2. H. Pylori
Past, Present and future
DR. SAMEH MOHAMED BADR
M.SC. GASTROENTEROLOGY & HEPATOLOGY
3. History (Before 1984)
During the last century hemorrhage from PUD was
treated by rest, starvation, and opium.
A widespread belief that blood transfusion would
restart bleeding and accordingly blood transfusion
was withheld
4. History (Before 1984)
Peptic ulcers have plagued men throughout the centuries, but the exact cause
of the condition was uncertain. In 1940, Dr. A. Stone Freedberg of Harvard
Medical School identified unusual curved bacteria in the stomachs of ulcer
victims; he suspected that they might be responsible for ulcers but abandoned
the research when his team was unable to grow the bacteria in the lab
(BMJ Feb. 1955)
6. Causes of Peptic Ulcer (1967)
Life
Style
Diet
Alcohol
Emotiona
l strain
Genotype
Personality
Smoking.
M. Susser, Journal of Chronic Diseases, Vol. 20 ;. 435-451 ;1967
This does not exclude the
possibility that a major single
causal effect awaits
discovery.
8. Helicobacter pylori and Peptic Ulcer Disease
• Gastroenterologists resisted Marshall & Warren’s idea.
“It was hard for them to accept that the disease could be simple
infection.”
• Bacteriologists were suspicious --- the stomach had long been
assumed to be too acidic to host bacteria.
13. Land Mark Changes in H.pylori
The name of the bacterium was grammatically corrected in 1987 to Campylobacter pylori and, in 1989
the bacterium was renamed Helicobacter pylori and assigned as the type species of a novel genus
due to its 16s rRNA sequence.
17. EPIDEMIOLOGY
• Helicobacter pylori is the most common chronic bacterial infection in humans .
• Studies involving genetic sequence analysis suggest that humans have been
infected with H. pylori since they first migrated from Africa around 58,000 years
ago.
• Infection is more frequent and acquired at an earlier age in developing
countries compared to industrialized nations .
ACG 2017
20. EPIDEMIOLOGY
Over half the population is infected in early childhood.
Most of those infected never have symptoms.
The bacteria are most likely spread from person to person through
fecal-oral or oral-oral routes.
Possible environmental reservoirs include contaminated water sources.
21. EPIDEMIOLOGY
• Intrafamilial clustering of infection further supports person-to-
person transmission.
• Iatrogenic infection: the use of a variety of inadequately
disinfected instruments (Endoscopy).
• Gastroenterologists and nurses appear to be at increased risk
for acquiring H. pylori;( occupational exposure).
22. EPIDEMIOLOGY
H. pylori infection is usually acquired during childhood. although the exact means of acquisition is not always clear. Risk factors for
acquiring the infection include low socioeconomic status, increasing number of siblings and having an infected parent—especially an
infected mother. In the Ulm (Germany) Birth Cohort Study, the odds ratio (OR) for acquiring H. pylori infection if a child’s mother was
infected was 13.0 (95% confi dence interval (CI) 3.0–55.2) Apart from intrafamilial spread, the infection may also be transmitted through
contaminated water supplies particularly in developing countries.
Although infection rates for male and female children are similar there may be a slight male preponderance of the infection in adulthood.
ACG 2017
24. Acute Infection With H. Pylori
• Initial one week with acid hypersecretion followed by
hypochlorhydria:
• Asymptomatic
• Nausea and vomiting
• Dyspepsia
• Next 3-6 months: symptoms resolve, acid returns
• Majority of individuals have asymptomatic, chronic
nonulcer pan-gastritis.
30. Helicobacter factors in pathogenesis of
PU
Some strains are more pathogenic than others. The Cag A
(cytotoxic) antigen is one important virulence factor
Human variability also plays a part (e.g. individuals who
produce high levels of IL-1b in inflammation get pan gastritis
and GU, lower levels associated with antral gastritis and DU)
32. Association of H. pylori with
gastric cancer
H. pylori infection has been linked with the development of
gastric cancer.
Associated cancers include adenocarcinoma of corpus and
antrum, and MALT lymphoma.
The relationship is probably causal.
36. Rationale for initial anti-H.pylori regimen in MALT
Treatment of H. pylori in gastric MALT lymphomas leads to
regression of the lymphoma
Cases of extragastric MALT lymphoma responding to anti-H.pylori
eradication have been reported.
In a Japanese series:
77% out of 420 patients treated for H. pylori infection showed
either complete histological response or probable minimal residual
disease .
Wundisch et al;2012 ; 143 : 936 – 42 . quiz e13-4
38. Other Diseases’ Association
Digestive
- Non-ulcer dyspepsia (NUD)
Vascular
- Ischaemic heart disease
- Raynaud’s phenomenon
- Headache and migraine
Autoimmune
- Henoch-Schönlein purpura
- Sjögren’s syndrome
Other
- Rosacea and urticaria
- Sideropaenic anaemia
- Growth retardation
- Amenorrhoea
- Halitosis
39. Diagnosis of H. pylori
Non-invasive tests
Serology
13/14C-urea breath test (UBT)
H.Pylori stool Ag
PCR in saliva and faeces
40. Diagnosis of H. pylori
-Rapid urease test
-Direct microscopy
-Histology
-Culture
-DNA probes/PCR
Endoscopy-based
41. Serology
The detection of Antibodies in active infection is
useful, But the tests are limited utility as antibodies
persist even after H.pylori infection is eradicated.
Several commercial kits are available, but lacks the role in
identifying acute infections.
42. Urea Breath Test
In this test 13C or 14C labelled urea is ingested by patients.
If H. pylori is present the urease activity generates labelled Co2
that can be detected in the patients exhaled breath.
Sensitivity and specificity of this test ra ng es from 94-98%.
43. Antigen Detection Test in Stool
Detection of H. pylori antigen in stool is appropriate test in
patients with H. pylori infection
Absence of antigen indicates cure of Infection after
Chemotherapy.
44. Rabid urease test
Rapid tests for detection of Urease activity are widely
used in presumptive identification of Gastric Biopsy
specimens.
Gastric Biopsy can be placed into urea containing
medium with color indicator.
If H.pylori is present the Urease rapidly splits urea
and resulting shift in pH yields a color change in the
medium
45. Culturing for H. pylori
Culturing of H.pylori needs specific conditions
Media
1/ Skirrow”s Medium
2/ Chocolate Medium
46. False Negative H.pylori Testing
Antimicrobial therapy
PPI
Biopsy sites and lab. errors.
47. False Negative H.pylori Testing
The antibacterial activity of antibiotics and bismuth
compounds necessitate their discontinuation for 4 weeks to
allow an increase of a detectable bacterial load.
48. False Negative H.pylori Testing
PPIs have an anti-H. pylori activity and decrease the load
of H. pylori leading to false-negative results on urease test,
UBT, and SAT.
The 14 days are considered a ‘safety’ interval, while a 7-day
withdrawal has been shown to be sufficient.
H2 receptor antagonists & antacids have minimal effect on
the sensitivity of UBT.
49. Endoscopic Biopsy
For assessment of H. pylori gastritis:
- A minimum standard biopsy setting:
* Two biopsies from the antrum (greater and lesser curvature
3 cm proximal to the pyloric region)
Two biopsies from the middle of the body.
Additional biopsy from the incisura is considered for detection of
precancerous lesions.
(Maastricht V/Florence )
50. Who should be offered H.pylori testing?
WHEN TO TEST?
51. WHEN TO TEST?
ACG recommendations :
H. pylori infection is common in the general
population.
Diagnostic testing for H. pylori should only be
performed if treatment is intended.
57. First line treatment of H. pylori
A. PPI
lansoprazole 30 mg twice daily, omeprazole 20 mg twice daily, pantoprazole 40 mg
twice daily, rabeprazole 20 mg twice daily, or esomeprazole 40 mg once daily).
B. Amoxicillin (1 g twice daily), and
C.Clarithromycin (500 mg twice daily) for 7 to 14 days
Metronidazole
(500 mg twice daily) can be substituted for amoxicillin but only in penicillin-allergic
individuals since metronidazole resistance is common and can reduce the efficacy of
treatment.
Eradication Rate : 70-85%
59. ANTIBIOTIC RESISTANCE
H. pylori are naturally resistant to several commonly used
antibiotics, including vancomycin, trimethoprim, and sulfonamides.
The incidence of metronidazole and clarithromycin resistance is
rising & appears to vary with geography.
Prior use of macrolide antibiotics or metronidazole appears to
increase the risk of H. pylori resistance against them.
61. ANTIBIOTIC RESISTANCE
Metronidazole resistance appears to be a "relative" phenomenon
that can be overcome in most instances by using a higher dose (500
mg) or using it in combination with a bismuth preparation.
Clarithromycin resistance appears to be an "absolute" condition that
can not be overcome by increasing the macrolide dose
66. Second Line Therapy
Quadruple therapy (Bismuth-based)
PPI twice daily
Bismuth-based therapy (Pepto Bismol 2 tablets, four times daily
Tetracycline 500 mg, four times daily.
High dose metronidazole 500 mg four times daily, preferably
given with meals for 14 days.
Eradication Rate >90% .
67. Second Line Therapy
Alternative Regimen
PPI
Tetracycline (500 mg).
Metronidazole (500 mg), and
Bismuth subcitrate caplets (240 mg),
Each given twice daily with the midday and evening meals for 2
weeks
68. Sequential triple therapy
10-day sequential regimen of :
First 5 days :
PPI. BID.
1 g of amoxicillin BID.
Remaining 5 days :
PPI BID.
500 mg of Clarithromycin BID ,and
500 mg of tinidazole BID .
69. Sequential triple therapy
10-day sequential regimen of :
First 5 days :
- PPI. BID.
- Amoxicillin 1 gm BID.
Remaining 5 days :
- PPI BID.
- Levofloxacin 250-500 mg BID ,and
- Tinidazole 500 mg BID
73. Hybrid Therapy
The first 7 days:
PPI + Amoxicillin 1gm BID.
The second 7 days: BID
PPI
Amoxicillin.
Clarithromycin.
Nitroimidazole (Metronidazole or Tinidazole).
Eradication rate :88-90 %.
Hsu PI et al ;Helicobacter 2011;16:139– 45.
Wu et al,Clin. Gastroenterology &Hepatology,2010;8-16
79. SHOULD WE TEST FOR TREATMENT SUCCESS AFTER
H. PYLORI ERADICATION THERAPY?
Recommendation:
Whenever H. pylori infection is identified and treated,
testing to prove eradication should be performed using:
- urea breath test.
fecal antigen test or
biopsy-based testing
NB: Serology can’t be used to check eradication.
80. Role of Culture And Sensitivity
It is important to perform culture &susceptibility testing in region of
high clarithromycin resistance before prescription of the first-line
treatment.
Furthermore, culture and susceptibility testing should be considered
in all regions before second-line treatment if endoscopy is carried
out.
Lastly, when a second-line treatment has failed , C &S should be ordered.
81. Role of Culture And Sensitivity
If culture is not possible, molecular tests (including
fluorescence in situ hybridisation) can be used to
detect H pylori and clarithromycin and/or
fluoroquinolone resistance in gastric biopsies.
Such tests have been developed recently and kits are
commercially available in certain countries.
82. Treatment During Pregnancy ?
Treatment is typically deferred till after delivery.
Some evidences that H. pylori can aggravate N/V in pregnancy up to
hyperemesis gravidarum.
With the exception of bisthmus, tetracycline and quinolones, all H. pylori
regimens are of low risk.
Thus if indicated, H. pylori Tx should be considered during pregnancy.
Some medications are not recommended during lactation.
83. REINFECTION
A large-scale multicentre, prospective open cohort observational study in
China reported an annual reinfection rate after successful eradication
treatment of 1.5% per person-year.
O'Connor A, Furuta T, Gisbert JP, O'Morain C. Review – Treatment of Helicobacter pyloriinfection
2020. Helicobacter. 2020;25(Suppl. 1):e12743.
