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Title: Sequelae of selected gastrointestinal infections : incidence, risk factors and economic impact on the National Health Service in England
Author: Esan, Oluwaseun
ISNI:       0000 0004 8507 3603
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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Background Sequelae of reactive arthritis (ReA), irritable bowel syndrome (IBS), Guillain-Barré syndrome (GBS), ulcerative colitis (UC), Crohn's disease (CD) and Rheumatoid arthritis (RA) following gastrointestinal (GI) infections can occur. Evidence suggests proton pump inhibitors (PPI) or antibiotics can increase the risk of GI infections, but their role in sequelae onset is unclear. Further, the impact on the National Health Service (NHS) of GI infections sequelae is unknown. Methods Four studies were conducted in this thesis. First, a systematic review (SR) to determine the association between prior use of PPI or treatment with antibiotics and the onset of ReA and IBS amongst patients with Campylobacter or non-typhoidal Salmonella (NTS) infections. Second, a population-based study of routinely collected linked primary care, hospital, deprivation and deaths data (2000-2015) to determine the incidence of ReA, IBS, GBS, UC, CD, and RA in the 12 months following Campylobacter or NTS infection. Third, a retrospective cohort study to assess the role of antibiotics or PPI in the onset of sequelae amongst patients with Campylobacter infection. Fourth, an economic assessment to determine the impact of sequelae of the selected GI infections on the volume, type and costs of all health care encounters in the periods' pre- and post-infection. Results In the SR, only one study reported an elevated risk in the onset of ReA amongst patients with the selected GI infections who had prior PPI prescription. There was no clear association between antibiotics and sequelae onset. In the population-based study, less than two per cent of the patients developed sequelae. Patients with sequelae were mainly females in comparison with those with GI infection only. Of all the sequelae considered, the incidence of IBS was highest in the 12 months post-infection (1.2%). Female Campylobacter patients on PPI were two and a half times more likely to develop IBS. There was no association with antibiotics and the onset of sequelae of campylobacteriosis. Sequelae significantly impacted the NHS with an additional £1.3 million in expenditure on average annually. Males, older people (65+), and those with underlying health conditions incurred the highest costs. Conclusions The findings raise the need to emphasise the negative consequences of Campylobacter and NTS infections. It highlights the significant impact of sequelae on the NHS and the patient groups with excess expenditure. This is vital in the evaluation of public health interventions to reduce the overall burden of these GI infections. Further evidence to determine the existence of a dose-response relationship between PPI and Campylobacter infection in the onset of IBS is warranted.
Supervisor: Violato, Mara ; Fanshawe, Thomas ; McCarthy, Noel ; Perera, Rafael Sponsor: NIHR Health Protection Research Unit in Gastrointestinal Infections
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Non-typhoidal Salmonella infections ; Proton pump inhibitors ; Economic burden ; Gastrointestinal infections epidemiology ; Campylobacter infections ; Foodborne infections ; Antibiotics ; Linked electronic health records ; Sequelae ; Irritable bowel syndrome