Point-of-Use Pathogen Identification Tool for Diarrhea

Objective

This is a cross-sectional study to validate a new, simple, rapid and affordable point-of-use
pathogen identification research tool (hence forth referred to as the "tool") of diarrheal
diseases for potential use in resource limited settings in the future. The tool was developed
under the terms of a National Institutes of Health (NIH) approved Clinical CRADA between NINR
and GoDx, Inc. The sensitivity and specificity of the tool in identifying several common
gastrointestinal (GI) pathogens in stool will be examined in participants with diarrhea. The
proposed validation study will constitute the initial assessment of the tool in a healthcare
environment. Once the detection validity and technical performance of the tool have been
evaluated in this context, the tool will be further tested in low resource healthcare
settings.

Study population

Study participants will be recruited from the Washington, DC, metropolitan area using
standard NIH recruitment practices, as well as from among participants in two existing
protocols (09-NR-0064, 12-NR-0195) which recruit and consent research participants with GI
disorders and diseases. Lastly, participants enrolled on other NIH protocols will be
recruited. Appropriate stool samples may also be sequestered from an exempt repository
protocol (09-NR-N228). All ages, ethnicities and both sexes will be considered for inclusion
in this study. The study population would reflect the demographics of the greater Washington
DC metropolitan area. Externally recruited participants and participants recruited from
existing protocols will be asked to supply stool samples. A total of 800 samples from
participants with diarrhea will be included in this study.

Design

Stool samples will be collected from participants with diarrhea for which pathogen testing
using the NIH standard of care, BioFire FilmArray GI Pathogen Panel (FDA approved PCR based
pathogen diagnostic) by the Department of Laboratory Medicine (DLM) is indicated. Collected
stool samples will be tested for pathogens causing GI disease, using the FilmArray GI panel
by the DLM. Technicians in the NINR laboratories will test aliquots from the same stool
samples using our tool. The tool has been designed for detection of the most common diarrhea
causing pathogens. Of primary interest for this study are: Enteropathogenic Escherichia coli
- EPEC, Clostridium difficile C. difficile, Enteroaggregative Escherichia coli - EAEC, and
Campylobacter spp. Pathogens of secondary interests, but for which the study is not
specifically powered, will also be included and are: Shigella sp., Shiga Toxin-Producing
Escherichia coli - STEC, Salmonella spp., and Cryptosporidium spp. Participants will not
receive results from the tool.

Outcome measures

The percent sensitivity (ability to make the correct positive identification), specificity
(ability to make the correct negative identification) and 95% confidence intervals will be
statistically determined by comparing the results yielded by the tool and the FilmArray GI
panel. Controlled laboratory experiments suggest >90% specificity and sensitivity of the tool
for the detection of the specified pathogens.

- INCLUSION CRITERIA:

1. We will include samples from participants with self-reported or clinical provider
documented diarrhea defined as one or more loose or watery stools per day as
defined by criteria a or b below:

- Cases of acute diarrhea (i.e., diarrhea which is currently active or was
experienced up to one day prior to sampling or still active during sampling)
will be included.

- Cases of persistent diarrhea (i.e., diarrhea which is chronic or
chronic-intermittently, i.e., once a week or more, experienced for at least
2 to 4 weeks prior to sampling), will be included. In the case of chronic
diarrhea, diarrhea does not have to be active on the day of, or immediately
prior to (i.e., one day) sampling.

2. Current enrollment in an active NIH protocol or enrollment in 12-NR-0195.

3. Able to provide 50ml stool sample within 2-3 hours.

4. Children will only be enrolled if they are currently enrolled in an active NIH
protocol or enrolled in 12-NR-0195.

EXCLUSION CRITERIA:

1. This protocol will exclude outpatients who are clinically unstable patients.
Clinically unstable patient is defined as someone requiring emergent care or
hospitalization.

2. Antibiotic use, which can affect intestinal flora, is not exclusionary but will be
controlled for via post-hoc analysis.

3. NINR employees, subordinates/relatives/ or co-workers.

4. Any NIH employee who is a subordinates/relatives/or co-workers of study investigator.