Proton pump inhibitors as a risk factor for norovirus infection

Abstract

SUMMARYNorovirus causes viral gastroenteritis, which is a major problem in health care. The disease causes death in elderly and seriously ill patients, and results in significant health costs each year. Proton pump inhibitors (PPIs) reduce gastric acidity, which is an important protection against microorganisms. We hypothesised that treatment with PPIs increases the risk of contracting norovirus infection. This has not previously been studied. The study was a retrospective case–control study, in which 192 hospitalised patients positive for norovirus in Örebro County, Sweden, were identified as cases. For each case, a hospitalised patient who did not have the infection was selected as a control, and matched with respect to ward, gender, admission date and age. Details of exposure, i.e. treatment with PPIs, were retrieved from the patient records. Odds ratio (OR) with confidence intervals (CIs) and P-values were calculated using McNemar's test. There was a significantly increased risk of norovirus infection in patients treated with PPIs compared with patients without PPI treatment (OR 1·73, 95% CI 1·07–2·81; P = 0·02). PPIs appear to be a risk factor for norovirus infection, and our results motivate future studies to further examine this association.

Further Evidence to Monitor Long-term Proton Pump Inhibitor Use

“…This risk is supported by the biological mechanism that PPIs may promote overgrowth of gut flora. 5 These results align with those of previous studies 7,8 that identified associations between PPI use and incidence of specific enteric illnesses, including those caused by Clostridium difficile and norovirus (a prominent pathogen associated with AGE). 5 Although Vilcu et al 5 thoroughly address limitations of their study, including outcome ascertainment using drug dispensing data and confounding by indication, it is important to reiterate that the possibilities of residual confounding and protopathic bias remain, particularly because adjustment for comorbidities relied on drug dispensation information alone.…”

Ongoing activities to influence the prescribing of proton pump inhibitors within the Scottish National Health Service: their effect and implications

“…Safety concerns include increasing the rate of community acquired pneumonia, increasing the number of fragility fractures, as well as increasing the number of clostridium difficile infections (CDI) possibly due to changes in the gut microbiomes. In addition, increasing the number of norovirus infections as well as increasing the extent of chronic kidney disease and hypomagnesemia (19,20,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). These concerns have resulted in guidance from the Greater Glasgow and Clyde Health Board in Scotland and others to suggest that patients on PPIs long term, and at risk of osteoporosis, should have an adequate intake of calcium and vitamin D (19,38).…”

Proton Pump Inhibitors are Risk Factors for Viral Infections: Even for COVID-19?

“…Since the publication in this journal of the narrative review by Fisher and Fisher related to acid-suppressive therapy and the risk of infections [ 6 ] citing these two articles [ 4 , 5 ], important information has emerged. Proton pump inhibitors appear also to be a risk factor for norovirus infection; in a retrospective case–control study, including 192 hospitalized patients positive for norovirus, Prag et al report that there was a significantly increased risk of norovirus infection in patients treated with PPIs compared with those without (odds ratio 1.73; 95% confidence interval 1.07–2.81; p = 0.02) [ 7 ]. In addition, more recently, Vilcu et al measured the association between continuous PPI therapy and the occurrence of acute gastroenteritis using a large French community pharmacy drug dispensation database; they found a significant association between PPI use and acute gastroenteritis (relative risk 1.81; 95% confidence interval 1.72–1.90), translating to a number needed to harm of 153 patients [ 8 ].…”