Iron status and Helicobacter pylori infection in symptomatic children: an international multi-centered study

Objective:Iron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country.Methods:In total 311 children (mean age 10.7±3.2 years) from Latin America - Belo Horizonte/Brazil (n = 125), Santiago/Chile (n = 105) - and London/UK (n = 81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA.Results:The prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (r = -0.26; p = 0.01) and MCH (r = -0.27; p = 0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (r = -0.29, p = 0.008) and active (r = -0.27, p = 0.002) inflammation.Conclusions:This study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively

Unequal burden of mortality from gastric cancer in Brazil and its regions, 2000-2015

Background: Gastric cancer (GC) is an important cause of morbidity and mortality worldwide. However, population-based data on GC mortality dynamics in low and middle income countries are scarce. Methods: We analyzed GC mortality in Brazil based on all GC-related deaths registered 2000-2015. Results: A total of 17,374,134 deaths were recorded, with GC identified in 214,808 (1.24%) cases203,941 (94.9%) as underlying cause, and 10,867 (5.1%) as associated cause of death. Adjusted rates for age and sex was 6.85 deaths/100,000 inhabitants [95% confidence interval (CI) 6.73-6.97]. The highest mortality rates were found in males [10.00; rate ratio (RR) 1.85; 95% CI 1.78-1.91; p<0.0001] and patients 45years of age (24.98; RR 3.79; 95% CI 3.55-4.05; p<0.0001). The South (7.56; RR 1.62; 95% CI 1.50-1.76; p<0.0001) and Southeast (7.36; RR 1.59; 95% CI 1.48-1.71; p<0.0001) regions had the highest regional rates. Spatial and spatiotemporal high-risk mortality areas in 2004-2007 were located mainly in the South, Southeast, and Central-West regions. After 2008, the Northeast region became a high-risk area, especially Ceara State. Conclusion: GC remains a significant public health problem with high mortality burden and unequal distribution in Brazilian states. The new patterns in poorer regions and the high risk in some specific populations show a clear process of epidemiological transition over time. There is a need to strengthen nationwide epidemiological monitoring, surveillance, prevention, and control for GC in the country

Increased gastric IL-1β concentration and iron deficiency parameters in H. pylori infected children.

Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1β and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1β and TNF-α gastric concentrations were observed in H. pylori-positive (n = 47) than in -negative (n = 78) children. Multiple linear regression models revealed gastric IL-1β, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1β expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1β can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood

Histological comparison of antral and corpus gastric mucosa of <i>H. pylori (HP)</i>-positive (n = 47) and -negative (n = 78) children^a.

a<p>One antral and 3 corpus gastric biopsy specimens from <i>HP</i>-positive and 7 antral and 1 corpus biopsy specimens from <i>HP</i>-negative children were deemed to be inadequate for histology assessment; n, number.</p><p>Neither atrophy, nor intestinal metaplasia was observed.</p

<i>IL1B</i>-31, <i>IL1RN</i> and <i>TNFA</i>-307 genotypic frequencies in <i>H. pylori-positive</i> (n = 47) and –<i>negative</i> children (n = 78).

a<p>It was not possible to genotype 1 <i>H. pylori</i>-positive children for <i>IL1B-</i>31 and 1 for <i>IL1RN</i>.</p>b<p>1 indicates all the long alleles and 2 the short allele. The loci did not deviate significantly from the expected Hardy-Weinberg distribution (P = 0.90 for <i>IL1B-3</i>1, P = 0.26 for <i>IL1RN</i> and P = 0.08 for <i>TNFA</i>-307) and all segregated independently.</p

Correlations between corpus IL-1β concentrations and concentrations of ferritin and haemoglobin in <i>H. pylori</i>-positive children (n = 47).

<p>Statistical analysis by Pearson’s correlation after log transformation in the case of IL-1β and ferritin.</p

Box plots representing the comparison of gastric IL-1β (A) and TNF-α (B) concentrations (pg/mg of protein) between <i>H. pylori</i>-positive (HP+, n = 47) and -negative (HP-, n = 78) children, and between antral and corpus concentration in <i>H. pylori</i>-positive and -negative groups.

<p>The upper and lower limits of the boxes represent the 75^th and 25^th percentiles, respectively. The horizontal bar across the box indicates the median and the capped bars indicate the minimum and maximum data values. Statistical analysis by Student’s t test after log transformation in the case of IL-1β; *p<0.001 and **p = 0.02.</p

Histological comparison of antral (n = 85) and corpus (n = 83) gastric mucosa of <i>H. pylori (HP)</i>-positive children and antral (n = 202) and corpus (n = 214) gastric mucosa of <i>H. pylori</i>-negative children.^*.

*<p>Twenty-four antral and 13 corpus gastric biopsy specimens were deemed to be inadequate for histology assessment. n, number.</p

Multiple linear regression models including ferritin or haemoglobin as dependent variables and age, gender, country of birth and <i>H. pylori</i> infection as independent variables in children from Chile (n = 105) and Brazil (n = 125).

<p>Multiple linear regression models including ferritin or haemoglobin as dependent variables and age, gender, country of birth and <i>H. pylori</i> infection as independent variables in children from Chile (n = 105) and Brazil (n = 125).</p