A novel diagnostic algorithm equipped on an automated hematology analyzer to differentiate between common causes of febrile illness in Southeast Asia

PLoS Negl Trop Dis. 2019 Mar 14;13(3):e0007183. doi: 10.1371/journal.pntd.0007183. eCollection 2019 Mar.

Abstract

Background: Distinguishing arboviral infections from bacterial causes of febrile illness is of great importance for clinical management. The Infection Manager System (IMS) is a novel diagnostic algorithm equipped on a Sysmex hematology analyzer that evaluates the host response using novel techniques that quantify cellular activation and cell membrane composition. The aim of this study was to train and validate the IMS to differentiate between arboviral and common bacterial infections in Southeast Asia and compare its performance against C-reactive protein (CRP) and procalcitonin (PCT).

Methodology/principal findings: 600 adult Indonesian patients with acute febrile illness were enrolled in a prospective cohort study and analyzed using a structured diagnostic protocol. The IMS was first trained on the first 200 patients and subsequently validated using the complete cohort. A definite infectious etiology could be determined in 190 of 463 evaluable patients (41%), including 89 arboviral infections (81 dengue and 8 chikungunya), 94 bacterial infections (26 murine typhus, 16 salmonellosis, 6 leptospirosis and 46 cosmopolitan bacterial infections), 3 concomitant arboviral-bacterial infections, and 4 malaria infections. The IMS detected inflammation in all but two participants. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IMS for arboviral infections were 69.7%, 97.9%, 96.9%, and 77.3%, respectively, and for bacterial infections 77.7%, 93.3%, 92.4%, and 79.8%. Inflammation remained unclassified in 19.1% and 22.5% of patients with a proven bacterial or arboviral infection. When cases of unclassified inflammation were grouped in the bacterial etiology group, the NPV for bacterial infection was 95.5%. IMS performed comparable to CRP and outperformed PCT in this cohort.

Conclusions/significance: The IMS is an automated, easy to use, novel diagnostic tool that allows rapid differentiation between common causes of febrile illness in Southeast Asia.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms*
  • Animals
  • Arbovirus Infections / diagnosis
  • Automation, Laboratory / methods*
  • Bacterial Infections / diagnosis
  • Blood Chemical Analysis / methods*
  • C-Reactive Protein / analysis
  • Diagnosis, Differential
  • Diagnostic Tests, Routine / methods*
  • Female
  • Fever of Unknown Origin / diagnosis*
  • Humans
  • Indonesia
  • Male
  • Mice
  • Middle Aged
  • Predictive Value of Tests
  • Procalcitonin / analysis
  • Prospective Studies
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Procalcitonin
  • C-Reactive Protein

Grants and funding

AvV and QdM received an unrestricted grant from Sysmex Corporation for the performance of this study. The funder had no role in study design or data acquisition. The funder contributed to data analysis by classifying the result of the IMS for each study participant while being blinded for the results of clinical examinations and results of microbiological examinations and biomarkers. The funder had no role in the decision to publish and preparation of the manuscript.