Helicobacter ISSN 1523-5378 doi: 10.1111/hel.12155

REVIEW ARTICLE

Helicobacter pylori and Public Health Anthony Axon University of Leeds, UK

Keywords gastric cancer, peptic ulcer, prevalence, prevention. Reprint requests to: Anthony Axon, Nidd Park House, Nidd, North Yorkshire HG33BN, UK. E-mail: [email protected]

Abstract Gastric cancer and peptic ulcer between them cause the death of over a million people each year. A number of articles this year have studied changes in the prevalence of the infection in a variety of countries and ethnic groups. They confirm the known risk factors for infection, principally a low standard of living, poor education, and reduced life span. The prevalence of infection in developed countries is falling, but more slowly now than was the case before, meaning that a substantial number of the population will remain infected in the years to come. Reinfection is more common in less developed countries. The incidence of gastric cancer is highest in populations with a high prevalence of infection. Population test and treat is a cost-effective means of preventing gastric cancer. Peptic ulcer is the commonest cause of death in patients undergoing emergency surgery. The alleged risk that treatment may cause some to develop reflux esophagitis remains controversial.

Background

Prevalence of H. pylori

Helicobacter pylori infection is the underlying cause of noncardia gastric cancer, the second commonest cause of death from cancer in the world, it is also responsible for deaths from peptic ulcer. Gastric cancer and peptic ulcer together cause more than a million deaths per year worldwide, it is therefore a serious public health problem. In spite of its being a transmissible infection with a high mortality, no preventive public health measures have been instigated to reduce the burden of Helicobacter infection or to prevent its spread. There are many reasons for this failure. The prevalence of the infection is falling in the developed world, and it is hoped the infection will eventually die out spontaneously. There have been suggestions that infection with H. pylori is “protective” against gastroesophageal reflux disease (GERD), esophageal adenocarcinoma, and possibly some allergic illnesses, so its elimination might cause unexpected problems. No vaccine is available. H. pylori infection is more difficult to cure than it was expected because of the emergence of resistant organisms. The widespread use of antibiotics is generally considered to be undesirable. It is uncertain what the reinfection rate might be in some countries. Public health measures might be unduly expensive.

van Blankenstein et al. [1] studied 1550 randomly selected blood donors from four regions in the southern half of the Netherlands, spread over 5- to 10-year age cohorts. They observed an age-specific decline in the mean seroprevalence of H. pylori from 48% in donors born between 1946 and 1935 to 16% for those born between 1987 and 1977. Their cohorts were limited to the native Dutch population, and their study population comprised volunteer blood donors so the results are not necessarily a true representation of the Dutch population. However, the authors point out that even with their data almost one in six of the young native Dutch population remains H. pylori positive, implying that, without specific intervention, the infection will remain common over the coming decades. Cheung et al. [2] performed an in-depth endoscopic study on 194 mainly aboriginal inhabitants in Arctic Canada. This group has a high prevalence of H. pylori and a three times greater incidence of gastric cancer than the average Canadian population. They completed a clinical interview and gastroscopy with gastric biopsies and concluded that severe inflammation and precancerous lesions of the gastric mucosa were highly prevalent in these native Canadians.

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Peleteiro et al. [3] identified 37 studies addressing the prevalence of H. pylori infection in 22 countries: five American, six Asian, ten European, and one from Australia. The prevalence of H. pylori increased with age, though tailing off in the oldest age-groups in some countries. Most reports provided prevalence estimates with a median age around 20 and 60 years. Considering data from the late 1990s and early 2000s, the prevalence estimates were generally higher among countries in Central/South America. At age 20 years, they ranged from 30% in Argentina to 70% in Mexico; at age 60 years from 70% in Chile to 90% in Mexico and Asia. In 1998, the prevalence was 50% at age 20 years and 70% at age 60 years in the Republic of Korea. Studies conducted in the United States of America yielded a prevalence of around 20% among young adults and 40% at older ages. In general, the prevalence was at least twofold higher in countries with high gastric cancer incidence, both in young adults and in older subjects. Changes leading to a higher socioeconomic status, better hygiene practices and less household overcrowding may have had an important contribution to the decrease in the prevalence of H. pylori infection. However, the cohort effect associated with these changes had become gradually less important in some countries, with consequent stabilization of the prevalence. The authors concluded that among countries with a high prevalence of H. pylori, there was ample scope for reducing its burden through prevention and control although in settings with an already low prevalence, further decline would require a more intensive effort. Portugal has the highest incidence of gastric cancer in Western Europe, Bastos et al. assessed the prevalence of H. pylori in Porto, Northern Portugal in two articles. The first related to adults [4] and the prevalence was 84.2%. The prevalence was lower in the more educated subjects, the difference in prevalence between the levels of education decreased with age, however, from nearly 30% in the youngest to 30 years of age and positive for the 13C-urea breath test. They underwent endoscopic screening and a 1-week clarithromycin-based triple therapy with a 10-day levofloxacin-based triple therapy for those who failed. There was a reduction in H. pylori infection of 79%; re-infection/recrudescence was 1% per personyear. Reduction in gastric atrophy incidence was 77%, but intestinal metaplasia was not significant. Compared with the 5-year period before chemoprevention was instituted, the gastric cancer incidence reduced by 25% and peptic ulcer disease by 67.4%; however, the incidence of esophagitis rose by 6% after treatment and two cases of Barrett’s esophagus were identified. The decline in gastric cancer before the intervention is shown in Fig. 5 but in spite of the conclusion drawn, a consideration of the apparent fall in incidence in the figure before the intervention, suggests that the end result might have occurred without the intervention.

Cost-Effectiveness of Screen and Treat Lansdorp-Vogelaar and Sharp [16] have reviewed ten studies that assessed the cost-effectiveness of H. pylori screen and treat for cancer prevention. All of them found that screening to prevent gastric cancer in the general population costs less than $50,000 per life year gained. This level is a commonly used threshold for cost-effectiveness (although this will depend upon the wealth of the community considering intervention) but not for retreatment of failed eradication. Most studies failed to consider either the broader benefits as well or the potential drawbacks in the widespread use of antibiotics. This is an up-to-date comprehensive analysis of the issues. Areia et al. [17] published a systematic review of the cost-effectiveness of screening for gastric cancer and the surveillance of premalignant lesions. They point out that for gastric cancer prevention, several options can be adopted: H. pylori screening with treatment of positive cases in order to prevent the evolution of normal gastric mucosa to premalignant lesions and to invasive cancer; endoscopic screening for EGC; or endoscopic surveillance of patients with premalignant lesions to allow detection of dysplastic lesions before they pro-

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Figure 4 Age standardized incidence of esophageal adenocarcinoma by calendar period for men.

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Figure 5 Incidence of gastric cancer between 1995 and 2008, correlated with mass eradication of Helicobacter pylori. gastric cancer incidence represented by the solid line for subjects on Matsu Island and by the dotted line for residents of Taiwan. The closed arrow indicates the start of the chemoprevention program in 2004, involving endoscopic screening and H. pylori treatment.

gress to cancer. They stated that although very different models, perspectives, assumptions, and data were used, the benefit of H. pylori eradication was unanimous in that H. pylori serology for endoscopic population screening was cost-effective even for populations with prevalence rates as low as 4.2 per 100,000. Endoscopic surveillance of premalignant gastric lesions, however, has conflicting results.

Conclusion There are few articles in this year’s literature that directly address the desirability of public health interventions to limit H. pylori infection. There has been progress in understanding the prevalence of H. pylori in different communities and the burden of both peptic ulcer and cancer. Issues relating to the cost-effectiveness and desirability of a population “Test and Treat” policy are controversial. Communities that could afford it are inversely related to those that need it most. The cost benefit arising from prevention of peptic ulcer and dyspepsia have been under-researched.

Acknowledgements and Disclosures Competing interests: The authors have no competing interests.

H pylori and Public Health

2 Cheung J, Goodman KJ, Girgis S, Bailey R, Morse J, Fedorak RN, Gerry J, Fagan-Garcia K, Veldhuyzen van Zanten. Disease manifestations of Helicobacter pylori infection in Arctic Canada: using epidemiology to address community concerns. BMJ Open 2014;4:e003689. 3 Peleteiro B, Bastos A, Ferro A, Lunet N. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig Dis Sci 2014; [epub ahead of print] DOI: 10.1007/s10620-014-3063-0. 4 Bastos J, Peleteiro B, Barros R, et al. Sociodemographic determinants of prevalence and incidence of Helicobacter pylori infection in Portuguese adults. Helicobacter 2013;18:413–22. 5 Bastos J, Peleteiro B, Pintoa H, Marinhoc A, Guimar~ aes JT, Ramosa E, La Vecchiae C, Barrosa H, Luneta N. Prevalence, incidence and risk factors for Helicobacter pylori infection in a cohort of Portuguese adolescents (EpiTeen.). Dig Liver Dis 2013;45:290–5. 6 Ueda J, Gosho M, Inui Y, et al. Prevalence of Helicobacter pylori infection by birth year and geographic area in Japan. Helicobacter 2014;19:105–10. 7 Yan TL, Hu QD, Zhang Q, Li YM, Liang TB. National rates of Helicobacter pylori recurrence are significantly and inversely correlated with human development index. Aliment Pharmacol Ther 2013;37:963–8. 8 Ferro A, Peleteiro B, Malvezzi M, Bosetti C, Bertuccio P, Levi F, Negri E, La Vecchia C, Lunet N. Worldwide trends in gastric cancer mortality (1980–2011), with predictions to 2015, and incidence by subtype. Eur J Cancer 2014;50:1330–44. 9 Arnold M, Moore SP, Hassler S, Ellison-Loschmann L, Forman D, Bray F. The burden of stomach cancer in indigenous populations: a systematic review and global assessment. Gut 2014;63:64–71. 10 Stewart B, Khanduri P, McCord C, Ohene-Yeboah M, Uranues S, Rivera SV, Mock C. Global disease burden of conditions requiring emergency surgery. Br J Surg 2014;101:e9–22. 11 Lee YY, Raj SM, Graham DY. Helicobacter pylori infection – A boon or a bane: lessons from studies in a low-prevalence population. Helicobacter 2013;18:338–46. 12 Edgren G, Adami HO, Weiderpass E, Nyr en O. A global assessment of the oesophageal adenocarcinoma epidemic. Gut 2013;62:1406–14. 13 Choi IJ. Current evidence of effects of Helicobacter pylori eradication on prevention of gastric cancer. Korean J Intern Med 2013;28:525–37. 14 Bae SE, Jung HY, Kang J, et al. Effect of Helicobacter pylori eradication on metachronous recurrence after endoscopic resection of gastric neoplasm. Am J Gastroenterol 2014;109:60–7. 15 Lee YC, Chen TH, Chiu HM, Shun CT, Chiang H, Liu TY, Wu MS, Lin JT. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut 2013;62:676–82. 16 Lansdorp-Vogelaar I, Sharp L. Cost-effectiveness of screening and treating Helicobacter pylori for gastric cancer prevention. Best Pract Res Clin Gastroenterol 2013;27:933–47. 17 Areia M, Carvalho R, Cadime AT, Goncalves FR, Dinis-Ribeiro M. Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies. Helicobacter 2013;18:325–37.

References 1 van Blankenstein M, van Vuuren AJ, Looman CW, Ouwendijk M, Kuipers EJ. The prevalence of Helicobacter pylori infection in the Netherlands. Scand J Gastroenterol 2013;48:794–800.

© 2014 John Wiley & Sons Ltd, Helicobacter 19 (Suppl. 1): 68–73

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Helicobacter pylori and public health.

Gastric cancer and peptic ulcer between them cause the death of over a million people each year. A number of articles this year have studied changes i...
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