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Observational Studies
Gunnhild S. Hunskar*, Guri Rortveit, Sverre Litleskare, Geir Egil Eide, Kurt Hanevik,
Nina Langeland and Knut-Arne Wensaas
Prevalence of fibromyalgia 10 years after infection
with Giardia lamblia: a controlled prospective
cohort study
https://doi.org/10.1515/sjpain-2021-0122
Received July 9, 2021; accepted September 21, 2021;
published online October 21, 2021
Abstract
Objectives: To investigate whether acute infection with
Giardia lamblia is associated with fibromyalgia 10 years
after infection and whether fibromyalgia is associated with
irritable bowel syndrome (IBS) and chronic fatigue (CF) in
this setting.
Methods: A cohort study was established after an outbreak
of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed
cases and a matched control group were followed for 10
years. The main outcome was fibromyalgia 10 years after
giardiasis, defined by the 2016 revisions of the fibromyalgia
diagnostic criteria using the Fibromyalgia Survey Question-
naire (FSQ).
Results: The prevalence of fibromyalgia was 8.6% (49/572)
among Giardia exposed compared to 3.1% (21/673) in con-
trols (p<0.001). Unadjusted odds for having fibromyalgia
was higher for Giardia exposed compared to controls (odds
ratio (OR): 2.91, 95% confidence interval (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 fibro-
myalgia 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).
Conclusions: We found a higher prevalence of fibromy-
algia among Giardia exposed compared to controls 10
years after the acute infection. Fibromyalgia was strongly
associated with IBS and CF, and the difference between the
exposed and controls can be attributed to the high preva-
lence of IBS and CF among the Giardia exposed. Notably,
this study was not designed to establish causality between
Giardia exposure and the outcomes.
Keywords: chronic fatigue; fibromyalgia; Giardia lamblia;
irritable bowel syndrome; medically unexplained physical
symptoms.
Introduction
The term medically unexplained physical symptoms (MUPS)
describes a range of symptoms that are not explained by
measurable pathology, but are seen to occur together and
lead to different symptom patterns, commonly described as
syndromes [1, 2]. There is a certain overlap in criteria for the
different syndromes and considerable overlap in the preva-
lence as patients frequently meet the criteria for several
conditions [3–6]. Whether MUPS should be considered
different presentations of one common condition or as
distinct and different syndromes is an ongoing discussion.
Many now support a view that this is a wide collection of
symptoms that might have shared etiology, but can also be
*Corresponding author: Gunnhild S. Hunskar, MD, Department of
Global Public Health and Primary Care, University of Bergen,
Årstadveien 17, N-5009 Bergen, Norway; Department of Dermatology,
Haukeland University Hospital, Bergen, Norway; and Research Unit for
General Practice, NORCE Norwegian Research Centre, Bergen,
Norway, E-mail: gunnhild.hunskar@uib.no
Guri Rortveit, Department of Global Public Health and Primary Care,
University of Bergen, Bergen, Norway; and Research Unit for General
Practice, NORCE Norwegian Research Centre, Bergen, Norway,
E-mail: guri.rortveit@uib.no
Sverre Litleskare and Knut-Arne Wensaas, Research Unit for General
Practice, NORCE Norwegian Research Centre, Bergen, Norway,
E-mail: svli@norceresearch.no (S. Litleskare),
knwe@norceresearch.no (K.-A. Wensaas)
Geir Egil Eide, Department of Global Public Health and Primary Care,
University of Bergen, Bergen, Norway; and Centre for Clinical
Research, Haukeland University Hospital, Bergen, Norway,
E-mail: geir.egil.eide@helse-bergen.no
Kurt Hanevik and Nina Langeland, Norwegian National Advisory Unit
for Tropical Infectious Diseases, Haukeland University Hospital,
Bergen, Norway; and Department of Clinical Science, University of
Bergen, Bergen, Norway, E-mail: kurt.hanevik@uib.no (K. Hanevik),
nina.langeland@uib.no (N. Langeland)
Scand J Pain 2022; 22(2): 348–355
Open Access. © 2021 Gunnhild S. Hunskar et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0
International License.
divided into subgroups [6, 7]. Irritable bowel syndrome (IBS),
chronic fatigue (CF) (including chronic fatigue syndrome
(CFS)), and fibromyalgiaareamongthemoststudiedinthis
group of disorders. They are associated with each other and
overlap [7–10].
CFS/CF and IBS are well-known complications following
infections. Previous studies have shown that long-term
fatigue can complicate different infections like mono-
nucleosis and viral meningitis, and fatigue has also been a
major concern following the recent COVID-19 pandemic
[11–13]. Post-infectious IBS may follow gastroenteritis caused
by parasites, bacteria and viruses [14–17]. Smaller studies on
fibromyalgia following infections such as mycoplasma,
Lyme disease and different viruses have not provided clear
supportforsuchanassociation[18–22].
In 2004, a main water reservoir for the city of Bergen,
Norway was contaminated with Giardia lamblia and an
estimated 48,000 inhabitants were exposed, and about
2,500 people were treated for giardiasis [23]. Giardiasis is a
rare condition in the Nordic countries and Europe, and
outbreaks of this size are uncommon [24]. Three years after
the outbreak, a large cohort study was set up including
1,252 patients with a confirmed infection during the
outbreak and a control group. Our research group has
previously reported a strong association between giardi-
asis and both IBS and CF three, six and ten years after the
acute infection [25–27]. An association between fibromy-
algia and giardiasis has not previously been explored.
Sporadic IBS and CFS/CF have often been studied
together with fibromyalgia, but this triad has not been
studied in the context of a preceding infection. Since we have
previously documented an association between giardiasis
and both IBS and CF, we wanted to investigate whether there
could also be an association with fibromyalgia [26]. In 2010,
new criteria for fibromyalgia formed the basis for the
developmentofaquestionnairethatwithfurthermodifica-
tions was suitable for epidemiological studies [28]. There-
fore, in our ten-year follow-up we included the Norwegian
version of the 2016 modified Fibromyalgia Survey Ques-
tionnaire (FSQ), a validated tool for assessment of fibromy-
algia without clinical examination [29].
The main aim of this study was to investigate whether
acute infection with G. lamblia was associated with fibro-
myalgia 10 years after infection and whether fibromyalgia
is associated with IBS and CF in this setting.
Methods
Study design
This was a prospective cohort study set up after an outbreak of
G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and
a control group recruited from the same area and matched 1:2 by age
and sex were followed three, six and ten years after exposure. The
study population included 1,252 exposed patients and 2,504 controls.
Controls reporting a physician-verified diagnosis of giardiasis in 2004
were excluded. This study is based on data from the ten-year follow-
up that was restricted to participants 18 years and older in 2014 [26].
For background, we give some previously published data on the
prevalence of IBS and CF here [26]. Ten years after the outbreak 43.1%
(n=248) of Giardia exposed had IBS compared to 13.7% (n=94) among
controls (p<0.001), and the prevalence of CF was 26.1% (n=153) in the
Giardia exposed group compared to 10.5% (n=73) among controls
(p<0.001) (Table 1).
Variables
The exposure in this study was identification of G. lamblia in stool
samples during the outbreak in 2004.
The main outcome variable was fibromyalgia. Fibromyalgia was
defined according to the 2016 revision of the 2010/2011 fibromyalgia
diagnostic criteria [30]. In 2010, the American College of Rheuma-
tology (ACR) approved a new set of diagnostic criteria, replacing the
ones used since 1990. The new criteria increased the focus on other
symptoms in addition to pain, in concordance with how the under-
standing of fibromyalgia has changed, and abandoned the need for an
examination of tender points [28]. The questionnaire and criteria were
modified in 2011 so that all items could be obtained by patient self-
administration using the Fibromyalgia Survey Questionnaire (FSQ),
feasible for epidemiological and clinical studies [31]. Several valida-
tion studies have been performed and the revision of the criteria in
2016 was based on the studies published up to that point. A validation
study of the Norwegian version of the FSQ was published in 2020 [29].
Table :Characteristics, demographics and outcomes in
Giardia exposed and controls years after an outbreak of
giardiasis in Bergen, Norway in .
Characteristics Exposed Controls p-Valuea
n (%) n (%)
Age groups,
years
– (.) (.) n.s.
– (.) (.)
– (.) (.)
– (.)(.)
Female sex (.) (.) n.s.
Marital status Single (.) (.).
Married (.) (.)
Divorced/
separated
(.) (.)
Widowed/
widower
(.) (.)
Education Primary school (.) (.) n.s.
Secondary
school
(.) (.)
University (.) (.)
IBS (.) (.)<.
CF (.) (.)<.
Fibromyalgia (.) (.)<.
aPearson’s two-sided exact chi-squared test. Abbreviations: IBS,
irritable bowel syndrome; CF, chronic fatigue; n.s., not significant,
p>..
Hunskar et al.: Prevalence of fibromyalgia after infection with G. lamblia 349
The FSQ consists of two parts; the Widespread Pain Index (WPI)
that assesses the number of painful body areas, and the Symptom
Severity Scale (SSS) that assesses the severity of certain symptoms [30].
The WPI includes 19 body areas and participants note if they had
pain in the specific area during the last week (score 0–19). The SSS
consists of six items. The first three indicate symptom severity of fatigue,
waking up unrefreshed and cognitive impairment during the last week
on a 4-item Likert scale (score 0–3). The last three items identify the
presence during the last six months of headaches, pain or cramps in the
lower abdomen and depression (score 0–3). The score on the different
items of the SSS are summed up to give the “SSS score”(range 0–12).
Patients have to meet three criteria for the diagnosis of fibro-
myalgia [30]: 1) Either WPI≥7 and SSS score≥5, or WPI 4–6 and SSS
score≥9; 2) Generalized pain defined as pain in at least four out of the
following five regions based on the WPI: left upper region, right upper
region, left lower region, right lower region and axial region; 3)
Symptoms have been generally present for at least three months.
IBS was defined according to the Rome III diagnostic criteria,
which require the presence of recurrent abdominal pain or discomfort
for at least three days per month in the last three months in relation to
defecation or stool changes [25, 32]. Fatigue was measured by the
validated Fatigue Questionnaire developed by Chalder et al. [33]. This
questionnaire consists of 13 questions where 11 of these measure
various aspects of physical and mental fatigue, and the last two how
long and which proportion of the time symptoms have been present.
CF criteria are fulfilled if there is a positive score on four or more of the
11 aspects of fatigue, and fatigue has been present for the last six
months or more. The scoring and use of these questionnaires have
previously been described [25].
Demographic variables included were sex (dichotomous), age
(categorized in groups of 20 years, but the first group including par-
ticipants from 18 years of age up to 39), marital status (four categories)
and level of education (three categories) (Table 1). These were all
evaluated as possible confounders by logistic regression modeling.
Statistical analyses
Participants with partially missing answers on the FSQ were allocated
to a group if the answers given would unambiguously decide group
affiliation.
We calculated descriptive statistics as percentages with p-values
for differences between groups. The exact chi-squared test was
applied to test differences in proportions. Binominal logistic regres-
sion was applied to investigate associations between fibromyalgia at
ten-year follow-up, and assumed relevant or confounding variables
were evaluated, i.e. Giardia status, IBS, CF, age, sex, marital status
and education. Interactions of interest from IBS or CF on the effect of
exposure status were tested in the regression model, and if not sig-
nificant, they were not included in the final models. The results of
these analyses are presented as odds ratio (OR) with 95% confidence
intervals (CI). The level of statistical significance was set at ≤0.05. All
analyses were performed in SPSS version 24.
Results
The overall response rate in the ten-year follow-up was
37.1% (1,300/3,506), with a 50.3% (592/1,176) response rate
among Giardia exposed and 30.4% (708/2,330) among
controls. Among Giardia exposed responders two ques-
tionnaires were returned incomplete and therefore excluded
from the study, making this group consisting of 590 par-
ticipants. Among controls six questionnaires returned were
from individuals who had Giardia in 2004 and six ques-
tionnaires were incomplete, and hence a total of 12 ques-
tionnaires were excluded making the control group consist
of 696 participants. There were no differences between the
groups with regard to age, sex or education. However, the
groups differed in marital status, as a higher proportion of
controls were married or cohabitants (Table 1).
The prevalence of fibromyalgia was 8.6% (49/572) in
the Giardia exposed group compared to 3.1% (21/673) in the
control group (p<0.001). Among the Giardia exposed with
fibromyalgia 87.0% (40/46) also had IBS and 69.4% also
had CF (34/49), compared to the controls with fibromyal-
gia, where 50.0% (10/20) had IBS and 42.9% (9/21) had CF
(p<0.001 for both) (Figure 1). Among Giardia exposed 4.6%
(27/590) had all three conditions (fibromyalgia, IBS and CF)
compared to 0.4% (3/696) in the control group (p<0.001).
Among the Giardia exposed with IBS 16.5% (40/242)
had fibromyalgia, compared to 11.2% (10/89) among con-
trols with IBS (p<0.001). Among the Giardia exposed with
CF 22.8% (34/149) had fibromyalgia, compared to 12.9%
(9/70) among controls with CF (p<0.001).
Table 2 shows the effects of exposure status (Giardia
exposed vs. controls), adjusted for IBS and CF, on the OR
for fibromyalgia at ten-year follow-up. Confounders eval-
uated were sex, age, marital status, and level of education.
The unadjusted OR for having fibromyalgia was higher for
Giardia exposed compared to 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). Regardless of exposure status,in par-
ticipants without CF the OR for fibromyalgia was 6.27 times
higher for participants with IBS than for those without
(95% CI: 3.31, 11.91). In participants without IBS the OR for
fibromyalgia was 4.80 times higher for those with CF than
for those without (95% CI: 2.75, 8.37).
Discussion
To our knowledge, this is the first study to report fibro-
myalgia in a large cohort of patients previously exposed to
a well-defined infection. We found that 10 years after an
outbreak of giardiasis there was a higher prevalence of
fibromyalgia in the exposed group compared to the con-
trols. Adjusted analyses indicate that the difference was
dependent on status for IBS and CF, implying that there
was no association between fibromyalgia and exposure to
350 Hunskar et al.: Prevalence of fibromyalgia after infection with G. lamblia
Giardia. In the Giardia exposed group, there was a higher
prevalence of both IBS and CF that could explain the higher
prevalence of fibromyalgia in this group.
Prevalence of fibromyalgia
A meta-analysis estimated the prevalence of fibromyalgia
worldwide at 1.78% in the general population, whereas
European studies have found a prevalence of 2.64%, with
prevalences varying from 0.29 to 11.10% [3]. This review
also showed that the prevalence of fibromyalgia in more
than 20 studies conducted from 1993 to 2015 based mainly
on the ACR 1990 criteria was 2.32%. The ACR criteria are
among the most used tools of diagnosis for studies on
fibromyalgia since 1990, but has been modified since 2010.
Two studies used the 2010 diagnostic criteria and one used
Figure 1: Venn diagram of fibromyalgia (FM), irritable bowel syndrome (IBS) and chronic fatigue (CF) in 590 Giardia exposed and 696 controls
10 years after the outbreak of giardiasis in Bergen, Norway in 2004.
Hunskar et al.: Prevalence of fibromyalgia after infection with G. lamblia 351
the modified criteria from 2011, which is obtained
completely by patient self-administration. The study using
the 2011 criteria found an age and sex adjusted prevalence
of fibromyalgia of 6.36% in the general population in a
county in Minnesota, USA, somewhat higher than in our
study [34]. None of the studies reviewed were performed
after 2015; hence, the 2016 fibromyalgia criteria revisions
were not evaluated. In our study, fibromyalgia was defined
according to the 2016 revision of the 2010/2011 fibromyal-
gia diagnostic criteria, which is the latest modification [30].
The European prevalence of 2.64% found in the review
article above corresponds well with the prevalence of 3.1%
in our control group, which is probably representative of
the general population.
Different viral infections are associated with fibromy-
algia [3]. Patients with chronic or carriers of inactive hepa-
titis B and chronic hepatitis C have reported a higher
prevalence of fibromyalgia, and among patients infected
with HTLV-1 there was also an association between this
infection and fibromyalgia [35–38]. Studies have shown that
Lyme disease may trigger fibromyalgia or widespread pain
during or after active infection, but the symptoms of Lyme
disease may be confused with fibromyalgia symptoms and
this makes the association difficult to prove [18]. Lyme dis-
ease has effective treatment and since fibromyalgia symp-
toms were found to persist this can possibly be seen as a
post-infectious complication. Mycoplasma infection and
fibromyalgia has also been studied but it is unclear if
infection can trigger or precipitate fibromyalgia [19].
Overlap of fibromyalgia, IBS and CF/CFS
Previous studies including patients with IBS have found a
prevalence of fibromyalgia ranging from 12.90 to 31.60%
[39–42]. These studies all based the diagnosis of fibromy-
algia on physical examination. The two studies with the
highest prevalence described the use of physical exami-
nation according to the 1990 ACR criteria [39, 41]. A large
study from Taiwan found a higher incidence of IBS in
fibromyalgia patients followed from 2000 to 2011, and
fibromyalgia was associated with a 1.54 times increased
risk of IBS [43].
A review article of overlap of diagnoses in patients with
fibromyalgia, found that 21–80% also had CFS, and
36–60% also had IBS. Most of the underlying studies used
the 1990 ACR criteria to diagnose fibromyalgia [44]. A twin
study examining comorbid clinical conditions associated
with CF showed a markedly higher prevalence of fibro-
myalgia and IBS in the fatigued compared to the non-
fatigued twin. Fibromyalgia was shown in 72–77% of the
fatigued twins depending on how strict the definition of
fatigue was classified, compared to 0–7% among the non-
fatigued twins. IBS was shown in 52–59% in the fatigued
twins compared to 9–14% in the non-fatigued twins [45].
The associations between the medically unexplained
conditions seen in other studies support our findings that
having IBS and/or CF was an important risk factor for also
having fibromyalgia. The number of respondents with
fibromyalgia was small, particularly in the control group,
but there was still a substantial overlap in line with pre-
vious literature on the association between these three
MUPS conditions [7–10].
Comparing findings in the literature to our study is not
straightforward considering the use of many different
outcome-measuring tools, both questionnaires and physical
examination. In addition, when examining several out-
comes, some of which are rare in the general population,
groups may be small and the strength of the analyses
decreases. Still, our findings cohere with the literature with
regard to the associations and higher prevalences of fibro-
myalgia when also IBS or CF is present, and patients meeting
the criteria of several MUPS simultaneously [9, 22, 46].
We report prevalence of fibromyalgia at 10 years after
the exposure, not incident cases after the exposure. We do
not know the prevalence of fibromyalgia at baseline or in
the following years up to our measuring point at 10 years.
Other studies have looked at infection as a trigger for
fibromyalgia, but the findings are inconsistent, where a
Table :Results from logistic regression analyses of fibromyalgia on Giardia, IBS and CF from , participants years after the outbreak
of giardiasis in Bergen, Norway in .
Variables Unadjusted Adjusted (n=,)
nOR % CI p-Value OR % CI p-Value
Constant , n.r. . n.r. n.r.
Giardia exposed/control , . (.,.)<. . (.,.).
IBS: yes/no , . (.,.)<. . (.,.)<.
CF: yes/no , . (.,.)<. . (.,.)<.
Abbreviations: IBS, irritable bowel syndrome; CF, chronic fatigue; OR, odds ratio; CI, confidence interval; p, p-value from likelihood ratio test;
n.r., not relevant.
352 Hunskar et al.: Prevalence of fibromyalgia after infection with G. lamblia
large review suggested that post-infectious fibromyalgia
was merely relevant for subgroups of the patients [22]. In
line with this, we find the higher prevalence of fibromyal-
gia in the exposed group to be associated with IBS and/or
CF and not necessarily associated with Giardia exposure.
These three conditions are associated, but the mechanisms
are unclear. We looked at these conditions from the
perspective of an infectious disease, but how this microbe
might influence these associations we do not know. A
previous article from our group investigating the preva-
lence of IBS and CF three, six and ten years after exposure,
showed that close to 25% in the exposed group had
persistent IBS and 14% had persistent CF, but there
were also considerable fluctuations in and out of these
diagnoses at the different time points [26]. This could also
be the case for fibromyalgia.
Strengths and limitations
This study was a cohort study with a large number of
participants. The exposed group had laboratory confirmed
infection with G. lamblia during the outbreak, making
exposure misclassification unlikely. Giardiasis is rare in
Norway and the risk of the controls having been exposed to
Giardia was small, except for during the outbreak.
Accordingly, controls who reported physician-verified
diagnosis of giardiasis in 2004 were excluded. The
exposed group consisted of participants who contacted a
physician during the outbreak which could indicate more
doctor-seeking behavior in this group. This could also
contribute to selection bias for patients with fibromyalgia.
We did not collect baseline data on fibromyalgia, and
we do not have prevalences of fibromyalgia, IBS or CF prior
to the outbreak in our study population. Higher preva-
lences of these conditions among the Giardia exposed
compared to the general population can therefore not be
excluded, though this is less likely to completely explain
the demonstrated differences.
We used validated and well-known questionnaires to
define outcomes. The FSQ includes a question on abdom-
inal pain and a question on fatigue that can explain parts of
the overlap with IBS and CF, but more symptoms are
required for these diagnoses so those questions probably
do not explain the overlap alone.
The response rates have declined at each point of
follow-up in the exposed group and varied in the control
group, making selection bias a possibility in that individuals
with symptoms are more likely to respond [26]. Some degree
of participation fatigue is likely. Participants might not feel
the questions concerned them, it was a long time since the
outbreak andthis was the third time that they were asked to
participate. For IBS, the prevalence decreased from 3 to 6
years and 3 to 10 years after the outbreak, but there was no
change from 6 to 10 years [26]. For CF, the prevalence
declined at all three measuring points. These decreases in
prevalence of IBS and CF through 10 years could explain
some of the decline in response rate as less participants
might feel the questions concerned them.
Conclusions
We investigated the association between fibromyalgia and
G. lamblia infection, IBS and CF. We found a higher preva-
lence of fibromyalgia in the Giardia exposed group compared
to the control group. Fibromyalgia was strongly associated
with IBS and CF, and the difference between the Giardia
exposed and the control group with regards to fibromyalgia
prevalence might be attributed to the high prevalence of IBS
and CF among the Giardia exposed. This study was not
designed to identify cause and effect in relation to Giardia
exposure and the syndromes investigated.
Research funding: The first author has been funded from
the Department of Dermatology, Haukeland University
Hospital, Bergen, Norway. The sponsors had no role in
study design, in collection, analysis, interpretation or data,
or in writing or deciding to submit the manuscript.
Author contributions: All authors have accepted responsibility
for the entire content of this manuscript and approved its
submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent has been obtained
from all individuals included in this study.
Ethical approval: The Regional Committee for Ethics in
Medical Research approved the study (ref. no. 2014/1372).
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