Incidence of gastrointestinal malignancies increases in persons received eradication therapy for Helicobacter pylori: A cohort study.

BACKGROUND: Long-term Helicobacter pylori infection increases the risk of gastric malignancies. Since the symptoms for H. pylori gastritis, as well as for several malignancies, may be nonexisting or highly unspecific, even H. pylori-positive subjects with underlying malignancies may receive eradication therapy. The aim was to assess the incidence of gastrointestinal and various other malignancies in individuals after eradication therapy for H. pylori infection. MATERIALS AND METHODS: A cohort of 217,554 subjects (120,344 women and 97,210 men), who had purchased specific combinations of drugs for H. pylori eradication therapy in 1994-2004, was identified by the Finnish National Prescription Registry and followed for cancer incidence until the end of 2008 (1.89 million person-years at risk). RESULTS: A total of 22,398 malignancies were identified in the cohort. In both genders, for the first 6 months after drug prescription, the standardized incidence ratios (SIRs) were between 5 and 32 for gastric, colorectal, and pancreatic cancers, and 2 and 3 for several other malignancies. Although later on the SIRs of most malignancies fell rapidly, those of gastric noncardia and lung cancers remained elevated up to 5 years of follow-up. The only SIRs below unity were seen in men for gastric cancers (cardia 0.61, 95% CI: 0.37-0.95; intestinal noncardia 0.74, 95% CI: 0.56-0.97) during the post-therapy period covering years 5-15. CONCLUSION: Incidence levels significantly above the population rates were detected for many malignancies. Although eradication of H. pylori may have a long-lasting protective effect against gastric cancer, H. pylori therapy may postpone the detection of malignancies possibly underlying unspecific gastrointestinal symptoms. Therefore, it should be emphasized that the diagnostic work-up for malignancies should not be stopped in case of detection and treatment of H. pylori infection.

Campylobacter coli Clade 3 Isolates Induce Rapid Cell Death In Vitro.

Campylobacter bacteria are major human enteropathogens. Campylobacter coli shows less genetic diversity than C. jejuni and clusters into three clades, of which clade 1 includes most human and farm animal isolates, while environmental C. coli isolates mainly belong to clades 2 and 3. Recently, we sequenced the whole genomes of eight C. coli clade 2 and 3 isolates cultivated from water, and here we studied their interaction with human HT-29 colon cancer cells compared to that of clinical clade 1 isolates. All C. coli clade 3 isolates already caused cell necrosis 1 to 2 h after inoculation, whereas none of the clade 1 and 2 isolates analyzed induced cell death. Isolates from clades 2 and 3 adhered to epithelial cells better than clade 1 isolates, but all isolates induced similar levels of interleukin-8 (IL-8). Alignment and phylogenetic analysis of the translated putative virulence genes cadF, flpA, iamA, ciaB, and ceuE revealed clade-specific protein sequence variations, with clade 1 and 2 sequences being more closely related and clade 3 sequences being further apart, in general. Moreover, when RNA levels were measured, clade 3 isolates showed significantly lower levels of expression of cadF, iamA, and ceuE than clade 2 isolates, while flpA expression levels were higher in clade 3 isolates. The cytolethal distending toxin genes were also expressed in clades 2 and 3, although there was no difference between clades. Our findings demonstrate differences between the effects of C. coli clade 1, 2, and 3 isolates on human cells and suggest that C. coli clade 3 might be more virulent than clade 2 due to the observed cytotoxicity.IMPORTANCECampylobacter coli is a common zoonotic cause of gastroenteritis in humans worldwide. The majority of infections are caused by C. coli clade 1 isolates, whereas infections due to clade 2 and 3 isolates are rare. Whether this depends on a low prevalence of clade 2 and 3 isolates in reservoirs important for human infections or their lower ability to cause human disease is unknown. Here, we studied the effects of C. coli clade 2 and 3 isolates on a human cell line. These isolates adhered to human cells to a higher degree than clinical clade 1 isolates. Furthermore, we could show that C. coli clade 3 isolates rapidly induced cell death, suggesting differences in the virulence of C. coli The exact mechanism of cell death remains to be revealed, but selected genes showed interesting clade-specific expression patterns.

Stool Microbiota Composition Differs in Patients with Stomach, Colon, and Rectal Neoplasms.

BACKGROUND: Microbial ecosystems that inhabit the human gut form central component of our physiology and metabolism, regulating and modulating both health and disease. Changes or disturbances in the composition and activity of this gut microbiota can result in altered immunity, inflammation, and even cancer. AIM: To compare the composition and diversity of gut microbiota in stool samples from patient groups based on the site of neoplasm in the gastrointestinal tract (GIT) and to assess the possible contribution of the bacterial composition to tumorigenesis. METHODS: We studied gut microbiota by16S RNA gene sequencing from stool DNA of 83 patients, who were diagnosed with different GIT neoplasms, and 13 healthy individuals. RESULTS: As compared to healthy individuals, stools of patients with stomach neoplasms had elevated levels of Enterobacteriaceae, and those with rectal neoplasms had lower levels of Bifidobacteriaceae. Lower abundance of Lactobacillaceae was seen in patients with colon neoplasms. Abundance of Lactobacillaceae was higher in stools of GIT patients sampled after cancer treatment compared to samples collected before start of any treatment. In addition to site-specific differences, higher abundances of Ruminococcus, Subdoligranulum and lower abundances of Lachnoclostridium and Oscillibacter were observed in overall GIT neoplasms as compared to healthy controls CONCLUSION: Our study demonstrates that the alterations in gut microbiota vary according to the site of GIT neoplasm. The observed lower abundance of two common families, Lactobacillaceae and Bifidobacteriaceae, and the increased abundance of Enterobacteriaceae could provide indicators of compromised gut health and potentially facilitate GIT disease monitoring.

Lipooligosaccharide locus classes and putative virulence genes among chicken and human Campylobacter jejuni isolates.

BACKGROUND: Campylobacter cause morbidity and considerable economic loss due to hospitalization and post infectious sequelae such as reactive arthritis, Guillain Barré- and Miller Fischer syndromes. Such sequelae have been linked to C. jejuni harboring sialic acid structures in their lipooligosaccharide (LOS) layer of the cell wall. Poultry is an important source of human Campylobacter infections but little is known about the prevalence of sialylated C. jejuni isolates and the extent of transmission of such isolates to humans. RESULTS: Genotypes of C. jejuni isolates from enteritis patients were compared with those of broiler chicken with pulsed-field gel electrophoresis (PFGE), to study the patterns of LOS biosynthesis genes and other virulence associated genes and to what extent these occur among Campylobacter genotypes found both in humans and chickens. Chicken and human isolates generally had similar distributions of the putative virulence genes and LOS locus classes studied. However, there were significant differences regarding LOS locus class of PFGE types that were overlapping between chicken and human isolates and those that were distinct to each source. CONCLUSIONS: The study highlights the prevalence of virulence associated genes among Campylobacter isolates from humans and chickens and suggests possible patterns of transmission between the two species.

Increase in the Prevalence of Atrophic Gastritis Among Adults Age 35 to 44 Years Old in Northern Sweden Between 1990 and 2009.

BACKGROUND & AIMS: Atrophic corpus gastritis (ACG) is believed to be an early precursor of gastric adenocarcinoma. We aimed to investigate trends of ACG in Northern Sweden, from 1990 through 2009, and to identify possible risk factors. METHODS: We randomly selected serum samples collected from 5284 participants in 1990, 1994, 1999, 2004, and 2009, as part of the population-based, cross-sectional Northern Sweden Multinational Monitoring of Trends and Determinants in Cardiovascular Disease study (ages, 35-64 y). Information was collected on sociodemographic, anthropometric, lifestyle, and medical factors using questionnaires. Serum samples were analyzed for levels of pepsinogen I to identify participants with functional ACG; data from participants with ACG were compared with those from frequency-matched individuals without ACG (controls). Blood samples were analyzed for antibodies against Helicobacter pylori and Cag pathogenicity island protein A. Associations were estimated with unconditional logistic regression models. RESULTS: Overall, 305 subjects tested positive for functional ACG, based on their level of pepsinogen I. The prevalence of ACG in participants age 55 to 64 years old decreased from 124 per 1000 to 49 per 1000 individuals between 1990 and 2009. However, the prevalence of ACG increased from 22 per 1000 to 64 per 1000 individuals among participants age 35 to 44 years old during this time period. Cag pathogenicity island protein A seropositivity was associated with risk for ACG (odds ratio, 2.29; 95% confidence interval, 1.69-3.12). Other risk factors included diabetes, low level of education, and high body mass index. The association between body mass index and ACG was confined to individuals age 35 to 44 years old; in this group, overweight and obesity were associated with a 2.8-fold and a 4.7-fold increased risk of ACG, respectively. CONCLUSIONS: Among residents of Northern Sweden, the prevalence of ACG increased from 1990 through 2009, specifically among adults age 35 to 44 years old. The stabilizing seroprevalence of H pylori and the increasing prevalence of overweight and obesity might contribute to this unexpected trend. Studies are needed to determine whether these changes have affected the incidence of gastric cancer.

Multilocus sequence typing (MLST) and whole-genome MLST of Campylobacter jejuni isolates from human infections in three districts during a seasonal peak in Finland.

A total of 95 human Campylobacter jejuni isolates acquired from domestic infections and collected from three districts in Finland during the seasonal peak (June to September) in 2012 were analyzed by PCR-based multilocus sequence typing (MLST) and by whole-genome sequencing (WGS). Four predominant sequence types (STs) were detected among the isolates: ST-45 (21%) and ST-230 (14%, ST-45 clonal complex [CC]), ST-267 (21%, ST-283 CC), and ST-677 (19%, ST-677 CC). In districts 1 and 3, most of the infections occurred from early July to the middle of August, with a peak at weeks 29 to 31, but in district 2, the infections were dispersed more evenly throughout 3 months (June to August). WGS data were used for further whole-genome MLST (wgMLST) analyses of the isolates representing the four common STs. Shared loci of the isolates within each ST were analyzed as distance matrices of allelic profiles by the neighbor-net algorithm. The highest allelic variations (>400 different alleles) were detected between different clusters of ST-45 isolates (1,121 shared loci), while ST-230 (1,264 shared loci), ST-677 (1,169 shared loci), and ST-267 isolates (1,217 shared loci) were less diverse with the clusters differing by <40 alleles. Closely related isolates showing no allelic variation (subclusters) were detected among all four major STs. In some cases, they originated from different districts, suggesting that isolates can be epidemiologically connected and may have the same infection source despite being originally identified as sporadic infections.

A prospective follow-up study on transmission of Campylobacter from poultry to abattoir workers.

Contact with poultry or poultry meat is a well-known risk factor for campylobacteriosis, but prospective studies on transmission of Campylobacter from chickens to humans during slaughter are scarce. In this study, we monitored transmission of Campylobacter from slaughtered chicken to originally culture-negative abattoir workers during the peak season of colonized chicken and human Campylobacter infection. Stool samples were obtained from 28 abattoir workers together with data on health status once a month between June and September 2010, with a follow-up sample collected in February 2011. Campylobacter-positive individuals and chicken flocks were identified by culture, and isolates were further characterized using molecular techniques. Campylobacter was isolated from seven asymptomatic individuals. Four of them had been newly employed and had not reported any previous Campylobacter infection. Four human isolates had matching genetic fingerprints with isolates from recently slaughtered chickens. Our results further support the role of chicken as the source of human Campylobacter infection but suggest that asymptomatic Campylobacter infection may occur even in individuals with only limited earlier exposure to Campylobacter.

Clonal distribution and virulence of Campylobacter jejuni isolates in blood.

Campylobacter jejuni bacteria are highly diverse enteropathogens. Seventy-three C. jejuni isolates from blood collected in Finland were analyzed by multilocus sequence typing and serum resistance. Approximately half of the isolates belonged to the otherwise uncommon sequence type 677 clonal complex. Isolates of this clonal complex were more resistant than other isolates to human serum.

Characterization of clinical Campylobacter jejuni isolates with special emphasis on lipooligosaccharide locus class, putative virulence factors and host response.

Recent studies have indicated a role of the lipooligosaccharide (LOS) of Campylobacter jejuni in the severe neurological Guillain Barré syndrome, as well as in development of more severe symptoms of acute enteritis. We evaluated the role of the LOS locus class in C. jejuni infection among 163 enteritis patients. The prevalence of LOS locus classes differed according to the origin of the isolates. Furthermore, LOS locus classes A and B were significantly associated with susceptibility or resistance to ciprofloxacin and doxycycline. However, our results do not corroborate earlier findings that isolates with potential to sialylate LOS might be associated with more severe symptoms of enteritis. Instead, in an infection model, such isolates gave weaker epithelial IL-8 responses than nonsialylated isolates. Absence of the iron transport protein encoded by the gene ceuE as well as the putative fucose permease gene cj0486 was associated with increased in vitro IL-8 secretion.

A nationwide study of Campylobacter jejuni and Campylobacter coli bacteremia in Finland over a 10-year period, 1998-2007, with special reference to clinical characteristics and antimicrobial susceptibility.

BACKGROUND: Campylobacter bacteremia is an uncommon condition, usually diagnosed in elderly and immunocompromised patients. METHODS: Blood culture isolates and clinical information were collected for patients with diagnoses of Campylobacter jejuni or Campylobacter coli bacteremia in Finland from 1998 through 2007. Bacterial species were identified by means of polymerase chain reaction analysis, and minimal inhibitory concentrations for ciprofloxacin, clindamycin, doxycycline, erythromycin, gentamicin, meropenem, and metronidazole were determined with an agar dilution method. Medical records and mortality data within 1 year after the bacteremic episode were reviewed. RESULTS: The study included 76 patients (median age, 46 years), for whom bacterial isolates (C. jejuni in 73, C. coli in 3) and clinical information were available. Most patients (70%) had no significant underlying diseases. The majority (82%) of the isolates were susceptible for all antimicrobial agents tested. However, antimicrobial therapy seemed to have only a limited effect, because no differences could be detected between patients with appropriate empirical antimicrobial treatment and those with delayed appropriate, inappropriate, or no antimicrobial therapy, either in the duration of hospitalization (median, 4 days for both groups) or in attributable mortality. The outcome of the infection was severe in 4 patients infected with C. jejuni; 2 died within 30 days, spondylodiscitis developed in 1, and Guillain-Barré syndrome developed in 1. CONCLUSIONS: C. jejuni and C. coli bacteremia occurred mainly in moderately young individuals without severe underlying diseases. The bacterial isolates were predominantly susceptible to antimicrobial agents, and the outcome of the disease was typically good, regardless of appropriate or inappropriate antimicrobial treatment given in the hospital.

Gastric cancers in Finnish patients after cure of Helicobacter pylori infection: A cohort study.

Helicobacter pylori infection is associated with gastric cancer. A total of 97% of the infected subjects have elevated levels of H. pylori antibodies. The antibody titers have been shown to decline rapidly (40-60% within 4-12 months) only after successful eradication therapy. We allocated 26,700 consecutive patients tested during 1986-1998 for H. pylori antibodies to 3 subcohorts: seropositive patients with rapidly falling antibody titers (Hp+CURED, n = 3,650), seropositive patients where no serological information indicating cure was obtained (Hp+NoInfo, n = 11,638) and seronegative patients (Hp-, n = 11,422). In the subcohorts, the standardised incidence ratios (SIRs) with 95% confidence intervals (CI) were defined for subsequent cancers of stomach, pancreas, colon, rectum, breast and prostate separately and for all cancers except stomach combined. The mean follow-up time was 10.1 years and the number of gastric cancers was 72. For the Hp+CURED, the SIR for gastric cancers for the first 5 follow-up years was 1.62 but decreased from the sixth follow-up year thereon to 0.14 (CI: 0.00-0.75). Likewise, the risk ratio, defined in a Poisson regression analysis using the Hp+NoInfo group as the reference, decreased from 1.60 to 0.13 (CI: 0.02-1.00, p = 0.049). The SIR for Hp- was not significantly higher than that for Hp+NoInfo for any of the cancers analysed. To conclude, cured H. pylori infection led to a significantly decreased incidence of gastric cancers from the sixth follow-up year. Advanced atrophic gastritis would be a plausible contributor to the elevated SIR in elderly Hp- patients.

Longitudinal analysis of serological responses of adults to Helicobacter pylori antigens.

Because Helicobacter pylori persist for decades in the human stomach, the aim of this study was to examine the long-term course of H. pylori-specific serum immunoglobulin G (IgG) responses with respect to subclass and antigenic target. We studied paired serum samples obtained in 1973 and in 1994 in Vammala, Finland, from 64 healthy H. pylori-positive adults and from other healthy control subjects. H. pylori serum immunoglobulin A, IgG, and IgG subclass responses were determined by antigen-specific enzyme-linked immunosorbent assays. H. pylori-specific IgG1 and IgG4 subtype responses from 47 subjects were similar in 1973 and 1994, but not when compared with unrelated persons. H. pylori-specific IgG1:IgG4 ratios among the participants varied >1000-fold; however, 57 (89.1%) of 64 subjects had an IgG1:IgG4 ratio >1.0, consistent with a predominant IgG1 (Th1) response. Furthermore, ratios in individual hosts were stable over the 21-year period (r = 0.56; P < .001). The immune response to heat shock protein HspA was unchanged in 49 (77%) of the 64 subjects tested; of the 15 whose serostatus changed, all seroconverted and were significantly younger than those whose status did not change. These findings indicate that H. pylori-specific antibody responses are host-specific with IgG1:IgG4 ratios stable over 21 years, IgG1 responses predominating, and HspA seroconversion with aging.

Changes to human faecal microbiota after international travel.

BACKGROUND: The aim was to investigate whether travelling to less-resourced destinations influences the composition of faecal microbiota in generally healthy adults. METHOD: In this prospective observational study, 47 adults (median age, 24 years; 73% females) travelled from Sweden to distant destinations for 1-12 weeks. Five faecal samples, two before and three after travel, were analysed by 16S amplicon massive parallel sequencing. Subjects had taken no antibiotics within three months of each sampling. RESULTS: The overall composition of faecal microbiota was not affected by travel. However, when looking at the relative abundance of individual bacterial taxa, Enterobacteriaceae demonstrated a 10-fold increase immediately after the trip as compared to the samples taken before travelling. Conversely, the relative abundance of Christensenellaceae had decreased equally much. Both these changes were reversible within nine weeks. CONCLUSIONS: International travel, even to less-resourced countries, did not appear to alter the overall diversity of human faecal microbiota as studied here after travelling. However, Enterobacteriaceae bacteria, often associated with infection, inflammation, and antibiotic resistance, showed dramatically elevated levels, and Christensenellaceae, frequently associated with healthy conditions, demonstrated remarkably declined levels in relative abundance as detected immediately after travel. Both these changes returned to original pre-travel levels within nine weeks.

Training and assessment of medical specialists in clinical microbiology and infectious diseases in Europe.

BACKGROUND: There is wide variation in the availability and training of specialists in the diagnosis and management of infections across Europe. OBJECTIVES: To describe and reflect on the current objectives, structure and content of European curricula and examinations for the training and assessment of medical specialists in Clinical (Medical) Microbiology (CM/MM) and Infectious Diseases (ID). SOURCES: Narrative review of developments over the past two decades and related policy documents and scientific literature. CONTENT: Responsibility for curricula and examinations lies with the European Union of Medical Specialists (UEMS). The ID Section of UEMS was inaugurated in 1997 and the MM Section separated from Laboratory Medicine in 2008. The sections collaborate closely with each other and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Updated European Training Requirements (ETR) were approved for MM in 2017 and ID in 2018. These comprehensive curricula outline the framework for delivery of specialist training and quality control for trainers and training programmes, emphasizing the need for documented, regular formative reviews of progress of trainees. Competencies to be achieved include both specialty-related and generic knowledge, skills and professional behaviours. The indicative length of training is typically 5 years; a year of clinical training is mandated for CM/MM trainees and 6 months of microbiology laboratory training for ID trainees. Each Section is developing examinations using multiple choice questions to test the knowledge base defined in their ETR, to be delivered in 2022 following pilot examinations in 2021. IMPLICATIONS: The revised ETRs and European examinations for medical specialists in CM/MM and ID provide benchmarks for national authorities to adapt or adopt locally. Through harmonization of postgraduate training and assessment, they support the promotion and recognition of high standards of clinical practice and hence improved care for patients throughout Europe, and improved mobility of trainees and specialists.

Genomic and Phenotypic Characteristics in Geographically Separated Clinical Campylobacter jejuni ST353CC Isolates.

Campylobacter jejuni fecal isolates of eight international travelers, 5 of which had traveled to Ecuador and 3 to Bangladesh, were characterized, and the possible relationship between bacterial traits and clinical symptoms was further analyzed. All eight isolates belonged to the same Multi-Locus Sequence Type clonal complex (ST353CC). The three isolates from Bangladesh were all of the same sequence type (ST-9438), and when compared to isolates of various other sequence types, they had a larger quantity of unique genetic content, higher expression levels of some putative virulence genes involved in adhesion and invasion (flpA, ciaB and iamA), and showed higher adhesion levels to human HT-29 colon cancer cells in an in vitro infection model. However, in contrast to the seemingly higher pathogenic potential of these bacterial isolates, travelers infected with the ST-9438 isolates had no or only very mild symptoms, whereas the other individuals, whose bacterial isolates seemed to have less pathogenic potential, generally reported severe symptoms. When studying the 16S rRNA gene-based fecal microbiota in samples collected prior to travel, there was an individual variation in the relative abundance of the three major bacterial phyla Actinobacteria, Bacteroidetes and Firmicutes, but there were no associations between composition and diversity of microbiota and development of severe symptoms from the infection. It remains to be confirmed by larger studies whether an individual's characteristics such as gut microbiota, might be related to the severity of symptoms in Campylobacter infections.

Gut microbiota of patients with different subtypes of gastric cancer and gastrointestinal stromal tumors.

BACKGROUND: Gastric adenocarcinoma is associated with H. pylori infection and inflammation that can result in the dysbiosis of gastric microbiota. The association of intestinal microbiota with gastric adenocarcinoma subtypes or with gastric gastrointestinal stromal tumors (GIST) is however not well known. Therefore, we performed 16S rRNA gene sequencing on DNA isolated from stool samples of Finnish patients and controls to study differences in microbiota among different histological subtypes of gastric adenocarcinoma, gastric GIST and healthy controls. RESULTS: We found that gut microbiota alpha diversity was lowest in diffuse adenocarcinoma patients, followed by intestinal type and GIST patients, although the differences were not significant compared to controls. Beta-diversity analysis however showed significant differences in microbiota composition for all subtypes compared to controls. Significantly higher abundance of Enterobacteriaceae was observed in both adenocarcinoma subtypes, whereas lower abundance of Bifidobacteriaceae was seen only in diffuse adenocarcinoma and of Oscillibacter in intestinal adenocarcinoma. Both GIST and adenocarcinoma patients had higher abundance of Enterobacteriaceae and lower abundance of Lactobacillaceae and Oscillibacter while lower abundance of Lachnoclostridium, Bifidobacterium, Parabacteroides and Barnesiella was seen only in the adenocarcinoma patients. CONCLUSIONS: Our analysis shows association of higher Enterobacteriaceae abundance with all types of gastric tumors. Therefore it could be potentially useful as a marker of gastric malignancies. Lower gut microbiota diversity might be indicative of poorly differentiated, invasive, advanced or aggressive tumors and could possibly be a prognostic marker for gastric tumors.

Characterization of multiple Helicobacter bizzozeronii isolates from a Finnish patient with severe dyspeptic symptoms and chronic active gastritis.

BACKGROUND: Helicobacter pylori is the primary cause of gastritis and peptic ulceration in humans. In a minority of patients with upper gastrointestinal symptoms, long tightly coiled spiral bacteria, provisionally named "Helicobacter heilmannii," are observed in gastric biopsies. These bacteria are extremely fastidious and only one previous study has succeeded in obtaining an isolate in vitro. MATERIALS AND METHODS: We used two different selective media to isolate "H. heilmannii" from the gastric mucosa of a Finnish patient presenting with severe dyspeptic symptoms. The isolates were characterized by testing for urease and catalase activity, by using light and electron microscopy, and by sequencing of the partial 16S rRNA and ureAB genes. Single-enzyme amplified fragment length polymorphism (sAFLP) was used to analyze the genetic diversity among the isolates. RESULTS: We obtained 15 isolates from different gastric biopsies prior and three after unsuccessful treatment of the patient. The isolates were identified as Helicobacter bizzozeronii. Eradication therapy was unsuccessful most probably due to high level of resistance to metronidazole. Persistent colonization by the same H. bizzozeronii clone was confirmed by sAFLP, however, small differences between the profiles suggested long-term colonization of the patient. CONCLUSIONS: Helicobacter bizzozeronii remains the only "H. heilmannii" species isolated from human gastric mucosa although it has been an infrequent observation among "H. heilmannii"-infected patients in PCR-based screening studies. The relevance of H. bizzozeronii and other potentially zoonotic gastric Helicobacter spp. in human disease remains to be determined.

A "screen-and-treat" approach for Helicobacter pylori infection: a population-based study in Vammala, Finland.

BACKGROUND: To accelerate the decline of Helicobacter pylori infection, and to study the significance of the possible risk factors for H. pylori infection in Finland, we started a voluntary H. pylori"screen-treat-retest-and-retreat" program for all young adults at primary health care in Vammala, Finland after a pilot study in 1994 including 504 subjects aged 15-75. MATERIALS AND METHODS: A total of 3326 aged 15-40 in 1996, and 716 aged 15 and 584 aged 45 in 1997-2000 were screened for H. pylori using serology. Helicobacter pylori positive were treated, cure was verified by serology. RESULTS: The eradication rates were 93.8%, 82.2%, and 77.6% per protocol in pilot study in 1994, in subjects invited in 1996 and 1997-2000, respectively. Helicobacter pylori seroprevalence rates were calculated to have decreased from 36% to 14% in pilot study, from 12% to 4% among subjects invited in 1996, from 3% to 2% among subjects aged 15 and from 27% to 12% among subjects aged 45 in 1997-2000. An epidemiologic questionnaire in 1996 revealed that crowding in the childhood household, low education of the mother, current smoking and alcohol consumption, unfavorable housing conditions, and sick leaves due to dyspepsia were independently associated with H. pylori infection. CONCLUSIONS: This intervention with high participation rates resulted in a significant decline in calculated H. pylori seroprevalence rates. Although the low prevalence of H. pylori infection may limit the cost efficiency of the program, the intervention is expected to reduce the burden of H. pylori-associated diseases.

Assessment of systemic matrix metalloproteinase and their regulator response in children with Helicobacter pylori gastritis.

BACKGROUND: Helicobacter pylori causes gastritis and is the most important risk factor of peptic ulcer disease and gastric cancer. In chronic adulthood H. pylori infection some matrix metalloproteinases (MMPs), which are proteolytic metalloendopeptidases regulated by tissue inhibitors of metalloproteinases (TIMPs), are upregulated. Our aim was to determine circulating levels of MMPs and their regulators TIMP-1, human neutrophil elastase (HNE) and myeloperoxidase (MPO) in childhood H. pylori infection. DESIGN AND METHODS: Twenty-six H. pylori positive and 34 H. pylori negative children whose H. pylori status was verified by histological examination of gastric biopsies were included. Serum samples were analysed by enzyme-linked immunosorbent assay. RESULTS: Significantly decreased serum levels of TIMP-1 were detected in H. pylori-infected children (median, 97.50 ng/mL) as compared to H. pylori-negative children (median, 118.5 ng/mL, p = 0.003). However, there were no significant differences in serum levels of MMP-2, -7, -8, -9, and their regulators HNE and MPO between H. pylori-positive and -negative children. CONCLUSIONS: Differing from the recent findings in adulthood H. pylori infection, only circulating TIMP-1 levels were significantly different between H. pylori-positive and -negative children. Whether this reflects the first sign of a proteolytic cascade later leading to increased levels of MMPs remains to be shown.

Genomic and Phenotypic Characterisation of Campylobacter jejuni Isolates From a Waterborne Outbreak.

Campylobacter infections are the leading cause of bacterial gastroenteritis. In Europe, over 246,000 cases are confirmed annually. Infections are often transmitted via contaminated food, such as poultry products, but water may be the source of infection as well. The aim of this study was to characterise a selection of Campylobacter jejuni human isolates, together with a water isolate, from a waterborne outbreak in Norway in 2019, including human isolates from early, mid-, and late epidemic. The isolates were characterised with whole-genome sequencing, analysing the expression of putative virulence genes and demonstrating the pathogenic potential in an in vitro adhesion model using HT-29 cells. All isolates belonged to the multilocus sequence type 1701 and ST45 clonal complex. In the genomic analysis, the water isolate clustered somewhat separately from the human isolates. There was some variation between the human isolates, but the water isolate seemed to display the greatest pathogenic potential, demonstrated by the highest levels of virulence gene expression, adhesion to epithelial cells and IL-8 induction. These results suggest that the water isolate of the study has potential to cause human infections, and that some bacterial changes due to host or environmental adaptation, may occur during a waterborne Campylobacter epidemic. This is, to the best of our knowledge, the first study on C. jejuni isolates from a waterborne outbreak, including both human isolates and a water isolate, characterised with genomic and phenotypic approaches.