Gifone A. Rocha

Evaluation of [13C]urea breath test and Helicobacter pylori stool antigen test for diagnosis of H. pylori infection in children from a developing country.

ABSTRACT The [13C]urea breath test (13C-UBT) and Helicobacter pylori stool antigen test (HpSA) for the diagnosis of H. pylori infection in children were validated. The sensitivity, specificity, and positive and negative predictive values were 93.8, 99.1, 97.8, and 98.0%, respectively, for the 13C-UBT and 96.9, 100, 100, and 98.0%, respectively, for HpSA. Both tests are appropriate for diagnosing H. pylori infection in children.

Effect of Helicobacter pylori eradication on antral gastrin- and somatostatin-immunoreactive cell density and gastrin and somatostatin concentrations

The density of antral gastrin (G)- and somatostatin (D)-immunoreactive cells and the contents of antral gastrin and somatostatin were investigated in endoscopic antral biopsy specimens from patients with duodenal ulcer before and after eradication of Helicobacter pylori. After H. pylori eradication both antral somatostatin concentration (p = 0.0002) and antral D-cell density (p = 0.01) increased significantly. Conversely, although the number of G-cells was unchanged, antral (p = 0.0002) and serum (p = 0.001) gastrin contents decreased significantly. The number of oxyntic D-cells did not change significantly. These results strongly suggest that the hypergastrinaemia observed in H. pylori-positive patients may be due to a deficiency in antral somatostatin, which normally inhibits the synthesis and release of gastrin.

Prevalence of Helicobacter pylori Infection in a Rural Area of the State of Mato Grosso, Brazil

The prevalence of Helicobacter pylori infection was evaluated by ELISA in 40 children and teenagers and in 164 adults from a rural area of the State of Mato Grosso, Brazil. Antibodies to H. pylori were detected in the serum of 31 (77.5%0 children and teenagers and in 139 (84.7%) adults. The prevalence of infection increased with age (x2 for trend, p < 0.01) even though no variations occurred in the region in the present century in terms of living conditions or sanitation, economical development and migratory influx supporting the hypothesis that the infection is also acquired during later life in developing countries. An inverse correlation was observed between the prevalence of infection and annual family income (x2 for trend, p < 0.013). There was no correlation between type of system for sewage disposal and prevalence of infection (p = 0.8). In conclusion, the prevalence of H. pylori infection in Nossa Senhora do Livramento, a rural area from Brazil, is very high and similar to that observed in other developing countries. Furthermore, the increase in the prevalence of infection with age observed in this population seems to be due to both, cohort effect and acquisition of the infection during later life.

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-β were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.

Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer

BackgroundHelicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis.ResultsThe number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR = 3.08, 95% CI = 1.74 to 5.45, p < 10-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p = 0.04) and intestinal metaplasia (p = 0.007). Furthermore, patients infected by cag A strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer.ConclusionsOur results demonstrate that infection with H. pylori strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer.Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.

Transmission of Helicobacter pylori infection in families of preschool-aged children from Minas Gerais, Brazil.

We evaluated the role of the family in the transmission of Helicobacter pylori infection in preschool‐aged children from a rural district in the State of Minas Gerais, Brazil. Sixty‐six families (66 index children, 63 mothers, 60 fathers and 134 siblings), defined as at least one parent living in the same household with at least one offspring up to 8 years old, were studied. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression controlling for age, gender, number of children in household and H. pylori status of the father, mother and siblings. The prevalence of the infection was 69.7% (469 of 673) and it increased with age (P < 0.001). Positive mothers were a strong and independent risk factor for infection (OR 22.70; 95% CI 2.31–223.21). Positive siblings were also positively associated with infection (OR 1.81; 95% CI 1.01–3.30).

babA2- and cagA-positive Helicobacter pylori strains are associated with duodenal ulcer and gastric carcinoma in Brazil.

ABSTRACT The babA2 and cagA genes were investigated in 208 Brazilian Helicobacter pylori strains. A strong association between babA2 and duodenal ulcer or gastric carcinoma was observed, even after adjusting for confounding factors, such as age, gender, and cagA status. cagA-positive strains were also independently associated with H. pylori-related diseases.

IL1RN polymorphic gene and cagA‐positive status independently increase the risk of noncardia gastric carcinoma

Helicobacter pylori cagA‐positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL‐1 gene cluster and tumor necrosis factor‐α (TNFA)‐307 polymorphisms, as well as cagA‐positive status, are associated with gastric carcinoma in a non‐Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori‐positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme‐linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B‐511/‐31, IL1RN (interleukin‐1 receptor antagonist) and TNFA‐307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2‐pair primers. We found that the IL1RN2 polymorphic allele (OR = 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA‐positive status was the strongest independent factor associated with gastric carcinoma (OR = 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA‐positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma.

New Pathogenicity Marker Found in the Plasticity Region of the Helicobacter pylori Genome

ABSTRACT Comparison of gastric carcinoma and gastritis isolates showed the presence of genes, probably carcinoma associated (JHP947 and JHP940), that are situated in a Helicobacter pylori genome region (45 kb in J99 and 68 kb in 26695) called the “plasticity region.” This region presents a great variability of DNA sequences. We investigated, by PCR, the presence of the JHP940 and JHP947 genes, as well as the presence of a third gene which seems to be associated with gastritis (HP986), on H. pylori strains isolated from 200 Brazilian patients, 79 of whom had gastric carcinomas and 53 of whom had duodenal ulcers, to confirm this association. Gastritis isolates (n = 68) were included as a control. We also evaluated if these genes were related to the virulence-associated cagA genotype. The present methodology did not permit definitive conclusions to be reached regarding the association between the JHP940 gene and gastric carcinoma or between the HP986 gene and gastritis. However, we showed that the JHP947 gene might be implicated in the development of both duodenal ulcer and gastric carcinoma. The presence of the JHP947 gene was associated with the cagA-positive genotype. The JHP947 gene is a novel virulence marker candidate of H. pylori.

Helicobacter pylori Primary Resistance to Metronidazole and Clarithromycin in Brazil

ABSTRACT Helicobacter pylori resistance to metronidazole was detected in 107 (52.97%) of 202 strains. Twenty (9.85%) strains, 18 of them harboring 23S ribosomal DNA mutations, were resistant to clarithromycin. Metronidazole resistance was associated with female gender. Resistance to metronidazole and resistance to clarithromycin were associated. Increasing clarithromycin resistance rates were observed over time.