In this study, CFS/ICF was diagnosed in 54.7% among 53 patients investigated five years after Giardia duodenalis infection, who had reported chronic fatigue three years after the infection. As much as 25% of the patients in this cohort had other diagnoses possibly explaining chronic fatigue underlining the importance of evaluating differential diagnoses.
A significant reduction in self-reported fatigue at five years compared to three years after giardiasis was found, suggesting that chronic fatigue following giardiasis has a protracted but self-limiting course, also supported by the finding that 20.8% in the cohort who had experienced post-Giardia chronic fatigue earlier had recovered at five years.
All chronic fatigue patients not diagnosed as Giardia
induced CFS/ICF had SAHS, depression or anxiety. According to Fukuda et al. (CDC criteria), sleep apnoea is an exclusion criteria for the diagnosis of CFS [1
]. In a report from patients evaluated in a CFS referral clinic in UK, sleep apnoea was the most common somatic cause of fatigue wrongly diagnosed as CFS by general practitioners [23
]. However, other researchers argue that SAHS is a common comorbidity rather than exclusion criterion in CFS. Polysomnographic evaluation revealed SAHS in 60% among patients with CFS in one report from Canada [24
]. Further studies by their research group reported that treatment of SAHS with continuous positive airway pressure (CPAP) did not improve fatigue in patients with CFS and SAHS, supporting that SAHS was a comorbid disease and not an exclusion criterion to the CFS diagnosis [25
]. Furthermore, both patients with CFS, and patients with SAHS without CFS, experienced worse sleep quality, fatigue and psychological functioning compared to a healthy control group [25
], supporting our finding that SAHS is an important differential diagnosis to CFS but also may be a possible comorbidity.
Psychiatric illness in chronic fatigue may be a comorbid condition or a consequence due to reduced quality of life, rejection and stigmatization often experienced by these patients. Severe psychiatric illness is defined as an important exclusion criterion to the diagnosis of CFS [1
], as such disorders will often have chronic fatigue as implicit symptom of the illness. However, depression and anxiety are commonly misdiagnosed as CFS [23
] with potentially severe consequences due to lack of adequate diagnosis and treatment. It may be difficult to differentiate psychiatric illness from secondary psychological symptoms found in CFS [25
], and evaluation by a psychiatrist may be needed in order to establish the correct diagnosis and treatment.
In our study, CFS was excluded when SAHS, depression and anxiety were diagnosed, although it should be taken into account that giardiasis may have contributed to or triggered chronic fatigue also among these patients.
A high prevalence of IBS [16
] and a highly significant association between chronic fatigue and IBS has previously been reported among patients who had laboratory confirmed giardiasis during the Bergen outbreak [16
]. A high level of IBS comorbidity was confirmed in the present study (Table
). Interestingly, a high prevalence of comorbid allergy (58.5%) and asthma (20.3%) was recorded in the present study, supporting the possible association between chronic fatigue and atopic disease reported and discussed previously [28
Those who had recovered from chronic fatigue were significantly younger than those who had chronic fatigue with other aetiology, supporting that higher age could be a risk factor for chronic fatigue as previously reported after the Giardia
]. No potential risk factors were found to be significantly associated with CFS/ICF compared to the other categories. However, the limited number of patients should be taken into account when interpreting the analyses of factors potentially associated with CFS/ICF in this study.
The participation rate was relatively low (21%), possibly influenced by factors such as lack of energy to participate in the extensive work up, interpretation of invitation to psychiatric treatment as an unwanted insinuation of chronic fatigue having psychiatric aetiology, recovery from chronic fatigue or severe fatigue hampering the patient’s ability to participate. However, the lack of representativeness among all Giardia positive individuals during the Bergen outbreak does not have important implications for the interpretation of the results in this clinical study, since it describes CFS and differential diagnoses in a cohort of self-reported fatigue following giardiasis, and does not aim at identifying the prevalence of post-Giardia CFS in the general population.
A strength in this study is the thorough clinical evaluation as basis for the CFS/ICF diagnosis. In a study by Næss et al. [17
] reporting CFS in 60% one to three years after giardiasis during the Bergen outbreak, patients were selected among those referred to department of neurology and not by invitation among all laboratory confirmed cases reporting chronic fatigue as in the present study and results are therefore not comparable. Næss et al. report a high level of depression and anxiety among their patients, however, evaluation by psychiatrist was not performed to evaluate these conditions as differential diagnoses to CFS.
The pathophysiology in post-infectious chronic fatigue is not well described, and in Giardia
induced chronic fatigue even less, but symptom pattern as well as infectious aetiology would support the hypothesis that immunological dysfunction could play a role. In a recent report from the present cohort investigating previously reported markers of immune dysfunction in CFS, a decreased level of natural killer cells was found among CFS patients, suggesting a possible immunological abnormality that should be investigated further [29