The progression of dengue fever into life-threatening dengue hemorrhagic fever or dengue shock syndrome can be predicted by analyzing patient serum for metabolites associated with dengue virus infection, a proof of concept study suggests.

Researchers led by Natalia V. Voge, Ph.D., of Colorado State University, Fort Collins, said that because dengue fever had the potential to develop into life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), “the ability to predict these severe outcomes using acute phase clinical specimens would be of enormous value to physicians and health care workers for appropriate triaging of patients for clinical management” (PLOS Negl Trop Dis. 2016. doi: 10.1371/journal.pntd.0004449 ).

Advances in the field of metabolomics provided new opportunities to identify host small molecule biomarkers (SMBs) in acute phase clinical specimens that differentiate dengue disease outcomes, they said.

Collaborating with colleagues from the University of California, Berkeley, the Nicaraguan Ministry of Health, and the University of Yucatan, Mexico, the researchers used liquid chromatography and mass spectrometry to analyze 88 serum samples from Nicaraguan pediatric patients with diagnosed DHF/DSS or ND, and 101 serum samples from pediatric and adult Mexican patients.

In the Nicaraguan samples, the researchers identified metabolites that were associated with and differentiated DHF/DSS, DF, and non-dengue febrile illness outcomes, primary and secondary virus infections, and infections with different dengue virus serotypes.

“These metabolites provide insights into metabolic pathways that play roles in dengue virus infection, replication, and pathogenesis,” they wrote.

For instance, some were associated with “lipid metabolism and regulation of inflammatory processes controlled by signaling fatty acids and phospholipids, and others with endothelial cell homeostasis and vascular barrier function.”

The findings were not seen in the Mexican samples, which Dr. Voge and her associates said could reflect the diversity of the disease and the Mexican patients, who had a larger age distribution, compared with the pediatric Nicaraguan population.

Nevertheless, their results provided a proof of concept that “differential perturbation of the serum metabolome” is associated with different dengue infections and disease outcomes, they said.

Dr. Voge and her associates cautioned that while the results were encouraging, they were based on a small sample size and additional studies would be needed to confirm the results.

The findings were restricted to pediatric Nicaraguan patients and the same metabolites may not be predictive of progression to DHF/DSS in adult Nicaraguan patients or in patients from other geographic, genetic, and environmental backgrounds, they added.

The research was supported by National Institutes of Health grants.


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