Pediatric Helicobacter pylori Infection

　　1. Etiology

　　1. Pathogenic Bacterium

　　(1) Establishment of the relationship between Hp and gastritis: A large amount of existing data supports that Hp is the pathogenic bacterium of chronic gastritis. Since Hp mainly settles in the gastric mucosa after entering the body, the detection rate of Hp in patients with chronic gastritis is very high, while almost no Hp is detected in normal gastric mucus. In addition, it is found that the number of Hp settled on the gastric mucus is proportional to the number of white blood cells infiltrating the gastric mucosa, and positively correlated with the degree of inflammation. In adults, the main component of gastritis inflammation is neutrophils; while in children, lymphocytes dominate, and the morphological changes of the mucosa under gastroscopy are mainly small nodules and small granules in the antrum mucosa. Macarthur et al. summarized the status of Hp infection in children with gastrointestinal symptoms in 20 articles, and found that the proportion of children with Hp infection who develop antral gastritis is significantly higher than that of children without Hp infection. The lowest is 1.9%, the highest reaches 71.0%, and the average is 11.38%. The study of Ruijin Hospital also found that the infection rate of Hp in children with chronic active gastritis is as high as 96.97%, while it is only 43.56% in non-active chronic gastritis. After Hp is cleared, the inflammation of the gastric mucosal tissue is significantly improved. Moreover, the Hp extracted from the stomach of children has successfully infected the animal model of mice, just like the reports in foreign literature on the artificial infection of Hp (Gnotobiotic pigs, Rhesus monkeys, etc.) to produce gastritis. Hp as a pathogenic bacterium of gastritis has reached the requirements of Koch's postulates. It can be seen that Hp infection is closely related to the occurrence of chronic active gastritis, and is an important pathogenic factor of chronic gastritis.

　　(2) The relationship between Hp and gastric or duodenal ulcers: Although there is no record of volunteers developing ulcers in human trials, nor is there an animal model for this, a large amount of clinical data in adults makes it believed that Hp infection is associated with peptic ulcer disease. The most interesting evidence is that the eradication of Hp changes the natural course of peptic ulcer disease, with the recurrence rate of ulcers one year later decreasing from 80% after the treatment with acid inhibitors to less than 3% after the eradication of Hp. The follow-up of children with peptic ulcer disease for 7 years also showed the same effect. At a special meeting hosted by the National Institutes of Health (NIH) in 1994, it was announced that peptic ulcer disease is an infectious disease, and it was recommended to use antibiotic treatment instead of the previous acid-suppressing treatment.

　　The prevalence of Helicobacter pylori (Hp) infection and gastric or duodenal ulcer in adults ranges from 70% to 100%, while in children, due to the lower incidence of primary ulcers, there are fewer literature reports on this aspect, but it also shows that Hp infection is associated with peptic ulcer disease. Pricto reported that among 91 children with Hp infection, 12 cases of gastric ulcers accounted for 9 cases (70%), and 11 cases of duodenal ulcers accounted for 10 cases (90%). In the 18 articles on pediatric Hp infection and peptic ulcer disease published in the United States, Canada, Spain, and other countries, it was found that in 176 cases of primary duodenal ulcers, the prevalence of Hp infection ranged from 33% to 100%, with an average of 92%, and in 33 cases of gastric ulcers, the prevalence of Hp infection ranged from 11% to 75%, with an average of 25%. The Department of Pediatrics at Shanghai Ruijin Hospital reported that the prevalence of Hp infection in duodenal ulcers was 83.93%, while in gastric ulcers it was only 28.57%. This suggests that Hp infection is closely associated with primary duodenal ulcer disease in children. However, as a cause of peptic ulcer disease, Hp does not meet the Koch's postulates, and some authors believe that the etiologic role of Hp in peptic ulcer disease is indirect, related to the gastric tissue inflammation caused by Hp. Follow-up of individuals with Hp infection showed that 1% to 6% of Hp patients had ulcerative pathological injury, and the chance of developing ulcers in individuals after Hp infection was four times higher than that in individuals without Hp infection.

　　2, Reservoir and Transmission Routes of Hp

　　The reservoir and transmission routes of Hp are not yet clear, and there is no confirmed host for it in nature. In addition to humans, it has a natural infection in non-human primates, and more evidence proves that Hp is transmitted from person to person. A study in Toronto found that 74% of parents and 82% of siblings had Hp-IgG serum antibodies positive, and the HP infection was confirmed by culture. The same study found that only 24% of parents and 13% of siblings in the control group had Hp-IgG serum antibodies positive, indicating that close contact between people during childhood is a decisive factor for the prevalence of Hp. Schutze et al. further used PCR to detect the polymorphism of Hp-DNA, the genotyping of the re-infection strain after treatment, and found that the isolated re-infection strain was almost consistent with that of the spouse. This provides the most convincing evidence for the transmission between people. However, how Hp is transmitted from person to person is not yet clear. At present, more evidence supports the oral-oral and fecal-oral transmission routes. As detected by PCR, Hp-DNA can be found in the saliva, dental plaque, and feces of patients, and there are also reports that Hp can be isolated and cultured from the dental plaque and feces of patients. Recently, there have been reports that the same Hp strain was isolated from multiple members of the same family. All these support the hypothesis of oral-oral and fecal-oral transmission routes of Hp. Some people suggest that the chewing of food before feeding a child by the mother or sharing a bowl during meals may be a transmission mechanism of Hp infection in developing countries, but so far, no definitive conclusion has been made about the reservoir and transmission routes of Hp.

　　Two, Pathogenesis

　　The exact pathogenic mechanism of Hp is not yet clear. In addition to the virulence factors of bacteria, the host's immune response and environmental factors also play a certain role. Recent research has found that the pathogenic mechanism of Hp depends on the virulence (colonization) factors and pathogenic factors of the bacteria, the spiral shape and motility of Hp, the ability to adapt to enzymes and proteins, and the ability to adhere to cells and mucosa, allowing it to survive in the gastric cavity. The toxins it secretes and the inflammatory mediators it induces directly destroy the gastric mucosal barrier, leading to gastric mucosal injury.

　　1. Virulence Factors

　　Among the virulence factors, motility is the most basic factor for Hp to colonize on the surface of gastric mucus. At one end of the Hp bacterial body, there are 2 to 6 flagella, which make Hp mobile and capable of penetrating the mucus layer. Hp produces a special adhesin that can adhere Hp to the gastric or duodenal metaplastic epithelial cells, causing deformation of the cell surface and changes in the cytoskeleton. The adhesion of Hp to the gastric mucosa is to prevent the loss of bacteria during the transport of food and in the continuously flowing mucus layer, which is necessary to maintain the infection. Since Hp only specifically colonizes in the gastric tissue, it is speculated that there are specific receptors on the surface of gastric epithelial cells, such as lewisb blood group antigens, etc.

　　Urease is the most important colonization factor of Hp. The amount of urease synthesized by Hp is very large, and the ammonia produced by the decomposition of urea can neutralize hydrochloric acid. This transient low acid and high pH allows bacteria to pass through the gastric mucus layer smoothly and reach the mucosal surface, where they can colonize and survive in this alkaline microenvironment. At the same time, the increase of ammonia produced by urease also has a toxic effect on the gastric mucosa.

　　2. Pathogenic Factors

　　Among the pathogenic factors, the role of cytotoxins has attracted attention. In adults, 60% of Hp strains have been reported, and 40% to 70% of Hp strains found in children have cytotoxin-associated gene A (cagA) related genes. This gene encodes a protein of 120-140 kD (cytotoxin-associated protein A, cagA). The cagA protein has a very high detection rate in patients with peptic ulcers and moderate to severe gastritis. The cagA protein has no cell vacuole activity, but it is related to the expression of cell vacuole toxins. The vacuolar cytotoxin (vaculating cytotoxin, vacA), encoded by the vacA gene, was first discovered by Leunk et al. The culture medium of Hp contains a substance that, when the culture filtrate of the bacteria is cultured with different cells, can cause partial cells such as Hela cells to undergo vacuolar degeneration, hence the name 'cell vacuole toxin'. The vacA is strongly activated at pH < 6 to pH 1.5, and has a very strong resistance to pepsin at pH 2.0. It is excreted into the intestinal tract through the pylorus. Before the activated vacA is digested by some proteases in the intestine, it causes vacuolation of duodenal epithelial cells, thus leading to duodenal ulcers in the absence of Hp in the duodenum, forming the leaky roof hypothesis (leaking roof hypothesis) for the formation of duodenal ulcers. The results of cagA, vacA detection and Hp virulence gene analysis in some children with gastric duodenal diseases are also consistent with the literature reports, 68.18% of serum samples from children with Hp infection gastritis can be detected with CagA antibodies, but in children with duodenal ulcers, 68.96% can detect both cagA and vacA simultaneously, which further illustrates that vacA is related to the occurrence of pediatric peptic ulcers.

　　1, Bleeding

　　Complications of bleeding can sometimes be the first symptom of an ulcer, without any prodromal signs. Hematemesis is generally seen in gastric ulcers, with vomit resembling coffee grounds, while black stools are more common in duodenal ulcers. When there is a large amount of bleeding, any type of ulcer can simultaneously manifest hematemesis and black stools. In children, the presence of blood in the gastric drainage suggests bleeding, but a negative drainage does not exclude the possibility of duodenal ulcer with bleeding (since blood can reflux back into the stomach via the pylorus).

　　2, Perforation

　　Perforation is much less common than bleeding, and ulcer perforation often occurs suddenly, without any prodromal symptoms. A few children may have no history of ulcer disease, with perforation as the first symptom. Operatively confirmed to be duodenal ulcer with perforation. Stress ulcer perforation can also be seen in the early neonatal period, manifested by abdominal pain and distension.

　　Children with chronic gastritis

　　Symptoms of dyspepsia vary in degree, with clinical manifestations ranging from mild to severe, and the course of the disease is protracted. The main symptoms are recurrent abdominal pain, without clear regularity, usually worsened after eating, with pain location not specific, often around the umbilicus. In young children, abdominal pain may only manifest as restlessness and changes in normal eating behavior. Older children may have symptoms similar to adults, often complaining of upper abdominal pain, followed by belching, early satiety, nausea, discomfort in the upper abdomen, acid regurgitation, difficulty in eating hard, cold, spicy foods, or exposure to cold, which can trigger or worsen symptoms when the temperature drops. Some children may have loss of appetite, fatigue, weight loss, and dizziness. Children with gastric erosion may experience black stools. Physical signs are often not prominent, and tenderness may be located in the upper abdomen or around the umbilicus, with a relatively wide range.

　　2. Pediatric peptic ulcer

　　The clinical manifestations are various, and the differences in symptoms are significant at different ages.

　　1. Neonatal period

　　It is mainly characterized by sudden upper gastrointestinal hemorrhage or perforation, often with acute onset, mainly manifested by hematemesis, melena, abdominal distension, and peritonitis. It is easy to be misdiagnosed. During this period, it is mostly acute stress ulcer, with a high mortality rate, and the most common onset is within 24 to 48 hours after birth.

　　2. Infancy

　　During this period, children are more likely to have acute onset, restlessness, poor appetite, sudden hematemesis, melena, and in the early stage, there may be decreased appetite, repeated vomiting, abdominal pain, and delayed growth and development.

　　3. Preschool age

　　During this period, abdominal pain symptoms are prominent, mostly located around the umbilicus, with intermittent attacks, unclear relationship with diet, nausea, vomiting, acid regurgitation, anemia, and upper gastrointestinal bleeding are also common.

　　4. School age

　　With the increase of age, the clinical manifestations are close to those of adults, mainly with epigastric pain, umbilical pain, and sometimes nocturnal pain, or acid regurgitation, belching, or chronic anemia. A few people may present with painless melena, fainting, or even shock.

　　1. Given that the source and transmission routes of Hp infection are not yet fully understood, it has brought difficulties to the prevention of Hp infection. Since the 1990s, significant progress has been made in the research of Hp vaccines, and it is expected that in the near future, the prevention and treatment of Hp infection through vaccination will become a reality, and it may also become an important measure for the prevention and treatment of Hp-related diseases in the future.

　　1. Three meals a day should be regular, attention should be paid to the hygiene of food and drink, and the diversity of dietary structure should be ensured, and do not overeat or overdrink.

　　1. Direct examination of bacteria

　　Direct detection of Hp in the gastric mucosa using culture, PCR, and histological methods.

　　1. Culture method

　　Endoscopic biopsy of the antral mucosa for Hp culture is the most accurate diagnostic method, which can serve as the gold standard for verifying other diagnostic tests. In addition, it can also provide drug sensitivity tests for bacteria, guiding the selection of drugs in clinical practice, especially for those who have failed treatment or live in countries and regions with high resistance to Hp. The characteristics of Hp culture are high specificity but moderate sensitivity, difficult operation techniques, and longer time consumption, requiring 3 to 6 days of culture. Even with experienced laboratory technicians operating, the success rate of culture reaches only 75% to 95%. There are many factors that can affect the growth of Hp and cause false-negative results, such as the culture specimen not containing Hp; swallowing surface anesthetic agents during gastroscopy; biopsy forceps contamination; or recent use of antibiotics or bismuth preparations, all of which can inhibit bacterial growth. In addition, the time of specimen inoculation and whether the culture medium is fresh also play a role.

　　Recently, it has been reported that Hp can also be cultured from human feces, but it requires centrifugation and concentration of bacteria in a microaerobic environment to obtain. Because currently, it can only be detected in the feces of 50% of Hp colonized patients, further research is needed on this non-invasive method.

　　2. Tissue section method

　　Another direct examination method for Hp can provide morphological information about the tissue. Because Hp resides in the mucosal layer of human gastric mucus and on the surface of epithelial cells, normally, there are no other bacteria in this location. Therefore, based on the morphological characteristics and distribution features (spiral-shaped organisms between gastric mucus and lumen) on tissue sections, Hp infection can be diagnosed, which is a relatively reliable method. The characteristics of histological examination include high sensitivity, the ability to perform pathological examination simultaneously, and the permanent preservation of data. There are many staining methods, including HE staining, Gram staining, carbol fuchsin staining, W-S (Warthin-Starry) staining, Giemsa (Giemsa) staining, etc. Gram staining is almost not used due to its low detection rate; standard HE staining can detect Hp, but it is not a reliable method. W-S silver staining is a good technique, although it is expensive and requires high technical standards, it is widely used in clinical applications due to its effectiveness. Giemsa staining is less expensive, and some authors believe that this method is of equal quality to W-S silver staining.

　　In addition to routine histological examination, there are immunohistochemical and immunofluorescence methods, but they require the use of immunofluorescence microscopes and immunological antibodies, making the examination more expensive and unable to provide information beyond routine histological findings. Therefore, they are not commonly used and are mostly used in laboratory research.

　　3. Direct smear staining

　　Direct microscopic examination of Hp in the gastric mucus on a slide can be performed using acridine orange staining, Gram staining, or Giemsa staining.

　　4. PCR (Polymerase Chain Reaction)

　　PCR is another method to detect the presence of Hp, characterized by its ability to quickly detect Hp in fresh gastric mucus specimens as well as in paraffin-embedded biopsy samples. The primers of PCR are specific to all Hp strains, thus it has high specificity. Compared with rapid urease, culture, and histology, PCR also has high sensitivity. However, some hidden factors can affect this high sensitivity and specificity, such as endoscopy and biopsy forceps cleaning, insufficient sterilization leading to DNA contamination, which reduces specificity, and factors that reduce sensitivity include patchy colonization of bacteria in the gastric mucosa or the presence of PCR inhibitors. PCR can be used for the clinical diagnosis of Hp infection, epidemiological surveys, and molecular genetic research of Hp.

　　Secondly, the indirect examination of bacteria

　　Utilizing the biological characteristics of bacteria, especially the ability of Helicobacter pylori (Hp) to hydrolyze urea, the breath test and urease test are produced. The serological test cannot provide evidence of the current presence of bacteria, so it cannot be used for the diagnosis of current infections. It is mainly used for screening or epidemiological surveys. For clinical physicians, choosing an appropriate method for patients based on the conditions of the hospital is important. Currently, the combined method is mainly used for diagnosis.

　　1. Rapid urease test

　　Since Hp is the only bacterium in the human stomach that can produce a large amount of urease, Hp infection can be diagnosed by detecting urease. Urease decomposes urea in the stomach to produce ammonia and carbon dioxide, reducing urea concentration and increasing ammonia concentration. Based on this principle, various detection methods have been developed.

　　The rapid urease test of gastric mucosal biopsy tissue is currently the most widely used method in clinical application, with advantages such as simplicity, practicality, rapidity, and sensitivity. However, it is prone to false-negative results when the number of bacteria in the biopsy tissue is very low. The sensitivity of the urease test is significantly reduced after treatment with bismuth subsalicylate, amoxicillin, or even H2 receptor antagonists. Therefore, this method is mainly used for the initial detection of Hp infection. Currently, there are the following two methods in use.

　　(1) pH indicator method: The reagent contains urea and pH indicator (such as phenol red, which is yellow-brown at pH 6.8 and pink at pH 8.4). The specimens usually taken from the stomach are acidic (pH < 6.0). Generally, the color of the reagent does not change. If there is an Hp infection in the stomach, when the mucosal specimen is placed in the reagent, the urease produced by Hp decomposes urea to produce ammonia, raising the pH value, and changing the reagent color to pink.

　　(2) Analytical chemistry method: Detect the final product of Hp urease using the principles of analytical chemistry. Since the positive chromogenic reaction does not depend on the pH change in the reagent, it can avoid false-negative results caused by factors affecting pH. The CPUT kit produced by Fujian Sanqiang Biochemical Co., Ltd. belongs to this method and can semi-quantitatively indicate the degree of Hp infection.

　　2. Breath test

　　The 13C-urea breath test uses a labeled urea, and the amount of labeled CO2 in the exhaled air is measured after oral administration, which can indirectly reflect the amount of urease. It is a non-invasive examination with the advantages of being rapid, reliable, safe, and painless, suitable for large-scale epidemiological surveys. It indicates whether there is an active Hp infection at the present time, rather than whether there has been an infection in the past, therefore, it is superior to serological tests. Studies have found that 2 hours after taking a bismuth subgallate suspension, the amount of 14CO2 is significantly reduced, making it a relatively sensitive indicator for efficacy observation and an ideal method for follow-up. The breath test is divided into 13C-urea breath test (breathtest) and 14C-urea breath test based on the different labels.

　　3. 13C-urea breath test

　　The subjects were orally administered 13C-urea at a dose of 5mg/kg, and then the exhaled samples were collected every 10 minutes for a continuous 3-hour period. If there is a Helicobacter pylori (Hp) infection in the stomach, the orally administered 13C-urea solution is decomposed into 13CO2 under the action of urease, absorbed through the gastrointestinal tract, and exhaled. The collected gas samples are analyzed by a mass spectrometer to calculate the 13CO2 content. Patients with Hp infection show an increase in 13CO2 levels 20 minutes after taking the test solution, and the levels continue to rise within 100 minutes. Patients without Hp infection do not exhale 13CO2. 13C is a stable isotope with no radioactivity, and it can be tested repeatedly. However, the determination of 13CO2 is complex, requires a mass spectrometer, and is expensive, so most hospitals are not able to carry out this test.

　　4. 14C-urea breath test

　　To overcome the disadvantages of the 13C-urea breath test, which is complex to operate and expensive, 14C-urea is used instead of 13C-urea to achieve the same satisfactory results. The detection of 14C can be done with a liquid scintillation counter, making it more practical. However, the disadvantage is that 14C has a certain level of radioactivity and is not suitable for pregnant women and children.

　　Factors affecting the accuracy of the breath test: the most common cause of false-negative results is the use of antibiotics, bismuth, or omeprazole soon after the breath test (generally required at least 1 month after treatment); the second is that urea is emptied from the stomach too quickly or the sample collection is too late, and the false-positive result is the presence of bacteria with urease activity in the body or in the oral cavity.

　　However, the breath test can only provide information about the presence of Hp, but cannot distinguish gastrointestinal diseases, and cannot replace gastroscopy. It cannot be used as the initial evaluation method for children with upper gastrointestinal symptoms.

　　5. Serological examination

　　Serological diagnosis of Hp is a non-invasive and indirect method, mainly used for epidemiology or screening, and cannot be used as the initial diagnostic tool for Hp infection alone, unless it is combined with other methods. The basis of serological examination is that Hp has the ability to induce local and systemic immune responses in the body. The three methods of bacterial agglutination, complement fixation, and ELISA can detect Hp antibodies. Due to its simplicity, rapid diagnosis, low cost, and high sensitivity, ELISA is widely used in clinical practice.

　　1. It is recommended to adopt the communal chopstick system and separate meals within the family, to disinfect tableware, and to avoid contact with infection. The traditional Chinese practice is to have a family dine together at the same table, and especially some parents like to chew food and feed it to their babies, which can increase the opportunity for the spread of Helicobacter pylori. This habit should be strictly prohibited.

　　2. Vomit and feces should be cleaned up in a timely manner, and hands and utensils should be disinfected.

　　First, treatment

　　1. Target population for Hp eradication treatment

　　Whether all Hp-infected children need to undergo Hp eradication treatment? Although children are susceptible to Hp, existing data also show that the infection rate of Hp in the Chinese children population is very high, and the outcomes after infection vary greatly; due to the difficulty of eradication treatment and the adverse reactions that may occur from the long-term use of antibiotics, it is obviously impossible and unrealistic to provide eradication treatment to all Hp-infected individuals. Since 1997, gastroenterology and microbiology experts from the United States, Europe, and the Asia-Pacific region have successively held consensus conferences on Hp. The following is a summary of the consensus on the target population for treatment reached at these conferences:

　　(1) Peptic ulcer infected with Hp, regardless of whether the ulcer is primary or recurrent, active or stationary, or whether there is a history of complications (hemorrhage, perforation), all require anti-Hp treatment.

　　(2) Gastric MALT lymphoma infected with Hp.

　　(3) Chronic gastritis with obvious gastric mucosal lesions such as erosion, atrophy, and metaplasia.

　　(4) After the radical treatment of early gastric cancer.

　　(5) Those who need to take non-steroidal anti-inflammatory drugs for a long time.

　　For children, it is currently mainly used for Hp infection gastritis and ulcers.

　　2. In vitro drug sensitivity test for anti-Hp

　　In vitro experiments show that Hp is most sensitive to penicillins; highly sensitive to aminoglycosides, cephalosporins (excluding cefametin and cefazolin), ofloxacin (flumequine), ciprofloxacin (ciprofloxacin), erythromycin, rifampin, etc.; moderately sensitive to macrolides, nitroimidazoles, furan derivatives, pipemidic acid, norfloxacin (norfloxacin); insensitive to sulfonamides, vancomycin, etc. However, Hp is moderately sensitive to bismuth salts.

　　3. Clinical efficacy evaluation of anti-Hp drugs

　　(1) Monotherapy: Although many antibiotics have good anti-Hp activity, they are not suitable for the treatment of Hp infection. The ideal drug should maintain the stability and activity of the drug within a wide pH range, have good liposolubility, and achieve a high concentration in the gastric mucus. pH has a significant effect on the activity of macrolides, aminoglycosides, quinolones, and cefametin. Moreover, quinolones and nitroimidazoles are prone to produce resistance, and these antibiotics are often ineffective when used alone in the body. Bismuth salts, amoxicillin (ampicillin), metronidazole, tinidazole (thymazole), furazolidone, nitrofurantoin (furazolidine), gentamicin, and others have only partial efficacy against Hp, with a high clearance rate but an eradication rate of less than 40％.

　　(2) Combination therapy with 2 or 3 drugs: Due to the unsatisfactory Hp eradication rate of drug therapy and the resistance of some strains, some scholars have discussed the efficacy of the combined application of 2 or 3 drugs. The combination of bismuth compounds with nitroimidazole and tetracycline or amoxicillin (ampicillin) can achieve an eradication rate of 80％～90％ for Hp. However, the adverse reactions are significant. The 9th World Gastroenterology Congress special session recommended a 2-week treatment plan (for adults): Colloidal bismuth potassium citrate (bismuth subcitrate) 120mg, 4 times/d; metronidazole 400mg, 3 times/d; amoxicillin (ampicillin) 500mg or tetracycline 500mg, 4 times/d.

　　4. Commonly used drugs for the treatment of Hp in children

　　(1) Antibiotics:

　　①Amoxicillin (ampicillin) 50mg/(kg·d), divided into 2～3 times.

　　②Tinidazole 20mg/(kg·d), divided into 2～3 times.

　　③Metronidazole (灭滴灵) 20mg/(kg·d), divided into 2～3 times.

　　④Clarithromycin 15mg/(kg·d), divided into 2 doses.

　　(2) Bismuth compounds:

　　①Bismuth potassium citrate (colloidal bismuth subcitrate, Denol) 7～8mg/(kg·d).

　　②Bismuth salicylate.

　　(3) Proton pump inhibitors (PPI): Omeprazole (Losec), 1mg/(kg·d), divided into 2 doses.

　　(4) Treatment plan:

　　①The scheme mainly using bismuth compounds: Bismuth compounds combined with 2 antibiotics: The most commonly used triple therapy in China is bismuth compounds + amoxicillin (ampicillin) + metronidazole, with a course of 2 weeks.

　　Antibiotics: amoxicillin (ampicillin), clarithromycin, metronidazole, tinidazole (thiamazole), furazolidone.

　　② Treatment plans mainly using proton pump inhibitors (PPI): PPI plus two antibiotics (as above).

　　Common methods used abroad: PPI + amoxicillin (ampicillin) + clarithromycin, for a course of 2 weeks or 1 week.

　　③ Treatment plans mainly using H2 receptor blockers: cimetidine and ranitidine or famotidine plus two antibiotics. Treatment plans for childhood Helicobacter pylori infection are still under discussion. Kibrigge reported that although 80% of the symptoms of Hp children improved with H2 receptor blockers, the recurrence and reinfection rate was as high as 68% after 2 years. DeGiantome reported that amoxicillin (Amoxicillin) alone could not improve symptoms in children. Oderdn reported that the recurrence rate was as high as 75% with a 4-week amoxicillin (Amoxicillin) therapy. Treatment with amoxicillin (Amoxicillin), tinidazole, resulted in symptom disappearance in 94% of children, 84% of whom had healed gastritis on re-examination, and the recurrence rate was 16.64% after 6 months. Baumm reported that a bismuth agent plus amoxicillin (Amoxicillin) treatment also achieved good results. Metronidazole has gradually been restricted due to the development of drug resistance. Walshdeng reported that a 1-week therapy with clarithromycin plus bismuth and metronidazole in 22 patients resulted in eradication in 21 cases, with an eradication rate of 95.45%. Ellc et al. reported that the eradication rates of Hp were 87.1% and 77% respectively when omeprazole was added to amoxicillin (Amoxicillin) and metronidazole or ranitidine plus the aforementioned two antibiotics. In summary, there is still a lack of safe and effective Hp treatment plans for children. However, the misuse of antibiotics can lead to the spread of drug-resistant strains in the population, making future treatment more difficult, especially in recent years, it has been found that clarithromycin and metronidazole have varying degrees of drug resistance. Therefore, finding an effective Hp eradication plan that is safe for children, has a high eradication rate, low recurrence rate, and short treatment duration is an urgent problem to be solved.

　　II. Prognosis

　　Generally, the prognosis is good, but it is prone to recurrence, which may lead to prolonged illness and affect the nutritional status and growth and development of children.