Helicobacter pylori

Morphology and habitat: Helicobacter pylori are spiral-shaped (or sometimes straight), Gram-negative bacilli approximately 0.5 x 3.0 micrometers in size. They are motile by means of 4-6 sheathed flagella that are attached to one pole (lophotrichous). H.pylori lives in the mucosal lining of duodenum and stomach.

Nomenclature: Originally, the organism was named Campylobacter pyloridis because it was structurally similar to other Campylobacter species. C.pyloridis was later renamed Campylobacter pylori and finally named Helicobacter pylori in 1989. Australian physiologists Robin Warren and Barry Marshall were awarded the 2005 Nobel Prize in medicine for their research in the early 1980's showing that peptic ulcers were primarily caused by bacteria not stress.

Cultural characteristics: It is microaerophilic and grows well in fresh, moist medium with humidity at 37^oC. It is cultivated on chocolate or blood agar and incubated for up to 5 days. It is catalase, oxidase, urease and phosphatase positive.

Pathogenesis:
Source of infection: Persons suffering from H.pylori infection shed the bacilli in their feces that might contaminate food and drinking water.

Mode of infection: H.pylori is believed to be transmitted orally food or water. It could be transmitted from the stomach to the mouth through gastro-esophagal reflux. The bacterium could then be transmitted through oral contact. About 10% of children get infected between the ages of 2 and 8.
The stomach is protected from its own gastric juice by a thick layer of mucus that covers the stomach lining. H.pylori takes advantage of this protection by living in the mucus lining. The antrum of the stomach is a region of moderate acidity where H.pylori usually prefers to colonize first. The bacterium uses its flagella and spiral shape to drill through the mucus layer in the stomach. It is known to produce some adhesions that help it adhere to epithelial cells of mucosa. It escapes the deleterious effect of HCl in the gastric juice by producing abundant of urease. Urease converts urea, which is in abundant supply in the stomach (from saliva and gastric juices), into bicarbonate and ammonia, which serves to neutralize the acidity.

CO(NH₂) 2 + H⁺ + 2H₂O ---urease---> HCO^3- + 2(NH⁴⁺)

Ammonia production from urease activity is toxic to mammalian cells. Epithelial cells undergo vacuolation because of urease activity. Other products of H.pylori, including protease, catalase, and phospholipases A2 and C cause weakening of the mucous layer of the GI tract and damage to surface epithelial cells. Lipopolysachaaride (LPS) may interfere with protective function of mucus layer and make epithelial cells at the surface vulnerable to acid. H.pylori is the only bacterium that stimulates pepsinogen secretion. 

Body's natural defenses cannot reach the bacterium in the mucus lining of the stomach. Neutrophils and killer T cells cannot reach the infection, as they cannot easily get through stomach lining. Cytokines are produced that attract and activate inflammatory cells. These cells spill their destructive compounds (superoxide radicals) on stomach lining cells. It is the inflammation of the stomach lining in response to H. pylori that causes peptic ulcer. Within a few days, gastritis and perhaps eventually a peptic ulcer results. Gastritis is an infiltration of the tissue with lymphocytes and plasma cells. Duodenal ulcers are associated with chronic superficial gastritis in the gastric antrum. Most gastric adenocarcinomas and lymphomas occur in persons with current or past infection with H. pylori. 

Laboratory diagnosis: There are invasive and non-invasive methods to diagnose H.pylori infections.

Invasive methods include endoscopy of a patient, during which biopsies are taken from multiple sites in the oesophagus, stomach, and duodenum. The biopsy specimen must be transported to laboratory immediately in sterile saline. The sample may be refrigerated in case of delay in transportation. When there is a delay of five hours of more, Stuart's transport medium can be used. 

The specimens are subjected to microscopic examination, culture and rapid urease test. The smears prepared from biopsy specimens are stained by Gram stain or Giemsa stain. The specimen is ground and inoculated on chocolate agar, blood agar or selective media such as Skirrow medium and incubated in microaerophilic conditions at 37^oC. Rapid urease test checks for the presence of the enzyme urease in the biopsy tissue sample. The test is positive in as little as 10 minutes.

Non-invasive testing includes culture from the stool specimen and urea breath test. In Urea breath test, the patient drinks a solution with C-13 or C-14 labeled urea with a meal. In an infected person, labelled CO₂ is detected in the breath, which is measured with a beta counter. Other methods of testing include testing for antibodies in serum or saliva of a patient. ELISA can be used to measure IgG in serum.

Treatment: The best treatment is a triple therapy routine including bismuth subcitrate, metronidazole, and either tetracycline or amoxycillin or clarithomycin.