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Background Bloodstream infections (BSIs) are a major cause of morbidity and mortality in hospitalized neonates. Data on antibiotic resistance in neonatal BSIs and their impact on clinical outcomes in Africa are limited. Methods We conducted a prospective cohort study at 2 tertiary level neonatal intensive care units (NICUs) in Ghana. All neonates admitted to the NICUs were included from October 2017 to September 2019. We monitored BSI rates and analyzed the effect of BSI and antibiotic resistance on mortality and duration of hospitalization. Results Out of 5433 neonates included, 3514 had at least one blood culture performed and 355 had growth of a total of 368 pathogenic microorganisms. Overall incidence of BSI was 1.0 (0.9-1.1) per 100 person days. The predominant organisms were Klebsiella pneumoniae 49.7% (183/368) and Streptococcus spp. 10.6% (39/368). In addition, 512 coagulase negative Staphylococci were isolated but considered probable contaminants. Among K. pneumoniae, resistance to gentamicin and amikacin was 91.8% and 16.4%, respectively, while carbapenem resistance was 4.4%. All-cause mortality among enrolled neonates was 19.7% (1066/5416). The mortality rate was significantly higher in neonates with BSI compared with culture-negative neonates in univariate analysis (27.9%, n = 99/355 vs. 16.5%, n = 520/3148; hazard ratio 1.4, 95% confidence interval 1.07-1.70) but not in multivariate analysis. Conclusion The diversity of etiological agents and the high risk of antibiotic resistance suggest that standard empirical treatment is unlikely to improve the outcome of BSIs in low and middle income. Such improvements will depend on access to reliable clinical microbiologic services.

Background Helicobacter pylori is the most infamous constituent of the gastric microbiota and its presence is the strongest risk factor for gastric cancer and other gastroduodenal diseases. Although historically the healthy stomach was considered a sterile organ, we now know it is colonised with a complex microbiota. However, its role in health and disease is not well understood. Aim To systematically explore the literature on the gastric microbiota in health and disease as well as the gut microbiota after bariatric surgery. Methods A systematic search of online bibliographic databases MEDLINE/EMBASE was performed between 1966 and February 2019 with screening in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomised controlled trials, cohort studies and observational studies were included if they reported next-generation sequencing derived microbiota analysis on gastric aspirate/tissue or stool samples (bariatric surgical outcomes). Results Sixty-five papers were eligible for inclusion. With the exception of H pylori-induced conditions, overarching gastric microbiota signatures of health or disease could not be determined. Gastric carcinogenesis induces a progressively altered microbiota with an enrichment of oral and intestinal taxa as well as significant changes in host gastric mucin expression. Proton pump inhibitors usage increases gastric microbiota richness. Bariatric surgery is associated with an increase in potentially pathogenic proteobacterial species in patient stool samples. Conclusion While H pylori remains the single most important risk factor for gastric disease, its capacity to shape the collective gastric microbiota remains to be fully elucidated. Further studies are needed to explore the intricate host/microbial and microbial/microbial interplay.

Helicobacter pylori is a common colonizer of the human stomach, and long-term colonization has been related to development of atrophic gastritis, peptic ulcers and gastric cancer. The increased gastric pH caused by H. pylori colonization, treatment with antibiotics or proton pump inhibitors (PPI) may allow growth of other bacteria. Previous studies have detected non-Helicobacter bacteria in stomach biopsies, but no conclusion has been made of whether these represent a transient contamination or a persistent microbiota. The aim of this study was to evaluate the transient and persistent bacterial communities of gastric biopsies. The washed or unwashed gastric biopsies were investigated by cultivation and microbiota analysis (16S rRNA gene-targeted amplicon sequencing) for the distribution of H. pylori and other non-Helicobacter bacteria. The number of cultured non-Helicobacter bacteria decreased in the washed biopsies, suggesting that they might be a transient contamination. No significant differences in the bacterial diversity were observed in the microbiome analysis between unwashed and washed biopsies. However, the bacterial diversity in biopsies shown H. pylori-positive and H. pylori-negative were significantly different, implying that H. pylori is the major modulator of the gastric microbiome. Further large-scale studies are required to investigate the transient and persistent gastric microbiota.

Weissella confusa is a Gram-positive coccus and a commensal bacterium of the human gastrointestinal tract with a potential to cause invasive infections. We report the presence of W. confusa in the blood of a 25-year-old male patient with Crohn’s disease, short bowel syndrome treated with home parenteral nutrition, and a history of recurrent bloodstream infections, admitted to our hospital with fever and malaise. A polymicrobial culture of W. confusa and Aeromonas hydrophila was identified from blood, for which treatment with meropenem and metronidazole was initiated. The literature was searched for previous cases of infection with W. confusa . In total, 14 reports describing infection of 28 patients were found, most cases presenting with bacteremia. The previous reports have described variable susceptibility to antibiotics; however, all were reported to be vancomycin resistant. Because of its similarities to other vancomycin-resistant cocci, isolates of W. confusa might be difficult to identify with traditional methods. Infection may be facilitated by its natural vancomycin resistance, leading to severe infection in hosts with underlying diseases. We describe the treatment of previous cases of infection and suggest treatment methods shown effective in other cases. Vancomycin is often used as treatment of infection with Gram-positive organisms, but this may need to be reevaluated, as several pathogenic bacteria are intrinsically vancomycin resistant. A review on reported treatments of bacteremia by W. confusa suggests the use of daptomycin, amoxicillin-clavulanate or piperacillin/tazobactam as recommendable antibiotic regimens.

Background Carriage of multidrug resistant (MDR) Gram-negative bacteria (GN) in hospitalized neonates may increase the risk of difficult-to-treat invasive infections at neonatal intensive care units (NICUs). Data on MDRGN carriage among hospitalized newborns in Africa are limited. Methods We conducted a cross-sectional study at the NICUs of 2 tertiary hospitals in Ghana. Swabs from the axilla, groin, perianal region, and the environment were cultured, GN were identified, and antibiotic susceptibility was tested. We obtained blood culture isolates from neonates with sepsis. Whole-genome sequencing was used to characterize carbapenemase-producing Klebsiella pneumoniae. Typing was done by multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis. Results A total of 276 GN were isolated from 228 screened neonates. Pathogenic GN were cultured in 76.8% (175 of 228) of neonates. Klebsiella spp (41.7%; 115 of 276) and Escherichia coli (26.4%; 73 of 276) were the commonest organisms. Carriage rates of MDRGN and third-generation cephalosporin resistant organisms were 49.6% (113 of 228) and 46.1% (105 of 228), respectively. Among Klebsiella spp, 75.6% (87 of 115) phenotypically expressed extended-spectrum β-lactamase activity, whereas 15.6% expressed carbapenemase and harbored bla-OXA-181 and bla-CTX-M-15. Overall, 7.0% (16 of 228) of neonates developed GN bloodstream infection. In 2 of 11 neonates, sequencing showed the same identity between carriage and the bloodstream isolate. Length of stay before specimen collection and antibiotic use were independently associated with carriage rates, which increased from 13% at admission to 42% by day 2 and reached a plateau at 91% by day 15. Conclusions High carriage rates of MDRGN, including carbapenemase-producing enterobacterales may be an emerging problem in NICUs in Africa., We show carriage rate of MDR enterobacterales among neonates in 2 NICUs in Ghana. MDR carriage is associated with duration of stay and antibiotic use. We also report OXA-181 carbapenemase-producing organism from Ghana. WGS showed identity between carriage and BSI.

The study evaluated primary antibiotic resistance of Helicobacter pylori within the period 2013-2015 and trends of antibiotic consumption over the last decade in Lithuania; 242 adults and 55 children were included in the study. E-tests were performed for amoxicillin, metronidazole, clarithromycin, ciprofloxacin, rifampicin and tetracycline. The presence of H. pylori and clarithromycin resistance was additionally tested by PCR. Helicobacter pylori culture was positive in 67 of 242 (28%) adult and in 12 of 55 (21.8%) children samples. Resistance rates among adults by E-tests were as follows: metronidazole - 32.8% (95% confidence interval (CI): 22.7-44.7%), ciprofloxacin - 7.5% (95% CI: 3.2-16.3%), rifampicin - 7.5% (95% CI: 3.2-16.3%), amoxicillin - 0%, whereas resistance rates in children were as follows: metronidazole - 25% (95% CI: 8.9-53.2%), rifampicin - 8.3% (CI: 1.5-35.4%), amoxicillin and ciprofloxacin - 0%. Accumulated clarithromycin resistance rates by E-tests and PCR were 8.2% (95% CI: 4.1-16.0%) in adults and 17.7% (95% CI: 6.2-41.0%) in children. Total use of macrolides and lincosamides in Lithuania increased from 1.26 to 1.86 defined daily dose (DDD)/1000 inhabitants/day among adults, while it has doubled from 1.10 to 2.22 DDD/1000/children/day in children within 2003-2015. There are no significant changes in the susceptibility of H. pylori to the most widely used antibiotics in adults over the last years in Lithuania; however, clarithromycin resistance among children exceeds 15% and mandates further larger-scale studies in paediatric population.

Objectives: To evaluate a genome-based surveillance of all Danish third-generation cephalosporin-resistant Escherichia coli (3GC-R Ec ) from bloodstream infections between 2014 and 2015, focusing on horizontally transferable resistance mechanisms.Methods: A collection of 552 3GC-R Ec isolates were whole-genome sequenced and characterized by using the batch uploader from the Center for Genomic Epidemiology (CGE) and automatically analysed using the CGE tools according to resistance profile, MLST, serotype and fimH subtype. Additionally, the phylogenetic relationship of the isolates was analysed by SNP analysis.Results: The majority of the 552 isolates were ESBL producers (89%), with bla CTX-M-15 being the most prevalent (50%) gene, followed by bla CTX-M-14 (14%), bla CTX-M-27 (11%) and bla CTX-M-101 (5%). ST131 was detected in 50% of the E. coli isolates, with the remaining isolates belonging to 73 other STs, including globally disseminated STs (e.g. ST10, ST38, ST58, ST69 and ST410). Five of the bloodstream isolates were carbapenemase producers, carrying bla OXA-181 (3) and bla OXA-48 (2). Phylogenetic analysis revealed 15 possible national outbreaks during the 2 year period, one caused by a novel ST131/ bla CTX-M-101 clone, here observed for the first time in Denmark. Additionally, the analysis revealed three individual cases with possible persistence of closely related clones collected more than 13 months apart.Conclusions: Continuous WGS-based national surveillance of 3GC-R Ec , in combination with more detailed epidemiological information, can improve the ability to follow the population dynamics of 3GC-R Ec , thus allowing for the detection of potential outbreaks and the effects of changing treatment regimens in the future.

Summary Background Viruses cause a major proportion of human infections, especially gastroenteritis and respiratory infections in children and adults. Indirect transmission between humans via environmental surfaces may play a role in infections, but methods to investigate this have been sparse. Aim To validate and test efficient and reliable procedures to detect multiple human pathogenic viruses on surfaces. Methods The study was divided into two parts. In Part A, six combinations of three different swabs (consisting of cotton, foamed cotton, or polyester head) and two different elution methods (direct lysis or immersion in alkaline glycine buffer before lysis) were tested for efficient recovery of human norovirus GII.7 and mengovirus from artificially contaminated surfaces. In Part B we determined the detection limit for norovirus GI.1 and GII.3 using the best procedure found in Part A linked with a commercial multiplex real-time quantitative polymerase chain reaction detection assay. Findings Combining the polyester swab with direct lysis allowed recovery down to 100 and 10 genome copies/cm 2 of norovirus GI.1 and GII.3, respectively. This procedure resulted in the significant highest recovery of both norovirus and mengovirus, whereas no differences in amplification efficiencies were observed between the different procedures. Conclusion The results indicate that it is possible to detect low concentrations of virus on environmental surfaces. We therefore suggest that a polyester swab, followed by direct lysis, combined with a multiplex qPCR detection assay is an efficient screening tool that merits study of different respiratory and gastrointestinal viruses on environment surfaces.

Objectives: The aim of this study was to identify clonally-related carbapenemase-producing Klebsiella pneumoniae complex members that could be involved in outbreaks among hospitalized patients in Denmark, and to identify possible epidemiological links. Methods: From January 2014 to June 2018, 103 isolates belonging to the K. pneumoniae complex were collected from 102 patients. From the whole-genome sequencing (WGS) data, presence of genes encoding carbapenemase and multilocal sequence typing (MLST) data were extracted. Core genome MLST (cgMLST) cluster analysis was performed. Using data from the Danish National Patient Registry (DNPR) and reported travel history, presumptive outbreaks were investigated for possible epidemiological links. Results: The most common detected carbapenemase gene was bla OXA-48, followed by bla NDM-1. The 103 K. pneumoniae complex isolates belonged to 47 sequence types (STs) and cgMLST subdivided the isolates into 80 different complex types. cgMLST identified 13 clusters with 2-4 isolates per cluster. For five of the 13 clusters, a direct link (the patients stayed at the same ward on the same day) could be detected between at least some of the patients. In two clusters, the patients resided simultaneously at the same hospital, but not the same ward. A possible link (same ward within 1-13 days) was detected for the patients in one cluster. For five clusters detected by cgMLST, no epidemiological link could be detected using data from DNPR. Conclusion: In this study, cgMLST combined with patient hospital admission data and travel information was found to be a reliable and detailed approach to detect possible clonal transmission of carbapenemase-producing K. pneumoniae complex members.

Infection with Helicobacter pylori is a critical cause of gastrointestinal diseases. A crucial host response associated with H. pylori infection includes gastric inflammation, which is characterized by a sustained recruitment of T-helper (Th) cells to the site of infection and distinct patterns of cytokine production. Adequate nutritional status, especially frequent consumption of dietary antioxidants, appears to protect against infection with H. pylori. The aim of the present study was to investigate whether astaxanthin (AXT) from shrimp cephalothorax may modulate cytokine release of splenocytes in H. pylori-infected mice (n = 60). Six- to eight-week-old female mice were divided into three groups (n = 20 per group) to receive a daily oral dose of 10 or 40 mg of AXT for six weeks. After six weeks, a trend toward interferon gamma (IFN-γ) upregulation was found (40 mg; p < 0.05) and a significant dose-dependent increase of interleukin 2 (IL-2) and IL-10 (both p < 0.05) was observed. These results suggest that AXT induces higher levels of IL-2 and a shift to a balanced Th1/Th2 response by increasing IFN-γ and augmenting IL-10. We concluded that AXT may influence the pattern of cytokines during H. pylori infection.

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the family Enterobacteriaceae. It has been described as an emerging human pathogen with the potential to cause severe infection in immunocompromised patients. The aim of this study was to describe a clinical case of infection with L. adecarboxylata and give a review of previous reports on infection. We report the presence of L. adecarboxylata in a patient initially admitted to our hospital for a lung transplant. She had diarrhoea, urinary tract infection and pneumonia caused by L. adecarboxylata. The isolate was resistant to trimethoprim-sulfamethoxazole and susceptible to 15 other antibiotics tested. The literature search for previous reports of infection with L. adecarboxylata resulted in 61 publications describing 74 cases. Bacteremia and wound infections were most often described, and only a few cases were fatal. L. adecarboxylata was most often found as a monomicrobial infection in immunocompromised patients, and as part of a polymicrobial infection in immunocompetent patients. The previously described isolates showed a high susceptibility to antibiotics, and treatment was efficient in most cases. Due to similarities in metabolic products, L. adecarboxylata might have been mistaken as Escherichia spp., but with new identification methods such as MALDI-TOF MS, it is possible to obtain a certain identification.

Background: Current literature examining the relationship between door-opening rate, number of people present, and microbial air contamination in the operating room is limited. Studies are especially needed from low- and middle-income countries, where the risk of surgical site infections is high. Aim: To assess microbial air contamination in operating rooms at a Ghanaian teaching hospital and the association with door-openings and number of people present. Moreover, we aimed to document reasons for door-opening. Methods: We conducted active air-sampling using an MAS 100® portable impactor during 124 clean or clean-contaminated elective surgical procedures. The number of people present, door-opening rate and the reasons for each door-opening were recorded by direct observation using pretested structured observation forms. Findings: During surgery, the mean number of colony-forming units (cfu) was 328 cfu/m3 air, and 429 (84%) of 510 samples exceeded a recommended level of 180 cfu/m3. Of 6717 door-openings recorded, 77% were considered unnecessary. Levels of cfu/m3 were strongly correlated with the number of people present (P = 0.001) and with the number of door-openings/h (P = 0.02). In empty operating rooms, the mean cfu count was 39 cfu/m3 after 1 h of uninterrupted ventilation and 52 (51%) of 102 samples exceeded a recommended level of 35 cfu/m3. Conclusion: The study revealed high values of intraoperative airborne cfu exceeding recommended levels. Minimizing the number of door-openings and people present during surgery could be an effective strategy to reduce microbial air contamination in low- and middle-income settings.

Using Nanopore sequencing, we describe here the circular genome of an Escherichia coli sequence type 410 (ST410) strain with five closed plasmids. A large 111-kb incompatibility group F (IncF) plasmid harbored bla NDM-5 and 16 other resistance genes. A 51-kb IncX3 plasmid carried QnrS1 and bla OXA-181 . E. coli isolates with both bla NDM-5 and bla OXA-181 carbapenemases are rare.

SUMMARYThe surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010–2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.

Summary Background The rising number of children in daycare nurseries increases opportunities for the transmission of infectious diseases. Pathogens may be transmitted directly from child to child via sneezing, coughing and touching, or indirectly via the environment. Toys are among the fomites with the highest pathogen load, but their role in disease transmission is unknown. Aim To determine if washing and disinfection of toys can reduce sickness absence and microbial pathogen load in the nursery environment. Methods Twelve nurseries (caring for 587 children) were randomized to intervention and control groups. The intervention consisted of washing and disinfection of toys and linen every two weeks for three months by a commercial cleaning company. The extent and causes of sickness absence among the children were recorded in both groups before and after introduction of the intervention. Ten sampling points in each nursery were examined for bacteria and respiratory viruses. Results The presence of respiratory virus DNA/RNA was widespread, but very few pathogenic bacteria were found in the environment. The intervention reduced the presence of adenovirus [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1–5.0], rhinovirus (OR 5.3, 95% CI 2.3–12.4) and respiratory syncytial virus (OR 4.1, 95% CI 1.5–11.2) compared with the control group, but the intervention had no effect on sickness absence or disease patterns in the nurseries. Conclusion Although cleaning and disinfection of toys every two weeks can decrease the microbial load in nurseries, it does not appear to reduce sickness absence among nursery children.

Environmental sampling in hospitals is becoming increasingly important because of the rise in nosocomial infections. In order to monitor and track these infections and optimize cleaning and disinfection, we need to be able to locate the fomites with the highest amount of microorganisms, but the optimal method for this is not clear. The aim of this study was to evaluate which of four different dipslides or a standard TSA contact plate were best at recovering human bacteria from the environment. We tested four different dipslides with selective and non-selective agars versus a standard TSA contact plate in order to find the best sampling media. Two hundred sites in a children's medical ward in Copenhagen University hospital were sampled in autumn 2012. There was no difference in total bacteria count between the TSA contact plate and the dipslides. Faecal indicator bacteria recovery was the same for the dipslides and the TSA contact plate. Dipslides may be equally well suited for environmental sampling and hygiene assessment as TSA contact plates. Dipslides have some advantages, such as better sample security, easier sampling in confined spaces and longer shelf life that may speak in favour of choosing these for bacteria environmental sampling in hospitals, depending on the task.

The study evaluated the changes in the prevalence of Helicobacter pylori strains with primary resistance to antibiotics during the last 10 years in Lithuania. H. pylori susceptibilities to antibiotics were tested in 89 patients in 1998, in 81 patients in 2001 and in 90 patients in 2007/2008. Susceptibility to metronidazole, clarithromycin, amoxicillin and tetracycline was tested using E-test or agar dilution method. Susceptibility to ciprofloxacin was only tested in 2007/2008. Data about utilization of all authorized and available on market macrolides and clindamycin in Lithuania during 2003-2007 were evaluated using WHO ATC/DDD methodology. A total of 260 H. pylori strains cultured from untreated adult patients were investigated. Primary resistance rates (1998, 2001 and 2007/2008) for metronidazole were 24.7%, 33.3%, and 35.6%, for clarithromycin 1.1%, 3.7%, and 3.3% and for tetracycline 0%, 2.5% and 0% respectively. No cases of amoxicillin resistance have been detected. The resistance rate for ciprofloxacin was 5.6% in 2007/2008. Data of total macrolides and clarithromycin utilization in Lithuania revealed that despite an increase of consumption of these drugs in Lithuania during 2003-2007 in 1.5 times, the total macrolide consumption remains one of the lowest in Europe. We have not observed any significant changes in the susceptibility of H. pylori to the most widely used antibiotics during the recent 10-year period. The low resistance rate to clarithromycin might be related to the policy to avoid use of macrolides as first-line treatment for pulmonary and other infections.

Helicobacter pylori represents the major etiologic agent of gastritis, gastric, and duodenal ulcer disease and can cause gastric cancer and mucosa-associated lymphoid tissue B-cell lymphoma. It is clear that the consequences of infection reflect diverse outcomes of the interaction of bacteria and host immune system. The hope is that by deciphering the deterministic rules – if any – of this interplay, we will eventually be able to predict, treat, and ultimately prevent disease. Over the past year, research on the immunology of this infection started to probe the role of small noncoding RNAs, a novel class of immune response regulators. Furthermore, we learned new details on how infection is detected by innate pattern recognition receptors. Induction of effective cell-mediated immunity will be key for the development of a vaccine, and new work published analyzed the relevance and contribution of CD4 T helper cell subsets to the immune reaction. Th17 cells, which are also induced during natural infection, were shown to be particularly important for vaccination. Cost-efficiency of vaccination was re-assessed and confirmed. Thus, induction and shaping of the effector roles of such protective Th populations will be a target of the newly described vaccine antigens, formulations, and modes of application that we also review here.

Aim: The aim of this study was to estimate the incidence and identify independent risk factors for nosocomial infections in a Danish Neonatal Intensive Care Unit and to compare these findings with international results. Methods: The study was performed prospectively from January 1, 2005 to December 31, 2005 in the Neonatal Intensive Care Unit at Rigshospitalet, Copenhagen. Specific criteria for blood stream infection and respiratory tract infection adapted for neonates in our ward were worked out. Results: Six hundred and eighty-three patients were included. The overall incidence of nosocomial infection was 8.8/1000 hospital days. Blood stream infection was the most frequent type of infection, with an incidence of 5.1/1000 hospital days. Multivariate analysis showed gestational age and heart disease to be significant independent risk factors for both first time blood stream infection and respiratory tract infection, and central venous catheter and parenteral nutrition risk factors for first time blood stream infection. Conclusion: This first prospective study of nosocomial infection in a Danish Neonatal Intensive Care Unit found an overall incidence of 8.8/1000 hospital days, which is low or similar compared to other studies. Further Danish multicentre studies are needed, and we suggest that procedures related to central venous catheters should be a future focus area.

The aim of the study was to assess and compare the IgG seroprevalence of H. pylori in children with recurrent abdominal pain with healthy children and to investigate the related symptoms. IgG antibodies against low-molecular weight H. pylori antigens were assessed in 438 children with recurrent abdominal pain and in 91 healthy controls. Sera with an ELISA unit-value above the cut-off level were confirmed by Western immunoblot. Only seropositive children with recurrent abdominal pain were examined by an oesophago-gastro-duodenoscopy. Symptomatology was recorded according to the localization of the abdominal pain, presence of pyrosis, nocturnal pain, relation of pain to meals and bowel irregularities. The seroprevalence was 21% (95% CI: 17-25%) in the children with recurrent abdominal pain and 10% (95% CI: 5–18%) in the healthy controls (p= 0:30). In seropositive children with RAP H. pylori was found in 46/66 by culture and histology. The presence of H. pylori was significantly associated with active or inactive chronic gastritis. The presence of H. pylori was associated with both parents being born in a country with a high prevalence and a low social class. Helicobacter pylori-positive children had more often pain related to meals than the H. pylori- negative children. No differences among the two groups were seen according to the levels of haemoglobin, leucocytes, thrombocytes, weight and height. In conclusion, the seroprevalence of H. pylori is comparable in children with recurrent abdominal pain and healthy children. No specific symptomatology was seen in H. pylori- positive children with RAP.

Campylobacter concisus has been as frequently isolated from human diarrhea as the important enteropathogen Campylobacter jejuni , but it also occurs in the feces of healthy individuals. The role of C. concisus in human disease has been difficult to determine, since the species comprises at least two phenotypically indistinguishable but genetically distinct taxa (i.e., genomospecies) that may vary in pathogenicity. We examined 62 C. concisus strains by amplified fragment length polymorphism (AFLP) profiling and correlated the results with clinical data. All C. concisus strains gave unique AFLP profiles, and numerical analysis of these data distributed the strains among four clusters. The clustering was of taxonomic significance: two clusters contained, respectively, the type strain (of oral origin) and a reference strain (from diarrhea) of each of the known genomospecies. Genomospecies 2 strains were more frequently isolated from immunocompetent patients and/or patients without concomitant infections that presented with fever, chronic diarrhea, and gut inflammation than was genomospecies 1, clustering with the type strain of oral origin. Bloody diarrhea was recorded only with C. concisus genomospecies 2 infections. We identified two additional C. concisus genomospecies: genomospecies 3 comprised a single strain from an immunocompetent patient, and genomospecies 4 contained five isolates from severely immunodeficient patients, i.e., organ transplantation recipients or those with hematological malignancies. All genomospecies 4 strains were of the same protein profile group and failed to react with a C. concisus species-specific PCR assay based on 23S rRNA gene sequences: the taxonomic position of this group requires closer investigation. Campylobacter concisus is genetically and taxonomically diverse and contains at least four distinct genomospecies that may exhibit differences in their spectra of virulence potential.

Objective To characterize and subgroup clinical strains of Campylobacter concisus isolated from patients with gastrointestinal disease. Methods A total of 109 C. concisus isolates from 98 patients obtained between June 1997 and December 1998 were analysed using protein profiles, conventional biochemical tube tests, ApiCampy, and susceptibility patterns by Neosensitabs and E-test. Results Two groups were identified by using protein profiles. One resembled the ATCC 33237 type strain of oral origin, and a second group differing from it, particularly in the high molecular weight zone. Considerable diversity exists in the lower molecular range of the gels, also within assigned subgroups. Biochemical testing showed differences between the groups in the ability to reduce nitrate, ApiCampy testing also yielded differences between the two assigned groups, although reactions were highly heterogeneous. Resistance to erythromycin, ciprofloxacin, ampicillin, ceftriaxone and tetracycline occurred in 3%, 13%, 7%, 11% and 0% of the isolates when using Neosensitabs. The E-test yielded comparable results 7%, 5%, 0%, 2% and 3%, respectively. Conclusion Results indicate that C. concisus can be assigned to two broad groups based on differences in protein profiles. No distinct phenotypic marker was identified. Susceptibility patterns are not suitable for discrimination between the two assigned groups. Further studies using a polyphasic approach including the application of genetic methods are needed to assess the complex taxonomy of this potential pathogen.

Background: Upregulation of proinflammatory endothelial cell adhesion molecules and decreased bioactivity of endothelial nitric oxide (NO) are important in the pathogenesis of atherosclerosis. We investigated the effects of co-infection with Chlamydia pneumoniae and Helicobacter pylori on these two events in apoE-KO mice. Methods: Thirty-two apoE-KO mice, 8 weeks old, were equally divided into 4 groups. The first 2 groups were infected with either C. pneumoniae or H. pylori, while the 3rd group was infected with both C. pneumoniae and H. pylori. Mice from the 4th group and 4 wild-type mice served as controls. Thoracic and abdominal aortas were harvested after 10 weeks, and staining for vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 was analyzed by immunocytochemistry. The endothelial vasomotor responses of thoracic aortas to methacholine were studied in organ chambers in the absence and presence of L-NAME. The plasma levels of nitrate/nitrite were measured. Results: Staining for VCAM-1 was more intense at the branching sites of aortas from mice with co-infection than in mono-infected or noninfected apoE-KO mice. The relaxation responses to methacholine and the plasma levels of nitrate/nitrite were significantly less in the co-infected group than in the other groups (p < 0.05). Conclusion: Co-infection of apoE-KO mice with C. pneumoniae and H. pylori seems to be associated with impaired bioactivity of endothelial NO and increased expression of VCAM-1 at branching sites. The findings may suggest an additive interaction of these pathogens in atherogenesis.

Treatment failures are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa when triple therapy including metronidazole is used. In patients with treatment failure and metronidazole-resistant H. pylori , a higher eradication rate for H. pylori was found after secondary treatment with bismuth/ranitidine in combination with antibiotics including metronidazole, compared with the same antibiotics combined with a standard dose of omeprazole. This agrees with our previous finding that bismuth was able to reduce the susceptibility of H. pylori to metronidazole. In this study, we have found that nizatidine, an H 2 -receptor antagonist, is also able to reduce the susceptibility of H. pylori to metronidazole in vitro, despite having no direct inhibitory effect on the growth of H. pylori. This agrees with earlier findings that compounds having the ability to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit the activity of fumarate reductase of H. pylori . This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could be an inhibition of a proton pump in H. pylori . Reversal of antimicrobial resistance with the help of different non-antibiotics seems to be possible by using quite different compounds, and is therefore to be explained by different molecular mechanisms.

A multicentre in vitro survey was carried out in 1998 in 22 European centres in order to assess the variation in the prevalence of Helicobacter pylori resistance. The susceptibility of 1,274 isolates to metronidazole, clarithromycin and amoxicillin was determined by the E test. The mean rate of resistance to metronidazole was 33.1% (95% CI, 7.5-58.9), to clarithromycin 9.9% (95% CI, 0-28.1) and to amoxicillin 0.8% (95% CI, 0-8.9). Resistance to metronidazole was significantly higher in females (P

Background. The role of Helicobacter pylori remains unclear in children with recurrent abdominal pain (RAP). In this study children with RAP were included in a double blind treatment study to elucidate whether symptoms disappear in children with a H. pylori infection and RAP, if the bacteria are eradicated. Methods. Thirty-seven H. pylori-infected children aged 4.9–14.5 years (median 9.8 years) with RAP were included. H. pylori was identified by histology and culture. The children were treated with amoxicillin and metronidazole for 14 days. A re-endoscopy including biopsies for histology and culture was done at least one month after the end of treatment. Simple questions for symptoms were asked and blood for serology was repeated 3 and 6 months after the end of treatment. During the observation period the results of the re-endoscopy and the serology 3 and 6 months after the re-endoscopy were blinded for 23 patients and opened to 14 of the patients according to the choice of the families. Results. The eradication rates were 81% (30/37) in the total group and 74% (17/23) in the blinded group. The IgG antibodies to H. pylori decreased significantly 3 (p = .03) as well as 6 months after end of treatment (p

Helicobacter pylori is a gram-negative bacterium affecting about half of the world population, causing chronic gastritis type B dominated by activated phagocytes. In some patients the disease evolves into gastric ulcer, duodenal ulcer, gastric cancer or MALT lymphoma. The pathogenesis is in part caused by the immunological response. In mouse models and in human disease, the mucosal immune response is characterized by activated phagocytes. Mucosal T-lymphocytes are producing IFN-gamma thus increasing mucosal inflammation and mucosal damage. A low dietary intake of antioxidants such as carotenoids and vitamin C may be an important factor for acquisition of H. pylori by humans. Dietary antioxidants may also affect both acquisition of the infection and the bacterial load of H. pylori infected mice. Antioxidants, including carotenoids, have anti-inflammatory effects. The aim of the present study was to investigate whether dietary antoxidant induced modulation of H. pylori in mice affected the cytokines produced by H. pylori specific T-cells. We found that treatment of H. pylori infected mice with an algal cell extract containing the antioxidant astaxanthin reduces bacterial load and gastric inflammation. These changes are associated with a shift of the T-lymphocyte response from a predominant Th1-response dominated by IFN-gamma to a Th1/Th2-response with IFN-gamma and IL-4. To our knowledge, a switch from a Th1-response to a mixed Th1/Th2-response during an ongoing infection has not been reported previously.

STUDY OBJECTIVES—To assess the incidence of seroconversion and seroreversion in IgG antibodies to Helicobacter pylori within a 11 year observation period using these events as markers for acquisition and loss of the infection, respectively. DESIGN—Population based prospective cohort study SETTING—Northern part of Copenhagen County, Denmark PARTICIPANTS AND METHODS—A random sample of 2527 Danish adults were examined and blood obtained in 1983 and in 1994. Matching pairs of sera were analysed for the presence of IgG and IgM antibodies to H pylori with an in house enzyme linked immunosorbent assay. Participants who were seronegative at study entry and seropositive at follow up and had a fourfold increase in baseline IgG antibody levels were categorised as seroconverters and regarded as having acquired H pylori infection. Participants who were seropositive at study entry and had at least a fourfold decrease in baseline IgG antibody levels at follow up were assumed to have lost the infection (seroreverters). RESULTS—The seroprevalence of H pylori infection was 24.7 (95% confidence intervals (95% CI) 23.0, 26.4) % in 1983 and 24.5 (95% CI 22.8, 26.2) % in 1994. A total of 14 participants seroconverted within the observation period (cumulative 11 year incidence proportion: 1.0 (95% CI 0.5, 1.5) %). Having increased IgM antibody levels at study entry significantly increased the likelihood of IgG seroconversion (relative risk 6.4 (95% CI 2.1, 19.6). Seroreversion was seen in 48 participants (cumulative 11 year incidence proportion: 7.7 (95% CI 5.6, 9.8) %). CONCLUSIONS—Changes in H pylori infection status with time are rare in Danish adults. Few adults become infected with H pylori in Denmark. Keywords: Helicobacter pylori; seroconversion; sero-reversion

Infection with Helicobacter pylori in childhood may be the initiation of a lifelong coexistence between microorganisms and epithelial cells resulting in chronic inflammation. The adhesion pattern of H. pylori found in antral biopsies from a group of H. pylori-infected children with recurrent abdominal pain was compared with a group of H. pylori-infected adults suffering from dyspepsia, in an attempt to reveal differences in the type of adhesion.The histology of antrum biopsies and the ultrastructure of adherent H. pylori in biopsies from 26 children (median age, 10.1 years) were compared with organisms in biopsies from 19 adults (median age, 54.4 years).More than 1000 adherent H. pylori were studied and divided into four types of adhesion: 1) contact to microvilli; 2) connection to the plasma membrane via filamentous material; 3) adhesive pedestal formation; and 4) abutting or making a depression in the plasma membrane. Contact to microvilli was significantly higher (69% versus 39%; P = 0.002) in children compared with adults and comprised two-thirds of all adherent organisms in children. The more intimate adhesion types as abutting or adhesive pedestals dominated in adults.These results indicate a change in contact types between H. pylori and gastric epithelial cells in adults compared with children and this may be a natural development in the lifelong infection of humans.

Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation induced by H. pylori strains with different virulence genotypes. Bacterial sonicates from 12 strains were used to induce phagocyte upregulation of adherence molecule CD 11b, assessed by fluorescence flow cytometry, and oxidative burst responses, assessed by chemiluminescence. A dose-dependent induction of the expression of CD11b was observed with sonicate from all H. pylori strains on both neutrophils and monocytes. Strains negative for cagA and picB genes had the same inducing activity of upregulation of CD 11b as strains positive for these genes. A vacA-S2 type strain had the same activity as vacA-S1 type strains. The induction of toxic oxygen radicals by H. pylori-activated neutrophils gave higher median values for the cagA-positive strains than for the cagA-negative strains. For the monocyte chemiluminescence response, cagA-negative strains gave higher median values compared to cagA-positive strains. We conclude that upregulation of the neutrophil and monocyte adherence molecule CD11b induced by H. pylori sonicates is not associated with the presence of cagA, picB or mosaic pattern of vacA, and that cagA, picB-negative strains and vacA-S2 strains retain their inflammatory capacity.

Background & Aims: Helicobacter pylori infection was recently associated with iron-deficiency anemia. The aim of this study was to examine the relationship between H. pylori infection, hemoglobin, and iron status using serum ferritin as a marker for total body iron. Methods: Serum ferritin, hemoglobin, and immunoglobulin G (IgG) antibodies against H. pylori were assessed in 2794 Danish adults who attended a population survey. IgG antibodies were measured with an in-house enzyme-linked immunosorbent assay, serum ferritin with an immunoradiometric assay, and hemoglobin with Coulter-S. Results: The seroprevalence of H. pylori infection did not relate to hemoglobin. Serum ferritin levels were significantly lower in men (114 vs. 120 μg/L; P = 0.01) and in postmenopausal women (63 vs. 77 μg/L; P = 0.02) who were IgG positive than in seronegative individuals. IgG-positive people more often had reduced serum ferritin levels (≤30 μg/L) than seronegative people. This association persisted in multivariate analysis after adjusting for possible confounding factors (odds ratio, 1.4; 95% confidence interval 1.1–1.8). Conclusions: Serum ferritin levels are reduced in people with increased IgG antibodies to H. pylori. H. pylori infection affects iron metabolism in humans. GASTROENTEROLOGY 1998;115:268-274

It has been suggested that antibodies against GM1 are involved in the pathogenesis of the Guillain-Barre syndrome (GBS). Recently, we have developed a standardized ELISA assay for anti-GM1 antibodies of IgM type well-suited for longitudinal patient studies. The relationship between serum antibodies against GM1 and Campylobacter jejuni was investigated in patients with GBS and in patients with C. jejuni infection. Patients with a short-lasting anti-GM1 elevation had a fast recovery, whereas patients with slow recovery had a long-lasting anti-GM1 elevation. A linear relationship was found between significant clinical recovery and the time until the anti-GM1 peak was halved (R = 0.9, p < 0.01). The absolute level of anti-GM1 did not predict the length of the recovery nor was the level of anti-GM1 related to the clinical disability at its nadir. Our data indicate that monitoring of the IgM anti-GM1 level can predict clinical recovery in GBS patients.

OBJECTIVES: This study examined the relationship between housing conditions, educational level, occupational factors, and serologically diagnosed acute and chronic Helicobacter pylori infection. METHODS: Immunoglobulin G and immunoglobulin M serum antibodies against H. pylori were measured in 3589 Danish adults who participated in a population study. RESULTS: Low socioeconomic status (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.7, 3.0), short duration of schooling (OR = 2.0, 95% CI = 1.3, 2.5), lack of training/education (OR = 1.4, 95% CI = 1.2, 1.7]), unskilled work (OR = 1.7, 95% CI = 1.2, 2.5), and high work-related energy expenditure (OR = 1.4, 95% CI = 1.1, 1.9) increased the likelihood of chronic H. pylori infection. Infection was frequent in people who had lived abroad. Increased levels solely of immunoglobulin M antibodies were found more often in people who were divorced (OR = 2.3, 95% CI = 1.2, 4.4) or unmarried (OR = 2.0, 95% CI = 1.1, 3.8) or who worked long hours (OR = 2.0, 95% CI = 1.1, 4.0). CONCLUSIONS: Educational and occupational factors relate to the likelihood of chronic H. pylori infection in adults. The rate of acute infection is high in single individuals.

The release from mucosal neutrophils of reactive oxygen species (ROS) is believed to be an important part of the pathogenesis of Helicobacter pylori-associated gastritis and duodenal ulcer. In this study, bacterial sonicates prepared from 1 reference and 29 patient strains were used to stimulate ROS release from peripheral blood neutrophils. In 29 H. pylori-positive patients, the neutrophil response toward the homologous strain was absent. In contrast, a significant response was observed toward the reference strain. In addition, on stimulation of neutrophils from 29 patients without H. pylori infection, ROS release was significant. The stimulatory effect on neutrophils by FMLP was comparable in the 2 groups. It is concluded that a specific neutrophil hyporesponsiveness in ROS release toward the homologous R. pylori strain exists. This feature has, to our knowledge, not been described previously for neutrophil responses to any human pathogen.

Only a minority of subjects with Helicobacter pylori infection develop clinical gastroduodenal disease. It is unclear whether host factors or bacterial virulence properties contribute to the pathogenic mechanisms. We have previously demonstrated a 25-35-kDa protein with phagocyte stimulatory activity in bacterial sonicates. Protein preparations were made from 15 H. neutrophil and monocyte chemotaxis and chemiluminescence was assessed with cells from healthy donors in comparison with N-f-methionyl-leucyl-phenylalanine and C5a anaphylatoxin. The potency of bacterial protein(s) for induction of monocyte chemiluminescence was significantly higher for strains from ulcer patients (1 +/- 1 microgram/ml induced > or = twofold increase of control response) and chronic active gastritis (1 +/- 1 microgram/ml) compared with superficial gastritis (> 1,000 microgram/ml, p

We conducted a retrospective epidemiologic study of catheter related bloodstream infections (CRBSI) in patients receiving long-term home parenteral nutrition (HPN) from January 2002 to December 2005. Our results showed that coagulase negative staphylococci (CoNS) were the most prevalent pathogens (44.7% of all CRBSI episodes), followed by Enterobacteriaceae (33.2%). Prevalence for candidemia and Enterococcus bacteremia was relatively high (14.4% and 10.8%, respectively). Cefuroxime resistance was observed in 65.4% CoNS and 31.5% Enterobacteriaceae. Based on the results from the study, a new empiric antimicrobial treatment regiment was suggested.

Helicobacter pylori-induced release of toxic substances by neutrophils could be of potential importance in the pathogenesis of gastroduodenal inflammatory diseases. Lipopolysaccharide (LPS) has the ability to induce neutrophil activation at very low concentrations. Neutrophil oxidative metabolism and enzyme release were assessed after stimulation of neutrophils with various preparations of LPS from H. pylori and compared with that obtained with Salmonella typhimurium LPS. No direct activation of neutrophils by LPS was observed. Preincubation with LPS showed a significant priming for increased activity on subsequent stimulation, particularly with rough-form LPS. The potency of H. pylori LPS was 10-fold lower than that of S. typhimurium LPS, probably reflecting the unique biochemical structure of H. pylori LPS. Chronic low-grade stimulation by H. pylori LPS in the gastric mucosa may render neutrophils primed for the excessive release of detrimental substances into the tissue on stimulation by other mediators.

The systemic humoral immune response to Helicobacter pylori antigens was investigated in 36 children with recurrent abdominal pain (RAP). H. pylori was cultured and Helicobacter-like organisms (HLO) were seen in six children, three of whom had active and two inactive chronic gastritis. None of these children had endoscopic abnormalities. All sex children had increased IgG antibodies to heat-stable H. pylori antigens which were of the IgG1 and IgG3 subclasses. Using six other IgG tests, four of which were commercially available, two to five H. pylori-positive children were found seropositive. Five of six H. pylori-negative children with inactive chronic gastritis and no endoscopic abnormalities had increased IgM antibody levels in addition to increased or borderline increased IgG antibody levels to H. pylori, indicating activity in a chronic H. pylori infection. Five children without H. pylori and with no morphological changes, but with gastritis or duodenitis by endoscopy, had significantly lower IgG and IgA antibody levels compared to other groups. Six of nineteen children without H. pylori, and with no morphological or endoscopic changes had increased IgG and IgM antibody levels to H. pylori. All H. pylori-negative children were seronegative by the four commercial kits. Overall, 12 (33%) of 36 children with RAP were either H. pylori positive by culture and microscopy or had increased IgG antibody levels to H. pylori, which is significantly different from the 10-14% seropositive rate of asymptomatic children. H. pylori may therefore be a cause of RAP in one quarter to one third of the children with RAP in whom other etiologies of RAP are excluded. Further studies on a large number of children are needed for an extended evaluation of the humoral immune response to H. pylori and for further examination of commercial kits which seem to give a high number of false-negative results.

Helicobacter pylori is a Gram-negative, microaerophilic curved rod, that possesses an unipolar bundle of two to six flagella which enables it to move to a specific target with high concentration of chemoattractants, such as urea. H. pylori is a pathogenic bacterium, which is present in more than half of the population worldwide with a range from 20 to 30% in developed countries to 60–80% in developing countries.

Selenomonas species are Gram-negative curved rods that morphologically resemble Campylobacter spp. and Helicobacter spp. The major differences between Selenomonas spp., Campylobacter spp. and Helicobacter spp. are shown in Table 1. Selenomonas spp. are natural inhabitants of the stomachs (rumen) of cattle [1]. They have occasionally been isolated from the human oral cavity, but have not been associated with human disease [2]. In the following, the isolation of a Selenomonas spp. from the gastric mucosa of a patient with peptic ulcer is reported.

Helicobacter pylori infects almost half of the population worldwide and represents the major cause of gastroduodenal diseases, such as duodenal and gastric ulcer, gastric adenocarcinoma, autoimmune gastritis, and B-cell lymphoma of mucosa-associated lymphoid tissue. Helicobacter pylori induces the activation of a complex and fascinating cytokine and chemokine network in the gastric mucosa. Different bacterial and environmental factors, other concomitant infections, and host genetics may influence the balance between mucosal tolerance and inflammation in the course of H. pylori infection. An inverse association between H. pylori prevalence and the frequencies of asthma and allergies was demonstrated, and the neutrophil activating protein of H. pylori was shown to inhibit the allergic inflammation of bronchial asthma. During the last year, significant progress was made on the road to the first efficient vaccine for H. pylori that will represent a novel and very important bullet against both infection and gastric cancer.

Electron microscopic studies have shown that Helicobacter pylori occurs in three stages: spiral forms, coccoid forms and degenerative forms. The spiral forms are viable, culturable, virulent and can colonize experimental animals and induce inflammation. The coccoid forms may also be viable but are nonculturable, less virulent and are less likely to colonize and induce inflammation in experimental animals than the spiral forms. The degenerative forms are pyknotic, nonculturable, coccoid forms of dead H. pylori. These forms cannot be cultured and the cell membrane has disintegrated but gene material can be detected by PCR in water supplies. There is no substantial evidence for viable H. pylori persisting in water supplies. Epidemiological studies suggest that environmental water is a risk factor for H. pylori infection when compared with tap water, and formation of H. pylori biofilm cannot be excluded. Helicobacter pylori does not seem to take part in biofilm formation in the oral cavity even though the bacterium may be detected.

When Helicobacter pylori arrives in the human stomach, it may penetrate the mucin layer and adhere to the gastric epithelial cells or it may pass through the stomach without colonizing the mucosa. In this paper, the colonization process and the ensuing immunological response will be briefly described. Urease production is necessary for H. pylori to establish a pH-neutral microenvironment around the bacteria. The flagella enable the bacteria to move and the shape of H. pylori makes it possible to penetrate the mucin layer where it comes into contact with the gastric epithelial cells. H. pylori contains several adhesins that enable it to adhere to the epithelial cells. This adherence activates IL-8 which, together with bacterial antigens, attracts polymorphs and monocytes and causes acute gastritis. Antigen-presenting cells activate lymphocytes and other mononuclear cells that are attracted to the inflamed mucosa, causing chronic superficial gastritis and initiating a cytotoxic or an antigen-producing Th response. The infection is established within a few weeks after the primary exposure to H. pylori. After this initial colonization, many chemical, biochemical, and immunologic reactions take place that are of importance in the progress of the infection and the development of disease.

Helicobacter pylori infects almost 50% of the world population and is the major cause of gastroduodenal diseases. H. pylori colonizes the gastric mucosa, activates Toll-like and Nod-like receptors, and usually elicits a T helper 1 (Th1) type of immune response, fully polarized in peptic ulcer patients. Among several bacterial factors, the neutrophil-activating protein represents a key factor driving Th1 inflammation. A complex and fascinating balance between H. pylori and host factors takes part in the gastric niche and allows the majority of infected individuals to be without any symptom during their entire life. Novel insights into the innate and adaptive responses against H. pylori, dealing with regulatory T cells and cytokines, CTLA-4 molecule, cholesterol glucosylation, and immune evasion have been elucidated during the past year and are discussed for the development of an effective vaccine.

The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.

Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytokines which may improve knowledge concerning the outcome of gastric diseases caused by H. pylori . Antral biopsies from 42 dyspeptic patients including 27 H. pylori -positive and 15 H. pylori -negative patients were tested for apoptotic activity by the TUNEL assay, and immuno-histochemically for p53 and the proliferative marker Ki-67. H. pylori infection, bacteria load and inflammatory activity were associated with increased cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53 was significantly correlated to IFN-γ, IL-8 and IL-10. The H. pylori -positive state was furthermore accompanied by varying degrees of altered distribution pattern of the markers studied, with occasional presence of apoptosis in the deeper pit zones, upward extension of Ki-67 and to a lesser degree of p53. Given a similar pattern of change in proliferation and apoptosis in some neoplastic lesions in other parts of the gastrointestinal tract, such studies in cell turnover may provide insights valuable in the investigations of potential precursors of gastric malignancies.

This article describes an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in two institutions for multi-handicapped children in Copenhagen. The aim of the study was to determine whether it was possible to eradicate MRSA in a setting with multi-handicapped children and staff where there was a high degree of physical interaction. This was a prospective interventional uncontrolled cohort study that took place from January 2003 to March 2005. All individuals in close contact with the two institutions and/or in close contact with an MRSA-colonized subject from the outbreak were included in the study: 38 children, 60 staff members and 12 close relatives of colonized subjects. Infection control measures included screening all individuals. When MRSA infection or colonization was found, an attempt was made to eradicate MRSA, staff education was undertaken and attempts were made to determine the route of transmission. Eleven individuals were found to be positive for MRSA (10.0%). All isolates were identical by pulsed-field gel electrophoresis and harboured the staphylococcal cassette chromosome mec (SCCmec) type IV. All colonized and infected individuals were associated with a single room in one of the institutions. MRSA was eradicated from all the colonized and infected subjects. This study shows that it is possible to control an MRSA outbreak in institutions for multi-handicapped children where there is a high degree of physical contact.