Dynamics of Helicobacter pylori infection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial.

OBJECTIVE: To evaluate the long-term effect of cumulative time exposed to Helicobacter pylori infection on the progression of gastric lesions. DESIGN: 795 adults with precancerous gastric lesions were randomised to receive anti-H. pylori treatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time of H. pylori exposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1-6). The score difference between baseline and 16 years was modelled by generalised linear models. RESULTS: Individuals who were continuously infected with H. pylori for 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected with H. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001). CONCLUSIONS: Long-term exposure to H. pylori infection was associated with progression of precancerous lesions. Individuals infected with H. pylori with these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.

Non-invasive genotyping of Helicobacter pylori cagA, vacA, and hopQ from asymptomatic children.

BACKGROUND: Helicobacter pylori infection is usually acquired in childhood, but little is known about its natural history in asymptomatic children, primarily due to the paucity of non-invasive diagnostic methods. H. pylori strains harboring cagA and specific alleles of hopQ and vacA are associated with increased risk for gastric cancer. Many studies of H. pylori virulence markers in children have the bias that symptomatic subjects are selected for endoscopy, and these children may harbor the most virulent strains. Our aim is to genotype cagA, hopQ, and vacA alleles in stool DNA samples of healthy Colombian children residing in an area with high incidence of gastric cancer, to avoid selection bias resulting from endoscopy. METHODS: H. pylori status of 86 asymptomatic children was assessed by (13) C-urea breath test (UBT) and PCR. H. pylori 16S rRNA, cagA, hopQ, and vacA genes were amplified from stool DNA samples and sequenced. RESULTS: UBT was positive in 69 (80.2%) of 86 children; in stool DNA analysis, 78.3% were positive by 16S rRNA PCR. cagA, vacA, and hopQ were detected in 66.1%, 84.6%, and 72.3% of stool DNA samples from 16S rRNA-positive children. Of the children's DNA samples, which revealed vacA and hopQ alleles, 91.7% showed vacA s1 and 73.7% showed type I hopQ. Type I hopQ alleles were associated with cagA positivity and vacA s1 genotypes (p < 0.0001). CONCLUSIONS: Using stool DNA samples, virulence markers of H. pylori were successfully genotyped in a high percentage of the asymptomatic infected children, revealing a high prevalence of genotypes associated with virulence. Type I hopQ alleles were associated with the presence of cagA and the vacA s1 genotype.

Effect of Helicobacter pylori infection on growth velocity of school-age Andean children.

BACKGROUND: Helicobacter pylori infection affects about half of the world's population and is usually acquired in childhood. The infection has been associated with chronic gastritis, peptic ulcer, and stomach cancer in adulthood. Little is known, however, about its consequences on child health. We examined the effect of H. pylori infection on growth among school-age children in the Colombian Andes by comparing growth velocity in the presence and absence of H. pylori infection. METHODS: Children who were 4-8 years old in 2004 were followed up in a community where infected children received anti-H. pylori treatment (n = 165) and a comparison community (n = 161) for a mean of 2.5 years. Anthropometry measurements were made every 3 months and H. pylori status ascertained by urea breath test every 6 months. Growth velocities (cm/month) were compared across person-time with and without infection, using mixed models for repeated measures. RESULTS: In the untreated community, 83% were H. pylori-positive at baseline and 89% were -positive at study end. The corresponding prevalences were 74% and 46%, respectively, in the treated community. Growth velocity in the pretreatment interval was 0.44 (standard deviation [SD] = 0.13) cm/month. Models that adjusted for age, sex, and height estimated that H. pylori-positive children grew on average 0.022 cm/month (95% confidence interval = 0.008 to 0.035) slower than H. pylori-negative children, a result that was not appreciably altered by adjustment for socioenvironmental covariates. CONCLUSIONS: This study suggests that chronic H. pylori infection is accompanied by slowed growth in school-age Andean children.

Long-term effects of clearing Helicobacter pylori on growth in school-age children.

BACKGROUND: A new Helicobacter pylori infection affects growth velocity negatively, and clearing the infection produces a small significant rebound, but it is not known whether height and weight in children are impacted over the long term. METHODS: We investigated 295 school-age children followed in 2 cohorts, treated (150) and untreated (145), from 2004 for 3.7 years with 1105 child-years of observation. Follow-up intervals were 3 months for anthropometry measurements and 6 months for H. pylori status ascertained by urea breath test. Height in centimeters and weight in kilograms were analyzed using growth models. RESULTS: A multivariate mixed model that adjusted for age, sex, father's education, and number of siblings found no significant differences in height or weight at baseline by H. pylori status. The same model showed a significant impact of clearing H. pylori across time, with increasing significant differences in average height and weight as the follow-up progressed. CONCLUSIONS: Children who were always negative or who cleared the infection grew significantly faster than those who stayed positive after adjusting for other covariates. This study suggests that school-age children's growth benefits from being treated for H. pylori infection.