Accuracy of rapid lateral flow immunoassays for human leptospirosis diagnosis: A systematic review and meta-analysis

Background: In the last two decades, several rapid lateral flow immunoassays (LFIs) for the diagnosis of human leptospirosis were developed and commercialized. However, the accuracy and reliability of these LFIs are not well understood. In this study, we aimed to evaluate the accuracy of leptospirosis LFIs as well as the factors affecting the test efficiency using systematic review and meta-analysis. Methods and results: Original articles reporting the accuracy of human leptospirosis LFIs against microagglutination tests (MAT) or immunofluorescent assays (IFA) were searched from PubMed, Embase, and Scopus, and selected as per pre-set inclusion and exclusion criteria. A total of 49 data entries extracted from 24 eligible records published between 2003 and 2023 were included for meta-analysis. A meta-analysis was performed using STATA. The quality of the included studies was assessed according to the revised QUADAS-2. Only nine studies (32.1%) were considered to have a low risk of bias and no concern for applicability. Pooled sensitivity and specificity were calculated to be 68% (95% confidence interval, CI: 57–78) and 93% (95% CI: 90–95), respectively. However, the ranges of sensitivity (3.6 – 100%) and specificity (53.5 – 100%) of individual entries are dramatically broad, possibly due to the heterogeneity found in both study designs and LFIs themselves. Subgroup analysis demonstrated that IgM detection has better sensitivity than detection of IgG alone. Moreover, the test performance seems to be unaffected by samples from different phases of infection. Conclusions: The pooled specificity of LFIs observed is somewhat acceptable, but the pooled sensitivity is low. These results, however, must be interpreted with caution because of substantial heterogeneity. Further evaluations of the LFIs with well-standardized design and reference test will be needed for a greater understanding of the test performance. Additionally, IgM detection type should be employed when leptospirosis LFIs are developed in the future. Author summary: Several rapid lateral flow immunoassays (LFIs) for the diagnosis of leptospirosis, the most common bacterial infection transmitted from animals to humans, have been developed during the last two decades. The test accuracy, however, seems inconsistent among studies, raising questions about their reliability and applicability. Systematic review and meta-analysis were exploited to answer these questions. A total of 28 studies evaluating the human leptospirosis LFIs were included in this review. Major findings from our analysis include: i) the overall specificity of the LFIs is likely acceptable (93%), but the sensitivity is significantly low (68%); ii) substantial variation among studies was observed, alerting the reliability of this meta-analysis results; iii) the accuracy of the LFIs seems to be unaffected by samples collected from different phases of infection (acute vs. convalescent); and iv) IgM detection LFIs exhibit higher sensitivity as compared to IgG detection type. From our findings, we suggest that IgM detection LFIs should be focused on for future development. Also, in order to understand the performance of the LFIs better, other evaluation studies are still needed.