Gastrointestinal Infections and the Importance of Laboratory Testing

Infectious gastroenteritis affects hundreds of millions of people across the globe every year. Among the common causes are viruses, bacteria and parasites and infections are usually contracted by ingestion of contaminated food, water or through contact with infected individuals. In the US, it is estimated that foodborne pathogens alone affect about 48 million people, leading to 128,000 hospital admissions and 3,000 deaths per year (1,2). The economic burden of foodborne illnesses is estimated to cost approximately $15.6 billion annually (1).

Timely and precise identification of causative agents of gastroenteritis is essential for patient care, public health, and disease monitoring. While some infections resolve without medical intervention, cases of persistent diarrhea and severe illness can lead to life-threatening complications and require pathogen-specific therapeutic interventions. Accurate diagnosis not only improves patient outcomes but also prevents unnecessary antibiotic use in cases with viral etiology or when antibiotics are contraindicated. As gastrointestinal infections easily spread in the community, outbreaks can occur, which further highlights the importance of diagnostic testing for public health. In recent years, molecular diagnostic methods have started to replace conventional culture approaches for detection of gastrointestinal pathogens due to their increased sensitivity and rapid turnaround times, both of which have significant impact on informing treatment decisions.

CAUSES OF GI INFECTIONS

The most common cause of infectious gastroenteritis are viral infections, with norovirus being the most prevalent pathogen, followed by rotavirus, astrovirus, sapovirus and enteric adenoviruses which are also prevalent in the US (3-5). However, in severe cases of infectious diarrhea, bacterial etiology is more frequently detected (6). Enteropathogenic bacteria include Salmonella, Escherichia coli (E. coli), Campylobacter, Shigella, Yersinia and Aeromonas among others (3-5). In cases with prolonged or chronic diarrhea, common etiology includes parasites such as Giardia, Entamoeba histolytica, Cryptosporidium, and Cyclospora (3-5,7). Patients at risk of severe or persistent infections include young children, the elderly, pregnant women, hospitalized patients, people in long-term care facilities, immunocompromised individuals, and travelers from regions with poor hygiene standards (8,9). For example, young children are at particular risk of developing complications from GI infections with rotavirus being noted as the main causative agent of diarrhea in children under 5 years old (10). Similarly, immunocompromised, pregnant women and the elderly are at higher risk of developing life-threatening complications due to infectious gastroenteritis (8). Moreover, in hospitals and long-term care facilities, nosocomial GI infections can be easily acquired and spread from person-to -person, for example infections caused by Clostridioides difficile, one of the leading causes of antibiotic use-associated diarrhea (11).

CHALLENGES IN THE DIAGNOSIS OF GI INFECTION

Most cases of infectious gastroenteritis are self-limiting and resolve spontaneously but, individuals with persistent or severe symptoms require specific treatment including antibiotics or other therapeutics to prevent complications. While clinical presentation of infectious gastroenteritis can vary from mild illness to severe disease, and certain pathogens may be associated with specific symptoms (e.g., bloody diarrhea), the clinical symptoms alone are not sufficient to determine the cause of infection and laboratory testing is often required to inform treatment decisions (12).

Diagnostic testing for GI infections is a complex task that involves overcoming various challenges related to the diverse range of causative pathogens and the inherent limitations of the available diagnostic tests. Prior to the introduction of molecular diagnostic testing, the standard diagnostic approach involved use of many different types of tests with variable sensitivity and specificity, including routine stool culture, antigen detection-based tests, or ova and parasite examinations which many labs still use today. The main limitations of these diagnostic approaches are complex ordering practices, limited coverage of prevalent pathogens which require special culturing conditions or non-standard microscopy evaluations, and most importantly, long time to result of up to (3-4) days, which has limited clinical utility (13-15). In practice, this has led to patients often receiving empiric treatment prior to obtaining test results. A significant challenge is also underdiagnosis of pathogens not included in the standard ordering practices, such as Cyclospora or Campylobacter upsaliensis (16,17), for example, or pathogens with challenging culture conditions requiring >7 days, such as Yersinia18. Detection of parasites, which mainly relied on microscopic evaluation, required highly skilled laboratory personnel and, while recommendations include evaluation of several stool samples to increase sensitivity of pathogen detection, these specimens are rarely received by the laboratories (19-22). More recently, molecular diagnostic methods such as, multiplex real-time polymerase chain reaction (PCR)-based tests, have started to replace conventional methods for diagnostic testing of gastrointestinal infections.

ADVANTAGES OF MOLECULAR TESTING

The main advantage of molecular diagnostics are high sensitivity, specificity, and short time-to-results compared to traditional methods like culture and microscopy (23-26). Multiplex PCR tests can simultaneously detect viral, bacterial, and parasitic pathogens in a single sample, including co-infections, thus helping clinicians make better informed treatment decisions that enable improved patient outcomes and contribute to antimicrobial stewardship (23-26). In patients suffering from non-infectious causes of gastroenteritis, molecular diagnostics offers a fast-track to conducting differential diagnosis. Molecular testing can also aid in reducing healthcare costs where rapid and accurate diagnosis leads to more efficient resource utilization, adjusted hospitalization numbers, and shorter hospital stays (23-27). Finally, as many gastrointestinal pathogens belong to nationally notifiable diseases due to their potential for causing outbreaks, molecular testing plays an important role in quick identification of pathogens involved in outbreaks and informing public health action aimed at limiting the spread of infections in the communities (28).

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