Dengue fever is a mosquito-borne tropical disease that can develop into the life-threatening dengue hemorrhagic fever/dengue shock syndrome. There are currently no standard biomarkers or algorithms for the prognosis of the progression to hemorrhagic fever or potentially fatal shock syndrome. In the latest issue of PLOS Neglected Tropical Diseases scientists from Colorado State University explore the use of small molecules in patient serum for diagnosis of dengue fever and potentially predicting progression to the severe disease.
In a collaboration with colleagues from the University of California, Berkeley, the Nicaraguan Ministry of Health, and the University of Yucatan, Mexico, the researchers analyzed serum samples from dengue patients in Mexico and Nicaragua. They used liquid chromatography and mass spectrometry to identify molecular features in patients diagnosed with dengue fever, dengue hemorrhagic fever/dengue shock syndrome or non-dengue disease groups. As per earlier studies by others, they confirmed that infection with dengue virus perturbs the human metabolome; the set of small molecule metabolites within the serum sample. They also found many metabolites had statistically significant differences in pair-wise comparisons between the three diagnostic groups.
In the Nicaraguan samples, distinct metabolic clusters were associated with the three different diagnostic groups. However this effect was not seen in the Mexican samples. The researchers suggest this may be due to much greater diversity in both the disease (two different serotypes and no available information on immune status) and the patients in Mexico, who had a larger age distribution compared with the pediatric-only Nicaraguan samples. It is clear that metabolic profiles for the disease will differ between region, patient age, genetic background, and disease status, nonetheless, similar trends were found for many metabolites that differentiated disease outcomes in the two groups.
In order to explore whether differences in the metabolome might be used to predict dengue outcomes, the researchers studied 31 samples from Nicaragua. 16 of these patients progressed from dengue fever to hemorrhagic fever/dengue shock syndrome while the remaining 15 did not. 65 metabolites were found that differentiated the two disease outcomes. Six of these prognostic metabolites have thus far been structurally confirmed.
By identifying and profiling molecules that differ between different forms of dengue, the researchers lay the foundations for finding biomarkers present at early-stage dengue that are able to predict disease development. An early predictor of dengue hemorrhagic fever/dengue shock syndrome would allow appropriate triaging of patients for management and treatment. An understanding of the metabolic profile of infected patients also provides insights into the intracellular pathways instrumental in dengue infection, replication and pathogenesis.
"Metabolomics provides new opportunities and a powerful approach to investigate potential viral, host, pathogenic and immunological determinants of dengue infection and pathogenesis," explains Dr. Barry Beaty, from the Colorado State University. The research team is currently conducting a prospective clinical study in Nicaragua to further identify small molecule biomarker "biosignatures" for efficient diagnosis and prognosis of dengue.
Please contact firstname.lastname@example.org if you would like more information about our content and specific topics of interest.
All works published in PLOS Neglected Tropical Diseases are open access, which means that everything is immediately and freely available. Use this URL in your coverage to provide readers access to the paper upon publication:
Funding: This work was supported by National Institute of Health grants U54AI065357 and R21/R33AI100186.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
About PLOS Neglected Tropical Diseases
PLOS Neglected Tropical Diseases is a peer-reviewed, open-access journal devoted to the pathology, epidemiology, prevention, treatment, and control of the neglected tropical diseases, as well as public policy relevant to this group of diseases. All works published in PLOS Neglected Tropical Diseases are open access, which means that everything is immediately and freely available subject only to the condition that the original authorship and source are properly attributed. The Public Library of Science uses the Creative Commons Attribution License, and copyright is retained by the authors.
About the Public Library of Science
The Public Library of Science (PLOS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.
PLOS Journals publish under a Creative Commons Attribution License, which permits free reuse of all materials published with the article, so long as the work is cited (e.g., Kaltenbach LS et al. (2007) Huntington Interacting Proteins Are Genetic Modifiers of Neurodegeneration. PLOS Genet 3(5): e82. doi:10.1371/journal.pgen.0030082). No prior permission is required from the authors or publisher. For queries about the license, please contact the relative journal contact indicated here: http://www.