Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA.
Am J Trop Med Hyg. 2011 May;84(5):825-9. doi: 10.4269/ajtmh.2011.10-0699.
A sensitive biomarker of malaria infection would obviate the need for placebo control arms in clinical trials of malaria prophylactic drugs. Antibodies to the 42-kDa fragment of merozoite surface protein-1 (MSP1(42)) have been identified as a potential marker of malaria exposure in individuals receiving prophylaxis with mefloquine. We conducted an open-label trial to determine the sensitivity of seroconversion to MSP1(42), defined as a fourfold rise in enzyme-linked immunosorbant assay (ELISA) titer, among 23 malaria naïve volunteers receiving mefloquine prophylaxis and 6 controls after Plasmodium falciparum sporozoite challenge. All members of the control cohort but none of the mefloquine cohort developed patent parasitemia. Four of six controls but zero of the mefloquine cohort seroconverted to MSP1(42). We conclude that malaria infection during suppressive prophylaxis does not induce antibody response to the blood-stage antigen MSP1(42) in a malaria-naïve study population.
一种灵敏的疟疾感染生物标志物将使临床试验中抗疟疾预防性药物不再需要安慰剂对照组。已经鉴定出对裂殖子表面蛋白 1(MSP1(42))的 42kDa 片段的抗体是接受甲氟喹预防的个体中疟疾暴露的潜在标志物。我们进行了一项开放标签试验,以确定血清转化率对 MSP1(42)的敏感性,其定义为 23 名疟疾初治志愿者接受甲氟喹预防和 6 名对照者在疟原虫孢子虫挑战后的酶联免疫吸附试验(ELISA)滴度增加四倍。对照组的所有成员均未出现疟疾原虫血症,但甲氟喹组均未出现。6 名对照者中有 4 名发生了对 MSP1(42)的血清转化,而甲氟喹组则无。我们得出结论,在抑制性预防期间的疟疾感染不会在疟疾初治的研究人群中引起对血液阶段抗原 MSP1(42)的抗体反应。