Severity of Giardia associated with ... fatigue and abdominal symptoms 2 yr after

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Severity of Giardia infection associated with post-infectious fatigue and abdominal symptoms two years after

Tom Kindlon's submission to CO-CURE was posted Dec 19 09

BMC Infect Dis.;9(1):206. [Epub ahead of print]

Morch K, Hanevik K, Rortveit G, Wensaas KA, Eide GE, Hausken T, Langeland N.

ABSTRACT:

BACKGROUND: A high rate of post-infectious fatigue and abdominal symptoms
two years after a waterborne outbreak of giardiasis in Bergen, Norway in
2004 has previously been reported. The aim of this report was to identify
risk factors associated with such manifestations.

METHODS: All laboratory confirmed cases of giardiasis (n = 1262) during the
outbreak in Bergen in 2004 received a postal questionnaire two years after.
Degree of post-infectious abdominal symptoms and fatigue, as well as
previous abdominal problems, was recorded. In the statistical analyses
number of treatment courses, treatment refractory infection, delayed
education and sick leave were used as indices of protracted and severe
Giardia infection. Age, gender, previous abdominal problems and symptoms
during infection were also analysed as possible risk factors. Simple and
multiple ordinal logistic regression models were used for the analyses.

RESULTS: The response rate was 81 % (1017/1262), 64% were women and median
age was 31 years (range 3-93), compared to 61% women and 30 years (range
2-93) among all 1262 cases. Factors in multiple regression analysis
significantly associated with abdominal symptoms two years after infection
were: More than one treatment course, treatment refractory infection,
delayed education, bloating and female gender. Abdominal problems prior to
Giardia infection were not associated with post-infectious abdominal
symptoms. More than one treatment course, delayed education, sick leave more
than 2 weeks, and malaise at the time of infection, were significantly
associated with fatigue in the multiple regression analysis, as were
increasing age and previous abdominal problems.

CONCLUSION: Protracted and severe Giardia infection seemed to be a risk
factor for post-infectious fatigue and abdominal symptoms two years after
the infection had been cleared.

PMID: 20003489 [PubMed - as supplied by publisher]

Free Full Text at:
http://www.biomedcentral.com/content/pdf/1471-2334-9-206.pdf or go to:
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Dolphin

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Related papers by the same authors

Related papers by the same authors

High rate of fatigue and abdominal symptoms 2 years after an outbreak of giardiasis.

Mrch K, Hanevik K, Rortveit G, Wensaas KA, Langeland N.

Trans R Soc Trop Med Hyg. 2009 May;103(5):530-2. Epub 2009 Jan 30.

National Centre for Tropical Infectious Diseases, Haukeland University Hospital, 5021 Bergen, Norway. kristine.moerch@helse-bergen.no

The aim of this study was to evaluate the prevalence of fatigue and abdominal symptoms 2 years after Giardia lamblia infection. All 1262 cases who had Giardia-positive stool samples during an outbreak in 2004 in Norway received a questionnaire in 2006 asking about fatigue and abdominal symptoms. Fatigue was reported by 41%, whereas 38% reported abdominal symptoms, and there was a highly significant association between these symptoms. Increasing age was a highly significant risk factor for fatigue. The symptoms were not due to chronic infection in this cohort. Our data warrant further investigations into the late effects of giardiasis.

Effects of albendazole/metronidazole or tetracycline/folate treatments on persisting symptoms after Giardia infection: a randomized open clinical trial.

Hanevik K, Mrch K, Eide GE, Langeland N, Hausken T.

Scand J Infect Dis. 2008;40(6-7):517-22.

Department of Medicine, Haukeland University Hospital, Bergen, Norway. kurt.hanevik@helse-bergen.no

After an epidemic of giardiasis, some patients experienced persisting abdominal symptoms despite becoming Giardia-negative in stool samples after metronidazole treatment. The study aimed to determine if these patients were suffering from treatment refractory, chronic, cryptic giardiasis. The design was a prospective randomized open clinical trial with 1 arm receiving anti-Giardia treatment in the form of albendazole and metronidazole (A/M) for 7 d (n=12) and the other arm receiving tetracycline and folic acid (T/F) for 28 d (n=13). Symptom scores and global improvement were outcome measures. Symptom scores were analysed regarding time and treatment using mixed linear modelling. In both groups total symptom scores improved at the end of treatment; the improvement was significant for the T/F group. Bloating decreased significantly in both groups at the end of treatment. One month after treatment, 3 patients in the T/F group (23.1%) and 1 patient (8.3%) in the A/M group reported global symptom improvement. Symptoms recurred in all of these, and after 1 y total symptom scores were unchanged from baseline in either group. Treatment of post-giardiasis persistent abdominal symptoms with T/F or A/M resulted in only temporary symptom relief, possibly due to the anti-inflammatory effect of both treatments. Cryptic chronic giardiasis was not the explanation for the persistent symptoms.

Giardiasis--why do the symptoms sometimes never stop?

Robertson LJ, Hanevik K, Escobedo AA, Mrch K, Langeland N.

Trends Parasitol. 2010 Feb;26(2):75-82. Epub 2010 Jan 6.

Parasitology Laboratory, Institute of Food Safety and Infection Biology, Norwegian School of Veterinary Science, Oslo, Norway. Lucy.robertson@nvh.no

Although giardiasis is considered by most medical practitioners to be an easily treated infection, prolonged symptoms due to, or following, Giardia duodenalis infection can have a significant impact on quality of life. Symptom recurrence, including abdominal symptoms and fatigue, can result from re-infection, treatment failure, disturbances in the gut mucosa or post-infection syndromes. In developed countries, these sequelae can have an enormous impact on quality of life; in developing countries, particularly in children, they add yet another burden to populations that are already disadvantaged. Here, we outline current knowledge, based on individual case sequelae from sporadic infections, observations of population effects following outbreaks and studies of phenotypic and genotypic diversity between morphologically identical isolates of parasites. We also raise further questions, looking for clues as to why giardiasis sometimes becomes an intrusive, long-term problem. 2009 Elsevier Ltd. All rights reserved.

PMID: 20056486 [PubMed - indexed for MEDLINE]
Persisting symptoms and duodenal inflammation related to Giardia duodenalis infection.

Hanevik K, Hausken T, Morken MH, Strand EA, Mrch K, Coll P, Helgeland L, Langeland N.

J Infect. 2007 Dec;55(6):524-30. Epub 2007 Oct 26.

Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway. kurt.hanevik@helse-bergen.no

OBJECTIVES: After a large waterborne outbreak of Giardia infection in Bergen, some patients experienced persisting abdominal symptoms despite metronidazole treatment. This study aimed at investigating possible causes for their symptoms.

METHODS: Over a 15 month period, 124 referred patients were evaluated in a prospective cohort analysis with a standardised investigation including duodenal biopsies and aspirate, blood tests and faecal parasite and calprotectin tests. Recovered subjects were recruited for symptom analysis.

RESULTS: Persisting Giardia duodenalis infection was found in 40 patients (32.3%). Duodenal biopsies showed signs of inflammation in 57 patients (47.1%). Microscopic duodenal inflammation was present in 34 (87.2%) of the Giardia positive and 23 (28.0%) of the Giardia negative patients. There were significant associations between persistent Giardia positivity, microscopic duodenal inflammation and a positive calprotectin test. Duodenal aspirate and duodenal biopsies performed poorly in diagnosis of persistent giardiasis.

CONCLUSIONS: In patients with persisting symptoms after metronidazole treated Giardia infection we commonly found chronic Giardia infection and microscopic duodenal inflammation, especially in illness duration less than 7 months. Both these findings subsided over time. Increasingly, investigations could not determine a definite cause for the persistent symptoms. The very long-term post-giardiasis diarrhoea, bloating, nausea and abdominal pain documented here need further study.
 

Dolphin

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Here are a few things I thought were of interest in the original paper for one reason or another (I just read the paper now -I like to wait till the final version goes up):

All laboratory confirmed cases of giardiasis (n = 1262) during the outbreak in Bergen in 2004 received a postal questionnaire two years after.
Laboratory-confirmed strengthens the findings.

Giardia infection
[..]
Only 1% became well without medication.
We have previously reported a high prevalence of fatigue (41%, 419/1017) and abdominal symptoms (38%, 389/1017), and a highly significant association between these symptoms, two years after the Bergen outbreak [8]. In this study we report an association between protracted and severe Giardia infection and such symptoms.
More than one treatment course is a reliable index of persistent infection and the finding of this as a highly significant risk factor in all analyses supports the hypothesis that protracted and severe infection may cause post-infectious complications.
If our findings are causal, then the surprisingly high level of fatigue and abdominal symptoms reported, may have two possible explanations: A substantial number of cases had protracted infection due to delayed treatment explained by late detection of the outbreak [7], and/or the infection caused inflammation in a high number of cases, also after clearing the parasites [31]. Giardiasis may cause damage to the intestinal epithelial brush border, villous atrophy and inflammation [32]. In duodenal biopsies from a sub-cohort of 124 cases with symptoms for 8 months (mean) from the Bergen outbreak, inflammation was found in 47% [31], which is surprisingly high compared to a previous report of duodenal inflammation in 4% of 462 Giardia cases from Germany [33]. This supports that protracted Giardia infection, and possibly protracted intestinal inflammation, may have induced PI-IBS and fatigue in this cohort. Low-grade inflammation in gut-mucosa has been described as a possible mechanism for IBS also following other infections [34].

The high prevalence of inflammation in this outbreak may be explained by immunological host factors, but probably also by parasite virulence factors. Studies addressing the possible association between Giardia genotypes and clinical manifestations have shown different results: Both genotype A and B have been responsible for severe symptoms, with the genotype less prevalent in the community responsible for more severe clinical manifestation [35-38]. In Norway 11% of raw water samples contains Giardia parasites in low concentrations, most commonly genotype A, while the outbreak strain in Bergen was assemblage B [39,40]. Previous studies from the outbreak suggest that some sub-genotypes induced a more severe infection [11,41], and one may speculate if particular sub-genotypes lead to an immune reaction responsible for protracted low-grade inflammation. Also in IBS following infections other than giardiasis, toxicity within species has been reported as a risk factor, as in Campylobacter infection [18].
Malaise during infection was associated with fatigue, and bloating with abdominal symptoms. This may either indicate recall bias influenced by symptoms present at the time of reporting, or a real risk of complications if these symptoms are prominent.
We have previously shown that all referred treatment refractory cases after the Bergen outbreak eradicated the parasite, evaluated by seven negative stool samples up to four weeks after treatment [11]. In 25 Giardia negative patients from this outbreak, treatment with metronidazole/albendazole or tetracycline/folic acid was not effective, and cryptic giardiasis was therefore excluded [51]. We have also described that IBS persisted in patients after normalisation of duodenal biopsies [17]. These reports support that chronic infection is not the cause of fatigue and abdominal symptoms in this cohort.
Conclusions
Protracted and severe Giardia infection, or possibly inflammation, seems to be a risk factor for post-infectious fatigue and abdominal symptoms two years after clearing the parasites. These symptoms are often pronounced, reduce quality of life and have economical implications in the society. If the observed association is causal, shortening the duration of Giardia infection by early diagnosis and treatment may be important also in order to reduce the risk for such complications.
In pre-publication comments:
Regarding possible recall bias on recording symptoms during infection two years earlier, this
was already addressed in the discussion section. However, our impression when interviewing
a subgroup of cases is that they remember very clearly their symptoms since most of them
were previously healthy and not used to be sick.
We agree that it would have been of interest to record fatigue prior to giardiasis. The
explanation for not including it in the questionnaire is the same as discussed above. However,
our impression after clinical evaluation of many of the patients over the years is that this is a
previously healthy cohort also regarding fatigue.
This question will be elucidated in future
studies from our centre.
We have previously reported a highly significant association between fatigue and abdominal
symptoms in this cohort; 66% of the cases with fatigue reported abdominal symptoms (Mrch
et al.
High rate of fatigue and abdominal symptoms 2 years after an outbreak of giardiasis.
Tran R Soc Trop Med Hyg (2009) 103, 530-532).