Abstract

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Chymase is a candidate biomarker that may aid dengue prognosis. This prospective study aimed to identify whether warning signs of severe dengue, including hypovolemia and fluid accumulation, were associated with elevated chymase. Serum chymase levels were quantified prospectively and longitudinally in hospitalized pediatric dengue patients in Sri Lanka. Warning signs were determined based on daily clinical assessments, laboratory tests and ultrasound findings. Chymase was significantly elevated during the acute phase of disease in DHF or Severe dengue, defined by either the 1997 or 2009 WHO diagnosis guidelines, and persisted longer in the most severe patients. Chymase levels were higher in patients with narrow pulse pressure and clinical warning signs such as severe leakage, fluid accumulation, pleural effusion, gall-bladder wall thickening and rapid haematocrit rise concurrent with thrombocytopenia. No association between chymase and liver enlargement was observed. This study confirms that serum chymase levels are associated with DHF/Severe dengue disease in hospitalized pediatric patients. Chymase levels correlate with warning signs of vascular dysfunction highlighting the possible functional role of chymase in vascular leakage during dengue.

Highlights

  • Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF)

  • Prior human studies have indicated that chymase is an efficient biomarker for DHF prognosis since the protein levels are increased in the acute-phase serum samples from both adult and pediatric Dengue virus (DENV) cases that subsequently are diagnosed with ­DHF33,35

  • We aimed to provide more information regarding the association of chymase with severe dengue disease

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Summary

Introduction

Dengue induces a spectrum of severity in humans from the milder dengue fever to severe disease, or dengue hemorrhagic fever (DHF). Warning signs appear late in DENV disease, usually around day 5 post-fever onset, making it extremely difficult to predict DHF/DSS or Severe dengue in the early acute/febrile phase of disease. Other factors, such as high viremia and high levels of viral secretory protein NS1 have been suggested to be associated with DHF/DSS, but with conflicting r­ eports[23,24,25,26,27,28,29,30,31,32]. We hypothesized that chymase levels would be elevated in patients experiencing signs of vascular leakage and fluid accumulation, such as pleural effusion and gall bladder wall thickening

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