Gastrointestinal disease is a major cause of morbidity and mortality worldwide, especially among young children and immunocompromised patients. Diarrhea may result from infection with a variety of microbial pathogens, including bacteria, viruses, or parasites. Historically, the diagnosis of infectious diarrhea has been made using microscopy, antigen tests, culture, and real-time PCR. A combination of these traditional tests is often required due to the inability to distinguish between infectious etiologies based on the clinical presentation alone. Recently, several multiplex molecular assays have been developed for the detection of gastrointestinal pathogens directly from clinical stool samples. These panels allow for the detection and identification of up to 20 pathogens in as little as 1 h. This review will focus on the multiplex molecular panels that have received clearance from the FDA for the diagnosis of diarrheal disease and will highlight issues related to test performance, result interpretation, and cost-effectiveness of these new molecular diagnostic tools.
Diarrheal disease remains a significant global health concern, with the World Health Organization estimating that there are ϳ1.7 billion total cases each year, resulting in Ͼ750,000 deaths among children younger than 5 years old (1). Gastrointestinal (GI) infection with bacteria (e.g., Clostridium difficile, Escherichia coli, Shigella), viruses (e.g., norovirus, rotavirus), or parasites (e.g., Cryptosporidium, Giardia) is a major cause of diarrheal illness worldwide, often resulting from contaminated food/water and poor sanitation. Rapid and accurate detection of GI pathogens is important so that appropriate therapy can be initiated and proper infection control and epidemiologic measures can be taken to help reduce or prevent the spread of disease (2, 3). Traditionally, the laboratory diagnosis of GI infections has relied on a combination of conventional techniques, including microscopy, culture, antigen detection, and individual real-time PCR assays. These methods have demonstrated good performance (4-6), but they are labor intensive, are time consuming, and require health care providers to select the appropriate tests, as a result of clinically indistinguishable illness caused by many infectious agents (7). Recently, there has been substantial interest in the development of multiplex molecular assays for the detection and identification of infectious diseases, including pathogens responsible for causing diarrhea. These syndromic panels allow health care providers to cast a broad net and achieve a timely diagnosis, which may be important in certain patient populations, such as immunocompromised hosts (ICH) and the critically ill (8). This review highlights three commercial multiplex panels (FilmArray GI panel [BioFire Diagnostics, Salt Lake City, UT], Luminex xTag GI pathogen panel [GPP] [Luminex Corporation, Toronto, Canada], and Nanosphere Verigene enteric pathogen [EP] test [Nanosphere, Inc., Northbrook, IL]) that have been cleared by the Food ...