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Helicobacter Pylori a Friend or a Foe?

Helicobacter Pylori a Friend or a Foe?. Nir Fireman Pediatric Gastroenterologist MacMurray Centre. Outline. Overview- History and microbiology The Good The Bad Diagnosis Treatment. Basic Facts. Gram negative spiral flagellated bacterium Human is the only known reservoir?

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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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