Important Recommendations Regarding the Test-and-Treat Strategy for Helicobacter pylori Infection in Children

Abstract

Helicobacter pylori is a commonly encountered pathogen in medical practice. It causes chronic gastritis in patients of different ages. Many published papers have provided different opinions on whether the test-and-treat strategy for H. pylori infection should be implemented in children. It is critical that the opinion in favor of this strategy was published in Europe, where ESPGHAN/NASPGHAN guidelines have not recommended the use of test-and-treat strategy for H. pylori in children. Herein, I propose my opinion regarding this debate using 4 main points. First, this strategy should be implemented in areas where its benefits outweigh the associated risks. Thus, if it is not tailored to the locality, the results of the test-and-treat strategy for H. pylori in children may be erroneous. Second, the association between H. pylori infection and other diseases such as asthma and other allergic diseases should not be factored in when considering the test-and-treat strategy. This is because these diseases are associated with H. pylori noninfection and not with its posteradication status. Third, there is evidence that H. pylori infection can significantly alter children’s intestinal microbiota. Finally, gastroscopy should not be performed in all H. pylori-positive children, particularly if the drug susceptibility test is not available. In the near future, it will be possible to easily conduct drug susceptibility tests for H. pylori using fecal samples. I believe that this report may expand the test-and-treat strategy for children infected with asymptomatic H. pylori outside of Japan and prevent not only gastric cancer but also minor diseases such as iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, and failure to thrive. Pediatricians are responsible for keeping children healthy not only during childhood but also in adulthood. Thus, even if there are only a few H. pylori-related diseases and no severe cases in children, it is necessary to take early measures to prevent problems (eg, incidence of gastric cancer) in adulthood.

• What do we already know about this topic?

• The ESPGHAN/NASPGHAN guidelines for the management of Helicobacter pylori infections employ a restrictive approach in the test-and-treat strategy for H. pylori compared with the adult guidelines.

• How does your research contribute to the field?

• This report recommends the use of test-and-treat strategies for H. pylori-infected children in Europe and the United States, where gastric cancer rates are low, as well as in Japan, where gastric cancer rates are high.

• What are your research’s implications toward theory, practice, or policy?

• This report aimed to expand the test-and-treat strategy for children infected with asymptomatic H. pylori outside of Japan and prevent not only gastric cancer but also minor diseases such as iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, and failure to thrive.

Dear Editor:

I have read the review by Manfredi et al ¹ with great interest, which suggested that treatment should not necessarily be ruled out for Helicobacter pylori (H. pylori)-infected children with no alarming signs, considering its possible association with ongoing infection, despite them being clinically paucisymptomatic or asymptomatic. I completely agree with the opinion that treating Western children with H. pylori infection, despite them having a low risk of developing H. pylori-related gastric cancer, could prevent the onset of certain related minor diseases, such as iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, and failure to thrive. The test-and-treat strategy for H. pylori in children and adolescents has been reported mainly in Japan. ² Since 2016, I have been implementing the test-and-treat program for H. pylori among third-year junior high school students in Saga Prefecture. ³ However, the pediatric guidelines from many learned societies on the management of H. pylori in children recommend the non-use of the test-and-treat strategy for H. pylori.^4,5 Similarly, Ravikumara ⁶ suggested that H. pylori eradication therapy should be administered in children with peptic ulcer disease but not in every child with H. pylori positivity. It is critical that Manfredi et al ’s study ¹ was published in Europe where ESPGHAN/NASPGHAN guidelines do not recommended the use of the test-and-treat strategy for H. pylori in children. Herein, I would like to emphasize 4 opinions from the standpoint of recommending the test-and-treat strategy for H. pylori in children.

First, in East Asian countries such as Japan, China, and South Korea, the incidence of gastric cancer is extremely high, unlike its low incidence mainly in Oceania, Europe, and the United States. ⁷ The lifetime incidence of gastric cancer in Japan is as high as 12.5%, which is considerably higher than that in Europe and the United States.^6,8 The test-and-treat strategy for H. pylori in children will be erroneous if it is not tailored to the locality. According to the pediatric guideline, in areas with a high prevalence of gastric cancer such as China or Japan, the benefits of treatment in reducing the risk of gastric cancer development may outweigh the risks of treatment. As the authors indicated, in addition to the prevention of serious gastric cancer, it is critical to consider the possibility of prevention of mild diseases such as iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, and failure to thrive. The pros and cons of the test-and-treat strategy for H. pylori from this viewpoint remain controversial; thus, the points described by the authors are pertinent.

Second, the authors discussed the relationship of H. pylori with asthma, allergic diseases, and gastroesophageal reflux disease. The increased incidence of these diseases was associated with H. pylori noninfection. The relationship between the prevalence of these diseases and the status after eradication of H. pylori has not been described. H. pylori noninfection and H. pylori eradication states are distinct in pathology; thus, they should not be discussed in a similar approach. It remains unclear whether diseases that involve H. pylori infection as a predisposing factor are disadvantaged after H. pylori eradication. To the best of our knowledge, only one study on inflammatory bowel disease showed increased mortality after H. pylori eradication therapy. ⁹

Third, we analyzed the effects of H. pylori infection on the intestinal microbiota of children. ¹⁰ This study included 80 H. pylori-infected and 79 noninfected 15-year-old adolescents. No significant differences were observed in sex, age, and body mass index between the 2 groups. Intestinal microbiota samples were collected from feces. The H. pylori-infected group had a significantly higher prevalence of the Prevotella genus than the noninfected group (P < .01). This finding is consistent with that reported by the authors. We speculate that this increase in the prevalence of Prevotella genus is associated with the increase in body mass index and glucose intolerance.^10,11

Fourth, we completely agree with the author’s opinion that gastroscopy should not be performed in all H. pylori-positive children, particularly if the drug susceptibility test is not available. Even in Japan, where the incidence of gastric cancer is high, the incidence of gastric cancer among children aged <15 years is almost zero. ¹² In Japan, H. pylori-infected adults are obligated to undergo gastroscopy under health insurance treatment, including the meaning of early gastric cancer detection. ¹³ To detect gastric cancer early, gastroscopy is not required alongside testing and treatment. We developed a new reagent for evaluating H. pylori genes and clarithromycin (CAM) resistance mutations using stool samples; it was developed as a dedicated reagent for Smart Gene™ point-of-care testing kit. ¹⁴ Using our developed equipment and reagents, even at the clinic level, H. pylori CAM resistance can be measured without requiring special skills, which can be a robust method for H. pylori eradication therapy. From the perspective of the need for drug susceptibility testing, gastroscopy may become unnecessary in the future.

Nevertheless, the test-and-treat strategy for pediatric H. pylori has certain side effects. Although the side effects might be tolerated by patients with H. pylori infection with peptic ulcer disease, it is inevitable that more scrutiny should be placed on side effects when eradicating H. pylori in asymptomatic infected children. Although no conclusion has been drawn regarding the safety of pediatric H. pylori eradication therapy, some reports have indicated that it is highly safe. ¹⁵ With regard to the safety of pediatric H. pylori eradication therapy, more cases must be accumulated in the future. There is also a lack of data regarding reinfection after H. pylori eradication in children.

In conclusion, the findings of this report provide evidence regarding the expansion of the test-and-treat strategy for children infected with asymptomatic H. pylori outside of Japan, which may prevent not only gastric cancer but also minor diseases such as iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, and failure to thrive. Pediatricians are responsible for keeping children healthy not only during childhood but also in adulthood. Thus, although there may be only a few H. pylori-related diseases and no severe cases in children, it is necessary to take early measures to prevent problems (eg, incidence of gastric cancer) in adulthood.