The nutritional status is a strong predictor of the risk and outcome of infections. Dengue infection is highly endemic in populations that are subject to nutritional deficiencies;yet little is known regarding the role that those deficiencies could playon the progression from dengue fever to life-threatening forms of dengue, including dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). Fatty acids obtained from diet play a significant role as modulators of immunity and inflammation. N-3 polyunsaturated fatty acids (PUFA) from fish exhibit potent anti-inflammatory and inflammation-resolving properties through the actions of resolvins, metabolic products that act on neutrophils, macrophages, dendritic cells, and T cells. N-3 PUFA also decrease mononuclear cell production of pro-inflammatory cytokines by modifying the activity of nuclear transcription factor B. Some n-6 fatty acids exhibit antiviral activity. In addition, incorporation of PUFA into immune cell membrane microdomains modulates MHC surface expression and antigen presentation activity. Several of these mechanisms may be involved in the pathophysiology of DHF/DSS but the potential role of fatty acids on progression to severe manifestations of dengue infection is unknown. In this study we examine the associations of serum n-3 and n-6 fatty acid concentrations among patients diagnosed with dengue fever (DF) and their risk of developing DHF/DSS. We will conduct a prospective investigation in the context of a cohort of patients diagnosed with DF at ambulatory health centers of the city of Bucaramanga, Colombia. The serum fatty acids profile at the time of DF diagnosis will be compared between 124 patients who developed DHF/DSS during follow-up of the acute episode and 504 patients who did not progress to DHF/DSS. Results of this study will provide a basis to consider the effect of supplementation with these inexpensive nutrients during treatment of acute DF to prevent progression to severe forms of the disease.

Public Health Relevance

The purpose of this study is to examine the associations of serum fatty acids with risk of progression to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) among patients with an acute episode of dengue fever (DF). This prospective study will be conducted using stored samples and data from a cohort of patients diagnosed with DF at ambulatory centers of the city of Bucaramanga, Colombia, who were followed during the acute episode. We propose to analyze fatty acids concentrations in stored serum samples and compare the fatty acids profile between patients who developed DHS/DSS and those who did not progress to these severe forms of the disease. This study will provide a basis to consider supplementation with fatty acids during treatment of acute DF for prevention of progression to life-threatening forms of the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI103364-01A1
Application #
8637385
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Cassetti, Cristina
Project Start
2014-02-01
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$212,447
Indirect Cost
$75,825
Name
University of Michigan Ann Arbor
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109