Diagnosis and treatment of Helicobacter pylori infection in Vietnamese children

Aim: The aim of the study was to find the optimal H. pylori eradication therapy for children in Vietnam, a developing country. Therefore, we evaluated a non-invasive diagnostic method and antibiotic susceptibility of H. pylori strains, the major determinant of treatment outcome, as well as the rate of reinfection after successful eradication, a determinant for the rational of H. pylori eradication. Materials: In a treatment trial, gastric biopsy, blood and faecal samples were obtained from 240 children (age 3-15 years) for various gastrointestinal complaints. H. pylori infection status was based on either positive culture or positive monoclonal antigen-in-stool test (Premier Platinum HpSA PLUS) at inclusion and positive monoclonal antigen-in-stool test after treatment and during one year of follow up. For evaluation of specificity of monoclonal antigen-in-stool test, blood and faecal samples from 241 children of similar age with non-gastrointestinal conditions were included. Methods: In a prospective randomized double-blind treatment trial, children received a combination of lansoprazole and amoxicillin with either clarithromycin (LAC) or metronidazole (LAM). The antigen-instool test was used to determine H. pylori status in the treatment trial and in the reinfection study. Culture of H. pylori from biopsies was performed by standard methods. Susceptibility testing of H. pylori to all three antibiotics was performed by Etest using microaerophilic incubation for ≥72h at 35 o C. Results: The sensitivity of Premier Platinum HpSA PLUS was 96.6% (95% CI 93.3-98.5%) and the specificity was 94.9% (95% CI 88.5-98.3%). The per protocol eradication rate was similar in the two treatment regimens, 62.1% for the LAM and 54.7% for the LAC regimens, respectively. The overall resistance to clarithromycin, metronidazole and amoxicillin was 50.9%, 65.3% and 0.5%, respectively. In LAC regimen, eradication was linked to the strains being sensitive (OR 7.23, 95% CI 2.10-24.9, relative to resistant strains). Twice-daily dosage was more effective for eradication of clarithromycin resistant strains than once-daily dosage (OR 6.92, 95% CI 1.49-32.13, relative to once-daily dose). Factual antibiotic dose per kilo body weight were significantly associated with eradication rates (OR 8.13, 95% CI 2.23-29.6). These differences were not seen for the LAM regimen. Low age was the most prominent independent risk factor for reinfection (adjusted HR among children aged 3-4, 5-6, and 7-8 years, relative to those aged 9-15 years, were respectively 14.3 [95% CI 3.8-53.7], 5.4 [1.8-16.3] and 2.6 [0.7-10.4]). Female sex tended to be associated with increased risk (adjusted HR among girls relative to boys 2.5, [95% CI 1.1-5.9]). Conclusion: The antigen-in-stool assay has a good performance in Vietnamese children. The two triple therapies with methronidazole or clarithromycin gave similar and low eradication rates, likely due to high rates of antibiotic resistance that was unexpected for clarithromycin. The twice-daily medications play an important role in eradication of especially clarithromycin-resistant strains. Age was found to be the main risk factor for reinfection rate in Vietnamese children, with the youngest children running the greatest risk. The high rates of antibiotic resistance imply the need to investigate alternative eradication strategies and the high reinfection rates in the youngest children, if the medical condition permits, to delaying eradication treatment. LIST OF PUBLICATIONS I. Evaluation of a novel monoclonal-based antigen-in-stool enzyme immunoassay (Premier Platinum HpSA PLUS) for diagnosis of Helicobacter pylori infection in Vietnamese children. Thi Viet Ha Nguyen, Carina Bengtsson, Gia Khanh Nguyen, Marta Granstrom. Helicobacter 2008;13: 269-273 II. Evaluation of two triple therapy regimens with metronidazole or clarithromycin for eradication of H. pylori infection in Vietnamese children: a randomized, double-blind clinical trial. Thi Viet Ha Nguyen, Carina Bengtsson, Gia Khanh Nguyen, Thi Thu Ha Hoang, Dac Cam Phung, Mikael Sorberg , Marta Granstrom. Helicobacter 2008; 13: 550-556 III. Eradication of Helicobacter pylori infection in Vietnamese children in relation to antibiotic resistance. Thi Viet Ha Nguyen, Carina Bengtsson, Li Yin, Gia Khanh Nguyen, Thi Thu Ha Hoang, Dac Cam Phung, Mikael Sorberg, Marta Granstrom. (Submitted) IV. Age as risk factor for Helicobacter pylori reinfection in Vietnamese children. Thi Viet Ha Nguyen, Carina Bengtsson, Gia Khanh Nguyen, Li Yin, Thi Thu Ha Hoang, Dac Cam Phung, Mikael Sorberg, Marta Granstrom. (Submitted)