Elevated chymase levels in serum predict severe dengue
Researchers identified elevated chymase as a prognostic biomarker of severe disease in adult and pediatric patients with dengue fever.
According to Annelies Wilder-Smith, MD, PhD, MIH, professor of infectious diseases at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, and president of the International Society of Travel Medicine, traditional indicators of severe dengue, or dengue hemorrhagic fever (DHF), include mucosal bleeding, liver enlargement, abdominal pain, rapid hematocrit increase, persistent vomiting and clinical fluid accumulation. However, the researchers noted that many of these signs present late and vary among patients with dengue virus (DENV) infection.
“There is an unmet need for diagnostic tests to identify severe DENV during the acute phase of disease, since clinical symptoms often fail to predict it with sufficient warning, and to understand whether those tests are robust in multiple patient populations,” the researchers wrote in The Journal of Infectious Diseases.
During a previous study, Wilder-Smith and colleagues found that chymase levels were higher among patients with DHF in Singapore. To further explore the association, the researchers measured chymase levels in serum samples obtained from 347 febrile patients with dengue fever who were treated at one of six clinical sites in the Colombo district of Sri Lanka. Among the participants, 91% were confirmed to have dengue fever and 29.6% (n = 99) were eventually diagnosed with DHF. Only 4% of those with DHF were diagnosed with the condition at the time of admission, underscoring the difficulty of predicting the clinical course of dengue fever during acute disease, according to the researchers.
Diarrhea was significantly associated with DHF among DENV-confirmed patients. However, the prevalence of other hemorrhagic manifestations, aside from bleeding per vaginam, were similar between patients with and without DHF.
The researchers found that early chymase elevation in serum was a significant predictor of subsequent DHF among DENV-confirmed patients before clinical signs were apparent (P = .0001). After adjusting for independent variables, the odds of having DHF were 1.32 (95% CI, 1.21-1.44) times higher with every unit increase in chymase. Chymase predicted DHF diagnosis with a sensitivity of 0.96 and specificity of 0.79 when using a cutoff value of 1.5 ng/mL. It was also associated with a positive predictive value of 76% and a negative predictive value of 97%.
“Together, our data demonstrate that chymase is a strong predictor of DHF in acute-phase febrile patients, with the potential to identify those at risk for complications more robustly and at earlier time points than many clinical warning signs,” Wilder-Smith and colleagues wrote.
The researchers conducted an additional analysis to assess whether pre-existing conditions may influence serum chymase levels during acute dengue infection. Although chymase levels were higher in patients with certain conditions, including obesity and lung-associated conditions, this did not significantly impact chymase as a biomarker of DHF.
Despite these findings, the researchers noted that chymase induction is not specific to DENV and may occur in patients with bacterial infections and noninfectious inflammatory conditions such as asthma or anaphylaxis.
“Thus, serum chymase alone should not serve as a diagnostic test for DENV and, for DENV prognosis, must be interpreted with other tests to confirm infection or in the context of a strong suspicion of DENV,” they wrote. – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.