Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions (original) (raw)

Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as coinfections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management. Dengue (DEN) and chikungunya (CHIK) are among the most important vector borne diseases, together affecting about 40 million people globally 1-3. Dengue is an acute systemic viral disease that has established itself globally in both endemic and epidemic transmission cycles 4. With more than one-third of the world population living in areas at risk of this infection, dengue virus is a leading cause of illness and death in the tropics and subtropics 5. Global distribution map of dengue has estimated and predicted India to be the worst affected 6. In India dengue contributes about 34% of the total global infections making it a transmission hub 7. Known to occur as either single infections or as co-infections with dengue 8,9 , Chikungunya virus (CHIKV) poses a serious threat to public health 10 with spread to many parts of the globe 11. In the Indian sub-continent, while as many as 1.2 million individuals were affected by CHIK in 2006 12 , recent trends have shown it be declining though numbers are still large 13. One of the main challenges that clinicians face during diagnosis of CHIK and DEN are overlapping symptoms of these two infections resulting in gross misdiagnosis and patient mismanagement 14. Recent studies have shown that almost ten percent of suspected dengue cases are in fact co-infected with chikungunya virus making it imperative to distinguish the difference between the two infections for better patient management 15. Additionally, misdiagnosis also obstructs the true incidence of chikungunya within a region thereby providing incorrect information of epidemiology of the disease and evolution of the virus. There are infection associated independent