1. Helicobacter Pylori a 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 2007 Y. Yamaoka, Mechanisms of disease: Helicobacter pylori virulence factors
Nature Reviews Gastroenterology & Hepatology 7, (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:
M.J Blaser, J.C Artherton J Clin Invest 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 Pharmacol Ther 2012;35.-
~130,000 patient cohort underwent GI endoscopy
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 NOT realated 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) Non invasive tests
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 ;

20. Treatment Triple therapy- 14 Days Sequential treatment- 10 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 no. of doses Daily dose Drug 2 1.5-2.5 mg/kg/d (max 40mg/d)
PPI
40-60 mg /kg/d (max 2 gr/d)
mg/kg/d (max 3 gr/d)
Amoxicillin
High Dose Amoxicillin
20 mg/kg/d (max 1 gr/d)
Metronidazole
Clarithromycin
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

25. 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

26. Thank you