Transcript H PYLORI - Selam Higher Clinic

H PYLORI
BY MARUF A.
Historical Background
 1982 - Marshall and Warren identified
and subsequently cultured the gastric
bacterium, Campylobacter pyloridis, later
reclassified as Helicobacter pylori.
 Unidentified curved bacilli in the stomach
of patients with gastritis and peptic
ulceration.
[Lancet 1984 Jun 16;1(8390):1311-5 ]
Epidemiology & Bacteriology
 The most common chronic bacterial infection in
humans
 The risk of acquiring H. pylori infection is related to
socioeconomic status and living conditions early in life
 developing nations: the majority of children are
infected before the age of 10, the prevalence in adults
peaks at more than 80 percent before age 50
 developed countries: evidence of infection in children is
unusual but becomes more common during adulthood.
 Intrafamilial clustering
 Possible hereditary susceptibility
 Twin studies also support genetic susceptibility to
infection
Epidemiology…
 Transmission — Route by which infection
occurs remains unknown
 transmission among persons sharing the
same living environment
 Person-to-person transmission of H.
pylori through either fecal/oral or oral/oral
exposure seems most likely.
Pathogenesis
 Helicobacter pylori is highly adapted to the gastric environment
 pathophysiology of H. pylori infection and its eventual clinical
outcome is a complex interaction between the host and the
bacterium
 Bacterial Factors:
Urease production and motility- first step of infection
 Bacterial Attachment
Three Hop proteins have been implicated in the pathogenesis of
H. pylori infection, BabA (HopS), OipA (HopH), and SabA (HopP)
H. pylori can also bind to class II MHC molecules on the surface of
gastric epithelial cells and induce apoptosis
 Release of Enzymes
Urease
phospholipases
Catalase Enzyme
Proteolytic Enzymes
Cag A & Vac A
Pathogenesis
HOST RESPONSE TO H. PYLORI
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Infection induces a vigorous systemic and mucosal
humoral response
Continuous gastric inflammation in virtually all
infected persons - recruitment of neutrophils,
followed by T and B lymphocytes, plasma cells, and
macrophages, along with epithelial-cell damage
The gastric epithelium of infected persons has
enhanced levels of interleukin-1b, interleukin-2,
interleukin-6, interleukin-8, and tumor necrosis factor.
Some H. pylori–infected patients have an
autoantibody response directed against the H+/K
+ATPase of gastric parietal cells that correlates with
increased atrophy of the corpus.
Clinical Outcomes
 Variable
 Influenced by microbial and Host factors
 Responsible for the majority of DU & GU
Ethiopian studies
1.Helicobacter pylori infection was detected in 93% of 174 patients
with a peptic ulcer compared with 63% of 116 patients with normal
findings (chi 2 = 37.3; P < 0.001) in a cohort of 834 consecutive
patients examined by gastroscopy in Yirga Alem Hospital in south
Ethiopia.
[Trans R Soc Trop Med Hyg. 1999 Mar-Apr;93(2):171-3. ]
2.There were no statistically significant differences in the frequency
of H. pylori seroprevalence between dyspeptic and non-dyspeptic
patients [Ethiop.J.Health Dev. 2005;19(1):55-59]
Clinical Outcome
1. Why some develop ulcers while
others not ?
 Host Genetics
 polymorphism of IL-1 beta (and possibly
IL-10 )- Determine the degree of
inflammation
Clinical Outcomes
H. pylori has been classified as a type I (definite)
carcinogen since 1994.
Gastric Ca Very strong Evidence
Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection
and the development of gastric cancer. N Engl J Med 2001;345:784-9.
Gastric MALT Lymphoma
 Significantly increases the risk
 72 to 98 percent of patients are infected
 Eradication alone induces regression of the
lymphoma in 70 to 80 percent of cases.
Br Med Bull 1998;54:79-85.
Lancet 1995;345:1591-4.
Clinical Outcomes
 GERD
- some case–control and cohort studies
have suggested that H. pylori infection
may protect against GERD.
- Recent Evidence: H. pylori eradication
did not negatively influence relapse rates
in patients with GERD.
[ Gastroenterology 2001;121:1120-6., Lancet 2001;358:1734]
Diagnostic Tests
 Testing for H. pylori is recommended
only if treatment is intended
 infection can be diagnosed by noninvasive methods or by
endoscopic biopsy of the gastric mucosa
= UBT- H. pylori– derived urease activity in the stomach qualitatively
detects active infection with a sensitivity and specificity of more
than 90 percent.
-Initial diagnosis of the infection and for follow-up of eradication
therapy
=serologic tests: cheap and widely used for the diagnosis of H. pylori
infection in patients before treatment.
-local validation is necessary
=Stool Ag Tests: sensitivity -89 to 98% specificity -over 90%
-suitable for follow-up
Diagnosis
=Endoscopic Biopsy
 Patients with alarming symptoms, such as anemia, GI bleeding, or
weight loss, >50 years of age.
=urease test on an antral-biopsy specimen
-Sensitivity 79 -100 %
-Specificity 92 to 100 %.
Ethiopian Study
[Annals of TropicalMedicine & Parasitology, Vol. 98, No. 2, 181–189
(2004)]
 Culture revealed H. pylori in only 69% of the patients. rapid urease
tests- 71%, PCR–denaturating gradient gel electrophoresis -91%
 histopathology- 81%
 silver staining - 75%
 stool-antigen tests -81%
Treatment
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Indications
1.Indications for which treatment is strongly recommended
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Duodenal or gastric ulcer (active or not, including complicated
disease)
MALT lymphoma
Atrophic gastritis
Recent resection of gastric cancer
First-degree relative of patient with gastric cancer
pepticulcer
2. Indications for which treatment is advised
 Functional dyspepsia
 Gastroesophageal reflux disease (in patients requiring long-term profound
acid suppression)
 Use of NSAIDs
Regimens
 Proton-Pump-Inhibitor–Based Triple
Therapies
 Ranitidine Bismuth Citrate–Based
Therapies
 Bismuth-Based Triple Therapies
Second Line Therapy
 Therapy is often associated with secondary antibiotic
resistance
 Retreatment should ideally be guided by data on
susceptibility
 quadruple therapies - a proton-pump inhibitor or an H2receptor antagonist is added to a bismuth-based triple
regimen with high-dose metronidazole
 If a clarithromycin-based regimen is used first, a
metronidazole-based regimen should be used
afterward,or vice versa.
 Rifabutin, given in association with amoxicillin and
pantoprazole for 10 days, achieved an 86 percent rate
of cure, even in patients with resistant strains
Ethiopian Study on Antimicrobial
susceptibility
 Susceptibility testing was performed on 50 clinical H.
pylori isolates obtained from adult dyspeptic patients
referred to the gastrointestinal (GI) Clinic of Tikur
Anbassa University Hospital
 all strains were sensitive to clarithromycin,
erythromycin and tetracycline, while 38/50 (76%) and
3/50 (6%) of the strains were resistant to metronidazole
and amoxicillin, respectively.
[Ethiopian Medical Journal, 2004 (Vol. 42) (No. 2) 79-85]