Cross-sectional descriptive design was employed in this study. The research was conducted on 140 PUG children in the Mekong Delta, Vietnam, from April 2017 to April 2019. The patient was included when he/she had all three inclusion criteria of (1) clinically, the child has one or more PUG symptoms of recurrent abdominal pain (> 3 times within 3 months), vomiting, nausea, indigestion, heartburn, gastric bleeding, black stools/vomiting blood, and iron deficiency anemia with unknown cause; (2) paraclinically, the gastro-duodenal endoscopy results with inflammatory lesions and/or peptic ulcers; and (3) family and patient consent to participate in the study. The exclusion criteria included (1) patients treated with antibiotics, antacids, and PPI in the previous 4 weeks; (2) patients possessed known allergy to one of the study medications; and (3) patients having acute heart, liver, or kidney failure.

HP infection was diagnosed by using two tests of (1) urease test and (2) stool antigen test (SAT) or urease breath test (UBT). The patients were categorized into two groups, including the HP (+) group, which represents patients who were both positive with urease test and SAT/UBT, and the HP (-) group, representing patients who had a negative result in one of the tests.

The PUG clinical symptoms were collected through clinical examination and questioning, including localized symptoms of the digestive tract (abdominal pain, vomiting, eructation, heartburn, and gastric bleeding). Endoscopy investigations in PUG children were determined and classified following the Sydney system (Erythematous/exudative; Flat erosive; Raised erosive; Nodular; Enterogastric reflux; Hemorrhagic; and Hypertrophy of the gastric mucosa) (Dixon et al. 1996). Additionally, the gastritis levels were also separated into different categories of mild (small visible vessels), moderate (visible vascular network), and severe (distinct, prominent vascular network). PUG children were then be divided according to the number of ulcers (1 foci, ≥ 2 foci) and the ulcer size (≥1 cm, < 1 cm).

The PAM regimen, the standard treatment for HP infection issued by the Vietnam Ministry of Health, was selected in the study. This includes amoxicillin (50 mg/kg/day, maximum 2 g/day, twice daily), metronidazole (20 mg/kg/day, maximum 500 mg/day, twice daily), and a PPI (esomeprazole or omeprazole 1 mg/kg/day, maximum 20 mg/day) for 2 weeks. Then, PPI was continued to suppress gastric acid secretion for another 6–8 weeks to heal the damage in the gastrointestinal tract.

The treated PUG children were follow-up at 3 times points, including (1) first time, one week after the onset of the PAM regimen, to evaluate the treatment efficiency and monitor drug side effects; (2) second time, after the completion of the PAM regimen (2 weeks), to re-evaluate the treatment efficiency and monitor drug side effects, continue to maintain the inhibition of gastric acid secretion to heal gastro-duodenal lesions; and (3) third time, after the patient has stopped antibiotics for ≥ 4 weeks and suppressed gastric acid secretion for 2 weeks, to evaluate the HP eradication by SAT/UBT, and observe the improvement in clinical symptoms of pediatric patients.

The results of HP eradication after using the treatment regimen are assessed by either breath test (if HP infection was previously diagnosed by urease test and breath test) or stool test (if HP infection was diagnosed by urease test and stool test). The treatment was considered successful when the breath test or stool test shows negative results. Other cases were deemed unsuccessful.

Statistical analysis was carried out utilizing the SPSS 18.0 program. The Chi-squared test (or Fisher’s exact test) was used to compute the correlations between variables. Variables with a test results of p < 0.05 will be analyzed in the multivariable regression model. A p-value of < 0.05 was considered significant.

Table 1 describes the study participants’ characteristics. The prevalence of HP infection in PUG children was 46.4%. The infected children have an average age of 10.88±2.6 years old. Most children participating in the study lived in urban areas (58.6%) and belonged to the Kinh ethnic group (96.4%) and wealthy families (72.1%).

The x² test showed that there was a relationship between the prevalence of HP infection in PUG children and the children living area (p = 0.006), family economy (p = 0.02), and family history of HP infection (p = 0.004) (Table 2). To this end, pediatric patients living in urban areas would have a 2.62 times higher rate of HP infection than children living in rural areas. The prevalence of HP infection in children with a wealthy family was 2.48 times higher than that of the children with average/poor economic families. Additionally, children with a family history of HP infection had a 2.68 times higher rate of HP infection for themselves than the other group. Nevertheless, multivariable logistic regression analysis demonstrates that only the relationship between family history of HP infection and the HP infection status in children was statistically significant (p = 0.018).

In terms of the clinical and paraclinical characteristics (Table 3), abdominal pain was the highest clinical symptom presented in PUG children (88.6%). According to the x² test, children without abdominal pain possessed a higher rate of HP infection than those with abdominal pain. In addition, children with eructation had a higher rate of HP infection than the other group. Regarding the endoscopy findings, we recorded 21 cases of peptic ulcers (15%) and 119 cases of gastritis (85%). The rate of HP infection in the peptic ulcers group (81%) was statistically (p < 0.05) higher than that of the gastritis group (40.3%).

For the PAM treatment outcome, our study recorded 65 PUG children with HP infection that were admitted to the standard treatment. For this, 9 children were excluded from the study population due to treatment abandonment and loss of track. Thus, the results were analyzed on 56 participants. The success rate of treating HP with the standard PAM regimen was only 51.8% (Table 4). There were 13 cases (23.3%) where patients reported suffering from side effects during treatment. Among them, the common side effects were diarrhea (8 cases), vomiting (4 cases), and anorexia (1 case). Most patients after completing the treatment process had improved clinical symptoms (Table 4). The rate of clinical symptom improvement of abdominal pain, anorexia, vomiting, eructation, and heartburn was 69.6%, 87.0%, 82.4%, 73.3%, and 83.3%, respectively.

In our study, the rate of PUG children with HP infection in the Mekong Delta, Vietnam was 46.4%. This number was in accordance with previous reports in other areas/cities/provinces in Vietnam. For instance, the prevalence of HP infection in children in Lang Son was 41.4% in 2016 (Nguyen et al. 2016c), in Dien Bien was 42.8% (Nguyen 2016a). Nevertheless, a high rate of HP infection was reported in Hue (76.4%) (Pham et al. 2018). In general, the prevalence of HP infection in Vietnamese children was higher than the world (33.3%) and other developed Asian countries’ average rate (Okuda et al. 2019a). In Hangzhou, China, the overall HP infection rate was 18.6% (Shu et al. 2017), whereas in Japan, the prevalence of HP infection in children accounts for only 4.8% (Nakayama et al. 2017). This can be explained because of the Vietnamese culture of using chopsticks to pick up food together, sharing food dishes and dipping cups, and chewing rice for children (i.e., mouth-to-mouth eating habit), to name a few. These traditions have increased the HP infection status of the community (Okuda et al. 2019a), which consequently reflects the high prevalence of HP infection in PUG children.

Regarding the associated factors, children with a family history of HP infection had a 2.35-times higher rate of HP infection than the other group (p < 0.05), similar to the previous studies (Hososah et al. 2015; Shu et al. 2017). In Dien Bien, children whose mother got infected with HP had 1.59-times higher risk than others (p < 0.05) (Nguyen 2016a). Moreover, in Vietnam, children who were born to HP (+) mothers possessed an increased risk of HP infection by 4.4 times (p < 0.01) (Nguyen et al. 2016c). In the study of Dao Viet Hang et al., in 2019, in households with people infected with HP, the rate of HP infection in the age group of < 8, 8–10, and 11–15 years old was 98.6%, 95.5%, and 88.5%, respectively; and up to 69.4% of households have 100% members with the disease (Dao et al. 2019). Explainably, since the main route of HP transmission from person to person is the mouth-to-mouth route, and Vietnamese people tend to eat the same food dishes, use chopsticks to pick up food for themselves and others, and women commonly chew rice to feed her child, it is easily for children to be infected with HP when their family member got previously infected.

The most dominant symptoms in the gastrointestinal tract in our study was abdominal pain, accounting for 88.6%. The prevalence of HP infection in children with abdominal pain (42.7%) was lower than those with no abdominal pain (75%) (p = 0.01). In contrast, a study in Iran showed that children with abdominal pain had a significant higher prevalence of HP infection than the group without abdominal pain (Alimohammadi et al. 2016; Castillo-Montoya et al. 2017). Meanwhile, another report stated that no significant difference was noted between HP infection and recurrent abdominal pain (Mansour et al. 2012). Thus, the relationship between abdominal pain and HP infection is still controversial. Therefore, the evaluation of HP infection status in children with abdominal pain should be considered, even with the non-invasive test results, because this symptom could cause anxiety for children and their family (Jones et al. 2017). Regarding other symptoms, the group of children with eructation had 62.7% chance of HP infections, significantly higher (p = 0.003) than the group without eructation (37.1%). Moreover, the percentages of other symptoms of vomiting and heartburn in our work were greater than other studies (Nguyen 2016b; Pham et al. 2018). This could be explained by the differences in the children ages in our study (6–15 years old) and the other studies (<6 years old). Conclusively, the clinical symptoms of HP infection in PUG children are often non-specific, change with age, and are easily confused with the symptoms of other diseases.

In terms of the endoscopic findings, on 140 children, we recorded 21 children with ulcerative lesions (peptic ulcers) and 119 children with inflammatory lesions (gastritis). In the group of peptic ulcers children, up to 85% of children were infected with HP, and this rate was only 40.3% in children with inflammatory lesions on endoscopy (p = 0.001). These results were consistent with the literature. In the previous studies, the rate of HP infection in peptic ulcers children was 83.3%, and in children with gastritis was only 50% (Ozbey et al. 2015; Tang et al. 2018b). The Koca’s group also recorded the prevalence of HP infection in the group of erosive gastritis was 20%, gastric ulcer was 40%, and duodenal ulcer was 71.5% (Koca et al. 2016). In summary, most studies show that there is a strong association between HP infection and PUG disease. Therefore, according to the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition, it is recommended to evaluate the status of HP infection in PUG children. In case of the HP (+), the child needs to be treated and evaluated the treatment outcome (Jones et al. 2017).

The rate of successful HP eradication with the 3-drug PAM regimen in our study was 51.8%. Similar results were recorded in the study of Nguyen Thi Ut et al (53.6%) (Nguyen 2016b), Nguyen Thi Viet Ha et al (66.7%) (Nguyen and Phan 2013), and Nguyen Phuc Thinh et al (36.4%) (Nguyen 2014). In general, studies in Vietnam indicate that the success rate of PAM regimen ranges from 50–70%, lower than that of other developed countries. In Slovenia, from 2011–2014, the successful rate of the PAM regimen in eradicating HP was up to 85.9% (Butenko et al. 2017). In northern Portuguese, this rate reached 97.8% in children (Sliva et al. 2018). In Japan, the successful eradication rate of HP by PAM regimen was 96.8% (Okuda et al. 2017; Mabe et al. 2018). Therefore, a 2019-report recommended using PAM regimen as a first-line choice in the eradication of HP in children in Japan (Okuda et al. 2019). One of the important reasons underlying the low efficiency of PAM regimen in Vietnamese children is the antibiotic resistance issue. In Vietnam, the prevalence of HP drug-resistant strain is accelerating (Nguyen et al 2021). Therefore, the success rate of HP eradication only ranges from 50–70% with the PAM regimen, and < 50% with the PAC regimen, even when the bacteria is sensitive to clarithromycin (Nguyen et al 2011; Le 2014; Do et al 2019). Recently, the role of bismuth has been increasingly confirmed to have a positive influence on the outcome of HP treatment (Cadranel et al. 2018). Therefore, the European Society for Paediatric Gastroenterology Hepatology and Nutrition has recommended bismuth and high-dose amoxicillin in the treatment regimen for eradication of HP in children (Jones et al. 2017). Conclusively, Vietnam policy-makers should consider these recommendations in improving the HP treatment outcome in children.

Regarding the side effects occurring during treatment, in 56 treated children, 13 children (23.2%) possessed observable side effects. Among them, 8 (61.5%) had diarrhea, 4 (30.8%) had vomiting, and 1 (7.7%) had anorexia. Similarly, previous publications also recorded an overall side effects rate of 15.4%–21.2% (Okuda et al. 2017; Mabe et al. 2018), in which diarrhea predominated, followed by vomiting, fatigue, fever, and itching (Butenko et al. 2017). Conclusively, the incidence of side effects was low and the side effects were mild, indicating that the PAM regimen is safe to use in children. Nevertheless, in clinical practice, medical practitioners need to be considerate to clearly distinguish between the drug side effects and the gastrointestinal symptoms of the diseases.