Abstract
Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31–365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51–64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17–95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05–6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89–3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis.
Highlights
Dengue fever, caused by dengue virus (DENV) infection, has become a significant global public health challenge due to its dramatically increasing incidence over 50-fold in the past five decades and continuing geographical expansion to new regions [1,2]
Dengue fever is a mosquito-borne tropical disease caused by the dengue virus
Our study suggested that dengue was significantly associated with an increased risk of nonvariceal upper GI bleeding within 30 days after infection but was not associated with increased medium-term (31–365 days) and long-term risks (>365 days) of upper GI bleeding
Summary
Dengue fever, caused by dengue virus (DENV) infection, has become a significant global public health challenge due to its dramatically increasing incidence over 50-fold in the past five decades and continuing geographical expansion to new regions [1,2]. DENV infection manifests as a spectrum of clinical severity that includes asymptomatic infection, classic dengue fever (DF), and severe dengue, previously known as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) [3]. Expanded dengue syndrome was coined by the World Health Organization (WHO) in 2012 to describe cases that did not fall into either DHF or DSS. Unusual manifestations with severe organ involvement, such as liver, kidneys, brain or heart involvement, have been increasingly reported in DHF cases and dengue patients without evidence of plasma leakage. These unusual manifestations may be associated with coinfections, comorbidities or complications of prolonged shock [4,5,6]. GI bleeding has been shown to be an indicator of poor prognosis in dengue patients and requires complex intensive supportive care [8,9]
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