Identification of diagnostic biomarkers for flea-borne typhus

Typhus group rickettsioses (TGRs) include epidemic typhus (ET) and murine typhus (MT), caused by Rickettsia prowazekii and R. typhi, respectively. MT continues to cause serious infectious in otherwise healthy individuals and results in increased health-care cost worldwide. ET is a bioterrorism and potential threat to public health in situations with poor hygiene. Due to unspecific symptoms and lack of a reliable laboratory test at the early stage of disease, diagnosis of TGRs has been problematic and accounts for the significant morbidity and disease burden. Although often under-recognized, MT is the second most frequently reported rickettsial infection in the US. Therefore, a novel antigen-based diagnostic assay for TGRs will be an important resource that will ensure the Nation’s capability to recognize and treat these diseases. Our objectives in this research are to identify the diagnostic biomarkers for TGRs and to develop a proof-of-concept immunoassay that can be further advanced to an acute diagnostic assay for these infections. Our pilot studies have identified two rickettsial proteins as the potential diagnostic targets by proteomic analysis using in vitro and in vivo experimental models of MT. These two molecules have both shown a greater than 95% identity based on their amino acid sequences in R. typhi compared to those in R. prowazekii. Thus, our central hypothesis is that immuno-detection of diagnostic biomarkers will provide an antigen-based assay for early diagnosis of MT.