Helicobacter Helicobacter pyloripylori

Dr.T.V.Rao MDDr.T.V.Rao MD

A Tribute to Warren and A Tribute to Warren and MarshallMarshall

for Discovery of H.pylorifor Discovery of H.pylori

Helicobacter pyloriHelicobacter pylori

Helicobacter pyloriHelicobacter pylori ( (H. pyloriH. pylori) is a type of ) is a type of bacteria. Researchers believe that bacteria. Researchers believe that H. pyloriH. pylori is is responsible for the majority of peptic ulcers.responsible for the majority of peptic ulcers.

H. pyloriH. pylori infection is common in the United infection is common in the United States. About 20 percent of people under 40 States. About 20 percent of people under 40 years old and half of those over 60 years have years old and half of those over 60 years have it. Most infected people, however, do not it. Most infected people, however, do not develop ulcers. Why develop ulcers. Why H. pyloriH. pylori does not cause does not cause ulcers in every infected person is not known. ulcers in every infected person is not known. Most likely, infection depends on Most likely, infection depends on characteristics of the infected person, the type characteristics of the infected person, the type of of H. pyloriH. pylori, and other factors yet to be , and other factors yet to be discovereddiscovered

Beginning of Scientific Beginning of Scientific understandingunderstanding

Peptic ulcers have plagued men Peptic ulcers have plagued men throughout the centuries, but the exact throughout the centuries, but the exact cause of the condition was uncertain. In cause of the condition was uncertain. In 1940, Dr. A. Stone Freedberg of Harvard 1940, Dr. A. Stone Freedberg of Harvard Medical School identified unusual Medical School identified unusual curved bacteria in the stomachs of ulcer curved bacteria in the stomachs of ulcer victims; he suspected that they might be victims; he suspected that they might be responsible for ulcers but abandoned the responsible for ulcers but abandoned the research when his team was unable to research when his team was unable to grow the bacteria in the lab grow the bacteria in the lab

History of H.pyloriHistory of H.pylori Helicobacter pyloriHelicobacter pylori (H.pylori for short) was (H.pylori for short) was

first discovered in the stomachs of patients first discovered in the stomachs of patients with gastritis & stomach ulcers nearly 25 with gastritis & stomach ulcers nearly 25 years ago by Dr Barry J. Marshall and Dr J. years ago by Dr Barry J. Marshall and Dr J. Robin Warren of Perth, Western Australia. At Robin Warren of Perth, Western Australia. At the time (1982/83) the conventional thinking the time (1982/83) the conventional thinking was that was that nono bacterium can live in the human bacterium can live in the human stomach as the stomach produced extensive stomach as the stomach produced extensive amounts of acid which was similar in strength amounts of acid which was similar in strength to the acid found in a car-battery. to the acid found in a car-battery. Marshall & Marshall & Warren literally “re-wrote” the text-books Warren literally “re-wrote” the text-books with reference to what causes gastritis & with reference to what causes gastritis & gastric ulcers.gastric ulcers.

Land Mark Changes in Land Mark Changes in H.pyloriH.pylori

The name of the bacterium was The name of the bacterium was grammatically corrected in 1987 to grammatically corrected in 1987 to Campylobacter pyloriCampylobacter pylori and, in and, in 1989 the 1989 the bacterium was renamed bacterium was renamed Helicobacter pylori Helicobacter pylori and assigned as the type species of a noveland assigned as the type species of a novel genus due to its 16s rRNAgenus due to its 16s rRNA sequence. sequence. Interest Interest in this bacterium is reflected in the increase in this bacterium is reflected in the increase in the number of papers on the subject from in the number of papers on the subject from 20 in 1984 to over 300 in 1990 and over 20 in 1984 to over 300 in 1990 and over 1000 in 1999 making it one of the most 1000 in 1999 making it one of the most active areas of research in the medical field active areas of research in the medical field

Helicobacter pyloriHelicobacter pylori

Helicobacter pylori Helicobacter pylori is a spiral gram is a spiral gram negative bacteria.negative bacteria.

It has a multiple It has a multiple polar flagella polar flagella above the pole and above the pole and motilemotile

Culturing H.pyloriCulturing H.pylori H.pylori grows onH.pylori grows on Skirrow”s medium with Skirrow”s medium with

1Vancomycin, 1Vancomycin, 2 Polymyxin2 Polymyxin 3 Trimethoprim3 TrimethoprimGrows in 3 -6 days at 37Grows in 3 -6 days at 3700ccColonies appear Colonies appear Translucent 1-2 mm in Translucent 1-2 mm in

diameterdiameterOptimal growth occurs in Optimal growth occurs in

Microaerophic Microaerophic environmentenvironment

Biochemical CharactersBiochemical Characters

Motile Motile Catalase +Catalase + Oxidase +Oxidase +

Strong producer of Strong producer of

UreaseUrease

Pathology and Pathology and PathogenesisPathogenesis

H.pylori is found in the deep mucus layerH.pylori is found in the deep mucus layer Grows optimally at pH 6.0 to 7.0Grows optimally at pH 6.0 to 7.0 But gastric mucosa has a strong buffering But gastric mucosa has a strong buffering

in spite of lower pH on the lumen side of in spite of lower pH on the lumen side of stomachstomach

H.pylori also produces a protease that H.pylori also produces a protease that modifies the gastric mucus and further modifies the gastric mucus and further reduces the ability of acid through the reduces the ability of acid through the mucusmucus

Mechanisms in Mechanisms in PathogenictyPathogenicty

PathogenesisPathogenesis

The potential character of H.pylori The potential character of H.pylori lie with production of potent Urease lie with production of potent Urease activity which yields production of activity which yields production of Ammonia and further buffering acid.Ammonia and further buffering acid.

H.pylori is quite motile even in H.pylori is quite motile even in mucus finds its way to epithelial mucus finds its way to epithelial surfacesurface

H.pylori overlies the gastric type but H.pylori overlies the gastric type but not intestinal epithelial cells.not intestinal epithelial cells.

Factors contributing to Factors contributing to Peptic ulcerationPeptic ulceration

There is a strong association There is a strong association between presence of H.pylori between presence of H.pylori infection and peptic ulcerationinfection and peptic ulceration

Mucosal inflammation and damage Mucosal inflammation and damage involves both bacterial and host involves both bacterial and host factorsfactors

H.Pylori causes Peptic ulcer H.Pylori causes Peptic ulcer in the Stomachin the Stomach

Factors influencing Factors influencing PathogenictyPathogenicty

Lipopolysaccharides - damage mucosal Lipopolysaccharides - damage mucosal cells and Ammonia produced by Urease cells and Ammonia produced by Urease acitivity may directly damage cells.acitivity may directly damage cells.

Gastritis – Chronic and active inflammation Gastritis – Chronic and active inflammation establishes Polymorphonuclear and establishes Polymorphonuclear and Mononuclear cell infiltration within the Mononuclear cell infiltration within the Epithelial and Lamina propria Epithelial and Lamina propria

Events lead to Destruction of epithelium is Events lead to Destruction of epithelium is common.common.

Glandular atrophy is common.Glandular atrophy is common.

Clinical ManifestationsClinical Manifestations

Acute infectionAcute infection

Upper Gastrointestinal illnessUpper Gastrointestinal illness

NauseaNausea

PainPain

Fever – very occasionally Fever – very occasionally

Acute symptoms lasts for < 1 week,Acute symptoms lasts for < 1 week,

May extend upto 2 weeksMay extend upto 2 weeks

Infection last for years, decades or even Infection last for years, decades or even lifetimelifetime

Consequences of H.pylori Consequences of H.pylori InfectionInfection

Association of Duodenal Association of Duodenal and Gastric ulcers in and Gastric ulcers in

H.pyloriH.pylori

About 90 % of patients with About 90 % of patients with Duodenal ulcer, and 50- 80 % of Duodenal ulcer, and 50- 80 % of gastric ulcers are associated with gastric ulcers are associated with H.pylori infection.H.pylori infection.

H.pylori may have greater role in H.pylori may have greater role in Gastric carcinoma and LymphomasGastric carcinoma and Lymphomas

Mechanism of Cancer in Mechanism of Cancer in H.pyloriH.pylori

Laboratory DiagnosisLaboratory Diagnosis

Specimens for histopathologySpecimens for histopathology – – Gastric biopsy specimens can be used Gastric biopsy specimens can be used for Histological examinationfor Histological examination

Specimens obtained after Specimens obtained after Gastroscopy, Biopsy, routine stains Gastroscopy, Biopsy, routine stains will demonstrate Gastritis and special will demonstrate Gastritis and special stains show curved spiral organismsstains show curved spiral organisms

Specimens collected in sterile saline Specimens collected in sterile saline mixed are used for culturingmixed are used for culturing

Endoscopy – Gastric Endoscopy – Gastric BiopsyBiopsy

Culturing for H.pyloriCulturing for H.pylori Culturing of H.pylori Culturing of H.pylori

needs specific conditions needs specific conditions MediaMedia Skirrow”s MediumSkirrow”s Medium withwith VancomycinVancomycin Polymyxin BPolymyxin B TrimethoprimTrimethoprimChocolate Medium Chocolate Medium

withwith Vancomycin, Nalidixic Vancomycin, Nalidixic

acidacid AmphotericinAmphotericin

SerologySerology The detection of The detection of

Antibodies in active Antibodies in active infection is useful infection is useful

But the tests are But the tests are limited utility as limited utility as antibodies persist even antibodies persist even after H.pylori infection after H.pylori infection is eradicated.is eradicated.

Several commercial kits Several commercial kits are available, but lacks are available, but lacks the role in identifying the role in identifying acute infections.acute infections.

Special Tests for H.pyloriSpecial Tests for H.pylori Rapid tests for detection Rapid tests for detection

of Urease activity are of Urease activity are widely used in widely used in presumptive identification presumptive identification of Gastric Biopsy of Gastric Biopsy specimens.specimens.

Gastric Biopsy can be Gastric Biopsy can be placed into urea placed into urea containing medium with containing medium with color indicatorcolor indicator..

If H.pylori is present If H.pylori is present the Urease rapidly splits the Urease rapidly splits urea and resulting shift urea and resulting shift in pH yields a color in pH yields a color change in the mediumchange in the medium

Urea Breath TestUrea Breath Test

H. pyloriH. pylori infection infection can be detected in can be detected in the exhaled breath the exhaled breath using this special using this special test. This test is test. This test is positive only if the positive only if the person has a current person has a current infection. Sensitivity infection. Sensitivity and specificity of and specificity of this test ranges this test ranges from 94-98from 94-98%. %.

Urea Breath TestUrea Breath Test

In this test In this test 1313C or C or 1414C labelled urea is C labelled urea is ingested by patientsingested by patients

If H.pylori is If H.pylori is present the present the urease activity urease activity generates labelled generates labelled CoCo22 that can be that can be detected in the detected in the patients exhaled patients exhaled breathbreath

Antigen Detection Test Antigen Detection Test in Stoolin Stool

Detection of Detection of H.pylori antigen in H.pylori antigen in stool is appropriate stool is appropriate test in patients with test in patients with H.pylori infection H.pylori infection

Absence of Absence of antigen indicates antigen indicates cure of Infection cure of Infection after after Chemotherapy.Chemotherapy.

TreatmentTreatment Triple therapy has prompt response, Triple therapy has prompt response,

contain a combination of following drugscontain a combination of following drugs 1 Metronidazole1 Metronidazole 2 Bismuth subsalicylate or Bismuth sub 2 Bismuth subsalicylate or Bismuth sub

citratecitrate 3 Amoxicillin or Tetracycles3 Amoxicillin or Tetracycles administered upto 14 daysadministered upto 14 days Eradicates H.pylori Eradicates H.pylori In 70 – 95 % of patientsIn 70 – 95 % of patients Acid suppressing agent is supportingAcid suppressing agent is supporting

Other Drug CombinationOther Drug Combination

Other alternativesOther alternatives

Proton pump inhibitor directly Proton pump inhibitor directly inhibit inhibit

H.pyloriH.pylori

Combined with Combined with

Amoxicillin Amoxicillin

Clarithromycin or AmoxicillinClarithromycin or Amoxicillin

And Metronidazole And Metronidazole

EpidemiologyEpidemiology In Developed countries H.pylori are present in In Developed countries H.pylori are present in

<20 % of the persons below 30 years.<20 % of the persons below 30 years. By 60 years prevalence increases to 40 – 60 %By 60 years prevalence increases to 40 – 60 % In Developing countries prevalence of In Developing countries prevalence of

infection is higher to 80 % even in younger infection is higher to 80 % even in younger individualsindividuals

Person to person transmission of H.pylori is Person to person transmission of H.pylori is likely because of interfamilial clustering of likely because of interfamilial clustering of infectioninfection

Acute epidemics of Gastritis suggest a common Acute epidemics of Gastritis suggest a common source of H.pylori.source of H.pylori.

Discovery of H.pylori Discovery of H.pylori changes the Peptic Ulcer changes the Peptic Ulcer

DiseaseDisease

Barry J. Marshall and J. Barry J. Marshall and J. Robin Warren have been Robin Warren have been awarded the 2005 Nobel awarded the 2005 Nobel

Prize in medicinePrize in medicine

Created for Created for Graduate Medical Graduate Medical

Students in Students in Devloping WorldDevloping WorldDr.T.V.Rao MDDr.T.V.Rao MD

EmailEmail

doctortvrao@gmail.comdoctortvrao@gmail.com