markers is useful in the monitoring and surveillance of malaria drug efficacy. This study aimed to determine the mutations and haplotypes frequencies of different genes linked with antimalarial drug resistance in certain areas in Sudan.
A total of 226 dried blood spots (DBS) of microscopically diagnosed P. falciparum isolates were collected from Khartoum and three other areas in Sudan during 2015-2017. Plasmodium falciparum confirmation and multiplicity of infection was assessed using the Sanger's 101 SNPs-barcode and speciation was confirmed using regions of the parasite mitochondria. Molecular genotyping of drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, exonuclease, Pfk13, parasite genetic background (PGB) (Pfarps10, ferredoxin, Pfcrt, Pfmdr2)) was also performed. All genotypes were generated by selective regions amplicon sequencing of the parasite genome using the Illumina MiSeq platform at the Wellcome Sanger Institute, UK then genotypes were translated into drug resistance haplotypes and species determination.
In total 225 samples were confirmed to be P. falciparum. A higher proportion of multiplicity of infection was observed in Gezira (P |
| doi_str_mv | 10.1371/journal.pone.0235401 |
| format | Article |
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A total of 226 dried blood spots (DBS) of microscopically diagnosed P. falciparum isolates were collected from Khartoum and three other areas in Sudan during 2015-2017. Plasmodium falciparum confirmation and multiplicity of infection was assessed using the Sanger's 101 SNPs-barcode and speciation was confirmed using regions of the parasite mitochondria. Molecular genotyping of drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, exonuclease, Pfk13, parasite genetic background (PGB) (Pfarps10, ferredoxin, Pfcrt, Pfmdr2)) was also performed. All genotypes were generated by selective regions amplicon sequencing of the parasite genome using the Illumina MiSeq platform at the Wellcome Sanger Institute, UK then genotypes were translated into drug resistance haplotypes and species determination.
In total 225 samples were confirmed to be P. falciparum. A higher proportion of multiplicity of infection was observed in Gezira (P<0.001) based on the Sanger 101 SNPs -barcode. The overall frequency of mutant haplotype Pfcrt 72-76 CVIET was 71.8%. For Pfmdr1, N86Y was detected in 53.6%, Y184F was observed in 88.1% and D1246Y was detected in 1.5% of the samples. The most frequently observed haplotype was YFD 47.4%. For Pfdhfr (codons 51, 59,108,164), the ICNI haplotype was the most frequent (80.7%) while for Pfdhps (codons 436, 437, 540, 581, 613) the (SGEAA) was most frequent haplotype (41%). The Quadruple mutation (dhfr N51I, S108N + dhps A437G, K540E) was the highest frequent combined mutation (33.9%). In Pfkelch13 gene, 18 non-synonymous mutations were detected, 7 of them were detected in other African countries. The most frequent Pfk13 mutation was E433D detected in four samples. All of the Pfk13 mutant alleles have not been reported to belong to mutations associated with delayed parasite clearance in Southeast Asia. PGB mutations were detected only in Pfcrt N326S\I (46.3%) and Pfcrt I356T (8.2%). The exonuclease mutation was not detected. There was no significant variation in mutant haplotypes between study areas.
There was high frequency of mutations in Pfcrt, Pfdhfr and Pfdhps in this study. These mutations are associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance. Many SNPs in Pfk13 not linked with delayed parasite clearance were observed. The exonuclease E415G mutation which is linked with piperaquine resistance was not reported.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0235401</identifier><identifier>PMID: 32817665</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Antimalarial agents ; Antimalarials - pharmacology ; Biology and Life Sciences ; Child ; Chloroquine ; Chloroquine - pharmacology ; Codons ; Control ; Control programs ; Deoxyribonucleic acid ; Dihydrofolate reductase ; DNA ; Drug efficacy ; Drug resistance ; Drug Resistance - genetics ; Drug therapy ; Entomology ; Erythrocytes ; Ethics ; Exonuclease ; Female ; Ferredoxin ; Gene frequency ; Genes ; Genetic aspects ; Genomes ; Genotypes ; Genotyping ; Haplotypes ; Humans ; Infections ; Malaria ; Malaria - epidemiology ; Malaria - parasitology ; Male ; Medical laboratories ; Medicine and Health Sciences ; Membrane Transport Proteins - genetics ; Membrane Transport Proteins - metabolism ; Microbial drug resistance ; Mitochondria ; Mortality ; Multiplicity of infection ; Mutants ; Mutation ; Parasites ; Parasitology ; People and Places ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Plasmodium falciparum - pathogenicity ; Protozoan Proteins - genetics ; Protozoan Proteins - metabolism ; Pyrimethamine ; Pyrimethamine - pharmacology ; Single-nucleotide polymorphism ; Speciation ; Statistics ; Sudan ; Sulfadoxine ; Sulfadoxine - pharmacology ; Tetrahydrofolate Dehydrogenase - genetics ; Tetrahydrofolate Dehydrogenase - metabolism ; Vector-borne diseases ; Young Adult</subject><ispartof>PloS one, 2020-08, Vol.15 (8), p.e0235401-e0235401</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Hussien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Hussien et al 2020 Hussien et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-cbe5bcab6cd76df0b7f1eec08890b870a8f64bb6b235d0c6c90b713cfb5250913</citedby><cites>FETCH-LOGICAL-c692t-cbe5bcab6cd76df0b7f1eec08890b870a8f64bb6b235d0c6c90b713cfb5250913</cites><orcidid>0000-0002-6157-4388</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446868/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446868/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32817665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Carvalho, Luzia Helena</contributor><creatorcontrib>Hussien, Maazza</creatorcontrib><creatorcontrib>Abdel Hamid, Muzamil Mahdi</creatorcontrib><creatorcontrib>Elamin, Elamin Abdelkarim</creatorcontrib><creatorcontrib>Hassan, Abdalla O</creatorcontrib><creatorcontrib>Elaagip, Arwa H</creatorcontrib><creatorcontrib>Salama, Abusofyan Hamattallah A</creatorcontrib><creatorcontrib>Abdelraheem, Mohammed H</creatorcontrib><creatorcontrib>Mohamed, Abdelrahim O</creatorcontrib><title>Antimalarial drug resistance molecular makers of Plasmodium falciparum isolates from Sudan during 2015-2017</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Current malaria control and elimination strategies rely mainly on efficacious antimalarial drugs. However, drug resistance is a major threat facing malaria control programs. Determination of drug resistance molecular markers is useful in the monitoring and surveillance of malaria drug efficacy. This study aimed to determine the mutations and haplotypes frequencies of different genes linked with antimalarial drug resistance in certain areas in Sudan.
A total of 226 dried blood spots (DBS) of microscopically diagnosed P. falciparum isolates were collected from Khartoum and three other areas in Sudan during 2015-2017. Plasmodium falciparum confirmation and multiplicity of infection was assessed using the Sanger's 101 SNPs-barcode and speciation was confirmed using regions of the parasite mitochondria. Molecular genotyping of drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, exonuclease, Pfk13, parasite genetic background (PGB) (Pfarps10, ferredoxin, Pfcrt, Pfmdr2)) was also performed. All genotypes were generated by selective regions amplicon sequencing of the parasite genome using the Illumina MiSeq platform at the Wellcome Sanger Institute, UK then genotypes were translated into drug resistance haplotypes and species determination.
In total 225 samples were confirmed to be P. falciparum. A higher proportion of multiplicity of infection was observed in Gezira (P<0.001) based on the Sanger 101 SNPs -barcode. The overall frequency of mutant haplotype Pfcrt 72-76 CVIET was 71.8%. For Pfmdr1, N86Y was detected in 53.6%, Y184F was observed in 88.1% and D1246Y was detected in 1.5% of the samples. The most frequently observed haplotype was YFD 47.4%. For Pfdhfr (codons 51, 59,108,164), the ICNI haplotype was the most frequent (80.7%) while for Pfdhps (codons 436, 437, 540, 581, 613) the (SGEAA) was most frequent haplotype (41%). The Quadruple mutation (dhfr N51I, S108N + dhps A437G, K540E) was the highest frequent combined mutation (33.9%). In Pfkelch13 gene, 18 non-synonymous mutations were detected, 7 of them were detected in other African countries. The most frequent Pfk13 mutation was E433D detected in four samples. All of the Pfk13 mutant alleles have not been reported to belong to mutations associated with delayed parasite clearance in Southeast Asia. PGB mutations were detected only in Pfcrt N326S\I (46.3%) and Pfcrt I356T (8.2%). The exonuclease mutation was not detected. There was no significant variation in mutant haplotypes between study areas.
There was high frequency of mutations in Pfcrt, Pfdhfr and Pfdhps in this study. These mutations are associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance. Many SNPs in Pfk13 not linked with delayed parasite clearance were observed. The exonuclease E415G mutation which is linked with piperaquine resistance was not reported.</description><subject>Adolescent</subject><subject>Antimalarial agents</subject><subject>Antimalarials - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Child</subject><subject>Chloroquine</subject><subject>Chloroquine - pharmacology</subject><subject>Codons</subject><subject>Control</subject><subject>Control programs</subject><subject>Deoxyribonucleic acid</subject><subject>Dihydrofolate reductase</subject><subject>DNA</subject><subject>Drug efficacy</subject><subject>Drug resistance</subject><subject>Drug Resistance - genetics</subject><subject>Drug therapy</subject><subject>Entomology</subject><subject>Erythrocytes</subject><subject>Ethics</subject><subject>Exonuclease</subject><subject>Female</subject><subject>Ferredoxin</subject><subject>Gene frequency</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genotypes</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Infections</subject><subject>Malaria</subject><subject>Malaria - epidemiology</subject><subject>Malaria - parasitology</subject><subject>Male</subject><subject>Medical laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Transport Proteins - genetics</subject><subject>Membrane Transport Proteins - metabolism</subject><subject>Microbial drug resistance</subject><subject>Mitochondria</subject><subject>Mortality</subject><subject>Multiplicity of infection</subject><subject>Mutants</subject><subject>Mutation</subject><subject>Parasites</subject><subject>Parasitology</subject><subject>People and Places</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Plasmodium falciparum - pathogenicity</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - metabolism</subject><subject>Pyrimethamine</subject><subject>Pyrimethamine - pharmacology</subject><subject>Single-nucleotide polymorphism</subject><subject>Speciation</subject><subject>Statistics</subject><subject>Sudan</subject><subject>Sulfadoxine</subject><subject>Sulfadoxine - pharmacology</subject><subject>Tetrahydrofolate Dehydrogenase - genetics</subject><subject>Tetrahydrofolate Dehydrogenase - metabolism</subject><subject>Vector-borne diseases</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjEmTJu2NMCx-DCysuOptOPloJ7NpMyat6L83s9NdprIXEmjCyXPe9LzJybLnGC0x4fjd1o-hB7fc-d4sUUFKivCD7BTXpFiwApGHR-uT7EmMW4RKUjH2ODshRYU5Y-Vpdr3qB9uBg2DB5TqMbR5MtHGAXpm8886oMW3mHVybEHPf5F8cxM5rO3Z5A07ZHYS0tNE7GEzMm-C7_GrU0Od6DLZv8wLhcpE-_Gn2KGVE82yaz7LvHz98O_-8uLj8tD5fXSwUq4thoaQppQLJlOZMN0jyBhujUFXVSFYcQdUwKiWTqWaNFFMpzDFRjSyLEtWYnGUvD7o756OYfIqioKTklGG0J9YHQnvYil1IDoQ_woMVNwEfWgFhsMoZoUuQ2lAuwUjKKQFKKCa1blilQBGWtN5Pp42yM1qZfgjgZqLznd5uROt_CU4pq1iVBN5MAsH_HE0cRGejMs5Bb_x4898s3W1NaEJf_YPeX91EtZAKsH3j07lqLypWjBBEk5E8Uct7qDS06axKj6qxKT5LeDtLSMxgfg8tjDGK9dXX_2cvf8zZ10fsxoAbNuk1jYP1fZyD9ACq4GMMprkzGSOx74lbN8S-J8TUEyntxfEF3SXdNgH5C4LcB14</recordid><startdate>20200820</startdate><enddate>20200820</enddate><creator>Hussien, Maazza</creator><creator>Abdel Hamid, Muzamil Mahdi</creator><creator>Elamin, Elamin Abdelkarim</creator><creator>Hassan, Abdalla O</creator><creator>Elaagip, Arwa H</creator><creator>Salama, Abusofyan Hamattallah A</creator><creator>Abdelraheem, Mohammed H</creator><creator>Mohamed, Abdelrahim O</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6157-4388</orcidid></search><sort><creationdate>20200820</creationdate><title>Antimalarial drug resistance molecular makers of Plasmodium falciparum isolates from Sudan during 2015-2017</title><author>Hussien, Maazza ; Abdel Hamid, Muzamil Mahdi ; Elamin, Elamin Abdelkarim ; Hassan, Abdalla O ; Elaagip, Arwa H ; Salama, Abusofyan Hamattallah A ; Abdelraheem, Mohammed H ; Mohamed, Abdelrahim O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cbe5bcab6cd76df0b7f1eec08890b870a8f64bb6b235d0c6c90b713cfb5250913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Antimalarial agents</topic><topic>Antimalarials - pharmacology</topic><topic>Biology and Life Sciences</topic><topic>Child</topic><topic>Chloroquine</topic><topic>Chloroquine - pharmacology</topic><topic>Codons</topic><topic>Control</topic><topic>Control programs</topic><topic>Deoxyribonucleic acid</topic><topic>Dihydrofolate reductase</topic><topic>DNA</topic><topic>Drug efficacy</topic><topic>Drug resistance</topic><topic>Drug Resistance - genetics</topic><topic>Drug therapy</topic><topic>Entomology</topic><topic>Erythrocytes</topic><topic>Ethics</topic><topic>Exonuclease</topic><topic>Female</topic><topic>Ferredoxin</topic><topic>Gene frequency</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Genotypes</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Infections</topic><topic>Malaria</topic><topic>Malaria - epidemiology</topic><topic>Malaria - parasitology</topic><topic>Male</topic><topic>Medical laboratories</topic><topic>Medicine and Health Sciences</topic><topic>Membrane Transport Proteins - genetics</topic><topic>Membrane Transport Proteins - metabolism</topic><topic>Microbial drug resistance</topic><topic>Mitochondria</topic><topic>Mortality</topic><topic>Multiplicity of infection</topic><topic>Mutants</topic><topic>Mutation</topic><topic>Parasites</topic><topic>Parasitology</topic><topic>People and Places</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - genetics</topic><topic>Plasmodium falciparum - pathogenicity</topic><topic>Protozoan Proteins - genetics</topic><topic>Protozoan Proteins - metabolism</topic><topic>Pyrimethamine</topic><topic>Pyrimethamine - pharmacology</topic><topic>Single-nucleotide polymorphism</topic><topic>Speciation</topic><topic>Statistics</topic><topic>Sudan</topic><topic>Sulfadoxine</topic><topic>Sulfadoxine - pharmacology</topic><topic>Tetrahydrofolate Dehydrogenase - genetics</topic><topic>Tetrahydrofolate Dehydrogenase - metabolism</topic><topic>Vector-borne diseases</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hussien, Maazza</creatorcontrib><creatorcontrib>Abdel Hamid, Muzamil Mahdi</creatorcontrib><creatorcontrib>Elamin, Elamin Abdelkarim</creatorcontrib><creatorcontrib>Hassan, Abdalla O</creatorcontrib><creatorcontrib>Elaagip, Arwa H</creatorcontrib><creatorcontrib>Salama, Abusofyan Hamattallah A</creatorcontrib><creatorcontrib>Abdelraheem, Mohammed H</creatorcontrib><creatorcontrib>Mohamed, Abdelrahim O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hussien, Maazza</au><au>Abdel Hamid, Muzamil Mahdi</au><au>Elamin, Elamin Abdelkarim</au><au>Hassan, Abdalla O</au><au>Elaagip, Arwa H</au><au>Salama, Abusofyan Hamattallah A</au><au>Abdelraheem, Mohammed H</au><au>Mohamed, Abdelrahim O</au><au>Carvalho, Luzia Helena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimalarial drug resistance molecular makers of Plasmodium falciparum isolates from Sudan during 2015-2017</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-08-20</date><risdate>2020</risdate><volume>15</volume><issue>8</issue><spage>e0235401</spage><epage>e0235401</epage><pages>e0235401-e0235401</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Current malaria control and elimination strategies rely mainly on efficacious antimalarial drugs. However, drug resistance is a major threat facing malaria control programs. Determination of drug resistance molecular markers is useful in the monitoring and surveillance of malaria drug efficacy. This study aimed to determine the mutations and haplotypes frequencies of different genes linked with antimalarial drug resistance in certain areas in Sudan.
A total of 226 dried blood spots (DBS) of microscopically diagnosed P. falciparum isolates were collected from Khartoum and three other areas in Sudan during 2015-2017. Plasmodium falciparum confirmation and multiplicity of infection was assessed using the Sanger's 101 SNPs-barcode and speciation was confirmed using regions of the parasite mitochondria. Molecular genotyping of drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, exonuclease, Pfk13, parasite genetic background (PGB) (Pfarps10, ferredoxin, Pfcrt, Pfmdr2)) was also performed. All genotypes were generated by selective regions amplicon sequencing of the parasite genome using the Illumina MiSeq platform at the Wellcome Sanger Institute, UK then genotypes were translated into drug resistance haplotypes and species determination.
In total 225 samples were confirmed to be P. falciparum. A higher proportion of multiplicity of infection was observed in Gezira (P<0.001) based on the Sanger 101 SNPs -barcode. The overall frequency of mutant haplotype Pfcrt 72-76 CVIET was 71.8%. For Pfmdr1, N86Y was detected in 53.6%, Y184F was observed in 88.1% and D1246Y was detected in 1.5% of the samples. The most frequently observed haplotype was YFD 47.4%. For Pfdhfr (codons 51, 59,108,164), the ICNI haplotype was the most frequent (80.7%) while for Pfdhps (codons 436, 437, 540, 581, 613) the (SGEAA) was most frequent haplotype (41%). The Quadruple mutation (dhfr N51I, S108N + dhps A437G, K540E) was the highest frequent combined mutation (33.9%). In Pfkelch13 gene, 18 non-synonymous mutations were detected, 7 of them were detected in other African countries. The most frequent Pfk13 mutation was E433D detected in four samples. All of the Pfk13 mutant alleles have not been reported to belong to mutations associated with delayed parasite clearance in Southeast Asia. PGB mutations were detected only in Pfcrt N326S\I (46.3%) and Pfcrt I356T (8.2%). The exonuclease mutation was not detected. There was no significant variation in mutant haplotypes between study areas.
There was high frequency of mutations in Pfcrt, Pfdhfr and Pfdhps in this study. These mutations are associated with chloroquine and sulfadoxine-pyrimethamine (SP) resistance. Many SNPs in Pfk13 not linked with delayed parasite clearance were observed. The exonuclease E415G mutation which is linked with piperaquine resistance was not reported.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32817665</pmid><doi>10.1371/journal.pone.0235401</doi><tpages>e0235401</tpages><orcidid>https://orcid.org/0000-0002-6157-4388</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-08, Vol.15 (8), p.e0235401-e0235401 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2435746101 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Antimalarial agents Antimalarials - pharmacology Biology and Life Sciences Child Chloroquine Chloroquine - pharmacology Codons Control Control programs Deoxyribonucleic acid Dihydrofolate reductase DNA Drug efficacy Drug resistance Drug Resistance - genetics Drug therapy Entomology Erythrocytes Ethics Exonuclease Female Ferredoxin Gene frequency Genes Genetic aspects Genomes Genotypes Genotyping Haplotypes Humans Infections Malaria Malaria - epidemiology Malaria - parasitology Male Medical laboratories Medicine and Health Sciences Membrane Transport Proteins - genetics Membrane Transport Proteins - metabolism Microbial drug resistance Mitochondria Mortality Multiplicity of infection Mutants Mutation Parasites Parasitology People and Places Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Plasmodium falciparum - pathogenicity Protozoan Proteins - genetics Protozoan Proteins - metabolism Pyrimethamine Pyrimethamine - pharmacology Single-nucleotide polymorphism Speciation Statistics Sudan Sulfadoxine Sulfadoxine - pharmacology Tetrahydrofolate Dehydrogenase - genetics Tetrahydrofolate Dehydrogenase - metabolism Vector-borne diseases Young Adult |
| title | Antimalarial drug resistance molecular makers of Plasmodium falciparum isolates from Sudan during 2015-2017 |
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