Diarrhea caused by bacterial, viral, and/or parasitic infection represents a significant worldwide healthcare burden. Each year, there are two billion instances of diarrheal disease globally, resulting in nearly two million deaths.1 The World Health Organization (WHO) estimates that diarrhea is the cause of or is a major contributor to approximately one-quarter of all post-neonatal childhood deaths.2 In the U.S., an estimated 1.4 episodes of acute diarrhea occur per person each year.3 Infectious diarrhea and foodborne illness are responsible for more than 300,000 emergency department visits and 225,000 inpatient stays each year in the U.S. and are associated with healthcare costs of about $1.8 billion.4
Management of diarrheal illness is greatly complicated by the overlapping symptoms associated with pathogenic and non-pathogenic causes of diarrhea. From afar, diarrheal infection can be classified into two categories based on the source of infection: healthcare-acquired diarrhea and community-acquired diarrhea. Healthcare-acquired diarrhea is a diarrheal infection acquired within the hospital or in connection with receiving medical care. Clostridium difficile is typically the cause of these infections, which are a major healthcare concern and require antimicrobial treatment. Community-acquired diarrhea, on the other hand, are those infections caused by environmental enteric bacteria, viruses, or parasites. These infections can be caused by a number of different sources including contaminated food and water sources, and are typically milder in presentation than healthcare-acquired diarrhea.
Community-acquired diarrhea affects millions alone each year in the United States alone, second only to respiratory il lness for prevalence and stated reason for physician visit. These infections are usually transmitted by contaminated food or water sources, but can also be transmitted person-to-person, as in the case of norovirus. Typically, in healthy adults, these infections are self-limiting and do not require antimicrobials to clear the infection. Community-acquired diarrhea can, however, have greater clinical implications in the very young, the elderly, and the immunocompromised. Symptoms associated with these infections range from asymptomatic to mild symptoms including watery diarrhea with nausea to the most severe symptoms, which include diarrhea and nausea accompanied with fever/chills, abdominal cramps, and hypotension. In the case of shiga-toxin producing E. coli (STEC), the potentially fatal condition hemolytic uremic syndrome (HUS) can occur.
The current diagnostic challenge associated with detection of community-acquired diarrhea is twofold. Since clinical presentation of diarrheal disease does not narrow down the potentially responsible pathogen(s), physicians often end up taking the “shotgun” approach to diagnostic testing by ordering testing for a majority of stool pathogens. If physicians are able to characterize the patient’s history, it could greatly narrow the number of diagnostic tests necessary for a given patient. On the diagnostic end, stool culture and ova and parasite (O&P) remain the gold standard diagnostics. Though generally considered sensitive and specific, these procedures are labor-intensive, unpleasant for technicians, can take as long as 5-7 days to produce definitive results in the case of stool cultures, and require a high degree of technical skill in the case of performing O&Ps. Together, the excessive ordering of stool pathogen testing by physicians paired with less-than-ideal diagnostic options has led to what some consider significant inefficiencies in the clinical laboratory. As a result, medical technologists can spend unnecessary time working up negative stools, which can account for upwards of 95% of stools samples submitted for testing. Confirmation of a negative stool sample takes as few as 1-2 hours with a rapid diagnostic test, allowing laboratories to reallocate medical technologist time to other priorities.
Since treatment decisions can vary depending on the identity of the infectious agent and the overall health of the patient, rapid identification of pathogenic bacteria, viruses, and parasites from a stool specimen is crucial. From a therapeutic standpoint, rapid testing for stool pathogens can improve patient management decisions and minimize the use of inappropriate or unnecessary antimicrobials. This is especially important when it comes to detection of STEC, where continued antimicrobial exposure may increase the risk of a patient developing HUS.5 From a public health standpoint, rapid diagnostics for stool pathogens can trigger outbreak investigations earlier for such pathogens as Salmonella and Vibrio. Rapid identification of contagious stool pathogens like norovirus and Shigella can allow for the proper infection control measures to be taken within a hospital or outside of a hospital at such places as long-term care or daycare facilities to minimize the spread of infection. Rapid diagnostic results can also mitigate further downstream testing, such as colonoscopies, when the origin of diarrheal infection is yet to be determined due to the slow turnaround time of conventional diagnostic methods.
Rapid diagnostics for stool pathogens have only recently emerged as viable options for testing for community-acquired diarrhea. Antibody-mediated EIA methods have shown the ability to shorten turnaround times for such stool pathogens as shiga-toxin producing E. coli (STEC), however, these kits lack the multiplexing capabilities necessary to replace culture for routine screening and may still require 12-24 hour turnaround times. Multiplex molecular methods are very well suited for stool pathogens, as these tests can target a majority of stool pathogens of interest at one time. The sample-to-result automation and rapid turnaround times of these tests has been shown repeatedly to improve workflow efficiency in the clinical laboratory.6 The improved sensitivity of molecular-based tests over culture will also provide the accurate results necessary for earlier optimization of patient management, better infection control, and quicker public health response to potential outbreaks.
Diarrheal illness will continue to be a burden to healthcare providers worldwide. Rapid diagnostic tests for stool pathogens may provide a means to minimize the impact of this burden throughout the entire hospital.
1. World Health Organization. Diarrhoeal Disease: Fact Sheet N°330 April 2013. http://www.who.int/mediacentre/factsheets/fs330/en/index.html. Accessed 28 March 2017.
2. Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO Estimates of the Causes of Death in Children. Lancet 2005; 365: 1147-1152.
3. Herikstad H, Yang S, Van Gilder TJ, Vugia D, Hadler J, Blake P, Deneen V, Shiferaw B, Angulo FJ. A Population-Based Estimate of the Burden of Diarrhoeal Illness in the Unites States: FoodNet, 1996-1997. Epidemiol Infect 2002; 129: 9-17.
4. Lucado J, Mohamoud S, Zhao M, Elixhauser A. Infectious Enteritis and Foodborne Illness in the United States, 2010: HCUP Statistical Brief #150. 2013. Agency for Healthcare Research and Quality, Rockville, MD. http://www.hcup-us.ahrq.gov/reports/statbriefs/sb150.pdf (Accessed May 2015).
5. Panos GZ, Betsi GI, Falagas ME. Systematic Review: Are Antibiotics Detrimental or Beneficial for the Treatment of Patients with Escherichia coli O157:H7 Infection? Aliment. Pharmacol. Ther. 2006; 24(5): 731 – 42.
6. Mortensen JE, Ventrola C, Hanna S, Walter A. Comparison of Time-Motion Analysis of Conventional Stool Culture and the BD MAXTM Enteric Bacterial Panel (EBP). BMC Clinical Pathology 2015; 15:9.
Bert Lopansri, M.D. Chief, Intermountain Division of Infectious Diseases Medical Director of Intermountain Central Laboratory Murray, Utah Associate Professor of Medicine, University of Utah School of Medicine Salt Lake City, Utah
Dr. Lopansri received his Doctor of Medicine from Loyola University of Chicago in 1997. He completed his residency at Loyola University of Chicago in Internal Medicine from 1997 – 2000 and a fellowship in infectious disease from the University of Utah Medical Center in Salt Lake City, Utah from 2000-2003. From 2003 through the present, Dr. Lopansri has worked at Intermountain Medical Center and is currently serving as Associate Professor of Medicine, Division of Infectious Diseases. Dr. Lopansri is board certified by the American Board of Internal Medicine for infectious diseases.Message Presenter
Kevin McNabb, Ph.D., MT(ASCP) Director of Microbiology, Immunology and Molecular Testing Department of Pathology and Laboratory Services New Hanover Regional Medical Center Wilmington, North Carolina
Dr. McNabb performed his doctoral work in initiation of immune response, autoimmune disease, and vaccine development at the University Of South Carolina School Of Medicine and earned his degree in 1999. Dr. McNabb has been the Director of Microbiology, Immunology and Molecular Testing at New Hanover Regional Medical Center since June of 2012.Message Presenter
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