Prevention of Increasing Rates of Treatment Failure by Combining Sulfadoxine-Pyrimethamine with Artesunate or Amodiaquine for the Sequential Treatment of Malaria
Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We c...
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| Veröffentlicht in: | The Journal of infectious diseases 2003-10, Vol.188 (8), p.1231-1238 |
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| creator | Dorsey, Grant Vlahos, Jonathan Kamya, Moses R. Staedke, Sarah G. Rosenthal, Philip J. |
| description | Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance–conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens |
| doi_str_mv | 10.1086/378523 |
| format | Article |
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For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance–conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/378523</identifier><identifier>PMID: 14551894</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject><![CDATA[Amodiaquine - administration & dosage ; Amodiaquine - pharmacology ; Amodiaquine - therapeutic use ; Animals ; Antimalarials ; Antimalarials - administration & dosage ; Antimalarials - pharmacology ; Antimalarials - therapeutic use ; Artemisinins - administration & dosage ; Artemisinins - pharmacology ; Artemisinins - therapeutic use ; Biological and medical sciences ; Child, Preschool ; Dihydropteroate Synthase - genetics ; Drug Administration Schedule ; Drug Combinations ; Drug resistance ; Drug Resistance - genetics ; Drug Therapy, Combination ; Falciparum malaria ; Fundamental and applied biological sciences. Psychology ; Health outcomes ; Human protozoal diseases ; Humans ; Infant ; Infections ; Infectious diseases ; Malaria ; Malaria, Falciparum - drug therapy ; Malaria, Falciparum - parasitology ; Medical sciences ; Medical treatment failures ; Microbiology ; Mutation ; Parasites ; Parasitic diseases ; Plasmodium falciparum - drug effects ; Pretreatment ; Protozoal diseases ; Pyrimethamine - administration & dosage ; Pyrimethamine - pharmacology ; Pyrimethamine - therapeutic use ; Relapse ; Sesquiterpenes - administration & dosage ; Sesquiterpenes - pharmacology ; Sesquiterpenes - therapeutic use ; Sulfadoxine - administration & dosage ; Sulfadoxine - pharmacology ; Sulfadoxine - therapeutic use ; Tetrahydrofolate Dehydrogenase - genetics ; Treatment Failure ; Treatment Outcome]]></subject><ispartof>The Journal of infectious diseases, 2003-10, Vol.188 (8), p.1231-1238</ispartof><rights>Copyright 2003 Infectious Diseases Society of America</rights><rights>2003 by the Infectious Diseases Society of America 2003</rights><rights>2004 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Oct 15 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-739a87329183219a4396e2cd759a8df60583bb0c4181585480eb0f3c241c2dba3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30075735$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30075735$$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=15227918$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14551894$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dorsey, Grant</creatorcontrib><creatorcontrib>Vlahos, Jonathan</creatorcontrib><creatorcontrib>Kamya, Moses R.</creatorcontrib><creatorcontrib>Staedke, Sarah G.</creatorcontrib><creatorcontrib>Rosenthal, Philip J.</creatorcontrib><title>Prevention of Increasing Rates of Treatment Failure by Combining Sulfadoxine-Pyrimethamine with Artesunate or Amodiaquine for the Sequential Treatment of Malaria</title><title>The Journal of infectious diseases</title><addtitle>The Journal of Infectious Diseases</addtitle><addtitle>The Journal of Infectious Diseases</addtitle><description>Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance–conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens</description><subject>Amodiaquine - administration & dosage</subject><subject>Amodiaquine - pharmacology</subject><subject>Amodiaquine - therapeutic use</subject><subject>Animals</subject><subject>Antimalarials</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - therapeutic use</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - pharmacology</subject><subject>Artemisinins - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Child, Preschool</subject><subject>Dihydropteroate Synthase - genetics</subject><subject>Drug Administration Schedule</subject><subject>Drug Combinations</subject><subject>Drug resistance</subject><subject>Drug Resistance - genetics</subject><subject>Drug Therapy, Combination</subject><subject>Falciparum malaria</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Health outcomes</subject><subject>Human protozoal diseases</subject><subject>Humans</subject><subject>Infant</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Malaria</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Medical sciences</subject><subject>Medical treatment failures</subject><subject>Microbiology</subject><subject>Mutation</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Pretreatment</subject><subject>Protozoal diseases</subject><subject>Pyrimethamine - administration & dosage</subject><subject>Pyrimethamine - pharmacology</subject><subject>Pyrimethamine - therapeutic use</subject><subject>Relapse</subject><subject>Sesquiterpenes - administration & dosage</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Sesquiterpenes - therapeutic use</subject><subject>Sulfadoxine - administration & dosage</subject><subject>Sulfadoxine - pharmacology</subject><subject>Sulfadoxine - therapeutic use</subject><subject>Tetrahydrofolate Dehydrogenase - genetics</subject><subject>Treatment Failure</subject><subject>Treatment Outcome</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd9u0zAUxi0EYqXAG4AMEtwF_N_OZVcxumnAxIaEuLGcxKHukrizE1gfhzfFUaoVISF8Y_n7fvrO8TkAPMXoDUZKvKVScULvgRnmVGZCYHofzBAiJMMqz4_Aoxg3CCFGhXwIjjDjPOlsBn5dBPvDdr3zHfQ1PO3KYE103Xf42fQ2jtpVUvo2MfDEuGYIFhY7uPRt4bqRuxya2lT-1nU2u9gF19p-bdr0gj9dv4aLkGKGLoVBH-Ci9ZUzN8No1-ndry28tDfD2IFp_iiV6n4wjQnOPAYPatNE-2R_z8GXk3dXy1V2_un96XJxnpVM4T6TNDdKUpJjRQnODaO5sKSsJE96VQvEFS0KVDKsMFecKWQLVNOSMFySqjB0Dl5PudvgU0Ox162LpW0a01k_RC255IoJ9l8Qq3SIIAl8-Re48UPo0ic0ITTHSEh0SCuDjzHYWm_TDE3YaYz0uFo9rTaBz_dpQ9Ha6oDtd5mAV3vAxNI0dTBd6eKB44TIcTpz8GLi_LD9d7FnE7OJvQ93FEUojYHy5GeT72Jvb-98E661kFRyvfr6TR-LsxX6SI71Gf0NnVPOYQ</recordid><startdate>20031015</startdate><enddate>20031015</enddate><creator>Dorsey, Grant</creator><creator>Vlahos, Jonathan</creator><creator>Kamya, Moses R.</creator><creator>Staedke, Sarah G.</creator><creator>Rosenthal, Philip J.</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>20031015</creationdate><title>Prevention of Increasing Rates of Treatment Failure by Combining Sulfadoxine-Pyrimethamine with Artesunate or Amodiaquine for the Sequential Treatment of Malaria</title><author>Dorsey, Grant ; Vlahos, Jonathan ; Kamya, Moses R. ; Staedke, Sarah G. ; Rosenthal, Philip J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-739a87329183219a4396e2cd759a8df60583bb0c4181585480eb0f3c241c2dba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amodiaquine - administration & dosage</topic><topic>Amodiaquine - pharmacology</topic><topic>Amodiaquine - therapeutic use</topic><topic>Animals</topic><topic>Antimalarials</topic><topic>Antimalarials - administration & dosage</topic><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - therapeutic use</topic><topic>Artemisinins - administration & dosage</topic><topic>Artemisinins - pharmacology</topic><topic>Artemisinins - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Child, Preschool</topic><topic>Dihydropteroate Synthase - genetics</topic><topic>Drug Administration Schedule</topic><topic>Drug Combinations</topic><topic>Drug resistance</topic><topic>Drug Resistance - genetics</topic><topic>Drug Therapy, Combination</topic><topic>Falciparum malaria</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Health outcomes</topic><topic>Human protozoal diseases</topic><topic>Humans</topic><topic>Infant</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Malaria</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Medical sciences</topic><topic>Medical treatment failures</topic><topic>Microbiology</topic><topic>Mutation</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Pretreatment</topic><topic>Protozoal diseases</topic><topic>Pyrimethamine - administration & dosage</topic><topic>Pyrimethamine - pharmacology</topic><topic>Pyrimethamine - therapeutic use</topic><topic>Relapse</topic><topic>Sesquiterpenes - administration & dosage</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Sesquiterpenes - therapeutic use</topic><topic>Sulfadoxine - administration & dosage</topic><topic>Sulfadoxine - pharmacology</topic><topic>Sulfadoxine - therapeutic use</topic><topic>Tetrahydrofolate Dehydrogenase - genetics</topic><topic>Treatment Failure</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dorsey, Grant</creatorcontrib><creatorcontrib>Vlahos, Jonathan</creatorcontrib><creatorcontrib>Kamya, Moses R.</creatorcontrib><creatorcontrib>Staedke, Sarah G.</creatorcontrib><creatorcontrib>Rosenthal, Philip J.</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>Dorsey, Grant</au><au>Vlahos, Jonathan</au><au>Kamya, Moses R.</au><au>Staedke, Sarah G.</au><au>Rosenthal, Philip J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevention of Increasing Rates of Treatment Failure by Combining Sulfadoxine-Pyrimethamine with Artesunate or Amodiaquine for the Sequential Treatment of Malaria</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>The Journal of Infectious Diseases</stitle><addtitle>The Journal of Infectious Diseases</addtitle><date>2003-10-15</date><risdate>2003</risdate><volume>188</volume><issue>8</issue><spage>1231</spage><epage>1238</epage><pages>1231-1238</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance–conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>14551894</pmid><doi>10.1086/378523</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of infectious diseases, 2003-10, Vol.188 (8), p.1231-1238 |
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| source | MEDLINE; Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Amodiaquine - administration & dosage Amodiaquine - pharmacology Amodiaquine - therapeutic use Animals Antimalarials Antimalarials - administration & dosage Antimalarials - pharmacology Antimalarials - therapeutic use Artemisinins - administration & dosage Artemisinins - pharmacology Artemisinins - therapeutic use Biological and medical sciences Child, Preschool Dihydropteroate Synthase - genetics Drug Administration Schedule Drug Combinations Drug resistance Drug Resistance - genetics Drug Therapy, Combination Falciparum malaria Fundamental and applied biological sciences. Psychology Health outcomes Human protozoal diseases Humans Infant Infections Infectious diseases Malaria Malaria, Falciparum - drug therapy Malaria, Falciparum - parasitology Medical sciences Medical treatment failures Microbiology Mutation Parasites Parasitic diseases Plasmodium falciparum - drug effects Pretreatment Protozoal diseases Pyrimethamine - administration & dosage Pyrimethamine - pharmacology Pyrimethamine - therapeutic use Relapse Sesquiterpenes - administration & dosage Sesquiterpenes - pharmacology Sesquiterpenes - therapeutic use Sulfadoxine - administration & dosage Sulfadoxine - pharmacology Sulfadoxine - therapeutic use Tetrahydrofolate Dehydrogenase - genetics Treatment Failure Treatment Outcome |
| title | Prevention of Increasing Rates of Treatment Failure by Combining Sulfadoxine-Pyrimethamine with Artesunate or Amodiaquine for the Sequential Treatment of Malaria |
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