Current Medical Science

, Volume 38, Issue 6, pp 1025–1031 | Cite as

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

  • Zhu-hua Wu
  • Ming-you Xing
  • Sheng Wei
  • Man-zhi Zhao
  • Wen-xia Wang
  • Lin Zhu
  • Ji-ling Zhu
  • Cai-feng Zheng
  • Si-jun Wang
  • Jun-ying Qi
  • Jian-xin SongEmail author


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.

Key words

fever of unknown origin predictive model etiology empiric therapy 


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We would like to thank all the physicians at the hospitals around the country for their participation and data collection. This project would not have been possible without their contributions.


  1. 1.
    Petersdorf RG, Beeson PB. Fever of unexplained origin: report on 100 cases. Medicine (Baltimore), 1961,40:1–30CrossRefGoogle Scholar
  2. 2.
    Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med, 1994,96(3):200–209Google Scholar
  3. 3.
    Horowitz HW. Fever of unknown origin or fever of too many origins? N Engl J Med, 2013,368(3):197–199CrossRefGoogle Scholar
  4. 4.
    Hu Y, Lu H, Zhang Y, et al. Fever of unknown origin: revisit of 142 cases in a tertiary Chinese hospital. Biosci Trends, 2008,2(1):44–46Google Scholar
  5. 5.
    Vanderschueren S, Knockaert D, Adriaenssens T, et al. From prolonged febrile illness to fever of unknown origin: the challenge continues. Arch Intern Med, 2003,163(9):1033–1041CrossRefGoogle Scholar
  6. 6.
    Cunha BA. 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):1137–1187CrossRefGoogle Scholar
  7. 7.
    Bleeker-Rovers CP, Vos FJ, de Kleijn EM, et al. A prospective multicenter study on fever of unknown origin: the yield of a structured diagnostic protocol. Medicine (Baltimore), 2007,86(1):26–38CrossRefGoogle Scholar
  8. 8.
    Kaya A, Ergul N, Kaya SY, et al. The management and the diagnosis of fever of unknown origin. Expert Rev Anti Infect Ther, 2013,11(8):805–815CrossRefGoogle Scholar
  9. 9.
    Efstathiou SP, Pefanis AV, Tsiakou AG, et al. Fever of unknown origin: discrimination between infectious and non-infectious causes. Eur J Intern Med, 2010,21(2):137–143CrossRefGoogle Scholar
  10. 10.
    Arvaniti V, D'Amico G, Fede G, et al. Infections in patients with cirrhosis increase mortality fourfold and should be used in determining prognosis. Gastroenterology, 2010,139(4):1246–1256CrossRefGoogle Scholar
  11. 11.
    Huelsenbeck JP, Hillis DM, Nielsen R. A likelihoodratio test of monophyly. Syst Biol, 1996,45(4):546–558CrossRefGoogle Scholar
  12. 12.
    Kim SE, Kim UJ, Jang MO, 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):211–218CrossRefGoogle Scholar
  13. 13.
    Li L, Zhang JZ, Zhao MZ, 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):253–256CrossRefGoogle Scholar
  14. 14.
    Si-Tahar M, Touqui L, Chignard M. Innate immunity and inflammation—two facets of the same anti-infectious reaction. Clin Exp Immunol, 2009,156(2):194–198CrossRefGoogle Scholar
  15. 15.
    Akgul Y, Word RA, Ensign LM, et al. Hyaluronan in cervical epithelia protects against infection-mediated preterm birth. J Clin Invest, 2014,124(12):5481–5489CrossRefGoogle Scholar
  16. 16.
    Yu Q, Yuan L, Deng J, et al. Lactobacillus protects the integrity of intestinal epithelial barrier damaged by pathogenic bacteria. Front Cell Infect Microbiol, 2015,5:26CrossRefGoogle Scholar
  17. 17.
    Yamaguchi T, Yamada H. Role of mechanical injury on airway surface in the pathogenesis of Pseudomonas aeruginosa. Am Rev Respir Dis, 1991,144(5):1147–1152CrossRefGoogle Scholar
  18. 18.
    Al Dahouk S, Nockler K, Hensel A, et al. Human brucellosis in a nonendemic country: a report from Germany, 2002 and 2003. Eur J Clin Microbiol Infect Dis, 2005,24(7):450–456CrossRefGoogle Scholar
  19. 19.
    Deshpande A, Smith GW, Smith AJ. Biofouling of surgical power tools during routine use. J Hosp Infect, 2015,90(3):179–185CrossRefGoogle Scholar
  20. 20.
    Maugars Y, Albert JD, Bard H, et al. Prevention of iatrogenic infections in interventional rheumatology: Optimal measures but adapted to each risk. Joint Bone Spine, 2016,83(3):250–253CrossRefGoogle Scholar
  21. 21.
    Higa JT, Gluck M, Ross AS. Duodenoscope-Associated Bacterial Infections: A Review and Update. Curr Treat Options Gastroenterol, 2016,14(2):185–193CrossRefGoogle Scholar
  22. 22.
    Mulders-Manders C, Simon A, Bleeker-Rovers C. Fever of unknown origin. Clin Med (Lond), 2015,15(3):280–284CrossRefGoogle Scholar
  23. 23.
    Ergonul O, Willke A, Azap A, et al. Revised definition of 'fever of unknown origin': limitations and opportunities. J Infect, 2005,50(1):1–5CrossRefGoogle Scholar
  24. 24.
    Bryan CS, Ahuja D. Fever of unknown origin: is there a role for empiric therapy? Infect Dis Clin North Am, 2007,21(4):1213–1220CrossRefGoogle Scholar
  25. 25.
    Berjohn CM, Fishman NO, Joffe MM, et al. Treatment and Outcomes for Patients with Bacteremic Pneumococcal Pneumonia. Medicine (Baltimore), 2008,87(3):160–166CrossRefGoogle Scholar
  26. 26.
    Cinel I, Dellinger RP. Advances in pathogenesis and management of sepsis. Curr Opin Infect Dis, 2007,20(4):345–352CrossRefGoogle Scholar
  27. 27.
    Clec'h C, Timsit JF, De Lassence A, et al. Efficacy of adequate early antibiotic therapy in ventilator-associated pneumonia: influence of disease severity. Intensive Care Med, 2004,30(7):1327–1333CrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2018

Authors and Affiliations

  • Zhu-hua Wu
    • 1
    • 3
  • Ming-you Xing
    • 1
  • Sheng Wei
    • 2
  • Man-zhi Zhao
    • 1
  • Wen-xia Wang
    • 1
  • Lin Zhu
    • 1
  • Ji-ling Zhu
    • 1
  • Cai-feng Zheng
    • 1
  • Si-jun Wang
    • 1
  • Jun-ying Qi
    • 1
  • Jian-xin Song
    • 1
    Email author
  1. 1.Department of Infectious Diseases, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of Oncologythe Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangChina

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