SEROPREVALENCE AND RISK FACTORS FOR HELICOBACTER PYLORI INFECTION AMONG SCHOOL STUDENTS IN SANA'A CITY, YEMEN

Wadhah Hassan Edrees1,2,3image 

1Medical Microbiology Department, Faculty of Applied Sciences, Hajjah University, Yemen.

2Medical Laboratory Department, Faculty of Medical Sciences, Al-Razi University, Yemen.

3Medical Laboratory Department, Faculty of Medical Sciences, Yemen and Gulf University for Sciences and Technology, Yemen.

 

ABSTRACT 

Background and Objectives: Helicobacter pylori is the most common bacterial infection affecting more than 50% of the population globally, especially in developing countries, while data on its prevalence in Yemen is still limited. Therefore, the current study aimed to estimate the seroprevalence and risk factors of H. pylori among school students in Sana'a city, Yemen.

Methods: A cross-sectional study was conducted in primary and secondary schools in Sana'a during the period from October to December 2021 in which two hundred and ninety-three (293) school students aged 11-21 years were enrolled in this study and tested for H. pylori in blood specimens by using a cassette Rapid antibody test. Associated risk factors were collected through a designed questionnaire. 

Result: Overall, H. pylori antibody was positive in 82/293(27.99%) students. The higher rate of seroprevalence of H. pylori antibodies was reported among male students (29.25%; P˃0.05), age group of 16-21 years (33.69%; P˂0.05), and secondary students in schools (31.66%; P˂0.05). Also, the highest rate of H. pylori infection was positive among students who drank untreated water (32.61%), consuming of unwashed vegetables (28.71%) and fruits (30.51%), not been infected previously (28.45%), one of their family infected (28.98%), sometimes eating out of home (32.47%), and non-use antibiotics (29.12%) and there was non-statistical significant difference (P˃0.05). In addition, there were no significant relationships between seropositivity of H. pylori and clinical signs and symptoms as well as antibiotic use. Finally, most of the students with blood group (O) had H. pylori antibodies (P ˃0.05).

Conclusion: It can be concluded that the increasing rate of H. pylori among school students will become a real serious health problem if it is not monitored. Therefore, an effective educational health program is important for the prevention and control of H. pylori infection among school students.

Keywords: Helicobacter pylori, Seroprevalence, Students, School, Sana’a, Yemen.

 

INTRODUCTION

 

Helicobacter pylori (H. pylori) is the commonest bacterium widespread in the world that infects more than 50% of individuals and over 80% of individuals infected with this bacterium are asymptomatic1. H. pylori causes long-term inflammation of the mucous membrane of the stomach representing gastric and duodenal ulcers which progress to develop into gastric cancer if untreated2,3,4. Also, it is accountable for iron deficiency anemia, decreasing blood platelet count, fetal deformity, and fetal growth retardation in pregnant women5. The acquisition of H. pylori infection rises often during childhood that could be referred to as outdoor activities and exposure to potential external sources6 . Seroepidemiologic reports have revealed that over 50% and 90% of adults in developed and developing countries, respectively, are positive for serum antibodies against H. pylori7. The route of H. pylori transmission is via person-to-person and fecal-oral routes.  Also, the overcrowding conditions, inadequate personal hygienic practices, low socioeconomic conditions, lack of waste treatment system, and use of contaminated water are the most factors that contribute to the increasing prevalence of bacterial infection in developing countries8-13.  In developing countries, school students are at higher risk of H. pylori infection due to the mentioned factors. Numerous studies documented the frequency of H. pylori infection among school students in several countries. In Nigeria, Mynepalli et al.,14 found 59% of participating school students had H. pylori infection. Also, it was found that 23.6% of examined school students were positive for H. pylori infection in Poland15. In Yemen, the seroprevalence of H. pylori antibodies among children was 9%. The prevalence according to age varied from 0% in children under 2 years to 12.5% in age group 9-10 years. In addition there was a correlation between the amounts of positive antibodies and increasing age. The prevalence rate of H. pylori antibodies was also significantly associated with the practice of drinking water from reused plastic jerry cans, with poor mouth hygiene and with co-infection by intestinal parasites6, but no study has been reported so far among schoolchildren. Therefore, the current study aimed to detect H. pylori infection among school students in Sana'a city, Yemen.

 

MATERIALS AND METHODS

 

Study area and period

This study is a cross-sectional study carried out at primary and secondary schools in Al-Meaen and Al-Thourah districts during the period from October to December 2021.

Sample size

Two hundred and ninety-three (293) blood specimens were randomly sampled from school students aged between 11-21 years old who attending the primary and secondary schools in Sana’a city.

Data collection

The required data were collected from enrolled school students by using a structured questionnaire. The data that included in the questionnaire such as gender, age, study level, parents’ educational status, family size, source of drinking water, consumption of raw vegetables and fruits, hand washing after defecation, infected previously, one of your family infected, and eating food out home were interviewed. Also, the clinical signs and symptoms such as heartburn, nausea, regurgitation, heartburn and regurgitation, abdominal pain, and weight loss as well as antibiotics used were obtained. The questionnaire was constructed in Arabic and translated into English. The students have voluntarily participated into this study. The age group was divided into a group that included; children (11-15 years) and adolescents (16-21 years).

Inclusion and exclusion criteria

The students who signed informed consent and delivered blood specimens were included. In contrast, the students who refused to full the questionnaire and sign the informed consent were excluded.

Specimen’s collection and examination 

About five mL of blood specimens were sampled from each student by venipuncture and transferred into a clean tube containing no anticoagulant. The detection of H. pylori antibody was performed by using the rapid test of ACON H. pylori Ab Test Cassette (ACON Laboratories, Inc, USA). One drop of whole blood was placed cassette test. Also, the blood group was assessed for each student.

Ethical statement

The ethical declaration of the this work was permitted by the Ethics Committee of the Gulf University For Science and Technology, Yemen and authorized by the Education office that belong to Sana’a capital of Yemen. Additional, the consent form that signed by the participants or investigator teams was obtained. 

Statistical analysis

The data were statistically analyzed using SPSS program (SPSS version 18.0). A significant difference between the variables was determined by P-value (<0.05) that was considered statistically significant.

 

RESULTS

 

Participated characteristics

In present result, 53.54% of the study participants were female students and 62.8% are between 16-21 years old. And (67.9%) of participants were studying in high school. (35.49%) of students' parents hold a high school certificate. Also, 50.51% are living with family sizes between 3-7 individuals and drinking treated water (84.3%) as well as consuming unwashed vegetables (65.53%) and fruits (59.73%). In addition, 81.23% are washing their hands after defecation and didn't infect previously (81.57%). And no one of their family infected (52.9%), always eating food out home, and didn't use antibiotics (70.31%) as summarized in Table (1). Table 2 shows that most of the specimens were collected the students did not suffer from clinical signs and symptoms such as heartburn, nausea, regurgitation, heartburn and regurgitation, abdominal pain, and weight loss. 

Seroprevalence of H. H. pylori antibodies

The present result showed that the sero-prevalence of H. H. pylori antibody was 82(27.99%) reported among participating students. While 211(72.01%) specimens were negative for H. pylori antibody (Figure 1).

Seroprevalence of H. pylori and its associated risk factors

The existing finding revealed that male students had a higher rate (29.25%) of H. pylori antibodies than females with a statistically non-significant difference (P=0.221). The result according to the age, the age group of 16-21 years had the highest H. pylori antibodies with 33.69% when compared to age group of 11-15 years with 18.34% with a statistically significant difference (P=0.031).  Also, it was detected that students attending secondary schools (31.66%) and whose parents graduated from university (31.46%) were more infected by H. pylori bacterium. Regarding family size, these findings showed that a higher rate of H. pylori antibodies was recorded among a small number of family sizes (3-7) at 50.51% (Table 3). However, a higher rate of seroprevalence of H. pylori antibodies was recorded among students who drank untreated water (32.61%), consuming of unwashed vegetables (28.71%) and fruits (30.51%), washed their hands after defecation with water and soap (29.41%), not infected previously (28.45%), one of their family infected (28.98%), sometimes eating out of home (32.47%), and didn't use of antibiotics (29.12%) (Table 3). Table 4 shows that the seroprevalence of H. pylori antibodies was higher among students who did not suffer from heartburn (31.13%), nausea (32.5%), regurgitation (30.05%), heartburn and regurgitation (31.45%), and abdominal pain (28.29%) with non-statistical differences (P ˃0.05). In contrast, the student with weight loss had more prevalence rate of H. pylori antibodies at 29.59%.In the present result regarding the blood group, it was noticed that the higher rate of H. pylori antibodies was 30.43%  recorded among students who had blood group (O) as listed in Table 5.

 

DISCUSSION

 

The current study showed that the overall positive prevalence of H. pylori antibodies was 27.99% among school students. This is consistent with studies reporting the prevalence of H. pylori antibodies among schoolchildren in the city of Makkah, Saudi Arabia (27.4%)16, as well as in southwestern Uganda (24.3%)17, and in Gruziadz, Poland (23.6%)15. However, the lower rate of H. pylori antibodies was recorded in the Sana'a city (9%)6, in Taiwan (15.1%)18, and in East of Sudan (21.8%)19. In contrast, the higher rate was reported in Yemen at 43.9% in Sana'a20, 68% in Hodeidah21, 75.8% in Dhamar22, and 55.8% in Iraq23. This result found that male students had a higher rate of H. pylori antibodies than females and were not statistically significant (P=0.221). This finding is similar to a report by Abbas et al.,19. In contrast, this finding is not constant with several reports that showed that female students had a higher rate of H. pylori infection21,22. These findings indicate that the higher rate was found among male students might be referred to activities performed outdoor which make them more exposed to potential external sources of H. pylori through eating contaminated foods due to fast food retailers or street vendors with inadequate hygienic practices. The present work indicated a high rate of H. pylori antibodies in the age groups of 16-21 years with insignificant differences (P=0.031). In similar study was conducted in Hadhramout, Yemen by Bin-Hameed and Barajash9 who noticed the older age group had a higher rate of H. pylori antibodies. Also, Mehata et al.,24 revealed that the highest rate of H. pylori infection was reported among age group 15-19 years old. In the present finding, it was found that the students with secondary school education level were more positive for H. pylori antibodies and significant association. A study by Bin-Hameed and Barajash9 revealed that the participated students educated at primary and high schools account for the majority of the positive results for H. pylori and there were non-statistical significant difference.

This work found that students whose parents graduated from the university were more infected by H. pylori bacterium and this is in agreement with the study by Mynepalli et al.,14.  The high rate of H. pylori  prevalence indicates that the education level did not influence the decrease in the transmission of pathogenic microorganisms in Yemen. Also, some reports mentioned that most individuals educated at the university level may lack awareness of the way pathogens are spread and transmitted25,26. With respect to family size, in current result findings revealed that the small-sized families number of family sizes (3-7 persons) were shown to have higher H. pylori antibodies with a non-statistical difference. This result is different than most of the reports carried out in different countries that proved that a large family size is more acceptable for the acquisition of H. pylori infection but didn't play an important role in H. pylori transmission between family individuals27,28.

The highest rate of H. pylori antibodies in the present study was observed among students who drank untreated water, consuming of unwashed vegetables and fruits, and washed their hands after defecation with water and soap, and there was no statistically significant difference. The results of this study are supported by Abebaw et al.,28 and Mynepalli et al.,14.

Yemen is a developing country where more than 90% of households lack the use of a safe water supply. They depend on obtaining water from surface rivers and water tanks which are available to everyone and more potentially contaminated by pathogenic micro-organisms29,30. Consumption of raw vegetables plays an important role in transmitting pathogenic micro-organisms in Yemen31-33. Most students who were positive for H. pylori antibodies in exiting work was not infected previously and one of their family infected as well as sometimes eating out of home and didn't use antibiotics with non-statistical significant differences. These results are consents with several reports conducted in different countries21,22,27.

Some reports documented that the antibiotics used were observed to be a significant risk factor for H. pylori infection34,35. H. pylori resistance to antibiotics is an increasing trend due to the overuse and mistreatment worldwide of antibiotics, especially in developing countries, for the treatment of other infections36-40 and resulting in falling success rates of H. pylori eradication and treatment41-44. The seroprevalence of H. pylori antibodies was higher among students who did not suffer from clinical signs and symptoms with non-significant differences and this result is similar to some studies9,15,43. H. pylori infection in many children may be asymptomatic throughout life45,46. According to the blood group, the present result revealed that a higher rate of H. pylori antibodies was reported among students possessing blood group (O) with non-statistically significant differences. In similar, Al-Kadassy et al.,21 found that the higher prevalence of H. pylori antibodies was among students with blood group (O) and non-significant differences.

Limitations

The limitations of the present work are represented in the sample size collected from some schools due to limited resources and equipment as a result of the economic circumstances in Yemen. In addition, the lack of advancing diagnostic techniques capable of accurate diagnosis and expensive commercial kits. 

 

CONCLUSION

 

The higher seroprevalence of H. pylori antibodies among school students is considered a threat to the health of the population in the future if it is not controlled. So, applying of health awareness program among school students that will be enhancing their hygienic practices as well as improve the water and sanitation system might decrease the risk of prevalence of H. pylori bacterium among schoolchildren in Yemen. 

 

CONFLICT OF INTEREST 

 

The author declares that this article's content has no conflict of interest. 

 

ACKNOWLEDGEMENTS 

 

The author thanks participating researchers; Abdulaziz Alshafli, Abdullah Shamsan, Afrah Al-Zain, Ismail Faydi, Najeba Al-Aqyadi, Ola’a Al Qobati, Saba Sarya, Shaima Al-Absi, and Soraya Alaoui for their help in collecting the specimens and data. Also, author would like to thank the Yemen and Gulf University for Science and Technology staff for their substantial help.

 

REFERENCES 

 

  1. Rossi-Aguiar SVP, Navarro-Rodriguez T, Mattar R, et al. Oral cavity is not a reservoir for Helicobacter pylori in infected patients with functional dyspepsia. Oral Microbiol Immunol 2009; 24(3): 255-259.https://doi.org/10.1111/j.1399-302X.2008.00491.x
  1. Brown LM. Helicobacter pylori: Epidemiology and routes of transmission. Epidemiol Rev 2000; 22 (2):283–297.https://doi.org/10.1093/oxfordjournals.epirev.a018040
  1. Salih BA. Helicobacter pylori infection in developing countries: The burden for how long? Saudi J Gastroenterol 2009; 15(3):201–207.https://doi.org/10.4103/1319-3767.54743
  1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide  burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893-2917. https://doi.org/10.1002/ijc.25516
  2. Franceschi F, Annalisa T, Teresa DR, et al. Role of Helicobacter pylori infection on nutrition and metabolism. World J Gastroenterol 2014; 20(36):12809–12817.https://doi.org/10.3748/wjg.v20.i36.12809 
  1. Al-Shamahy HA. Seroprevalence of Helicobacter pylori among children in Sana’a, Yemen. Ann Saudi Med 2005; 25(4):299-303.https://doi.org/10.5144/0256-4947.2005.299
  2. Chi H, Bair MJ, Wu MS, et al. Prevalence of Helicobacter pylori infection in high-school students on Lanyu Island, Taiwan: Risk factor analysis and effect on growth. J Formos Med Assoc 2009; 108(12): 929-936.https://doi.org/10.1016/S0929-6646(10)60005-8
  1. Tsongo L, Nakavuma J, Mugasa C, Kamalha E. Helicobacter pylori among patients with symptoms of gastro-duodenal ulcer disease in rural Uganda. Infect Ecol Epidemiol 2015; 5(1): Article ID26785.https://doi.org/10.3402/iee.v5.26785
  1. Bin-Hameed EA, Barajash HM. Screening for the prevalence of Helicobacter pylori infection among dyspeptic patients using simple fecal antigen and serum antibody diagnostic methods at Mukalla city hospitals, Hadhramout, Yemen. Afr J Microbiol Res 2021; 15(6): 325-333. https://doi.org/10.5897/AJMR2020.9413
  2. Edrees HW, Anbar AA. Prevalence and antibacterial susceptibility of bacterial uropathogens isolated from pregnant women in Sana'a, Yemen. PSM Biol Res 2020; 5(4): 157-165.
  3. Alhlale MF, Humaid A, Saleh AH, Alsweedi KS, Edrees WH. Effect of most common antibiotics against bacteria isolated from surgical wounds in Aden governorate hospitals, Yemen. Universal J Pharm Res 2020; 5(1): 21-24.https://doi.org/10.22270/ujpr.v5i1.358 
  1. Edrees WH, Mogalli NM, Alabdaly KW. Assessment of some clinical and laboratory profiles among dengue fever patients in Hajjah government, Yemen. Universal J Pharm Res 2021; 6(2):38-41.https://doi.org/10.22270/ujpr.v6i2.571 
  1. Alhlale FM, Saleh HA, Alsweedi SK, Edrees HW. The inhibitory effect of Euphorbia hirta extracts against some wound bacteria isolated from Yemeni patients. COPS 2019; 3(2): 780-786.
  2. Mynepalli SM, Maureen O, Mumuni A. Prevalence of Helicobacter pylori and hygiene practices among public secondary school students in Ikeja local government area, Lagos, Nigeria. Health 2014; 6: 250-258.http://dx.doi.org/10.4236/health.2014.64037 
  3. Szaflarska-Popławska A, Soroczyńska-Wrzyszcz A. Prevalence of Helicobacter pylori infection among junior high school students in Grudziadz, Poland. Helicobacter 2018; e12552. https://doi.org/10.1111/
  4. Telmesani AM. Helicobacter Pylori: Prevalence and relationship with abdominal pain in school children in Makkah City, western Saudi Arabia. Saudi J Gastroenterol 2009; 15(2): 100-103.https://doi.org/10.4103/1319-3767.45359 
  5. Aitila  P, Mutyaba N, Okeny S, Kasule  MN, 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 Tropic Medicine 2015; ID 9303072.https://doi.org/10.1155/2019/9303072 
  6. Lin B-D, Lin B-J, Chen YC, Chen C-S, Chen K-W. Seroprevalence of Helicobacter pylori infection among schoolchildren and teachers in Taiwan. Blackwell Publishing Ltd, Helicobacter 2007; 12: 258–264.https://doi.org/10.1111/j.1523-5378.2007.00496.x
  7. Abbas M, Sharif FA, Osman MS, Osman MA, et al. Prevalence and associated symptoms of Helicobacter pylori infection among schoolchildren in Kassala State, East of Sudan. Interdiscip Perspect Infect Dis 2018, Article ID 4325752. https://doi.org/10.1155/2018/4325752
  8. Alyahawi A, Ali Alkaf A, Alzaghrori S. Prevalence of Helicobacter pylori among asymptomatic populations in Sana’a, Yemen. Universal J Pharm Res 2018; 3(3): 30-34.https://doi.org/10.22270/ujpr.v3i3.163 
  9. Al-Kadassy AM, Suhail MA, H. Baraheem OH. The prevalence of Helicobacter pylori infection among medical sciences' students of Hodeidah University-Republic of Yemen. Bull HIPH. 2013; 43(1):121-126.https://doi.org/10.21608/JHIPH.2013.19998
  10.  Al-Badaii F, Bajah K, Ahmed S, Al-Ameri H, et al. Prevalence of Helicobacter pylori infection and associated risk factors among schoolchildren at Dhamar City, Yemen. Int J Sci Res Biol Sci 2021; 8(6): 16-22.   
  11. Hussen BM, Qader SS, Ahmed HF, Ahmed SH. The prevalence of Helicobacter pylori among university students in Iraq. Indian J Sci Tech 2013; 6(8): 5019-5023.https://doi.org/10.17485/ijst/2013/v6i8.4
  12. Mehata S, Parajuli KR, Pant ND, 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 Negl Trop Dis 2021; 15(6): e0009510. https://doi.org/10.1371/journal.pntd.0009510
  13. Edrees WH, Al-Asbahi AA, Al-Shehari WA, Qasem EA. Vulvovaginal candidiasis prevalence among pregnant women in different hospitals in Ibb, Yemen. Universal J Pharm Res 2020; 5(4):1-5.https://doi.org/10.22270/ujpr.v5i4.431
  14. Abdullah QY, Al-Helali MF, Al-Mahbashi A, Qaaed ST, Edrees WH. Seroprevalence of dengue fever virus among suspected patients in Taiz Governorate-Yemen. Universal J Pharm Res 2020; 5(5):21-26.https://doi.org/10.22270/ujpr.v5i5.482 
  15. Herbarth O, Krumbiegel P, Fritz GJ, et al. Helicobacter pylori prevalence and risk factors among school beginners in a German urban centre and its rural county. Environ Health Perspect 2001; 109: 573-577.https://doi.org/10.1289/ehp.01109573
  16. Abebaw W, Kibret M, Abera B. Prevalence and risk factors of H. pylori from dyspeptic patients in Northwest Ethiopia: A hospital based cross-sectional study. Asian Pac J Cancer Prev 2014; 15(11): 4459–4463.https://doi.org/10.7314/APJCP.2014.15.11.4459  
  17. Edrees WH. Antibacterial susceptibility and Sider honey activity against isolated bacteria from wound patients attending at Al-Gmohori hospital in Hajja City, Yemen. Al-Razi Univ J Med Sci 2021; 5 (2):1-8.https://doi.org/10.51610/rujms5.2.2021.108 
  18. Banafa AM, Edrees WH, Al-Falahi GH, Al-Shehari WA. Prevalence of hepatitis B surface antigen among orphans children living in orphanage in Sana'a city, Yemen. PSM Microbiol 2022; 7(1): 19-26.
  19. Qasem EA, Edrees WH, Al-Shehari WA, Alshahethi MA. Frequency of intestinal parasitic infections among schoolchildren in Ibb city-Yemen. Universal J Pharm Res 2020; 5(2):42-46. https://doi.org/10.22270/ujpr.v5i2.388
  20. Edrees WH, Alshahethi MA, Alariqi RR, et al. Detection of intestinal parasites of some fresh vegetables and their consumers in Sana'a City, Yemen. Al-Razi Univ J Med Sci 2021; 5 (2):19-25.https://doi.org/10.51610/rujms5.2.2021.112 
  21. Alshahethi MA, Edrees WH, Mogalli NM, Al-Halani AA, Al-Shehari WA, Reem A. Distribution and risk factors for Giardia lamblia among children at Amran governorate, Yemen. Universal J Pharm Res 2020; 5(3):34-37.https://doi.org/10.22270/ujpr.v5i3.413 
  22. Moharram ASS, Alqady A, Alhetary AA. Prevalence of Helicobacter pylori among gastritis patients in Sana'a, Yemen. Int J Curr Microbiol App Sci 2015; 4(3):769-778.
  23. Nguyen TH, Phan TB, Nguyen VB, et al. Prevalence and risk factors of Helicobacter pylori infection in Muong children in Vietnam. Annals Clin Lab Res 2017; 5(1).https://doi.org/10.21767/2386-5180.1000159   
  24. Al-Khawlany RS, Edrees WH, et al. Prevalence of methicillin-resistant Staphylococcus aureus and antibacterial susceptibility among patients with skin and soft tissue infection at Ibb city, Yemen. PSM Microbiol 2021: 6(1): 1-11.
  25. Edrees WH, Banafa AM. Antibacterial susceptibility of isolated bacteria from wound infection patients presenting at some government hospitals at Sana’a city, Yemen. Al-Razi Univ J Med Sci 2021; 5(1): 1-13.https://doi.org/10.51610/rujms5.1.2021.99 
  26. Al-Haik MW, Al-Haddad MA, Al-Kaf GA, Edrees HW. Antimicrobial activities for hadhrami honey on growth of some pathogenic bacteria. Universal J Pharm Res 2017: 2(6), 7-12. https://doi.org/10.22270/ujpr.v2i6.R2 
  27. Edrees HW, Al-Awar SM. Bacterial contamination of mobile phones of medical laboratory workers at Sana’a city, Yemen and their antimicrobial susceptibility. J Pharm Pharmacog Res 2020; 8 (6): 591-599. 
  28. Edrees WH, Anbar AM. Prevalence and antibiotic susceptibility of Streptococcus pyogenes isolated from schoolchildren in Sana’a city, Yemen. PSM Vet Res 2021; 6(2):  22-30.
  29. Mégraud F. Current recommendations for Helicobacter pylori therapies in a world of evolving resistance. Gut Microbes 2013; 4(6):541-548.https://doi.org/10.4161/gmic.25930 
  30. Suzuki S, Esaki M, Kusano C, Ikehara H, Gotoda T. Development of Helicobacter pylori treatment: How do we manage antimicrobial resistance? World J Gastroenterol 2019; 25(16):1907-1912.https://doi.org/10.3748/wjg.v25.i16.1907
  31. Jonaityte IR Ciupkeviciene E, Jonaitis P, Kupcinskas J, Petkeviciene J, Jonaitis L. Changes in the seroprevalence of Helicobacter pylori among the Lithuanian medical students over the last 25 years and its relation to dyspeptic symptoms. Medicina 2021; 57: 254.https://doi.org/10.3390/medicina57030254   
  32. Graff LB, Andersen LP, Gernow A, et al. Helicobacter pylori and rheumatoid arthritis. J Pre Clin Clin Res 2007;1(1):68–73.https://doi.org/10.1046/j.1365-2036.2002.01284.x 
  33. Mitchell H, Katelaris P. Epidemiology, clinical impacts and current clinical management of Helicobacter pylori  Med J Aust 2016; 204(10): 376-380.https://doi.org/10.5694/mja16.00104
  34. Graff LB, Andersen LP, Gernow A, et al. Effect of eradication of Helicobacter pylori in rheumatoid arthritis patients. J Pre Clin Clin Res 2007; 1(1):74–79.Al-Badaii F, Bajah K, Ahmed S, Al-Ameri H, et al. Prevalence of Helicobacter pylori infection and associated risk factors among schoolchildren at Dhamar City, Yemen. Int J Sci Res Biol Sci 2021; 8(6): 16-22.