Development and Validation of a Combined Pathogen-Host Genomic Assay for Diagnosis of Lyme Disease and Other Tick-Borne Infections
Abstract
Lyme disease is the most frequent vector-borne disease in the United States, with an estimated >300,000 cases a year. However, the Ixodes tick vector that carries the causative agent of Lyme disease, the bacterium Borrelia burgdorferi, also carries a number of other potential viral and bacterial pathogens that are often not specifically looked for. In addition, we currently lack a laboratory test that can accurately diagnose acute Lyme disease (when a patient presents with fever, rash, and a history of tick-borne exposure), as the bacterium is only present for a very short time in the blood and serological testing is hindered by the time it takes to generate detectable levels of antibody and an overall lack of sensitivity and specificity. Early diagnosis is critical since undiagnosed Lyme disease is associated with a number of complications ranging from myocarditis to debilitating arthritis and even sudden cardiac death. Furthermore, 10%-20% of people with acute Lyme have persistent and chronic symptoms that can significantly impair quality of life, a condition termed “post-treatment Lyme disease syndrome.” Thus, we urgently need an accurate and sensitive test for the diagnosis of Lyme disease and other tick-borne illnesses in the acute setting. The overriding scientific objective here is to develop such a diagnostic test by combining a panel of pathogen and host biomarkers. The pathogen biomarkers will be used to detect all major circulating pathogens in the tick vector, and the host biomarkers will be used to diagnose Lyme disease with a high level of sensitivity and specificity not achievable currently. In support of this goal, we have previously shown in a published study that acute Lyme disease elicits a human host response to infection (“biosignature”) that is specific to Lyme and that persists for up to 3 weeks following the initial clinical presentation. This project directly addresses the Fiscal Year 2016 Tick Borne Disease Research Program “diagnostics” Focus Area, and secondarily addresses the “pathogenesis” Focus Area. Our aims are (1) to test a ~2.1 million probe panel representing all known tick-borne pathogens and identify a subset of pathogen gene biomarkers that are the most informative (optimal) for detecting these agents, (2) to perform transcriptome (gene expression) profiling of pediatric and adult patients with acute Lyme disease at different time points and identify a set of host gene biomarkers that are optimal for discriminating patients with Lyme, and (3) to combine these pathogen and host biomarkers into a novel diagnostic test for Lyme disease and other tick-borne illnesses on a state-of-the-art nanopore sequencing platform. The nanopore sequencer is a “pocket-sized” device powered by the USB port on your laptop and capable of performing rapid real-time sequencing analysis. Ultimately, we aim to develop a diagnostic test that could be validated and implemented in clinical laboratories for patient testing. In summary, our study leverages novel high-throughput genomic methods for both direct detection of pathogens and host response to advance Lyme disease diagnostics. We will accelerate the development of an accurate and comprehensive diagnostic test for acute Lyme disease and other tick-borne illnesses. Such a test is urgently needed for timely patient care to prevent later complications of Lyme disease and to spur the development of effective drugs and vaccines. Given the high prevalence of Lyme disease in the United States (an estimated >300,000 cases a year) and its high morbidity when left undiagnosed and untreated, this study will have huge potential impact on patients. Ultimately, this research will benefit Service members, Veterans, their families, and the American public, all of whom are either directly affected by Lyme disease or likely know a family member or friend who either had acute Lyme or may be suffering from its complications -- and who would thus benefit from
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710681
Entities
People
- Charles Chiu
Organizations
- United States Army
- University of California, San Francisco