Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum.
BACKGROUND: The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism an...
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th-mahidol.7342023-03-31T12:08:22Z Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. Preeyaporn Monatrakul ปรียาภรณ์ โมนะตระกูล Mathirut Mungthin Dondorp, Arjen M. Srivicha Krudsood ศรีวิชา ครุฑสูตร Rachanee Udomsangpetch Polrat Wilairatana พลรัตน์ วิไลรัตน์ White, Nicholas J. Kesinee Chotivanich เกศินี โชติวานิช Kesinee Chotivanich Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Antimalarials Plasmodium falciparum Quinine Open Access article BACKGROUND: The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. METHODS: Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake. RESULTS: Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4). CONCLUSIONS: 'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent in vitro anti-malarial drug susceptibility of P. falciparum. The IC90 was much less affected than the IC50 measurement. 2012-10-10T07:23:26Z 2016-09-29T15:34:50Z 2012-10-10T07:23:26Z 2016-09-29T15:34:50Z 2010 2012-10-10 2010-11 Research Article Monatrakul P, Mungthin M, Dondorp AM, Krudsood S, Udomsangpetch R, Wilairatana P, et al. Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. Malar J. 2010 Nov 16;9:326. 10.1186/1475-2875-9-326 1475-2875 (electronic) https://repository.li.mahidol.ac.th/handle/123456789/734 eng Mahidol University BioMed Central application/pdf |
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Antimalarials Plasmodium falciparum Quinine Open Access article Preeyaporn Monatrakul ปรียาภรณ์ โมนะตระกูล Mathirut Mungthin Dondorp, Arjen M. Srivicha Krudsood ศรีวิชา ครุฑสูตร Rachanee Udomsangpetch Polrat Wilairatana พลรัตน์ วิไลรัตน์ White, Nicholas J. Kesinee Chotivanich เกศินี โชติวานิช Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. |
description |
BACKGROUND: The efficacy of anti-malarial drugs is determined by the level of
parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics,
and host factors including immunity. Host immunity improves the in vivo
therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of
this effect has not been characterized. This study characterized the effects of
'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P.
falciparum to anti-malarial drugs.
METHODS: Titres of antibodies against blood stage antigens (mainly the
ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples
obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was
selected and its effects on in vitro parasite growth and multiplication of the
Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The
in vitro susceptibility to quinine and artesunate was then determined in the
presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake
inhibition method. Drug susceptibility was expressed as the concentrations
causing 50% and 90% inhibition (IC50 and IC90), of 3H-hypoxanthine uptake.
RESULTS: Incubation with 'immune' plasma reduced parasite maturation and
decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine
incorporation after incubation with 'immune' plasma was decreased significantly
compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388
to 5,932] cpm) (p= 0.001). As a result 'immune' plasma reduced apparent
susceptibility to quinine substantially; median (range) IC50 6.4 (0.5 to 23.8)
ng/ml versus 221.5 (174.4 to 250.4) ng/ml (p = 0.02), and also had a borderline
effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2
to 2.3) ng/ml (p = 0.08). Effects were greatest at low concentrations, changing
the shape of the concentration-effect relationship. IC90 values were not
significantly affected; median (range) IC90 448.0 (65 to > 500) ng/ml versus
368.8 (261 to 501) ng/ml for quinine (p > 0.05) and 17.0 (0.1 to 29.5) ng/ml
versus 7.6 (2.3 to 19.5) ng/ml for artesunate (p = 0.4).
CONCLUSIONS: 'Immune' plasma containing anti-malarial antibodies inhibits
parasite development and multiplication and increases apparent in vitro
anti-malarial drug susceptibility of P. falciparum. The IC90 was much less
affected than the IC50 measurement. |
author2 |
Kesinee Chotivanich |
author_facet |
Kesinee Chotivanich Preeyaporn Monatrakul ปรียาภรณ์ โมนะตระกูล Mathirut Mungthin Dondorp, Arjen M. Srivicha Krudsood ศรีวิชา ครุฑสูตร Rachanee Udomsangpetch Polrat Wilairatana พลรัตน์ วิไลรัตน์ White, Nicholas J. Kesinee Chotivanich เกศินี โชติวานิช |
format |
Article |
author |
Preeyaporn Monatrakul ปรียาภรณ์ โมนะตระกูล Mathirut Mungthin Dondorp, Arjen M. Srivicha Krudsood ศรีวิชา ครุฑสูตร Rachanee Udomsangpetch Polrat Wilairatana พลรัตน์ วิไลรัตน์ White, Nicholas J. Kesinee Chotivanich เกศินี โชติวานิช |
author_sort |
Preeyaporn Monatrakul |
title |
Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. |
title_short |
Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. |
title_full |
Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. |
title_fullStr |
Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. |
title_full_unstemmed |
Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum. |
title_sort |
modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in plasmodium falciparum. |
publishDate |
2012 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/734 |
_version_ |
1764209914693025792 |