Hans Linde Nielsen

Increased Short- and Long-Term Risk of Inflammatory Bowel Disease After Salmonella or Campylobacter Gastroenteritis

BACKGROUND & AIMS Various commensal enteric and potentially pathogenic bacteria may be involved in the pathogenesis of inflammatory bowel diseases (IBD). We compared the risk of IBD between a cohort of patients with documented Salmonella or Campylobacter gastroenteritis and an age- and gender-matched control group from the same population in Denmark. METHODS We identified 13,324 patients with Salmonella/Campylobacter gastroenteritis from laboratory registries in North Jutland and Aarhus counties, Denmark, from 1991 through 2003, and 26,648 unexposed controls from the same counties. Of these, 176 exposed patients with IBD before the infection, their 352 unexposed controls, and 80 unexposed individuals with IBD before the Salmonella/Campylobacter infection were excluded. The final study cohort of 13,148 exposed and 26,216 unexposed individuals were followed for up to 15 years (mean, 7.5 years). RESULTS A first-time diagnosis of IBD was reported in 107 exposed (1.2%) and 73 unexposed individuals (0.5%). By age, gender, and comorbidity adjusted Cox proportional hazards regression analysis, the hazard ratio (95% confidence interval) for IBD was 2.9 (2.2-3.9) for the whole period and 1.9 (1.4-2.6) if the first year after the Salmonella/Campylobacter infection was excluded. The increased risk in exposed subjects was observed throughout the 15-year observation period. The increased risk was similar for Salmonella (n = 6463) and Campylobacter (n = 6685) and for a first-time diagnosis of Crohns disease (n = 47) and ulcerative colitis (n = 133). CONCLUSIONS In our population-based cohort study with complete follow-up, an increased risk of IBD was demonstrated in individuals notified in laboratory registries with an episode of Salmonella/Campylobacter gastroenteritis.

Oral and Fecal Campylobacter concisus Strains Perturb Barrier Function by Apoptosis Induction in HT-29/B6 Intestinal Epithelial Cells

Campylobacter concisus infections of the gastrointestinal tract can be accompanied by diarrhea and inflammation, whereas colonization of the human oral cavity might have a commensal nature. We focus on the pathophysiology of C. concisus and the effects of different clinical oral and fecal C. concisus strains on human HT-29/B6 colon cells. Six oral and eight fecal strains of C. concisus were isolated. Mucus-producing HT-29/B6 epithelial monolayers were infected with the C. concisus strains. Transepithelial electrical resistance (Rt) and tracer fluxes of different molecule size were measured in Ussing chambers. Tight junction (TJ) protein expression was determined by Western blotting, and subcellular TJ distribution was analyzed by confocal laser-scanning microscopy. Apoptosis induction was examined by TUNEL-staining and Western blot of caspase-3 activation. All strains invaded confluent HT-29/B6 cells and impaired epithelial barrier function, characterized by a time- and dose-dependent decrease in Rt either after infection from the apical side but even more from the basolateral compartment. TJ protein expression changes were sparse, only in apoptotic areas of infected monolayers TJ proteins were redistributed. Solely the barrier-forming TJ protein claudin-5 showed a reduced expression level to 66±8% (P<0.05), by expression regulation from the gene. Concomitantly, Lactate dehydrogenase release was elevated to 3.1±0.3% versus 0.7±0.1% in control (P<0.001), suggesting cytotoxic effects. Furthermore, oral and fecal C. concisus strains elevated apoptotic events to 5-fold. C. concisus-infected monolayers revealed an increased permeability for 332 Da fluorescein (1.74±0.13 vs. 0.56±0.17 10−6 cm/s in control, P<0.05) but showed no difference in permeability for 4 kDa FITC-dextran (FD-4). The same was true in camptothecin-exposed monolayers, where camptothecin was used for apoptosis induction. In conclusion, epithelial barrier dysfunction by oral and fecal C. concisus strains could mainly be assigned to apoptotic leaks together with moderate TJ changes, demonstrating a leak-flux mechanism that parallels the clinical manifestation of diarrhea.

High incidence of Campylobacter concisus in gastroenteritis in North Jutland, Denmark: a population-based study

The incidence of non-thermophilic Campylobacter species was assessed in an unselected population-based study in a mixed urban and rural community in North Jutland, Denmark. In a 2-year study period, 11,314 faecal samples from 8302 patients with gastroenteritis were cultured with supplement of the filter method. We recovered a high incidence of Campylobacter concisus (annual incidence 35/100,000 inhabitants), almost as high as the common Campylobacter jejuni/coli. In contrast, there was a very low incidence of other non-thermophilic Campylobacter species, such as Campylobacter upsaliensis. Campylobacter concisus was, unlike C. jejuni/coli, found more frequently among small children (<1 year) and the elderly (≥ 65 years). Around 10% of the patients with C. consisus had co-infections dominated by Clostridium difficile and Salmonella enterica, whereas co-infections occurred in about 5% of C. jejuni/coli patients. We observed a seasonal variation in C. jejuni/coli with a peak incidence in late summer months and autumn, whereas there was an almost constant monthly prevalence of C. concisus. Among patients participating in a questionnaire sub-study, there was a higher degree of close contacts with animals, especially dogs, as well as a higher travel exposure among C. jejuni/coli patients compared with C. concisus patients. We did not culture any C. concisus in stool samples from a small cohort of healthy individuals. Future studies have to focus on the clinical follow-up and the long-term risk of inflammatory bowel diseases in C. concisus-positive patients. We conclude that there is a high incidence of C. concisus in Denmark.

Actinobaculum schaalii: A common cause of urinary tract infection in the elderly population. Bacteriological and clinical characteristics

Abstract To-date only 21 clinical cases of Actinobaculum schaalii infection have been published, and A. schaalii has been considered a rare cause of urinary tract infection (UTI) and urosepsis. Between y 2005 and 2008, we isolated A. schaalii from 55 predisposed elderly patients. In these cases, microscopic findings of coccoid rods in wet smears of urine gave rise to clinical suspicion and subsequently to its isolation from urine. Typically only scant growth of A. schaalii occurred after incubation of the urine for 24 h, but it became visible after 2 days of incubation in 5% CO2. Preliminary biochemical identification was carried out by combining the API Coryne and Rapid ID32A test systems, and the identification was later confirmed by partial 16S rDNA gene sequencing. During the 4-y period, A. schaalii caused septicaemia, UTIs and asymptomatic bacteriuria. One patient was later infected with Actinobaculum massiliense. The incidence of A. schaalii infections is much higher than previously reported. We present numerous case reports and describe the bacteriological and clinical characteristics of this overlooked uropathogen.

Evaluation of fecal calprotectin in Campylobacter concisus and Campylobacter jejuni/coli gastroenteritis

Abstract Calprotectin (CP) is a calcium-binding cytosolic neutrophil protein and the concentration in feces reflects the migration of neutrophils into the gut lumen. Testing for fecal CP (f-CP) in patients with negative cultures for enteric pathogens is widely accepted as a useful screening tool for identifying patients who are most likely to benefit from endoscopy for suspected inflammatory bowel disease (IBD) with the assumption that a negative f-CP is compatible with a functional disorder. Campylobacter concisus has recently been reported to have a high incidence in the Danish population almost equal to Campylobacter jejuni and Campylobacter coli and has been reported to cause prolonged watery diarrhea. However, isolation of C. concisus from feces requires the filter method in a hydrogen-enriched microaerobic atmosphere, which is not commonly used in the laboratory, and the diagnosis may consequently be missed. The aim of this study was to evaluate the f-CP levels, as a marker for the intestinal inflammation in C. jejuni/coli- and C. concisus-infected patients. The authors found a high concentration of f-CP (median 631: IQR 221–1274) among 140 patients with C. jejuni/coli infection, whereas the f-CP level among 99 C. concisus-infected patients was significantly lower (median 53: IQR 20–169). The data correlate to the severe inflammatory gastroenteritis seen in patients infected with C. jejuni/coli, whereas C. concisus-infected patients have a much lower intestinal inflammation which could be compared with viral gastroenteritis. Nevertheless, clinicians should be aware of C. concisus infection, especially in patients with prolonged mild diarrhea, in the differential diagnosis to IBD.

Power System Operation with Large Scale Wind Power Integration

The Danish power system starts to face problems of integrating thousands megawatts of wind power, which produce in a stochastic behavior due to natural wind fluctuations. With wind power capacities increasing, the Danish Transmission System Operator (TSO) is faced with new challenges related to the uncertain nature of wind power. In this paper, proposed models of generations and control system are presented which analyze the deviation of power exchange at the western Danish-German border, taking into account the fluctuating nature of wind power. The performance of the secondary control of the thermal power plants and the spinning reserves control from the Combined Heat and Power (CHP) units to achieve active power balance with the increased wind power penetration is presented.

Psychometric scores and persistence of irritable bowel after Campylobacter concisus infection

Abstract Objective. Gastroenteritis with Campylobacter concisus is an emerging infection, but the risk of irritable bowel syndrome (IBS) following it is unknown. Material and methods. In a prospective, community-based study of gastroenteritis with C. concisus and C. jejuni/coli, we invited adult patients to participate in a questionnaire study, including IBS symptoms and psychometric scores, at baseline and at 6 months. We estimated adjusted RR (RRadj) (for age, sex and comorbidity) for IBS as the primary outcome. Results. The development of IBS symptoms at 6 months was reported in 26/106 (25%) patients with C. concisus infection, and in 30/162 (19%) of C. jejuni/coli patients. The baseline predictors for IBS in C. concisus infection were high anxiety scores (RRadj 2.0; 95% CI 1.1–3.6, p < 0.05), chills (RRadj 1.9; 95% CI 1.0–3.6, p < 0.05), headache (RRadj 2.5; 95% CI 1.1–6.0, p < 0.05), dizziness (RRadj 2.6; 95% CI 1.2–5.8, p < 0.05) and muscle ache (RRadj 3.6; 95% CI 1.4–8.9, p < 0.01). For all Campylobacter patients (n = 268), we confirmed previous reports of anxiety (RRadj 2.0; 95% CI 1.3–3.1), depression (RRadj 2.3; 95% CI 1.3–4.0) and high somatization scores (RRadj 3.0; 95% CI 1.5–6.0) as predictors for post-infectious IBS (PI-IBS). Conclusions. Gastroenteritis with C. concisus carries a 25% risk of IBS at 6-month follow-up. The risk factors for IBS are chills, headache, dizziness and muscle ache in the acute stage, as well as preexisting high psychometric scores for anxiety. Our findings suggest that psychological factors play a role in the development of PI-IBS.

The first, second and third wave of pandemic influenza A (H1N1)pdm09 in North Denmark Region 2009–2011: a population-based study of hospitalizations

Denmark experienced three waves of the new pandemic influenza A (H1N1)pdm09 from July 2009 to February 2011. The aim of the study was to describe the epidemiology and clinical characteristics of hospitalized patients in a defined population of North Denmark Region with a mixed urban and rural community of 579 000 inhabitants.

Neutrophil activation by Campylobacter concisus

BackgroundCampylobacter concisus is an emerging enteric pathogen associated with prolonged diarrhoea and possibly inflammatory bowel disease in children as well as adults, but the interaction with cells of the innate immune system is unclear. The magnitude of systemic immunoglobulin response in acute infection is unknown.MethodsNeutrophils from healthy volunteers were activated with five faecal isolates of C. concisus from patients with gastroenteritis as well as the oral reference strain C. concisus ATCC33237. Neutrophils were tested for the expression of adherence molecule CD11b by immunoflourescence and for oxidative burst response by chemiluminescence. The opsonic activity in a chemiluminescence assay was assessed with heat treated serum from patients with C. concisus infection.ResultsA strong and dose-dependent activation of neutrophil adherence molecule CD11b and oxidative burst response was demonstrated with all six C. concisus isolates. Bacteria opsonised in heat treated serum induced an increased chemiluminescence response. Heat treated serum from patients with C. concisus infection did not have a higher opsonic activity than heat treated serum from healthy volunteers.ConclusionC. concisus has the capability to activate the innate immune system by stimulating neutrophil cells to increased adherence molecule expression and oxidative burst response, both crucial for acute inflammation. In a chemiluminescence assay the opsonic activity of heat treated serum from patients was not increased compared to heat treated control serum suggesting a weak systemic IgG response to infection.

Comparison of polycarbonate and cellulose acetate membrane filters for isolation of Campylobacter concisus from stool samples

One thousand seven hundred ninety-one diarrheic stool samples were cultivated for Campylobacter spp. We found a high prevalence of Campylobacter concisus with use of a polycarbonate filter (n = 114) compared to a cellulose acetate filter (n = 79) (P < .0001). The polycarbonate filter is superior to the commonly used cellulose acetate filter for detection of C. concisus.