Abstract
The incidence of dengue in Latin America has increased dramatically during the last decade. Understanding the pathogenic mechanisms in dengue is crucial for the identification of biomarkers for the triage of patients. We aimed to characterize the profile of cytokines (IFN-γ, TNF-α, IL-1β, IL-6, IL-18 and IL-10), chemokines (CXCL8/IL-8, CCL2/MCP-1 and CXCL10/IP-10) and coagulation mediators (Fibrinogen, D-dimer, Tissue factor-TF, Tissue factor pathway inhibitor-TFPI and Thrombomodulin) during the dengue-4 epidemic in Brazil. Laboratory-confirmed dengue cases had higher levels of TNF-α (p < 0.001), IL-6 (p = 0.005), IL-10 (p < 0.001), IL-18 (p = 0.001), CXCL8/IL-8 (p < 0.001), CCL2/MCP-1 (p < 0.001), CXCL10/IP-10 (p = 0.001), fibrinogen (p = 0.037), D-dimer (p = 0.01) and TFPI (p = 0.042) and lower levels of TF (p = 0.042) compared to healthy controls. A principal component analysis (PCA) distinguished between two profiles of mediators of inflammation and coagulation: protective (TNF-α, IL-1β and CXCL8/IL-8) and pathological (IL-6, TF and TFPI). Lastly, multivariate logistic regression analysis identified high aspartate aminotransferase-to-platelet ratio index (APRI) as independent risk factors associated with severity (adjusted OR: 1.33; 95% CI 1.03–1.71; p = 0.027), the area under the receiver operating characteristics curve (AUC) was 0.775 (95% CI 0.681–0.869) and an optimal cutoff value was 1.4 (sensitivity: 76%; specificity: 79%), so it could be a useful marker for the triage of patients attending primary care centers.
Highlights
Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV), which belongs to the family Flaviviridae, genus Flavivirus
The aim of this study was to characterize the profile of cytokines/chemokines and coagulation mediators in order to better understand the events of the inflammatory response that have been correlated with severity in dengue, which could contribute to identification of biomarkers for the adequate triage of patients
In the period from January–March 2013, adults who met criteria for a suspected dengue case according to the guidelines of the Brazilian Ministry of Health [28] were enrolled at healthcare centers in the states of Rio de Janeiro (RJ) and Mato Grosso do Sul (MS): Rio Laranjeiras Hospital, RJ; Plantadores de Cana Hospital, RJ; Reference Center for Infectious and Parasitic Diseases (CEDIP), MS; and Guanandy Health Center, MS
Summary
Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV), which belongs to the family Flaviviridae, genus Flavivirus. Dengue is endemic in more than 100 countries, and it has been estimated that 96 million symptomatic infections occur per year with different degrees of severity [1]. America has increased dramatically during the last decade [2] due to several factors such as population growth, rapid and unplanned urbanization, migration, geographical conditions and barriers to preventive care, with a considerable economic impact on these countries [3]. In the current context of the COVID-19 pandemic, the Americas region in 2020 had a lower cumulative incidence rate of dengue than in the previous year, but this continued to be higher than the incidence rate reported for the 2016–2018 period [4]. Given the evidence of higher-than-expected persistence of dengue cases in endemic areas, the PAHO/WHO has recommended strengthening the triage of suspected dengue cases [4]
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