H PYLORIH PYLORI

BY MARUF A.BY MARUF A.

Historical BackgroundHistorical Background 1982 - Marshall and Warren identified 1982 - Marshall and Warren identified

and subsequently cultured the gastric and subsequently cultured the gastric bacterium, Campylobacter pyloridis, later bacterium, Campylobacter pyloridis, later reclassified as Helicobacter pylori.reclassified as Helicobacter pylori.

Unidentified curved bacilli in the stomach Unidentified curved bacilli in the stomach of patients with gastritis and peptic of patients with gastritis and peptic ulceration. ulceration.

[[Lancet 1984 Jun 16;1(8390):1311-5 ]Lancet 1984 Jun 16;1(8390):1311-5 ]

Epidemiology & BacteriologyEpidemiology & Bacteriology

The most common chronic bacterial infection in The most common chronic bacterial infection in humanshumans

The risk of acquiring H. pylori infection is related to The risk of acquiring H. pylori infection is related to socioeconomic status and living conditions early in lifesocioeconomic status and living conditions early in life

developing nations:developing nations: the majority of children are the majority of children are infected before the age of 10, the prevalence in adults infected before the age of 10, the prevalence in adults peaks at more than 80 percent before age 50peaks at more than 80 percent before age 50

developed countries:developed countries: evidence of infection in children is evidence of infection in children is unusual but becomes more common during adulthood.unusual but becomes more common during adulthood.

Intrafamilial clustering Intrafamilial clustering Possible hereditary susceptibility Possible hereditary susceptibility Twin studies also support genetic susceptibility to Twin studies also support genetic susceptibility to

infectioninfection

Epidemiology…Epidemiology…

Transmission Transmission — Route by which infection — Route by which infection occurs remains unknown occurs remains unknown

transmission among persons sharing the transmission among persons sharing the same living environment same living environment

Person-to-person transmission of H. Person-to-person transmission of H. pylori through either fecal/oral or oral/oral pylori through either fecal/oral or oral/oral exposure seems most likely.exposure seems most likely.

PathogenesisPathogenesis Helicobacter pylori is highly adapted to the gastric environment Helicobacter pylori is highly adapted to the gastric environment pathophysiology of H. pylori infection and its eventual clinical pathophysiology of H. pylori infection and its eventual clinical

outcome is a complex interaction between the host and the outcome is a complex interaction between the host and the bacteriumbacterium

Bacterial Factors:Bacterial Factors: Urease production and Urease production and motilitymotility- first step of infection - first step of infection

Bacterial AttachmentBacterial Attachment Three Hop proteins have been implicated in the pathogenesis of Three Hop proteins have been implicated in the pathogenesis of H. pylori infection, BabA (HopS), OipA (HopH), and SabA (HopP)H. pylori infection, BabA (HopS), OipA (HopH), and SabA (HopP) H. pylori can also bind to class II MHC molecules on the surface H. pylori can also bind to class II MHC molecules on the surface

of gastric epithelial cells and induce apoptosisof gastric epithelial cells and induce apoptosis

Release of EnzymesRelease of Enzymes UreaseUrease phospholipasesphospholipases Catalase EnzymeCatalase Enzyme Proteolytic EnzymesProteolytic Enzymes Cag A & Vac ACag A & Vac A

PathogenesisPathogenesis

HOST RESPONSE TO HOST RESPONSE TO H. PYLORIH. PYLORI

Infection induces a vigorous systemic and mucosal Infection induces a vigorous systemic and mucosal humoral responsehumoral response

Continuous gastric inflammation in virtually all Continuous gastric inflammation in virtually all infected persons - recruitment of neutrophils, infected persons - recruitment of neutrophils, followed by T and B lymphocytes, plasma cells, and followed by T and B lymphocytes, plasma cells, and macrophages, along with epithelial-cell damagemacrophages, along with epithelial-cell damage

The gastric epithelium of infected persons has The gastric epithelium of infected persons has enhanced levels of interleukin-1enhanced levels of interleukin-1bb, interleukin-2, , interleukin-2, interleukin-6, interleukin-6, interleukin-8interleukin-8, and tumor necrosis factor. , and tumor necrosis factor.

SomeSome H. pylori– H. pylori–infected patients have an infected patients have an autoantibody response directedautoantibody response directed against the H+/Kagainst the H+/K ++ATPase of gastric parietalATPase of gastric parietal cells that correlates with cells that correlates with increased atrophy of theincreased atrophy of the corpus. corpus.

Clinical OutcomesClinical Outcomes VariableVariable Influenced by microbial and Host factorsInfluenced by microbial and Host factors Responsible for the majority of DU & GUResponsible for the majority of DU & GU

Ethiopian studiesEthiopian studies1.Helicobacter pylori infection was detected in 93% of 174 patients 1.Helicobacter pylori infection was detected in 93% of 174 patients

with a peptic ulcer compared with 63% of 116 patients with normal 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 findings (chi 2 = 37.3; P < 0.001) in a cohort of 834 consecutive patients examined by gastroscopy in Yirga Alem Hospital in south patients examined by gastroscopy in Yirga Alem Hospital in south Ethiopia. Ethiopia.

[[Trans R Soc Trop Med Hyg. Trans R Soc Trop Med Hyg. 1999 Mar-Apr;93(2):171-3. ]1999 Mar-Apr;93(2):171-3. ]

2.There were no statistically significant differences in the frequency 2.There were no statistically significant differences in the frequency of of H. pyloriH. pylori seroprevalence between dyspeptic and non-dyspeptic seroprevalence between dyspeptic and non-dyspeptic patients [patients [Ethiop.J.Health Dev. Ethiop.J.Health Dev. 2005;19(1):55-59] 2005;19(1):55-59]

Clinical OutcomeClinical Outcome

1.1. Why some develop ulcers while Why some develop ulcers while others not ?others not ?

Host GeneticsHost Genetics polymorphism of IL-1 beta (and possibly polymorphism of IL-1 beta (and possibly

IL-10 )- Determine the degree of IL-10 )- Determine the degree of inflammationinflammation

Clinical OutcomesClinical OutcomesH. pylori H. pylori has been classified as a type I (definite) has been classified as a type I (definite)

carcinogen since 1994.carcinogen since 1994.Gastric Ca Gastric Ca Very strong Evidence Very strong EvidenceUemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infectionand 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 OutcomesClinical Outcomes

GERDGERD

- some case–control and cohort studies some case–control and cohort studies have suggested that have suggested that H. pylori H. pylori infection infection may protect against GERD.may protect against GERD.

- Recent Evidence: - Recent Evidence: H. pylori H. pylori eradication eradication did not negatively influence relapse rates did not negatively influence relapse rates in patients with GERD.in patients with GERD.

[ Gastroenterology 2001;121:1120-6., Lancet 2001;358:1734]

Diagnostic TestsDiagnostic Tests Testing for Testing for H. pylori H. pylori is recommended is recommended

only if treatment is intendedonly if treatment is intended infection can be diagnosed by noninvasive methods or by infection can be diagnosed by noninvasive methods or by

endoscopic biopsy of the gastric mucosa endoscopic biopsy of the gastric mucosa

= UBT- H. pylori– derived urease activity in the stomach qualitatively = UBT- H. pylori– derived urease activity in the stomach qualitatively detects active infection with a sensitivity and specificity of more detects active infection with a sensitivity and specificity of more than 90 percent.than 90 percent.

-Initial diagnosis of the infection and for follow-up of eradication -Initial diagnosis of the infection and for follow-up of eradication therapy therapy

=serologic tests: cheap and widely used for the diagnosis of H. pylori =serologic tests: cheap and widely used for the diagnosis of H. pylori infection in patients before treatment.infection in patients before treatment.

-local validation is necessary -local validation is necessary =Stool Ag Tests: sensitivity -89 to 98% specificity -over 90%=Stool Ag Tests: sensitivity -89 to 98% specificity -over 90%

--suitable for follow-upsuitable for follow-up

DiagnosisDiagnosis

=Endoscopic Biopsy=Endoscopic Biopsy Patients with alarming symptoms, such as anemia, GI bleeding, or Patients with alarming symptoms, such as anemia, GI bleeding, or

weight loss, >50 years of age.weight loss, >50 years of age. =urease test on an antral-biopsy specimen =urease test on an antral-biopsy specimen -Sensitivity 79 -100 %-Sensitivity 79 -100 % -Specificity 92 to 100 %. -Specificity 92 to 100 %.

Ethiopian Study 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%

TreatmentTreatment IndicationsIndications

1.Indications for which treatment is strongly recommended1.Indications for which treatment is strongly recommended

Duodenal or gastric ulcer (active or not, including complicated pepticulcer Duodenal or gastric ulcer (active or not, including complicated pepticulcer disease)disease)

MALT lymphomaMALT lymphoma Atrophic gastritisAtrophic gastritis Recent resection of gastric cancerRecent resection of gastric cancer First-degree relative of patient with gastric cancerFirst-degree relative of patient with gastric cancer

2. 2. Indications for which treatment is advisedIndications for which treatment is advised Functional dyspepsiaFunctional dyspepsia Gastroesophageal reflux disease (in patients requiring long-term profoundGastroesophageal reflux disease (in patients requiring long-term profound acid suppression)acid suppression) Use of NSAIDs Use of NSAIDs

RegimensRegimens Proton-Pump-Inhibitor–Based Triple Proton-Pump-Inhibitor–Based Triple

TherapiesTherapies Ranitidine Bismuth Citrate–Based Ranitidine Bismuth Citrate–Based

TherapiesTherapies Bismuth-Based Triple TherapiesBismuth-Based Triple Therapies

Second Line TherapySecond Line Therapy Therapy is often associated with secondary antibiotic Therapy is often associated with secondary antibiotic

resistance resistance Retreatment should ideally be guided by data on Retreatment should ideally be guided by data on

susceptibility susceptibility quadruple therapies - a proton-pump inhibitor or an H2-quadruple therapies - a proton-pump inhibitor or an H2-

receptor antagonist is added to a bismuth-based triple receptor antagonist is added to a bismuth-based triple regimen with high-dose metronidazole regimen with high-dose metronidazole

If a clarithromycin-based regimen is used first, a If a clarithromycin-based regimen is used first, a metronidazole-based regimen should be used metronidazole-based regimen should be used afterward,or vice versa.afterward,or vice versa.

Rifabutin, given in association with amoxicillin and Rifabutin, given in association with amoxicillin and pantoprazole for 10 days, achieved an 86 percent rate pantoprazole for 10 days, achieved an 86 percent rate of cure, even in patients with resistant strains of cure, even in patients with resistant strains

Ethiopian Study on Antimicrobial Ethiopian Study on Antimicrobial susceptibilitysusceptibility

Susceptibility testing was performed on 50 clinical Susceptibility testing was performed on 50 clinical H. H. pyloripylori isolates obtained from adult dyspeptic patients isolates obtained from adult dyspeptic patients referred to the gastrointestinal (GI) Clinic of Tikur referred to the gastrointestinal (GI) Clinic of Tikur Anbassa University HospitalAnbassa University Hospital

all strains were sensitive to clarithromycin, all strains were sensitive to clarithromycin, erythromycin and tetracycline, while 38/50 (76%) and erythromycin and tetracycline, while 38/50 (76%) and 3/50 (6%) of the strains were resistant to metronidazole 3/50 (6%) of the strains were resistant to metronidazole and amoxicillin, respectively. and amoxicillin, respectively.

[Ethiopian Medical Journal, 2004 (Vol. 42) (No. 2) 79-85][Ethiopian Medical Journal, 2004 (Vol. 42) (No. 2) 79-85]