Kurt Hanevik

Giardiasis – why do the symptoms sometimes never stop?

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.

Intestinal Microbiota And Diet in IBS: Causes, Consequences, or Epiphenomena?

Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.

Development of functional gastrointestinal disorders after Giardia lamblia infection

BackgroundFunctional gastrointestinal disorders (FGID) may occur following acute gastroenteritis. This long-term complication has previously not been described after infection with the non-invasive protozoan Giardia lamblia. This study aims to characterize persistent abdominal symptoms elicited by Giardia infection according to Rome II criteria and symptoms scores.MethodsStructured interview and questionnaires 12–30 months after the onset of Giardia infection, and at least 6 months after Giardia eradication, among 82 patients with persisting abdominal symptoms elicited by the Giardia infection. All had been evaluated to exclude other causes.ResultsWe found that 66 (80.5%) of the 82 patients had symptoms consistent with irritable bowel syndrome (IBS) and 17 (24.3%) patients had functional dyspepsia (FD) according to Rome II criteria. IBS was sub classified into D-IBS (47.0%), A-IBS (45.5%) and C-IBS (7.6%). Bloating, diarrhoea and abdominal pain were reported to be most severe. Symptoms exacerbation related to specific foods were reported by 45 (57.7%) patients and to physical or mental stress by 34 (44.7%) patients.ConclusionIn the presence of an IBS-subtype pattern consistent with post-infectious IBS (PI-IBS), and in the absence of any other plausible causes, we conclude that acute Giardia infection may elicit functional gastrointestinal diseases with food and stress related symptoms similar to FGID patients in general.

Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia

Aliment Pharmacol Ther 31, 883–891

Giardiasis: The Ever-Present Threat of a Neglected Disease

Although giardiasis has been a threat to mankind for thousands of years, this protozoan infection was, until recently, relatively neglected. Giardia duodenalis is recognised as a major cause of parasite-induced diarrhoea in humans and animals, and is currently an important public health problem, placing a heavy burden on both diagnostic and treatment services at health care institutions, mostly in developing countries, but also in highly developed countries. Steady progress in recent years, using a combination of molecular, immunological, and clinical approaches, has substantially increased our understanding of Giardia and important aspects of the clinical manifestations that it causes. The purpose of this review is to provide an overview of the extent of Giardia infection, the implications of water and food in Giardia transmission, new aspects regarding clinical diagnosis and environmental detection, treatment, and some approaches towards prevention and control. A number of future research priorities are also presented.

Treatment-ladder and genetic characterisation of parasites in refractory giardiasis after an outbreak in Norway

OBJECTIVES To evaluate the efficacy of a treatment ladder in metronidazole-refractory giardiasis, and to compare genetic characteristics of the parasites. METHODS A clinical observational study was carried out in 38 adult patients with metronidazole-refractory giardiasis, during an outbreak in Norway with more than 1200 cases. All patients were treated with albendazole in combination with metronidazole. Those who failed were treated with paromomycin. Those who failed on paromomycin were treated with quinacrine in combination with metronidazole. Giardia isolates from 17 patients were characterised by PCR and sequencing at two separate genes. RESULTS Metronidazole in combination with albendazole was effective in 30 (79%) out of 38 patients. Paromomycin was effective in three out of six patients. Quinacrine in combination with metronidazole was effective in 3 patients. Molecular characterisation of the Giardia isolates revealed that these parasites were identical at two different gene segments, while sequence profiles from isolates at the peak of the outbreak were more heterogenous. CONCLUSIONS Albendazole and quinacrine both in combination with metronidazole were effective in treating metronidazole-refractory giardiasis in this cohort. Paromomycin was less effective. Particular Giardia sub-genotypes may have been associated with the treatment-refractory giardiasis in these patients, although other undefined factors are probably also of importance.

Irritable Bowel Syndrome and Chronic Fatigue 6 Years After Giardia Infection: A Controlled Prospective Cohort Study

Giardia infection in a nonendemic setting is associated with an increased risk for irritable bowel syndrome and chronic fatigue 6 years later. These conditions should be considered a differential diagnosis in patients with persisting symptoms after eradication of the parasite.

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

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.

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

BackgroundA 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.MethodsAll 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.ResultsThe 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.ConclusionProtracted and severe giardiasis seemed to be a risk factor for post-infectious fatigue and abdominal symptoms two years after clearing the Giardia infection.

A novel, single-amplification PCR targeting mitochondrial genome highly sensitive and specific in diagnosing malaria among returned travellers in Bergen, Norway

BackgroundNested PCR is a commonly used technique in diagnosis of malaria owing to its high sensitivity and specificity. However, it is time-consuming, open to considerable risk of contamination and has low cost-efficiency. Using amplification targets presented in multiple copies, such as rRNA 18S, or mitochondrial targets with an even higher copy number, might increase sensitivity.MethodsThe sensitivity and specificity of two newly designed Plasmodium genus-specific single-round amplification PCR programmes, based on previously published primers targeting 18S and mitochondrial genome, were compared with a widely used nested 18S PCR. Analyses of dilution series from Plasmodium falciparum reference material were performed, as well as retrospective analyses of 135 blood samples, evaluated by routine microscopy, from 132 fever patients with potential imported malaria. Sequencing of the 220 bp mitochondrial PCR products was performed.ResultsAt the threshold dilution 0.5 parasites/μl, the sensitivity of the mitochondrial PCR was 97% (29/30 parallels), that of the single-round 18S PCR 93% and the reference nested 18S PCR 87%. All three assays detected as low as 0.05 p/μl, though not consistently. In the patient cohort, malaria was diagnosed in 21% (28/135) samples, defined as positive by at least two methods. Both single-round amplification assays identified all malaria positives diagnosed by nested PCR that had sensitivity of 96% (27/28). The mitochondrial PCR detected one additional sample, also positive by microscopy, and was the only method with 100% sensitivity (28/28). The sensitivity and specificity of the mitochondrial PCR were statistically non-inferior to that of the reference nested PCR. Microscopy missed two infections detected by all PCR assays. Sequencing of the genus-specific mitochondrial PCR products revealed different single nucleotide polymorphisms which allowed species identification of the 28 sequences with following distribution; 20 P. falciparum, six Plasmodium vivax, one Plasmodium ovale and one Plasmodium malariae.ConclusionsIn this study, design of PCR programmes with suitable parameters and optimization resulted in simpler and faster single-round amplification assays. Both sensitivity and specificity of the novel mitochondrial PCR was 100% and proved non-inferior to that of the reference nested PCR. Sequencing of genus-specific mitochondrial PCR products could be used for species determination.