Received Date: July 04, 2016; Accepted Date: July 15, 2016; Published Date: July 22, 2016
Citation: Akamatsu T, Uehara H, Okamura T, Iwaya Y, Suga T (2016) Screening and Treatment for Helicobacter pylori Infection in Teenagers in Japan. J Gastroint Dig Syst 6:454. doi:10.4172/2161-069X.1000454
Copyright: © 2016 Akamatsu T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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To elucidate the prevalence and effect of H. pylori infection in Japanese teenagers, we underwent an examination and treatment of it in one high school health screening between 2007 and 2015. The study subjects were students ages 16 to 17. Students who tested positive on this screening using urine-based rapid test kits (RUPIRAN®) examination visited Shinshu University Hospital and underwent esophagogastroduodenoscopy (EGD) and were taken biopsy samples to determine their H. pylori status using culture and histology. Cure of H. pylori infections was determined by urea breath test. For 9 years, 4,297 of 4,312 students (99.7%) received a screening examination for H. pylori infection. One hundred and sixty-two of 4,297 students (3.8%) were positive for H. pylori. Ninety-three of these 162 with H. pylori-positive students visited our hospital, and 91 underwent EGD and 78 (85.7%) were confirmed to be H. pylori infected. The most common endoscopic findings for H. pylori infection were nodular gastritis (80.8%) and closed-type atrophic gastritis (61.5%). A scar from duodenal ulcer was recognized in 6 of them (7.7%), and intestinal metaplasia was histologically present in two. All 78 students with H. pylori infection and their parents agreed to receive eradication therapy using regimens according to the susceptibility of H. pylori. Finally, all except 3 were successfully cured of H. pylori infection. Remaining 3 students have not yet been assessed the decision of H. pylori infection. If this procedure were to be introduced into nationwide health screening at Japanese high schools, we calculated that the cost of the prevention of a gastric cancer would be 495,958 yen (4,508.71dollars) for each person. The low rate of prevalence of H. pylori infection in present Japanese teenagers would make it possible to perform the screening examination and treatment for this infection in nationwide health screening of high school students in the way that is practical and feasible.
Helicobacter pylori; Gastric cancer; Teenager; Screening; Eradication; Cost-effectiveness
Helicobacter pylori (H. pylori) infection is etiologically related to several gastric diseases, such as gastritis, gastroduodenal ulcer, gastric cancer, and gastric MALT lymphoma. 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 [2,3] showing that eradication of H. pylori reduces the occurrence of gastric cancer. In 2003, Nozaki et al  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.
The purpose of this study is 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.
Screening and Treatment for H. pylori Infection 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 every year since 2007 [5,6]. All students of the second year in high school were annually examined about the status of H. pylori infection using urine-based rapid test kit (RUPIRUN®, Otsuka Pharmaceutical Co. Tokyo, Japan) . Students were between ages 16 and 17. The study was approved by the Ethics Committee of Shinshu University School of Medicine.
First examination of H. pylori infection
Participation rate of high school students in the first screening examination of H. pylori infection was showed in Table 1. Between 2007 and 2015, 4,297 of 4,312 students (99.7%) received a first screening examination. Positive rate of high school students in the first screening examination of H. pylori infection was showed in Table 2. One hundred and sixty-two of 4,297 students (3.8%) were positive for H. pylori.
|Year||No of Participating students||Participating rate of high school students|
Table 1: Participation rate of high school students in the first screening examination of H. pylori infection.
|Year||No of H. pylori positive students||H. pylori positive rates of High school students|
|Total (Male=77, Female=85)||162/4297||3.80%|
Table 2: Positive rate of high school students in the first screening examination of H. pylori infection.
Further examination for H. pylori infection
The first screening-positive students and their parents were recommended to receive further examination of the status of H. pylori in medical institutions by a school doctor. Ninety-three of 162 students visited Shinshu University Hospital. Ninety-one of them underwent further examination using EGD, but the remaining 2 students declined to undergo EGD. Other 10 students consulted other medical institutions, and the remaining 59 students were no response (Figure 1).
The students who visited to Shinshu University Hospital were performed EGD and taken biopsies (total 8 points) to examine the status of H. pylori infection using culture and immunohistological test with anti-H. pylori polyclonal antibody (DAKO, Carpinteria, CA, USA) after written informed consent. H. pylori infection was deemed to be present if either or both tests were positive, and absent if both tests were negative. Further, results of a urea breath test and a test for serum anti-H. pylori antibody if necessary to confirm the infection.
Positive rate of further examination of H. pylori infection
Positive rate of further examination of H. pylori infection was showed in Table 3. Seventy-eight of 91 students (85.7%) who underwent EGD were infected by H. pylori, and the remaining 13 students were not infected. However, serum anti-H.pylori antibody showed positive in 3 of the 13 students without H. pylori infection.
|H. pylori positive students||78/91 (85.7%)|
|H. pylori negative students||13*/91 (14.3%)|
|Serum and anti-H. pylori antibody showed positive in 3 of 13 students without H. pylori infection|
Table 3: Positive rate of further examination of H. pylori infection (n=91).
Symptoms of the students with H. pylori infection
Symptoms of 78 students with H. pylori infection were showed in Table 4. Abdominal pain was most common symptom (28.2%), however 65.4% of students had no symptom.
|abdominal pain||22 students (28.2%)|
|anemia||5 students (6.4%)|
|abdominal discomfort||2 students (2.6%)|
|appetite loss||1 student (1.3%)|
|heart burn||1 student (1.3%)|
|no symptom||51 students (65.4%)|
Table 4: Symptoms of students with H. pylori infection (n=78).
Endoscopic findings of the students with and without H. pylori infection
Endoscopic findings of 91 students with and without H. pylori infection were showed in Table 5.
|H. pylori positive n=78||H. pylori negative n=13|
|Nodular gastritis||positive||63 (80.8%)||0|
|Atrophic gastritis||non||30 (38.5%)||10|
|Duodenal ulcer (Scar)||6 (7.7%)||0|
|Duodenal erosion||4 (5.1%)||0|
|Gastric ulcer (Scar)||1 (1.1%)||0|
Table 5: Endoscopic findings (n=91). C: Closed type; O: Open type (Kimura-Takemoto classification).
The most common endoscopic appearance was nodular gastritis recognized in 63 of 78 students (80.8%) with H. pylori infection. Endoscopic findings of atrophic gastritis were found in 48 of them (61.5%). The endoscopic degree of atrophic gastritis according to Kimura-Takemoto classification  was the closed type in all 48 students. None had the open type atrophic gastritis which is thought to be advanced atrophic change compared with closed type. A scar from duodenal ulcer was present in 7.7% of the students with H. pylori infection, and duodenal erosion was observed in 5.1%.
On the other hand, normal endoscopic findings were present in 10 of 13 students without H. pylori infection. However, endoscopic findings of open type severe atrophic gastritis were identified in two of the remaining 3 who are 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 3 students were thought to have had H. pylori infection in the past and have rapidly developed atrophic changes caused by H. pylori infection.
Histological findings of biopsy specimen
Inflammatory cell infiltration and focal atrophic changes were recognized in all 78 students with H. pylori infection. Only two students had intestinal metaplasia.
Susceptibility of H. pylori to antibiotics
H. pylori was cultured in 74 of 78 students with H. pylori infection, and not cultured in the remaining 4. The susceptibility of H. pylori to clarithromycin, metronidazole, and amoxicillin was assessed by a modified agar plate dilution method. Clarithromycin resistance was present in 28 of 74 students (37.8%) with H. pylori infection. Metronidazole resistance was present in 27 of them (36.5%), and 22 of them (29.7%) had dual clarithromycin-metronidazole resistance. No amoxicillin resistance was present in any students (Table 6).
Table 6: Susceptibility of H. pylori to antibodies (n=74a). *MIC ≥ 1 μg/ml, **MIC ≥ 16 μg/ml, ***MIC ≥ 1 μg/ml. MIC: Minimal Inhibitory concentration. a: H. pylori were not cultured in other 4 cases.
Outcomes of H. pylori eradication therapy
After informed concent, eradication therapy was performed. Students with H. pylori that were sensitive to clarithromycin received clarithomycin based triple therapy for 7 days. On the other hand, if H. pylori had resistance to clarithromycin, using metronidazole based triple therapy was performed whether or not H. pylori had resistance to metronidazole. The decision of H. pylori was assessed more than 8 weeks after treatment by a urea breath test (UBT).
All 75 students except 3 (96.0%) with H. pylori infection were successfully cured by the first eradication therapy. Other 3 students were cured by the second eradication therapy. Remaining 3 students have not yet been assessed the decision of H. pylori infection.
No remarkable complications related EGD, including taking biopsy specimens, was recognized in any of the 91 students who received EGD.
On the other hand, skin rash was observed in 6 of 78 students (7.7%) who received eradication therapy for H. pylori. Three of them (3.8%) complicated of slightly diarrhea (Table 7). No student was suspended to take medicine of eradication therapy due to adverse events.
|Skin rash||6 students (7.7%)|
|Diarrhoea||3 students (3.8%)|
|Vomiting||1 student (1.3%)|
Table 7: Adverse events (n=78).
We calculated cost of the procedure of H. pylori infection in the nationwide health screening of high school students in Japan. Cost of the examination and treatment of H. pylori infection for each person was shown in Table 8. Cost of the first screening, further examination, and treatment of H. pylori infection was shown in Table 9, and total cost of it was calculated 2,699,994,000 yen ($24,545,400). Expected cost-effectiveness of the prevention of gastric cancer by curing H. pylori infection in teenagers was shown Table 10. The rate of persons with H. pylori infection who will suffer from gastric cancer in their lifetime is 14.8%. This data was calculated using Uemura’s cohort study . The rate of persons who will be prevented against suffering from gastric cancer by curing H. pylori infection in teenagers is 80%. This percentage estimated based on the results of an experiment using an animal model, which have been reported by Nozaki et al . Cost of prevention of gastric cancer for each person was 495,958 yen ($4,508.71). Treating patients with gastric cancer, especially those with advanced disease, is very costly. Furthermore, the curing of H. pylori infection would also prevent other H. pylori related diseases such as gastroduodenal ulcer, gastric MALT lymphoma, and idiopathic thrombocytopenic purpura etc. Therefore, the screening and treatment for H. pylori infection in young people is thought to be useful from the view point of medical economy . If further examination for H. pylori infection were to be performed not by using endoscopy but using UBT or the stool antigen of H. pylori, the total cost of this attempt would be more reduced , especially the cost of further examination of H. pylori infection would become about one fifth.
|1||The first screening examination|
|Cost of a urine-based rapid test kit of H.pylori infection (RUPIRAN®)||700 yen ($6.36)*|
|2||Further examination and treatment for H.pylori infection|
|Costs of endoscopy and taking biopsy samples||14,500 yen ($131.82)*|
|Costs of histopathological examination||10,300 yen ($93.64)*|
|Cost of culture and sensitivity testing||4,100 yen ($37.27)*|
|Change of medicines||6,000 yen ($54.55)*|
|Cost of urea breath test||5,400 yen ($49.09)*|
|Total||40,300 yen ($366.36)*|
Table 8: Cost of the examination and treatment of H. pylori infection for each person. *US dollar is calculated at the rate of 110 yen to the US dollar.
|1||Population of a 1-year generation in the present Japanese teenagers||1,210,000 personsa|
|2||Cost of the first screening examination for H.pylori infection||700 yen ($6.36)* x 1,210,000 = 847,000,000yen ($7,700,000)* (A)|
|3||Positive rate in the first screening examination for H.pylori infection||3.8%b|
|4||The number of students who required the further examination for H.pylori infection||1,210,000 persons x 0.038 = 45,980 persons|
|5||Cost of further examination and treatment of H.pylori infection||40,300yen × 45,980 = 1,852,994,000 yen ($16,845,400)* (B)|
|Total cost (A+B) 2,699,994,000 yen ($ 24,545,400)* per year|
Table 9: Cost of the first screening, further examination and treatment of H. pylori infection in the nationwide health screening of high school standards. *US dollar is calculated at the rate of 110 yen to the dollar. a. Current data of the Statistics Bureau in the Ministry of Public Management, Home Affairs, Posts and Telecommunications. b. Our data in the present study.
|1||The rate of persons with H.pylori infection who will suffer from gastric cancer in their timeline||14.8%a|
|2||The number of persons with H.pylori infection who will suffer from gastric cancer in their timeline||45,980 persons x 0.148 = 6,805 persons|
|3||The rate of persons who will be prevented against suffering from gastric cancer by curing H.pylori infection in teenagers||80%b|
|4||The number of persons who will be prevented against suffering from gastric cancer by curing H.pylori infection in teenagers||6,805 persons x 0.8 = 5,444 persons|
|5||Cost of prevention of gastric cancer for each person||Total cost (A+B)c /5,444 = 495,958yen ($4,508.71)*|
Table 10: Expected cost-effectiveness of the prevention of gastric cancer by curing H. pylori infection in teenagers. *US dollar is calculated at the rate of 110 yen to the dollar. a. See the test. b. See the test. c. See the Table 9.
Problems about children are different in each country. In Japan, the most serious problem is decreasing childbirth and reducing a population of children. Our country will become a super-aging society in the near future. Furthermore, total Japanese population is suspected to decrease. Gastric cancer is the most common malignant neoplasms in Japan, and about 50,000 persons die of this disease in per year. It is well known that a significant relationship is recognized between gastric cancer and H. pylori infection in East Asia. We believe that eradication therapy for H. pylori in young people is very effective to prevent the occurrence of gastric cancer, and to reduce the decreasing tendency of Japanese population. On the other hand, H. pylori infection is not so significant risk of gastric cancer in many countries except East Asia. However, gastroduodenal ulcer related H. pylori infection is an important problem in the worldwide, especially children in the developing countries sometimes die of a perforation and massive bleeding due to gastroduodenal ulcer.
From these reasons, we think that screening to identify and eradicate H. pylori infection in young people in worldwide is useful to prevent several diseases, and can reduce the number of death due to them such as gastric cancer and gastroduodenal ulcer.
This study has been performed in only one Japanese high school. We should expand this attempt in more other schools in the future. Furthermore, the cost of this attempt is not calculated including personnel expenses.
The low rate of prevalence of H. pylori infection in present Japanese teenagers would make it possible to perform the screening examination and treatment for this infection in nationwide health screening of high school students in the way that is practical and feasible.