Gastrointestinal (GI) System ORGAN SYSTEMS

Helicobacter pylori

Gram-negative spiral-shaped bacterium that inhabits the gastric environment.

Gram-negative spiral-shaped bacterium that inhabits the gastric environment.



  • Oral-oral transmission (M/C): Infection among members of same family via sharing of utensils
  • Fecal-oral transmission: Ingestion of contaminated water mainly due to unsatisfactory basic sanitation conditions

Bacterial pathogenecity:

There are four important components that lead to the formation of clinical diseases such as gastritis and ulcer in H. pylori infection.
  • Urease activity: Counters the acidic environment of the stomach
  • Flagella-mediated motility: Helps bacterium move toward host gastric epithelial cells
  • Adhesion: Bacterial adhesins interact with the host cell receptors, leading to successful colonization and persistent infection
  • Host tissue damage via effector proteins/toxins:
    • Cytotoxin-associated gene A (Cag A)
    • Vacuolating cytotoxin A (VacA)
  • Host factors: Both acute and chronic inflammation is seen in H. pylori gastritis as eosinophils, neutrophils, mast cells, and dendritic cells are stimulated. The gastric epithelial layer also secretes chemokines to initiate innate immunity and activates neutrophils that further damages the host tissue leading to the formation of gastritis and ulcer.
H.Pylori Virulence Factors | Y_tambe [GFDL( or CC BY-SA 2.5 (], via Wikimedia Commons


Hematoxylin and eosin (H&E) staining for visualizing the bacteria has a sensitivity and specificity up to 90%. Special stains like modified Giemsa stain, Warthin-Starry silver stain, Genta stain, and immunohistochemical (IHC) stain have shown to improve the specificity up to 100%. H&E staining is normally sufficient for visualizing H. pylori while Giemsa stain is more beneficial compared to other stains as it is simple and consistent. In the presence of inflammation on histology and absence of bacteria on H&E or Giemsa staining, specialized IHC stains may be more useful.
Cascade of histologic changes induced by Helicobacter pylori at level of gastric mucosa. | Mégraud, F., Bessède, E., & Varon, C. (2015). Helicobacter pylori infection and gastric carcinoma. Clinical Microbiology and Infection, 21(11), 984–990.


The clinical features of Helicobacter pylori range from asymptomatic gastritis to gastrointestinal malignancy. The majority of cases are asymptomatic. Symptoms, if present, are usually of gastritis or peptic ulcer disease such as abdominal pain, nausea, vomiting or dyspepsia.

Gastritis (M/C clinical manifestation):

Immediately after infection, bacteria causes an acute form of gastritis, characterized by hypochlorydia, which will later evolve into a chronic active gastritis that can affect either the antrum (associated with increased acid secretion and duodenal ulcers), the corpus (associated with gastric atrophy and achlorhydria) or both.
Gastric pathology and disease outcome in H. pylori infection. | Mégraud, F., Bessède, E., & Varon, C. (2015). Helicobacter pylori infection and gastric carcinoma. Clinical Microbiology and Infection, 21(11), 984–990.

Extra-intestinal manifestations:


Helicobacter pylori is a group I carcinogen. Patients with an early-stage disease are most likely to have a complete remission with the antibacterial treatment and those with a more extensive disease (ulcerations, nodular submucosal mass lesions, invasion throughout the wall or lymphadenopathy) are more likely to require standard lymphoma therapy. Patients with intestinal metaplasia (on routine biopsy) should be tested and treated for infection with Helicobacter pylori because intestinal metaplasia is an independent risk factor for gastric malignancy. After the eradication of the organism, the extent to which there is a regression of metaplasia is not currently known.
Model representing the role of H. pylori and other factors in gastric carcinogenesis | Correa, P., W. Haenszel, C. Cuello, S. Tannenbaum, and M. Archer. 1975. A model for gastric cancer epidemiology. Lancet ii:58-59.


H. pylori infection is diagnosed by both invasive and non-invasive methods. H. pylori testing is recommended in children having first-degree relatives with gastric cancer.

Noninvasive tests:

The stool antigen test and UBT have high sensitivity and specificity similar to the invasive methods.
  • Stool antigen detection test (also detected in serum, urine and oral samples)
  • Urea breath test (UBT): Ten to twenty minutes after swallowing a capsule containing urea, a breath sample is collected and analyzed for labeled carbon dioxide breath. A positive test signifies that there is an active infection. The test becomes negative shortly after eradication.

Invasive tests:

Require gastric tissue for detecting the organism and include culture, rapid urease tests (RUT), histopathology, polymerase chain reaction, and fluorescent in situ hybridization (FISH). Culture is the only method with 100% specificity, and a positive culture is sufficient to diagnose H. pylori infection, but it has a lower sensitivity. For this reason, concordant results of at least two tests are needed to define the H. pylori status. It is recommended that the initial diagnosis of H pylori infection should be based on either positive histopathology and positive RUT or a positive culture from gastric biopsies.
  • Current guidelines: UG-endoscopy with gastric biopsies (antrum & corpus) for histology, culture, and RUT
  • Determine H. pylori eradication: Both UBT and stool H. pylori antigen detection by ELISA are reliable non-invasive tests
    • Before a patient is tested for H. pylori eradication, it is recommended to wait at least 2 weeks after stopping proton pump inhibitors (PPIs) and 4 weeks after stopping antibiotics.

Differential diagnosis:


The eradication of Helicobacter pylori usually prevents the return of ulcers and ulcer complications even after appropriate medications such as PPIs are stopped. The eradication of Helicobacter pylori is important in the treatment of the rare condition of the stomach known as MALT lymphoma. The treatment of Helicobacter pylori to prevent stomach cancer is controversial.

Triple therapy:

Treatment of choice if the strain is susceptible to CLA and metronidazole (MET)
  • PPI (1-2 mg/kg/day), amoxicillin (AMO) (50 mg/kg/day), and clarithromycin (CLA) (20 mg/kg/day) for 14 days
    • Failure: CLA replaced with MET (20 mg/kg/day) without further antibiotic susceptibility testing
  • Alternative sequential therapy for 10 days: PPI with AMO for 5 days followed by PPI with MET and CLA for 5 days

Bismuth quadruple therapy:

In the case of resistance to both CLA and MET or when antimicrobial susceptibility is not known
  • Bismuth salts (8 mg/kg/day), PPI, AMO (in children younger than 8 years) or tetracycline (in children older than 8 years) and MET
Algorithm for first-line treatment | American College of Physicians (2003- ) MKSAP 17: medical knowledge self-assessment program. Philadelphia, Pa.: American College of Physicians; 2015 | Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/ Florence Consensus Report. Gut. 2016

Antibiotic resistance:

Development of resistance to antibiotics is a serious problem that varies from region to region. Using the macrolide group of antibiotics for respiratory tract infection has led to the emergence of H. pylori CLA resistance. With treatment failure, rescue therapy should be individualized based on antibiotic susceptibility. In comparison to Asians, Caucasian populations metabolize PPI more rapidly due to CYP2C19 genetic polymorphism. Therefore PPIs like esomeprazole and rabeprazole that are less prone to degradation by rapid metabolizers with CYP2C19 polymorphism, should be used when available. Also, probiotics have not shown to improve eradication rates or reduce side effects from current evidence.

One reply on “Helicobacter pylori”

Leave a Reply