Evaluation of combined rapid immunoglobulin M and immunoglobulin G lateral flow assays for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection

Abstract

© 2020, Faculty of Medicine Siriraj Hospital, Mahidol University. Objective: Leptospirosis, scrub typhus, and hantavirus infection are commonly identified as causes of acute undifferentiated fever in rural parts of Asia. Although the characteristic presentations of these infections are well described, many of them present with nonspecific manifestations. Diagnosis is usually made by combined history of exposure, clinical features and positive antibody detection. The development of rapid antibody detection assay, using an immunochromatographic test (ICT) for the diagnosis of multi-diseases, has provided tools for more accurate diagnosis and appropriate antibiotic treatment of the acute undifferentiated fever syndrome. Methods: We evaluated the diagnostic performance of a commercially available combined rapid ICT for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection, using archived blood samples from 434 patients with laboratory-confirmed leptospirosis (131) or scrub typhus (128), and from patients with other causes of fever as the negative control (175). Polysaccharide of nonpathogenic Leptospira patoc, a chimeric recombinant protein cr56 and two other recombinant proteins, r21 and kr56, from different serotypes of Orientia tsutsugamushi, and 21kDa species-specific antigen and recombinant CNP antigen derived from the Soochong virus were used as antigens for the diagnosis of leptospirosis, scrub typhus, and hantavirus infection in the combined ICT used in this study. Results: For the diagnosis of leptospirosis; in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 38.2% (95% CI, 29.9-46.5%), and 99.0% (95% CI 97.9-100%); while in convalescent phase, the same were 84.6% (95%CI, 77.1-92.0%), and 96.2% (95%CI, 92.5-99.8%), respectively. For scrub typhus, in acute phase, the sensitivity and specificity of the ICT detection of IgM/IgG were 71.9% (95% CI, 64.1-79.7%), and 97.4% (95% CI 95.6-99.2%); while in convalescent phase, the same were 84.6% (95%CI, 74.8-94.4%), and 90.2% (95%CI, 85.3-95.1%) respectively. For hantavirus infection, nine patients had detectable IgM for hantavirus infection. All these cases were diagnosed as scrub typhus by indirect immunofluorescent assay. Conclusion: The performance of this combined ICT for leptospirosis and scrub typhus were comparable to those published data of other ICTs. However, the rapid test for the diagnosis of leptospirosis, using antigen detection, is needed. Hantavirus infection was not detected in this study population.