Pathogen-specific Risk of Functional Gastrointestinal Disorders, Gastroesophageal Reflux Disease and Celiac Disease Following Acute Enteric Infection

Abstract

Purpose: The U.S. CDC recently estimated over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica. The costs of these infections are over $152 billion annually and are associated with significant numbers of outpatient visits, hospitalizations and deaths. Pathogen-specific risk estimates of chronic sequelae are lacking. We utilized a Dept. of Defense medical encounter database to evaluate the risk of functional gastrointestinal disorders (FGD) and celiac disease (CD) following select foodborne infections. Methods: Subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella (nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica, were matched with ≥4 subjects with unrelated diagnoses. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident FGD or CD. Relative risks were calculated using Poisson regression to determine the relationship between pathogen-attributable gastroenteritis and several sequelae while controlling for covariates. Results: A total of 1,753 pathogen-specific gastroenteritis cases (Campylobacter: 738, Salmonella,: 624, Shigella: 376, Yersinia: 17) were identified and followed for a median of 3.8 years (interquartile range: 2.1, 6.7). The incidence (per 100,000 person-years) of PI sequelae was as follows: IBS, 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.2; CD, 0.07. After controlling for important demographic covariates, we found pathogenspecific increased risks (Table 1).Table 1: Adjusted relative risks (95% confidence interval) of multiple sequelae following pathogen-specific gastroenteritisConclusion: These data confirm previous studies demonstrating risk of postinfection IBS following Shigella, Salmonella and Campylobacter infections, but find even higher risk following Yersinea enterocolita infections likely secondary to [unique pathology associated with this pathogen]. In addition, novel associations with other functional disorders (dyspepsia and Campylobacter, constipation and Shigella/Campylobacter). Other novel associations were increased risk of GERD after Campylobacter and Shigella infections, and higher risk of celiac disease after Campylobacter. These data highlight the additional preventable burden of disease associated with these infections which should inform better food security policies and practices, as well as prompt further research into pathogenic mechanisms associated with these infections and outcomes.