Ex vivo activity of Proveblue, a methylene blue, against field isolates of Plasmodium falciparum in Dakar, Senegal from 2013–2015
•Proveblue, a methylene blue preparation, was highly active against Plasmodium falciparum isolates (8.1 nM).•Proveblue was more active than standard antimalarial drugs, but less active than artemisinin derivatives.•A low significant positive correlation was found between Proveblue and artemisinin de...
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| Veröffentlicht in: | International journal of antimicrobial agents 2017-08, Vol.50 (2), p.155-158 |
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| creator | Fall, Bécaye Madamet, Marylin Diawara, Silman Briolant, Sébastien Wade, Khalifa Ababacar Lo, Gora Nakoulima, Aminata Fall, Mansour Bercion, Raymond Kounta, Mame Bou Amalvict, Rémi Benoit, Nicolas Gueye, Mamadou Wague Diatta, Bakary Wade, Boubacar Pradines, Bruno |
| description | •Proveblue, a methylene blue preparation, was highly active against Plasmodium falciparum isolates (8.1 nM).•Proveblue was more active than standard antimalarial drugs, but less active than artemisinin derivatives.•A low significant positive correlation was found between Proveblue and artemisinin derivatives and piperaquine.•The correlation between Proveblue and artemisinin derivatives and piperaquine was too low to indicate cross-resistance.•Proveblue is to be considered in triple artemisinin-based combination therapy for treatment of multidrug-resistant malaria.
Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs. The Proveblue IC50 of 76 P. falciparum isolates ranged from 0.5 nM to 135.1 nM, with a mean of 8.1 nM [95% confidence interval, 6.4–10.3]. Proveblue was found to be more active against P. falciparum parasites than chloroquine, quinine, monodesethylamodiaquine, mefloquine, piperaquine, doxycycline (P |
| doi_str_mv | 10.1016/j.ijantimicag.2017.03.019 |
| format | Article |
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Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs. The Proveblue IC50 of 76 P. falciparum isolates ranged from 0.5 nM to 135.1 nM, with a mean of 8.1 nM [95% confidence interval, 6.4–10.3]. Proveblue was found to be more active against P. falciparum parasites than chloroquine, quinine, monodesethylamodiaquine, mefloquine, piperaquine, doxycycline (P < 0.001) and lumefantrine (P = 0.014). Proveblue was as active as pyronaridine (P = 0.927), but was less active than dihydroartemisinin and artesunate (P < 0.001). The only significant cross-susceptibilities found were between Proveblue and dihydroartemisinin (r2 = 0.195, P = 0.0001), artesunate (r2 = 0.187, P = 0.0002) and piperaquine (r2 = 0.063, P = 0.029). The present study clearly demonstrates the potential of Proveblue as an effective therapeutic agent against P. falciparum. In this context, the use of Proveblue as part of the triple ACT treatment for multidrug-resistant malaria warrants further investigation.</description><identifier>ISSN: 0924-8579</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2017.03.019</identifier><identifier>PMID: 28689867</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Antimalarial drug ; Antimalarials - pharmacology ; Enzyme Inhibitors - pharmacology ; Human health and pathology ; Humans ; In vitro ; Infectious diseases ; Inhibitory Concentration 50 ; Life Sciences ; Malaria ; Malaria, Falciparum - parasitology ; Methylene blue ; Methylene Blue - pharmacology ; Parasitic Sensitivity Tests ; Plasmodium falciparum ; Plasmodium falciparum - drug effects ; Plasmodium falciparum - isolation & purification ; Resistance ; Senegal</subject><ispartof>International journal of antimicrobial agents, 2017-08, Vol.50 (2), p.155-158</ispartof><rights>2017 Elsevier B.V. and International Society of Chemotherapy</rights><rights>Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-114b22a2d14efac6754ee7e2e15ed8a37aa5bccfc87692428d19165e5cbfcd233</citedby><cites>FETCH-LOGICAL-c411t-114b22a2d14efac6754ee7e2e15ed8a37aa5bccfc87692428d19165e5cbfcd233</cites><orcidid>0000-0002-2360-3803</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijantimicag.2017.03.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28689867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01774701$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fall, Bécaye</creatorcontrib><creatorcontrib>Madamet, Marylin</creatorcontrib><creatorcontrib>Diawara, Silman</creatorcontrib><creatorcontrib>Briolant, Sébastien</creatorcontrib><creatorcontrib>Wade, Khalifa Ababacar</creatorcontrib><creatorcontrib>Lo, Gora</creatorcontrib><creatorcontrib>Nakoulima, Aminata</creatorcontrib><creatorcontrib>Fall, Mansour</creatorcontrib><creatorcontrib>Bercion, Raymond</creatorcontrib><creatorcontrib>Kounta, Mame Bou</creatorcontrib><creatorcontrib>Amalvict, Rémi</creatorcontrib><creatorcontrib>Benoit, Nicolas</creatorcontrib><creatorcontrib>Gueye, Mamadou Wague</creatorcontrib><creatorcontrib>Diatta, Bakary</creatorcontrib><creatorcontrib>Wade, Boubacar</creatorcontrib><creatorcontrib>Pradines, Bruno</creatorcontrib><title>Ex vivo activity of Proveblue, a methylene blue, against field isolates of Plasmodium falciparum in Dakar, Senegal from 2013–2015</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>•Proveblue, a methylene blue preparation, was highly active against Plasmodium falciparum isolates (8.1 nM).•Proveblue was more active than standard antimalarial drugs, but less active than artemisinin derivatives.•A low significant positive correlation was found between Proveblue and artemisinin derivatives and piperaquine.•The correlation between Proveblue and artemisinin derivatives and piperaquine was too low to indicate cross-resistance.•Proveblue is to be considered in triple artemisinin-based combination therapy for treatment of multidrug-resistant malaria.
Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs. The Proveblue IC50 of 76 P. falciparum isolates ranged from 0.5 nM to 135.1 nM, with a mean of 8.1 nM [95% confidence interval, 6.4–10.3]. Proveblue was found to be more active against P. falciparum parasites than chloroquine, quinine, monodesethylamodiaquine, mefloquine, piperaquine, doxycycline (P < 0.001) and lumefantrine (P = 0.014). Proveblue was as active as pyronaridine (P = 0.927), but was less active than dihydroartemisinin and artesunate (P < 0.001). The only significant cross-susceptibilities found were between Proveblue and dihydroartemisinin (r2 = 0.195, P = 0.0001), artesunate (r2 = 0.187, P = 0.0002) and piperaquine (r2 = 0.063, P = 0.029). The present study clearly demonstrates the potential of Proveblue as an effective therapeutic agent against P. falciparum. In this context, the use of Proveblue as part of the triple ACT treatment for multidrug-resistant malaria warrants further investigation.</description><subject>Antimalarial drug</subject><subject>Antimalarials - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>In vitro</subject><subject>Infectious diseases</subject><subject>Inhibitory Concentration 50</subject><subject>Life Sciences</subject><subject>Malaria</subject><subject>Malaria, Falciparum - parasitology</subject><subject>Methylene blue</subject><subject>Methylene Blue - pharmacology</subject><subject>Parasitic Sensitivity Tests</subject><subject>Plasmodium falciparum</subject><subject>Plasmodium falciparum - drug effects</subject><subject>Plasmodium falciparum - isolation & purification</subject><subject>Resistance</subject><subject>Senegal</subject><issn>0924-8579</issn><issn>1872-7913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxi0EotvCKyBzA6kJtvPHzrHathRpJZCAszVxJlsvTrzY2Yi9IfEIvCFPgpddKo6cxhr95vvG8xHykrOcM16_2eR2A-NkB2tgnQvGZc6KnPHmEVlwJUUmG148JgvWiDJTlWzOyHmMG8Z4VZTVU3ImVK0aVcsF-XHzjc529hTMZGc77anv6YfgZ2zdDi8p0AGn-73DEempswY7xon2Fl1HbfQOJox_xhzEwXd2N9AenLFbCOlpR3oNXyBc0o9JZA2O9sEPNG1d_Pr-M5XqGXmS-IjPT_WCfL69-bS8y1bv375bXq0yU3I-ZZyXrRAgOl5iD6aWVYkoUSCvsFNQSICqNaY3Stbp40J1vOF1hZVpe9OJorggr4-69-D0NtgBwl57sPruaqUPvXRIWUrGZ57YV0d2G_zXHcZJDzYadA5G9Luok7Ssa6mYSmhzRE3wMQbsH7Q504e89Eb_k5c-5KVZkdyaNPviZLNrB-weJv8GlIDlEcB0mNli0NFYHA12NqCZdOftf9j8BvYerTg</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Fall, Bécaye</creator><creator>Madamet, Marylin</creator><creator>Diawara, Silman</creator><creator>Briolant, Sébastien</creator><creator>Wade, Khalifa Ababacar</creator><creator>Lo, Gora</creator><creator>Nakoulima, Aminata</creator><creator>Fall, Mansour</creator><creator>Bercion, Raymond</creator><creator>Kounta, Mame Bou</creator><creator>Amalvict, Rémi</creator><creator>Benoit, Nicolas</creator><creator>Gueye, Mamadou Wague</creator><creator>Diatta, Bakary</creator><creator>Wade, Boubacar</creator><creator>Pradines, Bruno</creator><general>Elsevier B.V</general><general>Elsevier</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>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-2360-3803</orcidid></search><sort><creationdate>20170801</creationdate><title>Ex vivo activity of Proveblue, a methylene blue, against field isolates of Plasmodium falciparum in Dakar, Senegal from 2013–2015</title><author>Fall, Bécaye ; Madamet, Marylin ; Diawara, Silman ; Briolant, Sébastien ; Wade, Khalifa Ababacar ; Lo, Gora ; Nakoulima, Aminata ; Fall, Mansour ; Bercion, Raymond ; Kounta, Mame Bou ; Amalvict, Rémi ; Benoit, Nicolas ; Gueye, Mamadou Wague ; Diatta, Bakary ; Wade, Boubacar ; Pradines, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-114b22a2d14efac6754ee7e2e15ed8a37aa5bccfc87692428d19165e5cbfcd233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Antimalarial drug</topic><topic>Antimalarials - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>In vitro</topic><topic>Infectious diseases</topic><topic>Inhibitory Concentration 50</topic><topic>Life Sciences</topic><topic>Malaria</topic><topic>Malaria, Falciparum - parasitology</topic><topic>Methylene blue</topic><topic>Methylene Blue - pharmacology</topic><topic>Parasitic Sensitivity Tests</topic><topic>Plasmodium falciparum</topic><topic>Plasmodium falciparum - drug effects</topic><topic>Plasmodium falciparum - isolation & purification</topic><topic>Resistance</topic><topic>Senegal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fall, Bécaye</creatorcontrib><creatorcontrib>Madamet, Marylin</creatorcontrib><creatorcontrib>Diawara, Silman</creatorcontrib><creatorcontrib>Briolant, Sébastien</creatorcontrib><creatorcontrib>Wade, Khalifa Ababacar</creatorcontrib><creatorcontrib>Lo, Gora</creatorcontrib><creatorcontrib>Nakoulima, Aminata</creatorcontrib><creatorcontrib>Fall, Mansour</creatorcontrib><creatorcontrib>Bercion, Raymond</creatorcontrib><creatorcontrib>Kounta, Mame Bou</creatorcontrib><creatorcontrib>Amalvict, Rémi</creatorcontrib><creatorcontrib>Benoit, Nicolas</creatorcontrib><creatorcontrib>Gueye, Mamadou Wague</creatorcontrib><creatorcontrib>Diatta, Bakary</creatorcontrib><creatorcontrib>Wade, Boubacar</creatorcontrib><creatorcontrib>Pradines, Bruno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fall, Bécaye</au><au>Madamet, Marylin</au><au>Diawara, Silman</au><au>Briolant, Sébastien</au><au>Wade, Khalifa Ababacar</au><au>Lo, Gora</au><au>Nakoulima, Aminata</au><au>Fall, Mansour</au><au>Bercion, Raymond</au><au>Kounta, Mame Bou</au><au>Amalvict, Rémi</au><au>Benoit, Nicolas</au><au>Gueye, Mamadou Wague</au><au>Diatta, Bakary</au><au>Wade, Boubacar</au><au>Pradines, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ex vivo activity of Proveblue, a methylene blue, against field isolates of Plasmodium falciparum in Dakar, Senegal from 2013–2015</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>50</volume><issue>2</issue><spage>155</spage><epage>158</epage><pages>155-158</pages><issn>0924-8579</issn><eissn>1872-7913</eissn><abstract>•Proveblue, a methylene blue preparation, was highly active against Plasmodium falciparum isolates (8.1 nM).•Proveblue was more active than standard antimalarial drugs, but less active than artemisinin derivatives.•A low significant positive correlation was found between Proveblue and artemisinin derivatives and piperaquine.•The correlation between Proveblue and artemisinin derivatives and piperaquine was too low to indicate cross-resistance.•Proveblue is to be considered in triple artemisinin-based combination therapy for treatment of multidrug-resistant malaria.
Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs. The Proveblue IC50 of 76 P. falciparum isolates ranged from 0.5 nM to 135.1 nM, with a mean of 8.1 nM [95% confidence interval, 6.4–10.3]. Proveblue was found to be more active against P. falciparum parasites than chloroquine, quinine, monodesethylamodiaquine, mefloquine, piperaquine, doxycycline (P < 0.001) and lumefantrine (P = 0.014). Proveblue was as active as pyronaridine (P = 0.927), but was less active than dihydroartemisinin and artesunate (P < 0.001). The only significant cross-susceptibilities found were between Proveblue and dihydroartemisinin (r2 = 0.195, P = 0.0001), artesunate (r2 = 0.187, P = 0.0002) and piperaquine (r2 = 0.063, P = 0.029). The present study clearly demonstrates the potential of Proveblue as an effective therapeutic agent against P. falciparum. In this context, the use of Proveblue as part of the triple ACT treatment for multidrug-resistant malaria warrants further investigation.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28689867</pmid><doi>10.1016/j.ijantimicag.2017.03.019</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-2360-3803</orcidid></addata></record> |
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| ispartof | International journal of antimicrobial agents, 2017-08, Vol.50 (2), p.155-158 |
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| subjects | Antimalarial drug Antimalarials - pharmacology Enzyme Inhibitors - pharmacology Human health and pathology Humans In vitro Infectious diseases Inhibitory Concentration 50 Life Sciences Malaria Malaria, Falciparum - parasitology Methylene blue Methylene Blue - pharmacology Parasitic Sensitivity Tests Plasmodium falciparum Plasmodium falciparum - drug effects Plasmodium falciparum - isolation & purification Resistance Senegal |
| title | Ex vivo activity of Proveblue, a methylene blue, against field isolates of Plasmodium falciparum in Dakar, Senegal from 2013–2015 |
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