Журнал бактериологии и паразитологии

Абстрактный

Establishing a valid laboratory case definition for human leptospirosis

Marga G. A. Goris, Mariska M. G. Leeflang, Kimberly R. Boer, Marco Goyenbier, Eric K. M. van Gorp, Jiri F. P. Wagenaar, and Rudi A. Hartskeerl

The laboratory case definition of leptospirosis is hardly defined by a reliable assessment that determines the cut-off values ​​of the tests used. This study describes a process for determining the optimal cut-off titers of leptospirosis laboratory tests for reliable case definition of leptospirosis. In this case, the tests are the microscopic agglutination test (MAT) and the internal IgM enzyme immunoassay (EIA) on both single and paired serum samples using a positive culture as a control test in a Dutch population. Specificity was assessed using panels of sera from healthy donors, cases with known other illnesses, and non-leptospirosis cases with symptoms compatible with leptospirosis. Cases were divided into three periods confirming the acute phase (1-10 days post-onset (DPO)), early convalescent phase (11-20 DPO), and late convalescent phase (>20 DPO). The cut-off titers for MAT and IgM ELISA were determined to be 1:160 and 1:80, respectively, for all three periods. These cut-off titers combined 100% specificity with a sensitivity that varied depending on the disease stage for both tests. The low sensitivity in the early acute phase is consistent with the dynamics of the humoral immune response. IgM ELISA showed higher sensitivity compared to MAT in the acute and early convalescent phases. Moreover, the optimal sensitivity of MAT, the gold standard, was <82%, implying that a significant proportion of global cases are missed by this recommended test. MAT and IgM ELISA showed partial complementarity, resulting in higher sensitivity when the results of these two tests are combined. The presence of paired samples and adequate clinical and epidemiological data are other parameters that will significantly increase the sensitivity of laboratory confirmation. This study allows for improvements in the current laboratory definition to improve case detection and implies that reliable validation of laboratory parameters for case definition will improve both diagnostics for individual patient care and assessment of disease burden globally.