Seroprevalence of campylobacteriosis and relevant post-infectious sequelae.

Post-infectious sequelea such as Guillain Barré syndrome (GBS), reactive arthritis (RA), and inflammatory bowel disease (IBD) may arise as a consequence of acute Campylobacter-enteritis (AE). However, reliable seroprevalence data of Campylobacter-associated sequelae has not been established. The objectives of this study were, first, to identify the most specific and sensitive test antigen in an optimized ELISA assay for diagnosing a previous Campylobacter-infection and, second, to compare the prevalence of anti-Campylobacter antibodies in cohorts of healthy blood donors (BD), AE, GBS, RA, and IBD patients with antibodies against known GBS, RA and IBD triggering pathogens. Optimized ELISAs of single and combined Campylobacter-proteins OMP18 and P39 as antigens were prepared and sera from AE, GBS, RA and IBD patients and BD were tested for Campylobcter-specific IgA and IgG antibodies. The results were compared with MIKROGEN™-recomLine Campylobacter IgA/IgG and whole cell lysate-immunoblot. Antibodies specific for Helicobacter pylori, Mycoplasma pneumoniae, Yersinia enterocolitica, and Borrelia afzelii were tested with commercial immunoblots. ROC plot analysis revealed AUC maxima in the combination of OMP18 and P39 for IgA and in the P39-antigen for IgG. As a result, 34-49 % GBS cases, 44-62 % RA cases and 23-40 % IBD cases were associated with Campylobacter-infection. These data show that Campylobcater-seropositivity in these patient groups is significantly higher than other triggering pathogens suggesting that it plays an important role in development of GBS and RA, and supports the hypothesis that recurrent acute campylobacteriosis triggers IBD.

[Campylobacteriosis of man : livestock as reservoir for Campylobacter species]. / Die Campylobacteriose des Menschen : Nutztiere als Reservoir für Campylobacter-Arten.

Over the last few years, infections with Campylobacter have significantly increased in Europe and Germany and these bacteria have even surpassed Salmonella as the most prevalent bacteria, causing gastroenteritis. Especially contamination during the handling and consumption of meat products seems to be the most important risk factor which plays a prominent role for transmission to man. In addition, contact with pets and other animals, drinking raw or improperly pasteurized milk, and the tenacity of Campylobacter in different environments, especially water, have also to be considered for an adequate risk assessment. Besides gastroenteritis, arthralgia, and Guillain-Barré syndrome are important clinical complications of Campylobacter infections in man. At the same time, it is mostly unclear why the course of infection in man and in reservoir animals differs significantly, especially as only a few classical bacterial virulence factors have been identified so far. For these reasons, the development of efficient prevention strategies is of utmost importance in order to control campylobacteriosis.

Subcutaneous fistulae in a patient with femoral hypoplasia due to Actinomyces europaeus and Actinomyces turicensis.

Infections due to Actinomyces europaeus or Actinomyces turicensis have only rarely been reported. We describe a case of chronic fistulae caused by a coinfection with A. europaeus and A. turicensis in an immunocompetent male patient with a severe congenital femur hypoplasia. Actinomycosis is most probably the consequence of a postoperative wound infection after a prior surgical intervention. Both Actinomyces species were identified by 16S rRNA gene sequencing. The Actinomyces-caused fistulae were treated by excision and a 1-week course of i.v. vancomycin followed by a 1-week course of p.o. cefuroxime.

[Recurrent tonsillopharyngitis associated with Burkholderia cenocepacia : two case reports]. / Chronisch rezidivierende Tonsillopharyngitis infolge einer Burkholderia-cenocepacia-Infektion : 2 Fallberichte.

The Burkholderia cepacia complex comprises bacteria typically responsible for respiratory infections in immunocompromised and cystic fibrosis patients. However, these bacteria are rarely associated with infections in immunocompetent patients. In the presented case reports of two nonhospitalized immunocompetent female patients who underwent tonsillectomy as the ultimate therapy for recurrent tonsillopharyngitis, Burkholderia cenocepacia were demonstrated in the surgically removed tonsils. The clinical, histological, and microbiological findings of both cases are presented. The etiological relevance and the probable success of antibiotic treatment versus surgical measures are discussed.

Difficulties in species identification within the genus Haemophilus - A pilot study addressing a significant problem for routine diagnostics.

Diagnostic misidentifications of commensalic Haemophilus haemolyticus as pathogenic Haemophilus influenzae are frequent. This pilot study evaluates whether isolations of H. haemolyticus are frequent enough in Germany to cause a relevant diagnostic problem, considering the fact that even H. influenzae is a mere colonizer in about 30% of isolations. In microbiological laboratories of two hospitals located in Northern and Southern Germany, the distribution of Haemophilus spp. was analyzed during a six-month-period. Site of infection, sex, and age of the patients was taken into consideration. A total of 77 Haemophilus spp. isolates was acquired and discriminated on species level, comprising: 48 H. influenzae, 25 Haemophilus parainfluenzae, 3 H. haemolyticus, and 1 Haemophilus parahaemolyticus. The proportion of H. haemolyticus was calculated to range between 1.2% and 16.2 % within the 95% confidence limits. Commensalic Haemophilus spp. were isolated from oropharynx-associated sites only. H. influenzae, in contrast, was detected in clinically relevant materials like lower respiratory materials and conjunctiva swabs. Altogether, there was a low proportion of clinical H. haemolyticus isolates. Accordingly, the problem of unnecessary antibiotic therapies due to misidentifications of H. haemolyticus as H. influenzae is quantitatively negligible compared with the risk of confusing H. influenzae colonizations with infections.

Chemotaxis in Campylobacter jejuni.

Chemotaxis is the common way of flagellated bacteria to direct their locomotion to sites of most favourable living conditions, that are sites with the highest concentrations of energy sources and the lowest amounts of bacteriotoxic substances. The general prerequisites for chemotaxis are chemoreceptors, a chemosensory signal-transduction system and the flagellar apparatus. Epsilonproteobacteria like Campylobacter sp. show specific variations of the common chemotaxis components. CheV, a CheW-like linking-protein with an additional response regulator (RR) domain, was identified as commonly used coupling scaffold protein of Campylobacter jejuni. It attaches the histidine autokinase (CheAY), which also has an additional RR-domain, to the chemoreceptors signalling domains. These additional RR-domains seem to play an important role in the regulation of the CheAY-phosphorylation state and thereby in sensory adaptation. The Campylobacter-chemoreceptors are arranged into the three groups A, B, and C. Group A contains membrane-anchored receptors sensing periplasmic signals, group B consists only of one receptor with two cytoplasmic ligand-proteins representing a bipartite energy taxis system that senses pyruvate and fumarate, and group C receptors are cytoplasmic signalling domains with mostly unknown cytoplasmic ligand-binding proteins as sensory constituents. Recent findings demonstrating different alleles of the TLP7 chemoreceptor, specific for formic acid, led to an amendment of this grouping.

Spectrum of viral infections in patients with cystic fibrosis.

This review explores the extensive influence of viral infections leading to chronic deterioration of lung function in patients with cystic fibrosis (CF). The mechanisms how viral agents affect the pathogenesis as well as the inflammatory and immune response of CF are discussed. Viral infections of the upper and lower respiratory tract due to viruses in CF patients and methods for diagnosis of respiratory viruses are described in detail. The importance of respiratory and non-respiratory viral agents for the pathogenesis, especially for the exacerbation of bacterial lower respiratory tract infections and course of CF, is stressed, especially emphasizing respiratory syncytial virus, influenza virus, rhinovirus, and human herpes viruses. Possible harmful effects of further viruses like adenovirus, bocavirus, coronavirus, metapneumovirus, parainfluenzavirus on the lung function of CF patients are discussed. The potential use of adenovirus-based vectors for somatic gene therapy is mentioned.

The influence of virus infections on the course of COPD.

Chronic obstructive pulmonary disease (COPD) is extensively influenced by viral infections. The mechanisms of how viral agents affect the pathogenesis and prognosis of COPD are numerous. In general, patients with infectious exacerbations are characterized by longer hospitalization periods and greater impairment of several lung function parameters than those with non-infectious exacerbations. Prodromal, clinical, and outcome parameters fail to distinguish virally from non-virally induced illnesses in cases of exacerbations. The importance of infections with respiratory and non-respiratory viral agents for pathogenesis and course of COPD is detailed. Human adenovirus, non-respiratory viruses including human immunodeficiency virus, human metapneumovirus, influenza virus, human rhinovirus, and respiratory syncytial virus are especially stressed.

Is the Campylobacter jejuni secretory protein Cj0069 a suitable antigen for serodiagnostics?

Campylobacter spp. is the most common bacterial pathogen of gastroenteritis worldwide. Poultry is the main reservoir and consequently the main origin of infections for humans. As a consequence of a primary Campylobacter infection which typically manifests as diarrhea, there is an increased risk to suffer from post-infectious complications such as reactive arthritis, neuropathia, myositis or a Guillain-Barré Syndrome. Usually the verification of acute campylobacteriosis is made by stool culture. In contrast, post-infectious complications can be diagnosed by serological assays. Since most of them are based on whole cell lysates, an insufficient specificity results from cross-reactions between related species. Therefore, the use of recombinant antigens becomes more and more favorable. Campylobacter is able to secrete a number of proteins, which are amongst others necessary for cell invasion and therefore play a crucial role for virulence. One of these, Cj0069, has a similar specificity and sensitivity in the detection of anti-Campylobacter jejuni IgG compared to the well-established antigens OMP18 and P39. This makes it a suitable antigen for diagnosing C. jejuni post-infectious complications.

The viral genetic background determines the outcome of coxsackievirus B3 infection in outbred NMRI mice.

The reasons for the different outcome of coxsackievirus B3 (CVB3)-induced heart disease in humans are not well understood. Since there are no experimental data on the course of disease after infection with genetically different CVB3 in a natural variable population until now, we studied the outcome of virus infection in outbred NMRI mice after inoculation of genetically different CVB3 variants. Adult male mice were inoculated with seven closely related CVB3 variants. The histopathological changes of heart and pancreas tissue, antibody induction, virus titers, and persistence of viral positive- as well as negative-strand RNA in spleen and heart tissue were compared at day 7 or day 28 after infection to detect prerequisites and predictive factors for chronic myocarditis. Six CVB3 variants infected NMRI mice. CVB3 infection (i) did not induce detectable myocardial injury, (ii) caused signs of healing up acute myocarditis or (iii) ongoing chronic myocarditis. Neither IgG antibody responses nor the extent of destruction of exocrine pancreatic tissue or viral RNA load in spleen did correlate with myocardial histopathology. In contrast, a high persistent viral RNA load in heart tissue specimens was characteristic for mice developing chronic myocarditis. The results of the present study corroborate high viral load in the acute stage of myocarditis and high amounts of persisting CVB3 RNA in heart tissue as predictive marker of chronic myocarditis. The outcome of CVB3-induced heart disease in outbred NMRI mice depends strongly on the viral genetic background. In particular an important role of viral capsid proteins is suggested.

Heparan sulfates and coxsackievirus-adenovirus receptor: each one mediates coxsackievirus B3 PD infection.

Amino acid exchanges in the virus capsid protein VP1 allow the coxsackievirus B3 variant PD (CVB3 PD) to replicate in decay accelerating factor (DAF)-negative and coxsackievirus-adenovirus receptor (CAR)-negative cells. This suggests that molecules other than DAF and CAR are involved in attachment of this CVB3 variant to cell surfaces. The observation that productive infection associated with cytopathic effect occurred in Chinese hamster ovary (CHO-K1) cells, whereas heparinase-treated CHO-K1 cells, glucosaminoglycan-negative pgsA-745, heparan sulfate (HS)-negative pgsD-677, and pgsE-606 cells with significantly reduced N-sulfate expression resist CVB3 PD infection, indicates a critical role of highly sulfated HS. 2-O-sulfate-lacking pgsF-17 cells represented the cell line with minimum HS modifications susceptible for CVB3 PD. Inhibition of virus replication in CHO-K1 cells by polycationic compounds, pentosan polysulfate, lung heparin, and several intestinal but not kidney HS supported the hypothesis that CVB3 PD uses specific modified HS for entry. In addition, recombinant human hepatocyte growth factor blocked CVB3 PD infection. However, CAR also mediates CVB3 PD infection, because this CVB3 variant replicates in HS-lacking but CAR-bearing Raji cells, infection could be prevented by pretreatment of cells with CAR antibody, and HS-negative pgsD-677 cells transfected with CAR became susceptible for CVB3 PD. These results demonstrate that the amino acid substitutions in the viral capsid protein VP1 enable CVB3 PD to use specific modified HS as an entry receptor in addition to CAR.