Plasmodium falciparum Malaria in Laos: Chloroquine Treatment Outcome and Predictive Value of Molecular Markers
A 28-day treatment trial was undertaken, to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers (cg2, pfmdr1 and pfcrt) that were previously linked to chloroquine resistance. In total, 522 febrile patients were screened for falciparum malaria by rapi...
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Veröffentlicht in: | The Journal of infectious diseases 2001-03, Vol.183 (5), p.789-795 |
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description | A 28-day treatment trial was undertaken, to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers (cg2, pfmdr1 and pfcrt) that were previously linked to chloroquine resistance. In total, 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays. Of 81 patients (15.5% prevalence) who were positive by the assays and microscopy, 48 were eligible to participate in the 28-day trial. Nine patients defaulted. Chloroquine cured 54% (95% confidence interval, 45.8–61.8) of falciparum-infected patients. Of 18 (46%) patients with treatment failure, 13 (72%) experienced high-grade resistance. Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome. A mutation in PfCRT (K76T) was perfectly associated with in vivo chloroquine resistance. However, K76T was also present in in vivo–sensitive isolates, which suggests that the presence of this mutation was necessary, but not sufficient, to predict in vivo outcome in this cohort |
doi_str_mv | 10.1086/318836 |
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In total, 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays. Of 81 patients (15.5% prevalence) who were positive by the assays and microscopy, 48 were eligible to participate in the 28-day trial. Nine patients defaulted. Chloroquine cured 54% (95% confidence interval, 45.8–61.8) of falciparum-infected patients. Of 18 (46%) patients with treatment failure, 13 (72%) experienced high-grade resistance. Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome. A mutation in PfCRT (K76T) was perfectly associated with in vivo chloroquine resistance. However, K76T was also present in in vivo–sensitive isolates, which suggests that the presence of this mutation was necessary, but not sufficient, to predict in vivo outcome in this cohort</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/318836</identifier><identifier>PMID: 11181156</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Adolescent ; Adult ; Alleles ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Antiparasitic agents ; Biological and medical sciences ; Blood ; Child ; Child, Preschool ; Chloroquine - pharmacology ; Chloroquine - therapeutic use ; Cohort Studies ; Drug Resistance, Microbial - genetics ; Falciparum malaria ; Female ; Genetic Markers ; Genetic mutation ; Genotype ; Health outcomes ; Human protozoal diseases ; Humans ; Infections ; Infectious diseases ; Laos ; Major Articles ; Malaria ; Malaria, Falciparum - blood ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - genetics ; Male ; Medical sciences ; Medical treatment failures ; Middle Aged ; Mutation ; Parasites ; Parasitic diseases ; Parasitic Sensitivity Tests ; Pharmacology. Drug treatments ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prevalence ; Protozoal diseases ; Treatment Outcome</subject><ispartof>The Journal of infectious diseases, 2001-03, Vol.183 (5), p.789-795</ispartof><rights>Copyright 2001 Infectious Diseases Society of America</rights><rights>2001 by the Infectious Diseases Society of America 2001</rights><rights>2002 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Mar 1, 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-eaf2c72b2324f152468f45df5980ca7e2d42d64df76eb0b1e12c53391ddcdeb73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30110576$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30110576$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,27903,27904,57995,58228</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14156944$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11181156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pillai, Dylan R.</creatorcontrib><creatorcontrib>Labbé, Annie-Claude</creatorcontrib><creatorcontrib>Vanisaveth, Viengxai</creatorcontrib><creatorcontrib>Hongvangthong, Bouasy</creatorcontrib><creatorcontrib>Pomphida, Samlane</creatorcontrib><creatorcontrib>Inkathone, Souliya</creatorcontrib><creatorcontrib>Zhong, Kathleen</creatorcontrib><creatorcontrib>Kain, Kevin C.</creatorcontrib><title>Plasmodium falciparum Malaria in Laos: Chloroquine Treatment Outcome and Predictive Value of Molecular Markers</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>A 28-day treatment trial was undertaken, to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers (cg2, pfmdr1 and pfcrt) that were previously linked to chloroquine resistance. In total, 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays. Of 81 patients (15.5% prevalence) who were positive by the assays and microscopy, 48 were eligible to participate in the 28-day trial. Nine patients defaulted. Chloroquine cured 54% (95% confidence interval, 45.8–61.8) of falciparum-infected patients. Of 18 (46%) patients with treatment failure, 13 (72%) experienced high-grade resistance. Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome. A mutation in PfCRT (K76T) was perfectly associated with in vivo chloroquine resistance. However, K76T was also present in in vivo–sensitive isolates, which suggests that the presence of this mutation was necessary, but not sufficient, to predict in vivo outcome in this cohort</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alleles</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Antiparasitic agents</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chloroquine - pharmacology</subject><subject>Chloroquine - therapeutic use</subject><subject>Cohort Studies</subject><subject>Drug Resistance, Microbial - genetics</subject><subject>Falciparum malaria</subject><subject>Female</subject><subject>Genetic Markers</subject><subject>Genetic mutation</subject><subject>Genotype</subject><subject>Health outcomes</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Laos</subject><subject>Major Articles</subject><subject>Malaria</subject><subject>Malaria, Falciparum - blood</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - genetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medical treatment failures</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Parasitic Sensitivity Tests</subject><subject>Pharmacology. Drug treatments</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Prevalence</subject><subject>Protozoal diseases</subject><subject>Treatment Outcome</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1rFDEUhoModq36D5Qo6N1oviaZ9E4X7QpbWrSK9CZkkzOYdWayJjOi_94ss3RBEK8SeB-ec5IXoceUvKKkka85bRou76AFrbmqpKT8LloQwlhFG61P0IOct4QQwaW6j04opQ2ltVyg4aqzuY8-TD1ubefCzqZyvbCdTcHiMOC1jfkML791McUfUxgAXyewYw_DiC-n0cUesB08vkrggxvDT8BfbDcBji2-iB24qaiKMH2HlB-ie2VKhkeH8xR9fv_uermq1pfnH5Zv1pUTQo8V2JY5xTaMM9HSmgnZtKL2ba0b4qwC5gXzUvhWSdiQDQXKXM25pt47DxvFT9HL2bvbLw15NH3IDrrODhCnbBSRQuy_7H8gVZrwhrECPv8L3MYpDeURpqSa6LLj0eZSzDlBa3Yp9Db9NpSYfU9m7qmATw-2adODP2KHYgrw4gDY7GzXJju4kI-cKJAWonDPZi5Ou38PezIz2zzGdEtxQimp1T6v5jzkEX7d5qUxIxVXtVl9vTGrpa4_fjp_a274H4LkvGY</recordid><startdate>20010301</startdate><enddate>20010301</enddate><creator>Pillai, Dylan R.</creator><creator>Labbé, Annie-Claude</creator><creator>Vanisaveth, Viengxai</creator><creator>Hongvangthong, Bouasy</creator><creator>Pomphida, Samlane</creator><creator>Inkathone, Souliya</creator><creator>Zhong, Kathleen</creator><creator>Kain, Kevin C.</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><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>K9.</scope><scope>NAPCQ</scope><scope>M7N</scope><scope>7X8</scope></search><sort><creationdate>20010301</creationdate><title>Plasmodium falciparum Malaria in Laos: Chloroquine Treatment Outcome and Predictive Value of Molecular Markers</title><author>Pillai, Dylan R. ; Labbé, Annie-Claude ; Vanisaveth, Viengxai ; Hongvangthong, Bouasy ; Pomphida, Samlane ; Inkathone, Souliya ; Zhong, Kathleen ; Kain, Kevin C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-eaf2c72b2324f152468f45df5980ca7e2d42d64df76eb0b1e12c53391ddcdeb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Alleles</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>Antiparasitic agents</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chloroquine - pharmacology</topic><topic>Chloroquine - therapeutic use</topic><topic>Cohort Studies</topic><topic>Drug Resistance, Microbial - genetics</topic><topic>Falciparum malaria</topic><topic>Female</topic><topic>Genetic Markers</topic><topic>Genetic mutation</topic><topic>Genotype</topic><topic>Health outcomes</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Laos</topic><topic>Major Articles</topic><topic>Malaria</topic><topic>Malaria, Falciparum - blood</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Malaria, Falciparum - genetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medical treatment failures</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Parasitic Sensitivity Tests</topic><topic>Pharmacology. Drug treatments</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Prevalence</topic><topic>Protozoal diseases</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pillai, Dylan R.</creatorcontrib><creatorcontrib>Labbé, Annie-Claude</creatorcontrib><creatorcontrib>Vanisaveth, Viengxai</creatorcontrib><creatorcontrib>Hongvangthong, Bouasy</creatorcontrib><creatorcontrib>Pomphida, Samlane</creatorcontrib><creatorcontrib>Inkathone, Souliya</creatorcontrib><creatorcontrib>Zhong, Kathleen</creatorcontrib><creatorcontrib>Kain, Kevin C.</creatorcontrib><collection>Istex</collection><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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pillai, Dylan R.</au><au>Labbé, Annie-Claude</au><au>Vanisaveth, Viengxai</au><au>Hongvangthong, Bouasy</au><au>Pomphida, Samlane</au><au>Inkathone, Souliya</au><au>Zhong, Kathleen</au><au>Kain, Kevin C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasmodium falciparum Malaria in Laos: Chloroquine Treatment Outcome and Predictive Value of Molecular Markers</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>The Journal of Infectious Diseases</stitle><addtitle>The Journal of Infectious Diseases</addtitle><date>2001-03-01</date><risdate>2001</risdate><volume>183</volume><issue>5</issue><spage>789</spage><epage>795</epage><pages>789-795</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>A 28-day treatment trial was undertaken, to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers (cg2, pfmdr1 and pfcrt) that were previously linked to chloroquine resistance. In total, 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays. Of 81 patients (15.5% prevalence) who were positive by the assays and microscopy, 48 were eligible to participate in the 28-day trial. Nine patients defaulted. Chloroquine cured 54% (95% confidence interval, 45.8–61.8) of falciparum-infected patients. Of 18 (46%) patients with treatment failure, 13 (72%) experienced high-grade resistance. Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome. A mutation in PfCRT (K76T) was perfectly associated with in vivo chloroquine resistance. However, K76T was also present in in vivo–sensitive isolates, which suggests that the presence of this mutation was necessary, but not sufficient, to predict in vivo outcome in this cohort</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>11181156</pmid><doi>10.1086/318836</doi><tpages>7</tpages></addata></record> |
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subjects | Adolescent Adult Alleles Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antimalarials - pharmacology Antimalarials - therapeutic use Antiparasitic agents Biological and medical sciences Blood Child Child, Preschool Chloroquine - pharmacology Chloroquine - therapeutic use Cohort Studies Drug Resistance, Microbial - genetics Falciparum malaria Female Genetic Markers Genetic mutation Genotype Health outcomes Human protozoal diseases Humans Infections Infectious diseases Laos Major Articles Malaria Malaria, Falciparum - blood Malaria, Falciparum - drug therapy Malaria, Falciparum - genetics Male Medical sciences Medical treatment failures Middle Aged Mutation Parasites Parasitic diseases Parasitic Sensitivity Tests Pharmacology. Drug treatments Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - genetics Polymerase Chain Reaction Polymorphism, Genetic Prevalence Protozoal diseases Treatment Outcome |
title | Plasmodium falciparum Malaria in Laos: Chloroquine Treatment Outcome and Predictive Value of Molecular Markers |
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