**Core tip:** Whereas a decrease in the prevalence of *Helicobacter pylori* (*H. pylori*) has been confirmed in Western Europe, its prevalence in Central Europe, which has a substantial rural population, is unclear. Therefore, this study analyzed the prevalence of *H. pylori* among healthy volunteers in two Hungarian counties. The results of the study illustrated that the seropositivity of *H. pylori* in this area was 32%. The prevalence was higher in males, among people living in rural areas. Agricultural/industrial workers were more likely to be positive for infection than office workers. Meanwhile, rural subjects in Békés County had higher prevalence than those in Csongrád County.

INTRODUCTION
============

*Helicobacter pylori* (*H. pylori*) infection is one of the most common chronic human bacterial infections worldwide, affecting up to half of the world's population. It is the main cause of gastritis, gastroduodenal ulcer, gastric adenocarcinoma, and mucosa-associated tissue lymphoma. Its prevalence is variable in relation to geography, ethnicity, age, and socioeconomic factors\[[@B1],[@B2],[@B3]\].

The prevalence of *H. pylori* has declined worldwide, although wide variation has been observed.

According to a 2017 and a 2018 meta-analysis, the countries with the lowest *H. pylori* prevalence were Switzerland (13.1%-24.7%), Denmark (17.8%-26.5%), New Zealand (21.4%-26.5%), Australia (17.2%-32.1%), and Sweden (18.3%-34.1%) in the former meta-analysis, Indonesia (10.0%), Belgium (11.0%), Ghana (14.2%), and Sweden (15.0) in the latter, whereas those with the highest prevalence were Nigeria (83.1%-92.2%), Portugal (84.9%-87.9%), Estonia (75.1%-90.0%), Kazakhstan (74.9%--84.2%), and Pakistan (75.6%-86.4%) in the former study, Serbia (88.3%), South Africa (86.8%), Nicaragua (83.3), and Colombia (83.1%) in the latter. The former study used two periods to analyze the prevalence trend over time. The *H. pylori* prevalence after 2000 was lower than that before 2000 in Europe (48.8 *vs* 39.8), North America (42.7% *vs* 26.6%), and Oceania (26.6% *vs* 18.7%)\[[@B4],[@B5]\].

The major risk factors for *H. pylori* infection include socioeconomic status and the household hygiene of the patient and family during childhood. A previous Hungarian study revealed greater seropositivity among undereducated subjects, in persons living without sewers, those living in crowded homes or having three or more brothers and sisters, and those with high alcohol consumption, and they observed significant differences in prevalence between industrial and office workers. A Russian study reported that 88% of the Moscow working population is infected with *H. pylori*, 78% in people younger than 30 years, 97% in individuals older than 60 years. Recent epidemiologic studies revealed decreases in the prevalence of *H. pylori* in Western Europe and the United States. Conversely, little is known regarding the prevalence of *H. pylori* in Central Europe, in which a substantial population resides in rural areas\[[@B6],[@B7],[@B8],[@B9],[@B10]\].

The aims of this study were to obtain data regarding *H. pylori* prevalence in Csongrád and Békés Counties in Hungary, evaluate differences in prevalence between urban and rural areas, and establish factors associated with positive seroprevalence.

MATERIALS AND METHODS
=====================

One-thousand and one healthy blood donors \[male/female: 501/500, mean age: 40 (18--65) years\] were consecutively enrolled in Csongrád and Békés Counties. Detailed demographic data are shown in Figure [1](#F1){ref-type="fig"}\[[@B11],[@B12],[@B13]\].

![Csongrád and Békés Counties and detailed demographic data regarding Csongrád and Békés Counties.](WJG-25-6365-g001){#F1}

In Hungary, blood donation is allowed for individuals weighing more than 50 kg and aged 18--65 years. Data collection was performed using an anonymous questionnaire including 26 questions associated with demographic parameters (gender, age, place of birth, childhood residence, marital status, current residence, crowding in family, and educational status) and medical status (symptoms associated with *H. pylori* infection and gastroduodenal ulcer disease, smoking habits, alcohol consumption, and family history of *H. pylori* infection, gastroduodenal ulcer disease, and gastric malignancy).

On the basis of the childhood residence of the subjects, the following four groups of 250 subjects were established: Urban males, urban females, rural males, and rural females. Groups were matched by age. Subgroup analysis was performed according to living circumstances, residence in Békés or Csongrád County, smoking habits, alcohol and coffee consumption, occupation, intermittent agricultural work, pet or domestic animal rearing, gastrointestinal complaints, and family history of *H. pylori* infection, gastric ulcer, and gastric cancer.

All subjects were tested for *H. pylori* IgG antibody positivity using a Platelia *H. pylori* IgG enzyme-linked immunosorbent assay, which reportedly has 100% sensitivity and 90% specificity according to the manufacturer. These values were 95.6% and 85.1% in the validation study of Burucoa et al\[[@B14]\] respectively (Bio-Rad).

For the statistical analysis of different variables related to *H. pylori* infection, the chi-squared test or two-sample *t*-test was applied. The association between *H. pylori* infection and potential risk factors was established *via* univariate analysis, and odds ratios and 95% confidence intervals were calculated. In addition, a stratified analysis according to age (18--35, 35--50, and 50--65 years) was performed. The final model was developed using a generalized linear regression model *via* stepwise regression, with inclusion and exclusion criteria set at significance levels of 0.05 and 0.10, respectively. A two-sided *P* value \< 0.05 was considered statistically significant. All statistical analyses were performed using MATLAB (Mathworks, Natwick, MA, United States).

RESULTS
=======

The overall seropositivity of *H. pylori* was 32% in the studied healthy subjects. There was no statistically significant difference in prevalence between males and females (*P* = 0.0521) in our study. According to residence, the prevalence of *H. pylori* was significantly higher in rural areas than in urban areas (*P* = 0.0051). Furthermore, residence in rural areas for at least one year was associated with a significantly higher *H. pylori* prevalence than continuous urban residency (*P* = 0.0003). Parameters related to occupation were also associated with *H. pylori* infection. A higher prevalence was established for industrial workers and agricultural workers than for office workers and non-agricultural workers, respectively. Coffee consumption and pet or domesticated animal rearing were associated with *H. pylori* infection, whereas the rate of *H. pylori* positivity was similar for the remaining parameters. Detailed data are shown in Table [1](#T1){ref-type="table"}-[3](#T1){ref-type="table"}.

###### 

Sociodemographic factors associated with *Helicobacter pylori* prevalence

  **Socio-demographic factors**       ***H. pylori* positive**   ***H. pylori* negative**   **Total**   ***P* value**   **Odds ratio (univa-riate)**   **95%CI**            
  ----------------------------------- -------------------------- -------------------------- ----------- --------------- ------------------------------ ----------- -------- --------------------
  Sex                                                                                                                                                  0.0521               
  Female                              146                        29,2                       354         70,8            500                                        1.0      
  Male                                175                        34,9                       326         65,1            501                                        1.3016   \[0.9973, 1.6987\]
  Age                                                                                                                                                  0.000                
                                      44.5638                    10.7693                    37.3599     11.9457                                                    0.9484   \[0.9363, 0.9606\]
  18-25                               25                         14,9                       143         85,1            168                                                 
  25-35                               32                         16,9                       157         83,1            189                                                 
  35-45                               97                         34,4                       185         65,6            282                                                 
  45-55                               106                        43,6                       137         56,4            243                                                 
  55 +                                61                         51,3                       58          48,7            119                                                 
  Residence                                                                                                                                            0.0809               
  Urban                               185                        30,0                       431         70,0            616                                        1.0      
  Rural                               136                        35,3                       249         64,7            385                                        1.2725   \[0.9706, 1.6683\]
  Childhood                                                                                                                                            0.0051               
  Urban                               140                        27,9                       361         72,1            501                                        1.0      
  Rural                               181                        36,2                       319         63,8            500                                        1.4631   \[1.1201, 1.9110\]
  Min. one year in rural enviroment                                                                                                                    0.0003               
  Negative                            104                        25,6                       303         74,4            407                                        1.0      
  Positive                            217                        36,5                       377         63,5            594                                        1.6770   \[1.2695, 2.2153\]

*H. pylori*: *Helicobacter pylori*; CI: Confidence intervel.

###### 

Socioeconomic and lifestyle factors associated with *Helicobacter pylori* prevalence

  **Socio-economic** + **lifestyle factors**   ***H. pylori* positive**   ***H. pylori* negative**   **Total**   ***P* value**   **Odds ratio (univa-riate)**   **95%CI**            
  -------------------------------------------- -------------------------- -------------------------- ----------- --------------- ------------------------------ ----------- -------- --------------------
  Smoking                                                                                                                                                       0.1121               
  Non-smoker                                   169                        29,5                       403         70,5            572                                        1.0      
  Smoker                                       91                         34,2                       175         65,8            266                                        1.2400   \[0.9090, 1.6915\]
  Former smoker                                61                         37,4                       102         62,6            163                                        1.4261   \[0.9904, 2.0534\]
  Alcohol consumption                                                                                                                                           0.1420               
  Never                                        95                         36,0                       169         64,0            264                                        1.0      
  Occasional                                   216                        30,3                       497         69,7            713                                        0.7731   \[0.5740, 1.0413\]
  Regular                                      10                         41,7                       14          58,3            24                                         1.2707   \[0.5434, 2.9715\]
  Coffee                                                                                                                                                        0.0390               
  Never                                        82                         26,7                       225         73,3            307                                        1.0      
  1                                            94                         36,3                       165         63,7            259                                        1.5632   \[1.0929, 2.2358\]
  More than 1                                  145                        33,3                       290         66,7            435                                        1.3720   \[0.9943, 1.8931\]
  Household population                                                                                                                                          0.1649               
  Alone                                        51                         39,2                       79          60,8            130                                        1.0      
  Adults only                                  135                        31,5                       294         68,5            429                                        0.7113   \[0.4736, 1.0683\]
  Adults and children                          135                        30,5                       307         69,5            442                                        0.6812   \[0.4538, 1.0224\]
  Work                                                                                                                                                          0.0000               
  Industrial                                   186                        38,4                       299         61,6            485                                        1.0      
  Office                                       135                        26,2                       381         73,8            516                                        0.5696   \[0.4355, 0.7450\]
  Agricultural work                                                                                                                                             0.0012               
  No                                           140                        27,4                       371         72,6            511                                        1.0      
  Yes                                          181                        36,9                       309         63,1            490                                        1.5523   \[1.1882, 2.0279\]
  Domestic animals                                                                                                                                              0.0015               
  No                                           54                         23,5                       176         76,5            230                                        1.0      
  Yes                                          267                        34,6                       504         65,4            771                                        1.7266   \[1.2301, 2.4236\]

*H. pylori*: *Helicobacter pylori*; CI: Confidence intervel.

###### 

Factors in patient history associated with *Helicobacter pylori* prevalence

  **Patient history**              ***H. pylori* positive**   ***H. pylori* negative**   **Total**   ***P* value**   **Odds ratio (univar-iate)**   **95%CI**            
  -------------------------------- -------------------------- -------------------------- ----------- --------------- ------------------------------ ----------- -------- --------------------
  Familiy history of *H. pylori*                                                                                                                    0.8829               
  Negative                         161                        32,5                       335         67,5            496                                        1.0      
  Positive                         18                         31,0                       40          69,0            58                                         0.9363   \[0.5205, 1.6844\]
  NA                               142                        31,8                       305         68,2            447                                                 
  Family history of GI ulcer                                                                                                                        0.3810               
  Negative                         217                        33,3                       435         66,7            652                                        1.0      
  Positive                         57                         29,7                       135         70,3            192                                        0.8464   \[0.5965, 1.2009\]
  NA                               47                         29,9                       110         70,1            157                                                 
  Family history of GI cancer                                                                                                                       0.0014               
  Negative                         277                        32,1                       587         67,9            864                                        1.0      
  Positive                         17                         63,0                       10          37,0            27                                         3.6025   \[1.6284, 7.9701\]
  NA                               27                         33,8                       53          66,3            80                                                  
  Abdominal pain                                                                                                                                    0.8108               
  Negative                         264                        32,2                       555         67,8            819                                        1.0      
  Positive                         57                         31,3                       125         68,7            182                                        0.9586   \[0.6784, 1.3547\]
  Epigastrial pain                                                                                                                                  0.1105               
  Negative                         214                        30,5                       487         69,5            701                                        1.0      
  Positive                         107                        35,7                       193         64,3            300                                        1.2617   \[0.9481, 1.6789\]

*H. pylori*: *Helicobacter pylori*; CI: Confidence intervel; NA: Not applicable; GI: Gastrointestinal.

A significant positive association was observed between age and *H. pylori* positivity (Table [1](#T1){ref-type="table"}). To rule out this strong effect of age, three age groups were formed for further analysis. In the youngest group, the presence of epigastric pain was an independent risk factor for *H. pylori* positivity. By contrast, animal rearing was a risk factor for the middle age group, and male sex and living in rural areas for at least one year were risk factors in the oldest age group (Table [4](#T4){ref-type="table"}).

###### 

Independent risk factors associated with *Helicobacter pylori* prevalence

                                 **Age 18-35**                                      **Age 35-50**                                      **Age 50-65**
  ------------------------------ -------------------------------------------------- -------------------------------------------------- --------------------------------------------------
  Male sex                       Not significant                                    Not significant                                    *P* = 0.0389; OR = 0.5847; CI: \[0.0753 1.0940\]
  Rural residence in childhood   Not significant                                    Not significant                                    *P* = 0.0246; OR = 1.8537; CI: \[1.3154 2.3920\]
  Animal rearing                 Not significant                                    *P* = 0.0036; OR = 2.0855; CI: \[1.5897 2.5812\]   Not significant
  Epigastrial pain complaint     *P* = 0.0026; OR = 2.5514; CI: \[1.9422 3.1606\]   Not significant                                    Not significant

OR: Odds ratio; CI: Confidence intervel.

DISCUSSION
==========

This prospective study proved that the Hungarian prevalence of *H. pylori* infection has followed international trends, falling to 32% over the last two decades. The prevalence between 1990 and 2000 was similar throughout the country (58.6%--63.3%) excluding the capital, in which the prevalence was only 47.3% (Table [5](#T5){ref-type="table"}). Although the Southeastern region of the country was not studied prospectively before this study, the *H. pylori* Workgroup of our institute conducted a retrospective analysis in 2005 and 2010 among patients with dyspepsia and gastroduodenal ulcer disease. The rate of seropositivity decreased from 46% to 38%. The 2017 meta-analysis used two periods to analyze the changes of prevalence trend. The *H. pylori* prevalence after 2000 was lower than that before 2000 in Europe (48.8 *vs* 39.8), North America (42.7% *vs* 26.6%), and Oceania (26.6% *vs* 18.7%). In the surrounding Central European countries, such as the Czech Republic and Slovakia, the prevalence of *H. pylori* infection followed the trends of our region, decreasing from 42% to 23% after 10 years in the former from 62% to 35% after 15 years in the latter\[[@B4],[@B6],[@B15]-[@B21]\].

###### 

The prevalence between 1990 and 2000 throughout the country

  **Date**                        **1993**                  **1999**                **2000**                 **1998-2000**
  ------------------------------- ------------------------- ----------------------- ------------------------ ------------------------
  Region                          Tolna                     Vas                     Szabolcs-Szatmár-Bereg   Pest
  Authors                         Tamássy et al\[[@B15]\]   Lakner et al\[[@B6]\]   Iszlai et al\[[@B16]\]   Prónai et al\[[@B19]\]
  Method                          Serology                  Serology                Serology                 13C-UBT
  Population                      Blood donors              Blood donors            Healthy volunteers       Symptomatic patients
  *n* =                           400                       533                     756                      1027
  Prevalence of *H. pylori* (%)   63, 3                     62, 3                   58, 6                    47, 3

*H. pylori*: *Helicobacter pylori*.

Having examined the potential factors associated with a higher *H. pylori* prevalence, our results were in concordance with previous observations revealing a positive linear association with age. Furthermore, our study supported findings that rural subjects are more likely to be *H. pylori*-positive than urban residents. Although we could not establish a significant effect of gender on the seroprevalence, it is impressive that older rural males have an approximately sixfold higher risk of *H. pylori* positivity than young urban females (61.29% *vs* 11.11% *P* \< 0.0001). Such results are most commonly explained by differences in socioeconomic status and household hygiene of the family during childhood. Furthermore, a new original finding is that people who lived in rural conditions for at least one year also had an increased risk for *H. pylori* seropositivity. An evaluation of the occupations of the subjects provided further proof that socioeconomic factors can influence *H. pylori* infection risk. Meanwhile, the lack of difference in risk between urban and rural residence can be explained by the general improvement of living standards in our country over the last two decades, as most rural people currently have access to water supply and sanitation\[[@B6]-[@B8],[@B16],[@B20]-[@B23]\].

The link between epigastric pain and *H. pylori* seropositivity among young subjects supports the currently accepted, Rome IV diagnostic protocol for functional dyspepsia, which states the excluding *H. pylori* infection (known as "*H. pylori*-associated dyspepsia") should be the first step in the presence of such symptoms. Conversely, improved household hygiene in recent decades likely explains the lack of a relationship between socioeconomic status and *H. pylori* prevalence in this group. The findings further supported the hypothesis that hygiene differences between urban and rural areas were more significant at their childhood than nowadays. In addition, young males had poorer hygiene, than young females at that during childhood\[[@B24]\].

This study has a limitation. In Hungary, blood donors are unpaid, healthy, and conscious volunteers; therefore, they may not completely represent all segments of the population of Southeast Hungary.

In conclusion, we proved that in line with the worldwide trends, the prevalence of *H. pylori* infection has decreased in Southeast Hungary with changes of society, including improvements in socioeconomic status and living standards, during recent decades. Meanwhile, the prevalence remains high in the middle-aged and older rural populations. Generally accepted risk factors for *H. pylori* positivity appeared valid for the studied population, whereas the presence of dyspeptic symptoms was identified as an independent risk factor in the young population.

ARTICLE HIGHLIGHTS
==================

Research background
-------------------

Epidemiologic studies have revealed a decrease in the prevalence of *Helicobacter pylori* (*H. pylori*) infection in Western Europe. Conversely, little is known regarding its prevalence in Central Europe, in which a substantial population resides in rural areas.

Research motivation
-------------------

The last Hungarian epidemiologic studies on *H. pylori* were carried out approximately two decades ago and showed high seroprevalence rates. Therfore we aimed to obtain new data and to test whether it decreases similarly to the Western European tendencies.

Research objectives
-------------------

The aims of the present study were to obtain data regarding the prevalence of *H. pylori* in Csongrád and Békés Counties in Hungary, evaluate the differences in its prevalence between urban and rural areas, and establish factors associated with positive seroprevalence.

Research methods
----------------

One-thousand and one healthy blood donors were enrolled. Data collection was performed using an anonymous questionnaire including 26 questions associated with demographic parameters and medical status. All subjects were tested for *H. pylori* IgG antibody positivity using IgG enzyme-linked immunosorbent assay.

Research results
----------------

The overall seropositivity of *H. pylori* was 32%. The prevalence of *H. pylori* was significantly higher in rural areas than in urban areas. Residence in rural areas for at least one year was associated with a significantly higher *H. pylori* prevalence than continuous urban residency. A significant positive association was observed between age, occupation, coffee consumption, pet or domesticated animal rearing and *H. pylori* positivity. Three age groups were formed for further analysis, in the youngest group, the presence of epigastric pain was an independent risk factor for *H. pylori* positivity.

Research conclusions
--------------------

The prevalence of *H. pylori* infection decreased in recent decades in Southeast Hungary, it remains high in middle-aged rural populations. Generally accepted risk factors for *H. pylori* positivity appeared to be valid for the studied population. Furthermore, a new original finding is that people who lived in rural conditions for at least one year also had an increased risk for *H. pylori* seropositivity.

Research perspectives
---------------------

The results of this study seems to consider the subsequent changes in seropositivity of *H. pylori* in Hungary. It would be interesting to test whether the significant positive association between age and *H. pylori* positivity continuous observed after 10 or 15 years or rather not, "new" infected will appear, or in the older age will stay low seropositivity. The other experience of this study is the link between epigastric pain and *H. pylori* seropositivity among young subjects, which supports the recommendation in countries with high *H. pylori* seropositivity, that patients with dyspeptic symptoms should be examined for *H. pylori* infection (Rome IV diagnostic protocol).

Manuscript source: Unsolicited manuscript

Specialty type: Gastroenterology and hepatology

Country of origin: Hungary

Peer-review report classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): C, C, C

Grade D (Fair): 0

Grade E (Poor): 0

Institutional review board statement: The study was approved by the institutional review board of University of Szeged.

Informed consent statement: The institutional review board of University of Szeged waived the requirement to obtain informed consents from patients.

Conflict-of-interest statement: The authors have no conflict of interest to disclose.

Data sharing statement: No additional data are available.

STROBE statement: This study adopted the guidelines of the STROBE Statement.

Peer-review started: September 2, 2019

First decision: September 19, 2019

Article in press: October 18, 2019

P-Reviewer: Boyanova L, Mihara H, Reshetnyak VI, Triantafillidis JK S-Editor: Tang JZ L-Editor: A E-Editor: Zhang YL

[^1]: Author contributions: Bálint L, Rosztóczy A designed research, performed research, and wrote the paper; Tiszai A performed research; Kozák G designed research and analyzed data; Dóczi I contributed analytic tools; Szekeres V performed research; Inczefi O performed research; Ollé G performed research; Helle K performed research; Róka R performed research.

    Corresponding author: András Rosztóczy, MD, PhD, Associate Professor, Division of Gastroenterology, First Department of Medicine, University of Szeged, Korányi fasor 8-10, Szeged 6720, Hungary. <rosztoczy.andras@med.u-szeged.hu>

    Telephone: +36-62-545186 Fax: +36-62-545185
