Pathogen characterization and discovery by deep sequencing of two major vectors associated with Lyme disease and other tickborne infections

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Investigator: Charles Y. Chiu, MD, PhD
Sponsor: Lyme Research Alliance, Inc

Location(s): United States

Description

Lyme disease, a tickborne febrile illness caused by the bacterium Borrelia burgdorferi, is the most common vector-borne disease in the U.S, and incidence is increasing worldwide. An estimated 3.4 million commercial antibody-based tests are conducted annually in the U.S. for Lyme, yet these tests fail to diagnose up to 40% of acute Lyme disease cases. In addition, existing tests are unable to detect in a multiplexed fashion clinically significant co-pathogens in the tick vector, such as Babesia and Anaplasma. We will explore the use of emerging genomic technologies – microarrays and deep sequencing – to address the urgent clinical need for improved Lyme diagnostics.

A novel microarray platform called the TickChip has been developed and is able to detect all tickborne pathogens, including viruses, bacteria, and parasites from blood in a single assay. In preliminary data using spiked samples, we have shown that the TickChip has a sensitivity of detection of 1-10 genome copies of Borrelia burgdorferi or Babesia microti per milliliter of blood.

Whole-exome transcriptome profiling of Lyme disease patients by deep sequencing has identified a specific and robust host response signature for acute Lyme that persists for at least one month duration. This transcriptome data is currently being leveraged to design a multiplexed host response-based assay for acute Lyme disease diagnosis.

Unbiased deep sequencing for the detection and discovery of novel viruses in the hunt for the etiologic agent of STARI (Southern Tick-Associated Rash Illness), a Lyme-like illness that is spread by the Amblyomma tick, a vector which also harbors the pathogenic Heartland virus. The rising incidence and morbidity of Lyme and associated tick- borne illnesses demand the development of new diagnostics with the sensitivity to broadly detect these tickborne disease agents, both known and novel.