Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin

Abstract

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes. From January 2014 to September 2017, 431 patients with FUO were prospectively enrolled in the study population. This study established a list of 26 variables from the following 4 aspects: host factors, epidemiological factors, behavioral factors, and iatrogenic factors. Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model. The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified. These factors were incorporated into the predictive model. This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72, sensitivity of 0.71, and specificity of 0.63. The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

References

[1] PetersdorfRG, BeesonPB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore), 1961, 40: 1-30

[2] DurackDT, LukesAS, BrightDK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med, 1994, 96(3): 200-209

[3] HorowitzHW. Fever of unknown origin or fever of too many origins. N Engl J Med, 2013, 368(3): 197-199

[4] HuY, LuH, ZhangY, et al.. Fever of unknown origin: revisit of 142 cases in a tertiary Chinese hospital. Biosci Trends, 2008, 2(1): 44-46

[5] VanderschuerenS, KnockaertD, AdriaenssensT, et al.. From prolonged febrile illness to fever of unknown origin: the challenge continues. Arch Intern Med, 2003, 163(9): 1033-1041

[6] CunhaBA. Fever of unknown origin: focused diagnostic approach based on clinical clues from the history, physical examination, and laboratory tests. Infect Dis Clin North Am, 2007, 21(4): 1137-1187

[7] Bleeker-RoversCP, VosF d, KleijnEM, et al.. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore), 2007, 86(1): 26-38

[8] KayaA, ErgulN, KayaSY, et al.. The management and the diagnosis of fever of unknown origin. Expert Rev Anti Infect Ther, 2013, 11(8): 805-815

[9] EfstathiouSP, PefanisAV, TsiakouAG, et al.. Fever of unknown origin: discrimination between infectious and non-infectious causes. Eur J Intern Med, 2010, 21(2): 137-143

[10] ArvanitiV, D'AmicoG, FedeG, et al.. Infections in patients with cirrhosis increase mortality fourfold and should be used in determining prognosis. Gastroenterology, 2010, 139(4): 1246-1256

[11] HuelsenbeckJP, HillisDM, NielsenR. A likelihoodratio test of monophyly. Syst Biol, 1996, 45(4): 546-558

[12] KimSE, KimUJ, JangMO, et al.. Diagnostic use of serum ferritin levels to differentiate infectious and noninfectious diseases in patients with fever of unknown origin. Dis Markers, 2013, 34(3): 211-218

[13] LiL, ZhangJZ, ZhaoMZ, et al.. Applied value of monitoring serum hepcidin in differential diagnosis of infection versus tumor fevers. J Huazhong Univ Sci Technol Med Sci, 2017, 37(2): 253-256

[14] Si-TaharM, TouquiL, ChignardM. Innate immunity and inflammation—two facets of the same anti-infectious reaction. Clin Exp Immunol, 2009, 156(2): 194-198

[15] AkgulY, WordRA, EnsignLM, et al.. Hyaluronan in cervical epithelia protects against infection-mediated preterm birth. J Clin Invest, 2014, 124(12): 5481-5489

[16] YuQ, YuanL, DengJ, et al.. Lactobacillus protects the integrity of intestinal epithelial barrier damaged by pathogenic bacteria. Front Cell Infect Microbiol, 2015, 5: 26

[17] YamaguchiT, YamadaH. Role of mechanical injury on airway surface in the pathogenesis of Pseudomonas aeruginosa. Am Rev Respir Dis, 1991, 144(5): 1147-1152

[18] Al DahoukS, NocklerK, HenselA, et al.. Human brucellosis in a nonendemic country: a report from Germany, 2002 and 2003. Eur J Clin Microbiol Infect Dis, 2005, 24(7): 450-456

[19] DeshpandeA, SmithGW, SmithAJ. Biofouling of surgical power tools during routine use. J Hosp Infect, 2015, 90(3): 179-185

[20] MaugarsY, AlbertJD, BardH, et al.. Prevention of iatrogenic infections in interventional rheumatology: Optimal measures but adapted to each risk. Joint Bone Spine, 2016, 83(3): 250-253

[21] HigaJT, GluckM, RossAS. Duodenoscope-Associated Bacterial Infections: A Review and Update. Curr Treat Options Gastroenterol, 2016, 14(2): 185-193

[22] Mulders-MandersC, SimonA, Bleeker-RoversC. Fever of unknown origin. Clin Med (Lond), 2015, 15(3): 280-284

[23] ErgonulO, WillkeA, AzapA, et al.. Revised definition of 'fever of unknown origin': limitations and opportunities. J Infect, 2005, 50(1): 1-5

[24] BryanCS, AhujaD. Fever of unknown origin: is there a role for empiric therapy. Infect Dis Clin North Am, 2007, 21(4): 1213-1220

[25] BerjohnCM, FishmanNO, JoffeMM, et al.. Treatment and Outcomes for Patients with Bacteremic Pneumococcal Pneumonia. Medicine (Baltimore), 2008, 87(3): 160-166

[26] CinelI, DellingerRP. Advances in pathogenesis and management of sepsis. Curr Opin Infect Dis, 2007, 20(4): 345-352

[27] Clec'hC, TimsitJF, De LassenceA, et al.. Efficacy of adequate early antibiotic therapy in ventilator-associated pneumonia: influence of disease severity. Intensive Care Med, 2004, 30(7): 1327-1333

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