In 1984 a curved bacillus living in the stomach of patients with gastritis and peptic ulceration was discovered and isolated. This organism named as Helicobacter Pylori (HP), has been shown to play a major role in the causation of duodenal ulcers. Persistence of helicobacter pylori has been partly attributed to re-infection of the stomach, especially where sanitary conditions are poor. Recent developments in the field of duodenal ulcer therapy have raised the hopes that this therapeutic hurdle can now be overcome by an alternative approach.peer-reviewe

Pullicino, Edgar

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Maltese Medical Journal 4 Volume VII Issue I 1995 GUEST EDITORIALS ERADICATION OF GASTRIC HELICOBACTER PYLORI: ARE WE GETTING THERE? E. Pullicino In 1984 Marshall and Warren discovered and isolated a curved bacillus living in the stomach of patients with gastritis and peptic ulceration I. Subsequent workers2 demonstrated that they could induce persistent gastritis by ingesting the bacillus which had been up till then regarded as a commensal living in areas of gastric mucosal damage. Over the following decade, this organism named as Helicobacter Pylori (HP), has been shown to play a major role in the causation of duodenal ulcers. Benign ulcers appearing in stomachs which have not been exposed to non­steroidal anti-inflammatory drugs have also been strongly associated with gastric HP colonisation. HP has also been implicated in the aetiology of non-ulcer dyspepsia, gastric carcinoma and primary gastric lymphoma. Amongst these diseases, the most challenging problem in the last decade has been that of duodenal ulcer recurrence after initial healing by modern H2 Blocker drugs such as Ranitidine. This phenomenon is now largely attributed to coexisting colonisation of the stomach by H p3. The incidence of duodenal ulcer recurrence can be dramatically reduced if co-existing HP is successfully eradicated4. The recent consensus that HP-associated duodenal ulcer should be treated by HP eradication will probably be extended to HP-associated gastric ulcer in the near future. However, the potential benefit of eradication of HP in populations at high risk of gastric cancer has not yet been properly addressed. This spiral-shaped gram-negative rod has carved out for itself a unique ecological niche in or near the un stirred mucous layer lining the gastric surface and pits. This remarkable evolution has been achieved by acquiring the capacity to buffer lethal gastric acid with ammonia (produced in the bacillus by the action of urease on urea)5. Although the ecology of the organism has not yet been studied in detail, many publications have much greater acid-producing aCtIVIty in the gastric body suggests that mechanisms protecting HP against attack by gastric acid are not yet completely evolved. Colonisation of the gastric antrum stimulates the antral "G" cells to release an enterohormone called gastrin which in turn leads to excess production of acid by the gastric parietal cells. This hyperchlorhydria is believed to be one of the mechanisms by which H P produces duodenal ulceration. Hyperchlorhydria causes m:eas of gastric metaplasia7 to appear in the duodenum which are soon colonised by more HP organisms. This VICIOUS circle can be broken by administering antimicrobials selected on the basis of invitro sensitivities of the organism and on their ability to heal HP-associated gastritis. Because of the ease with which resistant strains of HP emerge, triple therapy (bismuth subcitrate, amoxycillin and metronidazole) continues to be the most popular regimen. Endoscopic studies of DU patients using multiple gastric biopsies have shown that DU healing and short term eradication can be achieved in over 85% of patients8. In such patients, the incidence of recurrence of HP in repeat gastric biopsies one year later is typically 50% 9,10. Duodenal ulcer recurrences are confined almost exclusively to those patients in whom HP persists in the gastric mucosal I. Persistence of HP, with its attendant risks of chronic duodenal ulcer, has been partly attributed to reinfection of the stomach. This is possible especially where sanitary conditions are poorl2 , Edgar Pullicino MD, DCH, MRCP, PhD Consultant in Gastroenterology and Clinical Nutrition St Luke's Hospital, G'Mangia shown that HP establishes itself in the gastric Lecturer in Physiology antrum in preference to the gastric body6. The Univerisity ofMalta Maltese Medical Journal 5 Volume VII Issue I 1995 m overcrowded areas!3, in paediatric institutions 14, and in endoscopy units if equipment is not adequately decontaminated. However, most failures of eradication of HP infections are thought to be due to incomplete antimicrobial action. This may result from poor drug compliance or from primary drug resistance. The large number of tablets prescribed in the triple therapy regimen increases the frequency of side effects and reduces compliance. Primary resistance to one or more of the antibiotics may precede the treatment especially in females who were prescribed metronidazole previously for pelvic inflammatory disease. The efficacy of these antibiotics is likely to be limited by the fact that key metabolic pathways in the bacterium that could be targeted by antimicrobials have not yet been elucidated in detail. In addition to its habitat in the gastric mucous, HP has been found inside gastric mucosal cells15 . This could further decrease its susceptibil'ty to antibiotics. Recent developments in the field of duodenal ulcer therapy have raised the· hopes that this therapeutic hurdle can now be overcome by an alternative approach. There have been several recent trials l6 • 17 in which a single antimicrobial (amoxycillin up to 3 grams daily) was combined with a potent gastric acid suppressor (Omeprazole up to 60 mg daily). These regimens achieved eradication rates of 80 to 90% which are similar to those obtained using triple antibiotic therapy. It is logical to postulate that an organism which has specialised and evolved in such a way as to flourish in acid conditions will fare badly when these conditions are suddenly removed by potent acid suppression. Indeed the addition of Omeprazole drastically reduces the minimum inhibitory concentration of amoxycillin on HP in vivo. It has been suggested that when acid is suddenly abolished much of the ammonia References: 1. 	 Marshall BI, Warren IR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984; 1:1311 2. 	 Morris AI, Ali MR, Nicholson GI. Long­term follow-up of self ingestion of Helicobacter pylori. Ann Intern Med 1991; 114; 662 3. 	 Lambert JR, Borromeo M, Konnan G. Campylobacter pylori and recurrence of duodenal ulcers: a 12-month follow up. Lancet 1987; 2: 1109-11 it produces accumulates intracellularly as this remains unbufferred; the organism dying in a suicidal act of self poisoning! Hopes of effective long term eradication have been raised by a recent report of a pilot study 18 of a seven-day regimen which combines Omeprazole (20 mg daily), low dose Clarithromycin (250 mg twice daily) and Tinidazole (500 mg twice daily). Clarithromycin is the only antimicrobial effective against HP in vivo when used as a single agent. This is the first regimen to achieve 100% eradication of H Pylori. If these exciting results are reproduced by further studies in the course of 1995, a decade of research into HP behaviour will have resulted in a potent tool for its eradication. This anticipated breakthrough will hopefully be complemented in the future by the development of an oral vaccine which will enable large-scale immunisation of children in endemic areas with the aim of reducing the incidence of carcinoma of the stomach in adulthood l9 . Effective immunisation has already been achieved in mice against murine strains of Helicobacter by prior oral administration of disrupted whole cells of these organisms20 . Notwithstanding his ingenuity and his successes in combating this unusual organism, man must remain vigilant, respecting this microbe's ability to adapt to the changing habitat of the stomach with relative ease. Already there are theoretical fears that the organism may assume coccoid forms similar to those found in drinking water, so as to survive in adverse conditions. Hopes of universal eradication of gastric HP, cannot be considered before the ecology of this organism has been further elucidated. 4. 	 Raws EAI, Tytgat GNI. Eradication of Helicobacter pylori cures duodenal ulcer disease. Lancet 1990; 1: 1233-5 5. 	 Hazell SL, Borody TJ, Gal A. Campylobacter pyloridis 1: Detection of urease as a marker of bacterial colonisation and gastritis. Am J Gastroenterol 1987; 82: 200 6. 	 Satoh K, Kimura K, Yoshida Y. A topographical relationship between H Pylori and gastritis. Quantitative assessments of H Pylori in the gastric mucosa. Am J Gastroenterol 1991; 86; 285 -91 Maltese Medical Journal 6 Volume VII Issue I 1995 7. 	 Wyatt 11, Ratbone Bl, Sobala G. The prevalence and distribution of gastric epithelium in the duodenum and its relationship to H Pylori and inflammation. 1 Clin Pathol 1990; 43: 981-6 8. 	 Biancho Porro G, Parente F, Lazzaroni M. Short and long term outcome of Helicobacter pylori positive resistant duodenal ulcers treated with colloidal bismuth subcitrate plus antibiotics or sucralphate alone. Gut 1993; 34:466-469 9. 	 Grigorjev PYA, Aruin U , Isakov V A. De­Nol plus oxacillin vs ranitidine and oxacillin in HP-posItive duodenal ulcers: effects on relapse. Rev Esp Enfirm Dig 1990; 78 Suppl 1: 122-3. 10. 	 Hentschel E, Brandstatter E, Dragosics B. Effect of Ranitidine and amoxycillin pius metronidazole on the eradication of H Pylori and the recurrence of duodenal ulcer. N Engl J Med 1993; 328: 308-12. 11. 	 George L, Hyland L, Morgan A. Smoking does not contribute to duodenal ulcer relapse after eradication. Gastroenterlogy 1990: 98; A48. 12. 	 Mendall MA, Goggin PM, Molineaux N et al. Childhood living conditions and H Pylori seropositivity in adult life Lancet 1992; 339: 896-7. 13. 	 Baker OP1, Coggon 0, Osmond C, Wickham C. Poor housing in childhood and high rates of stomach cancer. Br 1 Cancer 1990; 61: 575-8. 14. 	 Vincent P, Gotrand F, Pcrnes P , High prevalence of H Pylori infection in cohabiting children. Epidemiology of a cluster with special emphasis on molecular typing. Gut 1994; 35: 313 - 316 15. 	 Chan WY, Hui PK, Leung KM, Thomas TMM. Modes of Helicobacter colonisation and gastric epithelial damage. Histopathology 1992: 102; 1557-67. 16. 	 Labenz J, Ruhl GH, Bertrams .1, Borsch G et al. Amoxycillin plus Omeprazole versus triple therapy for eradication of H Pylori in duodenal ulcer disease: a prospective randomised and controlled study, Gut 1993: 34: 1167-70 17. 	 Labenz ], Gyenes E, Ruhl GH, Borsch G. Amoxycillin - Omeprazote treatment for eradication of H Pylori Eur J Gastroenetrol Hepatol 1991; J: Suppl 1: SI O. 18. 	 Bazzoli F, Zagari RM, Fossi S. Efficacy and tolerability of short term , low dose triple therapy for eradication of H Pvlori. Gastroeneterology 1993; 104: A40. 19. 	 Chen MH, Lee A, Hazell S. Immunisation against gastric infection with Helicobacter species: first step in the prophylaxis of gastric cancer? Zbl Bakt (Int ] Med Microbiol) 1993; 280: 155-65. 20. 	 Czinn Sl, Nedrud lG. Oral administration against H Pylori. Infect Immun 1991; 59: 2359-63 The copyright of this article belongs to the Editorial Board of the Malta Medical Journal. The Malta Medical Journal’s rights in respect of this work are as defined by the Copyright Act (Chapter 415) of the Laws of Malta or as modified by any successive legislation. Users may access this full-text article and can make use of the information contained in accordance with the Copyright Act provided that the author must be properly acknowledged.  Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder. This article has been reproduced with the authorization of the editor of the Malta Medical Journal (Ref. No 000001)  

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Eradication of gastric Helicobacter Pylori : are we getting there?

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Eradication of gastric Helicobacter Pylori : are we getting there?

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