Risk factors for contagious gastroenteritis in adult patients with diarrhoea in the emergency department - a prospective observational multicentre study

Acute gastroenteritis (GE) is a common reason for admission in emergency departments (ED) [1, 2]. Adult patients with Norovirus and toxigenic Clostridium difficile are prevalent in Northern Europe and require strict isolation, since they are highly contagious.

EDs are characterized by high patient volumes and a short duration of stay, and contact precautions (CP) are important for preventing the spread of contagious diseases to many other patients. According to international and national recommendations, patients with suspected Norovirus or C. difficile infection require a private room and toilet and health staff must wear personal protective equipment [3–5]. While the use of such isolation procedures minimizes the risk of disease spread, there are notable drawbacks since the isolation procedures demand more health-care resources, restrict patient mobility, decrease flexibility, and lead to less documented care and fewer physician visits [6–8].

At the time of admission there is a high degree of uncertainty with respect to GE aetiology, and the decision to initiate isolation is largely dependent on clinical judgement. It is, however, difficult to assess whether a patient has a contagious GE, based on clinical judgement and in a previous study we found that only one-quarter of the patients who were isolated had Norovirus or C. difficile infection [2].

Currently there are no evidence-based criteria for identifying the ED patients with acute GE due to Norovirus or C. difficile. The Kaplan criteria can be used to define Norovirus outbreaks [9], and the gastroenteritis severity score/Vesikari score can rate the severity of acute GE [10], but has no role in assessing whether a patient presenting to hospital with GE require isolation.

In 2012, a clinical prediction scale for hospital-acquired C. difficile infection was developed, but the scale was not designed for acutely admitted patients [11] and in 2014, a small Swedish study developed a risk score to predict viral gastroenteritis, but C. difficile were not included [12].

Biochemical markers have not been useful [11] and the results of stool samples can be delayed due to sampling and analysis time and are rarely available at the admission time when the decision of isolation precautions has to be made.

Thus, it is still unsettled whether a clinical evaluation, based on medical history and physical findings, can be used to distinguish GE caused by Norovirus or C. difficile infections requiring strict contact precautions from GE caused by less contagious pathogens, where no isolation is needed or if it possible to identify other information which might help the clinician to decide whether to isolate or not, before stool examination results are available.

The aims of the present study were to describe the aetiology of infectious gastroenteritis in an ED setting, to evaluate, if the current clinical judgment of need for strict contact precaution is able to identify the right patients, and to identify, if certain clinical information and findings can be used to identify patients with Norovirus or C. difficile infections and thus the need of strict contact precaution in the ED.

In total, the study included 227 patients, 198 (87%) in Denmark and 29 (13%) in Germany. 54% of the patients were female. The age group 18–44 years included 23% of the patients with a median age of 62 years.

Of all included patients, 163 (71%) submitted a faecal sample for Norovirus analysis, 171 (74%) for C. difficile analysis, and 173 (76%) for enteropathogenic bacteria. Figure 1 outlines the number of patients in the study and the number of samples.

Seasonal variation

Seasonal variation for Norovirus and C. difficile infections is illustrated in Fig. 2.

The prevalence of Norovirus was highest in winter and spring. In contrast, there was no seasonal variation for C. difficile infections.

This study revealed three major findings: The results of the faecal samples (13% positive for Norovirus, 13% positive for C. difficile, and 16% had another identifiable enteropathogenic bacterium), the ability to decide isolation criteria based on clinical judgement had a reasonable sensitivity of 83%, but a low specificity (33%) and accuracy (45%), and finally we confirmed well known risk factors for Norovirus (short duration, vomiting, other patients with Norovirus infection) and for C. difficile (longer duration, high age, recent antibiotic treatment, no vomiting).

Norovirus infections peaked in winter and spring, whereas in contrast there was no seasonal variation in the prevalence of C. difficile infections. Our findings concerning seasonal variation are similar to findings from an Australian study [18].

The identification rate of 42% for any stool pathogen mirrors results from other OECD countries as outlined in a 2013 review of the prevalence of gastrointestinal pathogens [15]. We presume that the different study periods do not give a difference in the aetiology. Our findings concerning the frequencies of C. difficile and Norovirus infections were comparable to results from the US [16–18]. Salmonella infections were found with similar frequencies, whereas Campylobacter infections were more frequent than in the US [19] and less frequent than in Germany [20].

Current isolation procedures, which are based on clinical judgement, resulted in the isolation of 71% of patients with GE symptoms. Current isolation practices appear consistent with findings from a 2014 study [2].

Well known risk factors for C. difficile include older age, the use of antibiotics, and hospitalization [21, 22]. One study looked at the following additional risk factors and found the most important to be antibiotic use, an overnight healthcare stay in the previous 3 months, and previous C. difficile infection [16]. The risk factors older age and previous antibiotic use were confirmed in our study. Furthermore we found additional possible risk indicators, specifically diarrhoea duration of more than 3 days and the presence of mucus in stool. The risk factor “low pulse rate” surprised for C. difficile infection. This infection mainly occurs in the patient groups of older age, and elderly do not always respond with tachycardia. Reasons for this might be electric heart diseases or treatment with Beta Blockers. A recent review investigates transmission pathways of C. difficile, where contact to symptomatic or asymptomatic carriers in the community setting is found a relevant source of infection [23]. In contrast, the risk factor “appearance of another patient in the ED with a positive sample for C. difficile within the last week” did not show significance in our study.

Known risk factors for Norovirus include contact with other individuals with gastroenteritis symptoms [9], treatment with Proton pump inhibitors [24] and belonging to high risk groups: young children, elderly, travellers, soldiers, and patients who are immunocompromised or have received an organ transplants [25]. Somewhat surprisingly, we found that male gender was a significant risk factor for Norovirus infection, although we did not identify a plausible explanation for this finding. Two other recent studies found no gender difference in the rate of infection for Norovirus infection [26, 27]. Thus, we suspect that our finding of gender differences is an incidental finding.

Contact with other individuals with symptoms of gastroenteritis did not have a significant association with Norovirus infection, neither in our study nor in a Swedish study [12]. There was, however, a significant association with the variable “appearance of another patient in the ED with a positive sample for Norovirus within the last week”. This likely reflects the fact that community-acquired Norovirus infections presents in out-breaks, but that transmission in most cases does not occur directly from a person recognized as contagious.

Our results need some considerations for clinical implication and further studies.

Around ¼ of all admitted patients to the ED has a very contagious GE which requires strict contact precautions but it is difficult to judge whom to isolate based on clinical judgement and it is a concern that the diagnostic accuracy is so low concerning isolations. Short duration, vomiting and similar cases in the department might aid to guide the clinician concerning norovirus infection, and high age and recent antibiotic treatment raises suspicion of C. difficile infection. However, we identified several factors that should be considered when evaluating the need for isolation in the ED. Further studies with a higher number of participants are needed to investigate whether these factors can be used to generate a simple, rapid, clinical-based scoring system that can assist front-line clinicians in making accurate patient isolation decisions. Of note, there is a likely need for two different risk scoring systems, one for Norovirus and another for C. difficile, since patients with these infections have distinct demographic characteristics and varied clinical presentations. Our data and previous publications indicate that developing such clinical rules will be challenging, and thus there is a need to explore other means of improving isolation procedures. Specifically, we believe that new rapid tests for faecal pathogens have an important role to play and should serve as a focus for future clinical studies. While we predict that such tests may not reduce the number of patients inappropriately placed in isolation, they may significantly reduce the time spend in isolation since time between obtaining a sample and the results can diminished.

The strengths of our study include systematic and prospective data collection in a relevant clinical context, an extended study period of 18 months, and a multicentre setting.

However, our study does have some limitations. Not all patients could deliver faecal samples, either because the diarrhoea resolved or they were discharged from hospital before their samples could be collected. While we do not believe that this had a major impact on our interpretation of the study data, we cannot exclude the possibility that patients with less severe disease had a different pathogen distribution. Specifically, it is plausible that such patients have a lower prevalence of C. difficile. Another study limitation is that approximately one-third of patients who met the inclusion criteria were not included in the study, in large part due to a failure to obtain consent. Thus, it is possible that elderly and the more fragile patients are under-represented in the study group. Since age and comorbidity are recognized risk factors for C. difficile, it is thus possible that the study underestimated the prevalence of C. difficile.

Norovirus and C. difficile are common pathogens in patients admitted with acute gastroenteritis. There are several risk factors which can help identify these patients, but it is uncertain whether this knowledge can be used to improve the rational use of isolation in the ED. More studies in this area are warranted. Rapid diagnostics may be an alternative approach and are a potential future research avenue.