University of Western Australia, Department of Microbiology, Room 1.11, L Block, Queen Elizabeth II. Medical Centre, NEDLANDS WA 6009, Australia. E-mail:admin{at}hpylori.com.au
I am not certain how I became aware of the paper by Susser and Stein in Lancet of 1962, I suppose it was from references in another article on peptic ulcer.1 It did amaze me that 20 years before the discovery of Helicobacter pylori the idea of a cohort effect in peptic ulcer had been considered, and various predictions made. Although brilliantly correct about an environmental effect peaking near the turn of the century, Susser and Stein still exhibited some of the tunnel vision regarding stress in all its forms as a peptic ulcer aetiology. One of their hypotheses for changes in ulcer mortality involved urbanization stress, its subsequent tolerance by communities and, more recently, increased affluence lowering the global urbanization stress level.
Susser and Stein's first point was that gastric ulcer perforations in young women were a new disease in the beginning of the 19th century, but a peak of the same disease in older women (the same cohort) occurred in the latter half of the 19th century. According to the original authors, the female epidemic related to acute gastric ulcers of the cardia, a disease characterized by lack of scarring at the ulcer base and location in the top half of the stomach. Similar perforation increases, but for duodenal ulcer in young to middle-aged men, and for gastric ulcer in older men, were later reported.
In the 20th century however, most of the interesting ulcer mortality related to pylor-duodenal ulcers, and occurred in men. Gastric ulcer mortality peaked in the early 1950s and duodenal ulcer mortality peaked in the late 1950s. Of secondary interest is the fact that the supposed executive ulcer never really existed in that no socioeconomic gradient existed for duodenal ulcer in the early 20th century, and its actual predilection for the working classes was well documented after 1940.
To explain some of these observations, we might try to place H. pylori into the above scenario. Although it is difficult to determine the prevalence of H. pylori in previous generations, some assumptions can be made based on the observed age-related sero-epidemiology in the US and from biopsy surveys of Estonians and Japanese in the past 50 years.2,3
First, we may assume that H. pylori was ubiquitous at the turn of the 20th century. Faecal-oral contamination of the water supply was present, families were large, children shared beds and in-house piped running water was uncommon so washing was difficult. Thus, most western countries had conditions now only seen in developing countries.
Second, there was a sharp decline in H. pylori after about 1960. According to the seroepidemiology reported in the epidemiologists survey4 and the Kaiser cancer study described by Parsonnet,5 the majority of 40-year-olds had H. pylori in the 1960s but then the prevalence decreased by half every 10 years after that. Similar findings were reported from the Busselton survey in Australia where almost no new cases, and even a slight decrease in infection, was seen between 1970 and 1990.6 Helicobacter pylori declined because of improved hygiene, smaller families and better socioeconomic conditions, but the decline accelerated after 1970. I recall that in 1976 amoxycillin was introduced in Australia and that my children consumed so many antibiotics for ear and throat infections that Helicobacter would have had a very difficult time establishing itself.
Although Sonnenberg7 has considered and discounted a role for aspirin as an explanation of the 19th century ulcer perforation epidemic, my amoxycillin theory has parallels in that era. An example of antibiotic effect on H. pylori was seen in the case of Arthur Morris who infected himself with H. pylori in 1986.8 Initially, Morris developed severe pain lasting 48 hours, almost requiring laparotomy. This must have reflected gastric erosion or ulceration in the presence of acid in the very acute stages of the infection, also described by some others.9 After very severe corpus gastritis developed on day 3, Morris became achlorhydric, without symptoms, for several months. During that time gastric pH remained above 5. Subsequently, Morris treated himself with doxycycline, suppressing but not eradicating the H. pylori. After this, acid secretion returned, although gastritis persisted in the antrum. So it is well documented that an asymptomatic low-acid state can convert to an acid secreting H. pylori infected state, merely by temporary suppression of H. pylori.
Thus, if people in the 19th century were infected with H. pylori in childhood, they would have had rather poor acid secretion and developing country gastric histology. However, after exposure to antibiotic they may have switched to the 20th century pattern of acid secretion in the presence of more localized antral gastritis, much as Morris reported. But did antibiotics exist in the 19th century? At least for H. pylori, the answer is yes. Use of bismuth was first popularized in Germany about 100 years before, mainly as bismuth subnitrate. In England, in 1864, Ogle advocated the use of bismuth subcitrate the fruit acid of bismuth for nervous disorders of the stomach.10 So there is no doubt that suppression of H. pylori was available and, perhaps as another coincidence, would have been especially advocated for young women with nervous stomach. Use of bismuth as a component of gastric medicines and antacids throughout Europe and the US persisted until the present time.
An alternative theory proposed by Blaser11 would contend that the changes are connected in some way to a change in the predominant gastric populations of H. pylori, with pre-20th century people being continuously infected with multiple strains, whereas in recent years single strain infection, with absent virulence genes in many cases has occurred, resulting in changed expression of the disease.
Regardless, once a cohort effect is taken as the basis for changes in age-related prevalence of H. pylori several predictions can be made. First, the incidence is closely reflected by the prevalence in the age group 110 years. In some locations, for example parts of Japan12 and New Zealand,13 the prevalence of H. pylori in children is less than 5% indicating that environmental sources of the infection are now quite rare. We can expect therefore that H. pylori related diseases such as new peptic ulcer and gastric cancer will almost disappear in the next generation.
The epidemiology of gastric cancer is another issue with controversy still raging. As expected, recent prospective studies show that individuals without H. pylori, even in a high-risk population, rarely develop cancer14 and, already, the incidence of gastric cancer in young Japanese is declining.
References
1 Susser M, Stein Z. Civilization and peptic ulcer. Lancet 1962;i:11519.
2 Sipponen P, Helske T, Jarvinen P et al. Fall in the prevalence of chronic gastritis over 15 years: analysis of outpatient series in Finland from 1977, 1985, and 1992. Gut 1994;35:116771.[Abstract]
3 Haruma K, Okamoto S, Kawaguchi H et al. Reduced incidence of Helicobacter pylori infection in young Japanese persons between the 1970s and the 1990s. J Clin Gastroenterol 1997;25:58386.[CrossRef][ISI][Medline]
4 Parsonnet J, Blaser MJ, Perez Perez GI, Hargrett Bean N, Tauxe RV. Symptoms and risk factors of Helicobacter pylori infection in a cohort of epidemiologists. Gastroenterology 1992;102:4146.[ISI][Medline]
5 Parsonnet J, Friedman GD, Vandersteen DP et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991;325: 112731.[Abstract]
6 Cullen DJ, Collins BJ, Christiansen KJ et al. When is Helicobacter pylori infection acquired? Gut 1993;34:168182.[Abstract]
7 Sonnenberg A. A personal history of giving birth to the cohort phenomenon. In: Marshall BJ (ed.). Helicobacter Pioneers. Blackwell Science Asia (in press).
8 Morris AJ, Ali MR, Nicholson GI, Perez-Perez GI, Blaser MJ. Long-term follow-up of voluntary ingestion of Helicobacter pylori. Ann Intern Med 1991;114:8,66263.[ISI][Medline]
9 Graham DY, Alpert LC, Smith JL, Yoshimura HH. Iatrogenic Campylobacter pylori infection is a cause of epidemic achlorhydria. Am J Gastroenterol 1988;83:97480.[ISI][Medline]
10 Ogle JW. Effervescing bismuth water.Br Med J 1864;i:24950.
11
Blaser MJ, Berg DE. Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest 2001;107:76773.
12 Fujisawa T, Kumagai T, Akamatsu T et al. Changes in seroepidemiological pattern of Helicobacter pylori and hepatitis A virus over the last 20 years in Japan. Am J Gastroenterol 1999;94:209499.[CrossRef][ISI][Medline]
13 Fawcett JP, Shaw JP, Brooke M, Walker A, Barbezat GO. Seroprevalence of Helicobacter pylori in a longitudinal study of New Zealanders at ages 11 and 21. Aust N Z J Med 1998;5:58182.
14
Uemura N, Okamoto S, Yamamoto S et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:78489.