An estimated 3-4 million children below the age of 5 years die each year as a result of complications related to diarrhea. Every year in the United States, there are an estimated 211 to 375 million episodes of acute diarrhea resulting in 5,000 deaths. The number and diversity of diarrhea causing pathogens, including viruses, bacteria, and protozoa along with the similarities in clinical presentation pose significant problems for diagnosis. Current microbiological methods used to identify the responsible pathogen are slow and laborious requiring days for a result. While individual patients suffer from these testing limitations, public health is also threatened by outbreaks that spread undetected. Idaho Technology Inc. (ITI) has developed the FilmArray System, an innovative molecular diagnostics device that streamlines pathogen identification in human samples. The FilmArray System simultaneously identifies up to 27 organisms in ~1 hour, and requires only a minimally trained operator to perform the test. The FilmArray System comprises a uniquely designed """"""""lab-in-a-pouch"""""""", which together with the FilmArray instrument, automatically performs all steps needed for detection and identification of pathogens, from nucleic acid extraction to multiplex real time PCR and data analysis. The goal of this project is to adopt this technology and incorporate assays, protocols and consumables to accurately identify the presence of 22 diarrhea- associated pathogens. ITI proposes the following Aims to develop and evaluate the FilmArray Gastrointestinal (GI) Pathogen System.
In Aim 1, the assays to detect diarrhea causing pathogens and the protocols to extract nucleic acids from stool will be developed and then combined to make the FilmArray GI pouch. The FilmArray instrument software will be adapted for the interpretation of the GI pathogen assays. The assays in FA GI pouch will be validated using stool samples that have been shown to be positive by conventional tests. After validation the FA GI pouches will be transferred from R &D to ITI's production facility so that pouches can be produced under current Good Manufacturing Practices (cGMP). Transfer will require quality control (QC) of raw materials and the final product, documentation of formulations and dispense protocols for reaction mixtures and pilot lot production.
In Aim 2, analytic testing will be performed to determine the sensitivity and specificity of the system, examine reproducibility, identify possible interferants in stool, and evaluate the potential for contamination between tests. The performance of the FA GI System will be evaluated in a clinical setting as a test of the feasibility of applying for FDA clearance of the FA GI System as an In Vitro Diagnostic Device. A large set of previously characterized archived stool samples and a small set of fresh samples will be tested using the FA GI Diagnostic System at Primary Children Medical Center (PCMC), Salt Lake City, UT. The challenge in diagnosing infectious diarrhea is the large number and diversity of the pathogens that are known to cause diarrhea, including viruses, bacteria and protozoa. We propose to develop the FilmArray Gastrointestinal Pathogen System, a rapid (<1 hour), automated, sensitive, objective and inexpensive test able to detect 22 diarrhea causing pathogens in a single step. This novel tool will overcome diagnostic difficulties, improve the treatment and reduce the cost of diarrheal illness for individual patients, and improve public health by rapid detection of outbreaks. Relevance: The challenge in diagnosing infectious diarrhea is the large number and diversity of the pathogens that are known to cause diarrhea, including viruses, bacteria and protozoa. We propose to develop the FilmArray Gastrointestinal Pathogen System, a rapid (<1 hour), automated, sensitive, objective and inexpensive test able to detect 22 diarrhea causing pathogens in a single step. This novel tool will overcome diagnostic difficulties, improve the treatment and reduce the cost of diarrheal illness for individual patients, and improve public health by rapid detection of outbreaks.
The challenge in diagnosing infectious diarrhea is the large number and diversity of the pathogens that are known to cause diarrhea, including viruses, bacteria and protozoa. We propose to develop the FilmArray Gastrointestinal Pathogen System, a rapid (<1 hour), automated, sensitive, objective and inexpensive test able to detect 22 diarrhea causing pathogens in a single step. This novel tool will overcome diagnostic difficulties, improve the treatment and reduce the cost of diarrheal illness for individual patients, and improve public health by rapid detection of outbreaks.
