Peter Schiellerup

Virulence Factors for Hemolytic Uremic Syndrome, Denmark

We present an analysis of strain and patient factors associated with the development of bloody diarrhea and hemolytic uremic syndrome (HUS) among Shiga toxin-producing Escherichia coli (STEC) patients registered in Denmark in a 6-year period. Of 343 STEC patients, bloody diarrhea developed in 36.4% and HUS in 6.1%. In a multivariate logistic regression model, risk factors for bloody diarrhea were the eae and stx2 genes, O groups O157 and O103, and increasing age. Risk factors for HUS were presence of the stx2 (odds ratio [OR] 18.9) and eae (OR undefined) genes, being a child, and having bloody diarrhea. O group O157, although associated with HUS in a univariate analysis (OR 4.0), was not associated in the multivariate analysis (OR 1.1). This finding indicates that, rather than O group, the combined presence of the eae and stx2 genes is an important predictor of HUS.

Etiology of Diarrhea in Young Children in Denmark: a Case-Control Study

ABSTRACT Infectious gastroenteritis is one of the most common diseases in young children. To clarify the infectious etiology of diarrhea in Danish children less than 5 years of age, we conducted a 2-year prospective case-control study. Stools from 424 children with diarrhea and 870 asymptomatic age-matched controls were examined, and their parents were interviewed concerning symptoms. Rotavirus, adenovirus, and astrovirus were detected by enzyme-linked immunosorbent assay, and norovirus and sapovirus were detected by PCR. Salmonella, thermotolerant Campylobacter, Yersinia, Shigella, and Vibrio spp. were detected by standard methods. Shiga toxin-producing (STEC), attaching-and-effacing (A/EEC), enteropathogenic (EPEC), enterotoxigenic, enteroinvasive, and enteroaggregative Escherichia coli were detected by using colony hybridization with virulence gene probes and serotyping. Parasites were detected by microscopy. Overall, a potential pathogen was found in 54% of cases. More cases than controls were infected with rotavirus, Salmonella, norovirus, adenovirus, Campylobacter, sapovirus, STEC, classical EPEC, Yersinia, and Cryptosporidium strains, whereas A/EEC, although common, was not associated with illness. The single most important cause of diarrhea was rotavirus, which points toward the need for a childhood vaccine for this pathogen, but norovirus, adenovirus, and sapovirus were also major etiologies. Salmonella sp. was the most common bacterial pathogen, followed by Campylobacter, STEC, Yersinia, and classical EPEC strains. A/EEC not belonging to the classical EPEC serotypes was not associated with diarrhea, underscoring the importance of serotyping for the definition of EPEC.

Sialylation of Campylobacter jejuni lipo-oligosaccharides is associated with severe gastro-enteritis and reactive arthritis

We used various genotyping methods to identify bacterial genetic markers for development of arthritic symptoms following Campylobacter enteritis. We genotyped a collection of population derived Campylobacter strains, with detailed information on clinical characteristics, including arthritic symptoms. Besides using whole genome screening methods, we focused on the lipo-oligosaccharide (LOS) gene locus in which marker genes for developing post-Campylobacter neurological disease are present. Patients with arthritic symptoms were more frequently infected with Campylobacter jejuni strains with a class A LOS locus. We also found that patients who were infected with a C. jejuni strain containing sialic acid-positive LOS (class A, B or C) more frequently had bloody diarrhoea and a longer duration of symptoms. Furthermore, the IgM antibody response against Campylobacter was stronger in patients with a sialic acid containing LOS. Ganglioside auto-antibodies were observed in a small number of patients following infection with a class C strain. We conclude that sialylation of C. jejuni LOS is not only a risk factor for development of post-infectious symptoms, but is also associated with increased severity of enteric disease.

Risk factors for diarrhea among children in an industrialized country.

Background: Risk factors for childhood diarrhea in industrialized countries are not well characterized, although diarrhea remains an important cause of morbidity. Methods: We conducted a case–control study of 422 cases and 866 controls over 22 months in Denmark. We selected cases among children under 5 years of age with diarrhea. Age-matched healthy controls were selected from the background population using a population register. Parents were interviewed about possible exposures and underlying conditions. In addition, stool samples from both cases and controls were analyzed for viruses, parasites, and bacteria. We analyzed risk factors for diarrhea in general and for diarrhea of a viral, bacterial, or “unknown” etiology using logistic regression. Results: The following factors were independently associated with an increased risk of diarrhea: recent foreign travel, contact with symptomatic persons (particularly in daycare centers), hospitalization, contact with a dog with diarrhea, private daycare, consumption of products containing formula milk, unemployment and low educational status of parents, and prior diagnosis of several types of atopic diseases. In a pathogenic-specific analysis of diarrhea of bacterial (73 patients), viral (88), or “unknown” (222) etiology, the major risk factor for viral diarrhea was contact with symptomatic persons. For bacterial diarrhea, foreign travel and socioeconomic factors were the main risk factors. Conclusions: Viral diarrhea appears to be transmitted predominantly from person to person, whereas bacterial diarrhea appears to be primarily foodborne. A substantial portion of the diarrheal episodes may be of noninfectious etiology. Limiting child-to-child transmission of disease in daycare centers may substantially reduce the disease burden.

Determination of new cutoff values for indirect immunofluorescence antibody test for Q fever diagnosis in Denmark

Q fever is a ubiquitous zoonosis caused by Coxiella burnetii. The disease is emerging in many parts of the world, likely because of increased awareness and availability of better diagnostics. The diagnosis is primarily based on serology. Because the prevalence of the disease varies worldwide, the establishment of local cutoff values is needed. A baseline for antibodies against C. burnetii in Denmark was defined by testing sera from healthy Danish volunteers using a commercially available immunofluorescence antibody test. Cross-reactivity was studied on sera obtained from patients experiencing clinically related diseases. The cutoff titers suggested by the manufacturer were found to result in very low specificity of the test. The specificity was, however, effectively increased by using cutoff titers based on the local baseline and equal to immunoglobulin M (IgM) phase I > or =128, IgM phase II > or =256, IgG phase I > or =512, and IgG phase II > or =1024.

The role of Campylobacter jejuni cytolethal distending toxin in gastroenteritis: toxin detection, antibody production, and clinical outcome

Mortensen NP, Schiellerup P, Boisen N, Klein BM, Locht H, AbuOun M, Newell D, Krogfelt KA. The role of Campylobacter jejuni cytolethal distending toxin in gastroenteritis: toxin detection, antibody production and clinical outcome. APMIS 2011.

Antimicrobial treatment of asymptomatic carriers of verocytotoxin-producing Escherichia coli: An empiric study

Antimicrobial treatment of acute infection caused by verocytotoxin toxin-producing Escherichia coli (VTEC) is controversial due to risk of inducing haemolytic uraemic syndrome. We review the treatment of 9 persons who experienced serious social problems due to prolonged, asymptomatic carriage of non-O157 VTEC. Eradication of VTEC was successful and without complications.

Low seroprevalence of bartonella species in danish elite orienteers.

In the 1990s, studies were conducted to investigate 16 episodes of sudden unexpected cardiac death (SUCD) among Swedish elite orienteers during the period from 1979 to 1992. A case control study revealed that a significantly higher proportion of Swedish elite orienteers were B. elizabethae seropositive compared to controls. The aim of our study, designed as a case-control study, was to determine whether similarly high rates of B. elizabethae seropositivity were present among Danish elite orienteers. Cases were 43 elite orienteers; controls were 159 blood donors and 63 elite indoor sportsmen. All participants were tested for antibodies against B. henselae, B. quintana and B. elizabethae using immunofluorescent antibody tests. Surprisingly, Bartonella antibodies were only detected in sera from 5 persons: B. henselae from 1 elite orienteer, 1 handball player and 1 blood donor. B. elizabethae antibodies were detected in 1 handball player and 1 basketball player. We found no association between elite orienteers and the prevalence of Bartonella antibody positivity. This is in contrast to the Swedish study, and might be explained by the use of different serological methods in the 2 studies; to determine whether it is a true difference, a new study is needed.

No Serological Evidence for Rickettsial Diseases among Danish Elite Orienteerers

Abstract:  A series of sudden unexpected cardiac deaths among Swedish elite orienteerers in the 1980s have resulted from the combination of infectious diseases and physical exercise. Studies in the late 1990s have pointed to Chlamydia and Barontella, which both had a high seroprevalence among Swedish elite orienteerers. We conducted a case–control study aimed to elucidate the serologic prevalence of rickettsial diseases among Danish elite orienteerers. Ticks are known as vectors for some rickettsial diseases. None of the orienteerers had a positive antibody titer against any of the tested Rickettsia despite a very high frequency of tick bites in this group.