Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice

Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Arya SheelaNair [verfasserIn] Aleksandra S. Romanczuk [verfasserIn] Rosemary A. Aogo [verfasserIn] Rohit Nemai Haldar [verfasserIn] Lianne I. M. Lansink [verfasserIn] Deborah Cromer [verfasserIn] Yandira G. Salinas [verfasserIn] R. Kiplin Guy [verfasserIn] James S. McCarthy [verfasserIn] Miles P. Davenport [verfasserIn] Ashraful Haque [verfasserIn] David S. Khoury [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance

Übergeordnetes Werk:	In: Malaria Journal - BMC, 2003, 21(2022), 1, Seite 10
Übergeordnetes Werk:	volume:21 ; year:2022 ; number:1 ; pages:10

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12936-022-04075-z

Katalog-ID:	DOAJ013643649

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520			\|a Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
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700	0		\|a Rosemary A. Aogo \|e verfasserin \|4 aut
700	0		\|a Rohit Nemai Haldar \|e verfasserin \|4 aut
700	0		\|a Lianne I. M. Lansink \|e verfasserin \|4 aut
700	0		\|a Deborah Cromer \|e verfasserin \|4 aut
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700	0		\|a Miles P. Davenport \|e verfasserin \|4 aut
700	0		\|a Ashraful Haque \|e verfasserin \|4 aut
700	0		\|a David S. Khoury \|e verfasserin \|4 aut
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allfields	10.1186/s12936-022-04075-z doi (DE-627)DOAJ013643649 (DE-599)DOAJ3f61cc61389a4e4f8205817745258ad5 DE-627 ger DE-627 rakwb eng RC955-962 RC109-216 Arya SheelaNair verfasserin aut Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine Infectious and parasitic diseases Aleksandra S. Romanczuk verfasserin aut Rosemary A. Aogo verfasserin aut Rohit Nemai Haldar verfasserin aut Lianne I. M. Lansink verfasserin aut Deborah Cromer verfasserin aut Yandira G. Salinas verfasserin aut R. Kiplin Guy verfasserin aut James S. McCarthy verfasserin aut Miles P. Davenport verfasserin aut Ashraful Haque verfasserin aut David S. Khoury verfasserin aut In Malaria Journal BMC, 2003 21(2022), 1, Seite 10 (DE-627)355986582 (DE-600)2091229-8 14752875 nnns volume:21 year:2022 number:1 pages:10 https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 kostenfrei https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/toc/1475-2875 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2022 1 10
spelling	10.1186/s12936-022-04075-z doi (DE-627)DOAJ013643649 (DE-599)DOAJ3f61cc61389a4e4f8205817745258ad5 DE-627 ger DE-627 rakwb eng RC955-962 RC109-216 Arya SheelaNair verfasserin aut Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine Infectious and parasitic diseases Aleksandra S. Romanczuk verfasserin aut Rosemary A. Aogo verfasserin aut Rohit Nemai Haldar verfasserin aut Lianne I. M. Lansink verfasserin aut Deborah Cromer verfasserin aut Yandira G. Salinas verfasserin aut R. Kiplin Guy verfasserin aut James S. McCarthy verfasserin aut Miles P. Davenport verfasserin aut Ashraful Haque verfasserin aut David S. Khoury verfasserin aut In Malaria Journal BMC, 2003 21(2022), 1, Seite 10 (DE-627)355986582 (DE-600)2091229-8 14752875 nnns volume:21 year:2022 number:1 pages:10 https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 kostenfrei https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/toc/1475-2875 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2022 1 10
allfields_unstemmed	10.1186/s12936-022-04075-z doi (DE-627)DOAJ013643649 (DE-599)DOAJ3f61cc61389a4e4f8205817745258ad5 DE-627 ger DE-627 rakwb eng RC955-962 RC109-216 Arya SheelaNair verfasserin aut Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine Infectious and parasitic diseases Aleksandra S. Romanczuk verfasserin aut Rosemary A. Aogo verfasserin aut Rohit Nemai Haldar verfasserin aut Lianne I. M. Lansink verfasserin aut Deborah Cromer verfasserin aut Yandira G. Salinas verfasserin aut R. Kiplin Guy verfasserin aut James S. McCarthy verfasserin aut Miles P. Davenport verfasserin aut Ashraful Haque verfasserin aut David S. Khoury verfasserin aut In Malaria Journal BMC, 2003 21(2022), 1, Seite 10 (DE-627)355986582 (DE-600)2091229-8 14752875 nnns volume:21 year:2022 number:1 pages:10 https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 kostenfrei https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/toc/1475-2875 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2022 1 10
allfieldsGer	10.1186/s12936-022-04075-z doi (DE-627)DOAJ013643649 (DE-599)DOAJ3f61cc61389a4e4f8205817745258ad5 DE-627 ger DE-627 rakwb eng RC955-962 RC109-216 Arya SheelaNair verfasserin aut Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine Infectious and parasitic diseases Aleksandra S. Romanczuk verfasserin aut Rosemary A. Aogo verfasserin aut Rohit Nemai Haldar verfasserin aut Lianne I. M. Lansink verfasserin aut Deborah Cromer verfasserin aut Yandira G. Salinas verfasserin aut R. Kiplin Guy verfasserin aut James S. McCarthy verfasserin aut Miles P. Davenport verfasserin aut Ashraful Haque verfasserin aut David S. Khoury verfasserin aut In Malaria Journal BMC, 2003 21(2022), 1, Seite 10 (DE-627)355986582 (DE-600)2091229-8 14752875 nnns volume:21 year:2022 number:1 pages:10 https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 kostenfrei https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/toc/1475-2875 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2022 1 10
allfieldsSound	10.1186/s12936-022-04075-z doi (DE-627)DOAJ013643649 (DE-599)DOAJ3f61cc61389a4e4f8205817745258ad5 DE-627 ger DE-627 rakwb eng RC955-962 RC109-216 Arya SheelaNair verfasserin aut Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites. SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine Infectious and parasitic diseases Aleksandra S. Romanczuk verfasserin aut Rosemary A. Aogo verfasserin aut Rohit Nemai Haldar verfasserin aut Lianne I. M. Lansink verfasserin aut Deborah Cromer verfasserin aut Yandira G. Salinas verfasserin aut R. Kiplin Guy verfasserin aut James S. McCarthy verfasserin aut Miles P. Davenport verfasserin aut Ashraful Haque verfasserin aut David S. Khoury verfasserin aut In Malaria Journal BMC, 2003 21(2022), 1, Seite 10 (DE-627)355986582 (DE-600)2091229-8 14752875 nnns volume:21 year:2022 number:1 pages:10 https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 kostenfrei https://doi.org/10.1186/s12936-022-04075-z kostenfrei https://doaj.org/toc/1475-2875 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2022 1 10
language	English
source	In Malaria Journal 21(2022), 1, Seite 10 volume:21 year:2022 number:1 pages:10
sourceStr	In Malaria Journal 21(2022), 1, Seite 10 volume:21 year:2022 number:1 pages:10
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine Infectious and parasitic diseases
isfreeaccess_bool	true
container_title	Malaria Journal
authorswithroles_txt_mv	Arya SheelaNair @@aut@@ Aleksandra S. Romanczuk @@aut@@ Rosemary A. Aogo @@aut@@ Rohit Nemai Haldar @@aut@@ Lianne I. M. Lansink @@aut@@ Deborah Cromer @@aut@@ Yandira G. Salinas @@aut@@ R. Kiplin Guy @@aut@@ James S. McCarthy @@aut@@ Miles P. Davenport @@aut@@ Ashraful Haque @@aut@@ David S. Khoury @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	355986582
id	DOAJ013643649
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ013643649</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230310055855.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230226s2022 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12936-022-04075-z</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ013643649</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ3f61cc61389a4e4f8205817745258ad5</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC955-962</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC109-216</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Arya SheelaNair</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SJ733</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pyronaridine</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Artesunate</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Plasmodium berghei</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Parasite clearance</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Arctic medicine. Tropical medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Infectious and parasitic diseases</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Aleksandra S. 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callnumber-first	R - Medicine
author	Arya SheelaNair
spellingShingle	Arya SheelaNair misc RC955-962 misc RC109-216 misc SJ733 misc Pyronaridine misc Artesunate misc Plasmodium berghei misc Parasite clearance misc Arctic medicine. Tropical medicine misc Infectious and parasitic diseases Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice
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topic_title	RC955-962 RC109-216 Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance
topic	misc RC955-962 misc RC109-216 misc SJ733 misc Pyronaridine misc Artesunate misc Plasmodium berghei misc Parasite clearance misc Arctic medicine. Tropical medicine misc Infectious and parasitic diseases
topic_unstemmed	misc RC955-962 misc RC109-216 misc SJ733 misc Pyronaridine misc Artesunate misc Plasmodium berghei misc Parasite clearance misc Arctic medicine. Tropical medicine misc Infectious and parasitic diseases
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title	Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice
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title_full	Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice
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author_browse	Arya SheelaNair Aleksandra S. Romanczuk Rosemary A. Aogo Rohit Nemai Haldar Lianne I. M. Lansink Deborah Cromer Yandira G. Salinas R. Kiplin Guy James S. McCarthy Miles P. Davenport Ashraful Haque David S. Khoury
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title_sort	similarly efficacious anti-malarial drugs sj733 and pyronaridine differ in their ability to remove circulating parasites in mice
callnumber	RC955-962
title_auth	Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice
abstract	Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
abstractGer	Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
abstract_unstemmed	Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
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title_short	Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice
url	https://doi.org/10.1186/s12936-022-04075-z https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 https://doaj.org/toc/1475-2875
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However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. 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Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice

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