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Helicobacter Pylori a Friend or a Foe?

This comprehensive outline provides an overview of the history, microbiology, and impact of Helicobacter pylori infections. Understand the good and bad aspects, diagnosis, treatment, and associated diseases. Discover why H. pylori is crucial for immune response and learn about related research findings. Explore the impact on conditions like asthma, IBD, and celiac disease. Delve into the complexities of H. pylori persistence, immune evasion, and transmission mechanisms. Stay informed on the latest insights and guidelines in managing H. pylori infections.

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Helicobacter Pylori a Friend or a Foe?

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  1. Helicobacter Pyloria Friend or a Foe? Nir Fireman Pediatric Gastroenterologist MacMurray Centre

  2. Outline • Overview- History and microbiology • The Good • The Bad • Diagnosis • Treatment

  3. Basic Facts • Gram negative spiral flagellated bacterium • Human is the only known reservoir? • Most common enteric infection worldwide • 80% in developing, and 10% in developed countries • In New Zealand – 10-50%

  4. Transmission • Infection occurs in early childhood and unless treated, persists for life • Adult rarely become infected. Seroconvertion rates 0.33%-0.5% per person year • Rate of reinfection 2.3%-20% • The mechanism of transmission is not fully understood. • Person-person appears to be the most likely mode of transmission • Fecal-oral • Oral-oral

  5. Appeared in the human stomach at least since the migration of our ancestor from Africa 60,000 years ago Linz B et al. An African origin for the intimate association between human and H pylori. Nature 2007Y. Yamaoka, Mechanisms of disease: Helicobacter pylori virulence factors Nature Reviews Gastroenterology & Hepatology 7, 629-641 (November 2010)

  6. H.pylori persistence • Motility- the flagella allowing the bacteria to move through gastric mucus • Urease activity – raises the pH in the mucus surrounding the bacteria. UreI protein- pH sensitive channel

  7. H.pylori persistence • Immune evasion mechanisms- • Minimal tissue invasion • Minimal innate immune system recognition- • Highly methylated DNA • Relatively anergic LPS • VacA- • Suppress macrophages • Inhibits antigen presentation in T cells • suppress proliferation of T cells • T regulatory induction and down regulation of Th17/ Th1 effects • J Kao, M Zhang et al. Helicobacter pylori immune escape. Gastroenterology 2010;138:1046-1054 • M.J Blaser, J.C Artherton J Clin Invest. 2004 Feb;113(3):321-3

  8. Up regulation of Treg leads to decreased production of pro-inflammatory cytokines J.Luther, M Dave, P Higgins and J Kao. Association between Helicobacter pylori infection and IBD. Inflamm Bowel Dis. 2010; Vol 16

  9. H.pylori is Good For You • H pylori may protect against childhood onset asthma, and other immune mediated disorders including inflammatory bowel disease and celiac disease.

  10. H.pylori is Good For You • Low prevalence of Helicobacter Pylori infection among patients with inflammatory bowl disease. A sonnenberg, R.M Genta. Aliment PharmacolTher 2012;35.- • ~130,000 patient cohort underwent GI endoscopy 2008-2010 • Association between Helicobacter pylori infection and inflammatory bowel disease: a meta-analysis and systemic review of the literature. J.Luther et al. Inflamm Bowel Dis. 2010 • Helicobacter pylori colonization is inversely associated with childhood asthma. Y chen and M Blaser. JID 2008 • Decreased risk of celiac disease in patients with Helicobacter pylori colonization. Lebwohl B, Blaser MJ, Ludvigsson JF, et al. Am J Epide- miol 2013

  11. Diseases Associated With H pylori • Chronic Gastritis- • All children colonized with H.pylori will develop chronic gastritis • The majority remain asymptomatic throughout their lives • A small proportion will develop peptic ulcer, and even smaller will develop gastric cancer

  12. Diseases Associated With H pylori • Duodenal ulcer- • Duodenal ulcer is very rare in children- <5% in children younger than 12, and ~10% in teenagers • H.Pylori is found in the antrum of 90% of children and 80% of adults with duodenal ulcer. • Gastric ulcer- H pylori is associated in 60% of adult and rarely in children

  13. Diseases Associated With H pylori • Gastric Adenocarcinoma- • 4th most frequent cancer and 2nd leading cause of death from cancer. • Extremely rare in children • Multifactorial- • H.pylori was classified as class 1 carcinogen by the WHO • Corpus/pan gastritis –IL-1β, TNFα, IL10 • Familial clustering • Diet?, smoking

  14. Diseases Associated With H pylori • MALT Lymphoma- • H.pylori consider to be an etiologic factor. • Eradication may lead to complete resolution in 75%. MALT lymphoma with t(11;18)(q21;q21) translocation do not respond to eradication • Typically occur in adulthood with only few case reports in children

  15. Non GI manifestation- Refractory IDA (increase demand, sequestration, hypochloridia inhibits the reduction of iron to ferrous) • Chronic ITP? • H pylori is NOTrealated to- AOM, URTI, periodontal dis, food allergy, SIDS, and short stature

  16. H.Pylori and Abdominal Pains • Differential diagnosis of abdominal pain and dyspepsia is different in children • Most abdominal pain and dyspepsia are functional • There is no evidence that H.pylori gastritis in the absence of duodenal ulcer causes symptoms in children • ESPGHAN, NASPGHAN 2011, 2016 guidelines- • The primary goal of clinical investigation of GI symptoms is to determine the underlying cause of the symptoms and not solely the presence of H pylori infection • Diagnostic testing for H pylori infection is not recommended in children with functional abdominal pain.

  17. Who should be tested? A “test and treat” strategy in not recommended in children Except- • ?First degree relatives with gastric cancer • ?Refractory iron deficiency anemia (when other causes have been ruled out)

  18. Diagnosis • Invasive tests (based on tissue biopsy) • Culture- 100% specific • Rapid Urease Test (CLO) • Histopathology • FISH • PCR • Non invasive tests • C13-urea breath test • ELISA detection of H pylori antigen in stool • Antibodies (IgG, IgA) in blood, urine, saliva

  19. Who should be treated? • H.pylori positive peptic ulcer disease (PUD) – Eradication treatment is recommended • H.pylori infection in the absence of PUD- Eradication treatment may be consider • Refractory Iron Deficiency Anemia • ?Chronic ITP • ?FHx of Gastric Cancer Evidence-based Guidelines From ESPGHAN and NASPGHAN for Helicobacter pylori Infection in Children .JPGN 2011 53;230-242

  20. Treatment • Triple therapy- 14 Days • PPI+ Amoxicillin + Metronidazole • PPI+ Amoxicillin+ Clarithromycin • Bismuth salts + Amoxicillin + Metronidazole • Sequential treatment- 10 Days • PPI+ Amoxicillin- for 5 days • Followed by – PPI+ Clarithromycin+ Metronidazole- for 5 days

  21. Treatment Guidelines for the Management of H pylori in Children and Adolescents JPGN, Vol 64, No 6, June 2017

  22. Treatment Guidelines for the Management of H pylori in Children and Adolescents JPGN, Vol 64, No 6, June 2017

  23. John Hsiang et al NZMJ 18 October 2013

  24. Take Home Message • H.pylori infection is very common but rarely symptomatic in children • H.pylori became multi resistant bug • In functional abdominal pain – Don’t test, don’t treat • H.pylori infection might be beneficial • In Paediatric gastrointestinal complaints- search for the cause, not for the H.pylori infection

  25. Thank you http://www.enfermania.com/en/83-giants-01microbios

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