Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance
Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance. We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimal...
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creator | Gupta, Himanshu Galatas, Beatriz Chidimatembue, Arlindo Huijben, Silvie Cisteró, Pau Matambisso, Gloria Nhamussua, Lidia Simone, Wilson Bassat, Quique Ménard, Didier Ringwald, Pascal Rabinovich, N Regina Alonso, Pedro L Saúte, Francisco Aide, Pedro Mayor, Alfredo |
description | Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance.
We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique.
None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05).
This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention. |
doi_str_mv | 10.1371/journal.pone.0240174 |
format | Article |
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We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique.
None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05).
This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0240174</identifier><identifier>PMID: 33075062</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antimalarials ; Antimalarials - administration & dosage ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Antimicrobial agents ; Artemisinin ; Artemisinins ; Artemisinins - administration & dosage ; Artemisinins - pharmacology ; Artemisinins - therapeutic use ; Biological markers ; Biology and Life Sciences ; Deoxyribonucleic acid ; Dihydroartemisinin ; DNA ; Dosage and administration ; Drug Combinations ; Drug Resistance ; Drug Resistance - genetics ; Epidemiology ; Hospitals ; Human health and pathology ; Infectious diseases ; Life Sciences ; Malaria ; Malaria - parasitology ; Malaria - prevention & control ; Markers ; Medicine and Health Sciences ; Microbiology and Parasitology ; Mozambique ; Mutation ; Parasites ; Parasitology ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Plasmodium falciparum - pathogenicity ; Polymorphism, Genetic ; Population ; Protozoan Proteins ; Protozoan Proteins - genetics ; Protozoan Proteins - metabolism ; Public health ; Quinolines ; Quinolines - administration & dosage ; Quinolines - pharmacology ; Quinolines - therapeutic use ; Risk factors ; Statistical analysis ; Tropical diseases</subject><ispartof>PloS one, 2020-10, Vol.15 (10), p.e0240174</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Gupta 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>Attribution</rights><rights>2020 Gupta et al 2020 Gupta et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c730t-7bd659b6e8f6d9b5b9a31d8eb1f012b00d0d726c919b00be7bb0ceff0710db2c3</citedby><cites>FETCH-LOGICAL-c730t-7bd659b6e8f6d9b5b9a31d8eb1f012b00d0d726c919b00be7bb0ceff0710db2c3</cites><orcidid>0000-0003-3890-2897 ; 0000-0003-4867-6301 ; 0000-0003-0875-7596 ; 0000-0003-1357-4495</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/PMC7571678/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571678/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33075062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://pasteur.hal.science/pasteur-03274274$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Gupta, Himanshu</creatorcontrib><creatorcontrib>Galatas, Beatriz</creatorcontrib><creatorcontrib>Chidimatembue, Arlindo</creatorcontrib><creatorcontrib>Huijben, Silvie</creatorcontrib><creatorcontrib>Cisteró, Pau</creatorcontrib><creatorcontrib>Matambisso, Gloria</creatorcontrib><creatorcontrib>Nhamussua, Lidia</creatorcontrib><creatorcontrib>Simone, Wilson</creatorcontrib><creatorcontrib>Bassat, Quique</creatorcontrib><creatorcontrib>Ménard, Didier</creatorcontrib><creatorcontrib>Ringwald, Pascal</creatorcontrib><creatorcontrib>Rabinovich, N Regina</creatorcontrib><creatorcontrib>Alonso, Pedro L</creatorcontrib><creatorcontrib>Saúte, Francisco</creatorcontrib><creatorcontrib>Aide, Pedro</creatorcontrib><creatorcontrib>Mayor, Alfredo</creatorcontrib><title>Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance.
We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique.
None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05).
This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.</description><subject>Analysis</subject><subject>Antimalarials</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Antimicrobial agents</subject><subject>Artemisinin</subject><subject>Artemisinins</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - pharmacology</subject><subject>Artemisinins - therapeutic use</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Deoxyribonucleic acid</subject><subject>Dihydroartemisinin</subject><subject>DNA</subject><subject>Dosage and administration</subject><subject>Drug Combinations</subject><subject>Drug Resistance</subject><subject>Drug Resistance - genetics</subject><subject>Epidemiology</subject><subject>Hospitals</subject><subject>Human health and pathology</subject><subject>Infectious diseases</subject><subject>Life Sciences</subject><subject>Malaria</subject><subject>Malaria - parasitology</subject><subject>Malaria - prevention & control</subject><subject>Markers</subject><subject>Medicine and Health Sciences</subject><subject>Microbiology and Parasitology</subject><subject>Mozambique</subject><subject>Mutation</subject><subject>Parasites</subject><subject>Parasitology</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Plasmodium falciparum - pathogenicity</subject><subject>Polymorphism, Genetic</subject><subject>Population</subject><subject>Protozoan Proteins</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - metabolism</subject><subject>Public health</subject><subject>Quinolines</subject><subject>Quinolines - administration & dosage</subject><subject>Quinolines - pharmacology</subject><subject>Quinolines - therapeutic use</subject><subject>Risk factors</subject><subject>Statistical analysis</subject><subject>Tropical diseases</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99v0zAQxyMEYmPwHyCIhITgocWOEzt5QaqmwSoVTeLXq2U759YltTs7mRj_Bv8w17Wb2mkPKJHinD_3vfP5LsteUjKmTNAPyzBEr7rxOngYk6IkVJSPsmPasGLEC8Ie762PsmcpLQmpWM350-yIMSIqwovj7O-ZtWD6PNh8pVLKW7e4bmNQsYeVS847P1q7NUR1OTgPuWpXaEt9VL0LPnc-T2HoFxB9_iX8USvtLgfIcQdtuVExOjWHG_HQgRk6FTFM_AUxbYzK926l0OhUl0dIKKy8gefZE6u6BC9235Psx6ez76fno9nF5-npZDYygpF-JHTLq0ZzqC1vG13pRjHa1qCpJbTQhLSkFQU3DW3wR4PQmhiwlghKWl0YdpK93uquu5Dkrp5JFmVVkJoJxpCYbok2qKVcR8w2XsugnLwxhDiXWClnOpCVLajmllGuitJo0gjCSMXLRtQCKiFQ6-Mu2qBX0BrwWMXuQPRwx7uFnIcrKSpBuahRYLQVWNxzO5_M5FqlHoYoCStEie8VRf7dLmAMeCupl3ijBrpOeQjD9pxl05Byk9ube-jD1dhRc4UHdt4GzNNsROWEs7rmFSkbpMYPUPi02FEGm9U6tB84vD9wQKaH3_1cDSnJ6bev_89e_Dxk3-6xC1Bdv0ihGzadmw7BcguaGFKKYO-qS4nczNptNeRm1uRu1tDt1f6F3jndDhf7B11DJxs</recordid><startdate>20201019</startdate><enddate>20201019</enddate><creator>Gupta, Himanshu</creator><creator>Galatas, Beatriz</creator><creator>Chidimatembue, Arlindo</creator><creator>Huijben, Silvie</creator><creator>Cisteró, Pau</creator><creator>Matambisso, Gloria</creator><creator>Nhamussua, Lidia</creator><creator>Simone, Wilson</creator><creator>Bassat, Quique</creator><creator>Ménard, Didier</creator><creator>Ringwald, Pascal</creator><creator>Rabinovich, N Regina</creator><creator>Alonso, Pedro L</creator><creator>Saúte, Francisco</creator><creator>Aide, Pedro</creator><creator>Mayor, Alfredo</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>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3890-2897</orcidid><orcidid>https://orcid.org/0000-0003-4867-6301</orcidid><orcidid>https://orcid.org/0000-0003-0875-7596</orcidid><orcidid>https://orcid.org/0000-0003-1357-4495</orcidid></search><sort><creationdate>20201019</creationdate><title>Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance</title><author>Gupta, Himanshu ; Galatas, Beatriz ; Chidimatembue, Arlindo ; Huijben, Silvie ; Cisteró, Pau ; Matambisso, Gloria ; Nhamussua, Lidia ; Simone, Wilson ; Bassat, Quique ; Ménard, Didier ; Ringwald, Pascal ; Rabinovich, N Regina ; Alonso, Pedro L ; Saúte, Francisco ; Aide, Pedro ; Mayor, Alfredo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c730t-7bd659b6e8f6d9b5b9a31d8eb1f012b00d0d726c919b00be7bb0ceff0710db2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Antimalarials</topic><topic>Antimalarials - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</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>Gupta, Himanshu</au><au>Galatas, Beatriz</au><au>Chidimatembue, Arlindo</au><au>Huijben, Silvie</au><au>Cisteró, Pau</au><au>Matambisso, Gloria</au><au>Nhamussua, Lidia</au><au>Simone, Wilson</au><au>Bassat, Quique</au><au>Ménard, Didier</au><au>Ringwald, Pascal</au><au>Rabinovich, N Regina</au><au>Alonso, Pedro L</au><au>Saúte, Francisco</au><au>Aide, Pedro</au><au>Mayor, Alfredo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-10-19</date><risdate>2020</risdate><volume>15</volume><issue>10</issue><spage>e0240174</spage><pages>e0240174-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance.
We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique.
None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05).
This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33075062</pmid><doi>10.1371/journal.pone.0240174</doi><tpages>e0240174</tpages><orcidid>https://orcid.org/0000-0003-3890-2897</orcidid><orcidid>https://orcid.org/0000-0003-4867-6301</orcidid><orcidid>https://orcid.org/0000-0003-0875-7596</orcidid><orcidid>https://orcid.org/0000-0003-1357-4495</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2020-10, Vol.15 (10), p.e0240174 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_2452083733 |
source | MEDLINE; Public Library of Science; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; EZB Electronic Journals Library |
subjects | Analysis Antimalarials Antimalarials - administration & dosage Antimalarials - pharmacology Antimalarials - therapeutic use Antimicrobial agents Artemisinin Artemisinins Artemisinins - administration & dosage Artemisinins - pharmacology Artemisinins - therapeutic use Biological markers Biology and Life Sciences Deoxyribonucleic acid Dihydroartemisinin DNA Dosage and administration Drug Combinations Drug Resistance Drug Resistance - genetics Epidemiology Hospitals Human health and pathology Infectious diseases Life Sciences Malaria Malaria - parasitology Malaria - prevention & control Markers Medicine and Health Sciences Microbiology and Parasitology Mozambique Mutation Parasites Parasitology Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Plasmodium falciparum - pathogenicity Polymorphism, Genetic Population Protozoan Proteins Protozoan Proteins - genetics Protozoan Proteins - metabolism Public health Quinolines Quinolines - administration & dosage Quinolines - pharmacology Quinolines - therapeutic use Risk factors Statistical analysis Tropical diseases |
title | Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance |
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