ABSTRACT
Dengue, an arboviral disease is a global threat to public health as the number of Dengue cases increases through the decades and this trend is predicted to continue. Non-communicable diseases such as diabetes and obesity are also on an upward trend. Moreover, past clinical studies have shown comorbidities worsen the clinical manifestation of especially Severe Dengue. However, discussion regarding the underlying mechanisms regarding the association between these comorbidities and dengue are lacking. The hallmark of Severe Dengue is plasma leakage which is due to several factors including presence of pro-inflammatory cytokines and dysregulation of endothelial barrier protein expression. The key factors of diabetes affecting endothelial functions are Th1 skewed responses and junctional-related proteins expression. Additionally, obesity alters the lipid metabolism and immune response causing increased viral replication and inflammation. The similarity between diabetes and obesity individuals is in having chronic inflammation resulting in endothelial dysfunction. This review outlines the roles of diabetes and obesity in severe dengue and gives some insights into the plausible mechanisms of comorbidities in Severe Dengue.
ABSTRACT
BACKGROUND: The loss of a close relative is one of the most stressful life events. In pregnancy, this experience has been associated with a higher risk of fetal death and under-five mortality, but little is known about potential effects on long-term mortality in offspring. We examined the association between prenatal maternal bereavement and mortality in a cohort of 5.3 million children followed until up to 37 years of age. METHOD: The population-based cohort study included 5 253 508 live singleton births in Denmark (1973-2004) and Sweden (1973-2006). Children born to mothers who lost a child, spouse, sibling, or parent during or 1 year before pregnancy were categorized as exposed. RESULTS: Prenatal maternal bereavement was associated with a 10% increased all-cause mortality risk in offspring [mortality rate ratio (MRR) 1.10, 95% confidence interval (CI) 1.03-1.18]. The association was the most pronounced for children of mothers who lost a child/spouse (MRR 1.28, 95% CI 1.14-1.44) and was stronger during the first 10 years of life. Prenatal maternal bereavement may have stronger effects on natural causes of death in offspring, including infectious/parasitic disease (MRR 1.86, 95% CI 1.07-3.23), endocrine/nutritional/metabolic diseases (MRR 3.23, 95% CI 2.02-5.17), diseases of nervous system (MRR 3.36, 95% CI 2.47-4.58), and congenital malformations (MRR 1.39, 95% CI 1.08-1.80). No excess mortality risk in offspring was observed for unnatural causes of death. CONCLUSION: Prenatal maternal bereavement was associated with an increased long-term mortality risk in offspring, particularly for selected natural causes of diseases and medical conditions. Our results support the fetal programming hypothesis that prenatal stress may contribute to ill health from physical diseases later in life.