Assessment Of Patients With Borrelia Infection

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Tickborne diseases are a serious health threat that has steadily risen, with reported cases more than doubling over the past 13 years. Lyme disease, or Lyme borreliosis, accounts for more than 80% of the reported cases of tickborne diseases in the US. It is estimated that over 476,000 cases of Lyme disease diagnosed and treated per year in the US, and over 200,000 cases estimated in Europe. Our current work addresses the following areas in Lyme disease: development of new tests and biomarkers for infection, investigation of persistence of infection with B. burgdorferi in humans, and investigation of the role of immune response in Lyme disease and post treatment Lyme disease syndrome (PTLDS). We have four clinical protocols exploring diverse aspects of Lyme disease and tickborne infections that are currently open to recruitment. This include a new clinical protocol, in collaboration with University of Maryland, to evaluate patients with suspected tickborne infections. In these, and past clinical studies, we have evaluated more than 700 patients. Together with this large clinical database, we have assembled a large biorepository that has served to explore multiple avenues of research in Lyme borreliosis and tickborne diseases. Early detection is critical for prompt and effective treatment of acute infectious diseases. Molecular assays are the optimal method for early and rapid detection of pathogenic agents. For tick-borne diseases, the lack of accurate early diagnosis can result in delayed treatment, augment morbidity, and increase the likelihood of developing persistent symptoms. A major scientific advance of the past year is our work in collaboration with Dr. Rafal Tokarz (Columbia University) on the development of a capture sequencing assay for enhanced detection and genotyping of tick-borne pathogens, named TBDCapSeq. This is a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. For Borrelia burgdorferi and Babesia microti, the sensitivity of TBDCapSeq was comparable and/or exceeded agent-specific quantitative PCR and resulted in 25 to>10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. Using the TBDCapSeq enabled genome analyses directly from samples from vertebrates and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches. We also investigated the phylogeny of the filarial nematode in Ixodes scapularis. and its potential for human infection. We showed that this agent is a new species in the genus Monanema and its presence in vector ticks does not impact the burden of B. burgdorferi and we found no evidence that this nematode contributes to the spectrum of human tick-borne infections.