Helicobacter pylori

Briann McGovern
(microbiology spR)

Background
1983-discovered by Warren and Marshall in
Australia
Discovery revolutionised the treatment of
duodenal and gastric ulcers
Earned them the Nobel Prize for Medicine in
2005
Formerly known as Campylobacter pyloridis

 Nearly 20 species of Helicobacter are now

recognised
The gastric helicobacters colonise the stomachs
of animals. The monkey, cat, dog, cheetah all
harbour their own species
H. cinaedi and H. fennelliae are associated with
proctitis in homosexual men
H. pylori are found in the human stomach.
Molecular studies suggest transmission from an
animal source.

Helicobacter pylori

McColl K. N Engl J Med 2010;362:1597-1604

Description
Gram-negative spiral bacillus
Fastidious in terms of growth requirements
:strictly micro-aerophilic
:require C02 for growth
:on charcoal medium
Has a tuft of sheathed unipolar flagella;
specially adapted to colonise mucous
membranes

Gram stain of H. pylori recovered from an individual without prior

antimicrobial therapy. Organisms display typical seagull-like appearance.

 Hallmark of the species is production of

urease enzyme
-urease breaks urea down to C02+NH3
-amonia is a strong base
-process helps H. pylori survive
strongly acidic stomach conditions
Very fragile (a point of importance
when referring samples to the lab)

Epidemiology
H. pylori infection occurs worldwide
Prevalence varies greatly among
countries and population groups
20 50% prevalence in middle age adults
in industrialised countries
>80% prevalence in middle age adults in
developing countries
:may reflect poorer living conditions

Transmission

Oral ingestion of bacterium

within families (esp children)
person-person contact
faecal-oral transmission
?role of waterborne transmission

Usually contracted in the first 2 years of life

Site of infection
Highly adapted organism that lives only
on gastric mucosa
Gastric antrum is the most favoured
site
Present in the mucus that overlies the
mucosa

Gastric-biopsy specimen showing Helicobacter pylori adhering to gastric epithelium and

underlying inflammation

McColl K. N Engl J Med 2010;362:1597-1604

Course of infection

After several days incubation period,

patients suffer mild attack of acute gastritis
-abdominal pain
-nausea
-flatulence
-bad breath

Symptoms last about 2/52 but

hypochlorhydria can last up to one year

 Despite a
substantial ab
response, infxn and
chronic gastritis
persist
After decades there
may be progression
to atrophic gastritis
(conditions which
are inhospitable for
the bacteria) and
numbers reduce

The outcome of infection by H. pylori

reflects an interaction between:

H. pylori infection directly

associated with

PUD
-lifetime risk 3% in US, 25% Japan
-eradication provides long-term cure
Gastric carcinoma
-strong evidence of increased risk 0.13%
-unclear whether eradication reduces
the
risk of gastric cancer

MALT lymphoma
-72% 98% of MALT lymphoma
infected with H. pylori

H. pylori may be
implicated
in: Non-ulcer dyspepsia
-increased prevalence of H. pylori but
data inconsistent (symptomatic
improvement only 9%)
-little evidence that chronic H. pylori
infection in the absence of ulceration
causes upper GI symptoms
GORD
-recent meta-analysis : no significant
association

Laboratory diagnosis:
non-invasive tests
Serology : detect an immune response by
examining a blood sample for abs to the
organism (ELISA)
: poor accuracy
Urea breath test : a urea solution labelled
with C14 isotope is given to pt. The C02
subsequently exhaled by the pt contains the
C14 isotope and this is measured. A high
reading indicates presence of H. pylori

 Faecal antigen test : detect H. pylori

antigens in faecal specimens
Polymerase chain reaction (PCR) :
can detect HP within a few hours. Not
routine in clinical use.

Invasive testing
1. Histological examination of biopsy
specimens of gastric/duodenal mucosa
take at endoscopy
2. CLO-test : based again on ureaseproduction by the organism->NH3
production->rise in pH=>change in the
colour indicator of the kit
-High sensitivity and specificity
-Prompt result

Invasive testing
3. Culture :
-no more sensitive than skilled
microscopy of histological
sections
-used for antibiotic resistance
testing
-requires selective agars and
incubation periods

Tests for Helicobacter pylori Infection

McColl K. N Engl J Med 2010;362:1597-1604

Indications for therapy

Strongly recommended
Duodenal or gastric ulcer
MALT lymphoma
Atrophic gastritis
Recent resection of gastric cancer
Maastricht 2-2000 Consensus Report

Indications for therapy

Treatment advised
Functional dyspepsia
Gastro-oesophageal reflux disease
(patients requiring long-term acid
suppressive therapy)
Use of NSAIDs
Maastricht 2-2000 Consensus Report

Treatment
Goal of treatment to eradicate infection
Triple therapy regimens consist of one
anti-secretory agent and two
antimicrobial agents for 7 to 14 days
Triple therapy regimens must
- have cure rate of approximately 80%
- be without major side effects
- minimal induction of resistance

First line treatment

Combination of two or more
antimicrobial agents increases rates of
cure and reduces the risk of selecting
for resistant H. pylori
Many factors may result in failure of
treatment
microbial factors
patient compliance
geographical differences

First line therapy

PPI b.d. + clarithromycin 500mg b.d.
+
amoxicillin 1000mg b.d. or metronidazole 400mg BD minimum of
7 days

In case of failure

Second line therapy

PPI b.d. + bismuth subsalicylate/subcitrate 120mg QDS +
metronidazole 500mg t.d.s. + tetracycline 500mg q.d.s.
for a minimum of 7 days
If bismuth is not available, PPI based triple therapies should be
used
Subsequent failures should be handled on a case-case basis.
Patients failing second-line therapy in primary care should be
referred
Maastricht 2-2000 Consensus

NEJM 2002;347:1175-86

Guidelines for Evaluation and Management of Helicobacter pylori Infection

McColl K. N Engl J Med 2010;362:1597-1604

Reinfection
Reinfection following successful bacterial
cure is unusual
Commonly represents recrudescence of the
original bacterial strain
In adults, reacquisition of the bacteria occurs
in <2%/persons/year which is similar to the
rate of primary infection in adults

Failure of treatment
Failure of initial course occurs in 1 in 5
2nd-line Tx :
either an alternative regimen
quadruple Tx (PPI+bismuth+2
antibx)

Key points
->H. pylori is a flagellated spiral micro-aerobe
->Infection is a risk factor for gastric cancer
->Causes PUD and gastritis
->Produces a cell-damaging toxin
->Transmission route is unclear
->Dz rates are falling in industrialised
countries
->Tx is by eradication using combination
therapy

Recommendations
The noninvasive test-and-treat strategy for H. pylori infection is
reasonable for younger patients who have upper gastrointestinal
symptoms but not alarm symptoms
Noninvasive testing can be performed with the use of the urea
breath test, fecal antigen test, or serologic test; the serologic test is
the least accurate
Triple therapy with a proton-pump inhibitor, clarithromycin, and
amoxicillin or metronidazole remains an appropriate first-line
therapy
Recurrence or persistence of symptoms after eradication therapy
for uninvestigated dyspepsia is much less likely to indicate that
treatment has failed than to indicate that the symptoms are
unrelated to H. pylori infection.

Recommendations
Further eradication therapy should not be considered unless
persistent H. pylori infection is confirmed
Data are lacking to inform the optimal management of
recurrent or persistent dyspepsia after noninvasive testing
and treatment of H. pylori infection
Options include symptomatic acid-inhibitory therapy,
endoscopy to check for underlying ulcer or another cause of
symptoms, and repeat of the H. pylori test-and-treat strategy;
other potential reasons for the symptoms should also be
reconsidered

Clinical Practice

Helicobacter pylori Infection

Kenneth E.L. McColl, M.D.
N Engl J Med
Volume 362(17):1597-1604
April 29, 2010

Thanks for your attention!