Challenge model for Helicobacter pylori infection in human volunteers.

Graham DY, Opekun AR, Osato MS, El-Zimaity HM, Lee CK, Yamaoka Y, Qureshi WA, Cadoz M, Monath TP
Gut. 2004 53 (9): 1235-43

PMID: 15306577 · PMCID: PMC1774191 · DOI:10.1136/gut.2003.037499

BACKGROUND - A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates.

METHODS - A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 10(4)-10(10) cfu of H pylori in beef broth the next morning. Infection was confirmed by (13)C urea breath test ((13)C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology.

RESULTS - Twenty subjects (nine women and 11 men; aged 23-33 years) received a H pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >10(3) viable/ml H pylori. By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation. The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge.

CONCLUSION - Challenge reliably resulted in H pylori infection. Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island. Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.

MeSH Terms (19)

Adolescent Adult Anti-Bacterial Agents Bacterial Vaccines Dyspepsia Female Follow-Up Studies Gastric Acidity Determination Gastritis Helicobacter Infections Helicobacter pylori Humans Hydrogen-Ion Concentration Interleukins Male Microbial Sensitivity Tests Middle Aged Nontherapeutic Human Experimentation Virulence

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