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 dr...
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ftdoajarticles:oai:doaj.org/article:3f61cc61389a4e4f8205817745258ad5 2023-05-15T15:13:14+02:00 Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice 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 2022-02-01T00:00:00Z https://doi.org/10.1186/s12936-022-04075-z https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 EN eng BMC https://doi.org/10.1186/s12936-022-04075-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-022-04075-z 1475-2875 https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 Malaria Journal, Vol 21, Iss 1, Pp 1-10 (2022) SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2022 ftdoajarticles https://doi.org/10.1186/s12936-022-04075-z 2022-12-31T15:08:39Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 21 1 |
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Directory of Open Access Journals: DOAJ Articles |
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SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 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 Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice |
topic_facet |
SJ733 Pyronaridine Artesunate Plasmodium berghei Parasite clearance Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
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 |
author_facet |
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 |
author_sort |
Arya SheelaNair |
title |
Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice |
title_short |
Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice |
title_full |
Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice |
title_fullStr |
Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice |
title_full_unstemmed |
Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice |
title_sort |
similarly efficacious anti-malarial drugs sj733 and pyronaridine differ in their ability to remove circulating parasites in mice |
publisher |
BMC |
publishDate |
2022 |
url |
https://doi.org/10.1186/s12936-022-04075-z https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 21, Iss 1, Pp 1-10 (2022) |
op_relation |
https://doi.org/10.1186/s12936-022-04075-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-022-04075-z 1475-2875 https://doaj.org/article/3f61cc61389a4e4f8205817745258ad5 |
op_doi |
https://doi.org/10.1186/s12936-022-04075-z |
container_title |
Malaria Journal |
container_volume |
21 |
container_issue |
1 |
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1766343815111639040 |