Application of WHO International Biological Reference Standards to evaluate commercial serological tests for chronic Chagas disease

BACKGROUND Chagas disease, resulting from Trypanosoma cruzi infections, continues to be a health concern mainly in Latin American countries where the parasite is endemic. The laboratory diagnosis of a chronic infection is determined through serological assays for antibodies against T. cruzi and several tests are available that differ in key components, formats and methodologies. To date, no single test meets the criteria of a gold standard. The situation is further complicated by the difficulties associated with performance comparisons between different immunoassays or methodologies executed at different times and geographical areas. OBJECTIVE To improve the diagnosis of Chagas disease, the WHO coordinated the development of two International Biological Reference Standards for antibodies against anti-T. cruzi: NIBSC 09/186 and NIBSC 09/188 that respectively represent geographical regions with the highest prevalence of TcII and TcI lineages of the parasite. METHODS The principle goal of this study was to verify the behavior of these standards when assayed by several commercially available serological tests that employ different methods to capture and detect human anti-T. cruzi antibodies. FINDINGS AND MAIN CONCLUSIONS The results reinforce the recommendation that these standards be considered for performance evaluations of commercialised immunoassays and should be an integral step in the development of new test components or assay paradigms.一、背景 恰加斯病（Chagas disease）由克氏锥虫（Trypanosoma cruzi）感染引发，目前仍是该寄生虫地方性流行的拉丁美洲国家的主要公共卫生关切。慢性感染的实验室诊断通过针对克氏锥虫抗体的血清学检测（serological assays）实现，现有多款检测试剂在核心组分、检测格式与方法学上存在差异。截至目前，尚无单一检测方法可满足金标准（gold standard）的要求；且不同时间、不同地理区域开展的不同免疫测定（immunoassays）或方法学之间的性能比对存在困难，进一步加剧了这一困境。 二、研究目标 为优化恰加斯病的诊断方案，世界卫生组织（World Health Organization, WHO）牵头开发了两款针对克氏锥虫抗体的国际生物参考标准（International Biological Reference Standards）：NIBSC 09/186与NIBSC 09/188（NIBSC为英国国家生物标准与控制研究所，National Institute for Biological Standards and Control），二者分别对应寄生虫TcII与TcI谱系流行率最高的地理区域。 三、研究方法 本研究的核心目标是验证：当采用多款通过不同方法捕获并检测人抗克氏锥虫抗体的商用血清学检测试剂盒对上述标准品进行检测时，该标准品的检测表现。 四、研究结果与主要结论 本研究结果进一步支持了相关建议：应将上述标准品用于商业化免疫测定试剂盒的性能评估，且其应成为新型检测组分或检测范式（assay paradigms）开发过程中不可或缺的环节。