Large-scale, national, family-based epidemiological study on Helicobacter pylori infection in China: the time to change practice for related disease prevention
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* Xian-Zhu Zhou
* Nong-Hua Lyu
* Hui-Yun Zhu
* Quan-Cai Cai
* Xiang-Yu Kong
* Pei Xie
* Li-Ya Zhou
* Song-Ze Ding
* Zhao-Shen Li
* Yi-Qi Du

## Abstract

**Background and aims** Current practice on *Helicobacter pylori* infection mostly focuses on individual-based care in the community, but family-based *H. pylori* management has recently been suggested as a better strategy for infection control. However, the family-based *H. pylori* infection status, risk factors and transmission pattern remain to be elucidated.

**Methods** From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based *H. pylori* infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for *H. pylori* infection.

**Results** Among all participants, the average individual-based *H. pylori* infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1–7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05).

**Conclusion** Familial *H. pylori* infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from *H. pylori* individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.

*   GASTRIC CANCER
*   HELICOBACTER PYLORI - EPIDEMIOLOGY
*   HELICOBACTER PYLORI INFECTION
*   HELICOBACTER PYLORI - GASTRITIS
*   GASTRIC PRE-CANCER

#### WHAT IS ALREADY KNOWN ON THIS TOPIC

*   On important feature of *Helicobacter pylori* is family cluster infection and intrafamilial transmission of *H. pylori* has been suggested as an important source for its spread; a family-based *H. pylori* management strategy is recently proposed for infection control, but the family-based *H. pylori* infection status, risk factors and transmission pattern remain to be evaluated.

#### WHAT THIS STUDY ADDS

*   This national wide study revealed that the family-based *H. pylori* infection rate is much higher than the individual-based infection rate in most provinces in China and stratified analyses indicated important intrafamilial transmission patterns that correlated to the incidence of infection, suggesting a major source for its spread.

#### HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

*   The study provides supporting evidences to implement family-base *H. pylori* management to curb its intrafamilial spread in highly infected area. The results have important clinical implications in refinement of eradication strategies and impact on public health policy formulation for related disease prevention.

## Introduction

*Helicobacter pylori*, the major cause of chronic gastritis, peptic ulcers and gastric cancer, infects around 50% of the world’s population, is also closely associated with multiple extragastrointestinal diseases.1–4 One important feature of *H. pylori* is family-cluster infections.5 6 Accumulating evidence has demonstrated that the transmission of *H. pylori* is mainly by oral–oral, faecal–oral routes and water sources6–8 and intrafamilial spread are common.8–10 Within the family unit, infected parents, especially mothers, have been suggested to play an important role in its transmission, with spread also occurring between spouses and among siblings.11–15 Therefore, treatment of whole-family *H. pylori* infection has important clinical and public health implications for related disease prevention.16–18 

Large-scale clinical investigations4 19–21 and international consensus reports1–3 22 have both recommended population-wide screening and eradication of *H. pylori* for gastric cancer prevention in highly infected areas. In addition to the ‘test and treat’ and ‘screen and treat’ strategies, which are traditionally available for individual-based management of *H. pylori* infection in various infected populations,1 2 the newly introduced ‘family-based *H. pylori* infection control and management’ strategy6 in China has provided a promising and efficient avenue to curb intrafamilial spread and advanced clinical practice in managing *H. pylori* infection.

China is one of both *H. pylori* and gastric cancer prevalent areas. The 2021 national statistics indicated that the country has a population of 1.41 billion and 494 million families, with an average family size of 2.62 persons.23 The *H. pylori* infection rate is 49.6%,24 and the gastric cancer incidence is 28.68/100 000.25 Global cancer statistics in 202025 estimated that stomach cancer incidence and mortality were 1 089 103 and 768 793 cases worldwide, with 478 508 and 373 789 cases in China, respectively. Chronic *H. pylori* infection is considered to be the major cause of gastric cancer. Despite a few scattered reports, no large-scale family-based *H. pylori* infection survey has been performed in the general population, nor is it clear about the factors that affect *H. pylori* spread and cause disease within the household.

We aimed to determine family-based *H. pylori* infection, risk factors and transmission routes in general household in all 31 provinces in mainland China, and compare these with individual-based infection status. Investigations in this area will provide important evidence on familial *H. pylori* infection and help to formulate public health policies and refine eradication strategies for infection control and related disease prevention. Results and conclusions from the current investigation will not only benefit Chinese residents but also be valuable as a reference for other highly infected areas globally.

## Methods

### Study design and family-based participant enrolment

This large-scale, national, family-based, cross-sectional survey was conducted from September 2021 to December 2021 in all 31 provinces of mainland China. The participants were cohabitants of households. The investigation adopted a non-probability (convenience) sampling method from each region, but also referred to the probability sampling for sample size calculation,26 which showed that a sample size of 9317 would produce a two-sided 95% CI with a width equal to 0.020 when the sample infection rate is 40% (formula26: n = t2pq/d2; n, t, p, q and d are sample size, t value, positive rate, negative rate and acceptable error, respectively). Considering the additional bias of the convenience sampling method, we, therefore, expanded the sample size to more than 10 000 households. The sampling numbers for each region were determined based on regional population, and considering the cost, accessibility, testing facilities and COVID-19 factors. A stratified analysis of infection status was performed based on each province and geographical region of China. Because of the global COVID-19 pandemic from 2019, data from two provinces, Guangxi and Xizang (Tibet), were not available; therefore, data from only 29 of 31 provinces were analysed.

To avoid biased sample selection, enrolled families were selected from at least four different locations in a province, and could be from up to nine cities. A physician from a local tertiary hospital was assigned in each province to guide and monitor the screening and enrolment processes in communities and villages. Publicity methods included phone call, door-to-door campaigns and public posters. At least 20% of the screening sites in each province were in rural communities to ensure the inclusion of a sufficient urban and rural population comparable to the national census data.23 

Families containing two or more family members (living together for more than 10 consecutive months per year) were invited to participate in the survey. A family could have one couple, with or without children, or more couples of different generations, or single parent with children, but with no limitation on the maximum number of persons living within a household. An infected family was defined as a household with at least one *H. pylori*-infected member. To ensure the accuracy of 13C-urea breath test (13C-UBT) and avoid false-negative results, the family was excluded if any member had used antibiotics within the past month, proton pump inhibitors within 2 weeks, or *H. pylori* treatment within the past 3 months. However, family members who had previously eradicated *H. pylori* beyond 3 months were eligible for inclusion. Other exclusion criteria were severe cardiac, hepatic or renal insufficiency and contraindications to performing 13C-UBT.

This study was registered in the Chinese Clinical Trial Registry ([www.chictr.org.cn](http://www.chictr.org.cn)) with registration number ChiCTR2100051229, where the protocol is freely accessible from the website after registration.

### Questionnaires for family members

After the programme was introduced to the community, residents were enrolled voluntarily with no specific incentive applied. All members of the family had to participate. A trained physician was onsite to guide and help the enrolment processes and fill out the questionnaire forms (online supplemental file 1). For each eligible family, members were asked to complete a questionnaire using mobile devices. The survey questionnaire contained a self-calibration system to avoid unserious answers, and household head was responsible for entering details such as family general information, the number of family members, annual household income, living area, and family sanitary and animal rearing conditions. A guardian was required to fill in personal information for children and adolescents (<18 years old), including number of siblings, parental mouth-to-mouth feeding, and the habit of holding toys in mouth. The overall questionnaire completion rate was 73.90% among all participants. Data were kept confidential and used for analysis only.

### Supplementary data

[[gutjnl-2022-328965supp001.pdf]](pending:yes) 

### *H. pylori* testing for all family members

*H. pylori* infection was tested using a 13C-UBT Kit (UREA-13C breath test Heliforce kits, Beijing Richen-Force Science & Technology, Beijing, China) for all enrolled family members, following the manufacturer’s instructions. The sensitivity and specificity of the assay were 95.52% and 94.74%, respectively, according to the manufacturer’s introduction. A delta over baseline (DOB) of ≥4.0 was considered positive for *H. pylori*, and a DOB<4.0 was considered negative.

### Statistical analysis

Ordinal categorical variables were compared using Wilcoxon rank-sum test or Kruskal-Wallis H test. Unordered categorical variables were compared using the χ2 test or Fisher’s exact test where appropriate. Continuous variables were summarised as mean±SD and compared using the Wilcoxon rank-sum test. All variables on univariate analysis with p<0.10 were included in the multivariate logistic regression analysis (stepwise, sls=0.10, sle=0.05) to investigate associations between risk factors and *H. pylori* infection. ORs and 95% CIs were calculated. A p<0.05 was considered statistically significant.

### Role of the funding sources

The funders of this study had no role in study design, data collection, data analysis, data interpretation, report writing or decision to submit the manuscript.

## Results

### General information of enrolled families and individuals

Family enrollment information is shown in figure 1. A total of 17 041 families registered, but only 10 735 families were enrolled, and 31 098 participants from 10 735 households were finally analysed. Evaluation of demographic information between current study population and the seventh national census data of China showed that the study population was comparable to the national data (online supplemental table 1).23 The mean age of the study population was 43.49 years; 13 478 (43.34%) participants were male, and 17 620 (56.66%) were female; 24 092 (77.47%) were married; 3781 (12.16%) were children and adolescents. Of the participants, 12 646 (40.66%) were infected by *H. pylori*, and 1699 (13.44%) had received successful treatment; another 10 947 (35.20%) participants were infected cases newly identified. The average household size of the 10 735 enrolled families was 2.90 persons; 7636 (71.13%) families had at least one infected person. The overall average individual-based *H. pylori* infection rate was 40.66%; with 43.45% for adult, and 20.55% for children and adolescents. A significant association between age and *H. pylori* infection was observed in different age groups, and the highest infection rates were between ages 31 and 70 years (figure 2A).

### Supplementary data

[[gutjnl-2022-328965supp002.pdf]](pending:yes) 

![Figure 1](http://gut.bmj.com/https://gut.bmj.com/content/gutjnl/72/5/855/F1.medium.gif)

[Figure 1](http://gut.bmj.com/content/72/5/855/F1)

Figure 1 
Flow chart of household and individual enrolment processes. (A) These households failed to submit, or submitted incomplete questionnaires, the exact number of family members in these households were not available. (B) Infected household is defined as a household with at least one *Helicobacter pylori*-infected family member. (C) Uninfected household is defined as a household without any *H. pylori*-infected family member.

![Figure 2](http://gut.bmj.com/https://gut.bmj.com/content/gutjnl/72/5/855/F2.medium.gif)

[Figure 2](http://gut.bmj.com/content/72/5/855/F2)

Figure 2 
*Helicobacter pylori* infection status of the enrolled families. (A) *H. pylori* infection status of enrolled participants and their infection rates in different age groups. Left y axis represents the number of participants enrolled, and right y axis represents the percentage of their infection rates, x axis indicates different age groups. (B, C) figure 2B indicates *H. pylori* infection status of 10 735 enrolled families, and figure 2C indicates stratified 7636 *H*. *pylori*-infected families. y axis represents family size, which ranges from 2 to 7 (or more) persons, and x axis represents the number of infected persons within the household. Numbers within square represents the number of infected families; percentage numbers within the bracket and curve lines indicate the percentage of infected families in the same family size groups. Infected family: at least one person in the family was infected; non-infected family: all members in the family were not infected. Children: participant’s age is less than 18 years for short, including children and adolescents.

### Household *H. pylori* infection status and risk factors

Table 1 shows the household member infection information and risk factors of the 10 735 enrolled families; to further identify the detailed familial infection status, stratified information is presented in figure 2B,C. Among the 10 735 families, 5305 (49.42%) were two-person families, and 123 (1.15 %) were seven-member families; 28.87% of families had no infection, but in 14.01% of families, all members were infected. The remaining 6132 (57.12%) families had 1–6 infected members (figure 2B).

View this table:
[Table 1](http://gut.bmj.com/content/72/5/855/T1)

Table 1 
Demographic information of enrolled households and *Helicobacter pylori* infection risk factors

A stratified presentation of the correlation between family size and family member infection is presented in figure 2C. Among the 7636 infected families, 4051 (53.05%) had only one infected member. In 1504 (19.7%) families, all members were infected, and the remaining 2081 (27.25%) families had 2–6 infected family members. In the 3339 two-person families, 32.91% had both members infected (figure 2C).

An average of 1.66 persons were infected in the 7636 infected households, accounting for 54.53% of the total household members (online supplemental table 2). In addition, in order to understand the cluster level of the infected families, we mapped the family infection index of *H. pylori*-infected patients within the household in all 29 provinces analysed (online supplemental figure 1).

Of the enrolled families, 7961 (74.16%) were urban residents, and 2774 (25.84%) were from rural areas (table 1). Among many variables, household location or geographical area (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and family size (eg, family of three: OR: 1.97, 95% CI 1.76 to 2.21) were independent risk factors for increased infection risk (p<0.001), and more generations living in a household (eg, three generations: OR: 0.79, 95% CI 0.68 to 0.92) was an independent protective factor. However, the role of generations as a risk/protective factor appeared to be biphasic and was closely related to the family size, it was a risk factor for household infection before multivariate logistic regression analysis, but a protective factor after adjustment, and became a risk factor again when it was adjusted excluding the family size (table 1), while all other variable adjustments did not change this conclusion.

Other factors did not affect infection risk (p>0.05), such as dishwashing; tableware sterilisation; drinking boiled water, tap water, bottled water, purified water or well water; family members sharing dishes, cups or dental appliances; and having pets, poultry or livestock in the household. However, using serving chopsticks or spoons reduced the infection risk (p<0.05), whereas a family history of gastric cancer increased the infection risk (p<0.05). Although the household infection rate did not differ among various income groups (table 1), stratified analysis showed that high-income groups had a lower average infection rate and lower all-member-infection rate, and vice versa (p<0.05, figure 3A,B).

![Figure 3](http://gut.bmj.com/https://gut.bmj.com/content/gutjnl/72/5/855/F3.medium.gif)

[Figure 3](http://gut.bmj.com/content/72/5/855/F3)

Figure 3 
Stratified analysis of *Helicobacter pylori* infection in the enrolled families. (A) Correlation of annual household income, average family size and proportion of infected person in different household income groups. Left: y axis represents average family size, and right: y axis represents average percentage of infected participants, and x axis indicates annual household income. *p<0.05 when compared with household income < ¥100 000 group. (B) Correlation of stratified annual household income and infection rate in 10 735 families. The y axis represents percentage of families, and x axis indicates annual household income. \***|p<0.001 when compared with household income < ¥100 000 group; NS, not significant when these groups were compared with each other, p>0.05. (C) Distribution of couples/generations number per household in 10 735 enrolled families; y axis represents the number of family, and x axis represents the number of couples/generations within the family. (D) Infection status of the total 7961 couples; y axis represents the number of couples, and x axis indicates the infection status of these couples. (E) Correlation of couple cohabitation time and *H. pylori* infection rate of 7961 couples. The y axis represents percentage of couples, and x axis indicates couple cohabitation time (years). *p<0.05 and **p<0.01, when compared with 0–5 years cohabitation group; NS, not significant when these groups were compared with each other, p>0.05. (F) Correlation of annual household income and couple infection status. The y axis represents percentage of couples, and x axis indicates annual household income. *p<0.05 when compared with household income <¥100 000 group; NS when these groups were compared with each other, p>0.05. (G) The total 3781 children’s cohabitation status with their parents, y axis represents children number, and x axis indicates children’s cohabitation status with their parents, the percentages inside the bracket are the percentages of the total children number. (H) Parental infection status of 1976 children who cohabitated with them, y axis represents children number, and x axis indicates *H. pylori* infection status of these parents. (I) Correlation of parental infection status and children infection rate, y axis represents the infection rate, x axis indicates *H. pylori* infection status of these parents. **p<0.01, \***|p<0.001 when infection rates between the two groups were compared.

The general family *H. pylori* infection rates in 29 of the 31 provinces ranged from 50.27% to 85.06%, and the average infection rate was 71.21% (table 2). Among the 29 provinces, 26 had household infection rates above 60%, and 20 provinces had infection rates above 70%. In five provinces—Qinghai, Hainan, Gansu, Jiangsu and Liaoning—the infection rates were alarmingly above 80%. The average family infection rate (71.21%) was much higher than the individual average *H. pylori* infection rate (40.66%). Detailed *H. pylori* infection rate and its correlation with age in the 29 provinces by different geographical regions are presented in online supplemental figure 2 . We failed to correlate the infection rates with per capita gross domestic product (GDP) or general GDP levels in all 29 provinces (online supplemental figure 3), but found the infection rate correlated well with the gastric cancer incidence in most provinces in China (online supplemental figure 4).

View this table:
[Table 2](http://gut.bmj.com/content/72/5/855/T2)

Table 2 
*Helicobacter pylori* infection status among different provinces

### Individual-based *H. pylori* infection status and risk factors

Individual-based infection status and risk factors are presented in table 3. A higher *H. pylori* infection risk was observed for individuals who were male, not living in southwest areas, married and living in rural areas, as well as those who reported more roadside restaurant dining, were exposed to infected family members, and previously tested *H. pylori*-positive (p<0.05). Individuals with higher education levels, reporting more cafeteria dining and previously tested negative had a lower infection risk (p<0.05).

View this table:
[Table 3](http://gut.bmj.com/content/72/5/855/T3)

Table 3 
Demographic information of enrolled individuals and *Helicobacter pylori* infection risk factors

In multivariate logistic analysis, individual infection was strongly associated with the presence of infected members (eg, five infected members per household group: OR 2.72, 95% CI 1.86 to 4.00). In addition, geographical area of residence (eg, northwest China: OR 1.64, 95% CI 1.48 to 1.82), male sex (OR 1.14, 95% CI 1.08 to 1.21), being married (OR 1.31, 95% CI 1.18 to 1.45) and previous positive *H. pylori* tests (OR: 6.28, 95% CI: 5.41 to 7.28) were independent infection risk factors. Younger age (OR 0.57, 95% CI 0.46 to 0.70), higher education level (OR 0.85, 95% CI 0.79 to 0.91) and previous negative *H. pylori* tests (OR 0.44, 95% CI 0.39 to 0.48) were independent protective factors (table 3).

The individual infection rate also varied greatly depending on different provinces (table 2). It was as high as 59.61% in Qinghai, northwest China, and as low as 25.33% in Guizhou, southwest China (table 2). These infection rates were in accordance with household infection rates (table 1). A summary of the overall risk and protective factors was presented in online supplemental figure 5.

### *H. pylori* infection status and risk factors in couples

To further investigate the risk factors and the transmission pattern between couples, we analysed the infection status in this group of population. Among 10 735 families, 6145 (57.24%) contained one couple, and 877 (over 8%) contained more than two generations or couples (figure 3C); 3713 (34.59%) families only had either a wife or a husband (figure 3C). Of the total of 7961 couples (figure 3D), 1830 (22.99%) were both *H. pylori*-infected, 2644 (33.21%) were both not infected, and the rest had either the husband or wife infected. The infection rate increased with the duration of cohabitation (p<0.05, figure 3E); couples with a shorter cohabitation time (figure 3E) and higher income had lower infection rates, and *vice versa* (figure 3F, p<0.05).

### *H. pylori* infection status and risk factors for children and adolescents

In order to explore the *H. pylori* infection risk factors, and their correlation with parental infection status in children and adolescent, we further analysed their infection status and the possible transmission routes within the household. A total of 3781 children and adolescents were enrolled in this cohort (figure 3G, table 4); 2310 (61.09%) were from a one-child family and had no siblings (table 4). The rest had 1–3 or more siblings (table 4). The overall *H. pylori* infection rate in the 3781 children and adolescents was 20.55% (table 2, figure 1), which varied hugely depending on geographical area. For example, in Qinghai, a developing province in northwest China, the infection rate was 54.84%, but in Beijing, Shanghai, and other well-developed regions or provinces, the infection rates were all below 15% (table 2).

View this table:
[Table 4](http://gut.bmj.com/content/72/5/855/T4)

Table 4 
Demographic information and risk factors for *Helicobacter pylori* infection in children and adolescents

The risk factors for *H. pylori* infection in children and adolescents were similar to those in adults (table 4). For example, frequent dining at roadside restaurants (OR=1.38) increased the infection risk (p<0.05), whereas washing hands before meals and after defecation, and avoiding drinking tap water reduced the infection risk (p<0.05). The number of siblings and birth order were not associated with the childhood infection risk (p>0.05) (online supplemental figure 3, table 4). Notably, an *H. pylori*-infected mother, father, grandmother or siblings was associated with increased infection risk (p<0.001), but only infected mothers (OR=1.70) and fathers (OR=1.68) were independent risk factors for infection (p<0.05; table 4).

To evaluate the impact of parental infection status on childhood infection rate, a stratified analysis was performed on subgroups. A total of 1976 children and adolescents cohabitated with parents (figure 3G), their parental infection status is shown in figure 3H. We noted that their infection rate increased along with parental infection (p<0.001), from 13.57% in the group with no parent infected to 34.32% in the group with both parents infected (p<0.001; figure 3I).

## Discussion

This work investigated family-based *H. pylori* infection together with individual-based infection pattern in mainland China. The results reveal that the family-based *H. pylori* infection rate was much higher than the individual-based infection rates, and a large portion of Chinese families were infected. In several provinces, the infection rates were alarmingly above 80%, which is a serious condition that has not been recognised previously. In addition, we noted that the infection is concentrated in certain groups of families, instead of being evenly distributed in the population.

These results provide evidences to support the novel concept of ‘whole family-based *H. pylori* infection control and management’16 17 for related disease prevention, and the sister consensus publication of this investigation: the ‘Chinese consensus report on family-based *H. pylori* infection control and management (2021 edition)’.6 Together, they can be considered landmark events to transform *H. pylori* treatment from individual-based care to family-based infection control in clinical practice. Because this approach is more effective and convenient, it facilitates *H. pylori* management through better engagement of family members, higher eradication rates, lower reinfection rates16 17 and cost-effectiveness.27 Despite previous reports have demonstrated *H. pylori* family-cluster infection,9–15 18 28 large scale, detailed analysis the relationship of family member infection status, risk factor and pattern of infection has not been reported, this work provide novel insights on family-based *H. pylori* infection status at the national level.

Previously scattered small studies have investigated the relationship between household member *H. pylori* infection and various lifestyle risks.8 29–31 To assess *H. pylori* intrafamilial transmission in the general population and the role of the family’s social background, for example, one study in northern Italy in 1999 examined 416 families (3289 residents). The results indicated that family social status was independently related to infection in children, with blue-collar or farming families showing an increased infection risk compared with children of white-collar workers.29 Another study conducted on 2752 household members in northern California in 2006 found that exposure to an *H. pylori*-infected person with gastroenteritis, particularly vomiting, markedly increased the risk for new infection.8 

A community-based study in 2017 in Vietnam on 219 households (918 individuals) also showed that high monthly income, not regularly being fed chewed food, and being breastfed were protective factors against *H. pylori* infection. Risk factors for infection in children were not regularly handwashing after defecation, an *H. pylori*-infected mother and grandfather, the father’s occupation, mother’s education, and household size.30 One 2022 family-based *H. pylori* infection survey on 282 families (772 individuals) also reported that the household infection rate was 87.23% in central China.31 The current work is in line with these studies and provides important evidence indicating that the clustering of infections within the same family was due to increased infection, not simply by chance. It also highlights the importance of implementing family-based *H. pylori* infection control and management in clinical practice.

This survey enrolled families of largely urban residence (74.61%) and a small portion of rural residents (25.39%), which differs from a previous investigation in 1992.32 However, it reflects the current social structure in Chinese society, because decades-long urbanisation and industrialisation have profoundly changed its population structure. The latest national census in 202123 revealed that the proportion of urban residents in 2021 (urban 64.72%, rural 35.28%) was much higher than that in 1990 (urban 26.41%, rural 73.59%), and the average family size has shrunk to 2.62 persons in 2021 from 4.05 persons in 1990. The present enrolments thus are consistent with the latest national demographic trends.23 

Earlier small studies have provided clues on the correlation of marriage time and infection risk,12 33 34 and the result supported a spouse-to-spouse transmission, although the infection between couples were thought to be infrequent and dependent on the social economic status. The current work with 7961 couples have demonstrated that there are indeed increased infection rate from 17% to 22%–24% when their cohabitation time increase from 5 to 30 years (figure 3E). However, it is not clear if the increased infection rate is because of the transmission between couple themselves or from outside the family, or both. As *H. pylori* infection rate increase with age (figure 2A), future studies using the DNA fingerprinting technology are required to clarify the infection pattern between couples.

In addition, the role of generation in household infection appears biphasic and only closely related to family size in current study, since it showed opposite effects before and after multivariate logistic adjustment (table 1). The generation was a risk factor for household infection before multivariable logistic adjustment, but a protective factor after adjustment, and became a risk factor again when it was not adjusted by the family size, furthermore, testing on all other variable adjustments did not change this conclusion. This result is not expected, and was not reported before, previously studies have clearly demonstrated that large family size, crowded condition, more sibling, poor household hygiene are risk factors for *H. pylori* infection,8 28–30 and more generation in a household tend to have larger family size, but no study have focused on the role of generation on household infection prior to this work. These results unexpectedly revealed its role in household infection and indicated a complex pattern of *H. pylori* intrafamilial spread. The explanation for these subtle discrepancies could be due to the fact that at a given family size, more generations in a family means fewer members in each generation, and possibly higher income, lower infection risk; while at a given number of generations, larger family size is a risk factor for infection, which is in line with the current concept and observations. However, future studies may be required to clarify the role of generation in the household infection in more detail.

The general *H. pylori* infection status at national level has not been evaluated in China. *H. pylori* infection rate has been declining both globally and in China,35 but existing infected individuals still pose a great health threat to the uninfected population. One meta-analysis24 in 2020 in China which included 670 572 participants found that the infection rates during 1983–1994, 1995–2005 and 2006–2018 were 63.8%, 57.5% and 46.7% respectively, with an annual decline rate of 0.9%. The current overall infection rate of 40.66% is thus in line with such trend. This could be attributed to the continued education, improved economic and sanitary conditions, better water quality and interventions over the past decades. However, we also noted that only 13.44% (1,699/12,646) of *H. pylori*-infected patients had received treatment. Although this number may not be exactly proportional to the national eradication level, it indicates a critical challenge that has yet to be met for population-wide infection control.

Geographical location is important for diverse *H. pylori* infection status due to various lifestyle among different countries, in accordance with the already known risk factors from previous studies,29–32 36 this survey reveals risk factors that have not been well recognised, and some are unique to China or Asian countries. One of them is that using serving chopsticks and spoons was associated with a lower infection rate. Sharing food with the same utensils or dishes is a traditional habit preserved in China and many Asian countries for centuries. This was considered a risk factor for *H. pylori* infection because the saliva culture of *H. pylori*-infected patients has confirmed the existence of oral *H. pylori*,37 and *H. pylori* DNA can be detected on chopsticks.38 Another family habit is chewing food before feeding it to children, a practice that was very common previously but is now rare in childcare. This is also supported by a population-based study in China36 in 2015, which showed that individually served meals represented an independent protective factor for *H. pylori* infection.

*H. pylori* infection rates vary greatly depending on different geographical locations in China, the north and northwest regions are high prevalence regions for both *H. pylori* infection and gastric cancer incidence, and are also economically developing areas historically, this correlated well with the social economic status, living conditions and lifestyle habits.24 39 40 For example, in Qinghai and Gansu, the two developing pasturing northwest region, has the higher *H. pylori* infection rate and gastric cancer incidence (online supplemental figure 4). In addition, a previous positive *H. pylori* test was shown as a risk factor in the current work. According to the questionnaire, this was partially due to a small proportion of enrolled participants who were either unable or unwilling to receive treatment, and thus had persistent infections.

Contaminated water has been recognised as a source of *H. pylori* spread,41 however, whether or not it is still an important factor for current *H. pylori* spread in China remains to be evaluated. In this work, we noted drinking various types of water was not an independent risk factor for infection. This is probably because tap water and sewer systems are routinely available in all urban areas and most rural villages in China, and acquiring *H. pylori* infection from this route appears rare now.

*H. pylori* plays an important role in the increased prevalence of precancerous changes in relatives of gastric cancer patients, however, compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria but a similar prevalence of *H. pylori* infection.18 A study in Germany showed that the prevalence of *H. pylori* infection was much higher among participants with a parental history of stomach cancer than among other participants.42 Another study in San Marino indicated that *H. pylori* seropositivity was significantly associated with peptic ulcer in patients and their close relatives, in siblings and gastric cancer in fathers. In contrast, *H. pylori* seropositivity was not significantly associated with gastroduodenal diseases in partners.43 In the current work, a familial history of gastric cancer was a risk factor for *H. pylori* infection, but a family history of either gastric cancer or peptic ulcer was not an independent factor for *H. pylori* infection. These results are partially in line with the described observations and indicate a complex pattern of *H. pylori* spread among family members, which deserves further delineation.

In the current study, the risk factors for childhood infection were infected family members, older age and unhygienic living habits, and the most vulnerable time for infection is at preschool and school ages. This is in line with previous small studies36 44 and a 2022 meta-analysis report45 that included 152 650 children. The result of the latter indicated that paediatric *H. pylori* infection was significantly associated with lower economic status, having an infected mother or infected sibling, and older age. However, due to the previous national ‘one-child-per-family’ policy between 1982 and 2016, most Chinese families only have one child and two generations. These children usually have no or few siblings, so transmission among siblings may not be the major route in the Chinese setting. This is also indicated in the current study data that 61.09% of children had no siblings.

This study has limitations. First, the survey adopted a convenience sampling method instead of randomised sampling, which might have biased the selection of the population. However, due to the large sample size, the impact might be minor and does not affect the conclusions. Second, *H. pylori* infection was evaluated using 13C-UBT test, and not combined with serum antibody or stool antigen tests. This only indicates the current infection status, therefore, it was not a complete landscape of *H. pylori* infection, and probably underestimated the real infection rate. Third, this is a cross-sectional study without data from endoscopy, thus missing more in-depth information on related diseases. Fourth, the work was performed in the Chinese setting, and the results may not apply to other areas. Fifth, the *H. pylori* genotype in infected families was not evaluated due to the lack of bacteria strain culture and DNA fingerprinting data; future in-depth studies are warranted. However, even with these limitations, the study has provided important evidence and novel points about family-based *H. pylori* infection.

## Conclusions

The current work provides insights on family-based *H. pylori* infection in Chinese society, and important sources for its spread. These evidences support shifting from current individual-based care to family-based *H. pylori* infection management in clinical practice. Therefore, the test/treat strategies in family setting have important clinical and public health implications for infection control and related disease prevention, and are also valuable to other communities that have high infection rates and gastric cancer burdens.

## Data availability statement

The original data from this study are freely accessible from the National Clinical Research Center for Digestive Diseases website ( [http://www.ncrcgastro.org](http://www.ncrcgastro.org/) ) after registration through the administrator.

## Ethics statements

### Patient consent for publication

Not applicable.

### Ethics approval

The research protocol was approved by the ethics committee of Changhai Hospital (CHEC2021-131). Participants gave informed consent to participate in the study before taking part.

## Acknowledgments

The authors would like to thank all the regional and provincial site leaders and team members for their time, effort and dedication on the survey (the list is in alphabetical order of family name).

Prof Ping Chen from The Affiliated Hospital of Inner Mongolia Medical University;

Prof Wei-Gang Chen from The First Affiliated Hospital, School of Medicine, Shihezi University;

Prof Ye Chen from Shenzhen Hospital of Southern Medical University;

Prof Xiao-Song Dai from Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital;

Prof Hui-Zhen Fan from Yichun People’s Hospital;

Prof Shui-Xiang He from The First Affiliated Hospital of Xi’an Jiaotong University;

Prof Ren-Wei Hu from West China Hospital of Sichuan University;

Prof Xiao-Xi Huang from Haikou People’s Hospital;

Prof Rui Ji from The First Hospital of Lanzhou University;

Prof Chun-Hui Lan from Daping Hospital of Army Medical University;

Prof Bing-Qing Li from Affiliated Hospital of Chengde Medical University;

Prof Chang-Ping Li from The Affiliated Hospital of Southwest Medical University;

Prof Pei-Yuan Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;

Prof Yan-Qing Li from Qilu Hospital, Cheeloo College of Medicine, Shandong University;

Prof Zhi-Hui Lin from Fujian Provincial Hospital;

Prof Bin Lu from Zhejiang Provincial Hospital of Chinese Medicine;

Prof Ying-Lei Miao from First Affiliated Hospital of Kunming Medical University;

Prof Bo Qu from The Second Affiliated Hospital of Harbin Medical University;

Prof Yi-Hai Shi from Shanghai Pudong Gongli Hospital;

Prof Bi-Guang Tuo from Affiliated Hospital of Zunyi Medical University;

Prof Bang-Mao Wang from Tianjin Medical University General Hospital;

Prof Fen Wang from The Third Xiangya Hospital of Central South University;

Prof Jiang-Bin Wang from China–Japan Union Hospital of Jilin University;

Prof Jun-Ping Wang from Shanxi Provincial People’s Hospital;

Prof Meng-Chun Wang from Shengjing Hospital of China Medical University;

Prof Xue-Hong Wang from Qinghai University Affiliated Hospital;

Prof Ying Wu from The Second People's Hospital of Shaanxi Province;

Prof Jian-Ming Xu from The First Affiliated Hospital of Anhui Medical University;

Prof Shao-Qi Yang from General Hospital of Ningxia Medical University;

Prof Zhi-Gang Yang from Yinchuan Hospital of Traditional Chinese Medcine;

Prof Guo-Xin Zhang from First Affiliated Hospital of Nanjing Medical University;

Prof Xiao-Lan Zhang from The Second Hospital of Hebei Medical University;

Prof Peng-Yuan Zheng from The Fifth Affiliated Hospital of Zhengzhou University

Credit also goes to Prof Cheng Wu from the Department of Statistics of Naval Medical University for her helpful advice on statistical analysis and Dr Hua-Xiang Xia from Medjaden Inc for assistance in revising the manuscript.

## Footnotes

*   X-ZZ, N-HL and H-YZ are joint first authors.

*   X-ZZ, N-HL and H-YZ contributed equally.

*   Contributors Y-QD, Z-SL, and S-ZD take responsibility for the integrity and accuracy of the overall content. Conception and design: Y-QD, Z-SL, N-HL and S-ZD. Drafting of manuscript: X-ZZ, S-ZD and H-YZ. Data collection and analysis: X-ZZ, S-ZD, H-YZ and Q-CC. Initial district survey: X-YK and PX. Coordination and monitoring of survey processes: N-HL and L-YZ. Administrative, technical or material support: Y-QD, Z-SL, N-HL and S-ZD. All authors had full access to the data used to generate results in this article and have critically reviewed and approved the manuscript for publication.

*   Funding The study was supported by grants from the National Clinical Research Center for Digestive Diseases (Shanghai, 19MC1910200), Program of National Key Research and Development (2019YFC1315900), Program of Shanghai Academic Research Leader (21XD1404900), Project of Shanghai Municipal Health Commission (2019SY001), National Natural Science Foundation of China (U1604174), Henan Provincial Government-Health and Family Planning Commission (20170302, SBGJ202002004), and Henan Provincial Government—Health and Family Planning Commission Science Research Innovative Talents Project (51282).

*   Competing interests None declared.

*   Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

*   Provenance and peer review Not commissioned; externally peer reviewed.

*   © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

*   Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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