{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:00:28Z","timestamp":1791205228762,"version":"4.1.0"},"reference-count":47,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    A reliable challenge model is needed to evaluate\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    vaccine candidates.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    A\n                    <jats:italic>cag<\/jats:italic>\n                    pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of\n                    <jats:italic>H pylori<\/jats:italic>\n                    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\n                    <jats:sup>4<\/jats:sup>\n                    \u201310\n                    <jats:sup>10<\/jats:sup>\n                    cfu of\n                    <jats:italic>H pylori<\/jats:italic>\n                    in beef broth the next morning. Infection was confirmed by\n                    <jats:sup>13<\/jats:sup>\n                    C urea breath test (\n                    <jats:sup>13<\/jats:sup>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Twenty subjects (nine women and 11 men; aged 23\u201333 years) received a\n                    <jats:italic>H pylori<\/jats:italic>\n                    challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained &gt;10\n                    <jats:sup>3<\/jats:sup>\n                    viable\/ml\n                    <jats:italic>H pylori<\/jats:italic>\n                    . By two weeks post challenge gastric histology showed typical chronic\n                    <jats:italic>H pylori<\/jats:italic>\n                    gastritis with intense acute and chronic inflammation. The density of\n                    <jats:italic>H pylori<\/jats:italic>\n                    (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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Challenge reliably resulted in\n                    <jats:italic>H pylori<\/jats:italic>\n                    infection. Infection was associated with typical\n                    <jats:italic>H pylori<\/jats:italic>\n                    gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the\n                    <jats:italic>cag<\/jats:italic>\n                    pathogenicity island. Experimental\n                    <jats:italic>H pylori<\/jats:italic>\n                    infection is one of the viable approaches to evaluate vaccine candidates.\n                  <\/jats:p>","DOI":"10.1136\/gut.2003.037499","type":"journal-article","created":{"date-parts":[[2004,8,11]],"date-time":"2004-08-11T19:02:47Z","timestamp":1092250967000},"page":"1235-1243","source":"Crossref","is-referenced-by-count":170,"title":["Challenge model for\n                    <i>Helicobacter pylori<\/i>\n                    infection in human volunteers"],"prefix":"10.1136","volume":"53","author":[{"given":"D Y","family":"Graham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A R","family":"Opekun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M S","family":"Osato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H M T","family":"El-Zimaity","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C K","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Yamaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W A","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Cadoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T P","family":"Monath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2004,8,11]]},"reference":[{"key":"2025121221202525000_53.9.1235.1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0924-8579(97)00368-3","volume":"8","year":"1997","journal-title":"Int J Antimicrob Agents"},{"key":"2025121221202525000_53.9.1235.2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.3.1605-1612.2001"},{"key":"2025121221202525000_53.9.1235.3","first-page":"155","volume":"280","year":"1993","journal-title":"Int J Med Microbiol Virol Parasitol Infect Dis"},{"key":"2025121221202525000_53.9.1235.4","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1128\/IAI.66.2.581-586.1998","volume":"66","year":"1998","journal-title":"Infect Immun"},{"key":"2025121221202525000_53.9.1235.5","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1128\/iai.59.7.2359-2363.1991","volume":"59","year":"1991","journal-title":"Infect Immun"},{"key":"2025121221202525000_53.9.1235.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70084-3"},{"key":"2025121221202525000_53.9.1235.7","first-page":"40","volume":"2","year":"2001","journal-title":"Curr Opin Invest Drugs"},{"key":"2025121221202525000_53.9.1235.8","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1348-0421.2000.tb01243.x","volume":"44","year":"2000","journal-title":"Microbiol Immunol"},{"key":"2025121221202525000_53.9.1235.9","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1128\/IAI.66.6.2879-2886.1998","volume":"66","year":"1998","journal-title":"Infect Immun"},{"key":"2025121221202525000_53.9.1235.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(98)00365-X"},{"key":"2025121221202525000_53.9.1235.11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.9.1467"},{"key":"2025121221202525000_53.9.1235.12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6494-6498.2002"},{"key":"2025121221202525000_53.9.1235.13","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1517\/13543784.11.8.1127","volume":"11","year":"2002","journal-title":"Expert Opin Invest Drugs"},{"key":"2025121221202525000_53.9.1235.14","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.11.3219-3227.2000"},{"key":"2025121221202525000_53.9.1235.15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5378.1998.08056.x"},{"key":"2025121221202525000_53.9.1235.16","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1128\/JCM.37.7.2274-2279.1999","volume":"37","year":"1999","journal-title":"J Clin Microbiol"},{"key":"2025121221202525000_53.9.1235.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)02617-0"},{"key":"2025121221202525000_53.9.1235.18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12778"},{"key":"2025121221202525000_53.9.1235.19","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1128\/JCM.36.8.2258-2263.1998","volume":"36","year":"1998","journal-title":"J Clin Microbiol"},{"key":"2025121221202525000_53.9.1235.20","doi-asserted-by":"publisher","DOI":"10.1086\/515105"},{"key":"2025121221202525000_53.9.1235.21","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(94)90191-0"},{"key":"2025121221202525000_53.9.1235.22","first-page":"732","volume":"122","year":"1998","journal-title":"Arch Pathol Lab Med"},{"key":"2025121221202525000_53.9.1235.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(96)90135-5"},{"key":"2025121221202525000_53.9.1235.24","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/157.3.472"},{"key":"2025121221202525000_53.9.1235.25","doi-asserted-by":"crossref","first-page":"456","DOI":"10.4269\/ajtmh.1976.25.456","volume":"25","year":"1976","journal-title":"Am J Trop Med Hyg"},{"key":"2025121221202525000_53.9.1235.26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4269\/ajtmh.1992.47.276","volume":"47","year":"1992","journal-title":"Am J Trop Med Hyg"},{"key":"2025121221202525000_53.9.1235.27","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4049\/jimmunol.107.1.123","volume":"107","year":"1971","journal-title":"J Immunol"},{"key":"2025121221202525000_53.9.1235.28","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1056\/NEJM197010012831406","volume":"283","year":"1970","journal-title":"N Engl J Med"},{"key":"2025121221202525000_53.9.1235.29","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4269\/ajtmh.1952.1.30","volume":"1","year":"1952","journal-title":"Am J Trop Med Hyg"},{"key":"2025121221202525000_53.9.1235.30","first-page":"98","volume":"60","year":"1956","journal-title":"Trans Assoc Amer Phys"},{"key":"2025121221202525000_53.9.1235.31","doi-asserted-by":"crossref","first-page":"436","DOI":"10.5694\/j.1326-5377.1985.tb113443.x","volume":"142","year":"1985","journal-title":"Med J Aust"},{"key":"2025121221202525000_53.9.1235.32","doi-asserted-by":"crossref","first-page":"662","DOI":"10.7326\/0003-4819-114-8-662","volume":"114","year":"1991","journal-title":"Ann Intern Med"},{"key":"2025121221202525000_53.9.1235.33","first-page":"192","volume":"82","year":"1987","journal-title":"Am J Gastroenterol"},{"key":"2025121221202525000_53.9.1235.34","first-page":"974","volume":"83","year":"1988","journal-title":"Am J Gastroenterol"},{"key":"2025121221202525000_53.9.1235.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14648"},{"key":"2025121221202525000_53.9.1235.36","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02714.x"},{"key":"2025121221202525000_53.9.1235.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.130079797"},{"key":"2025121221202525000_53.9.1235.38","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.37074"},{"key":"2025121221202525000_53.9.1235.39","first-page":"1962","volume":"90","year":"1995","journal-title":"Am J Gastroenterol"},{"key":"2025121221202525000_53.9.1235.40","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1523-5378.1996.tb00048.x","volume":"1","year":"1996","journal-title":"Helicobacter"},{"key":"2025121221202525000_53.9.1235.41","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/S0016-5107(94)70067-2","volume":"40","year":"1994","journal-title":"Gastrointest Endosc"},{"key":"2025121221202525000_53.9.1235.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(99)90303-9"},{"key":"2025121221202525000_53.9.1235.43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01431.x"},{"key":"2025121221202525000_53.9.1235.44","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.23.2240"},{"key":"2025121221202525000_53.9.1235.45","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1998.00482.x"},{"key":"2025121221202525000_53.9.1235.46","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/172.1.161"},{"key":"2025121221202525000_53.9.1235.47","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(97)00203-X"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.2003.037499","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T05:20:36Z","timestamp":1765603236000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.2003.037499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,11]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2004,8,11]]},"published-print":{"date-parts":[[2004,9]]}},"alternative-id":["10.1136\/gut.2003.037499"],"URL":"https:\/\/doi.org\/10.1136\/gut.2003.037499","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8,11]]}}}