Department of Clinical Tropical Medicine, Mahidol University, 420/6 Rajvithi, Bangkok, Thailand.
Malar J. 2010 Nov 16;9:326. doi: 10.1186/1475-2875-9-326.
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.
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.
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).
'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.
抗疟药物的疗效取决于寄生虫的敏感性水平、抗疟药物的生物利用度和药代动力学以及包括免疫在内的宿主因素。宿主免疫可提高抗疟药物的体内治疗效果，但这种效果的机制和程度尚未确定。本研究旨在描述“免疫”血浆对恶性疟原虫感染红细胞表面抗原[RESA]的影响。
测量来自泰国急性恶性疟患者的血浆样本中针对血阶段抗原（主要是环感染红细胞表面抗原[RESA]）的抗体滴度。选择“免疫”血浆，并通过光镜评估其对泰国恶性疟原虫实验室株 TM267 的体外寄生虫生长和繁殖的影响。然后，使用 3H-次黄嘌呤摄取抑制法，在存在和不存在“免疫”血浆的情况下，确定奎宁和青蒿琥酯的体外敏感性。药物敏感性用 3H-次黄嘌呤摄取的 50%和 90%抑制浓度（IC50 和 IC90）表示。
与对照组相比，“免疫”血浆孵育后寄生虫成熟和繁殖减少呈剂量依赖性（中位数[范围]；181.5[0 至 3269] cpm 与 1222.5[388 至 5932] cpm）（p=0.001）。因此，“免疫”血浆明显降低了奎宁的表观敏感性；中位数（范围）IC50 6.4（0.5 至 23.8）ng/ml 与 221.5（174.4 至 250.4）ng/ml（p=0.02），并且对青蒿琥酯的敏感性也有临界影响；IC50 0.2（0.02 至 0.3）ng/ml 与 0.8（0.2 至 2.3）ng/ml（p=0.08）。在低浓度下效果最大，改变了浓度-效应关系的形状。IC90 值没有受到显著影响；奎宁的中位数（范围）IC90 448.0（65 至>500）ng/ml 与 368.8（261 至 501）ng/ml（p>0.05）和青蒿琥酯的 17.0（0.1 至 29.5）ng/ml 与 7.6（2.3 至 19.5）ng/ml（p=0.4）。
含有抗疟抗体的“免疫”血浆可抑制寄生虫的发育和繁殖，并增加恶性疟原虫体外抗疟药物的敏感性。IC90 比 IC50 测量受影响小得多。
