Challenge model for Helicobacter pylori infection in human volunteers.
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.


CONCLUSIONS
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.
Graham
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Veterans Affairs Medical Center, Rm 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX 77030, USA. dgraham@bcm.tmc.edu
Opekun
A R
AR
Osato
M S
MS
El-Zimaity
H M T
HM
Lee
C K
CK
Yamaoka
Y
Y
Qureshi
W A
WA
Cadoz
M
M
Monath
T P
TP
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001428:Bacterial Vaccines; D004415:Dyspepsia / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D005745:Gastric Acidity Determination; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D033281:Nontherapeutic Human Experimentation; D014774:Virulence
D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D007378:Interleukins