Helicobacter pylori: transmission, virulence, and associated gastric disease

Helicobacter Pylori

Helicobacter (genus) pylori (species), commonly known as H. pylori, is a bacterium that causes gastritis of the inner lining of the stomach in humans and is the most common cause of ulcers worldwide (Delaney, Moayyedi and Forman 536). Ingestion of contaminated food and water and person-to-person contact is the most likely means of acquiring H. pylori. Portals for entry are largely oral, as oral-oral and oral-fecal contact are the most common contamination methods. About 30% of the adult population in the United States are infected and is more common in crowded living conditions with poor sanitation (Malcolm et al. 137). Infected individuals typically carry the infection indefinitely unless they are treated with medications to eradicate the bacterium. Other than the human stomach, there appears to be no natural reservoir for this bacterium. One out of every six patients with H. pylori infection will develop ulcers of the duodenum or stomach. The bacterium contains virulence factors such as urease, the vacuolating toxin, the cytotoxin-associated antigen CagA, or blood-group-antigen-binding adhesin, and likely account for the development of conditions other than gastritis and ulcers. H. pylori is associated with stomach cancer and a rare type of lymphocytic tumor of the stomach called MALT lymphoma (Sugiyama and Asaka 150).

History of H. Pylori

The bacterium was first described by Robin Warren and Barry Marshall, who isolated and cultured organisms from human mucosal specimens (Delaney, Moayyedi and Forman 536). Warren and Marshall contended that most stomach ulcers and gastritis were caused by colonization with this bacterium, not by stress or spicy food as the medical community had long assumed. The medical community was slow to recognize the role of this bacterium in stomach ulcers and gastritis, believing that no bacterium could survive for long in the acidic environment of the stomach. In 1994, the National Institutes of Health published an opinion stating that most recurrent gastric ulcers were caused by H. pylori, and recommended that antibiotics be included in the treatment regimen. Many stomach ulcers are treated with antibiotics effective against H. pylori in practice today.

Structure

H. pylori is a spiral-shaped gram-negative bacteria ~3 micrometers long with a diameter of ~0.5 micrometers. It has 4-6 flagella and is microaerophilic, i.e. It requires oxygen at lower levels than those contained in the atmosphere. With its flagella and its spiral shape, the bacterium drills through the mucus layer of the stomach and attaches to epithelial cells. It contains the enzyme urease, which converts urea into ammonia and bicarbonate. The ammonia is useful to the bacterium since it partially neutralizes the very acidic environment of the stomach.

Sufficient colony growth can be seen in 3 days when the organism is plated onto Brucella-sheep blood agar and placed in a microaerophilic environment. A gram-stain will reveal weakly stained rod with a unique curvature. H. pylori is also strongly urease-positive, which may help in identification. Other laboratory indications include positive for urease and caalase, as well as motile and microaerophile (Hofman et al. 17).

Mode of Transmission

H. pylori is transmitted from person to person. While the exact mode of transmission is not entirely understood, evidence suggests that contact with infected vomit or stool will increase the risk of developing an infection due to H. pylori. The use of contaminated gastric tubes and the act of belching have been implicated in transferring H. pylori from the gastric cavity to the oral cavity and consequently to a new victim through oral contact. The direct consumption of H. pylori contaminated water, food, gastric contents or fecal matter will significantly increase the risk of developing infection (Perez-Perez, Rothenbacher and Brenner 4).

Immune Response Avoidance

The severe immune response to H. pylori is characterized by an increase in IgG antibodies in the plasma that remain present for months following infection. Production of IgA antibodies also increase upon infection by H. pylori. An intense inflammatory response also follows infection by H. pylori, which leads to infiltration of numerous B. And T cells into the gastric mucosa. H. pylori is able to increase the number of T cells infiltrating the mucosa. It is thought that this ability to influence T cell activity may be the key to H. pylori's evasion of the immune response (Hofman et al. 19).

Therapy

In gastric ulcer patients where H. pylori is present, the first-line therapy is the eradication of the organism causing the ulcer. The standard first-line therapy is a 1 week triple-therapy of amoxicillin, clarithromycin and omeprazole (Nakayama and Graham 604). Occasionally, a different proton pump inhibitor is substituted, or metronidazole is used in place of amoxicillin in those allergic to penicillin. Such a therapy has revolutionized the treatment of gastric ulcers and has made a cure to the disease possible, where previously symptom-control using antacids or H2-antagonists was the only option. Unfortunately, an increasing number of infected individuals are found to harbor bacteria resistant to first-line antibiotics. This results in initial treatment failure and requires additional rounds of antibiotic therapy (Nakayama and Graham 604; McLoughlin et al. 45).