What was old is new again: using the host response to diagnose infectious disease

Abstract

A century of advances in infectious disease diagnosis and treatment changed the face of medicine. However, challenges continue to develop including multi-drug resistance, globalization that increases pandemic risks and high mortality from severe infections. These challenges can be mitigated through improved diagnostics, focusing on both pathogen discovery and the host response. Here, we review how ‘omics’ technologies improve sepsis diagnosis, early pathogen identification and personalize therapy. Such host response diagnostics are possible due to the confluence of advanced laboratory techniques (e.g., transcriptomics, metabolomics, proteomics) along with advanced mathematical modeling such as machine learning techniques. The road ahead is promising, but obstacles remain before the impact of such advanced diagnostic modalities is felt at the bedside.

Keywords:

• communicable diseases
• early diagnosis
• host–pathogen interactions
• metabolome
• molecular diagnostics
• proteome
• respiratory tract infection
• sepsis
• transcriptome
• tuberculosis

Financial & competing interests disclosure

E Tsalik has received funding from NIAID, The Henry Jackson Foundation and Novartis. E Tsalik also has pending patents for infectious disease diagnostics. G Ginsburg has received funding from DARPA, NIAID, The Henry Jackson Foundation and Novartis. G Ginsburg has pending patents for infectious disease diagnostics. C Woods has received funding from DARPA, NIAID, The Henry Jackson Foundation and Novartis. C Woods has relationships with Novartis Diagnostics, BioFire, bioMerieux and Nanosphere, including research grants and advisory positions. C Woods has pending patents for infectious disease diagnostics. M McClain has received a grant from Veteran’s Affairs Center, number 1IK2CX000611 (MTM). M McClain has pending patents for infectious disease diagnostics. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Single and pauci-analyte biomarkers are helpful to determine the severity of illness and prognosis.

• Systems biology research using ‘omics’ technologies have developed classifiers that demonstrate improved sensitivity and specificity over traditional single or pauci-analyte biomarkers.

• Host response classifiers have shown promise in discriminating sepsis from systemic inflammatory response syndrome, early pathogen identification and offering prognostic information to personalize the management of infectious diseases.

• Classifiers that discriminate between bacterial and viral pathogens have the potential to greatly reduce unnecessary antibiotic prescriptions, especially in acute respiratory illnesses.

• Human viral challenge experiments provide a controlled way to understand the host response to viral infection, leading to an accurate viral classifier that can identify infected but pre-symptomatic individuals.

• Classifiers could be used to discriminate different infectious disease states such as active versus latent TB.

• Infectious disease classifiers must be rapid, reproducible and generalizable to a broad cross-section of society in order to be clinically safe and effective.

• Partnerships between industry, academics and regulatory bodies are necessary to move ‘omics’ classifiers into clinical utility studies, eventually to be disseminated for widespread clinical use.

Notes