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Review 2: "Obesity is Associated with Increased Pediatric Dengue Virus Infection and Disease: A 9-year Cohort Study in Managua, Nicaragua"

Reviewers found this preprint generally reliable with the significant strength of including annual testing for evidence of asymptomatic dengue infection. 

Published onMay 21, 2024
Review 2: "Obesity is Associated with Increased Pediatric Dengue Virus Infection and Disease: A 9-year Cohort Study in Managua, Nicaragua"
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Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua
Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua
Description

ABSTRACT Background Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question.Methods We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers.Results From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight.Conclusions Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.Key points We describe a doubling in the prevalence of obesity in a cohort of 5,940 Nicaraguan children followed over 9 years. Children with obesity were more likely to be infected with dengue virus and had higher risk of developing dengue disease.

RR:C19 Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review: Among the pediatric population, there is an association between obesity and dengue virus infection, which also correlates with the onset of dengue disease. Obesity can significantly influence viral infections, impacting both infection severity and the body's ability to combat them, not only in adults but also in children. Generally, obesity is correlated with an elevated risk of contracting specific viral infections. This heightened susceptibility may stem from various factors, including impaired antiviral immune function due to metabolic stress, leading to increased vulnerability to infection in specific environments and delayed viral clearance. Moreover, obese individuals are more prone to experiencing severe complications due to dysregulated or excessive chronic inflammatory responses following acute viral infection, which can lead to tissue damage.

In the case of dengue virus (DENV) infection, a potentially hazardous pathogen associated with hemorrhagic complications, obesity-related metabolic stress serves as a risk factor for vascular diseases. Acute viral infections can exacerbate this risk by triggering coagulation abnormalities, increasing the likelihood of bleeding, organ damage, and mortality. However, the precise mechanisms through which obesity affects DENV infection and disease progression remain unclear. While severe dengue cases in adults have been extensively studied for their epidemiological association with comorbidities such as obesity, hypertension, and vascular dysfunction, it remains uncertain whether similar associations exist in children.

Addressing this gap, Mercado-Hernandez et al. conducted a 9-year cohort study to investigate the relationship between obesity and DENV infection in children. Their findings reveal that obesity is linked to a heightened vulnerability to DENV infection and the occurrence of dengue, irrespective of age, gender, or pre-existing DENV antibody levels. However, obesity appears to be only partially associated with part dengue syndromes, such as fever, headache, and rash, and not with hemorrhagic manifestations, arthralgia, myalgia, leukopenia, and thrombocytopenia. These results suggest that differences in metabolic stress and immunopathogenesis between children and adults may influence the progression of dengue disease under obese conditions. To mitigate the impact of obesity on viral infections, lifestyle interventions such as dietary adjustments, increased physical activity, and weight management programs are essential. Additionally, promoting vaccination and preventive healthcare measures among obese individuals can help reduce their risk of infection and complications from dengue and other viral diseases.

In regions where dengue fever is prevalent, children frequently succumb to severe illnesses as a result of infection. Obesity frequently coexists with various infectious diseases, and this research demonstrates that obese children are particularly vulnerable to dengue virus infection and its associated symptoms. Hence, alongside efforts to prevent and treat viral infections, it is imperative to concurrently focus on educating and enhancing strategies for obesity prevention and treatment.

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