Diarrhoea in the community – Defining the burden of undiagnosed pathogenic E. coli

Gastrointestinal infections are associated with considerable cost to society in lost working days, public health interventions and distress to those affected. Unfortunately, the majority of patients with diarrhoea do not receive a diagnosis. Standard diagnostic laboratory tests fail to identify a cause for diarrhoea in over 80% of stool samples received.

For this translational research project, we want to obtain a broader picture of the range of diarrhoeal-causing bacteria circulating in Nottinghamshire. We will screen for pathogenic Escherichia coli (E. coli), a group of bacteria known to cause diarrhoea and associated severe disease, but which are not included in our current diagnostic pathway. We will determine the impact of these pathogenic E. coli to diarrhoeal illness in our community by analysing stool samples from 100 patients with diarrhoea.

Many strains of E. coli are normally found in the gastrointestinal tract and cause no adverse effects. However, there are six types of pathogenic E. coli known to cause disease and significant morbidity during infection. These are: (1) Enterohaemorrhagic (EHEC which includes E. coli O157), (2) Enteroinvasive (EIEC), (3) Enteropathogenic (EPEC), (4) Enterotoxigenic (ETEC), (5) Enteroaggregative (EAEC), and (6) the less well-defined Diffuse Adherent E. coli (DAEC).

For example, E. coli O157 is well known for haemolytic uraemic syndrome (HUS), which can be fatal in young children and the elderly. E. coli O157 is included in our diagnostic pathway; however, this is just one of a number of EHEC responsible for severe diarrhoea. Non-O157 EHECs are equally virulent in causing HUS; traditional culture techniques cannot detect them.

A recent European outbreak of one such EHEC (O104) involved over 3800 patients. Fifty-three patients died, and a further 845 developed significant renal impairment. In 2014 in Nottingham, there were two-linked outbreaks of an Enteroinvasive E. coli (Khyber Pass takeaway and a wedding party), which affected 157 individuals, 14 required admission to hospital. Rapid molecular diagnostics was central to diagnosis in this outbreak.

We will determine the local burden of pathogenic E. coli  within our trust’s catchment area. At present, we do not know what is circulating in our community or within the UK. Therefore we will address the impact of this diagnostic gap. To put this in context, some recent EU studies have shown that these pathogenic E. coli can be isolated in one third of diarrhoeal cases, and their identification has been shown to have a positive impact on patient management and antimicrobial stewardship programmes.

This study is important, as standard diagnostic tests are not able to detect these infections. Patients presenting with them (even with apparently mild symptoms) may rapidly deteriorate i.e. renal failure when treated with antibiotics. Early microbiological diagnosis is essential for initiation of appropriate therapy for E. coli infections e.g. HUS, as well as cessation of harmful contra-indicated use of antibiotics, or costly and ineffective treatments (e.g. Eculizumab £5000-20,000 per-dose depending on patient) for mimicking conditions.

Project currently pending Ethics Review – This abstract is taken from a successful grant proposal which I wrote. The project is due to begin in November 2018.