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Helicobacter pylori Helicobacter pylori Prof. Md. Akram Hossain Prof. Md. Akram Hossain 12/24/2013 12/24/2013 1 Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain, H.pylori H.pylori

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Transcript of Prof. Md. Akram Hossain file/H. pylori by akram.pdf · X % Nonulcer dyspepsia ((5500% non ulcer...

  • Helicobacter pyloriHelicobacter pylori

    Prof. Md. Akram HossainProf. Md. Akram Hossain

    12/24/201312/24/2013 11Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • HHelicobacterelicobacter pyloripylori

    •• HH pyloripylori isis aaspiralspiral shapedshapedGramGram--negative,negative,microaerophilicmicroaerophilic,, andand flagellatedflagellated bacteriumbacteriumthatthat isis foundfound inin thethe gastricgastric mucusmucus layerlayer ororadherentadherent toto thethe epithelialepithelial lininglining ofof thethestomachstomach..

    •••• HH pyloripylori causescauses moremore thanthan 9090%% ofofduodenalduodenal ulcersulcers andand moremore thanthan 8080%% ofofgastricgastric ulcersulcers

    •• 50% of world population is infected and is the cause 50% of world population is infected and is the cause ofof: : Duodenal/gastric ulcers and gastric cancerDuodenal/gastric ulcers and gastric cancer

    •• 555,000 new cases of Stomach Cancer: per year due 555,000 new cases of Stomach Cancer: per year due to to Helicobacter pyloriHelicobacter pylori12/24/201312/24/2013 22

    Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain, H.pyloriH.pylori

  • Barry J Marshal and J Robbin Warren discovered in 1982

    12/24/201312/24/2013 33Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • Helicobacter pylori (blue bars, curved, 2-4 microns) localized in the mucus on the mucosa surface, at the intercellular lines. Photo: tangential section of the gastric mucosa

    12/24/201312/24/2013 44Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • 12/24/201312/24/2013 55Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • The way to the prizeThe way to the prize--11

    •• GastroenterologistsGastroenterologists resistedresisted MarshallMarshall && Warren’sWarren’sideaidea..

    –– “It“It waswas hardhard forfor themthem toto acceptaccept thatthat thethe diseasediseasecouldcould bebe simplesimple infectioninfection..””

    •• DrugDrug companiescompaniesthatthat profitedprofited fromfrom thethe antianti--ulcerulcer drugdrug•• DrugDrug companiescompaniesthatthat profitedprofited fromfrom thethe antianti--ulcerulcer drugdrugmarketmarket werewere soso activelyactively resistantresistant..

    •• BacteriologistsBacteriologists werewere suspicioussuspicious ------ thethe stomachstomach hadhadlonglong beenbeen assumedassumed toto bebe tootoo acidicacidic toto hosthost bacteriabacteria..

    •• InIn frustration,frustration, MarshallMarshall diddid thethe causecause--andand--effecteffectexperimentexperiment::

    –– HeHe swallowedswallowed aa solutionsolution containingcontaining thethe bacteria,bacteria, andandcamecame downdown withwith gastritisgastritis andand ulcersulcers.. (He(He laterlaterrecoveredrecovered withoutwithout treatmenttreatment..))12/24/201312/24/2013 66

    Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain, H.pyloriH.pylori

  • The way to the prizeThe way to the prize--22

    •• TheThe criticscritics hashas notnot beenbeen softened,softened, becausebecause ofof hishisyouth,youth, andand thethe factfact thatthat RoyalRoyal PerthPerth hospitalhospital hashasnono strongstrong academicacademic reputationreputation..

    •• InIn 19911991,, thethe centerscenters forfor diseasedisease controlcontrol andandpreventionprevention declareddeclared aa linklink betweenbetween HH..pyloripylori andandgastricgastric diseasedisease..gastricgastric diseasedisease..

    •• InIn 19941994,, thethe nationalnational instituteinstitute ofof healthhealth publishedpublishedanan opinionopinion statingstating thatthat mostmost recurrentrecurrent gastricgastriculcersulcers werewere causedcaused byby HH..pyloripylori..

    •• InIn 20052005,, WarrenWarren && MarshallMarshall werewere awardedawarded thethenobelnobel prizeprize..

    12/24/201312/24/2013 77Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • H pyloriH pylori and diseaseand disease

    Half of worlds population infectedHalf of worlds population infected

    100 %100 % damage to gastric structuredamage to gastric structure

    Many infected indiviudals no (silent) diseaseMany infected indiviudals no (silent) disease

    17 % 17 % Peptic ulcerPeptic ulcer ((9090 % duodenal ulcer patients% duodenal ulcer patients has Hp)has Hp)17 % 17 % Peptic ulcerPeptic ulcer ((9090 % duodenal ulcer patients% duodenal ulcer patients has Hp)has Hp)((7070 % gastric ulcer patients% gastric ulcer patients has Hp)has Hp)

    2 %2 % GGastric carcinomaastric carcinoma ((8585 % % of of patients patients has Hp)has Hp)

    X %X % Nonulcer dyspepsiaNonulcer dyspepsia (5(500 % non ulcer dyspepsia patients% non ulcer dyspepsia patients))

    Malt lymphomaMalt lymphoma

    Coronary Artery DiseaseCoronary Artery Disease

    OthersOthers12/24/201312/24/2013 88

    Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain, H.pyloriH.pylori

  • Epidemiology..1Epidemiology..1

    •• Approximately twoApproximately two--thirds of the world's thirds of the world's population is infected with population is infected with H. pyloriH. pylori..

    –– 70% 70% -- 90% in developing countries90% in developing countries

    –– 25% 25% -- 50% in developed countries50% in developed countries–– 25% 25% -- 50% in developed countries50% in developed countries

    •• Over half the population is infected in early Over half the population is infected in early childhood in China.childhood in China.

    •• Most of those infected never have symptoms.Most of those infected never have symptoms.

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    H.pyloriH.pylori

  • Epidemiology Epidemiology of of HH ppyloriylori

    12/24/201312/24/2013 1010Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • Epidemiology..2Epidemiology..2

    •• TheThe bacteriabacteria areare mostmost likelylikely spreadspread fromfrompersonperson toto personperson throughthrough fecalfecal--oraloral oror oraloral--oraloral routesroutes..

    •••• PossiblePossible environmentalenvironmental reservoirsreservoirs includeincludecontaminatedcontaminated waterwater sourcessources..

    •• TheThe sourcesource ofof HH..pyloripylori isis notnot yetyet knownknown..

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    H.pyloriH.pylori

  • SymptomsSymptoms

    •• TheThe mostmost commoncommon ulcerulcer symptomsymptom isis burningburningpainpain inin thethe epigastriumepigastrium (the(the upperupper middlemiddle regionregionofof thethe abdomen)abdomen).. TheThe painpain typicallytypically occursoccurs whenwhenthethe stomachstomach isis emptyempty..

    •• LessLess commoncommon symptomssymptoms includeinclude nausea,nausea,•• LessLess commoncommon symptomssymptoms includeinclude nausea,nausea,vomiting,vomiting, andand lossloss ofof appetiteappetite..

    •• BleedingBleeding cancan alsoalso occuroccur..•• RecentRecent studiesstudies havehave shownshown anan associationassociation

    betweenbetween longlong--termterm infectioninfection andand thethedevelopmentdevelopment ofof gastricgastric cancer,cancer, whichwhich isis thethe mostmostcommoncommon cancercancer inin ChinaChina..

    12/24/201312/24/2013 1212Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • PathogenicityPathogenicity

    •• HH..pyloripylori liveslives inin thethe mucusmucus lininglining totoescapeescape fromfrom thethe highlyhighly acidicacidicgastricgastric juicejuice.. (Its(Its helicalhelical shapeshapefacilitatesfacilitates itsits penetrationpenetration ofof thethemucusmucus layerlayer..))

    Stomach acid

    mucusmucus layerlayer..))

    •• ItIt cancan fightfight thethe acidacid byby excretingexcreting ananenzymeenzyme calledcalled ureaseurease..

    Gastric epithelium

    12/24/201312/24/2013 1313Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • Pathogenicity..2Pathogenicity..2

    •• TheThe immuneimmune systemsystem respondsresponds toto thetheinfectioninfection byby sendingsending whitewhite cells,cells, killerkillerTT cells,cells, andand otherother infectioninfection fightingfightingagentsagents..

    •• However,However, theythey cannotcannot easilyeasily getgetthroughthrough stomachstomach lininglining toto reachreach thethe

    Stomach acid

    throughthrough stomachstomach lininglining toto reachreach thetheinfectioninfection..

    •• AsAs thethe immuneimmune responseresponse grows,grows,immuneimmune cellscells diedie andand releasereleasedestructivedestructive compoundscompounds onon thethestomachstomach lininglining cellscells..

    •• WithinWithin aa fewfew days,days, gastritisgastritis andandperhapsperhaps eventuallyeventually aa pepticpeptic ulcerulcerresultsresults.. Gastric epithelium

    12/24/201312/24/2013 1414Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • •• AdhesionAdhesion•• ColonizationColonization factorsfactors

    •• UreaseUrease•• PhospholipasePhospholipase AA && BB

    ••

    Virulence factorsVirulence factors

    •• PhospholipasePhospholipase AA && BB•• ResponsibleResponsible forfor destructiondestruction ofof thethe protectiveprotective

    mucousmucous zonezone

    •• LossLoss ofof thisthis protectiveprotective barrierbarrier allowsallows thethe stomachstomachacidacid andand digestivedigestive enzymesenzymes toto havehave directdirect accessaccess totothethe gastricgastric epitheliumepithelium..

    •• ToxinsToxins-- CytotoxinsCytotoxins

    12/24/201312/24/2013 1515Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • How To Diagnose How To Diagnose HH pyloripylori

    •• Invasive tests (biopsy through endoscope)Invasive tests (biopsy through endoscope)–– Rapid Urease Test (RUT)Rapid Urease Test (RUT)

    –– CultureCulture

    –– HistologyHistology

    –– Polymerase Chain Reaction (PCR)Polymerase Chain Reaction (PCR)–– Polymerase Chain Reaction (PCR)Polymerase Chain Reaction (PCR)

    •• NonNon--Invasive testsInvasive tests–– Urea Breath Tests (UBT) Urea Breath Tests (UBT)

    –– Serological testsSerological tests

    –– 13C bicarbonate assay13C bicarbonate assay

    –– Salivary assaySalivary assay

    –– UrineUrine

    –– Stool antigen testsStool antigen tests12/24/201312/24/2013 1616Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • The Basis for Urea Breath TestThe Basis for Urea Breath Test

    Urea HydrolysisUrea Hydrolysis

    Urea HydrolesisUrea Hydrolesis

    214,13

    3

    2214,13

    2 2)( CONHOHNHCONHEnzymeUrease + →+

    Urea HydrolesisUrea Hydrolesis

    H pyloryH pylory servival strategy in the acid servival strategy in the acid environment of the stomachenvironment of the stomach

    UUrea isrea is broken down to ammonia and broken down to ammonia and carboncarbon dioxidedioxide

    12/24/201312/24/2013 1717Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • Comparison Matrix (1)Comparison Matrix (1)

    MethodMethod SpecimentSpeciment Time to resultTime to result SensitivitySensitivity SpecificitySpecificity

    Quick SerologyQuick Serology SerumSerum 1 hour1 hour 9595 8585

    SerologySerology SerumSerum 1 day1 day 9595 9595SerologySerology SerumSerum 1 day1 day 9595 9595

    UBTUBT COCO22 15 min15 min 9595--9898 9595--9898

    RUTRUT Mucosal biopsiesMucosal biopsies 1 hour1 hour 9090--9595 9898

    CultureCulture Mucosal biopsiesMucosal biopsies 11--3 days3 days 9090--9595 100100

    HistologyHistology Mucosal biopsiesMucosal biopsies 1 day1 day 9898 9898

    StoolStool StoolStool 11--3 days3 days 9595 9595

    12/24/201312/24/2013 1818Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • HP TestsHP Tests

    MMeetthhoodd SSppeecciimmeenn TTiimmee ttoo tteesstt SSeennssiiiittyy SSppeecciiffiicciittyy %%

    QQuuiicckk SSeerroollooggyy SSeerruumm 11 hhoouurr 9955 8855

    QQuuiicckk SSaalliivvaa SSaalliivvaa 11 hhoouurr 9900 8855

    MMaacchhiinnee rreeaadd EELLIISSAA SSeerruumm 11 ddaayy 9955 9955

    UUBBTT BBrreeaatthh 1155 mmiinn 9955--9988 9955--9988

    UUrreeaassee tteesstt ooff bbiiooppssyy MMuuccoossaall bbiiooppssiieess 11 hhoouurr 9900--9955 9988

    HHiissttoollooggyy TTwwoo mmuuccoossaall 11 ddaayy 9988 9988HHiissttoollooggyy TTwwoo mmuuccoossaall

    bbiiooppssiieess11 ddaayy 9988 9988

    BBiiooppssyy CCuullttuurree OOnnee mmuuccoossaall

    bbiiooppssiieess11--33 ddaayyss 9900--9955 110000

    SSttooooll CCuullttuurree SSttooooll 11--33 ddaayyss 3300--5500 110000

    PPCCRR SSttooooll,, GGaassttrr iicc jjuuiiccee,,

    bbiiooppssiieess11 ddaayy 9955 9955

    12/24/201312/24/2013 1919Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • Treatment of Treatment of HH ppyloriylori

    Treatment Treatment (Eradication) (Eradication) of of H pyloriH pylori infection should be initiated in infection should be initiated in allall patients with documented peptic ulcer disease.patients with documented peptic ulcer disease.

    First line therapyFirst line therapyFirst line therapyFirst line therapy

    •• PPI + Clarithromycin + Amoxicillin for a minimum of 7 daysPPI + Clarithromycin + Amoxicillin for a minimum of 7 days

    Second line therapySecond line therapy

    •• PPI + Bismuth + Metronidazole + Tetracycline for a minimum of PPI + Bismuth + Metronidazole + Tetracycline for a minimum of 7 days7 days

    12/24/201312/24/2013 2020Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • Infectious Etiologies of Chronic DiseasesInfectious Etiologies of Chronic Diseases

    POTENTIAL FOR PREVENTIONPOTENTIAL FOR PREVENTION

    Peptic Ulcer Disease

    19841980 2001

    Helicobacter pylori

    Stress, diet, acid, etc. H. pylori

    12/24/201312/24/2013 2121Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • H. pylori H. pylori Eradication RegimensEradication Regimens(All given for one week)(All given for one week)

    Treatments of ChoiceTreatments of Choice

    PPI PPI -- ACAC BIDBID Amoxicillin 1 g bidAmoxicillin 1 g bidClarithromycin 500 mg bidClarithromycin 500 mg bid

    RegimenRegimen PPIPPI AntibioticsAntibiotics

    PPI PPI -- MCMC BIDBID Metronidazole 500 mg bidMetronidazole 500 mg bidClarithromycin 250 mg bidClarithromycin 250 mg bid

    AlternateAlternatePPI PPI -- BMTBMT BIDBID Bismuth 2 tabs qidBismuth 2 tabs qid

    Metronidazole 250 mg qidMetronidazole 250 mg qidTetracycline 500 mg qidTetracycline 500 mg qid

    12/24/201312/24/2013 2222Prof. Muhammad Akram Hossain, Prof. Muhammad Akram Hossain,

    H.pyloriH.pylori

  • PreventionPrevention

    •• InhibitorsInhibitors ofof adhesionadhesion (some(some vegetablesvegetables &&plantplant fruits)fruits)–– Cranberry juiceCranberry juice

    –– Seaweed Seaweed Cladosiphon fucoidanCladosiphon fucoidan

    –– Spice turmericSpice turmeric

    –– Fruit of okra plantFruit of okra plant

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    H.pyloriH.pylori

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    H.pyloriH.pylori 2424