Metabolite Profiling Predicts Outcome of Dengue Virus Infection

Dengue fever is a mosquito-borne tropical disease caused by the Dengue virus. Symptoms typically begin three to fourteen days after infection. This may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Recovery generally takes less than two to seven days. In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.

As epidemics of dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis and patient care in developing countries, identifying a panel of biomarkers in acute-phase serum specimens for prognosis of severe dengue disease would be of enormous value for appropriate triaging of patients for management.

Investigators at Colorado State University (Fort Collins, USA) decided to take advantage of advances in the field of metabolomics and analytic software to identify host small molecule biomarkers (SMBs) in acute phase clinical specimens that could differentiate dengue disease outcomes. Metabolomics is the analysis of low molecular weight biological molecules that result from metabolic processes. Disease states result in changes in metabolism in cells and systems that affect the profile of metabolites. Analysis of metabolite profiles in disease conditions and comparison with the profiles of non-diseased individuals can be used in diagnosis.

The investigators used hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry (MS) to identify small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND) diagnosis groups. They worked with serum samples obtained from dengue patients from Nicaragua and Mexico.

Results revealed that in the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes, while in the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes. Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS).

"Metabolomics provides new opportunities and a powerful approach to investigate potential viral, host, pathogenic, and immunological determinants of dengue infection and pathogenesis," said Dr. Barry Beaty, professor of virology at Colorado State University.

The work was published in the February 25, 2016, online edition of the journal PLOS Neglected Tropical Diseases.

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