| Summary: | <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>
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