Extra-intestinal complications following acute giardiasis

Abstract

Background: Giardia lamblia is a common waterborne protozoan parasite worldwide. A large outbreak occurred in Bergen, Norway, in 2004. It was caused by heavy rainfall overloading the sewage system leading to contamination of the main water reservoir to the city centre. Approximately 48 000 people were exposed. A cohort study was established after the outbreak including 1252 individuals with laboratory confirmed diagnosis of giardiasis and a matched control group. Giardia typically causes shortterm gastroenteritis, whereas information on long-term complications and extraintestinal complications was limited before the outbreak.

Aims: The overall aim of the studies in this thesis was to investigate extra-intestinal longterm complications following acute giardiasis.

Methods: As part of the established cohort study Paper I and Paper II were based on data collected three years after the outbreak and Paper III on data collected ten years after the outbreak. Questionnaires were mailed to 1252 patients with laboratory confirmed giardiasis during the outbreak. A control group with 2:1 matching on age and sex was included.

In Paper I the main outcome was atopic disease and whether it influences the prevalence of irritable bowel syndrome (IBS) and chronic fatigue (CF) three years after giardiasis. Atopic diseases investigated were asthma and allergy which were self-reported, and the diagnoses were based on questions applied in other studies.

In Paper II the main outcomes were excessive daytime sleepiness, insomnia, and level of sleep need three years after infection with Giardia compared with a control group. The validated Epworth Sleepiness Scale (ESS) was used for evaluation of excessive daytime sleepiness, insomnia was evaluated by a single question, and sleep need by self-reported hours of sleep to feel rested.

In Paper III the main outcome was fibromyalgia ten years after acute infection with Giardia lamblia. Fibromyalgia was defined according to the 2016 Fibromyalgia criteria based on the response to the validated Fibromyalgia Survey Questionnaire (FSQ).

IBS and CF were outcome variables in each paper. IBS was defined according to the Rome III diagnostic criteria and CF was defined by the validated Fatigue Questionnaire.

Results: In the three-year follow-up the response rate was 65.3 % (817/1252) among Giardia exposed and 31.4 % (1128/3598) among controls. In the ten-year follow-up the corresponding response rates were 50.3% (592/1176) and 30.4% (708/2330).

In Paper I we found an association between atopy and both IBS and CF in the control group, but not in the exposed group. Among the Giardia exposed with asthma three years after the outbreak, 47.8 % (43/90) had IBS compared with 45.3 % (291/642) among Giardia exposed without asthma (p = 0.662). Among controls with asthma 23.9 % (32/134) had IBS compared with 12.2 % (114/936) among controls without asthma (p < 0.001). The relative risk (RR) for IBS among Giardia exposed with asthma was 2.03 (95% confidence interval (CI): 1.45, 2.62) compared with controls with asthma. The RR for IBS among Giardia exposed without asthma was 3.80 (95% CI: 3.30, 4.32) compared with controls without asthma. Among Giardia exposed with asthma the prevalence of CF was 51.5 % (51/99) compared with 44.9 % (295/657) in Giardia exposed without asthma (p = 0.218). Among controls with asthma 19.3 % (26/135) had CF compared with 10.7 % (102/949) among controls without asthma (p = 0.004). The RR for CF among Giardia exposed with asthma was 2.73 (95% CI: 1.98, 3.45) compared with controls with asthma. The RR for CF among Giardia exposed without asthma was 4.25 (95% CI: 3.66, 4.85) compared with controls without asthma. For allergy, the results were similar.

In Paper II, excessive daytime sleepiness was reported by 31.5 % (245/777) of the Giardia exposed compared with 14.1 % (154/1090) among controls (p < 0.001) three years after the outbreak. Mean (SD) self-reported sleep need was 8.0 (1.4) hours among Giardia exposed and 7.5 (1.1) hours among controls (p < 0.001). Excessive daytime sleepiness and increased sleep need were both found to be independently associated with Giardia exposure. In multivariate analysis the adjusted odds ratio (OR) for excessive daytime sleepiness was 1.40 (95% CI: 1.06-1.86). By multiple linear regression analyses the adjusted regression coefficient for sleep need was 0.12 (95% CI: 0.01-0.24) meaning that Giardia exposure increased the sleep need with 0.12 hours. Insomnia was reported by 15.4% (125/811) of Giardia exposed and 8.8% (98/1116) of controls (p < 0.001), but in the adjusted analyses there was no association between Giardia exposure and insomnia (OR 0.93 (95% CI: 0.65-1.35)).

In Paper III we report the prevalence of fibromyalgia ten years after the Giardia outbreak. The prevalence of fibromyalgia was 8.6 % (49/572) among Giardia exposed and 3.1 % (21/673) among controls (p < 0.001). Unadjusted odds for having fibromyalgia was higher for Giardia exposed compared with controls (OR: 2.91, 95% CI: 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37). Fibromyalgia, IBS, and CF are conditions known to overlap.

Conclusion: These studies show an association between acute giardiasis and several extraintestinal complications three and ten years later. We found the studied complications to be highly associated with IBS and CF. These findings provide novel insight into the complexity of long term consequences after infection and will be useful both for patient management and further research.