2023 Impact Factor
A limited number of studies are available regarding the long-term natural history of post-infectious irritable bowel syndrome (PI-IBS). We aimed to investigate the long-term clinical course of PI-IBS.
A prospective cohort study was conducted from a 2001 shigellosis outbreak in a Korean hospital with about 2000 employees. A cohort of 124 hospital employees who were infected by
The
Patients who were infected by
Irritable bowel syndrome (IBS) is one of most common chronic gastrointestinal disorders, and is characterized by abdominal pain or discomfort associated with disturbed and altered bowel habit in the absence of organic disease.1 IBS is a common digestive disease, with a variable prevalence of 4–22% worldwide.2 Although it is not a life-threatening disorder, IBS poses significant quality of life concerns and remains a substantial burden on the health care system.3
The pathophysiology of IBS is thought to be multifactorial, and possible mechanisms of IBS include altered bowel motility, visceral hypersensitivity, psychosocial distress, abnormal brain-gut interaction, enteric infection, gut-immune activation, low grade inflammation, intestinal permeability, and alterations in intestinal microflora.4–9
The role of enteric infection in the pathogenesis of IBS has been recognized since Chaudhary and Truelove10 first reported the association between infectious gastroenteritis and persistent gastrointestinal symptoms. While many enteric infections cause self-limiting illness, 5–30% of people experience new gastrointestinal symptoms that persist after bacterial dysentery, despite clearance of the inciting pathogen.11 Additionally, approximately 10% of IBS patients reported that their symptoms began following a bout of infectious dysentery.12
Post-infectious IBS (PI-IBS) is defined as the acute onset of new IBS symptoms in an individual who has not previously met the criteria for IBS immediately following an acute illness characterized by 2 or more of the following: fever, vomiting, diarrhea, or positive bacterial stool culture.12
Although there have been many reports regarding PI-IBS associated with pathogens such as
We previously reported on the clinical course of PI-IBS in a homogenous cohort comprised of patients recovered from shigellosis.17,23,24 In the current study, we report on the collective results of a 10-year, long-term follow-up of our small, well-followed, homogenous cohort of patients that developed PI-IBS after shigellosis.
In December 2001, a shigellosis outbreak took place at Gangnam Severance Hospital (formerly “Youngdong Severance Hospital”) in Seoul, Korea, due to the consumption of contaminated food in the hospital employee cafeteria. The causative pathogen was
To serve as a control population, we recruited healthy age- and sex-matched volunteers who were working for the hospital at the time of the shigellosis outbreak (they were not exposed to the contaminated food), and among them, subjects who already had symptoms of IBS before shigellosis was excluded from control cohort and followed separately as sporadic IBS subjects in subsequent analyses.
For the 10-year follow-up survey, we built a list of 124 subjects in the
Both the
For the 10-year follow-up survey, investigators performed the survey questionnaire preferentially by face-to-face interview, and by telephone interview, if necessary. A small financial reward ($10) was given in acknowledgement of subjects’ participation in the study. Written informed consent was obtained from each subject before the survey, and the University of Yonsei Medical School Ethics Committee approved the study protocol (IRB approval number: 3-2011-0242).
Cohort members and their controls were compared by independent
A total of 229 subjects (124 in the
The prevalence of IBS after the shigellosis outbreak was analyzed at each time point after exclusion of subjects who had symptoms of IBS prior to the outbreak (Table 2).
The prevalence of IBS after 1 year was 13.1% in the
The incident of IBS during each time interval was defined as newly-developed IBS among subjects who did not report IBS symptoms in the previous survey (Table 3). The incidence of newly-developed IBS was significantly higher in the
We were able to follow-up 12 patients who developed PI-IBS among the
The figure represents the 10-year natural history of PI-IBS patients (Figure A) and sporadic IBS patients (Figure B). About half of the PI-IBS patients showed remission of IBS symptom after 5 years. However, approximately 25–30% of PI-IBS patients had persistent IBS symptoms even after 8 to 10 years. The natural history of the 14 sporadic IBS (not-related to shigellosis) patients was quite similar to the prognosis of PI-IBS patients.
We analyzed the risk factors which were associated with the ever-developed PI-IBS in the
Since Chaudhary and Truelove10 first reported the concept of PI-IBS in 1962, there has been a substantial amount of epidemiologic data published regarding the association between PI-IBS and various pathogens, including bacterial, protozoal, and viral pathogens. Several studies have established the causative pathogens of PI-IBS, including
The reported incidence of PI-IBS varies from about 5–30%,11 and PI-IBS is now a well-recognized consequence of acute infectious gastroenteritis. There is little doubt that bouts of infectious enteritis may cause some patients to suffer from chronic IBS symptoms, and this fact was also validated by the results of our study. However, little data is available for long-term natural history of PI-IBS.
As far as we know, there have been only 3 studies that have followed participants with PI-IBS for more than 5 years.20–22 Among these relatively long-term reports, one is a 6-year follow-up study from a British cohort,20 another is a 5-year follow-up study from a Swedish cohort,21 and the other is an 8-year follow-up study from a Canadian cohort.22 However, our study followed Korean patients for 10 years, and as such is the longest follow-up study concerning PI-IBS. Moreover, our cohort consisted of a homogenous group of patients who were infected with a single pathogenic strain (
Our current study might improve our understanding of long-term prognosis of PI-IBS. Approximately half of the patients in our study recovered 5 years post-infection, whereas 25–33% still suffered from PI-IBS even 8–10 years post-infection. These results are generally consistent with those of previous long-term studies.20–22 Additionally, we found that the long-term natural course of PI-IBS was similar to that of sporadic IBS in our cohort. Although we found a slightly higher incidence of IBS in the
The risk of newly-developing PI-IBS in the
The mechanisms that underlie PI-IBS remain largely unclear, but several mechanisms have been proposed including immune activation, chronic low grade inflammation, enterochromaffin cell hyperplasia, and alteration of epithelial permeability and neuromuscular function.12,27 Additionally, functional gastrointestinal disorders following acute infectious gastroenteritis not only include PI-IBS, but also post-infectious dyspepsia.18,28,29 The final symptom complex depends on the interaction between local mucosal injury and central factors including adverse life events, personality, and external stressors. Additionally, local injury is often more highly influenced by the nature of the infectious agent. Rotavirus and
Risk factors for PI-IBS in the results of our study are consistent with those from previously published studies, which suggest that duration and severity of initial illness, toxicity of infecting pathogens, female sex, younger age, previous history of functional gastrointestinal disorder, and psychosocial factors are risk factors for developing PI-IBS. In our study, younger age, previous history of FBD, and duration of diarrhea showed statistically significant associations with PI-IBS development, whereas female sex and fever showed increased but statistically nonsignificant odds ratios, possibly due to the small number of study subjects. Additionally, we found no association between vomiting and PI-IBS, which may be explained by the nature of
We followed our cohort with regular surveys on bowel symptoms 1, 3, 5, 8, and 10 years after outbreak. During the course of the surveys, the response rate and final number of participants were lowest at the 5-year survey, and gradually rose to about 70% at the 10-year survey. The small number of participants at the time of the 5-year survey might be due to the exclusion of all subjects who had been excluded from 1-year and 3-year analysis. The response rate of the 10-year survey was relatively higher than previous surveys, because we tried multiple contacts using both face-to-face interview and telephone interview.
The prevalence of IBS increased between 8–10 years post-outbreak in both the infected and control groups. The cumulative incidence of IBS between 8 to 10 years post-outbreak was 15.5% in the infected group and 14.9% in the control group, which are values quite high compared with other interval periods. We cannot definitively explain this increased IBS rates, but we posit that hospital workers may have been exposed to a stressful work environment during that period. Indeed, a series of hospital qualifying programs (Joint Commission International accreditation and Korean Institute for Healthcare accreditation) continued to proceed at the time of the 10th year survey, and the workload of many hospital workers was heavier than usual. We presume that stressful workload might be associated with increase of IBS at the 10th year survey.
The current study has also several limitations. Firstly, the relatively small size of cohorts may decrease the statistical reliability. Secondly, we tried to exclude new PI-IBS due to additional enteric infection after the initial bout of shigellosis, by surveying the history of additional enteric infection between the periods, however there might be some recall bias. Thirdly, the diagnosis of IBS was made by symptoms at only each time points of the surveys, and was not continuously monitored throughout the 10 years, and so, time dependent Cox regression analysis could not be applied to clarify the prognosis of PI-IBS.
In conclusion, the relative risk of PI-IBS was significantly higher in the infected group compared to the control group up to 3 years after shigellosis, but gradually decreased thereafter. The natural history of PI-IBS and sporadic IBS seem to be similar, and in our study approximately half of patients in each group recovered after 5 years, whereas symptoms persisted for 10 years in about one third of patients. The duration of diarrhea as an index of severity of initial illness, previous history of FBD, and younger age were risk factors for PI-IBS.