Culture-Independent Tests Gain Clinical Traction, Hamper Public Health

Laboratory developed tests are not the only item on the U.S. Food and Drug Administration's (FDA) agenda that involves the diagnostics industry. The FDA is also focusing significant resources on food safety. The FDA released in 2015 new rules under the FDA Food Safety Modernization Act (FSMA), which seeks to strengthen the U.S. food safety system. And President Obama's 2017 FY Budget Request included $25.3 million for implementing the FSMA. A study published April 15 in Morbidity and Mortality Weekly Report indicates the relevance of diagnostics to these national efforts to protect food safety and combat foodborne illnesses.

A clear shift is underway in the way foodborne illness is diagnosed. Testing for enteric pathogens is rapidly moving away from culture-based methods and towards culture-independent diagnostic tests (CIDTs), according to the study. The researchers say while CIDT can more rapidly diagnose illness, it poses a challenge for identifying antibiotic resistance and outbreaks. To address these concerns, regulators, laboratories, and public health must work together to address strategies, such as reflex culturing positive CIDT cases, in order to ensure appropriate data for public health practice.

"The continued shift from culture-based methods to CIDTs that do not produce the isolates needed to distinguish between strains and subtypes affects the interpretation of public health surveillance data and ability to monitor progress toward prevention efforts," write the authors led by Jennifer Huang, from the National Center for Emerging and Zoonotic Infectious Diseases at the U.S. Centers for Disease Control and Prevention (CDC). "Expanded case definitions and strategies for obtaining bacterial isolates are crucial during this transition period."

The researchers analyzed data from the CDC's Foodborne Diseases Active Surveillance Network (FoodNet), which has been tracking the incidence of laboratory-confirmed infections caused by nine pathogens (Campylobacter, Cryptosporidium, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli [STEC], Shigella, Vibrio, and Yersinia) commonly transmitted through food. FoodNet—a collaboration between CDC, 10 state health departments, the U.S. Department of Agriculture's Food Safety and Inspection Service, and the FDA—conducts population-based surveillance at 10 U.S. sites that account for about 15 percent of the U.S. population.

In 2015, FoodNet reported 20,107 confirmed cases (defined as culture-confirmed bacterial infections and laboratory-confirmed parasitic infections), as well as 4,531 hospitalizations, and 77 deaths. FoodNet also received reports of 3,112 positive CIDTs without culture-confirmation in 2015. STEC was the only infection for which the majority of cases were identified by CIDT. The percentage of foodborne infections diagnosed only by CIDT nearly doubled compared to 2012-2014. CIDTs were most commonly used for Campylobacter and STEC, while the highest percentage increase in use, compared with the previous 3-year average, was seen for Shigella and Salmonella. The researchers say this was most likely due to laboratories using newly available DNA-based syndrome panels. On the other hand decreased incidence of salmonella, they say, is likely due to poultry vaccines, implementation of new performance standards, and other preventive efforts.

"The ability to assess and interpret change is impeded as the number of positive CIDT reports continues to rise because of important limitations in the understanding of CIDTs and possible changes in clinician and laboratory practices surrounding them," writes Huang and her colleagues. "For example, analyses need to consider the likelihood of false-positive CIDTs and of CIDTs that are more sensitive than routine culture methods. … The availability of CIDTs might also increase testing for some pathogens. Surveillance systems need to adapt to these changes by expanding case definitions to include positive CIDT reports."

Huang explains that isolates are still needed for antimicrobial susceptibility testing, serotyping, subtyping, and whole genome sequencing. To address this need for isolate in the short term, the researchers propose clinical laboratories perform a culture with positive CIDT results. For a longer-term solution, CDC is working with partners to develop advanced testing methods that, without culture, will give health care providers information to diagnose illness, but also provided detailed information about the bacteria so that public health officials can detect and investigate outbreaks. Ideally these methods, Huang says, would include the ability to detect the genetic sequences of pathogens directly and rapidly from stool specimens, which could benefit both clinical and public health practice.

Takeaway: The search is on for diagnostic methods that can help diagnose individuals with foodborne illness and also assist public health authorities detect and investigate outbreaks.