Kinetics of IgM and IgG antibodies after scrub typhus infection and the clinical implications

George M Varghese,Veera Manikandan Rajagopal,Paul Trowbridge,Divya Purushothaman,Sherry Joseph Martin

doi:10.1016/j.ijid.2018.03.018

George M Varghese, Veera Manikandan Rajagopal + Show 3 more

Open Access

https://doi.org/10.1016/j.ijid.2018.03.018

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Abstract

ObjectivesThe serological detection of IgM antibodies is the most widely used test to diagnose scrub typhus infection. However, the kinetics of IgM and IgG antibodies post-infection remain elusive, which could contribute to false positivity. The objective of this study was to document the nature of the evolution of these antibody titres after infection. MethodsAdult patients previously confirmed to have scrub typhus by IgM ELISA, positive PCR, or both, were included in this cross-sectional study. The levels of IgM and IgG antibodies in serum samples were tested using an ELISA and the distribution curve was plotted. ResultsTwo hundred and three patients were included in this study. Post-infection serum sampling was done between 1 month and 46 months after documented infection. IgM levels declined gradually but remained elevated above the diagnostic cut-off for up to 12 months post-infection. However, IgG levels continued to rise reaching a peak at 10 months, followed by a gradual decline over several months. In the majority of cases, the IgG levels remained above the cut-off threshold for more than 36 months. ConclusionsClinicians need to be cautious in using a single serum sample for the detection of IgM to diagnose scrub typhus, as it remains elevated for up to 12 months after the infection, whereas the serum IgG level could be used as an indicator of past infection.

Highlights

Scrub typhus is a zoonotic infection caused by the bacterium Orientia tsutsugamushi
ELISA detects IgM antibodies against the 56-kDa antigen, the major immunodominant protein located on the outer membrane of the bacteria, using a recombinant antigen (Blacksell et al, 2015)
Understanding the post-infection antibody kinetics of scrub typhus is important to guide the interpretation of IgM and IgG ELISA results

Summary

Introduction

Scrub typhus is a zoonotic infection caused by the bacterium Orientia tsutsugamushi. The clinical presentation may vary from a mild febrile illness to a life-threatening disseminated infection with serious complications such as acute respiratory distress syndrome, hepatitis, renal failure, meningitis, and multiple organ failure, making the diagnosis difficult (Varghese et al, 2013). The laboratory diagnosis of scrub typhus relies on serology or the detection of bacterial DNA in whole blood or eschar samples. ELISA detects IgM antibodies against the 56-kDa antigen, the major immunodominant protein located on the outer membrane of the bacteria, using a recombinant antigen (Blacksell et al, 2015). IgG antibody detection is usually used to diagnose past infection or to determine the community prevalence

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