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.

Geographic Variation of Infectious Disease Diagnoses Among Patients With Fever of Unknown Origin: A Systematic Review and Meta-analysis

“…Seven studies utilized a structured diagnostic protocol [ 7–9 , 17 , 19 , 23 , 24 , 31 ]. Nine studies [ 7–9 , 17–21 , 30 , 31 ] (47.4%, total n = 1268) used Peterdorf’s criteria [ 5 , 11 ] for FUO, 7 studies [ 2 , 23 , 24 , 26 , 28 , 29 , 32 ] (36.8%, total n = 1135) used Durack’s criteria [ 6 , 11 ], and 3 studies [ 22 , 25 , 27 ] (15.8%, total n = 264) used either criterion. There were 1049 (39.3%) infections, 568 (21.3%) NIIDs, and 404 (15.1%) cancers with 1236 (46.3%) total female participants.…”

“…Therefore, the ages of participants ranged from 10 to 94 years. Undiagnosed cases were reported in all but 2 studies [ 29 , 30 ] (n = 616) and occurred in 449 of 2051 (21.9%) cases. The contribution of PDCs, biochemical and immunological serology, and microbiology cultures, as well as histological and imaging studies, was insufficiently reported in several studies for analysis.…”

“…Three studies represent this region [ 2 , 29 , 30 ], although only 1 series [ 29 ] yielded additional information following attempts to contact authors of these reports [ 2 , 29 , 30 ]. Wu et al [ 29 ] from China reported 241 infections ( Table 3 ) among 431 (55.9%) patients in a single-center university hospital observational study, notably to develop a predictive model intended to distinguish infectious vs noninfectious etiologies. The contributions of diagnostic methods were not reported.…”

“…In that report, 11 cases were further confirmed by a positive CMV-DNA polymerase chain reaction (PCR) blood assay [ 34 ]. Among Western Pacific [ 29 ] and South-East Asian [ 27 ] cohorts in our analysis, EBV accounted for 18 of 21 herpesvirus cases (85.7%). Although there were 2 CMV diagnoses in our study supported by a 4-fold rise in IgG titer [ 7 , 8 ] or positive PCR [ 28 ], the majority of cases were supported by IgM serology and no study reported on clinical findings or treatment of herpesvirus infections.…”

Prospective Studies Comparing Structured vs Nonstructured Diagnostic Protocol Evaluations Among Patients With Fever of Unknown Origin

“…The total sample consisted of 2627 participants, of whom 11.7% to 58.6% had an infectious diseases etiology, 6.0% to 34.0% had a noninfectious inflammatory disorder, and 2.9% to 30.1% had an underlying oncologic condition. Undiagnosed cases were reported in all but 2 studies 27 , 29 and ranged from 6.9% to 50.7%. Nine studies 1 , 2 , 6 , 15 , 16 , 17 , 18 , 19 , 29 , 30 with 1228 of the 2627 total participants (46.7%) used the criteria of Peterdorf and Beeson 4 to classify FUO, and 7 studies 21 , 22 , 24 , 26 , 27 , 28 , 31 combining 1135 participants (43.2%) were classified by the criteria of Durack and Street.…”