Helicobacter pylori Screening and Eradication in Junior High School Students in Yokosuka, Japan: Prevalence, Eradication Rates, and Challenges.

1
Introduction

Helicobacter pylori
(
H. pylori
) is a gram‐negative bacterium that infects humans and causes various diseases, such as gastroduodenal ulcers, gastric cancer, MALT lymphoma, and immune thrombocytopenia [1, 2]. The global average infection rate among adults between 2015 and 2022 is reported to be 43.9% [3]. Infection rates vary significantly across countries and regions, with high‐prevalence areas such as Jordan (88.6%), Guatemala (83.3%), and Ecuador (85.7%), contrasting with countries like Switzerland (18.9%), Sweden (15.7%), and the United States (17.6%), where prevalence is relatively low [3]. Adult
H. pylori
infection rates are influenced by factors such as urbanization, sanitation, and socioeconomic status, with developing countries generally showing higher prevalence rates than developed nations [3]. Thus, effective control strategies must be tailored to regional conditions.
Building on this global understanding of adult infection patterns, recent attention has turned to adolescents and young adults. Although infection rates among adolescents are generally lower than those in adults and have been declining globally, it is estimated that 31.5% of adolescents worldwide are infected [3].
H. pylori
infection in younger individuals is of particular concern because of the risk of gastric cancer, especially in regions with a high prevalence of gastric cancer. The risk of developing gastric cancer due to
H. pylori
infection varies according to race and region. In Asian regions with a high incidence of gastric cancer, the cumulative lifetime risk of gastric cancer in individuals with chronic
H. pylori
infection is estimated to be 17.0% for men and 7.7% for women [4]. Although eradication therapy has been shown to reduce the risk of gastric cancer [5], early intervention before the progression of intestinal metaplasia is more effective [6]. The Maastricht VI/Florence consensus report recommends targeting individuals aged 20–40 years for test and treat programs, as this approach can efficiently lower their risk of developing gastric cancer and reduce the rate of infection transmission to their children [7, 8]. The effectiveness of test and treat programs for
H. pylori
in individuals in their 30s has been demonstrated in Europe [9]. In contrast, validation for those in their 20s and teenage years remains limited.
In Japan, where the prevalence of gastric cancer is high, with approximately 1.1 million new cases of gastric cancer per year and a 40.0% infection rate of
H. pylori
, efforts to conduct population‐wide
H. pylori
screening among younger individuals have been expanding [10, 11]. Utilizing Japan's compulsory education system and regular health check‐ups at schools, comprehensive
H. pylori
testing for middle and high school students has been implemented in several cities [12, 13, 14, 15, 16]. According to a survey by the Japanese Society for Helicobacter Research, as of 2019, at least 80 municipalities have undertaken similar initiatives [17]. While many of these efforts are led by local governments, infection rates, screening methods, and implementation frameworks vary, necessitating localized programs [7, 8]. While numerous municipalities have implemented such screening programs, most published reports focus on rural areas. Reports specifically examining
H. pylori
screening among adolescents in urban settings remain limited. Urban areas in Japan generally have better water infrastructure, less reliance on well water, and fewer multi‐generational households compared to rural regions, which may influence
H. pylori
infection dynamics.
Against this background, this study evaluates a 3‐year administrative test and treat project targeting young individuals in Yokosuka City, an urban city in Japan. In 2019, Yokosuka City and the local medical association launched a program to screen second‐year junior high school students for
H. pylori
infection. Students who tested positive were administered eradication therapy. The primary aim of this study was to assess the real‐world effectiveness of this municipal
H. pylori
test and treat program in an urban adolescent population. Specifically, we aimed to evaluate (1) the prevalence of
H. pylori
infection, (2) first‐ and second‐line eradication success rates, (3) adverse events associated with therapy, (4) participation and follow‐up rates, and (5) the infection status of household members of infected students. These outcomes may provide insight into the challenges and opportunities in implementing adolescent‐targeted
H. pylori
control strategies in urban areas. In this study, we retrospectively analyzed the project over a 3‐year period to identify challenges and propose potential improvements for enhancing the effectiveness of adolescent screening programs.

2
Materials and Methods
2.1
Study Participants and Screening System
We retrospectively analyzed the results of a population‐based screening program for
H. pylori
conducted between 2019 and 2021 among second‐year junior high school students in Yokosuka City, Kanagawa Prefecture, Japan. Yokosuka City is an urban area near Tokyo with a population of approximately 370,000 people. The screening program used a two‐tiered approach. The initial screening was performed using an ELISA‐based urine antibody test kit (URINELISA; Otsuka Pharmaceutical Co. Ltd.). Students who tested positive for
H. pylori
antibodies were then referred for a secondary urea breath test to confirm the infection. Confirmed cases were subsequently treated with eradication therapy. The screening program is offered annually to all second‐year students enrolled in junior high schools throughout Yokosuka City. Invitations to participate were distributed to parents and eligible students in their respective schools. Students attending public junior high schools (23 schools) who opted to participate provided urine samples between April and June, coinciding with their scheduled school health checkups. Students enrolled in private junior high schools submitted urine samples to designated healthcare facilities or registered medical institutions. All samples were processed by the public health office and tested centrally, and results were mailed to participants. Antibody‐positive students underwent a confirmatory urea breath test and confirmed cases received eradication therapy.

2.2
Eradication Regimen
First‐line eradication therapy consisted of a one‐week triple‐therapy regimen with amoxicillin 750 mg twice daily, clarithromycin 400 mg twice daily, and esomeprazole 20 mg twice daily (PAC). Treatment efficacy was assessed 8 weeks after the completion of therapy using the urea breath test. The second‐line regimen consisted of a one‐week triple‐therapy with amoxicillin 750 mg twice daily, metronidazole 250 mg twice daily, and esomeprazole 20 mg twice daily (PAM). Due to regulatory restrictions on the use of metronidazole in children under 16 years of age in Japan, second‐line therapy was deferred until the participants reached 16 years of age. The side effects associated with eradication therapy were monitored by the participating medical institutions and reported to a public health center.

2.3
Survey for Positive Cases Regarding
H. pylori
Infection Status of Their Relatives
Participants who underwent first‐line eradication therapy were asked to complete a survey regarding the
H. pylori
infection status of blood relatives residing in the same household. The survey inquired about the infection status of siblings, parents, and grandparents, with response options of “infected (or previously infected),” “not infected,” or “unknown/not tested.”

2.4
Data Analysis
We analyzed the data collected by the public health center on the participation rate in this program, screening results, eradication outcomes, reported side effects, and the
H. pylori
infection status of
H. pylori
‐positive students' relatives. Descriptive statistics were calculated for the participation rates in
H. pylori
screening, positive test rates, and eradication success rates by year. Informed consent was obtained from all eligible students and their parents prior to participation in the project. This study was approved by the Ethics Committee of Yokosuka Medical Association (approval no. 202403).

3
Results
3.1
Screening Outcome
Between 2019 and 2021, 9879 junior high school students in Yokosuka City were eligible for
H. pylori
screening (Supplementary Table S1, Figure 1). A total of 6270 students (63.5%) underwent an initial urine antibody test. Of these, 266 (4.2%) tested positive for
H. pylori
antibodies. Subsequently, 231 students completed the confirmatory urea breath test, and 73 (31.6%) were diagnosed as positive. The estimated prevalence of
H. pylori
infection over 3 years was 1.2%. Additionally, information on the
H. pylori
infection status of blood relatives was obtained from 68 of the 73
H. pylori
‐positive students (five did not give valid responses). Among the 68 respondents, 33 (48.5%) reported having at least one
H. pylori
‐positive family member (Table 1). The positivity rates among family members were 23.5% (16/68) for fathers, 26.5% (18/68) for mothers, 4.4% (3/68) for siblings, and 16.2% (11/68) for grandparents. Furthermore, six students (8.8%) reported that none of their family members were infected.

3.2
Eradication Results
All 73 students with a positive urea breath result received first‐line eradication therapy. Three students (4.1%) did not undergo posttreatment eradication assessment with the urea breath test. The success rate of first‐line eradication therapy was 50.7% (37/73) in the intention‐to‐treat (ITT) analysis and 52.9% (37/70) in the per‐protocol (PP) analysis. Of the 33 students in whom first‐line eradication failed, four did not undergo second‐line treatment. Of the remaining 29 students, 24 received second‐line eradication treatment, and five pursued treatments outside the project. Four second‐line treatment recipients did not undergo post‐treatment eradication assessment. The success rate of second‐line eradication was 70.8% (17/24) in the ITT analysis and 85.0% (17/20) in the PP analysis. The overall eradication success rate, combining first‐ and second‐line treatments, was 74.0% (54/73) in the ITT analysis and 94.7% (54/57) in the PP analysis.

3.3
Side Effects
An analysis of side effects was conducted on all 73 students who underwent first‐line eradication therapy and on 23 of the 24 students who received second‐line treatment. Side effects were observed in 20 students (27.0%) who received the first‐line treatment (Table 2). No severe reactions requiring hospitalization were reported. Diarrhea was the most common side effect, occurring in 12 students (16.0%), with 11 cases (92.0%) occurring within 3 days and four cases (33.0%) lasting for 1–2 days. Abdominal pain was the second most common side effect, reported by six students (8.2%). One student discontinued the treatment because of an allergic reaction. Among the 23 students who received second‐line eradication therapy and provided side effect reports, five (22.0%) reported side effects, with diarrhea being the most common, none of which required further treatment.

4
Discussion
In this study, we report the results of
H. pylori
screening and eradication treatment among second‐year junior high school students in Yokosuka City between 2019 and 2021. Leveraging the compulsory education system, this project aimed to mitigate the future incidence of gastric cancer through comprehensive screening and eradication of
H. pylori
. Over 3 years, the screening participation rate was 63.5%, and the prevalence of
H. pylori
was 1.2%, which was lower than that reported in other cities in Japan. The overall eradication rate after the first‐ and second‐line treatments was 94.7%, with the first‐line eradication success rate being particularly low, indicating the need for countermeasures. Despite manageable side effects, eradication therapy has demonstrated an acceptable safety profile. A notable number of students were lost to follow‐up, including those who did not complete the confirmatory testing or post‐eradication assessments, underscoring the need for a more structured program to enhance adherence and follow‐up.
The
H. pylori
prevalence reported in this study averaged 1.2% over 3 years (2019–2021), which was lower than the infection rates reported for the same age group in other Japanese cities. For example, a cohort study in Takatsuki City from 2014 to 2017 found a 2.6% infection rate, while a 2015 study in Akita Prefecture reported a 4.8% infection rate among second‐ and third‐year junior high school students [13, 14]. Generally, the infection rate of
H. pylori
among young people is related to regional sanitary conditions and the infection rate in the parental generation [18, 19]. Yokosuka City is an urban area with relatively good sanitary conditions, which may have contributed to the low prevalence of
H. pylori
. While this study reflects the current situation in urban Japan, further investigation in other urban areas is required to confirm this finding. Additionally, it is important to acknowledge the reported decline in
H. pylori
prevalence among adolescents and adults in Japan. National estimates indicate a decrease from 10.0% among those born in 1985 to 2.7% among those born in 2011 [20]. This suggests that the lower prevalence in Yokosuka City may also reflect this broader temporal trend. Continued surveillance across regions is necessary to track
H. pylori
epidemiology among Japanese adolescents.
In addition, when examining the infection status of the family members of
H. pylori
‐positive students, 48.5% of those surveyed had at least one infected relative, whereas 8.8% reported that all family members were negative. Among relatives, 23.5% of fathers and 26.4% of mothers tested positive. However, as the infection status of many relatives remained unknown, the rate of family transmission appeared lower than previously reported in Japan [21]. To better understand parent‐to‐child transmission risk, it is necessary to assess the infection status of the parents of students who tested negative as well. Infection in children is significantly associated with the presence of infected household members. For example, a study in China found that the infection rate in children was 34.3% when parents were infected, compared to only 13.6% when parents were not [22, 23]. These findings suggest that screening and eradicating
H. pylori
in family members could help prevent intergenerational transmission and highlight the potential utility of implementing family‐based screening and treatment strategies. It is also reported that eradication of
H. pylori
in two or more family members may further reduce the risk of transmission within the household [24]. Systematic evaluation of household contacts―particularly parents and siblings―could facilitate early detection and lower the risk of reinfection. While such an approach requires careful planning and coordination, integrating family‐oriented measures into adolescent screening programs may enhance the long‐term effectiveness of
H. pylori
control efforts.
The first‐line eradication success rate in this study was 50.7%, lower than the success rates reported in similar youth programs in Japan [12, 13, 14]. A study investigating the effectiveness of PAC therapy among 13‐ to 19‐year‐olds reported a 60.0% eradication rate in 2018 [25]. One possible reason for this low eradication rate is rising clarithromycin‐resistant bacteria. Previous studies conducted between 1996 and 2003 on 149 Japanese children aged 1–18 (mean age: 12.6) with
H. pylori
infection found that 34.7% were resistant to clarithromycin [26]. Another study conducted between 2003 and 2007 on 61 children aged 4–18 (mean age: 12.6) reported a resistance rate of 40.7% [27]. It is believed that the rate of clarithromycin resistance among Japanese children has been increasing, which may have contributed to the lower first‐line eradication success rate observed in this study. As this project involved a non‐invasive intervention, we did not collect data on antimicrobial resistance, and therefore the exact resistance rate among the participants remains unknown. Diagnostic methods to detect clarithromycin‐resistant
H. pylori
from stool samples are now under evaluation. Incorporating such testing into school‐based screening programs is valuable for optimizing treatment strategies [28].
Based on the findings of this study, the low eradication rate observed with PAC therapy suggests that alternative first‐line regimens should be considered for adolescents. However, treatment options for
H. pylori
eradication in this population are currently limited in Japan. To date, clinical evidence for
H. pylori
eradication in adolescents remains limited. Randomized controlled trials have compared only two regimens: PAC (proton pump inhibitor, amoxicillin, clarithromycin) and PAM (proton pump inhibitor, amoxicillin, metronidazole) [25]. In addition, cohort studies have reported outcomes for PAC, PAM, and VAC (vonoprazan, amoxicillin, clarithromycin) [12, 13, 14, 15], but robust comparative data are lacking. As in adults, fluoroquinolones and tetracyclines may be effective; however, further research is required. According to the 2024 guidelines from the Japanese Society for Helicobacter Research, PAC, VAC, and PAM therapy are the first‐line options for
H. pylori
treatment in children [29]. Given the high rates of clarithromycin‐resistant bacteria, studies have reported higher eradication rates for PAM therapy than for PAC. However, in Japan, the use of metronidazole is not regulatory approved for children under 16 years of age, which restricts its practical application. Consequently, PAC therapy is often chosen as first‐line treatment for screening and treatment projects for adolescents. Recently, VAC therapy has also shown promising results. A study conducted in the Saga Prefecture reported an 86.8% eradication rate among 15‐year‐olds with
H. pylori
when using VAC therapy [13]. However, vonoprazan has not been approved for
H. pylori
eradication in adolescents owing to the absence of safety data. From a clinical perspective, both metronidazole and vonoprazan are considered safe for use in children [30, 31], and this regulatory restriction presents a significant barrier. Therefore, efforts to review and revise these regulations are warranted in order to expand access to more effective treatment options.
Another possible explanation for the relatively low first‐line eradication rate observed in this study is variability in adherence to therapy. Adherence has been shown to markedly affect treatment success—for example, one pediatric study reported an eradication rate of 89.9% among children with ≥ 90.0% adherence, versus 36.8% in those with lower adherence [32]. This issue is particularly critical in adolescent settings, where factors such as treatment understanding, parental oversight, and side‐effect management may influence compliance. While adherence in adult or clinical trial contexts is generally high, it cannot be assumed in school‐based programs. Therefore, future initiatives should implement systems to monitor and support adherence among adolescents.
In this study, the average participation rate in the first screening round was 63.0%, relatively low compared to the previous similar projects [12, 13, 14, 15]. One possible reason for this is participation barriers. This project aimed to improve participation rates by obtaining a primary screening urine sample on the same day as the mandatory school screening day. However, students had to submit separate samples for school health exams and
H. pylori
screening, which may have lowered participation. In contrast, a program in Akita Prefecture reported a participation rate of 97.3%, as
H. pylori
antibody testing was conducted using urine samples already submitted for mandatory school health examinations, thereby minimizing the burden on students [13]. Furthermore, our program involved students from both public and private schools, potentially increasing background heterogeneity and complicating recruitment efforts. These structural factors likely contributed to the relatively lower participation rate in our study. Therefore, it is important to design a screening system that facilitates participation by incorporating
H. pylori
testing into the existing framework of routine school health examinations. Additionally, in this study, 13.0% (35 students) of the first screening participants who tested positive did not undergo confirmatory testing, and seven students dropped out without undergoing post‐eradication effectiveness evaluation. Low participation rates, along with students not progressing to confirmatory testing or treatment evaluation, are key issues in
H. pylori
screening for junior high school students. This may be partly due to the lack of understanding among students and their guardians regarding the importance of
H. pylori
screening. In fact, a survey of parents of first‐year junior high school students in Yokosuka found that 66.7% of those who did not want their children to be tested for
H. pylori
considered the test unnecessary [33]. Generally, preventive measures against cancer starting in childhood are difficult to understand, leading to low participation rates. Similar to other preventive health interventions targeting adolescents, such as vaccinations, participation in
H. pylori
screening can be influenced by awareness and perceptions of future cancer risk. For example, human papillomavirus (HPV) is a key risk factor for cervical cancer, and HPV vaccination is recommended for its prevention. However, the vaccination rate remains lower than that of other vaccines [34, 35]. Improving awareness and understanding of cancer prevention in adolescents and their guardians is therefore critical [36, 37]. Studies have shown that people with more knowledge about cancer and prior exposure to vaccine recommendations are more likely to accept HPV vaccination [38]. These findings suggest that similar educational approaches may help increase participation in
H. pylori
screening, while improving adherence requires better communication of the importance of childhood cancer prevention.
In this study, the side effects of
H. pylori
eradication were consistent with reports from other junior high school screenings in Japan, with diarrhea being the most common, followed by abdominal pain. Most side effects required no treatment and resolved with observation alone, suggesting that the treatment was safe. These results are consistent with previous reports identifying diarrhea as the most frequent side effect. However, the frequency of side effects varied across regions and regimens: 7.1%–13.3% for Takatsuki city study, and 42.7% for Saga study [12, 14]. These differences may be due to the type of drugs used, but the regional variation suggests the need for further investigation of the causes. In adults, probiotics have been shown to be effective in preventing diarrhea during
H. pylori
eradication [39], and similar findings have been reported in pediatric populations [40]. The 2024 guidelines from the Japanese Society for Helicobacter Research also suggest the potential use of probiotics during eradication therapy; however, the recommendation remains weak due to the low level of supporting evidence [29]. Nonetheless, considering the frequency of diarrhea and abdominal pain observed in this study, and existing reports suggesting their mitigation through probiotic use, co‐administration of probiotics should be considered in future programs [41].
In this study, urine antibody testing was used for the initial screening, but alternative methods merit consideration. Urine antibody testing is minimally invasive and has few barriers to participation, making it the most accessible method when conducted within the framework of school health examinations. In spite of its high sensitivity and low specificity, it is a low‐cost test, making it widely used in many similar programs in Japan [16]. The usefulness of stool and blood tests as primary tests remains to be investigated in the future.
This study has some limitations. First, the sample size is small, and a larger cohort would provide more accurate estimates of the infection and eradication rates. In addition, although the participation rate of 63.0% among eligible students may be considered sufficient for analysis, the voluntary nature of the program may have introduced selection bias. Participants may have been more health‐conscious or had greater parental support than non‐participants. Ideally, broader coverage through more inclusive recruitment would help improve the generalizability of the findings. Second, the study only broadly examined the incidence and severity of side effects. A more detailed investigation of these side effects could provide a better understanding of the health effects of eradication therapy on adolescents. Finally, we did not collect background information on the students, such as gastrointestinal symptoms, previous
H. pylori
infections, or household dietary practices. Inclusion of such data could have helped identify potential risk factors for infection and patterns of household transmission. This remains an important area for future research.

5
Conclusion

H. pylori
infection has a low prevalence among junior high school students in an urban area of Japan, with a modest eradication rate. The current rates of screening participation and program dropout indicate a need for improving the effectiveness of screening.

Conflicts of Interest
The authors declare no conflicts of interest.

Supporting information

Table S1: Participation rates and infection rates for each year.