People exposed to the protozoan Giardia lamblia are at increased risk of having irritable bowel syndrome and chronic fatigue years after their gastrointestinal infections have been treated, a team of Norwegian researchers has found.
Although other types of acute gastrointestinal infections have been associated with ongoing disorders including both fatigue and irritable bowel syndrome (IBS), the finding challenges the assumption that acute giardiasis, once treated, does not cause long-term complications.
Among a cohort of people who became ill during a 2004 outbreak of giardiasis in the Norwegian city of Bergen, nearly half reported having chronic fatigue, IBS, or both 3 years later. Prescription data from the time of the outbreak, which was traced to a contaminated reservoir, suggested that the vast majority of those affected had been treated with metronidazole. Giardiasis is not endemic in Norway.
For their research, published online Sept. 12 in the journal Gut (doi:10.1136/gutjnl-2011-300220), Dr. Knut-Arne Wensaas of the University of Bergen and Uni Health in Bergen, and his colleagues, collected data using validated questionnaires from 817 patients who had laboratory-confirmed G. lamblia infection in 2004, and 1,128 age- and sex-matched controls (mean age, 36; about 66% female) not infected in that outbreak.
Of the exposed cases, 46.1% reported IBS at 3 years, compared with 14% in the control group, for a relative risk of 3.4 (95% CI, 2.9-3.8) after adjustment for potential confounding factors. The same percentage – 46.1% – of the exposed group reported chronic fatigue, compared with 12% of controls (adjusted RR, 4.0; 95% CI, 3.5-4.5).
Despite the study’s observational design, the association between prior infection and the two disorders was seen as so strong, Dr. Wensaas said in an interview, that "it suggests a causal relationship" that warrants further investigation.
In the exposed group, 62.6% of those with IBS had chronic fatigue, as did 30.6% of those without IBS, compared with 32% and 9% for controls. That the two disorders, IBS and chronic fatigue, were found to occur together more frequently among those with previous giardiasis suggested that there could be commonalities in the pathogenesis of giardiasis, IBS, and chronic fatigue. One possible link, the researchers hypothesized, is an immune response involving T lymphocytes.
While a majority of cases were women, sex was not seen as an effect modifier for IBS or for chronic fatigue. The prevalence of IBS was higher among women than men in both the exposed group (48.9% vs. 40.8%) and the control group (15.9% vs. 10.4%).
The authors noted that their definition of IBS was based on the Rome III criteria: "recurrent abdominal pain or discomfort at least 3 days a month in the past 3 months and associated with at least two of three criteria related to defecation (onset associated with a change in frequency or form of stool, or improvement with defecation)."
Dr. Wensaas said that the idea for the study came in part from his and his colleagues’ clinical observations treating patients in Bergen in the years following the outbreak. A previous study, by another research team, had also looked at the same outbreak and outcomes at a 2-year end point (Trans. R. Soc. Trop. Med. Hyg. 2009;103:530-2).
Dr. Wensaas, a general practitioner, said that not only had a large number of patients presented with fatigue and/or IBS following their giardiasis infections, but that they continued to have these symptoms well past the 3-year end point of the study, suggesting that the effects could continue even longer. Dr. Wensaas pointed to one Canadian study that found an elevated risk for IBS at 8 years after acute bacterial gastroenteritis (Gut 2010;59:605-11).
The investigators acknowledged as a weakness of their study the potential for selection bias inherent in its observational design and use of questionnaires. "There is a possibility that those having had acute giardiasis will be more aware of symptoms and more likely to find them abnormal than the controls, and thus report more complaints," they wrote, noting also that the city of Bergen had originally compensated those affected by the outbreak, potentially encouraging exaggerated complaints.
An additional weakness reported was that chronic giardiasis could not be ruled out among respondents.
Dr. Wensaas and his colleagues received funding for their study from the city of Bergen and the Norwegian Medical Association’s Funds for Research in General Practice; none of the study authors said they had relevant financial disclosures.