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Patients were screened for dengue and chikungunya virus, <jats:italic>Plasmodium<\/jats:italic>,<jats:italic> Brucella<\/jats:italic>, <jats:italic>Neisseria meningitidis<\/jats:italic>, group A streptococcus and <jats:italic>Leptospira<\/jats:italic>. Clinical history and biochemical parameters from blood tests were collected. Patient sera of selected disease\u2010confirmed infections were quantified for immune mediators by multiplex microbead\u2010based immunoassays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Approximately 20% of febrile patients were tested positive for one of the pathogens, and they presented overlapping clinical and laboratory parameters. Nonetheless, eight disease\u2010specific immune mediators were identified as potential biomarkers for dengue (MIP\u20101\u03b1, MCP\u20101), malaria (TNF\u2010\u03b1), streptococcal and meningococcal (eotaxin, GRO\u2010\u03b1, RANTES, SDF\u20101\u03b1 and PIGF\u20101) infections, with high specificity and sensitivity profiles. Notably, based on the conditional inference model, six of these mediators (MIP\u20101\u03b1, TNF\u2010\u03b1, GRO\u2010\u03b1, RANTES, SDF\u20101\u03b1 and PIGF\u20101) were revealed to be 68.4% accurate in diagnosing different febrile infections, including those of unknown diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study is the first extensive characterisation of the clinical analysis and immune biomarkers of several clinically important febrile infections in Saudi Arabia. Importantly, an immune signature with robust accuracy, specificity and sensitivity in differentiating several febrile infections was identified, providing useful insights into patient disease management in the Arabian Peninsula.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1163","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T02:43:42Z","timestamp":1598150622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Systematic analysis of disease\u2010specific immunological signatures in patients with febrile illness from Saudi Arabia"],"prefix":"10.1002","volume":"9","author":[{"given":"Yiu\u2010Wing","family":"Kam","sequence":"first","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology and Research (A*STAR) Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed 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