ABSTRACT
Helicobacter pylori (H. pylori) has expanded to infect about half the world’s population. Although there were many studies on the prevalence of H. pylori infection for defined areas in the 1990s throughout the world, there were only limited sources tracking its latest prevalence among large populations. In the present study, we estimated the prevalence of H. pylori among the inhabitants of Nagoya, an urban area of Japan. Study subjects were 5,167 participants (1,467 males and 3,700 females) aged 35 to 69 years from the Daiko Study, a part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). A urinary anti-H. pylori antibody was used to detect H. pylori infection. The history of eradication treatments for H. pylori infection was obtained using self-administered questionnaires. The prevalence detected by the urinary test included 19.6% (95% confidence interval; 16.8–22.6%) for those aged 35–39 years, 25.8% (23.5–28.2%) for 40–49 years, 39.4% (36.8–42.1%) for 50–59 years, 50.3% (47.8–52.7%) for 60–69 years, and 36.4% (35.1–37.7%). Among 5,167 participants, 266 (5.1%) stated that they had received an eradication treatment. Since 167 subjects with negative urinary tests replied that they had been seropositive for H. pylori in the past, they were included among the ever-infected inhabitant group. Consequently, the overall rate of those with a history of persistent infection was 39.6% (38.3–40.9%). The prevalence of H. pylori infection observed in Nagoya seemed to be lower than the corresponding prevalence reported in other studies of Japan. That lower rate might be due to the reduced exposure from improved urban sanitary conditions.
Key Words: Helicobacter pylori, Prevalence, Eradication, Nagoya
INTRODUCTION
Helicobacter pylori (H. pylori) is a Gram-negative bacterium colonizing human gastric mucosa identified by Marshall et al. in 1983, which increases the risk of gastric diseases, including stomach cancer.1,2) The infection rate has been estimated to cover half of the world’s population.3,4) The infection rate in Japan has been reported to be higher than that in other industrialized countries, but lower than that in developing countries.5) The gastric cancer incidence was higher in Japan because the strains of East Asian CagA are so dominant.6,7) Persistent H. pylori infection also causes ulcers, atrophic gastritis, mucosa-associated lymphoid tissue lymphoma, and intestinal metaplasia.8-11)
It is well known that H. pylori is transmitted from person to person through oral-oral or fecal-oral routes during childhood, and the infection lasts for decades unless the bacterium is eradicated.12,13) Though infection among adults is possible, it is highly limited.14,15) Factors directly affecting possible transmission routes, such as sewage systems, are considered among the essential environmental components of prevalence. Although the mechanism has not been clarified, lifestyle factors such as salty food intake,16) low intake of fruits,17) and smoking,18-21) might play important roles in persistence of the infection.
Although several studies have reported the prevalence of H. pylori infection in different areas of Japan in the 1990s, they were mainly restricted to rural areas.22-24) This study aimed to investigate the recent prevalence among the inhabitants of Nagoya (an urban area of Japan) in 2008–2010. Past eradication treatments were examined to estimate the influence on those ever-infected. The ethics committee of the Nagoya University School of Medicine approved the present study protocol (approval number 618).
SUBJECTS AND METHODS
Subjects
Subjects were 5,167 participants (1,467 males and 3,700 females) aged 35 to 69 years as reported in the Daiko Study, a part of the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).25,26) The participants were enrolled at the Daiko Medical Center from June, 2008 to May, 2010. All participants have provided a written informed consent form and completed a questionnaire on their lifestyles, including a history of H. pylori test and/or eradication treatments. Four who withdrew from this study, and one without a urine sample for the detection of anti-H. pylori antibody, were excluded. An antibody-kit for urine, Rapiran (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was used to detect persistent H. pylori infections.
Statistical analysis
Confidence intervals (CIs) of proportion were estimated based on a binominal distribution. Differences in the proportion between two groups were examined using a chi-square test. Differences in mean were examined with a Student’s t-test. The age-standardized rates were calculated based on the distribution of all subjects of this study. The odds ratios (ORs) were estimated through a logistic regression model. A Stata MP/11 (Stata Corp., College Station, TX, USA) was used for the calculations.
RESULTS
Table 1 shows the characteristics of the study subjects. They were 1,467 males (28.4%) and 3,700 females (71.6%) in total 5,167. Among them, those aged 50 years or over accounted for 58.5%. The mean ± standard deviation of age was 53.6 ± 10.3 years in males and 52.2 ± 10.3 years in females. Current smokers were 24.1% in males and 6.9% in females, while current drinkers were 74.9% and 45.9%, respectively. Among 5,167 subjects, 487 (9.4%) replied that they had a history of a H. pylori test, 325 (6.3%) were found to be positive, and 171 (3.3%) were successfully treated. Three did not reply to any queries regarding H. pylori. Eleven failed to specify “yes” for “past tests for H. pylori,” but replied to “results of past tests.” Although five did not reply to “results of past tests,” one of them answered the question on “eradication treatments.” In addition, four males replied that their “eradication treatments” had succeeded, though they forgot the “results of past tests” or stated it to be negative. One subject with a past positive result did not reply to the question about “eradication treatments.” Since 24 (0.5%) of 5,167 subjects had inconsistent responses to questions regarding H. pylori, those with negative urinary tests were regarded as being negative.
Table 1.
Characteristics of subjects
| Characteristics | Male n=1,467 |
Female n=3,700 |
Total n=5,167 |
||||
|---|---|---|---|---|---|---|---|
| Age (years) | |||||||
| 35–39 | 191 | 571 | 762 | ||||
| 40–49 | 347 | 1,033 | 1,380 | ||||
| 50–59 | 403 | 945 | 1,348 | ||||
| 60–69 | 526 | 1,151 | 1,677 | ||||
| Wards | |||||||
| Central area | 550 | 1,323 | 1,873 | ||||
| Eastern area | 825 | 2,096 | 2,921 | ||||
| Western area | 92 | 281 | 373 | ||||
| Drinking | |||||||
| Current | 1,099 | 1,699 | 2,798 | ||||
| Former | 45 | 60 | 105 | ||||
| Never | 323 | 1,940 | 2,263 | ||||
| Unknown | 0 | 1 | 1 | ||||
| Smoking | |||||||
| Current | 354 | 255 | 609 | ||||
| Former | 639 | 386 | 1,025 | ||||
| Never | 474 | 3,058 | 3,532 | ||||
| Unknown | 0 | 1 | 1 | ||||
| Past tests for H. pylori | |||||||
| No | 1,235 | 3,366 | 4,601 | ||||
| Yes | 188 | 299 | 487 | ||||
| Do not remember | 44 | 32 | 76 | ||||
| Unspecified | 0 | 3 | 3 | ||||
| Results of past tests | |||||||
| Positive | 133 | 192 | (2)a) | 325 | (2)a) | ||
| Negative | 43 | (1)a) | 104 | (8)a) | 147 | (9)a) | |
| Forgotten | 13 | 8 | 21 | ||||
| Unspecified | 0 | 5 | 5 | ||||
| Eradication treatments | |||||||
| No | 19 | 36 | (1)b) | 55 | (1)b) | ||
| Yes: succeeded | 74 | (4)b) | 97 | 171 | (4)b) | ||
| Yes: failed | 19 | 24 | 43 | ||||
| Yes: unknown | 20 | 32 | 52 | ||||
| Do not remember | 4 | 4 | 8 | ||||
| Unspecified | 1 | 0 | 1 | ||||
a) In parentheses are those who did not specify “yes” to the question addressing “past tests for H. pylori.”
b) In parentheses are those who did not specify “positive” to the question addressing “results of past tests.”
The prevalence of persistent H. pylori infection detected by urinary testing according to sex is shown in Table 2, i.e. 19.6% (95% CI; 16.8–22.6%) for those aged 35–39 years, 25.8% (23.5–28.2%) for 40–49 years, 39.4% (36.8–42.1%) for 50–59 years, 50.3% (47.8–52.7%) for 60–69 years, and 36.4% (35.1–37.7%).
Table 2.
Prevalence (%) of H. pylori infection and 95% confidence interval (95% CI) measured with a urinary anti-H. pylori antibody test
| Age | Male | Female | Total | |||||
|---|---|---|---|---|---|---|---|---|
| N | Prevalence (95% CI) | N | Prevalence (95% CI) | N | Prevalence (95% CI) | |||
| 35–39 | 191 | 23.0 (17.3–29.7) | 571 | 18.4 (15.3–21.8) | 762 | 19.6 (16.8–22.6) | ||
| 40–49 | 347 | 25.6 (21.1–30.6) | 1,033 | 25.8 (23.2–28.6) | 1,380 | 25.8 (23.5–28.2) | ||
| 50–59 | 403 | 39.5 (34.7–44.4) | 945 | 39.4 (36.2–42.6) | 1,348 | 39.4 (36.8–42.1) | ||
| 60–69 | 526 | 54.0 (49.6–58.3) | 1,151 | 48.6 (45.6–51.5) | 1,677 | 50.3 (47.8–52.7) | ||
| Total | 1,467 | 39.3 (36.8–41.8) | 3,700 | 35.2 (33.7–36.8) | 5,167 | 36.4 (35.1–37.7) | ||
There were 167 participants with negative urine tests who replied that they had been H. pylori seropositive in the past, 113 of whom replied that they had successful eradication treatments, 27 that they had received eradication treatments with an unknown result, 13 that they had failed their eradication treatments, 11 that they had not had any eradication treatment, and 3 that they had forgotten to get their eradication treatments. Table 3 shows the number of all ever-infected inhabitants according to sex including the above 167 participants; 20.7% (17.9–23.8%) for those aged 35–39 years, 27.6% (25.3–30.0%) for 40–49 years, 43.3% (40.7–46.0%) for 50–59 years, 55.0% (52.6–57.4%) for 60–69 years, and 39.6% (38.3–40.9%). The percentage of ever-infected participants as a whole was higher in males than in females (χ2=15.85, p<0.001).
Table 3.
Proportion of H. pylori ever-infection and 95% confidence interval (CI) measured with a urinary anti-H. pylori antibody test, when 167 subjects were added with negative results replying that they had been seropositive
| Age | Male | Female | Total | |||||
|---|---|---|---|---|---|---|---|---|
| N | Ever-infected (95% CI) | N | Ever-infected (95% CI) | N | Ever-infected (95% CI) | |||
| 35–39 | 191 | 24.6 (18.7–31.3) | 571 | 19.4 (16.3–22.9) | 762 | 20.7 (17.9–23.8) | ||
| 40–49 | 347 | 28.8 (24.1–33.9) | 1,033 | 27.2 (24.5–30.0) | 1,380 | 27.6 (25.3–30.0) | ||
| 50–59 | 403 | 44.2 (39.3–49.2) | 945 | 43.0 (39.8–46.2) | 1,348 | 43.3 (40.7–46.0) | ||
| 60–69 | 526 | 60.6 (56.3–64.8) | 1,151 | 52.5 (49.5–55.4) | 1,677 | 55.0 (52.6–57.4) | ||
| Total | 1,467 | 43.9 (41.3–46.5) | 3,700 | 37.9 (36.3–39.5) | 5,167 | 39.6 (38.3–40.9) | ||
The prevalence of H. pylori was examined among those in the Nagoya area. The central area (the six wards of Atsuta, Higashi, Kita, Mizuho, Naka, and Showa) was downtown, while the eastern area (the five wards of Chikusa, Meito, Midori, Moriyama, and Tenpaku) and the western area (the five wards of Minami, Minato, Nakagawa, Nakamura, and Nishi) were in the suburbs. The age-standardized rate was similar; 40.1% for the central area, 39.3% for the eastern area, and 38.3% for the western area. However, the rate among those aged 35–40 years in the western area (8.3%) was significantly lower (p=0.027) than that in the other areas.
The prevalence according to smoking habit was 39.1% (35.2–43.1%) for smokers, 38.0% (35.0–41.0%) for former smokers, and 35.4% (33.8–37.0%) for never smokers. The age-sex adjusted ORs of H. pylori infection were 1.21 (95% CI; 1.00–1.47, p=0.054) for smokers and 1.00 (0.85–1.18, p=0.976) for former smokers relative to never smokers among the subjects, excluding one without a reply to smoking history (N=5,166). The prevalence according to drinking habit was 35.3% (33.6–37.2%) for drinkers, 41.9% (32.3%–51.9%) for former drinkers, and 37.4% (35.4–39.4%) for never drinkers. The age-sex adjusted ORs of H. pylori infection were 0.95 (0.84–1.08, p=0.436) for drinkers and 1.25 (0.83–1.89, p=0.285) for former drinkers relative to never drinkers among the subjects, excluding one with no reply to drinking history.
DISCUSSION
In 2008–2010, we documented the prevalence of H. pylori infection among the inhabitants of Nagoya, an urban area of Japan. Although the persistent infection detected by the urinary tests was found to be relatively low as a whole (36.4%), that rate rose higher with age. The ever-infected inhabitants with negative urinary tests were 3.2% as a whole. The age-sex adjusted OR of H. pylori infection was marginally significantly higher for smokers relative to never smokers (p=0.054).
Several studies have so far reported the prevalence among the Japanese population in defined areas during periods when eradication treatments were not generally provided. After those uninfected with eradication treatments were added, the prevalence in the present study was lower than those from previous studies (Fig. 1). Even when the year of the survey was taken into account, the reduction was marked. Although the prevalence among smokers (39.1%) was significantly higher than that among never smokers (35.4%), as noted in previous reports,18-21) even such a small difference in the prevalence between smokers and never smokers could not account for the reduced prevalence. Though the influence of a transfer of populations was unknown, it seemed to be limited because the transfer to other areas of groups with high infection rates and/or the transfer to the city of groups with low infection rates were not plausible. Such transfers were regarded as being independent of the infection. Accordingly, the observed lower prevalence might be due to the high prevalence of washing toilet together with the sanitary drainage in Nagoya.
Fig. 1.
Prevalence (%) in different areas of Japan within the survey year obtained from the references22,23)
One limitation of this study was that the sensitivity and specificity of Rapiran26-29) could not be measured directly. According to the document on Rapiran, the sensitivity was 89.6% and the specificity was 93.8%. As for the false-positives and false-negatives in this study, the following information was available. Of 1,879 participants with a positive urinary test, 112 (6.0%) visited the Daiko Medical Center for eradication treatments. Among them, we found that eight (7.1%) were negative both for an urea breath test (UBT) and a serum anti-H. pylori antibody, three (2.7%) were negative for a UBT and positive for a serum anti-H. pylori antibody as a false-positive, one (0.9%) was positive for a UBT and negative for a serum anti-H. pylori antibody, and one (0.9%) was without a UBT but was negative for a serum anti-H. pylori antibody. A total of 12 subjects (10.7% of 112) were determined not to be infected in spite of a positive urinary test when they had participated in the Daiko Study, indicating that the positive predictive value was 89.3%. Accordingly, the possibility of the false-positive should be taken into account. In addition, the false-negative must be similarly considered; 11 subjects who replied that they have been seropositive in the past without eradication treatments were found to be negative when given a urinary test. If the false-positives were similar to the false-negatives, the prevalence estimated in the present study may reflect the actual prevalence.
Although it is expected that the prevalence would be declining hereafter due to eradication treatments and sanitary condition improvements in many areas of the world, surveillance for H. pylori infection might be important for estimating the future risk of H. pylori-related diseases, including gastric cancer in each region. Thus, monitoring the prevalence of H. pylori infection in various regions worldwide would be required.
ACKNOWLEDGMENTS AND DISCLOSURES
This work was supported in part by a Grant-in-Aid for Scientific Research on Special Priority Areas of Cancer from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. The authors are very grateful to Ms. Yoko Mitsuda and Ms. Keiko Shibata for their technical assistance. All authors of the manuscript entitled “Prevalence of Helicobacter pylori infection measured with urinary antibody in an urban area of Japan, 2008–2010” declare that they have no conflict of interest related to the publication of this manuscript.
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