Serum fatty acids and progression from dengue fever to dengue haemorrhagic fever/dengue shock syndrome

Abstract

Polyunsaturated fatty acids (PUFA) might modulate inflammatory responses involved in the development of severe dengue. We aimed to examine whether serum PUFA concentrations in patients diagnosed with dengue fever (DF) were related to the risk of progression to dengue hemorrhagic fever / dengue shock syndrome (DHF/DSS). A secondary aim was to assess correlations between fatty acids (FA) and inflammatory biomarkers in DF patients. We conducted a prospective case-control study nested within a cohort of DF patients who were followed during the acute episode. We compared the distribution of individual FA % of total FA concentration at onset of fever between 109 cases who progressed to DHF/DSS and 235 DF non progressing controls using unconditional logistic regression. We estimated correlations between baseline FA and cytokine concentrations, and compared FA concentrations between the acute episode and >1 y post-convalescence in a subgroup. Docosahexaenoic acid (DHA) was positively related to progression to DHF/DSS (multivariable adjusted odds ratio [AOR] for DHA in quintile 5 vs. 1 = 5.34, 95% confidence interval [CI]: 2.03, 14.1; P, trend = 0.007). Dihomo-γ-linolenic acid (DGLA) was inversely associated with progression (AOR for quintile 5 vs. 1 = 0.30, 95% CI: 0.13, 0.69; P, trend = 0.007). Pentadecanoic acid concentrations were inversely related to DHF/DSS. Correlations of PUFA with cytokines at baseline were low. PUFA were lower during the acute episode than in a disease-free period. In conclusion, serum DHA in DF patients predicts higher odds of progression to DHF/DSS whereas DGLA and pentadecanoic acid predict lower odds.

Metabolomic Insights into Human Arboviral Infections: Dengue, Chikungunya, and Zika Viruses

“…Glycerolipids can have one, two, or three fatty acyl groups esterified to a glycerol backbone and are termed mono-, di- and triacylglycerols (or triglycerides). Glycerolipid usage is altered in humans during infection with DENVs [24,88,89]. Increased levels of four triacylglycerols differentiated DENV4-infected patients in Brazil during febrile illness from healthy controls [89].…”

“…The fatty acyls assayed by Khedr et al [88] were chemically derived from lipids in whole blood, unlike the free fatty acids that Cui et al [20] and Voge et al [22] assayed in human sera. This work was extended by Villamor et al [24], who assayed levels of most of the same fatty acids chemically derived from larger lipid molecules using targeted GC-MS metabolomics to prognostically differentiate DHF/DSS from DF. The sera used were collected from Columbian dengue patients within 96 hours of the onset of fever.…”

“…The sera used were collected from Columbian dengue patients within 96 hours of the onset of fever. Villamor et al [24] found that elevated DHA and AA levels and lower levels of DGLA and pentadecanoic acid relative to total fatty acids indicated the patient likely had DHF/DSS rather than DF. Because it inhibits inflammatory eicosanoid biosynthesis, Villamor et al [24] proposed DGLA as a potential therapeutic against DENVs.…”

“…Comparing patients infected with DENVs to febrile patients that have illnesses not caused by DENVs identified metabolites that may improve the clinical diagnosis of DENVs [21,22]. Prognostic biosignatures that separate severe forms of dengue from milder forms have been developed [21,22,23,24]. Metabolomic studies have suggested that prescribing uric acid or dihomo-γ-linolenic acid (DGLA) may ameliorate dengue disease [24,25].…”

“…Prognostic biosignatures that separate severe forms of dengue from milder forms have been developed [21,22,23,24]. Metabolomic studies have suggested that prescribing uric acid or dihomo-γ-linolenic acid (DGLA) may ameliorate dengue disease [24,25]. Another study linked metabolites to the symptoms of CHIKV infection [26].…”