Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children
In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate r...
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| Veröffentlicht in: | The American journal of tropical medicine and hygiene 1999-07, Vol.61 (1), p.125-130 |
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| container_title | The American journal of tropical medicine and hygiene |
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| creator | Jelinek, T Kilian, AH Curtis, J Duraisingh, MT Kabagambe, G von Sonnenburg, F Warhurst, DC |
| description | In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108. |
| doi_str_mv | 10.4269/ajtmh.1999.61.125 |
| format | Article |
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Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.</description><identifier>ISSN: 0002-9637</identifier><identifier>EISSN: 1476-1645</identifier><identifier>DOI: 10.4269/ajtmh.1999.61.125</identifier><identifier>PMID: 10432069</identifier><identifier>CODEN: AJTHAB</identifier><language>eng</language><publisher>Lawrence, KS: ASTMH</publisher><subject>Alleles ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials - therapeutic use ; Antiparasitic agents ; Biological and medical sciences ; Blood - parasitology ; Child, Preschool ; Cotrimoxazole ; DHFR gene ; DHPS gene ; Dihydropteroate Synthase - chemistry ; Dihydropteroate Synthase - genetics ; DNA Primers - chemistry ; DNA Restriction Enzymes - chemistry ; DNA, Protozoan - chemistry ; Drug Resistance ; Electrophoresis, Agar Gel ; Female ; Genetic Variation - genetics ; Humans ; Infant ; Malaria, Falciparum - drug therapy ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Plasmodium falciparum ; Plasmodium falciparum - chemistry ; Plasmodium falciparum - genetics ; Polymerase Chain Reaction ; Tetrahydrofolate Dehydrogenase - chemistry ; Tetrahydrofolate Dehydrogenase - genetics ; Trimethoprim, Sulfamethoxazole Drug Combination - therapeutic use ; Tropical medicine ; Uganda</subject><ispartof>The American journal of tropical medicine and hygiene, 1999-07, Vol.61 (1), p.125-130</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-541a186079f06a679a4e2ad360a73273e4796e2b6325c4377230f07a9fa0952d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1897425$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10432069$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jelinek, T</creatorcontrib><creatorcontrib>Kilian, AH</creatorcontrib><creatorcontrib>Curtis, J</creatorcontrib><creatorcontrib>Duraisingh, MT</creatorcontrib><creatorcontrib>Kabagambe, G</creatorcontrib><creatorcontrib>von Sonnenburg, F</creatorcontrib><creatorcontrib>Warhurst, DC</creatorcontrib><title>Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children</title><title>The American journal of tropical medicine and hygiene</title><addtitle>Am J Trop Med Hyg</addtitle><description>In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.</description><subject>Alleles</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimalarials - therapeutic use</subject><subject>Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Blood - parasitology</subject><subject>Child, Preschool</subject><subject>Cotrimoxazole</subject><subject>DHFR gene</subject><subject>DHPS gene</subject><subject>Dihydropteroate Synthase - chemistry</subject><subject>Dihydropteroate Synthase - genetics</subject><subject>DNA Primers - chemistry</subject><subject>DNA Restriction Enzymes - chemistry</subject><subject>DNA, Protozoan - chemistry</subject><subject>Drug Resistance</subject><subject>Electrophoresis, Agar Gel</subject><subject>Female</subject><subject>Genetic Variation - genetics</subject><subject>Humans</subject><subject>Infant</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - chemistry</subject><subject>Plasmodium falciparum - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Tetrahydrofolate Dehydrogenase - chemistry</subject><subject>Tetrahydrofolate Dehydrogenase - genetics</subject><subject>Trimethoprim, Sulfamethoxazole Drug Combination - therapeutic use</subject><subject>Tropical medicine</subject><subject>Uganda</subject><issn>0002-9637</issn><issn>1476-1645</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEokvhB3BBPgC3LP5I7DW3quJLqgQHeramtrNxZceL7SiUv8KfxdldCW6crJGeeWfGT9O8JHjbUS7fwX0J45ZIKbecbAntHzUb0gneEt71j5sNxpi2kjNx0TzL-R5jsqOEPG0uCO4YxVxumt_fPOQQjZsDGsBrd4A0h_coW291cXFCcahFcpNFBO_WyrjxwaQ4RA_FomTNrAtki8xcqT0qyUIJdiorO086hoN3uqIGBfCQHKDFlRHp2JbkQvwJv6K3yE3odg-TgQnp0XmT7PS8eVJXyvbF-b1sbj9--H79ub35-unL9dVNq9lOlLbvCJAdx0IOmAMXEjpLwTCOQTAqmO2E5JbecUZ73TEhKMMDFiAHwLKnhl02b0-5hxR_zDYXFVzW1nuYbJyz4lIyxjvyX5CIugtnfQXJCdQp5pzsoA71VEgPimC1qlNHdWpVpzhRVV3teXUOn--CNf90nFxV4PUZgKzBDwkm7fJfbidFd8x5c8JGtx8Xl6zK9d99TSVqWZZ12nHeH5fZsaM</recordid><startdate>19990701</startdate><enddate>19990701</enddate><creator>Jelinek, T</creator><creator>Kilian, AH</creator><creator>Curtis, J</creator><creator>Duraisingh, MT</creator><creator>Kabagambe, G</creator><creator>von Sonnenburg, F</creator><creator>Warhurst, DC</creator><general>ASTMH</general><general>Allen Press</general><scope>IQODW</scope><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>M7N</scope><scope>7X8</scope></search><sort><creationdate>19990701</creationdate><title>Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children</title><author>Jelinek, T ; Kilian, AH ; Curtis, J ; Duraisingh, MT ; Kabagambe, G ; von Sonnenburg, F ; Warhurst, DC</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-541a186079f06a679a4e2ad360a73273e4796e2b6325c4377230f07a9fa0952d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antimalarials - therapeutic use</topic><topic>Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Blood - parasitology</topic><topic>Child, Preschool</topic><topic>Cotrimoxazole</topic><topic>DHFR gene</topic><topic>DHPS gene</topic><topic>Dihydropteroate Synthase - chemistry</topic><topic>Dihydropteroate Synthase - genetics</topic><topic>DNA Primers - chemistry</topic><topic>DNA Restriction Enzymes - chemistry</topic><topic>DNA, Protozoan - chemistry</topic><topic>Drug Resistance</topic><topic>Electrophoresis, Agar Gel</topic><topic>Female</topic><topic>Genetic Variation - genetics</topic><topic>Humans</topic><topic>Infant</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - chemistry</topic><topic>Plasmodium falciparum - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Tetrahydrofolate Dehydrogenase - chemistry</topic><topic>Tetrahydrofolate Dehydrogenase - genetics</topic><topic>Trimethoprim, Sulfamethoxazole Drug Combination - therapeutic use</topic><topic>Tropical medicine</topic><topic>Uganda</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jelinek, T</creatorcontrib><creatorcontrib>Kilian, AH</creatorcontrib><creatorcontrib>Curtis, J</creatorcontrib><creatorcontrib>Duraisingh, MT</creatorcontrib><creatorcontrib>Kabagambe, G</creatorcontrib><creatorcontrib>von Sonnenburg, F</creatorcontrib><creatorcontrib>Warhurst, DC</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of tropical medicine and hygiene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jelinek, T</au><au>Kilian, AH</au><au>Curtis, J</au><au>Duraisingh, MT</au><au>Kabagambe, G</au><au>von Sonnenburg, F</au><au>Warhurst, DC</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children</atitle><jtitle>The American journal of tropical medicine and hygiene</jtitle><addtitle>Am J Trop Med Hyg</addtitle><date>1999-07-01</date><risdate>1999</risdate><volume>61</volume><issue>1</issue><spage>125</spage><epage>130</epage><pages>125-130</pages><issn>0002-9637</issn><eissn>1476-1645</eissn><coden>AJTHAB</coden><abstract>In vivo testing for resistance of Plasmodium falciparum to co-trimoxazole (trimethoprim/sulfamethoxazole) was performed in Uganda in 41 children with uncomplicated malaria, and blood samples were screened before and after treatment for polymorphisms in the antifolate target genes for dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). Selection towards a specific genotype at some codons of the DHFR and DHPS genes was observed in samples collected after exposure to co-trimoxazole drug pressure. The alleles 51-isoleucine, 59-arginine, and 108-serine of DHFR were significantly associated with clinical resistance, as was allele 581-alanine of DHPS. Resistance against antifolate combinations probably requires resistance-related polymorphisms in both the DHFR and the DHPS genes. In addition, it appears that the trimethoprim-resistant DHFR genotype differs from that for pyrimethamine at residue 108.</abstract><cop>Lawrence, KS</cop><pub>ASTMH</pub><pmid>10432069</pmid><doi>10.4269/ajtmh.1999.61.125</doi><tpages>6</tpages></addata></record> |
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| subjects | Alleles Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antimalarials - therapeutic use Antiparasitic agents Biological and medical sciences Blood - parasitology Child, Preschool Cotrimoxazole DHFR gene DHPS gene Dihydropteroate Synthase - chemistry Dihydropteroate Synthase - genetics DNA Primers - chemistry DNA Restriction Enzymes - chemistry DNA, Protozoan - chemistry Drug Resistance Electrophoresis, Agar Gel Female Genetic Variation - genetics Humans Infant Malaria, Falciparum - drug therapy Male Medical sciences Pharmacology. Drug treatments Plasmodium falciparum Plasmodium falciparum - chemistry Plasmodium falciparum - genetics Polymerase Chain Reaction Tetrahydrofolate Dehydrogenase - chemistry Tetrahydrofolate Dehydrogenase - genetics Trimethoprim, Sulfamethoxazole Drug Combination - therapeutic use Tropical medicine Uganda |
| title | Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with co-trimoxazole in Ugandan children |
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