Abstract
BackgroundScrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk.Methods/principal findingsWe studied IgG antibody levels against O. tsutsugamushi at presentation in 636 scrub typhus patients using enzyme-linked immunosorbent assays (ELISA). The association between ELISA optical density (OD) and risk of severe infection was modelled using Poisson regression. OD was categorised as low (<1.0), intermediate (1.0 to 2.9), and high (≥3.0). OD was also modelled as a continuous variable (cubic spline). Median age of cases was 41 years (range 0–85), with 37% having severe infection. Compared to the low category, the age-adjusted risk of severe infection was 1.5 times higher in the intermediate category (95%CI 1.2, 1.9), and 1.3 times higher in the high category (95%CI 1.0, 1.7). The effect was stronger in cases <40 years, doubling the risk in the intermediate and high categories compared to the low category. The effect was more pronounced in cases tested within 7 days of fever onset when IgG ODs are more likely to reflect pre-infection levels.Conclusions/SignificanceIntermediate and high IgG antibody levels at the time of diagnosis are associated with a higher risk of severe scrub typhus infection. The findings may be explained by severe infection eliciting an accelerated IgG response or by previous scrub typhus infection enhancing the severity of subsequent episodes.
Highlights
Scrub typhus is a potentially life-threatening febrile illness caused by bacterial species belonging to the genus Orientia [1]
The findings may be explained by severe infection eliciting an accelerated IgG response or by previous scrub typhus infection enhancing the severity of subsequent episodes
Scrub typhus is caused by intracellular bacteria of the Orientia genus, and is among the most common causes of febrile illness in many parts of Asia
Summary
Scrub typhus is a potentially life-threatening febrile illness caused by bacterial species belonging to the genus Orientia (family Rickettsiaceae) [1]. Scrub typhus occurs over much of tropical and subtropical Asia as well as Chile [3]. Scrub typhus accounts for 15% to 40% of febrile illness leading to hospitalisations [4,5,6]. Common manifestations of severe infection include acute respiratory distress syndrome (ARDS), meningo-encephalitis, shock and renal failure [4,9]. Scrub typhus is a dominant cause of febrile illness in many parts of Asia. Immunity is limited by the great strain diversity of Orientia tsutsugamushi. It is unclear whether previous infection protects from severe infection or enhances the risk
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