Abstract
There is no definitive predictor of dengue severity, and this has led to a very large number of unnecessary hospitalizations worldwide. Although mast cell mediators are believed to a play role in dengue severity, the lack of precise kinetic data demands further research on early predictors. We enrolled 111 patients with confirmed dengue and 85 with “other febrile illness” (OFI) in a hospital-based prospective study in Vietnam. Dengue patients were classified as level 1, 2, or 3 based on the clinical intervention received. Blood samples were collected from each patient every day (pre- and post-defervescence) and after discharge. Plasma chymase, total IgE, and dengue-specific IgE were measured. Dengue-specific IgE levels showed an increasing trend during the course of illness and remained high even at post-discharge, although no significant difference was observed among severity levels. Total IgE showed no such trend. The specific IgE/total IgE ratio (S/T ratio) remained constantly higher in level 3 patients compared to other levels, with a significant difference at some time points. The S/T ratio of acute phase samples (before defervescence) tended to increase with increasing severity (level 1 < 2 < 3), and was significantly higher in level 3 patients than in level 1 and OFI patients. As an early predictor of severity allowing level 3 patients to be distinguished from other dengue patients, the S/T ratio achieved a sensitivity of 75% and specificity of 68%. We describe the kinetic profiles of IgEs, their ratio, and chymase levels at different severity levels. The S/T ratio was found to be associated with dengue severity, suggesting that it could potentially be used as an early predictor of severity.
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Acknowledgments
The authors would like to thank all of the participants who generously enrolled in this study. This study was conducted (in part) at the Joint Usage/Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan.
Funding
This work was supported by Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) (Grant Number 16fm0108001h0002 to KH).
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MI, SPD, LNW, VTQH, KM, NTH, KH conceived and designed the study. MI, SPD, MMNT, LHP, NVT, TVA, LNW, VTQH performed the experiments and collected samples. MI, SPD, SM, DHM, NTH, KH analyzed and interpreted the data. SPD, MI, NTH, KH wrote the draft. All authors contributed to the writing and revisions and approved the final manuscript.
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Ethical approval for this study was obtained from the Institutional Review Boards (IRBs) of the Pasteur Institute in Ho Chi Minh City, Vietnam (No. 602/ QD-Pas 27/12/10) and the Institute of Tropical Medicine, Nagasaki University, Japan (No. 11063072). All procedures performed in studies involving human participants were in accordance with the ethical standards of the IRBs and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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All of the participants were duly informed about the study, and written informed consent was obtained from the study participants or their guardians/parents (in the case of minors) prior to their enrolment in the study.
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Inokuchi, M., Dumre, S.P., Mizukami, S. et al. Association between dengue severity and plasma levels of dengue-specific IgE and chymase. Arch Virol 163, 2337–2347 (2018). https://doi.org/10.1007/s00705-018-3849-z
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DOI: https://doi.org/10.1007/s00705-018-3849-z