Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria
Since 2012, a single low dose of primaquine (SLDPQ; 0.25 mg/kg of body weight) with artemisinin-based combination therapies has been recommended as the first-line treatment of acute uncomplicated malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance,...
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| creator | Vantaux, Amélie Kim, Saorin Piv, Eakpor Chy, Sophy Berne, Laura Khim, Nimol Lek, Dysoley Siv, Sovannaroth Mukaka, Mavuto Taylor, Walter R Ménard, Didier |
| description | Since 2012, a single low dose of primaquine (SLDPQ; 0.25 mg/kg of body weight) with artemisinin-based combination therapies has been recommended as the first-line treatment of acute uncomplicated
malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance, including artemisinin resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and a lack of data on its efficacy. In this randomized controlled trial, 109 Cambodians with acute uncomplicated
malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. The transmission-blocking efficacy of SLDPQ was evaluated on days 0, 1, 2, 3, 7, 14, 21, and 28, and recrudescence by reverse transcriptase PCR (RT-PCR) (gametocyte prevalence) and membrane feeding assays with
mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP-SLDPQ reduced gametocyte carriage 3-fold compared to that achieved with DP. Of 48 patients tested on day 0, only 3 patients were infectious to mosquitoes (∼6%). Posttreatment, three patients were infectious on day 14 (3.5%, 1/29) and on the 1st and 7th days of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission-blocking efficacy. Our study confirms the effective gametocyte clearance of SLDPQ when combined with DP in multidrug-resistant
infections and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP, and ASMQ-SLDPQ has been deployed to treat all patients with symptomatic
infections to further support the elimination of multidrug-resistant
in Cambodia. (This study has been registered at ClinicalTrials.gov under identifier NCT02434952.). |
| doi_str_mv | 10.1128/AAC.02108-19 |
| format | Article |
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malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance, including artemisinin resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and a lack of data on its efficacy. In this randomized controlled trial, 109 Cambodians with acute uncomplicated
malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. The transmission-blocking efficacy of SLDPQ was evaluated on days 0, 1, 2, 3, 7, 14, 21, and 28, and recrudescence by reverse transcriptase PCR (RT-PCR) (gametocyte prevalence) and membrane feeding assays with
mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP-SLDPQ reduced gametocyte carriage 3-fold compared to that achieved with DP. Of 48 patients tested on day 0, only 3 patients were infectious to mosquitoes (∼6%). Posttreatment, three patients were infectious on day 14 (3.5%, 1/29) and on the 1st and 7th days of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission-blocking efficacy. Our study confirms the effective gametocyte clearance of SLDPQ when combined with DP in multidrug-resistant
infections and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP, and ASMQ-SLDPQ has been deployed to treat all patients with symptomatic
infections to further support the elimination of multidrug-resistant
in Cambodia. (This study has been registered at ClinicalTrials.gov under identifier NCT02434952.).</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.02108-19</identifier><identifier>PMID: 32179526</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Epidemiology and Surveillance ; Human health and pathology ; Infectious diseases ; Life Sciences ; Pharmaceutical sciences ; Pharmacology</subject><ispartof>Antimicrobial agents and chemotherapy, 2020-05, Vol.64 (6)</ispartof><rights>Copyright © 2020 Vantaux et al.</rights><rights>Attribution</rights><rights>Copyright © 2020 Vantaux et al. 2020 Vantaux et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a456t-c09e171cccf555c07376131de530bc425f2aa2f842f3ba299d9d05f489393dbe3</citedby><cites>FETCH-LOGICAL-a456t-c09e171cccf555c07376131de530bc425f2aa2f842f3ba299d9d05f489393dbe3</cites><orcidid>0000-0002-7945-961X ; 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/PMC7269483/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269483/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32179526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/pasteur-02865145$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Vantaux, Amélie</creatorcontrib><creatorcontrib>Kim, Saorin</creatorcontrib><creatorcontrib>Piv, Eakpor</creatorcontrib><creatorcontrib>Chy, Sophy</creatorcontrib><creatorcontrib>Berne, Laura</creatorcontrib><creatorcontrib>Khim, Nimol</creatorcontrib><creatorcontrib>Lek, Dysoley</creatorcontrib><creatorcontrib>Siv, Sovannaroth</creatorcontrib><creatorcontrib>Mukaka, Mavuto</creatorcontrib><creatorcontrib>Taylor, Walter R</creatorcontrib><creatorcontrib>Ménard, Didier</creatorcontrib><title>Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Since 2012, a single low dose of primaquine (SLDPQ; 0.25 mg/kg of body weight) with artemisinin-based combination therapies has been recommended as the first-line treatment of acute uncomplicated
malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance, including artemisinin resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and a lack of data on its efficacy. In this randomized controlled trial, 109 Cambodians with acute uncomplicated
malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. The transmission-blocking efficacy of SLDPQ was evaluated on days 0, 1, 2, 3, 7, 14, 21, and 28, and recrudescence by reverse transcriptase PCR (RT-PCR) (gametocyte prevalence) and membrane feeding assays with
mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP-SLDPQ reduced gametocyte carriage 3-fold compared to that achieved with DP. Of 48 patients tested on day 0, only 3 patients were infectious to mosquitoes (∼6%). Posttreatment, three patients were infectious on day 14 (3.5%, 1/29) and on the 1st and 7th days of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission-blocking efficacy. Our study confirms the effective gametocyte clearance of SLDPQ when combined with DP in multidrug-resistant
infections and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP, and ASMQ-SLDPQ has been deployed to treat all patients with symptomatic
infections to further support the elimination of multidrug-resistant
in Cambodia. (This study has been registered at ClinicalTrials.gov under identifier NCT02434952.).</description><subject>Epidemiology and Surveillance</subject><subject>Human health and pathology</subject><subject>Infectious diseases</subject><subject>Life Sciences</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kk1v1DAQhiMEoqVw44x8BIkUf8RJfEGKltIibcWq256tiePsukrsre202r_Mr8BhSwVInGyP33nGM36z7C3Bp4TQ-lPTLE4xJbjOiXiWHRMs6rzkonyeHWNclnlR4-IoexXCLU5nLvDL7IhRUglOy-Psx9psrOmNAhvRWT9v1B65HgFaG7sZNFq6B_TFBT0HV96McDcZq9HCjTvwukPRoXUE2-XN4FK88VGPJhhr7KxpjYVonEXXW-1ht0cpfKW7SSU4OodRR6f2MeHAewMbPd8vYGxdZ8CiVcrVNgb0YOIW3ViVig7piTHVvZyGaDo_bfIrHUyIcwOrAcKYUqcR9TAok16YtpcwQIK_zl6kYNBvHteT7Obr2fXiIl9-P_-2aJY5FLyMucJCk4oopXrOucIVq0rCSKc5w60qKO8pAO3rgvasBSpEJzrM-6IWTLCu1ewk-3zg7qZ21J1KDXgY5G6end9LB0b-fWPNVm7cvaxoKYqaJUB-AGz_SbtolnIHIerJS0zrkpOC39Okf_9Y0Lu7SYco0wcoPQxgtZuCpKyqcbIFm9EfD1LlXQhe9098guVsJ5nsJH_ZSRKR5B8O8jRWKm_d5G2a3P-07_5s-wn822vsJ8p22Fk</recordid><startdate>20200521</startdate><enddate>20200521</enddate><creator>Vantaux, Amélie</creator><creator>Kim, Saorin</creator><creator>Piv, Eakpor</creator><creator>Chy, Sophy</creator><creator>Berne, Laura</creator><creator>Khim, Nimol</creator><creator>Lek, Dysoley</creator><creator>Siv, Sovannaroth</creator><creator>Mukaka, Mavuto</creator><creator>Taylor, Walter R</creator><creator>Ménard, Didier</creator><general>American Society for Microbiology</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7945-961X</orcidid><orcidid>https://orcid.org/0000-0003-1357-4495</orcidid></search><sort><creationdate>20200521</creationdate><title>Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria</title><author>Vantaux, Amélie ; Kim, Saorin ; Piv, Eakpor ; Chy, Sophy ; Berne, Laura ; Khim, Nimol ; Lek, Dysoley ; Siv, Sovannaroth ; Mukaka, Mavuto ; Taylor, Walter R ; Ménard, Didier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a456t-c09e171cccf555c07376131de530bc425f2aa2f842f3ba299d9d05f489393dbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Epidemiology and Surveillance</topic><topic>Human health and pathology</topic><topic>Infectious diseases</topic><topic>Life Sciences</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vantaux, Amélie</creatorcontrib><creatorcontrib>Kim, Saorin</creatorcontrib><creatorcontrib>Piv, Eakpor</creatorcontrib><creatorcontrib>Chy, Sophy</creatorcontrib><creatorcontrib>Berne, Laura</creatorcontrib><creatorcontrib>Khim, Nimol</creatorcontrib><creatorcontrib>Lek, Dysoley</creatorcontrib><creatorcontrib>Siv, Sovannaroth</creatorcontrib><creatorcontrib>Mukaka, Mavuto</creatorcontrib><creatorcontrib>Taylor, Walter R</creatorcontrib><creatorcontrib>Ménard, Didier</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - 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><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vantaux, Amélie</au><au>Kim, Saorin</au><au>Piv, Eakpor</au><au>Chy, Sophy</au><au>Berne, Laura</au><au>Khim, Nimol</au><au>Lek, Dysoley</au><au>Siv, Sovannaroth</au><au>Mukaka, Mavuto</au><au>Taylor, Walter R</au><au>Ménard, Didier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2020-05-21</date><risdate>2020</risdate><volume>64</volume><issue>6</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Since 2012, a single low dose of primaquine (SLDPQ; 0.25 mg/kg of body weight) with artemisinin-based combination therapies has been recommended as the first-line treatment of acute uncomplicated
malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance, including artemisinin resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and a lack of data on its efficacy. In this randomized controlled trial, 109 Cambodians with acute uncomplicated
malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. The transmission-blocking efficacy of SLDPQ was evaluated on days 0, 1, 2, 3, 7, 14, 21, and 28, and recrudescence by reverse transcriptase PCR (RT-PCR) (gametocyte prevalence) and membrane feeding assays with
mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP-SLDPQ reduced gametocyte carriage 3-fold compared to that achieved with DP. Of 48 patients tested on day 0, only 3 patients were infectious to mosquitoes (∼6%). Posttreatment, three patients were infectious on day 14 (3.5%, 1/29) and on the 1st and 7th days of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission-blocking efficacy. Our study confirms the effective gametocyte clearance of SLDPQ when combined with DP in multidrug-resistant
infections and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP, and ASMQ-SLDPQ has been deployed to treat all patients with symptomatic
infections to further support the elimination of multidrug-resistant
in Cambodia. (This study has been registered at ClinicalTrials.gov under identifier NCT02434952.).</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>32179526</pmid><doi>10.1128/AAC.02108-19</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7945-961X</orcidid><orcidid>https://orcid.org/0000-0003-1357-4495</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Epidemiology and Surveillance Human health and pathology Infectious diseases Life Sciences Pharmaceutical sciences Pharmacology |
| title | Significant Efficacy of a Single Low Dose of Primaquine Compared to Stand-Alone Artemisinin Combination Therapy in Reducing Gametocyte Carriage in Cambodian Patients with Uncomplicated Multidrug-Resistant Plasmodium falciparum Malaria |
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