Department of Medicine, University of California San Francisco, San Francisco, California, USA.
PLoS One. 2012;7(12):e52571. doi: 10.1371/journal.pone.0052571. Epub 2012 Dec 19.
Antibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessment of response to partially effective antimalarial therapy, which requires the host to assist in clearing parasites, offers an opportunity to measure protection independent of exposure.
A cohort of children aged 1-10 years in Kampala, Uganda were treated with amodiaquine+sulfadoxine-pyrimethamine for uncomplicated malaria. Serum samples from the time of malaria diagnosis and 14 days later were analyzed for total IgG to 8 P. falciparum antigens using a quantitative indirect ELISA. Associations between antibody levels and risk of treatment failure were estimated using Cox proportional hazard regression.
Higher levels of antibodies to apical membrane antigen 1 (AMA-1), but to none of the other 7 antigens were significantly associated with protection against treatment failure (HR 0.57 per 10-fold increase in antibody level, CI 0.41-0.79, p = 0.001). Protection increased consistently across the entire range of antibody levels.
Measurement of antibody levels to AMA-1 at the time of malaria may offer a quantitative biomarker of blood stage immunity to P. falciparum, a tool which is currently lacking.
抗体在控制恶性疟原虫血期感染中起着重要作用。由于暴露的异质性，哪些抗体反应负责甚至与保护相关尚不清楚。评估部分有效的抗疟治疗的反应提供了一个机会，可以在不考虑暴露的情况下衡量保护作用。
乌干达坎帕拉的一个年龄在 1-10 岁的儿童队列接受了阿莫地喹+磺胺多辛-乙胺嘧啶治疗无并发症疟疾。在疟疾诊断时和 14 天后采集血清样本，使用定量间接 ELISA 分析针对 8 种恶性疟原虫抗原的总 IgG。使用 Cox 比例风险回归估计抗体水平与治疗失败风险之间的关联。
高水平的抗顶膜抗原 1（AMA-1）抗体与治疗失败的保护显著相关，但与其他 7 种抗原均无显著相关性（抗体水平每增加 10 倍，风险比为 0.57，95%置信区间为 0.41-0.79，p=0.001）。保护作用在整个抗体水平范围内持续增加。
在疟疾发生时测量 AMA-1 的抗体水平可能提供恶性疟原虫血期免疫的定量生物标志物，这是目前缺乏的工具。
