H.

PYLORI

Dr Heersh HMH Raof Saeed

 Gastric organisms were first observed more than
100 years
 gastritis has been recognized since the 1970s

 1982 Marshall and Warren identified and

subsequently cultured the gastric
bacterium, Campylobacter pyloridis
EPIDEMIOLOGY
 H. pylori is the most common chronic bacterial infection in
humans
 genetic sequence analysis suggest that humans have been
infected with H. pylori since they first migrated from Africa
around 58,000 years ago
 Conservative estimates suggest that 50 percent of the world's
population is affected
 In developing nations, where the majority of children are infected
before the age of 10, the prevalence in adults peaks at more than
80 percent before age 50
 he risk of acquiring H. pylori infection is related to socioeconomic
status and living conditions early in life
 density of housing, overcrowding,
 number of siblings,
 sharing a bed,
 lack of running water
H. PYLORI TRANSMISSION

 Person-to-person transmission of H. pylori through

either fecal/oral or oral/oral exposure seems most likely
 Intrafamilial clustering of infection further supports
person-to-person transmission
 H. pylori has been isolated from primates in captivity and
from domestic cats
 cats, isolation of viable organisms from saliva and gastric
juice samples suggests that transmission to humans might
occur
 identification of H. pylori in milk and gastric tissue of sheep
suggesting that sheep may be a natural host for the
organism
 he organism remains viable in water for several days
 Bacteriology
 H. pylori is a spiral(coccoid forms occasionally seen ) shaped,
microaerophilic, gram negative bacterium
 biochemically characterized as catalase, oxidase, and urease positive
 factors that allow it to survive and proliferate in the gastric milieu:
 urease,
 motility,
 ability to adhere to gastric epithelium

 Bacterial urease hydrolyzes gastric luminal urea to form ammonia

that helps neutralize gastric acid and form a protective cloud around
the organism
 ts spiral shape, flagella, and the mucolytic enzymes which it produces
facilitate its passage through the mucus layer to the gastric surface
epithelium
 H. pylori then attaches to gastric epithelial cells by means of specific
receptor-mediated adhesion .
 Bacterial phospholipases can alter the phospholipid content of the
gastric mucosal barrier
 Bacteriology

 Bacterial strain differences

 VacA behaves as a passive urea transporter that is potentially
capable of increasing the permeability of the gastric epithelium to
urea, thereby creating a favorable environment for H.
pylori infectivity.
H. pylori strains with different VacA alleles have differing
toxicity
 CagA :Virulent strains of H. pylori encode cag PAI, which
expresses a type IV secretion system (T4SS). This T4SS forms a
syringe-like pilus structure for the injection of virulence factors
such as the CagA effector protein into host target cells
 he clinical significance of CagA positivity is demonstrated in two
different disorders:
 Approximately 85 to 100 percent of patients with duodenal ulcers have
CagA+ strains, compared to 30 to 60 percent of infected patients who do
not develop ulcers . Cag A positivity has also been associated with
gastroduodenal disease in adults and children .
 CagA strains are associated with a higher frequency of precancerous
lesions and gastric cancer . The risk of malignancy may be related to
specific amino acid sequences (EPIYA) in the CagA protein
 Bacteriology

 Other virulence factors — In addition to CagA, several other H.

pylori virulence factors have been described . The strength of these
associations has not been well defined in large populations.
 Induced by contact with epithelium" (iceA) has been associated
with peptic ulcers .
 Blood group antigen-binding adhesin" (babA2) has been associated
with duodenal ulcers and gastric cancer .
 Outer inflammatory protein" (oipA) has been associated with
duodenal ulcers .

 ANTIBODY RESPONSE
 Detection of IgM antibodies is an insensitive indicator of acute
infection and generally is not clinically useful, even in children
 IgA and IgG antibodies are produced in response to infection,
remain present as long as infection is active, and quantitatively
decrease after infection is cured .
 Antibodies to CagA protein are detectable in gastric tissue and
serum and permit the identification of infection with presumably
more virulent organisms
Classic H. pylori-associated diseases

 Dyspepsia
 Gastritis

 Gastric cancer

 Iron deficiency anemia

 Idiopathic thrombocytopenic purpura

 Skin diseases

 Liver and gallbladder

 Ocular diseases

 Neurodegenerative diseases

 Cardiovascular disease
 gastritis due to Helicobacter pylori

 Acute Helicobacter pylori gastritis

healthy volunteers ingested the organisms and they developed
 mild illness (consisting of epigastric pain, nausea, and vomiting without fever)
 acute inflammatory changes on gastric biopsy:ntense neutrophilic infiltration
of the mucous neck region and lamina propria. When severe, pit abscesses occur, along with
mucin loss, erosion of the juxtaluminal cytoplasm, and desquamation of surface foveolar
cells.

 development of hypochlorhydria
 Chronic Helicobacter pylori gastritis:
Chronic H. pylori gastritis affects two-thirds of the world's population
 H. pylori organisms reside primarily in the unstirred layer of gastric mucus, adjacent to
epithelial cells at the mucosal surface and in gastric pits
 he major clinical associations with chronic H. pylori gastritis are peptic ulcer disease and,
less commonly, gastric cancer and MALT lymphoma.

frequency of H. pylori localization:

Antrum and body – 80 percent

Antrum only – 8 percent
Body only – 10 percent(modified by PPIs
or marked atrophy and intestinal metaplasia)
Indications and diagnostic tests for Helicobacter pylori
infection
2017 guidelines from the American College of Gastroenterology and the Maastricht
V consensus report
 endividuals with unexplained iron deficiency anemia
 testing for H. pylori is recommended prior to starting long-term NSAID
therapy
 chronic idiopathic thrombocytopenia
 All patients with active peptic ulcer disease (PUD), a past history of PUD
(unless previous cure of H. pylori infection has been documented),
 patients with uninvestigated dyspepsia without alarm symptom .patients
who present with alarm symptoms of vomiting, gastrointestinal bleeding,
or weight loss in patients or are over 45 years of age should proceed with
an endoscopic evaluation
 When upper endoscopy is undertaken in patients with dyspepsia, gastric
biopsies should be taken to evaluate for H. pylori infection
 When upper endoscopy is undertaken in patients with dyspepsia, gastric
biopsies should be taken to evaluate for H. pylori infection
 There is insuffi cient evidence to support routine testing for and treatment
of H. pylori in asymptomatic individuals with a family history of gastric
cancer or patients with lymphocytic gastritis
THE EUROPEAN SOCIETY FOR PAEDIATRIC
GASTROENTEROLOGY HEPATOLOGY AND NUTRITION/NORTH
AMERICAN SOCIETY FOR PEDIATRIC GASTROENTEROLOGY
2017
1. The primary goal of clinical investigation of gastrointestinal symptoms should be to determine
the underlying cause of the symptoms and not solely the presence of H pylori infection.
2. a. Additional biopsies for rapid urease test and culture should only be taken during endoscopy if treatment is to
be offered upon confirmation of infection.
b. If H pylori infection is an incidental finding at endoscopy, treatment may be considered after a thorough discussion
of the risks and benefits of treatment with the patient and or parents.
c. The guidelines do not recommend a ‘‘test and treat’’ strategy for pediatric H pylori infection.
3. Testing for H pylori should be performed in children with gastric or duodenal ulcers. If H
pylori infection is identified, then treatment should be advised and eradication be confirmed.
4. Diagnostic testing for H pylori infection in children with functional abdominal pain is not
recommended.
5. Testing for H pylori during upper endoscopy may be considered for children with refractory
iron deficiency anemia in which other causes have been ruled out
6. Noninvasive diagnostic testing for H pylori infection may be considered when investigating
causes of chronic immune thrombocytopenic purpura
7. Diagnostic testing for H pylori infection when investigating causes of short stature is not
recommended
8. Wait at least 2 weeks after stopping proton pump inhibitor and 4 weeks after stopping
antibiotics before testing for H pylori.
9. Using antibody-based tests (IgG, IgA) for H pylori in serum, whole blood, urine, and saliva in the clinical
setting is not recommended
10. We recommend that the diagnosis of H pylori infection should be based on either (a) histopathology (H pylori–
positive gastritis) plus at least 1 other positive biopsy-based test or (b) positive culture
 APPROACH TO DIAGNOSTIC TESTING
 the choice of test used to diagnose H. pylori depends on:
 requires an upper endoscopy for evaluation of symptoms or surveillance
 recent use of medications that can suppress the bacterial load of H.
pylori
 the prevalence of H. pylori, test availability, and cost.

Medications that should be

discontinued prior to testing

PPI use within one to two

weeks
and bismuth/antibiotic use
within four weeks of testing can
decrease the sensitivity of all
endoscopy-based tests and non-
invasive tests of active H.
pylori infection (stool antigen
and urea breath test).
 Patients not undergoing upper endoscopy

 should be made with a test for active infection (stool antigen assay or urea
breath test)
If patients are unable or unwilling to stop PPI therapy :positive test results are
true positives; negative results may represent false negatives

Serologic testing for H. pylori should be avoided altogether

Patient undergoing upper endoscopy

No active peptic ulcer bleeding

without recent PPI/bismuth/antibiotic use who do not require biopsies of the stomach for
histology, the diagnosis of H. pylori can be established with a biopsy urease test
 In patients with visible endoscopic abnormalities (eg, gastric ulcer, gastropathy), and patients
with recent antisecretory/bismuth/antibiotic use, we perform histology to diagnose H. pylori
refractory to two courses of antibiotic therapy we perform culture and antibiotic sensitivity
testing on gastric biopsies

Active peptic ulcer bleeding : In patients with bleeding duodenal or gastric ulcer on upper
endoscopy, we perform a gastric mucosal biopsy
 NONINVASIVE TESTING
 Urea breath testing :
 based upon the hydrolysis of urea by H. pylori to produce
CO2 and ammonia
 The sensitivity and specificity of UBT are approximately 88
to 95 percent and 95 to 100 percent, respectively
 false-positive results are uncommon
 False-negative results may be observed in patients who are
taking PPIs, bismuth, or antibiotics
 dose of radiation is small, the non-radioactive 13C test is
preferred in young children and pregnant women.

Stool antigen assay:

 The detection of bacterial antigen indicates an ongoing H. pylori infection
 is the most cost-effective in areas of low to intermediate prevalence of H. pylori
The sensitivity and specificity of the laboratory-based monoclonal enzyme immunoassay (94
and 97 percent, respectively) are comparable to the UBT

Polymerase chain reaction:

Quantitative polymerase chain reaction (PCR) testing on gastric biopsies
can be used to detect low bacterial loads
However, the use of PCR based testing is limited by its high cost
 Serology:
 overall sensitivity and specificity of 85 and 79 percent,
respectively
 Serology does not reliably distinguish between active and
past infection
 Detection of IgM antibodies is an insensitive indicator of
acute infection and generally is not clinically useful, even in
children
 IgA and IgG antibodies are produced in response to
infection
 concerns over its accuracy have limited its use
 A quantitative ELISA test is generally used in research
settings. It allows for determination of IgG titers of paired
sera from the acute and convalescent (three to six months
or longer) phase and can confirm eradication of the
infection. However, this is not performed in clinical
 Management of Helicobacter pylori infection—the Maastricht
V/Florence Consensus Report

Statement: H. pylori gastritis has to be excluded before a reliable diagnosis of functional dyspepsia can be
made

Grade of recommendation:
Level of evidence: high
high

Dyspeptic symptoms are very common, and can occur as a result of a range of
different upper GI conditions. When a dyspeptic patient has no diagnostic
work-up, the condition is classified as ‘non-investigated dyspepsia’. If patients
have an endoscopic work-up, this may yield different diagnoses, including
GERD or peptic ulcer. Patients with dyspepsia but without endoscopic lesions
are classified as having ‘functional dyspepsia’.
H. pylori gastritis is an infectious disease that leads to chronic active gastritis
of varying severity in all infected subjects. Cure of H. pylori infection heals
the inflamed gastric mucosa.

For these reasons, a diagnosis of true ‘functional’ dyspepsia can only

be made in the absence of H. pylori. This can be either by primary
exclusion of H. pylori gastritis, or confirmation of successful
eradication
JOINT ESPGHAN/NASPGHAN
GUIDELINES
 Recommendation :
We recommend against diagnostic testing for H pylori
infection in children with functional abdominal pain
disorders.
GRADE: Strong recommendation.
Quality of evidence: high. Agreement: 100%.
 treatment regimens for Helicobacter

 combinations
 concomitantly or sequentially
 “first-line”
 Clarithromycin triple therapy
 14 days oftreatment with a PPI, clarithromycin, and amoxicillin (clarithromycin-based triple therapy) or—in patients
with an allergy to
penicillin — metronidazole as an alternative to amoxicillin
 eradication rates for clarithromycin triple therapy were
reported to be 70–85%

 Bismuth quadruple therapy

 PPI or histamine-2 receptor antagonist, bismuth, metronidazole, and tetracycline
 eradication rate with
this regimen given for 10 days was 91%
 efcacy of bismuthquadruple therapy is not affected by clarithromycin resistance

 Concomitant therapy
 PPI, amoxicillin, clarithromycin, and a nitroimidazole (tinidazole or metronidazole) given together for 3–10 days
 cure rate of 88%

 Sequential therapy :
 PPI plus amoxicillin for 5 days, followed by a PPI, clarithromycin, and a
nitroimidazole for an additional 5 days
 eradication rate for sequential therapy was 84.3%
 TREATMENT REGIMENS FOR
HELICOBACTER PYLORI
 Multiple antibiotic regimens
have been evaluated
for Helicobacter
pylori therapy
 Approach to selecting an
antibiotic regimen
 In patients with risk factors
for macrolide resistance,
clarithromycin-based therapy
should be avoided

Risk factors for macrolide

resistance include:
rior exposure to macrolide therapy for any
reason
High local clarithromycin resistance rates ≥15
percent
 eradication rates with clarithromycin triple
therapy ≤85 percent
 ROLE OF PROBIOTICS IN FIRST-LINE THERAPY
 Probiotics as adjuvant therapy in the treatment of H. pylori infection.
 inhibitory effect of Lactobacillus and Bifdobacterium species on H. pylori.
 increased cure rates with probiotic supplementation
 reduced the incidence of total
side effects

The main determinants of successful H. pylori eradication are

1. the choice of regimen,
2. patient’s adherence to a multi-drug regimen with frequent side-effects
3. sensitivity of the H. pylori strain to the combination of antibiotics
administered
4. Genetic factors may also influence the success of H. pylori eradication
therapy like in PPI we have pooe mtabolizer

 Whenever H. pylori infection is identifed and treated, testing to

prove eradication should be performed using a urea breath test,
fecal antigen test or biopsy-based testing at least 4 weeks afer the
completion of antibiotic therapy and afer PPI therapy has been
withheld for 1–2 weeks
In patients with persistent H. pylori infection, every effort should be made
to avoid antibiotics that have been previously taken by the patient


 Bismuth quadruple therapy or levofloxacin salvage

regimens are the preferred treatment options if a patient
received a frst-line treatment containing clarithromycin
 Clarithromycin- or levofloxacin-containing salvage regimens
are the preferred treatment options if a patient received frst-
line bismuth quadruple therapy
 Rifabutin-based triple regimen (PPI, amoxicillin,
rifabutin:PAR)
 Te proven efcacy of rifabutin in the treatment of H. pylori
infection should be balanced against its high cost
 the rare riskof myelotoxicity (almost always reversible)
 the concerns for inducing resistance among Mycobacterium
tuberculosis strains
thanks