Co-expression in Helicobacter pylori of cagA and non-opsonic neutrophil activation enhances the association with peptic ulcer disease

AIMS: To investigate the association of cagA positivity and non-opsonic neutrophil activation capacity in wild-type Helicobacter pylori strains with peptic ulcer disease or chronic gastritis only. METHODS: Helicobacter pylori were isolated from antral biopsies of 53 consecutive patients with chronic antral gastritis, of whom 24 had peptic ulcer disease endoscopically. The presence of cagA, a marker for the cag pathogenicity island, was determined by polymerase chain reaction with specific oligonucleotide primers, and non-opsonic neutrophil activation capacity by luminol enhanced chemiluminescence. RESULTS: The cagA gene was present in 39 of 53 (73.6%) strains, 20 of which (83.3%) were from the 24 patients with peptic ulcer disease and 19 (65.5%) from the 29 patients with chronic gastritis only. Non-opsonic neutrophil activation was found in 29 (54.7%) strains, 16 of which (66.7%) were from patients with peptic ulcer disease, and 13 (44.8%) from those with chronic gastritis. Non-opsonic neutrophil activation was found more frequently in cagA+ than cagA- strains (59% v 42.9%). Whereas four of the 14 cagA- strains and eight of the 24 non-opsonic neutrophil activation negative strains were from patients with peptic ulcer disease, only two of 24 (8.3%) peptic ulcer disease strains expressed neither cagA nor non-opsonic neutrophil activation. The cagA gene and non-opsonic neutrophil activation capacity were co-expressed in 14 of 24 (58.3%) strains from patients with peptic ulcer disease, and in nine of 29 (31%) strains from individuals with chronic gastritis. CONCLUSIONS: Positivity for cagA and non-opsonic neutrophil activation occur independently in wild-type H pylori strains. However, co-expression of the two markers enhanced the prediction of peptic ulcer disease.     

Campylobacter etiology in human gastroenteritis demonstrated by antibodies to acid extract antigen

Campylobacter antibodies of the immunoglobulin G (IgG), IgM, and IgA classes were determined by enzyme immunoassay with acid glycine extract antigen in patients and controls involved in two Campylobacter outbreaks and in 266 unselected patients with acute enteritis. The assay showed a specificity of 99% for each immunoglobulin class in sera from 200 healthy blood donors. Elevated Campylobacter antibody titers were shown in 97% of stool culture-positive patients involved in the outbreaks. Rapid changes of IgA and IgM Campylobacter antibodies were typical of the early phase of serologic response in the outbreaks and thus offered the best diagnostic value in the serologic diagnosis of acute campylobacteriosis. In unselected patients with acute enteritis, the assay revealed elevated Campylobacter antibody titers in 37 patients, of whom only 12 had had positive Campylobacter stool cultures. In the sera of patients with other bacterial findings in addition to high titers of Campylobacter antibodies, no cross-reacting antibodies were found, but there was evidence of several mixed infections.     

Incidence of Helicobacter pylori strains activating neutrophils in patients with peptic ulcer disease.

A total of 61 human gastric isolates of Helicobacter pylori were studied for their ability to induce an oxidative burst in human neutrophils measured by luminol enhanced chemiluminescence. About one third of the strains induced strong and rapid chemiluminescence in neutrophils even without serum opsonins and agglutinated these cells on glass slides within two minutes. For other strains complement was required, although even then the reactions remained at a lower level. The activating and agglutinating property was bound to the cells, heat labile, and sensitive to several enzymes but resistant to acid. Strains possessing such activity were more common in patients with peptic ulcer disease than in patients with active chronic gastritis only (p = 0.0261, Fisher's exact test, two tailed). The activity shown might be a new indicator for ulcerogenic strains and could also partly explain the accumulation of neutrophils in the gastric mucosa during H pylori infection.     

Prospective study of the etiology of diarrhea in adult outpatients and inpatients

A prospective study of the etiology of diarrhea in 253 adult outpatients and inpatients was conducted in Helsinki in 1985-86. The outpatients constituted 84.6% of all patients studied. A broad panel of diagnostic techniques was applied, including detection of bacteria and parasites in the feces and determination of the serologic responses to campylobacter, salmonella, Yersinia enterocolitica, and several viruses. Pathogens were identified for 28.5% of the patients. The commonest findings were Campylobacter jejuni/coli in 13.0% and Salmonella species in 7.1% of the patients. Mixed infections of several pathogens were found in 16 patients.     

Domestically acquired Campylobacter infections in Finland

Campylobacter jejuni isolates (n = 533) from domestic cases diagnosed in Finland during a 3-month peak period were studied. The highest rate was observed among those 70-74 years of age. Domestic C. jejuni isolates were especially frequent in the eastern districts. Six serotypes covered 61% of all C. jejuni isolates.     

An outbreak of gastroenteritis from a non-chlorinated community water supply

STUDY OBJECTIVE: To determine the source and the extent of a community wide outbreak of gastroenteritis. DESIGN: A matched case-control study with postal questionnaires. Subtyping of campylobacter strains by pulsed field gel electrophoresis (PFGE). SETTING: A rural municipality with a population of 8600 in southern Finland, August 2000. Two thirds of the population receive non-chlorinated ground water from the municipal water supply. PARTICIPANTS: Cases were randomly selected among residents of the municipality who contacted the municipal health centre because of gastroenteritis and had illness onset between 31 July and 20 August 2000. Community controls were identified from the population registry and matched according to sex, year of birth, and postal code. Main results: Four hundred and sixty three persons contacted the municipal health centre because of gastroenteritis. Campylobacter jejuni was isolated from stool samples of 24 persons. One hundred and thirty seven cases and 388 controls were enrolled in the case-control study. In multivariate analysis, drinking unboiled water from the municipal supply was significantly associated with illness (odds ratio 11.1, 95% confidence interval 1.4 to 90.2). C jejuni was isolated from one tap water sample. The water isolate and all but one of the patient isolates were indistinguishable by PFGE. CONCLUSIONS: Combining epidemiological investigation with molecular subtyping methods provided strong evidence that water was the source of the outbreak. Non-chlorinated small ground water systems may be susceptible to waterborne outbreaks and constitute a risk to rural populations.     

Role of metronidazole resistance in therapy of Helicobacter pylori infections.

Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate.