Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it>
<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo <...
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doaj-54a9f05b414244e3a9876183129d707a2020-11-24T23:58:54ZengBMCMalaria Journal1475-28752010-11-019132610.1186/1475-2875-9-326Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it>Udomsangpetch RachaneeKrudsood SrivichaDondorp Arjen MMungthin MathirutMonatrakul PreeyapornWilairatana PolratWhite Nicholas JChotivanich Kesinee<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>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 <it>Plasmodium falciparum</it>on the <it>in vitro </it>susceptibility of <it>P. falciparum </it>to anti-malarial drugs.</p> <p>Methods</p> <p>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 <it>in vitro </it>parasite growth and multiplication of the Thai <it>P. falciparum </it>laboratory strain TM267 were assessed by light microscopy. The <it>in vitro </it>susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the <sup>3</sup>H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC<sub>50 </sub>and IC<sub>90</sub>), of <sup>3</sup>H-hypoxanthine uptake.</p> <p>Results</p> <p>Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. <sup>3</sup>H-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) (<it>p</it>= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC<sub>50 </sub>6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (<it>p </it>= 0.02), and also had a borderline effect on artesunate susceptibility; IC<sub>50 </sub>0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (<it>p </it>= 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC<sub>90 </sub>values were not significantly affected; median (range) IC<sub>90 </sub>448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (<it>p </it>> 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (<it>p </it>= 0.4).</p> <p>Conclusions</p> <p>'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent <it>in vitro </it>anti-malarial drug susceptibility of <it>P. falciparum</it>. The IC<sub>90 </sub>was much less affected than the IC<sub>50 </sub>measurement.</p> http://www.malariajournal.com/content/9/1/326 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Udomsangpetch Rachanee Krudsood Srivicha Dondorp Arjen M Mungthin Mathirut Monatrakul Preeyaporn Wilairatana Polrat White Nicholas J Chotivanich Kesinee |
spellingShingle |
Udomsangpetch Rachanee Krudsood Srivicha Dondorp Arjen M Mungthin Mathirut Monatrakul Preeyaporn Wilairatana Polrat White Nicholas J Chotivanich Kesinee Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it> Malaria Journal |
author_facet |
Udomsangpetch Rachanee Krudsood Srivicha Dondorp Arjen M Mungthin Mathirut Monatrakul Preeyaporn Wilairatana Polrat White Nicholas J Chotivanich Kesinee |
author_sort |
Udomsangpetch Rachanee |
title |
Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it> |
title_short |
Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it> |
title_full |
Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it> |
title_fullStr |
Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it> |
title_full_unstemmed |
Modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>Plasmodium falciparum</it> |
title_sort |
modulating effects of plasma containing anti-malarial antibodies on <it>in vitro </it>anti-malarial drug susceptibility in <it>plasmodium falciparum</it> |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2010-11-01 |
description |
<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>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 <it>Plasmodium falciparum</it>on the <it>in vitro </it>susceptibility of <it>P. falciparum </it>to anti-malarial drugs.</p> <p>Methods</p> <p>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 <it>in vitro </it>parasite growth and multiplication of the Thai <it>P. falciparum </it>laboratory strain TM267 were assessed by light microscopy. The <it>in vitro </it>susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the <sup>3</sup>H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC<sub>50 </sub>and IC<sub>90</sub>), of <sup>3</sup>H-hypoxanthine uptake.</p> <p>Results</p> <p>Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. <sup>3</sup>H-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) (<it>p</it>= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC<sub>50 </sub>6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (<it>p </it>= 0.02), and also had a borderline effect on artesunate susceptibility; IC<sub>50 </sub>0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (<it>p </it>= 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC<sub>90 </sub>values were not significantly affected; median (range) IC<sub>90 </sub>448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (<it>p </it>> 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (<it>p </it>= 0.4).</p> <p>Conclusions</p> <p>'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent <it>in vitro </it>anti-malarial drug susceptibility of <it>P. falciparum</it>. The IC<sub>90 </sub>was much less affected than the IC<sub>50 </sub>measurement.</p> |
url |
http://www.malariajournal.com/content/9/1/326 |
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