Helicobacter pylori

Vivekanandan AMD General Medicine II yearInstitute of Internal MedicineMadras Medical College

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Introduction

▪ Helicobacter pylori (H. pylori) remains one of the most common worldwide human infections and

▪ It is associated with a number of important upper gastrointestinal (GI) conditions – including chronic gastritis, – peptic ulcer disease, – gastric malignancy.

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Epidemiology

▪ Almost 50% of worlds population is affected by H.pylori

▪ Genetic studies shows that humans are infected for more than 58000 years at time they migrated from Africa

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Time of acquisition of infection

The majority of children's are infected before the age of 10 years

And almost reaching 80% in adults reaching the age of 50 years

In developing nations

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Unusual before the age of 10 years

Reaches 10% in adults in the age between 18 – 30 years

Reaches almost 50% in those older than 60 years

In united states..

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Risk factors

1. Socioeconomic status• Density of housing• Over crowding• Number of siblings • Sharing the same bed• Lack of running water

2. Consumption of salted food- increases persistence of infections and also predisposes to risk of gastric cancer

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Hereditary and genetic factors

▪ Hispanics and African-Americans have a higher rate of infection than Caucasians.

▪ Monozygotic twins raised in different households have a greater concordance of H. pylori infection than do dizygotic twins raised apart

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Routes of transmission

▪ Humans are the major reservoir of the H.pylori

▪ Person to person transmission in the form of

1. Fecal – oral2. Oral – oral3. Gastric – oral

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Risks of transmission

▪ Childrens who consume untreated stream water, uncooked vegetables

▪ Exposure to diarrheal stools, vomitus of the infected persons

▪ Dentists and oral hygienists who have exposures to dental plaques and saliva

▪ Iatrogenic infection in the form of contaminated endoscopes and other gastric devices

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Microbiology

▪ Morphology:

• H. pylori is a spiral shaped,

• microaerophilic, gram negative bacterium

• measuring approximately 3.5 microns in length

and 0.5 microns in width 

• It has multiple unipolar flagella and it is actively

motile

• biochemically characterized as catalyse, oxidise,

and urease positive.

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Growth and culture characters

▪ Growth and culture characters

• It’s a slow growing organism

• can be cultured on blood agar

• selective media is Skirrow's media (with

vancomycin, polymyxin B, and trimethoprim,

chocolate medium) incubated at 37ºC in a 5 percent

oxygen atmosphere for three to seven days

• The colonies are translucent and 1–2 mm in

diameter.

11/04/2023 12Pathophysiology

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Conditions associated with H.pylori

▪ Esophagus1. GERD2. Barrett’s esophagus3. adenocarcinoma

▪ Stomach1. Acute gastritis ( sometimes self limiting)2. Chronic active gastritis3. Peptic ulcer disease4. Gastric adenocarcinoma5. MALT

▪ Duodenum1. Peptic ulcer

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Non gastrointestinal diseases associated to H.pylori

▪ Coronary artery disease

▪ Immune thrombocytopenic purpura

▪ Iron deficiency anemia

▪ Reynaud's phenomenon

▪ Scleroderma

▪ Idiopathic urticaria

▪ Acne rosacea

▪ Thyroiditis

▪ GBS

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Diagnosis – when to test

ACG recommendations

▪ Testing for H. pylori should be performed only if the clinician plans to offer treatment for positive results

▪ Testing is indicated in patients with gastric MALT lymphoma, active peptic ulcer disease, or a past history of documented peptic ulcer

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Diagnosis – when to test

▪ patients with uninvestigated dyspepsia who are under the age of 55 years and have no alarm features

▪ Deciding which test to use in which situation relies heavily upon whether a patient requires evaluation with upper endoscopy and the strengths, weaknesses, and costs of the individual tests

alarm features

▪ bleeding,

▪ anaemia,

▪ early satiety,

▪ unexplained weight loss,

▪ Progressive

▪ dysphagia, odynophagia,

▪ recurrent vomiting,

▪ family history of GI cancer, previous esophagogastric malignancy

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Indications for testing and treatment of H.pylori infection

▪   ▪

  

▪ GERD  

▪  

▪  

Supported by the evidence Controversial

Active peptic ulcer disease (gastric or duodenal ulcer)  

Functional dyspepsia

Confirmed history of peptic ulcer Persons using NSAIDs or before starting NSAIDs

Gastric MALT-lymphoma (low grade)  

Unexplained iron deficiency anaemia or ITP

Following endoscopic resection of early gastric cancer  

Populations at higher risk of gastric cancer

Uninvestigated dyspepsia (if H. pylori population prevalence high)

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Types of diagnostic test

Non endoscopic tests

1. Serology (quantitative or qualitative IgG)

2. Urea breath test (13C or 14C)

3. Stool antigen test

Endoscopic tests

1. Histology

2. Rapid urease test

3. Culture

4. Polymerase chain reaction assay

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Serology

▪ ELISA technology to detect IgG antibodies is inexpensive, non-invasive.

▪ high sensitivity (90 to 100%), variable specificity (76 to 96%) & accuracy( 83 to 98%).

▪ It needs confirmation with another method such as a stool antigen or urea breath test before starting treatment

▪ The “serological scar’ may be present even after successful eradication of organism

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Urea breath test (UBT)

▪ detects active H. pylori infection, confirming the accuracy of serology and documenting successful treatment.

▪ The specificity is more than 95%, sensitivity of the test is 88% to 95%

▪ false-negative results reported in patients taking antisecretory therapy such as PPIs,bismuth, or antibiotics.

▪ antibiotics should be stopped at least four weeks and PPIs at least one week before breath testing.

▪ UBT is not accurate in patients who have had gastric respective surgery.

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Urea breath test (UBT)

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Stool antigen assay

▪ It is an immunoassay to detect the presence of h.pylori antigen in stools

▪ The sensitivity and specificity are 94% and 97%, respectively

▪ sensitivity of stool testing is negatively affected by PPIs, bismuth, and antibiotics which affects the bacterial load

▪ Its used both for diagnosis and confirm the eradication .

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Endoscopic tests – biopsy urease testing

Tissue from the antral biopsy is placed in agar well containing urea and pH reagent

The urease cleaves the urea to liberate ammonia

This process changes the medium alkaline and produces a color change

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Biopsy urease testing

▪ commercially available kits include CLOtest, PyloriTek, and Hp-fast

▪ The CLOtest may become positive as early as one hour after collection, but a final reading at 24 hours is recommended

▪ The sensitivity is 90 to 95% & specificity is 95 to 100%

▪ false positive tests are unusual. False negative results occur in recent gastrointestinal bleeding or with the use of PPIs, H2 antagonists, antibiotics, or bismuth-containing compounds

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Rapid urease testing

▪ To know patient's H. pylori status before discharge from the endoscopy suite.

▪ biopsy specimens are sandwiched between a reagent strip with a pH indicator and a pad containing urea.

▪ One hour sensitivity is 89 to 98 percent and specificity is 89 to 93 percent.

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Rapid urease test

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Histology

▪ In addition to make diagnosis of H.pylori the biopsy and histology also reveals intestinal metaplasia, MALT omas, dysplasia and neoplasia

▪ In addition to biopsying “clinically suspicious” areas, taking multiple biopsies and sampling lesser and greater curvatures of gastric antrum and body are important.

▪ It is gold standard for identifying infection, with reported sensitivity and specificity as high as 95% and 98%

▪ Limitations…

▪ Brush cytology….

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A silver stain (Warthin Starry) of H.pylori on gastric mucus-secreting epithelial cells (x1000). This picture is notorious because it is of Dr. Marshall's stomach biopsy taken 8 days after he drank a culture of H. pylori.

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Culture

▪ Its fastidious and difficult to culture and require special culture media

▪ Culture is indicated when treating cases not responding to treatment and suspected antibiotic resistance

▪ Even though the in vitro sensitivity will not guarantee the treatment results

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This is a 3 day culture of H.pylori on blood agar

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Treatment

▪ Triple therapy

▪ Quadruple therapy

▪ Sequential therapy

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Triple therapy

▪ It’s the most commonly recommended therapy

▪ The duration of therapy must be 14 days and all drugs in BD dose

▪ The cure rate is >80%

▪ Metronidazole 500mg can be substituted for amoxy in penicillin allergic patients

PPI

Clarithromycin

500mg

Amoxycillin1000mg

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Quadruple therapy

▪ Dose : 4 times a day

▪ Duration : 14 days

▪ appropriate as initial therapy in areas in which the prevalence of resistance to clarithromycin or metronidazole is >20%

▪ in patients with recent or repeated exposure to clarithromycin or metronidazole

PPI

Bismuth 525 mg

Metronidazole 250 mg

Tetracycline 500 mg

Eradication rate 70 – 85%

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Sequential regimen

Regimen Days Eradicationrate

(PPI + Amoxy 1000 mg) BD

followed by(PPI+ Clarithromycin 500 mg + Tinidazole 500 mg) BD

5 + 5 90%

• It has overall eradication rate better than triple therapy 90% vs 80%

•Particularly superior if bacteria is clarithromycin resistant ( 89% Vs 29%)

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Eradication confirmation

▪ Eradication may be confirmed by a urea breath test, fecal antigen test, or upper endoscopy performed four weeks or more after completion of therapy.

▪ Its indicated in following situations1. Patients who have persistent symptoms after H.

pylori treatment for dyspepsia2. Patients who had an H. pylori associated ulcer3. Patients who had gastric mucosa associated

lymphoid tissue (MALT) lymphoma4. Patients who had resection for early gastric cancer.

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Treatment failures and persisitance of H.pylori

▪ The initial treatment results in 25% failures

▪ The reasons for failure are1. Resistant organism2. Poor compliance with medication3. Alcohol consumption4. Smoking5. Prior antibiotic use6. Underlying condition (FD Vs PUD)

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Antibiotic resistance

▪ Resistance to metronidazole is 40% in US and 11% for clarithromycin

▪ Resistace to amox and tetracycline is less than 1%

▪ The resistance to metronidazole is overcome by increasing doses or combining with bismuth

▪ Macrolide resistance cant overcome by increasing dose because these are due to alterations in 23S ribosomal RNA(A2143G, A2142G & A2142C) which interferes with ribosomal macrolide binding

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Rescue therapy

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Side effects of treatment

▪  Side effects are reported in up to 50 percent of patients taking one of the triple therapy regimens .

▪ The adverse effects are usually mild; fewer than 10 percent of patients stop treatment due to side effects1. The most common side effect is a metallic taste due to 

metronidazole or clarithromycin.2. Metronidazole can cause a peripheral neuropathy,

seizures, and a disulfiram-like reaction when taken with alcohol.

3. Clarithromycin can cause taste alteration, nausea, vomiting, abdominal pain, and rarely QT prolongation.

4. Tetracycline can induce a photosensitivity reaction in some cases. It should also not be administered to pregnant women or young children.

5. Amoxicillin can cause diarrhea or an allergic reaction with skin rash.

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Take home message

1. H. pylori is a common worldwide infection.

2. Established indications for H. pylori cure include peptic ulcer,(MALT) and uninvestigated dyspepsia.

3. Non-endoscopic and endoscopic tests are available toidentify H. pylori.

4. Proton pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole or a PPI, bismuth, tetracycline,and metronidazole for 10–14 days are accepted first line treatment

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Thank you….

John Robin Warren

Barry James Marshall