Lee Nelson, Baker Joanne, Andrews Kathy T, Gatton Michelle L, Bell David, Cheng Qin, McCarthy James
Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and School of Population Health, University of Queensland, Queensland, Australia.
J Clin Microbiol. 2006 Aug;44(8):2773-8. doi: 10.1128/JCM.02557-05.
The ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparum isolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities.
准确诊断疟疾感染的能力，尤其是在实验室设施欠发达的环境中，对于控制这种疾病至关重要。快速诊断检测（RDTs）为满足这一需求提供了巨大潜力。基于检测恶性疟原虫富含组氨酸蛋白2（HRP2）（PfHRP2）的RDTs在现场性能方面存在显著差异的报告，以及PfHRP2中存在显著的序列多态性，促使我们评估四种HRP2特异性单克隆抗体（MABs）与来自地理上不同的恶性疟原虫分离株的寄生虫蛋白的结合情况，确定这些MABs识别的表位，并将表位的拷贝数与MAB反应性相关联。我们观察到相同的MAB对不同分离株的反应性以及用单个分离株测试的不同MAB之间存在显著差异。当确定三种MABs的靶表位并将其定位到现场分离株的肽序列上时，观察到这些表位的频率存在显著差异。这些发现支持序列变异可解释基于HRP2的RDTs性能差异这一观点，并指出了提高其诊断敏感性的可能方法。
