Disease-specific plasma protein profiles in patients with fever after traveling to tropical areas

Abstract

Objectives Fever is common among individuals seeking healthcare after traveling to tropical regions. Despite the association with potentially severe disease, the etiology is often not determined. Cytokines are soluble mediators dynamically regulated in the response to infection. Measuring cytokines in the blood can therefore be informative to understanding the host-response to infection and can potentially indicate the type of pathogen that causes the disease. Method In this study, we measured 49 host-response proteins in the plasma of 124 patients with fever after travel to tropical or subtropical regions. The patients had confirmed diagnosis of either P. falciparum malaria, dengue virus, influenza virus, bacterial respiratory tract infection, or culture-confirmed bacterial gastroenteritis, representing the most common disease etiologies. We used multivariate and machine learning methods to assess host-response protein profiles between the different disease groups and healthy control subjects with the aim to identify disease-specific protein signatures. Results The host-response varied between disease groups and combinations of cytokines and other proteins could accurately distinguish infected patients from healthy controls, and from each other. Malaria displayed the most unique protein signature, indicating a strong immunoregulatory response with high levels of IL10, sTNFRI and II, and sCD25 but low levels of sCD40L. In contrast, bacterial gastroenteritis had high levels of sCD40L, APRIL, and IFN-g, while dengue was the only infection with elevated IFNa2. Conclusions These results suggest that characterization of the inflammatory profile of individuals with fever can help to identify disease-specific host-responses, which in turn can be used to guide further diagnostic strategies.