GENETAG TECHNOLOGY, INC — Department of Health and Human Services SBIR Phase I: NCIRD

Description

Detecting species specific bacterial meningitis markers with iDDS probes Confidential PI Shafer David A PhD PROJECT SUMMARY Rapid and accurate molecular diagnostics assays empower physicians to make informed treatment decisions Meningitis may be caused by infection with microorganisms such as viruses gram negative GN and gram positive GP bacteria fungi or parasites Most frequently meningitis results from infections with non polio enteroviruses EV and parechoviruses PV which typically self resolve within days In contrast bacterial meningitis has a high mortality rate that approaches if not treated Meningitis patients present with similar symptoms regardless of origin thus timely diagnosis of the causative agent is paramount for patient care Patients are commonly treated with an empiric regimen of antibiotics until a definitive diagnosis can be made Nucleic acid amplification tests NAATs reduce diagnosis turnaround times by several days compared to standard culturing methods allowing shortened hospital stays appropriate use of antibiotics and a reduced financial burden to patients and the health care system Currently there are only two FDA approved NAATs for diagnosing viral and or bacterial meningitis Unfortunately these tests are only approved for use on the manufacturer s fully automated systems the costs of which are often prohibitive and may not determine the etiological agent of bacterial meningitis GeneTAG Technology Inc has developed instrument independent error preventing DNA Detection Switch iDDS probes which employ a fluorescent labeled probe and a slightly mismatched quencher labeled antiprobe In the absence of the intended target the antiprobes hybridize to the probes quenching their fluorescence and preventing off target detection Recently we developed EV and PV assays employing two iDDS probes for each target providing simultaneous color signaling and automatic confirmation of positive or negative test results We have also developed iDDS probes for GN and GP detection In the proposed studies we are interested in developing a reflex test that can be used to determine which of common bacterial species is present based on the detection of species specific genetic markers for each bacterial species Such a reflex test is important because knowing the bacterial species can guide physicians in prescribing appropriate antibiotic treatment After initial validation studies this test will be re formulated into a lyophilized format where all reagents primers and probes are included and the test would only require adding sample and molecular grade water The lyophilized test will be re evaluated with genomic DNA samples representing each bacterial test species and cerebrospinal fluid specimens Ultimately we are interested in gaining FDA approval for our lyophilized meningitis assay Delivering a high fidelity cost effective meningitis assay should positively impact meningitis diagnostics guide physicians in selecting appropriate therapy and provide a direct benefit to public health Detecting species specific bacterial meningitis markers with iDDS probes Confidential PI Shafer David A PhD PROJECT NARRATIVE Determining the etiological agent of spinal meningitis is critical for patient care Unfortunately the only FDA approved nucleic acid amplification tests for bacterial and viral meningitis require expensive instrumentation which limits point of care testing and slows diagnosis and may not identify the bacterial species involved which is key for selecting effective antibiotics Previously we developed assays for distinguishing bacterial and viral meningitis that can be used on various real time PCR instruments already present in diagnostic labs We will upgrade our test to include species specific bacterial markers so that physicians can first discern between bacterial and viral meningitis and then decide appropriate therapy in the case of bacterial meningitis