Helicobacter pylori seropositivity and its associated factors in children from suburban area in Yangon

INTRODUCTION

Helicobacter pylori (H. pylori) is a spiral, flagellated Gram-negative bacterium that uniquely inhabits the human stomach.¹ H. pylori has infected about 50% of the global population. The infection rate in children differs across countries, being lower in high-income nations (34.7%) compared to low- and middle-income countries (50.8%). The bacterium is more prevalent in adults than in children and its distribution can differ across regions within the same country.² This infection is particularly prevalent in low-income countries and areas lacking proper sanitation facilities. The incidence of infection is greatly influenced by socioeconomic status.³ It is believed that H. pylori infections are predominantly acquired during childhood, with the frequency gradually rising with age after the initial years of life.⁴

The clinical symptoms of H. pylori infection are non-specific and may sometimes be explained by complications.^5,6 A significant association with nausea has been noted, but no clear link has been established between infection and gastrointestinal symptoms, pain, or pain characteristics.⁷ Some studies have reported that symptoms can lessen in frequency and severity, or even disappear, with or without bacterial eradication. A meta-analysis aimed to explore the connection between infection and symptoms but found no link to vomiting, diarrhea, flatulence, chronic functional abdominal pain, halitosis, regurgitation, constipation, or nausea, although a significant association with epigastric pain was observed.⁸ H. pylori is the causative agent of peptic ulcer disease and chronic gastritis. It is also linked to the onset of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer.⁹ H. pylori is a major infectious contributor to cancer globally, with approximately 80% of adult gastric cancers being linked to this infection.¹⁰

Research on seroprevalence and identifying potential risk factors linked to H. pylori infection is crucial for developing effective health strategies to prevent H. pylori-related diseases in the community. The number of research on H. pylori infection is escalating globally. However, there remains a shortage of data specifically concerning the study of H. pylori infection in children in Myanmar. Thus, this study aimed to assess the risk factors associated with the seroprevalence of H. pylori infection among individuals aged 2 to 16 in Insein Township, Yangon Division, Myanmar.

METHODS

A community-based cross-sectional study was conducted in Insein Township in 2008. A total of 193 children, aged 2 to 16 years and of both genders, were randomly selected from a list covering 21 wards in the township. Data were collected using a validated questionnaire by trained interviewers. Written informed consent was obtained from the parents or guardians. The approved questionnaire was employed, and trained interviewers gathered the data. Information regarding demographic characteristics such as age, gender, place of residence, number of family members, number of siblings were collected. We also took history of recurrent abdominal pain and family history of duodenal ulcer in each subject.

Recurrent abdominal pain (RAP) is defined as abdominal pain on three or more occasions over a period exceeding three months, and the pain is sufficiently intense to disrupt regular activities.¹¹

The weight and height measurements were also carried out and nutritional status classification was done according to WHO z scores tables.

Under strict aseptic measures, two milliliters (mls) of blood were collected and transferred to the laboratory on the day of collection to be processed and stored at 2-8^°C. An in-house enzyme-linked immunosorbent assay (ELISA), developed by Miyoshi et al, was used to determine serum H. pylori IgG antibodies. Both the sensitivity and specificity of the test were 90%. The test was carried out at the Experimental Medicine Unit of the Department of Medical Research located in Yangon.

The data analysis included various tabulations and cross-correlations. Statistical analysis was performed using chi-squared tests, and mean scores between groups were compared using two-sample t-tests. The significant level was set at p values below 0.05.

The study received approval from the Master's Degree Protocol Board at the University of Medicine 2, Myanmar, in 2005-2006 academic year. Consent for the children's participation was obtained from their caregivers.

RESULTS

The study involved 193 children, whose ages ranged from 2 to 16 years. Among them, 130 of them (67.36%) were tested positive for H. pylori antibodies. The average age of the participants was 7.6±3.85 years. The mean age of boys was 7.584±3.735 years, whilst that of girls was 7.618±3.971 years. Among children who tested positive for H. pylori, the average age was 8.18±3.8 years, whereas for those who tested negative, it was 6.41±3.7 years (p=<0.05). It is worth nothing that those children positive for H. pylori infection were significantly older than those negative for H. pylori infection (Table 1).

In the examined group, there were 92 males and 101 females. It was observed that 64 out of 92 males (69.57%) and 66 out of 101 females (65.35%) tested positive for H. pylori antibodies. However, no significant distinction was observed between males and females (p = 0.532). These results suggest that H. pylori infection can affect both sexes equally, without any sex predilection (Table 1).

In the studied group, there were 167 children between median and -1 SD and 26 children between -2 and -3 SD. Among them, 111 children in the group between median and -1 SD (66.47%) and 19 children in the group between -2 and -3 SD were found H. pylori antibody positive. Although there is no statistical difference, it was found that prevalence of H. pylori infection was higher in malnourished children (73.08%) than the well-nourished ones (66.47%) (Table 1).

69 children in birth order 1, 65 children in birth order 2, 36 children in birth order 3, 23 children in birth order 4 and above, were studied. Among them, 49 (71.01%), 45 (69.23%), 23 (63.89%), 13 (56.52%) in birth order 1, 2, 3 and 4 and above respectively, were found to be H. pylori antibody positive. The mean birth order of H. pylori positive children was 2.03±1.06 and that of negative ones 2.29±1.24 (p-0.163). Although there was no significance statistically (p-0.583), it is worth to note that H. pylori positivity was highest among those with birth order 1 (71.01%) and lowest in those of birth order 4 and above (56.52%) (Table 2 and Figure 3).

Among the 193 children, 27 reported experiencing recurrent abdominal pain (RAP), while 166 did not. In the group experiencing recurrent abdominal pain, 21 participants (87.77%) tested positive for H. pylori antibodies, while in the other group, 109 (65.66%) were found to be H. pylori positive. While the result lacks statistical significance, it is worth mentioning that there was a higher percentage of H. pylori seropositivity among children with recurrent abdominal pain (Figure 1).

Out of the 193 children, 14 had a family history of peptic ulcer, while the remaining 179 did not. Among those with a family history of peptic ulcer, H. pylori antibodies were detected in 12 children (85.71%), whereas in the other group, 118 children (65.92%) tested positive for H. pylori. It is evident that the rate of H. pylori antibody positivity was higher (85.71%) among those with a family history of peptic ulcer (Figure 2).

DISCUSSION

Myanmar faces a significant burden of H. pylori in the Southeast Asian region, with infection rates of 67.7% in asymptomatic adults and 48.0% in patients with dyspepsia.^12,13 Over the past two decades, an increase in H. pylori infections has been observed among children in Myanmar, with various diagnostic methods used across studies. In 2015, the prevalence of H. pylori based on fecal tests among asymptomatic school children at a high school in Mandalay, Upper Myanmar, was found to be 17.8%.¹⁴ The prevalence rate (64.36%) observed in our study was not different from the study in adults (67.7%).¹²

Globally, there are a wide range differences in the prevalence rate in various regions. Compared to the findings in Asia, our finding was similar to that documented in Yemen (65%), Nepal (75%) and Bangladesh (84%) but different from that observed in China (18.6%), Korea (12.5%-28.9%) and Japan (18.8%).^15-20 The difference might be related to the diagnostic methods, socioeconomic and sanitation status of the studied population.

This study found no gender predominance in H. pylori infection, accounting 63.57% in males, while 65% in females. Similarly, Wangda et al study in Bhutan and Aitila et al study in South West Uganda did not reveal significant differences in the prevalence of H. pylori infection between boys and girls.^21,22 Contrariwise, another report from Uganda and Sudan stated that boys are more likely to be infected with H. pylori compared to girls.^23,24 Whereas, the discoveries in Yemen, Nepal and China revealed that girls were more frequently infected than boys.^15,25-27 The relationship between H. pylori infection and gender remains a subject of debate.

The prevalence of H. pylori infection decreased with birth order. Among the firstborn children, the prevalence was 71%, 69% for the second child, declining to 63% for the third child, followed by a decrease to 56% for the fourth and younger ones, although this trend was not statistically significant (p value=0.583). The study conducted in Nigeria also reported comparable finding.²⁸

The current study found no correlation between H. pylori infection and BMI. However, a recent meta-analysis indicated that H. pylori infection negatively affected growth outcomes in children, particularly height-for-age Z (HAZ) scores.²⁹ In Eastern Sudan, where the prevalence of H. pylori infection was high (21.8%), the majority of children (84%) had BMI scores below the normal range.²³ In the present study, although the difference was not statistically significant, the prevalence of H. pylori infection was found to be higher in malnourished children compared to those who were well-nourished.

The present study did not reveal the association between H. pylori infection and recurrent abdominal pain. Likewise, a Romanian study demonstrated similar finding.³⁰ However, it pointed out the positive association between H. pylori infection and epigastric pain. The present study did not include the history of epigastric pain. A study carried out in Europe by Kori et al reported that the most common presentations of children came for endoscopy were dyspepsia and abdominal pain.³¹ Similarly, an African study also demonstrated significant association between H. pylori infection and abdominal pain.²³

Although it is not statistically significant, the seropositivity of children with family history of peptic ulcer disease was significantly higher (85.71%) than their counterparts (65.92%). A Romanian study also found no significant statistical association between H. pylori infection and a family history of upper digestive disorders.³⁰

The main limitations of this study include the small number of participants from a single geographical region-Insein Township in Yangon Division. So, it cannot represent the Myanmar children from various parts of the country.

CONCLUSION

Pediatric H. pylori infection has distinct epidemiology, clinical characteristics, associated conditions, and approaches to diagnosis and treatment. In Myanmar, specific risk factors for pediatric H. pylori infection include inadequate sanitation in schools and homes, as well as overcrowded living conditions. The infection rate of H. pylori remains high among children, highlighting the need for comprehensive prevention and treatment programs. Early diagnosis can greatly reduce complications later in adulthood and could have a significant impact on the country’s socio-economic status. Future research should be carried out at the various regions of the nation and concentrate on the influence of lifestyle and environmental factors in children and their families that may contribute to the prevalence of H. pylori infection.

ACKNOWLEDGEMENTS

We would like to thank Dr U. Myo Khin, Retired Director General, Department of Medical Research, Myanmar for his supervision and support for this study. We also offer our gratitude to the children and their parents.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee of the University of Medicine, Myanmar

REFERENCES

1. 1. Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. 1983;321(8336):1273-5.
2. 2. Hassan MN, Arif A, Shahzad MS, Ibrahim M, Rahman HA, Razaq MA, et al. Global prevalence of Helicobacter pylori and its effect on human health. Pure Appl Biol. 2020;9(1):936-48.
3. 3. Okuda M, Lin Y, Kikuchi S. Helicobacter pylori infection in children and adolescents. Helicobacter pylori in Human Diseases: Advan Microbiol InfectDis Publ Heal. 2019;11:107-20.
4. 4. Mitchell HM, Li YY, Hu PJ, Liu Q, Chen M, Du GG, Wang ZJ, et al. Epidemiology of Helicobacter pylori in southern China: identification of early childhood as the critical period for acquisition. J Infect Dis. 1992;166(1):149-53.
5. 5. Jones NL, Koletzko S, Goodman K, Bontems P, Cadranel S, Casswall T, et al. Joint ESPGHAN/ NASPGHAN guidelines for the management of Helicobacter pylori in children and adolescents (update 2016). J Pediatr Gastroenterol Nutr. 2017;64:991-1003.
6. 6. Cilleruelo PM, González MM. Helicobacter pylori infection in children: is it overdiagnosed?. Act Pediatr Aten Prim. 2018;11:60-2.
7. 7. Correa Silva RG, Machado NC, Carvalho MA, Rodrigues MA. Helicobacter pylori infection is high in paediatric nonulcer dyspepsia but not associated with specific gastrointestinal symptoms. Acta Paediatr. 2016;105(5):e228-31.
8. 8. Spee LA, Madderom MB, Pijpers M, van Leeuwen Y, Berger MY. Association between Helicobacter pylori and gastrointestinal symptoms in children. Pediatrics 2010;125:e651-69.
9. 9. Pacifico L, Anania C, Osborn JF, Ferraro F, Chiesa C. Consequences of Helicobacter pylori infection in children. WJG. 2010;16(41):5181.
10. 10. de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Heal. 2020;8(2):e180-90.
11. 11. Ukarapol N, Lertprasertsuk N, Wongsawasdi L. Recurrent abdominal pain in children: the utility of upper endoscopy and histopathology. Sing Medi J. 2004;45(3):121-4.
12. 12. Aye TT, Ni N, Myint T, San Aye K, Myint WP, et al. Helicobacter pylori infection among Buddhist monks in the selected regions of Myanmar. Myanmar Med J. 2015;57(1):17-23.
13. 13. Myint T, Shiota S, Vilaichone RK, Aye TT, Matsuda M, Tran TT, et al. Prevalence of Helicobacter pylori infection and atrophic gastritis in patients with dyspeptic symptoms in Myanmar. World J Gastroenterol. 2015;21(2):629-36.
14. 14. Swe HM, Ni N, Soe LL, Myint AA, Tar T. Fecoprevalence and determinants of Helicobacter pylori infection among asymptomatic children in Myanmar. Int J Gastroenterol Hepatol Transpl Nutr. 2016;1(ii):50-4.
15. 15. Mohanna MA, Al-Zubairi LM, Sallam AK. Prevalence of Helicobacter pylori and parasites in symptomatic children examined for Helicobacter pylori antibodies, antigens, and parasites in Yemen. Saudi Med J. 2014;35(11):1408.
16. 16. Mehata S, Parajuli KR, Pant ND, Rayamajhee B, Yadav UN, Mehta RK, et al. Prevalence and correlates of Helicobacter pylori infection among under-five children, adolescent and non-pregnant women in Nepal: Further analysis of Nepal national micronutrient status survey 2016. PLoS Neglec Tropi Dis. 2021;15(6):e0009510.
17. 17. Mahalanabis D, Rahman MM, Sarker SA, Bardhan PK, Hildebrand P, Beglinger C, et al. Helicobacter pylori infection in the young in Bangladesh: prevalence, socioeconomic and nutritional aspects. Inter J Epidemiol. 1996;25(4):894-8.
18. 18. Shu X, Ping M, Yin G, Jiang M. Investigation of Helicobacter pylori infection among symptomatic children in Hangzhou from 2007 to 2014: a retrospective study with 12,796 cases. PeerJ. 2017;5:e2937.
19. 19. Park JS, Jun JS, Ryu EY, Yeom JS, Park ES, Seo JH, et al. Changes in seroprevalence of Helicobacter pylori infection over 20 years in Jinju, Korea, from newborns to the elderly. J Kor Medi Sci. 2020;35(32).
20. 20. Miyamoto R, Okuda M, Lin Y, Murotani K, Okumura A, Kikuchi S. Rapidly decreasing prevalence of Helicobacter pylori among Japanese children and adolescents. J Infect Chemother. 2019;25(7):526-30.
21. 21. Wangda S, Richter JM, Kuenzang P, Wangchuk K, Choden T, Tenzin K, et al. Epidemiology of Helicobacter pylori Infection in asymptomatic schoolchildren in Bhutan. Helicobacter. 2017;22(6):e12439.
22. 22. Aitila P, Mutyaba M, Okeny S, Ndawula Kasule M, Kasule R, Ssedyabane F, et al. Prevalence and risk factors of Helicobacter pylori Infection among children aged 1 to 15 years at Holy innocents Children’s hospital, Mbarara, South Western Uganda. J Trop Med. 2019;2019():9303072.
23. 23. Abbas M, Sharif FA, Osman SM, Osman AM, El Sanousi SM, Magzoub M, et al. Prevalence and associated symptoms of Helicobacter pylori infection among schoolchildren in Kassala State, East of Sudan. Interdiscip Perspect Infect Dis. 2018;2018(1):4325752.
24. 24. Hestvik E, Tylleskar T, Kaddu-Mulindwa DH, Ndeezi G, Grahnquist L, Olafsdottir E, et al. Helicobacter pylori in apparently healthy children aged 0–12 years in urban Kampala, Uganda: a community-based cross-sectional survey. BMC Gastroenterol. 2010;10:62.
25. 25. Ansari S, Gautam R, Nepal HP, Subedi SN, Shrestha S, Mandal F, et al. Helicobacter pylori colonization in Nepal; assessment of prevalence and potential risk factors in a hospital-based patient cohort. BMC Res Notes. 2016;9:59.
26. 26. Zhang D, Zhou L, Lin S, Ding S, Huang Y, Gu F, et al. Recent changes in the prevalence of Helicobacter pylori infection among children and adults in high- or low-incidence regions of gastric cancer in China. Chin Med J. 2009;122(15):1759-63.
27. 27. Zhu Y, Zhou X, Wu J, Su J, Zhang G. Risk factors and prevalence of Helicobacter pylori infection in persistent high incidence area of gastric carcinoma in Yangzhong city. Gastroenterol Res Pract. 2014;2014(1):481365.
28. 28. Emerenini FC, Nwolisa EC, Iregbu FU, Eke CB, Ikefuna AN. Prevalence and risk factors for helicobacter pylori infection among children in Owerri, Nigeria. Niger J Clin Pract. 2021;24(8):1188-93.
29. 29. Xu C, Wu Y, Xu S. Association between Helicobacter pylori Infection and growth outcomes in children: a meta-analysis. Helicobacter. 2022;27(1):e12861.
30. 30. Rosu OM, Gimiga N, Stefanescu G, Anton C, Paduraru G, Tataranu E, et al. Helicobacter pylori infection in a pediatric population from Romania: risk factors, clinical and endoscopic features and treatment compliance. J Clin Med. 2022;11(9):2432.
31. 31. Kori M, Le Thi TG, Werkstetter K, Sustmann A, Bontems P, Lopes AI, et al. Helicobacter pylori infection in pediatric patients living in Europe: results of the EuroPedHP registry 2013 to 2016. J Pedia Gastroenterol Nutrit. 2020;71(4):476-83.