Why is multiplex molecular testing for gastrointestinal (GI) pathogens important?

The spectrum of pathogens that cause GI infections is quite broad and typically requires an assortment of classical detection methods (culture, antigen detection, stool parasite microscopy) to identify the causative agent. Many of these classical methods suffer from variable specificity and sensitivity, and are often poorly utilized due to a lack of physician understanding of each method’s intended use. In comparison, multiplex molecular tests enable labs to test at once for several of the most common GI pathogens while providing improved analytical specificity and sensitivity. These tests detect infections that would otherwise go undiagnosed.

Are all multiplex molecular GI tests the same?

The analytical and clinical performance of the various Food and Drug Administration-cleared multiplex molecular GI tests has been largely comparable in clinical studies, but the targets included in each assay differ by manufacturer. The methodology and turnaround time also vary, with assay requirements ranging from extensive molecular expertise and sample batching to no molecular expertise and random-access testing. Laboratories need to consider all of these variables when deciding which assay, if any, fits their clinical needs.

Are multiplex molecular tests cost-effective?

Studies to establish the true cost-effectiveness of these methods are purportedly underway. In the meantime, using a very basic reagent cost comparison, labs could contrast the aggregate direct reagent cost of their classical methods (and any referred testing expenses) with the price of a single multiplex assay reagent. The reduced labor expenses for a single multiplex molecular test might augment any cost differences in favor of molecular testing, but labs should also model these costs for existing assays and compare them to predicted test volumes of a single molecular assay. In addition, some laboratories have stopped performing classical methods in order to further boost their indirect labor and reagent costs. 

Are there downsides to multiplex molecular GI pathogen testing?

Yes, but they can be addressed. Multiplex molecular GI tests do not yield a bacterial isolate; instead, they simply provide a result. These results should be reported to public health departments in accordance with state and federal mandates. However, for specific pathogens, public health laboratories also require the actual bacterial isolate in order to properly conduct outbreak investigations. Therefore, labs absolutely must reach out to their public health laboratory well in advance of adopting a multiplex molecular GI test in order to determine how specimens will be cultured for outbreak investigations, who will perform the cultures, and how the specimens will be collected and transported, etc.

Similar to classical tests, multiplex molecular tests may also be improperly utilized. A single expensive molecular test could be ordered when the results will not likely benefit clinical care—such as when a positive test result would not change the care provider’s plan for the patient. Alternatively, physicians sometimes order the test on multiple consecutive stool samples, a practice that is not valuable and only adds extra expense. To avoid this, laboratories should ideally institute ordering restrictions for test frequency, specimen adequacy (e.g. formed stool is rejected), and perhaps specific patient populations.

What is an example of multiplex molecular GI testing’s utility?

Using multiplex molecular testing, laboratories around the U.S. have been able to detect foodborne outbreaks of Cyclospora cayetanesis significantly earlier than labs that rely on classic microscopy. In particular, parasitology testing, especially for protozoa, stands to gain significant diagnostic value from multiplex molecular testing due to this method’s increased analytical sensitivity and panel-based approach.

Marc Roger Couturier, PhD, D(ABMM), is a medical director of infectious diseases and immunology at ARUP Laboratories in Salt Lake City, and an assistant professor of pathology at the University of Utah School of Medicine. +Email: [email protected]