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. 1996 Jun;40(6):1486–1490. doi: 10.1128/aac.40.6.1486

Use of PCR and culture to detect Helicobacter pylori in naturally infected cats following triple antimicrobial therapy.

S E Perkins 1, L L Yan 1, Z Shen 1, A Hayward 1, J C Murphy 1, J G Fox 1
PMCID: PMC163354  PMID: 8726024

Abstract

Helicobacter pylori causes gastritis and peptic ulcers and is linked to gastric cancer. Domestic cats from a commercial source were found to be naturally infected with H. pylori, and studies were undertaken to eradicate H. pylori from infected cats by using triple antimicrobial therapy. Eight cats infected with H. pylori were used in the study. Six cats received a 21-day course of oral amoxicillin, metronidazole, and omeprazole, and two cats served as controls. Two weeks and 4 weeks posttreatment (p.t.), all six treated cats were negative at several sites (saliva, gastric juice, and gastric mucosa) for H. pylori by culture. However, as determined by PCR with primers specific for the 26-kDa product, the majority of cats at 2 and 4 weeks p.t. had gastric fluid samples which were positive for H. pylori and three of three cats at 2 weeks p.t. had dental plaque which was positive for H. pylori. At 6 weeks p.t., all six cats had H. pylori-negative cultures for samples from several gastric sites taken at necropsy, and only one cat had H. pylori cultured from gastric juice. PCR analysis revealed that five of six cats had H. pylori DNA amplification products from plaque, saliva, and/or gastric fluid samples. Negative bacterial cultures for cats for which there was demonstrable PCR amplification of H. pylori DNA may reflect the inability of in vitro culture techniques to isolate small numbers of H. pylori organisms, focal colonization at sites not cultured, or a failure of the antibiotics to successfully eradicate H. pylori from extragastric sites which allowed subsequent recolonization of the stomach after cessation of therapy. Alternatively, the treatment strategy may have induced in vivo viable but nonculturable coccoid forms of H. pylori. The H. pylori cat model should allow further studies to test these hypotheses as well as the efficacies of other combined therapeutic regimens. Also, because 100% of these cats were naturally infected with H.pylori, this model should prove useful in exploring mechanisms whereby human populations in underdeveloped countries, which have H. pylori infection rates approaching 100%, have a high rate of recurrence of H. pylori infection after use of prescribed antibiotic therapies that successfully eradicate H. pylori in individuals in developed countries.

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Selected References

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  1. Baskerville A., Newell D. G. Naturally occurring chronic gastritis and C pylori infection in the rhesus monkey: a potential model for gastritis in man. Gut. 1988 Apr;29(4):465–472. doi: 10.1136/gut.29.4.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bayerdörffer E., Mannes G. A., Sommer A., Höchter W., Weingart J., Hatz R., Lehn N., Ruckdeschel G., Dirschedl P., Stolte M. Long-term follow-up after eradication of Helicobacter pylori with a combination of omeprazole and amoxycillin. Scand J Gastroenterol Suppl. 1993;196:19–25. doi: 10.3109/00365529309098337. [DOI] [PubMed] [Google Scholar]
  3. Bell G. D., Powell K. U., Burridge S. M., Bowden A. N., Rameh B., Bolton G., Purser K., Harrison G., Brown C., Gant P. W. Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens. Q J Med. 1993 Nov;86(11):743–750. [PubMed] [Google Scholar]
  4. Bell G. D., Powell K., Burridge S. M., Pallecaros A., Jones P. H., Gant P. W., Harrison G., Trowell J. E. Experience with 'triple' anti-Helicobacter pylori eradication therapy: side effects and the importance of testing the pre-treatment bacterial isolate for metronidazole resistance. Aliment Pharmacol Ther. 1992 Aug;6(4):427–435. doi: 10.1111/j.1365-2036.1992.tb00556.x. [DOI] [PubMed] [Google Scholar]
  5. Bode G., Mauch F., Malfertheiner P. The coccoid forms of Helicobacter pylori. Criteria for their viability. Epidemiol Infect. 1993 Dec;111(3):483–490. doi: 10.1017/s0950268800057216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Borody T. J., George L. L., Brandl S., Andrews P., Lenne J., Moore-Jones D., Devine M., Walton M. Helicobacter pylori eradication with doxycycline-metronidazole-bismuth subcitrate triple therapy. Scand J Gastroenterol. 1992 Apr;27(4):281–284. doi: 10.3109/00365529209000075. [DOI] [PubMed] [Google Scholar]
  7. Bronsdon M. A., Schoenknecht F. D. Campylobacter pylori isolated from the stomach of the monkey, Macaca nemestrina. J Clin Microbiol. 1988 Sep;26(9):1725–1728. doi: 10.1128/jcm.26.9.1725-1728.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cellini L., Allocati N., Angelucci D., Iezzi T., Di Campli E., Marzio L., Dainelli B. Coccoid Helicobacter pylori not culturable in vitro reverts in mice. Microbiol Immunol. 1994;38(11):843–850. doi: 10.1111/j.1348-0421.1994.tb02136.x. [DOI] [PubMed] [Google Scholar]
  9. Cellini L., Allocati N., Di Campli E., Dainelli B. Helicobacter pylori: a fickle germ. Microbiol Immunol. 1994;38(1):25–30. doi: 10.1111/j.1348-0421.1994.tb01740.x. [DOI] [PubMed] [Google Scholar]
  10. Correa P., Fox J., Fontham E., Ruiz B., Lin Y. P., Zavala D., Taylor N., Mackinley D., de Lima E., Portilla H. Helicobacter pylori and gastric carcinoma. Serum antibody prevalence in populations with contrasting cancer risks. Cancer. 1990 Dec 15;66(12):2569–2574. doi: 10.1002/1097-0142(19901215)66:12<2569::aid-cncr2820661220>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  11. Eaton K. A., Catrenich C. E., Makin K. M., Krakowka S. Virulence of coccoid and bacillary forms of Helicobacter pylori in gnotobiotic piglets. J Infect Dis. 1995 Feb;171(2):459–462. doi: 10.1093/infdis/171.2.459. [DOI] [PubMed] [Google Scholar]
  12. Fabre R., Sobhani I., Laurent-Puig P., Hedef N., Yazigi N., Vissuzaine C., Rodde I., Potet F., Mignon M., Etienne J. P. Polymerase chain reaction assay for the detection of Helicobacter pylori in gastric biopsy specimens: comparison with culture, rapid urease test, and histopathological tests. Gut. 1994 Jul;35(7):905–908. doi: 10.1136/gut.35.7.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fantry G. T., Zheng Q. X., James S. P. Conventional cleaning and disinfection techniques eliminate the risk of endoscopic transmission of Helicobacter pylori. Am J Gastroenterol. 1995 Feb;90(2):227–232. [PubMed] [Google Scholar]
  14. Fox J. G., Batchelder M., Marini R., Yan L., Handt L., Li X., Shames B., Hayward A., Campbell J., Murphy J. C. Helicobacter pylori-induced gastritis in the domestic cat. Infect Immun. 1995 Jul;63(7):2674–2681. doi: 10.1128/iai.63.7.2674-2681.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fox J. G., Blanco M., Murphy J. C., Taylor N. S., Lee A., Kabok Z., Pappo J. Local and systemic immune responses in murine Helicobacter felis active chronic gastritis. Infect Immun. 1993 Jun;61(6):2309–2315. doi: 10.1128/iai.61.6.2309-2315.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fox J. G. Campylobacter infections and salmonellosis. Semin Vet Med Surg (Small Anim) 1991 Aug;6(3):212–218. [PubMed] [Google Scholar]
  17. Fox J. G., Correa P., Taylor N. S., Lee A., Otto G., Murphy J. C., Rose R. Helicobacter mustelae-associated gastritis in ferrets. An animal model of Helicobacter pylori gastritis in humans. Gastroenterology. 1990 Aug;99(2):352–361. doi: 10.1016/0016-5085(90)91016-y. [DOI] [PubMed] [Google Scholar]
  18. Fox J. G., Correa P., Taylor N. S., Zavala D., Fontham E., Janney F., Rodriguez E., Hunter F., Diavolitsis S. Campylobacter pylori-associated gastritis and immune response in a population at increased risk of gastric carcinoma. Am J Gastroenterol. 1989 Jul;84(7):775–781. [PubMed] [Google Scholar]
  19. Fox J. G., Lee A., Otto G., Taylor N. S., Murphy J. C. Helicobacter felis gastritis in gnotobiotic rats: an animal model of Helicobacter pylori gastritis. Infect Immun. 1991 Mar;59(3):785–791. doi: 10.1128/iai.59.3.785-791.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fox J. G., Otto G., Taylor N. S., Rosenblad W., Murphy J. C. Helicobacter mustelae-induced gastritis and elevated gastric pH in the ferret (Mustela putorius furo). Infect Immun. 1991 Jun;59(6):1875–1880. doi: 10.1128/iai.59.6.1875-1880.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Genta R. M., Hamner H. W., Graham D. Y. Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy. Hum Pathol. 1993 Jun;24(6):577–583. doi: 10.1016/0046-8177(93)90235-9. [DOI] [PubMed] [Google Scholar]
  22. Genta R. M., Hamner H. W. The significance of lymphoid follicles in the interpretation of gastric biopsy specimens. Arch Pathol Lab Med. 1994 Jul;118(7):740–743. [PubMed] [Google Scholar]
  23. Genta R. M., Huberman R. M., Graham D. Y. The gastric cardia in Helicobacter pylori infection. Hum Pathol. 1994 Sep;25(9):915–919. doi: 10.1016/0046-8177(94)90011-6. [DOI] [PubMed] [Google Scholar]
  24. Graham D. Y. Campylobacter pylori and peptic ulcer disease. Gastroenterology. 1989 Feb;96(2 Pt 2 Suppl):615–625. doi: 10.1016/s0016-5085(89)80057-5. [DOI] [PubMed] [Google Scholar]
  25. Graham D. Y., Lew G. M., Klein P. D., Evans D. G., Evans D. J., Jr, Saeed Z. A., Malaty H. M. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med. 1992 May 1;116(9):705–708. doi: 10.7326/0003-4819-116-9-705. [DOI] [PubMed] [Google Scholar]
  26. Graham D. Y., Opekun A. R., Klein P. D. Clarithromycin for the eradication of Helicobacter pylori. J Clin Gastroenterol. 1993 Jun;16(4):292–294. doi: 10.1097/00004836-199306000-00004. [DOI] [PubMed] [Google Scholar]
  27. Hammar M., Tyszkiewicz T., Wadström T., O'Toole P. W. Rapid detection of Helicobacter pylori in gastric biopsy material by polymerase chain reaction. J Clin Microbiol. 1992 Jan;30(1):54–58. doi: 10.1128/jcm.30.1.54-58.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Handt L. K., Fox J. G., Dewhirst F. E., Fraser G. J., Paster B. J., Yan L. L., Rozmiarek H., Rufo R., Stalis I. H. Helicobacter pylori isolated from the domestic cat: public health implications. Infect Immun. 1994 Jun;62(6):2367–2374. doi: 10.1128/iai.62.6.2367-2374.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Handt L. K., Fox J. G., Stalis I. H., Rufo R., Lee G., Linn J., Li X., Kleanthous H. Characterization of feline Helicobacter pylori strains and associated gastritis in a colony of domestic cats. J Clin Microbiol. 1995 Sep;33(9):2280–2289. doi: 10.1128/jcm.33.9.2280-2289.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Henry G. A., Long P. H., Burns J. L., Charbonneau D. L. Gastric spirillosis in beagles. Am J Vet Res. 1987 May;48(5):831–836. [PubMed] [Google Scholar]
  31. Karita M., Kouchiyama T., Okita K., Nakazawa T. New small animal model for human gastric Helicobacter pylori infection: success in both nude and euthymic mice. Am J Gastroenterol. 1991 Nov;86(11):1596–1603. [PubMed] [Google Scholar]
  32. Kimura K., Ido K., Saifuku K., Taniguchi Y., Kihira K., Satoh K., Takimoto T., Yoshida Y. A 1-h topical therapy for the treatment of Helicobacter pylori infection. Am J Gastroenterol. 1995 Jan;90(1):60–63. [PubMed] [Google Scholar]
  33. Krakowka S., Morgan D. R., Kraft W. G., Leunk R. D. Establishment of gastric Campylobacter pylori infection in the neonatal gnotobiotic piglet. Infect Immun. 1987 Nov;55(11):2789–2796. doi: 10.1128/iai.55.11.2789-2796.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lee A., Fox J. G., Otto G., Murphy J. A small animal model of human Helicobacter pylori active chronic gastritis. Gastroenterology. 1990 Nov;99(5):1315–1323. doi: 10.1016/0016-5085(90)91156-z. [DOI] [PubMed] [Google Scholar]
  35. Lee A., Fox J., Hazell S. Pathogenicity of Helicobacter pylori: a perspective. Infect Immun. 1993 May;61(5):1601–1610. doi: 10.1128/iai.61.5.1601-1610.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Logan R. P., Gummett P. A., Schaufelberger H. D., Greaves R. R., Mendelson G. M., Walker M. M., Thomas P. H., Baron J. H., Misiewicz J. J. Eradication of Helicobacter pylori with clarithromycin and omeprazole. Gut. 1994 Mar;35(3):323–326. doi: 10.1136/gut.35.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Newell D. G., Hudson M. J., Baskerville A. Naturally occurring gastritis associated with Campylobacter pylori infection in the rhesus monkey. Lancet. 1987 Dec 5;2(8571):1338–1338. doi: 10.1016/s0140-6736(87)91236-0. [DOI] [PubMed] [Google Scholar]
  38. Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
  39. Otto G., Fox J. G., Wu P. Y., Taylor N. S. Eradication of Helicobacter mustelae from the ferret stomach: an animal model of Helicobacter (Campylobacter) pylori chemotherapy. Antimicrob Agents Chemother. 1990 Jun;34(6):1232–1236. doi: 10.1128/aac.34.6.1232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Parsonnet J., Friedman G. D., Vandersteen D. P., Chang Y., Vogelman J. H., Orentreich N., Sibley R. K. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991 Oct 17;325(16):1127–1131. doi: 10.1056/NEJM199110173251603. [DOI] [PubMed] [Google Scholar]
  41. Parsonnet J. The incidence of Helicobacter pylori infection. Aliment Pharmacol Ther. 1995;9 (Suppl 2):45–51. [PubMed] [Google Scholar]
  42. Radin M. J., Eaton K. A., Krakowka S., Morgan D. R., Lee A., Otto G., Fox J. Helicobacter pylori gastric infection in gnotobiotic beagle dogs. Infect Immun. 1990 Aug;58(8):2606–2612. doi: 10.1128/iai.58.8.2606-2612.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sung J. J., Chung S. C., Ling T. K., Yung M. Y., Leung V. K., Ng E. K., Li M. K., Cheng A. F., Li A. K. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995 Jan 19;332(3):139–142. doi: 10.1056/NEJM199501193320302. [DOI] [PubMed] [Google Scholar]
  44. WEBER A. F., HASA O., SAUTTER J. H. Some observations concerning the presence of spirilla in the fundic glands of dogs and cats. Am J Vet Res. 1958 Jul;19(72):677–680. [PubMed] [Google Scholar]
  45. Wotherspoon A. C., Ortiz-Hidalgo C., Falzon M. R., Isaacson P. G. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991 Nov 9;338(8776):1175–1176. doi: 10.1016/0140-6736(91)92035-z. [DOI] [PubMed] [Google Scholar]

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