The Changing Landscape of Tracking Infectious Diseases

In a webinar on clinical diagnostics and tracking infectious diseases, presented on October 18, by the Centers for Disease Control and Prevention (CDC), a panel of speakers discussed how culture-independent diagnostic tests (CIDTs) are changing the landscape of diagnosing infectious diseases.

CIDTs provide a new method for diagnosing infections, and are frequently used to identify food-borne illness. Although culture has been the focus of diagnostic testing for food-borne pathogens for the past several decades, this technique may take two or three days to produce a result. As a consequence, many clinical laboratories are now adopting culture-independent methods. These newer tests detect the presence of a specific genetic sequence or antigen of a pathogen, and produce results much faster than culture testing does.

According to Tom Frieden, MD, MPH, Director of the CDC, Atlanta, Georgia, CIDTs allow clinicians to determine which pathogen is causing disease in a patient—often when the patient is still in the healthcare facility.

The Impact of Culture-independent Diagnostic Testing in Food-borne Diseases

Discussing the effect of CIDTs in food-borne diseases, Chris Braden, MD, Deputy Director of the National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta, Georgia, highlighted a major expansion in availability of US Food and Drug Administration (FDA)-cleared multiplex polymerase chain reaction (PCR) panels. These tests use real-time amplification methods and can facilitate simultaneous detection of multiple pathogens, and are often designed around disease syndromes, such as gastrointestinal infections, said Dr Braden.

CIDT use is increasing, and, for enteric infections, this increased uptake also varies by pathogen. Use of CIDTs may also affect surveillance trends. For example, Dr Braden noted that the increased incidence of infections with Cryptosporidium and non-O157 Shiga toxin-producing Escherichia coli (STEC) in 2015 might be due, at least in part, to greater use of CIDTs.

Dr. Braden emphasized that the benefits of CIDTs are impressive, especially for clinical care. In addition to yielding results faster, he stressed that culture-independent diagnostic testing is probably more sensitive than culture testing; a single test can also detect or rule out multiple types of pathogens (such as bacteria, viruses, and parasites); and this technique is often the only practical way to detect viral pathogens, he said.

However, these tests also have drawbacks, said Dr Frieden. They do not provide some of the more detailed information that culture tests can provide. For example, because CIDTs do not yield isolates that can be further tested, these tests cannot help clinicians to determine whether a bacterial pathogen is resistant to certain antibiotics.

Reflex culturing (culturing a specimen after CIDT produces a positive result) is therefore often needed to further characterize the pathogen and tailor treatment, Dr Braden added.

CIDT also involves other drawbacks, he noted, especially because positive results can be difficult to interpret in some situations. For example, even DNA from dead microorganisms can produce a positive result. Clinicians may therefore be challenged to know whether a patient is still contagious, and may therefore be unclear about whether an adult patient should return to work, or a child patient to a day care facility. Also, because a single test can detect multiple pathogens, it may identify some that are not causing the patient’s current illness. According to one study, more than 30% of positive tests detected multiple enteric pathogens, said Dr Braden.

Nevertheless, pathogen characterization is an important component of food safety. “Each year, 48 million people get sick, 128,000 are hospitalized, and 3,000 die from food-borne diseases,” Dr Braden emphasized.

Managing New Diagnostic Tests in Colorado

Alicia Cronquist, RN, MPH, Foodborne Disease Program Manager, Communicable Disease Branch, Colorado Department of Public Health and Environment, Denver, shared some specific updates about how CIDT has affected surveillance and isolate recovery in Colorado.

“So far, in 2016, 40% of bacterial enteric cases reported were tested using PCR,” she said. And reflex culture was performed for 89% of the cases of Salmonella, Shigella, and STEC infection that were diagnosed using multiplex PCR testing.

According to Cronquist, routine survey of clinical laboratory methods began in 2009 in Colorado, as a way to ensure accurate case reporting. She highlighted that, although labor intensive, it is important to collect the appropriate information from laboratories. With this in mind, disease surveillance databases in the state have been modified to capture data from newer diagnostic tests, and so that electronic laboratory reporting data flow correctly. Education and communication have been critical aspects of the process to improve accuracy of case reporting, in particular to help reduce the problem of human error in interpreting multiplex panel results. For example, some laboratory personnel may be confused by certain microorganism names (such as Shigella and STEC), she noted, but personnel must be able to differentiate these bacteria when they report cases.

Cronquist also noted that the preferred policy in Colorado is to perform isolate recovery at the clinical laboratory. In particular, this produces results more quickly, reduces concern about transport of raw specimens, and means that susceptibility test results are available more quickly for improved patient care

Clinical materials may also be sent to state public health laboratories for further characterization, especially in the case of priority pathogens such as STEC, Salmonella, Shigella, and Vibrio are priority pathogens, she added. In order to facilitate rapid transport of such specimens from clinical laboratories, the state public health laboratories provide a courier service and transport media, as well as written guidance based on studies performed by the Association of Public Health Laboratories.

When investigating cases, state public health laboratories need to prioritize, based on the particular disease and associated test results. For example, the laboratory would investigate a case suspected to involve a highly infectious respiratory disease as a higher priority than a Campylobacter-positive case.

With respect to worker and childcare exclusion or restriction, Cronquist emphasized that Colorado treats a PCR-positive result in the same way as a culture-positive result. The state public health laboratories also frequently perform followup testing at no charge, she added. And, in cases in which patients are CIDT-positive for two or more reportable conditions, she stressed that the state recommends that clinicians use control measures for the pathogen with the greatest risk of transmission.

In concluding, Dr Braden emphasized that the CDC uses PulseNet, a national laboratory network that connects cases of food-borne illness to detect outbreaks. This network uses bacterial subtyping methods to quickly detect clusters of food-borne disease, which are often the first indication of an outbreak. Since it was formed 1996, PulseNet has improved food safety through identifying outbreaks early, preventing more than 270,000 illnesses from Salmonella, Listeria, and E. coli every year.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.