The purpose of this study was to elucidate the prevalence and effect of Helicobacter pylori infection in Japanese teenagers. The study subjects were students ages 16 to 17 from one high school studied between 2007 and 2013. Students who tested positive on this screening examination underwent esophagogastroduodenoscopy and biopsy samples to determine their H pylori status using culture and histology. Cure of H pylori infections was determined by urea breath test. The low rate of prevalence of H pylori infection in present Japanese teenagers makes it possible and cost effective to perform examinations and carry out treatment of this infection in nationwide health screenings of high school students.
Key points
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The rate of prevalence of Helibobacter pylori infection in Japanese teenagers is 4% to 5% at present.
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A very high participation rate of screening examination for H pylori infection using urine-based rapid test kit was achieved in high school health screening.
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The most common endoscopic findings for students with H pylori infection are nodular gastritis and closed-type atrophic gastritis.
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If this procedure was introduced nationwide, the cost of the prevention of a gastric cancer would be 481,144 yen ($4184 dollars) per person.
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The low rate of prevalence of H pylori infection makes it possible to perform this nationwide plan from a viewpoint of medical economy.
Introduction
Helicobacter pylori infection is etiologically related to several gastric diseases, such as gastritis, gastroduodenal ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric cancer is one of the common malignant neoplasms in East Asia including Japan, and many people die of gastric cancer each year. Recently, it has been confirmed that H pylori infection is a significant risk factor for gastric cancer epidemiologically, experimentally, and clinically. This has been proved by experiments using animals and also by randomized clinical studies showing that eradication of H pylori reduces the occurrence of gastric cancer. Furthermore, Nozaki and colleagues reported that early stage eradication of H pylori was more effective in reducing the late occurrence of gastric cancer compared with late-stage eradication in animal experimentation. From these data, eradication of H pylori is thought to be beneficial for the prevention of human gastric cancer, and it is more effective to treat H pylori infection in young people compared with old people. Furthermore, H pylori –related diseases, especially complicated gastroduodenal ulcer, which can cause death and emergency operations because of perforation or bleeding, can be prevented by cure of H pylori . Most Japanese experts of H pylori infection agree that H pylori should be treated in young people, but the method of mass screening for H pylori infection and the most suitable age for receiving the treatment remain controversial.
This article presents our attempts at examination and treatment of H pylori infection in high school health screening between 2007 and 2013. The purpose of this study was to collect data regarding the screening for H pylori infection in health screenings in school, and to identify the actual effects of H pylori infection in Japanese teenagers.
Introduction
Helicobacter pylori infection is etiologically related to several gastric diseases, such as gastritis, gastroduodenal ulcer, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric cancer is one of the common malignant neoplasms in East Asia including Japan, and many people die of gastric cancer each year. Recently, it has been confirmed that H pylori infection is a significant risk factor for gastric cancer epidemiologically, experimentally, and clinically. This has been proved by experiments using animals and also by randomized clinical studies showing that eradication of H pylori reduces the occurrence of gastric cancer. Furthermore, Nozaki and colleagues reported that early stage eradication of H pylori was more effective in reducing the late occurrence of gastric cancer compared with late-stage eradication in animal experimentation. From these data, eradication of H pylori is thought to be beneficial for the prevention of human gastric cancer, and it is more effective to treat H pylori infection in young people compared with old people. Furthermore, H pylori –related diseases, especially complicated gastroduodenal ulcer, which can cause death and emergency operations because of perforation or bleeding, can be prevented by cure of H pylori . Most Japanese experts of H pylori infection agree that H pylori should be treated in young people, but the method of mass screening for H pylori infection and the most suitable age for receiving the treatment remain controversial.
This article presents our attempts at examination and treatment of H pylori infection in high school health screening between 2007 and 2013. The purpose of this study was to collect data regarding the screening for H pylori infection in health screenings in school, and to identify the actual effects of H pylori infection in Japanese teenagers.
An examination and treatment of Helicobacter pylori in high school students
We have proposed that a screening for H pylori infection should be introduced into health screenings in school, and have performed this procedure in one Japanese high school since 2007. The study was approved by the Ethics Committee of Shinshu University School of Medicine.
First Screening Examination for Helicobacter pylori Infection
All students of the second year in high school were annually examined about the status of H pylori infection using a urine-based rapid test kit (RUPIRAN; Otsuka Pharmaceutical Co, Tokyo, Japan). Students were between ages 16 and 17. Between 2007 and 2013, a total of 3251 of 3263 students (99.6%) received a first screening examination. One hundred and thirty-six of 3251 students (4.2%) were positive for H pylori ; the remaining 3115 were negative ( Table 1 ). A summary of the results is shown in Fig. 1 .
| Year | Number of Participating Students | Number of Positive Students |
|---|---|---|
| 2007 | 409/414 (98.8%) | 14/409 (3.4%) |
| 2008 | 370/373 (99.2%) | 28/370 (7.6%) |
| 2009 | 445/445 (100%) | 22/445 (4.9%) |
| 2010 | 478/480 (99.6%) | 23/478 (4.8%) |
| 2011 | 400/401 (99.8%) | 12/400 (3.0%) |
| 2012 | 539/539 (100%) | 17/539 (3.2%) |
| 2013 | 610/611 (99.8%) | 20/610 (3.3%) |
| Total | 3251/3263 (99.6%) (M, 1489; F, 1762) | 136/3251 (4.2%) (M, 63; F, 73) |
Further Examination for Helicobacter pylori Infection
Seventy-four of 136 students who were determined to be H pylori –positive visited Shinshu University Hospital. Another 11 consulted other medical institution; the remaining 51 did not accept the invitation to visit a medical institution.
Seventy-two of the 74 students who visited Shinshu University Hospital underwent esophagogastroduodenoscopy (EGD) with sedation using 0.1 mg/kg of midazolam after providing written informed consent; two declined to undergo EGD.
H pylori status was assessed by histology (six sites) and culture (two sites) of biopsy specimens obtained from the antrum and corpus of the stomach. The biopsy samples were stained with hematoxylin and eosin, and immunostained for H pylori with rabbit anti– H pylori polyclonal antibody (DAKO, Carpinteria, CA) if necessary. H pylori infection was deemed to be present if either or both tests were positive, and absent if both tests were negative. Furthermore, the results of a urea breath test (UBT) and a test for serum anti– H pylori antibody using an E-plate (Eiken Chemical, Tochigi, Japan) were examined if necessary to confirm the infection. Sixty of 72 students (83.3%) who underwent EGD were infected by H pylori and 12 (16.7%) were not infected. However, 3 of the 12 students without H pylori infection tested positive for serum anti– H pylori antibody.
Endoscopic Findings
The most common endoscopic appearance was nodular gastritis recognized in 50 of 60 students (83.3%) with H pylori infection ( Table 2 ). Endoscopic findings of atrophic gastritis were found in 36 of these students (60.0%). The endoscopic degree of atrophic gastritis according to Kimura-Takemoto classification was the closed type (C-1:9, C-2:23, C-3:4) in all 36 cases. None had the open type atrophic gastritis. A scar from duodenal ulcer ( Fig. 2 ) was present in 4 of the 60 students (6.7%) with H pylori infection; duodenal erosion ( Fig. 3 ) was observed in another four (6.7%).
| Infected with Helicobacter pylor i (N = 60) | Not Infected with Helicobacter pylori (N = 12) | |
|---|---|---|
| Nodular gastritis | 50 (83.3%) | 0 |
| Atrophic gastritis | 36 (60.0%) (C-I, 9; C-II, 23; C-III, 4) | 3 (25.0%) a (C-II, 1; O-II, 1; O-III, 1) |
| Duodenal erosion | 4 (6.7%) | 0 |
| Duodenal ulcer scar | 4 (6.7%) | 0 |
a Three cases show positive for serum anti– H pylori antibody.
Normal endoscopic findings were present in 9 of the 12 students without H pylori infection. However, endoscopic findings of open-type severe atrophic gastritis (ie, extensive atrophy) were identified in two of the remaining three who were also positive for serum anti– H pylori antibody despite no active H pylori infection. Type A gastritis was ruled out because these students showed negative results for anti–parietal cell antibody and did not have hypergastrinemia. These three students were thought to have had H pylori infection in the past and to have rapidly developed atrophic changes caused by H pylori infection.
Histologic Findings
Inflammatory cell infiltration and focal atrophic changes were recognized in all 60 students with H pylori infection; only two had intestinal metaplasia.
Normal histologic findings were found in 9 of the 12 students without H pylori infection who showed normal endoscopic findings. However, inflammatory cell infiltration and focal to moderate atrophic change was recognized in the remaining three who had endoscopic findings of atrophic change without currently active H pylori infections.
Susceptibility of Helicobacter pylori to Clarithromycin, Metronidazole, and Amoxicillin
The susceptibility of H pylori to clarithromycin (CAM), metronidazole (MNZ), and amoxicillin (AMC) was assessed by a modified agar plate dilution method ( Table 3 ). The minimal inhibitory concentration of a given agent was defined here as the lowest concentration of the agent that was able to inhibit visual growth under the culture concentrations. Strains were considered to be resistant to CAM, MNZ, and AMC when the minimal inhibitory concentrations were equal to or above 1, 16, and 1 μg/mL, respectively.
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