Helicobacter pylori was first observed in 1983 infecting human stomachs and causing gastritis. It is a unique, fastidious bacterium that colonizes the gastric mucosa and is highly adapted to survive the acidic stomach environment. H. pylori infection is strongly associated with peptic ulcer disease, gastric cancer, and gastric MALT lymphoma. Successful treatment requires combination antibiotic therapy alongside proton pump inhibitors or bismuth compounds to eradicate the infection.

6. Helicobacter
pylori
((Campylobacter pyloridisCampylobacter pyloridis))

7. HelicobacterpyloriHelicobacterpylori

8. History of HelicobacterHistory of Helicobacter
 First observed in 1983 asFirst observed in 1983 as CampylobacterCampylobacter-like-like
organisms (CLO) in stomachs with gastritisorganisms (CLO) in stomachs with gastritis
 HelicobacterHelicobacter was coined in 1989.was coined in 1989. 20 spp. Are known.20 spp. Are known.
Only 3 cause human d.Only 3 cause human d.
1. Hp1. Hp (human;(human; no animal reservoir)no animal reservoir)
2. H. cinaedi2. H. cinaedi (male homosexuals; rodents)(male homosexuals; rodents)
3. H. fenneliae3. H. fenneliae (do)(do)

9.  1983:1983: discovered by Warren and Marshall (Australia)discovered by Warren and Marshall (Australia)
 ItIt revolutionisedrevolutionised Rx of DU and GURx of DU and GU
 Earned themEarned them NobelNobel in 2005in 2005
 HpHp colonises stomach. Molecular studies: transmissioncolonises stomach. Molecular studies: transmission
occurred from animaloccurred from animal
 Monkey, cat, dog, cheetahMonkey, cat, dog, cheetah all harbour their own speciesall harbour their own species
History of Hp …History of Hp …

10. HpHp DescriptionDescription
G-ve, motile, flagellate, helical; pleomorphic rod:G-ve, motile, flagellate, helical; pleomorphic rod:
penetrates and colonizespenetrates and colonizes gastricgastric mucosa (corkscrew)mucosa (corkscrew)
Fastidious in growth: strictly micro-aerophilic; require
C02. Becomes coccoid in O2 or upon prolonged cultureBecomes coccoid in O2 or upon prolonged culture
Highly adaptiveHighly adaptive
Has a tuft of unipolar flagellae; specially adapted to
colonise mucosa
Very fragile (important! when referring samples to lab)

11. HpHp is unique!is unique!
 50%50% world popn. are inf.world popn. are inf.
 Survives acidity even at pH <2Survives acidity even at pH <2
 Colonization is chr. and may be lifelongColonization is chr. and may be lifelong
 Motility is essential for colonisationMotility is essential for colonisation
 Hallmark isHallmark is urease:urease: urea to C02 + NH3(a strong base;urea to C02 + NH3(a strong base;
neutralizes strong acid). It isneutralizes strong acid). It is essential for survivalessential for survival
 It is a carcinogenIt is a carcinogen
 Vacuolating cytotoxin (VacA): increases bacterial fitnessVacuolating cytotoxin (VacA): increases bacterial fitness
 StaysStays remote and protected from immune sys.remote and protected from immune sys.

12. EpidemiologyEpidemiology
 Worldwide. Varies greatly among countries and popn.Worldwide. Varies greatly among countries and popn.
 20 – 50% among mid-age adults in20 – 50% among mid-age adults in HICsHICs
 >80%>80% inin L&MICs;L&MICs; 85% by 2yoa85% by 2yoa
Transmission:Transmission: ingestion; commonest: family contact (esp.ingestion; commonest: family contact (esp.
children).children). HpHp has been cultured from feces, dentalhas been cultured from feces, dental
caries.caries. Transmission increases with ageTransmission increases with age
Site of inf.:Site of inf.: gastric antrum (most favoured), bodygastric antrum (most favoured), body
 Present in the mucus secretionPresent in the mucus secretion

14. PATHOPHYSIOLOGYPATHOPHYSIOLOGY
HpHp is the first recognized bacterialis the first recognized bacterial carcinogencarcinogen and is 1 ofand is 1 of
most successful pathogens. Colonization is usually lifelongmost successful pathogens. Colonization is usually lifelong
It causesIt causes chr. gastritischr. gastritis (may be asymptomatic),(may be asymptomatic), PUD, gastricPUD, gastric
Ca, gastric MALT lymphoma, gastric atrophyCa, gastric MALT lymphoma, gastric atrophy
Outcome depends on interplay between host &Outcome depends on interplay between host & Hp.Hp. HostHost
immunity and gastric a. largely determine colonizationimmunity and gastric a. largely determine colonization
HpHp makesmakes ammoniaammonia (toxic to epith),(toxic to epith), proteasesproteases,, vacuolatingvacuolating
cytotoxin A (VacA)cytotoxin A (VacA) [damages epith, disrupts tight junctions[damages epith, disrupts tight junctions
and causes apoptosis),and causes apoptosis), phospholipases.phospholipases. CytotoxinCytotoxin
associated geneassociated gene CagACagA can causes inflam. and is carcinogencan causes inflam. and is carcinogen

15. PUD:PUD: acid & pepsin overcome mucosal defenceacid & pepsin overcome mucosal defence
Site of colonizationSite of colonization affects location of ulceraffects location of ulcer
 In large amounts of acid,In large amounts of acid, HpHp colonizes the antrum; avoidcolonizes the antrum; avoid
fundal parietal cellsfundal parietal cells
 In normal or reduced acid,In normal or reduced acid, HpHp colonizes rest of stomachcolonizes rest of stomach
Inflam. in antrum inducesInflam. in antrum induces G cellsG cells to secrete gastrin: moreto secrete gastrin: more
acid, also increases parietal cell number. Increased acidacid, also increases parietal cell number. Increased acid
load damages duodenum (DU)load damages duodenum (DU)
When Hp colonizes other areas of stomach, inflam. can result When Hp colonizes other areas of stomach, inflam. can result
in atrophy of the stomach lining and eventually ulcers; Cain atrophy of the stomach lining and eventually ulcers; Ca

16. HpHp infinf directlydirectly associateassociatedd withwith
 PUDPUD
- lifetime risk 3% in US, 25% Japan- lifetime risk 3% in US, 25% Japan
- eradication provides long-term cure- eradication provides long-term cure
 Gastric CaGastric Ca
- strong evidence of risk 0.1-3%- strong evidence of risk 0.1-3%
-- unclearunclear if eradication reduces the riskif eradication reduces the risk
 MALT lymphomaMALT lymphoma
-- 72%→ 98% of MALT lymphoma infected with72%→ 98% of MALT lymphoma infected with HpHp
Mucosa-associated lymphoid tissue: MALT

17. Damaging Effects of Hp

20. ChildhoodChildhood HpHp gastric Ca isgastric Ca is not reportednot reported. Gastric atrophy and. Gastric atrophy and
intestinal metaplasia are risk factors for Caintestinal metaplasia are risk factors for Ca
HpHp inf typically causes (CMI) gastritis: hypergastrinaemia andinf typically causes (CMI) gastritis: hypergastrinaemia and
hyperacidity. Infected stomach can have normal secretionhyperacidity. Infected stomach can have normal secretion
Antral predominant d.Antral predominant d. commonly has hypergastrinaemia,commonly has hypergastrinaemia,
DU, gastric metaplasia of duodenum.DU, gastric metaplasia of duodenum.Antral predominant d.Antral predominant d.
is probably higher in childrenis probably higher in children
But gastric Ca is more common in body predominant d.:But gastric Ca is more common in body predominant d.:
hypochorhydria and atrophy of parietal cells. Whenhypochorhydria and atrophy of parietal cells. When Hp Hp willwill
cause an antral/body predominant d. is unclearcause an antral/body predominant d. is unclear
Host response …Host response …

21. EM:EM: HpHp on the gastricon the gastric
mucosa of a childmucosa of a child

22. Section of a gastric biopsy:Section of a gastric biopsy: HpHp gastritisgastritis

23. EndoscopicEndoscopic
view ofview of
lymphoidlymphoid
nodularnodular
hyperplasiahyperplasia
of gastricof gastric
antrumantrum

24. McColl K. N Engl J Med 2010;362:1597-1604
Gastric-biopsy:Gastric-biopsy: HpHp adhering to epithelium and underlying inflammationadhering to epithelium and underlying inflammation

25. DISEASE IN CHILDRENDISEASE IN CHILDREN
 Ac. & chr. GastritisAc. & chr. Gastritis
 PUD:PUD: typically DU. Classic CF are not reliable in youngtypically DU. Classic CF are not reliable in young
children; only Dx by endoscopychildren; only Dx by endoscopy
 AP without PUDAP without PUD (adult: non-ulcer dyspepsia)(adult: non-ulcer dyspepsia)
HpHp eradication doesn’t help (9%). Resolution of nodulareradication doesn’t help (9%). Resolution of nodular
lymphoid hyperplasia may take 6mo to resolve andlymphoid hyperplasia may take 6mo to resolve and
inflam. infiltrate 4y. It isn’t sure ifinflam. infiltrate 4y. It isn’t sure if HpHp has a major rolehas a major role
 GERD:GERD: there may actually be an rise in reflux inthere may actually be an rise in reflux in Hp Hp eradication Rx.eradication Rx.
SS of above d. can be v. similar. Upper GI endoscopy is the only reliableSS of above d. can be v. similar. Upper GI endoscopy is the only reliable
method of Dx, and hencemethod of Dx, and hence Hp RxHp Rx. In UK 5% of 5–16y are colonized. In UK 5% of 5–16y are colonized
withwith Hp. Hp. Most have no SSMost have no SS

26. Recurrent APRecurrent AP
Chr. gastritis without PU could be a c/of RAP in children, andChr. gastritis without PU could be a c/of RAP in children, and
screening is often done; but no consistent evidence. Mostscreening is often done; but no consistent evidence. Most
likely it is a co-existence of 2 common but unrelated d. Hplikely it is a co-existence of 2 common but unrelated d. Hp
eradication doesn’t helperadication doesn’t help
IDAIDA
HpHp can be a/with IDA in asymptomatic children at puberty.can be a/with IDA in asymptomatic children at puberty.
Whether this is c/by iron loss or less absorption is unclear.Whether this is c/by iron loss or less absorption is unclear.
IfIf HpHp is identified in a case of IDA, it should be eradicatedis identified in a case of IDA, it should be eradicated
Growth falteringGrowth faltering
HpHp inf. may lead to it. Confounding variables may contributeinf. may lead to it. Confounding variables may contribute
to both Mn & earlyto both Mn & early Hp Hp colonization. Ifcolonization. If HpHp were found to bewere found to be
a significant c/of it then global impact would be enormous.a significant c/of it then global impact would be enormous.

27. DIAGNOSTIC TESTSDIAGNOSTIC TESTS
Indications:Indications: SS of PUD (RAP, wt loss, NV, anemia)SS of PUD (RAP, wt loss, NV, anemia),,
indigestion, fullness/bloating, belchingindigestion, fullness/bloating, belching
1.1.UBT:UBT: sensitivity/sp. 90%. Psensitivity/sp. 90%. Presence ofresence of HpHp. C UBT are non-. C UBT are non-
radioactive; widely available.radioactive; widely available. False-ve:False-ve: active/recentactive/recent
bleeding, AB/antisecretory Rxbleeding, AB/antisecretory Rx
2.2.Serology:Serology: 82.4% sensitive and 85% sp. It82.4% sensitive and 85% sp. It is widelyis widely
available. High conc. in blood/ saliva are found in activeavailable. High conc. in blood/ saliva are found in active
inf; after Rx, these gradually fall; so, not suitable forinf; after Rx, these gradually fall; so, not suitable for
establishing short/medium term successestablishing short/medium term success
3.3. Fecal Ag tests.Fecal Ag tests. 89-98% sensitivity & >90% sp. G89-98% sensitivity & >90% sp. Goodood
guide to successful eradication. It is simple; should beguide to successful eradication. It is simple; should be
test of choice for assessing eradicationtest of choice for assessing eradication

28. 4. Endoscopy & biopsy are indicated:4. Endoscopy & biopsy are indicated:
remains theremains the gold standardgold standard for Dx. Antral biopsiesfor Dx. Antral biopsies
have the highest yield (unless pt is on PPI)have the highest yield (unless pt is on PPI)
• Indications:Indications: Severe SS, anemia, wt loss, age >50ySevere SS, anemia, wt loss, age >50y
• RUT:RUT: rapid detection (S 79–100%, sp. 92–100%). It hasrapid detection (S 79–100%, sp. 92–100%). It has aa
poor positive predictive value in childhood and need to bepoor positive predictive value in childhood and need to be
confirmed by histologyconfirmed by histology
• Histology:Histology: if urease test negative (>90% sens.if urease test negative (>90% sens.
&sp.)&sp.)
5. Stool immunoassay & PCR5. Stool immunoassay & PCR (under(under
investigation)investigation)

31. WHO SHOULD BE TESTED?WHO SHOULD BE TESTED?
Test in all situations that may influence Mx: test only if youTest in all situations that may influence Mx: test only if you
want to treat.want to treat. For adults:For adults: all cases ofall cases of HpHp should be treated,should be treated,
regardless of lesionregardless of lesion
Strategy of Rx dyspepsia without rapid wt loss, GI bleed, orStrategy of Rx dyspepsia without rapid wt loss, GI bleed, or
anemia: PPI x1moanemia: PPI x1mo
Do endoscopy only in persistent SS. There is a low thresholdDo endoscopy only in persistent SS. There is a low threshold
in testingin testing HpHp colonisation in adults, and even though non-colonisation in adults, and even though non-
ulcer dyspepsia is unlikely to resolve swiftly afterulcer dyspepsia is unlikely to resolve swiftly after
eradication, the balance of risk to the individual pt iseradication, the balance of risk to the individual pt is
thought to favor empirical Rxthought to favor empirical Rx

34. First line therapyFirst line therapy
PPI b.d. + clarithromycin 500mg b.d.PPI b.d. + clarithromycin 500mg b.d.
++
amoxicillin 1000mg b.d/metro- 400mg BD minimum of 7damoxicillin 1000mg b.d/metro- 400mg BD minimum of 7d
In case of failureIn case of failure
Second line therapySecond line therapy
PPI b.d. + bismuth subsalicylate/subcitrate 120mg QDS + metro- 500mgPPI b.d. + bismuth subsalicylate/subcitrate 120mg QDS + metro- 500mg
t.d.s. + tetracycline 500mg q.d.s. min. 7dt.d.s. + tetracycline 500mg q.d.s. min. 7d
If bismuth is NA, PPI based triple therapies should be usedIf bismuth is NA, PPI based triple therapies should be used
Subsequent failures should be handled on a case-case basis. PatientsSubsequent failures should be handled on a case-case basis. Patients
failing second-line therapy in primary care should be referredfailing second-line therapy in primary care should be referred
TreatmentTreatment

35. TREATMENTTREATMENT
Principles are similar to any inf, but more bactericidal effect isPrinciples are similar to any inf, but more bactericidal effect is
essential. Even v. small residual Hp will re-coloniseessential. Even v. small residual Hp will re-colonise
 Re-colonization means risk ofRe-colonization means risk of ABR.ABR. So, ensure complianceSo, ensure compliance
 Treat only those who will benefit. Check eradication with aTreat only those who will benefit. Check eradication with a
UBT/fecal Ag 8w later. If failed, consider 2nd line.UBT/fecal Ag 8w later. If failed, consider 2nd line.
Repeated failures need repeat endoscopy & CSRepeated failures need repeat endoscopy & CS
 Non-invasive testing of family, & Rx may be usefulNon-invasive testing of family, & Rx may be useful
 PUDPUD further requires antacid and a 3mo PPIfurther requires antacid and a 3mo PPI
 Lymphomata require oncological consult, but are veryLymphomata require oncological consult, but are very
uncommon in childrenuncommon in children

36. RecommendationsRecommendations
• Noninvasive test-&-treat strategy forNoninvasive test-&-treat strategy for HpHp is reasonable foris reasonable for
children with upper GI SS but not alarm symptomschildren with upper GI SS but not alarm symptoms
• Ig test is the least accurateIg test is the least accurate
• Recurrence/persistence of SS after eradication Rx forRecurrence/persistence of SS after eradication Rx for
uninvestigated dyspepsia is much less likely to be Rxuninvestigated dyspepsia is much less likely to be Rx
failure; rather SS are unrelated tofailure; rather SS are unrelated to HpHp
• In areas where Hp and its complications are common, Drs. testIn areas where Hp and its complications are common, Drs. test
healthy people for it. Whether there is a benefit to treatinghealthy people for it. Whether there is a benefit to treating
Hp when you have no SS is controversialHp when you have no SS is controversial

37. Key pointsKey points
>> HpHp is a flagellated spiral micro-aerobeis a flagellated spiral micro-aerobe
>> Inf. is a risk factor for gastric CaInf. is a risk factor for gastric Ca
>> Causes PUD and gastritisCauses PUD and gastritis
>> Produces a cell-damaging toxinProduces a cell-damaging toxin
>> Transmission route is unclearTransmission route is unclear
>> Rates are falling in HICsRates are falling in HICs
>> Rx is by eradication using combination therapyRx is by eradication using combination therapy

38. Common Questions/FAQCommon Questions/FAQ
Does everyone withDoes everyone with HpHp get PU?get PU?
No, many have inf. but no PU. The reason is not yet clearNo, many have inf. but no PU. The reason is not yet clear
Should everyone be tested forShould everyone be tested for HpHp??
No, only recommended for those who have SSNo, only recommended for those who have SS
How did I get infected withHow did I get infected with HpHp??
Foodborne, contaminated with human feces, vomit, saliva.Foodborne, contaminated with human feces, vomit, saliva.
Exposure from family members seems to be commonestExposure from family members seems to be commonest
Does everyone treated forDoes everyone treated for HpHp get better?get better?
The majority get rid of it. ABR may occurThe majority get rid of it. ABR may occur

39. Can I get anotherCan I get another H. pyloriH. pylori infection?infection?
Rx does not make a person immune, so there is always theRx does not make a person immune, so there is always the
potential for becoming infected againpotential for becoming infected again
Why is Ig test forWhy is Ig test for HpHp not recommended?not recommended?
We do not recommend it for routine use for Dx or Rx, as itWe do not recommend it for routine use for Dx or Rx, as it
cannot DD between a present and past inf. But, many stillcannot DD between a present and past inf. But, many still
use ituse it
If it is negative, then it is unlikely ofIf it is negative, then it is unlikely of HpHp. But if it is positive,. But if it is positive,
then a currentthen a current Hp Hp inf. should be confirmed with a stoolinf. should be confirmed with a stool
Ag/UBT/endoscopyAg/UBT/endoscopy

40. PreventionPrevention
 No vaccineNo vaccine
 Improved sanitation decreased HP; will ultimatelyImproved sanitation decreased HP; will ultimately
eliminate it in US. But, without intervention it mayeliminate it in US. But, without intervention it may
remain endemic for another centuryremain endemic for another century
 Spontaneous elimination in children is probably aided bySpontaneous elimination in children is probably aided by
ABT for other reasonsABT for other reasons

42. Najat Vallaud-
Belkacem (born 4
Oct 1977) is the
first French woman
to be Minister of
Ed, (age 38).
Moroccan

43. MCQMCQ
 Hp is a carcinogenHp is a carcinogen
 It can grow anywhere in GITIt can grow anywhere in GIT
 Monotherapy is recommendedMonotherapy is recommended
 It can cause atrophic gastritisIt can cause atrophic gastritis
 Best test is SerologicalBest test is Serological
 It causes more DU than GUIt causes more DU than GU