helicobacter pylori, this presentation includes epidemiology, pathogenisis,diagnosis and treatment of h.pylori

1. Helicobacter pylori
Vivekanandan A
MD General Medicine II year
Institute of Internal Medicine
Madras Medical College
1/8/2014
1

2. Introduction
▪ Helicobacter pylori (H. pylori) remains one of the most common
worldwide human infections and
▪ It is associated with a number of important upper
gastrointestinal (GI) conditions
– including chronic gastritis,
– peptic ulcer disease,
– gastric malignancy.
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3. Epidemiology
▪ Almost 50% of worlds population is affected by
H.pylori
▪ Genetic studies shows that humans are infected
for more than 58000 years at time they migrated
from Africa
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4. Time of acquisition of
infection
In developing nations
The majority of
children's are
infected before
the age of 10
years
And almost
reaching 80%
in adults
reaching the
age of 50
years
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5. In united states..
Unusual
before the
age of 10
years
Reaches
10% in
adults in the
age between
18 – 30 years
Reaches
almost 50%
in those
older than
60 years
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6. Risk factors
1. Socioeconomic status
•
•
•
•
•
Density of housing
Over crowding
Number of siblings
Sharing the same bed
Lack of running water
2. Consumption of salted food- increases
persistence of infections and also predisposes to
risk of gastric cancer
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7. Hereditary and genetic
factors
▪ Hispanics and African-Americans have a higher
rate of infection than Caucasians.
▪ Monozygotic twins raised in different households
have a greater concordance of H. pylori infection
than do dizygotic twins raised apart
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8. Routes of transmission
▪ Humans are the major reservoir of the H.pylori
▪ Person to person transmission in the form of
1.
2.
3.
Fecal – oral
Oral – oral
Gastric – oral
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9. Risks of transmission
▪ Childrens who consume untreated stream
water, uncooked vegetables
▪ Exposure to diarrheal stools, vomitus of the
infected persons
▪ Dentists and oral hygienists who have exposures to
dental plaques and saliva
▪ Iatrogenic infection in the form of contaminated
endoscopes and other gastric devices
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10. Microbiology
▪ Morphology:
• H. pylori is a spiral shaped,
• microaerophilic, gram negative bacterium
• measuring approximately 3.5 microns in length and 0.5
microns in width
• It has multiple unipolar flagella and it is actively motile
• biochemically characterized as catalyse, oxidise, and
urease positive.
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11. Growth and culture characters
▪ Growth and culture characters
• It’s a slow growing organism
• can be cultured on blood agar
• selective media is Skirrow's media (with
vancomycin, polymyxin B, and trimethoprim, chocolate
medium) incubated at 37ºC in a 5 percent oxygen
atmosphere for three to seven days
• The colonies are translucent and 1–2 mm in diameter.
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12. Pathophysiology
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13. Conditions associated with
H.pylori
▪
Esophagus
1.
2.
3.
GERD
Barrett’s esophagus
adenocarcinoma
▪ Stomach
1.
2.
3.
4.
5.
▪
Acute gastritis ( sometimes self limiting)
Chronic active gastritis
Peptic ulcer disease
Gastric adenocarcinoma
MALT
Duodenum
1.
Peptic ulcer
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14. Non gastrointestinal diseases
associated to H.pylori
▪ Coronary artery disease
▪ Immune thrombocytopenic purpura
▪ Iron deficiency anemia
▪ Reynaud's phenomenon
▪ Scleroderma
▪ Idiopathic urticaria
▪ Acne rosacea
▪ Thyroiditis
▪ GBS
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15. Diagnosis – when to test
ACG recommendations
▪ Testing for H. pylori should be performed only if
the clinician plans to offer treatment for positive
results
▪ Testing is indicated in patients with gastric MALT
lymphoma, active peptic ulcer disease, or a past
history of documented peptic ulcer
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16. Diagnosis – when to test
▪ patients with
uninvestigated
dyspepsia who are
under the age of 55
years and have no
alarm features
alarm features
▪ Deciding which test to use
in which situation relies
heavily upon whether a
patient requires evaluation
with upper endoscopy and
the strengths, weaknesses,
and costs of the individual
tests
▪ unexplained weight loss,
▪ bleeding,
▪ anaemia,
▪ early satiety,
▪ Progressive
▪ dysphagia, odynophagia,
▪ recurrent vomiting,
▪ family history of GI
cancer, previous
esophagogastric
malignancy
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17. Supported by the evidence
Controversial
Indications for testing and
treatment of H.pylori infection
Active peptic ulcer disease (gastric or
Functional dyspepsia
duodenal ulcer)
▪
Confirmed history of peptic ulcer
▪
▪
Gastric MALT-lymphoma (low grade)
▪ Unexplained iron deficiency anaemia
GERD
Persons using NSAIDs or before
starting NSAIDs
or ITP
Following endoscopic resection of early
gastric cancer
▪ Populations at higher risk of gastric
cancer
▪
Uninvestigated dyspepsia (if H. pylori
population prevalence high)
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18. Types of diagnostic test
Non endoscopic tests
Endoscopic tests
1. Serology
(quantitative or
qualitative IgG)
1. Histology
2. Urea breath test (13C
or 14C)
3. Culture
3. Stool antigen test
2. Rapid urease test
4. Polymerase chain
reaction assay
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19. Serology
▪ ELISA technology to detect IgG antibodies is
inexpensive, non-invasive.
▪ high sensitivity (90 to 100%), variable specificity
(76 to 96%) & accuracy( 83 to 98%).
▪ It needs confirmation with another method such
as a stool antigen or urea breath test before
starting treatment
▪ The “serological scar’ may be present even after
successful eradication of organism
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20. Urea breath test (UBT)
▪ detects active H. pylori infection, confirming the
accuracy of serology and documenting successful
treatment.
▪ The specificity is more than 95%, sensitivity of the test
is 88% to 95%
▪ false-negative results reported in patients taking
antisecretory therapy such as PPIs,bismuth, or
antibiotics.
▪ antibiotics should be stopped at least four weeks and
PPIs at least one week before breath testing.
▪ UBT is not accurate in patients who have had gastric
respective surgery.
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21. Urea breath test (UBT)
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22. Stool antigen assay
▪ It is an immunoassay to detect the presence of
h.pylori antigen in stools
▪ The sensitivity and specificity are 94% and
97%, respectively
▪ sensitivity of stool testing is negatively affected by
PPIs, bismuth, and antibiotics which affects the
bacterial load
▪ Its used both for diagnosis and confirm the
eradication .
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23. Endoscopic tests – biopsy
urease testing
Tissue from the antral biopsy is
placed in agar well containing
urea and pH reagent
The urease cleaves the urea to
liberate ammonia
This process changes the
medium alkaline and produces a
color change
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24. Biopsy urease testing
▪ commercially available kits include
CLOtest, PyloriTek, and Hp-fast
▪ The CLOtest may become positive as early as one
hour after collection, but a final reading at 24 hours
is recommended
▪ The sensitivity is 90 to 95% & specificity is 95 to
100%
▪ false positive tests are unusual. False negative
results occur in recent gastrointestinal bleeding or
with the use of PPIs, H2
antagonists, antibiotics, or bismuth-containing
compounds
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25. Rapid urease testing
▪ To know patient's H. pylori status before discharge
from the endoscopy suite.
▪ biopsy specimens are sandwiched between a
reagent strip with a pH indicator and a pad
containing urea.
▪ One hour sensitivity is 89 to 98 percent and
specificity is 89 to 93 percent.
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26. Rapid urease test
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27. Histology
▪ In addition to make diagnosis of H.pylori the biopsy and
histology also reveals intestinal metaplasia, MALT
omas, dysplasia and neoplasia
▪ In addition to biopsying “clinically suspicious”
areas, taking multiple biopsies and sampling lesser and
greater curvatures of gastric antrum and body are
important.
▪ It is gold standard for identifying infection, with
reported sensitivity and specificity as high as 95% and
98%
▪ Limitations…
▪ Brush cytology….
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28. 1/8/2014
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29. A silver stain (Warthin Starry) of H.pylori
on gastric mucus-secreting epithelial cells
(x1000).
This picture is notorious because it is of
Dr. Marshall's stomach biopsy taken 8
days after he drank a culture of H. pylori.
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30. Culture
▪ Its fastidious and difficult to culture and require
special culture media
▪ Culture is indicated when treating cases not
responding to treatment and suspected antibiotic
resistance
▪ Even though the in vitro sensitivity will not
guarantee the treatment results
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31. This is a 3 day culture of
H.pylori on blood agar
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32. Treatment
▪ Triple therapy
▪ Quadruple therapy
▪ Sequential therapy
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33. Triple therapy
▪ It’s the most commonly
recommended therapy
▪ The duration of therapy must
be 14 days and all drugs in
BD dose
▪ The cure rate is >80%
▪ Metronidazole 500mg can be
substituted for amoxy in
penicillin allergic patients
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34. Quadruple therapy
▪ Dose : 4 times a day
▪ Duration : 14 days
▪ appropriate as initial
therapy in areas in which the
prevalence of resistance
to clarithromycin or
metronidazole is >20%
▪ in patients with recent or
repeated exposure to
clarithromycin or
metronidazole
Eradication rate 70 – 85%
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35. Sequential regimen
Regimen
Days
(PPI + Amoxy 1000 mg) BD 5 + 5
followed by
(PPI+ Clarithromycin 500
mg + Tinidazole 500 mg) BD
Eradication
rate
90%
• It has overall eradication rate better than triple
therapy 90% vs 80%
•Particularly superior if bacteria is clarithromycin
resistant ( 89% Vs 29%)
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36. Eradication confirmation
▪ Eradication may be confirmed by a urea breath test, fecal
antigen test, or upper endoscopy performed four weeks or
more after completion of therapy.
▪ Its indicated in following situations
1.
2.
3.
4.
Patients who have persistent symptoms after H. pylori treatment
for dyspepsia
Patients who had an H. pylori associated ulcer
Patients who had gastric mucosa associated lymphoid tissue
(MALT) lymphoma
Patients who had resection for early gastric cancer.
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37. Treatment failures and
persisitance of H.pylori
▪ The initial treatment results in 25% failures
▪ The reasons for failure are
1.
2.
3.
4.
5.
6.
Resistant organism
Poor compliance with medication
Alcohol consumption
Smoking
Prior antibiotic use
Underlying condition (FD Vs PUD)
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38. Antibiotic resistance
▪ Resistance to metronidazole is 40% in US and 11%
for clarithromycin
▪ Resistace to amox and tetracycline is less than 1%
▪ The resistance to metronidazole is overcome by
increasing doses or combining with bismuth
▪ Macrolide resistance cant overcome by increasing
dose because these are due to alterations in 23S
ribosomal RNA(A2143G, A2142G & A2142C) which
interferes with ribosomal macrolide binding
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39. Rescue therapy
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40. Side effects of treatment
▪ Side effects are reported in up to 50 percent of patients taking one
of the triple therapy regimens .
▪ The adverse effects are usually mild; fewer than 10 percent of
patients stop treatment due to side effects
1. The most common side effect is a metallic taste due
to metronidazole or clarithromycin.
2. Metronidazole can cause a peripheral neuropathy, seizures, and
a disulfiram-like reaction when taken with alcohol.
3. Clarithromycin can cause taste alteration, nausea, vomiting,
abdominal pain, and rarely QT prolongation.
4. Tetracycline can induce a photosensitivity reaction in some
cases. It should also not be administered to pregnant women or
young children.
5. Amoxicillin can cause diarrhea or an allergic reaction with skin
rash.
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41. Take home message
1. H. pylori is a common worldwide infection.
2. Established indications for H. pylori cure include
peptic ulcer,(MALT) and uninvestigated
dyspepsia.
3. Non-endoscopic and endoscopic tests are
available toidentify H. pylori.
4. Proton pump inhibitor (PPI), clarithromycin, and
amoxicillin or metronidazole or a
PPI, bismuth, tetracycline,and metronidazole for
10–14 days are accepted first line treatment
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42. Thank you….
John Robin Warren
Barry James Marshall 42
1/8/2014