H pylori infection in children is it really that bad?

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? Most common enteric infection worldwide 80% in developing, and 10% in developed countries In New Zealand 10-50%

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 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 2007 Y. Yamaoka, Mechanisms of disease: Helicobacter pylori virulence factors

Nature Reviews Gastroenterology & Hepatology 7, 629-641 (November 2010) 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 H.pylori persistence

Immune evasion mechanismsMinimal tissue invasion Minimal innate immune system recognitionHighly 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 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

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. H.pylori is Good For You Low prevalence of Helicobacter Pylori infection among patients with inflammatory bowl disease. A sonnenberg, R.M Genta. Aliment

Pharmacol Ther 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 Diseases Associated With H pylori Chronic GastritisAll 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 Diseases Associated With H pylori Duodenal ulcerDuodenal 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 Diseases Associated With H pylori Gastric Adenocarcinoma4th 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-1, TNF, IL10 Familial clustering Diet?, smoking Diseases Associated With H pylori MALT LymphomaH.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 Non GI manifestation- Refractory IDA (increase demand, sequestration, hypochloridia inhibits the reduction of iron to ferrous) Chronic ITP? H pylori is NOT realated to- AOM, URTI,

periodontal dis, food allergy, SIDS, and short stature 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 guidelinesThe 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. ? 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)

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 ?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 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 Treatment no. of doses Daily dose Drug 2

1.5-2.5 mg/kg/d (max 40mg/ PPI d) 2 40-60 mg /kg/d (max 2 gr/d) Amoxicillin 2 60-100 mg/kg/d (max 3

gr/d) High Dose Amoxicillin 2 20 mg/kg/d (max 1 gr/d) Metronidazole 2

20 mg/kg/d (max 1 gr/d) Clarithromycin Guidelines for the Management of H pylori in Children and Adolescents JPGN, Vol 64, No 6, June 2017 Treatment Guidelines for the Management of H pylori in Children and Adolescents JPGN,

Vol 64, No 6, June 2017 John Hsiang et al NZMJ 18 October 2013 Take Home Message H.pylori infection is very common but rarely symptomatic in children H.pylori became multi resistant bug In functional abdominal pain Dont test, dont treat

H.pylori infection might be beneficial In Paediatric gastrointestinal complaintssearch for the cause, not for the H.pylori infection Thank you http://www.enfermania.com/en/83-giants-01microbios

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