Alimentary Pharmacology and Therapeutics

Prevalence and risk factors of Helicobacter pylori infection in

asymptomatic Chinese children: a prospective, cross-sectional,
population-based study
Z. Ding*, S. Zhao*, S. Gong†, Z. Li‡, M. Mao§, X. Xu* & L. Zhou‡

*Department of Gastroenterology, SUMMARY

Beijing Children’s Hospital of Capital
Medical University, Beijing, China.
†
Department of Gastroenterology,
Background
Guangzhou Women and Children’s Limited research has been published on current Helicobacter pylori infection rate in
Medical Center of Guangzhou asymptomatic children in China.
Medical College, Guangzhou, China.
‡
Department of Gastroenterology,
Aim
Peking University Third Hospital,
Beijing, China. To assess current Helicobacter pylori infection rate, distribution characteristics and
§
Department of Pediatrics, West risk factors in Chinese asymptomatic children.
China Second Hospital of Sichuan
University, Chengdu, China. Methods
A prospective, cross-sectional, population-based study was performed from 2009 to
Correspondence to: 2011 in three cities of China. Helicobacter pylori infection was diagnosed by a stool
Dr X. Xu, Department of antigen test. Multi-stage cluster random sampling was used to select asymptomatic
Gastroenterology, Beijing Children’s children including neonates. Socioeconomic details were obtained through a stan-
Hospital of Capital Medical University, dardised questionnaire.
56 Nan Lishi Road, Xicheng District,
Beijing 100045, China.
E-mail: xuxiweibch@163.com
Results
Dr L. Zhou, Department of Among total of 3491 children (0–18 years), the global infection rate was 6.8% and
Gastroenterology, Peking University there were no significant differences between genders. Age specific infection rate
Third Hospital, 49 North Garden Rd., between regions was significantly different (P < 0.05). The infection rate signifi-
Haidian District, Beijing 100191, China.
cantly increased with age (P for trend <0.01). It was low during the newborn (0.6%)
E-mail: liyazhou@medmail.com.cn
to preschool period and was significantly increased in high school students (13.5%)
(P < 0.01). Multivariable regression indicated that hand sanitisation, individually
Publication data served meals, higher education level of mother, above average living space and resi-
Submitted 19 June 2015
dence in urban areas were significantly protective against infection (OR 0.749, 0.698,
First decision 7 July 2015
Resubmitted 22 July 2015
0.720, 0.838 and 0.770 respectively). Conversely, consuming meals in unsanitised
Accepted 23 July 2015 conditions, sharing towels, receiving pre-chewed food from the mother, artificial
EV Pub Online 14 August 2015 feeding and family history of gastrointestinal disease were significantly associated
with the risk of infection (OR 1.200, 1.965, 2.002, 1.071 and 2.093 respectively).
This article was accepted for publication
after full peer-review.
Conclusions
Helicobacter pylori infection rate increases with age in Chinese asymptomatic chil-
dren and is common after 10 years of age. The rate of infection is related to socioe-
conomic status.

Aliment Pharmacol Ther 2015; 42: 1019–1026

ª 2015 John Wiley & Sons Ltd 1019

doi:10.1111/apt.13364
Z. Ding et al.
INTRODUCTION
The occurrence of Helicobacter pylori infection is signifi-
cantly higher in developing countries when compared to
developed nations. It is one of the most common
chronic bacterial infections in China.1–4 H. pylori infec-
tion is closely related to the occurrence of chronic gastri-
tis, peptic ulcer and gastric cancer.5 The high prevalence
of H. pylori infection and gastrointestinal diseases in
adults is closely related to H. pylori infection during
childhood.6 From the information gathered, it is evident
that in developing countries such as China, the conse-
quences of attracting H. pylori will directly affect the
quality of life and the probability of developing other
diseases during adulthood. Therefore, the best period for
H. pylori infection prevention is during childhood. Inves-
tigation of H. pylori infection in children from different
regions in China and identification of relevant risk fac-
tors are thus necessary. Previous investigations of the
epidemiology and relevant risk factors of H. pylori infec-
tion in Chinese children have mainly focused on symp-
tomatic children in individual hospital from a single
region, or the information obtained as secondary data
from epidemiological research on adults.2, 3, 7, 8 In addi-
tion, most of the previous studies have involved the use
of serological detection of Hp-IgG antibody.1, 2, 7 Pre-
sently, there has been a lack of epidemiological investiga-
tion of current H. pylori infection rate in asymptomatic
children of different ages (including newborns) from dif-
ferent regions in China.
Therefore, this prospective, cross-sectional, popula-
tion-based study was carried out in three cities of China
using an H. pylori stool antigen (HpSA) test which is a
reliable, non-invasive and easily used tool in children.
The children’s family background and lifestyle were
investigated using a questionnaire survey. The study
results were used to analyse H. pylori infection rate and
relevant risk factors in natural populations of
asymptomatic children in different regions of China.
METHODS
Study subjects
The present study was conducted between June 2009
and January 2011 in China. Children were selected using
multi-stage cluster random sampling from resident pop-
ulations in Beijing, Guangzhou and Chengdu. The first
random sampling was performed within three basic sam-
pling districts from each city. The second random sam-
pling was conducted within 12 basic sampling units
(child care centres, kindergartens and schools) based on
1020
the selected sampling districts. Participants would be
included in the study if: (i) Aged <18 years; (ii) They
were healthy without gastrointestinal symptoms; (iii) An
informed consent can be obtained from primary care-
taker. Healthy neonates born during the study period
were selected from the same areas and were sampled to
fully understand the pattern of H. pylori distribution in
children of all ages.
The study was approved by the Ethics Committee of
Peking University Health Science Center, Beijing Chil-
dren’s Hospital, Guangzhou Women and Children’s
Medical Center and West China Second Hospital. Writ-
ten informed consents were obtained from all partici-
pants or their guardians.
Data collection
The selected children were from each grade level and
were surveyed using a comprehensive and practical ques-
tionnaire form adapted from a previous H. pylori infec-
tion questionnaire used nationwide. The questionnaire
consisted of three categories which totalled to 33 items.
The categories involve questions with regard to basic
individual and household characteristics, individual and
household hygiene habits and household socioeconomic
status. Research assistants and teachers were trained by
professional researchers. The selected students and their
parents subsequently completed each questionnaire item
under the guidance of the researchers, research assistants
and teachers.
HpSA test
A stool sample was requested from each participant and
HpSA test was performed on the stool sample. Fresh
stool specimens were collected from each subject in ster-
ile containers by the parents or the health staff and then
preserved at 4 °C until the analysis were carried out dur-
ing the same day. The sample would be brought back to
room temperature before the test. The HpSA test was
performed using a commercial double-antibody sandwich
enzyme-linked immunosorbent assay (PUMC Pharma-
ceutical Co., Ltd., Beijing, China) in accordance with
manufacturer’s instructions and method, which has been
validated in Chinese children before the study. Based on
manufacturer’s guidelines and recommended cut-off val-
ues, an optical density (OD, 450/650 nm) of greater than
0.12 was considered to be positive.
Sample size
OpenEpi (http://www.openepi.com) is used to calculate
sample size. According to published data, we assumed
Aliment Pharmacol Ther 2015; 42: 1019–1026
ª 2015 John Wiley & Sons Ltd

that hypothesised H. pylori infection rate in asymp-
tomatic children would be 20%. Based on a Confidence
Limit of 1.5% and a 95% CI for the estimates:
Sample size n = [DEFF 9 Np(1 p)]/[(d2/Z21 a/2
9 (N 1) + p 9 (1 p)]. A sample size of 2731 is
required for all three cities. We added at least 20% to
allow for contingency, a total of 3491.
Statistical analysis
The data were analysed using SPSS 19.0 software (IBM
SPSS Inc., Armonk, NY, USA). Group comparisons of
count data (H. pylori infection rate, regional distribution
and age distribution) were performed using the v2 test.
Chi-square linear trend among different age groups was
also carried out. Analysis of relevant risk factors was
performed using multiple logistic regression. The pres-
ence or absence of H. pylori infection is then set as the
dependent variable, which was determined using the pre-
viously described cut-off values. A value of P < 0.05 was
considered statistically significant.
RESULTS
Demographic characteristics of the investigated
population
A total of 3491 children were selected from the three
cities. They ranged in age from 1 day to 18 years
(mean age 7.3  5.4 years). The participants consisted
of 1760 males and 1731 females, including 330 new-
borns, 319 infants 1–12 months, 289 children of 1–
3 years old, 624 of 4–6 years old, 528 of 7–9 years old,
308 of 10–12 years old, 685 of 13–15 years old and 408
of 16–18 years old.
Helicobacter pylori infection rate
Among the 3491 healthy children, 237 (6.8%) were posi-
tive for H. pylori infection (134 males (56.5%) and 103
females (43.5%). The remaining 3254 children that were
tested negative for H. pylori infection consisted of 1626
males (49.9%) and 1628 females (50.1%).
In the specific gender groups, the infection rates
were 7.6% in 1760 males and 6.0% in 1731 females,
and the differences between genders were not statisti-
cally significant (P > 0.05). However, further analysis
revealed that although there were no statistically
significant gender-related differences in Beijing and
Guangzhou (P > 0.05), the infection rate between
males (6.9%) and females (4.0%) in Chengdu was
significantly different (P = 0.04).
Aliment Pharmacol Ther 2015; 42: 1019–1026
ª 2015 John Wiley & Sons Ltd
Prevalence and risk factors of H. pylori in children
Regional distribution of H. pylori infection
The overall H. pylori infection rates were 7.3% in Beijing,
6.7% in Guangzhou and 5.6% in Chengdu. Data compar-
ison between southern and northern regions revealed
that the infection rate tended to be higher in the north
compared with the south, but the difference was not sta-
tistically significant (P > 0.05).
However, with regard to age specific difference, the
infection rate was significantly different among three
regions (P < 0.05; Figure 1). Among the age group 1–
12 months, 1–3 years and 4–6 years, children in Beijing
have a higher infection rate than the other two cities
(P < 0.05). The pattern changed after age group 13–
15 years, especially among the age group 16–18 years in
Guangzhou, where the prevalence has reached 33% com-
pared to 13% in Beijing (P < 0.05).
Age distribution of H. pylori infection
The results of grouping analysis in school age children
have indicated that the overall infection rate displayed a
linear growth trend with increasing age. Furthermore, the
infection rate differed significantly among the various age
groups (P < 0.01; Table 1, Figure 1). Chi-square for lin-
ear trend among the age groups was statistically signifi-
cant (P < 0.01). The infection rate was low in children
<4-year old, but exhibited two distinct peaks after four
and 10-year old. The infection rate was significantly
higher in high school students (13.5%) when compared
with other school age children (P < 0.01). In addition, the
infection rate has reached up to 33% in high school stu-
dents in Guangzhou. Age specific difference between dif-
ferent regions has been discussed previously (Figure 1).
To compare with the previous studies performed, the
infection rate in children aged 8–10 years in Beijing was
obtained separately to match the same age group
enrolled in 1991 and 2006 in the same city.8 A decrease
in infection rate in Beijing was observed when the result
of 2009 to 2011 (11.2%) was compared with the data
obtained in 1991 (24.1%, P < 0.05) and 2006 (19.1%,
P < 0.05), while there was no significant decline from
1991 to 2006 (P>0.05).
Risk factors for H. pylori infection
The factors related to H. pylori infection were analysed
using multivariate logistic regression (Tables 2–3). Results
from the study shows that the difference in living condi-
tions, sanitation habits, living habits and family back-
ground will significantly impact the infection rate among
the participants. By comparing the test results to the
1021
Z. Ding et al.

35 33.3
Beijing
30 Guangzhou
Chengdu
25
21.4
Infection rate (%)

20
17.2

15 13
12.1 12.5
11.5
9.7
10 8.6
7.1
5.6 5.7 6.2
4.9 5
5 3.8 4.1 3.6 3.9

0.3 0 0 0.7 0.6

0
Newborns 1-12 months 1-3 years 4-6 years 7-9 years 10-12 years 13-15 years 16-18 years
Age group

Figure 1 | Helicobacter pylori infection rate in different regions according to each age group.

Table 1 | Helicobacter pylori infection rate by age group Table 2 | Multivariate logistic regression analysis of
according to all participants from three regions basic individual and household situations and hygiene
habits related to Helicobacter pylori infection
Age H. pylori
categories Total number, N positive, n (%) P Risk factors OR 95% CI P
Newborns 330 2 (0.6) 0.000 Receiving pre-chewed 2.002 1.357–2.954 0.000
1–12 months 319 8 (2.5) food by the mother
1–3 years 289 6 (2.1) in early childhood
4–6 years 624 45 (7.2) Artificial or mixed feeding 1.071 1.006–1.140 0.032
7–9 years 528 32 (6.1) History of family member 2.093 1.307–3.351 0.002
10–12 years 308 34 (11.0) with gastrointestinal disease
13–15 years 685 55 (8.0) Frequently hand sanitisation 0.749 0.593–0.946 0.015
16–18 years 408 55 (13.5) Consuming meals 1.200 1.011–1.425 0.037
Total 3491 237 (6.8) in unsanitised conditions
Individually served meals 0.698 0.553–0.882 0.003
N/n, number.
Sharing towels 1.965 1.243–3.107 0.004
and mouth-rinsing glass
information collected from the questionnaires, it is evi- OR, odds ratio; CI, confidence interval.
dent that certain factors including frequently hand saniti-
sation, individually served meals, higher education level tively. It is apparent that practices such as sharing towels,
of the participant’s mother, above average living space, feeding pre-chewed food by the mother, and history of
and residence in urban areas will considerably reduce the family members with gastrointestinal disease will increase
odds ratio. The odds ratios for these factors are 0.749, the risk of infection by more than 100%.
0.698, 0.720, 0.838 and 0.770, respectively. Conversely,
factors including consuming meals in unsanitised condi- DISCUSSION
tions, sharing towels and mouth-rinsing glass, receiving Acquisition of H. pylori infection mainly occurs in chil-
pre-chewed food from the mother in early childhood, dren.9–11 The prevalence of infection in children varies
artificial or mixed feeding, and history of family members between 4.9% and 73.3% worldwide depending on
with gastrointestinal disease will result in an increase in different countries, target population, range of ages, years
the risk of infection. The odds ratios for the factors listed of specimen collection, sample size and detection meth-
above were 1.200, 1.965, 2.002, 1.071 and 2.093 respec- ods used in the studies.12–16 Infection prevention at an

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ª 2015 John Wiley & Sons Ltd

Table 3 | Multivariate logistic regression analysis of
household socioeconomic conditions related to
Helicobacter pylori infection
Risk factors OR 95% CI P same range of ages in Beijing was 11.2% during 2009–
Higher education 0.720 0.584–0.887 0.002
level of the mother
Above average 0.838 0.717–0.980 0.027
living space
Residence in urban 0.770 0.612–0.969 0.026
areas rather than
in rural areas
OR, odds ratio; CI, confidence interval.
earlier age including childhood may reduce the overall
infection rate and the incidences of gastric diseases.17–24
In China, the infection rate is 29.2–53.2% among symp-
tomatic children in hospitals. Furthermore, this figure
increases significantly after 12 years of age.3, 7 Results
from the present study indicated that the overall H.
pylori infection rate in asymptomatic children was 6.8%
in three cities in China. Considering that the present
study was conducted in a country with high H. pylori
prevalence, it is interesting that the overall infection rate
of 6.8% is the second lowest reported in children in the
last 20 years worldwide.14, 15 This is most likely due to a
wider age range (from newborn to 18 years), a larger
sample size, specimen collection in more recent years
and different detection method used in the study.
The rates of H. pylori infection and related diseases
have been declining yearly in developed and rapidly
developing countries, although the infection is still com-
mon in some geographic areas.19, 25–29 Some studies
from Asian countries also have shown decreasing rates
of H. pylori infection over the past 40–50 years.15, 30–34
In Japan, the overall seroprevalence rate decreased from
72.7% in 1974 to 39.3% in 1994, which may has led to a
decline in gastric cancer in Japan.25, 34 In South Korea,
the seroprevalence rate was 66.9% in 1998, which
decreased to 59.6% in 2005.34 In a study including Chil-
dren from Guangzhou province in southern China, the
seroprevalence of H. pylori was found to significantly
decrease from 62.5% in 1993 to 49.3% in 2003.35 Results
from the present study indicated that infection in
children was related to the socioeconomic status of the
family. Thus, the recent rapid development of China’s
economy, improvement in living standard, reduction in
average household size after the implementation of the
one child policy, enhancement of the level of education,
and continuous improvement in public health conditions
might have helped reduce the infection rate in children.
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Prevalence and risk factors of H. pylori in children
Zhang et al. reported that the H. pylori infection rate in
asymptomatic children aged 8–10 years in Beijing area
was 24.1% in 1991 and it declined to 19.1% in 2006.8
The present study indicated that the infection rate in the
2011. Therefore, the infection rate may have declined
compared with 1991 and 2006. As a result of different
sampling districts, sample sizes and detection methods
used in different studies, study results may be biased and
further standardised studies should be performed.
There was an overall increasing trend with increasing
age in the present study, which was consistent with the
findings in the literature.21–23 Helicobacter pylori infec-
tion was generally not present during the neonatal per-
iod, while the rate increased significantly after 10 years
of age, especially in high school students. Increasing
trend in students after 10 years of age may be attributed
to the significant changes of environment and lifestyle.
Potential H. pylori infection in children without symp-
toms may not be ignored, especially in high-risk areas
for stomach cancer. So far, the need of testing young
asymptomatic children for long-term surveillance of gas-
tric diseases remains unclear. Considering of the rates of
spontaneous eradication and re-infection, the necessity
of early screening of infection, long-term follow-up for
relevant diseases and early eradication (especially for
high school age) need to be further clarified.
Although the overall difference was not significant
between different regions, age specific difference can be
significantly observed. In children aged <13 years, we
detected a higher prevalence in Beijing compared to the
other two cities. However, the pattern significantly chan-
ged in children aged >13 years. There was no significant
increasing trend in Beijing while a higher prevalence
could be found in the other two cities. In children aged
16–18 years, the prevalence has reached 21% in Chengdu
and 33% in Guangzhou compared to 13% in Beijing.
The change of pattern in age difference may be associ-
ated with regional differences in eating habits, customs
and lifestyle including socio-demographic situation.
Risk factors for H. pylori infection including family
background and lifestyle have been reported in a number
of previous studies.22, 23, 36, 37 The results of surveys
worldwide have revealed that socioeconomic level may
play an important role in the risk for H. pylori infection,
although it still remains controversial due to the
characteristics of the target population and the variables
used to evaluate the risk factors.22, 23, 38–43 The most
likely mode of transmission is from person to person by
mouth through either oral-oral route (possibly saliva) or
1023
Z. Ding et al.
faecal-oral route.37 According to the present study, sig-
nificant aggregation will occur within the family as a
result of poor sanitation habits and health awareness
(Table 2). Therefore, it is critical to educate and empha-
sise the importance of proper strategies to children at an
early age to reduce the risk of infection. These strategies
include individually served meals, common serving chop-
sticks and sufficient hygiene habits. It is evident from
the concordance patterns determined by past studies that
mother–child and sib–sib transmission remains to be the
primary transmission pathways of H. pylori.15, 44–46 As a
result, mothers and children tend to harbour the same
strains of H. pylori and mother-to-children infection is
the dominant transmission route. However, this will
unlikely occur between fathers and children.15, 45, 46 The
relationship between the parents’ education level and H.
pylori infection has been reported by several studies.38–43
In the present study, high educational level of the partic-
ipant’s mother correlates with lower risk of infection and
plays a protective role, while the educational level of the
participant’s father plays no factor against the infection.
This is likely related to the different geographic back-
grounds of the population. H. pylori colonisation in the
caretakers or siblings should be further investigated to
identify the main transmission pattern in Chinese family.
Investigations of H. pylori infection in asymptomatic
children have been performed in other regions of China.
In 2000, an Hp-IgG antibody test was used to detect
infection in 526 asymptomatic children aged 35 days to
14 years in Tianjin city.7 The infection rate was 31.18%
(164/526) in Tianjin, which was higher than that in the
present study. The overall high infection rate in Tianjin
may be the consequence of the potential inaccuracy of
the infection status in the participants, since the half-life
of Hp-IgG is relatively long and antibodies obtained
from the mother via the placenta can be present during
infancy. Therefore, the HpSA test is the more appropri-
ate method used for screening H. pylori infection within
population of newborns and small infants to reflect the
current infection status. The HpSA test is a proven
method that is non-invasive, rapid, low cost and reliable
in the diagnosis of H. pylori infection in both adults and
children.47–54 The method has been used to evaluate the
prevalence of H. pylori infection in a population-based
sample of asymptomatic children including newborn,
infant and toddler populations.22, 42, 49, 55 The sensitivity
and specificity of the HpSA test in Chinese children were
1024
94.7% and 95.1% respectively.55 Therefore, the HpSA test
was selected as the testing method used for the present
study.
The limitations of the present study mainly include: (i)
The small sample size might cause heterogeneity between
regions; (ii) The H. pylori antibody test was not combined
with the stool test; (iii) Family members did not contribute
stool samples and effect of presence/number of siblings on
risk for H. pylori was not observed; (iv) No incidence
study was carried out; and (v) There was no detection of
H. pylori subtype strains. Therefore, the plan for future
research will be to develop solutions for the problems
mentioned above. Further studies should be conducted to
clarify the necessity of early screening, long-term surveil-
lance and early eradication of H. pylori infection in asymp-
tomatic children exposed to high-risk factors.
CONCLUSIONS
In summary, H. pylori infection rate among Chinese
asymptomatic children increases with age and is high
after the age of 10. Significant age specific differences
among different regions are present, although there are
no overall regional differences. Helicobacter pylori infec-
tion rate in children may have declined in Beijing in
recent years.
AUTHORSHIP
Guarantor of the article: Dr Xiwei Xu is the guarantor
and takes full responsibility for the integrity of the data
from inception to the published article.
Author contributions: Zhaolu Ding participated in the
conception and design of the study, analysed data and
drafted manuscript. Shuai Zhao collected samples and
performed H. pylori stool antigen test. Sitang Gong, Zail-
ing Li and Meng Mao participated in the implementa-
tion of the study, collected samples and managed data.
Xiwei Xu and Liya Zhou designed the study, reviewed
data and revised manuscript. All authors approved the
final version of the article.
ACKNOWLEDGEMENTS
Declaration of personal interests: None.
Declaration of funding interests: This study was funded
in full by the Key Projects in the National Science &
Technology Pillar Program of China during the 11th
Five-Year plan period, grant no. 2007BAI04B02. Other
funding interests: None.
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ª 2015 John Wiley & Sons Ltd

REFERENCES
1. Mitchell HM, Li YY, Hu PJ, et al.
Epidemiology of Helicobacter pylori in
southern China: identification of early
childhood as the critical period for
acquisition. J Infect Dis 1992; 166: 149–
53.
2. Zhang WD, HU FL, Xiao SD, Xu ZM.
Prevalence of Helicobacter pylori
infection in China. Mod Digestion
Interv 2010; 15: 265–70.
3. Li HY, Deng T, Zhan YJ, Pi XY.
Clinical analysis of Helicobacter pylori
infection of 3368 children in Wuhan.
Chin J Gastroenterol Hepatol 2012; 21:
63–5.
4. Liu Y, Yue H, Li A, et al. An
epidemiologic study on the correlation
between oral Helicobacter pylori and
gastric H. pylori. Curr Microbiol 2009;
58: 449–53.
5. Torres J, P
erez-P
erez G, Goodman KJ,
et al. A comprehensive review of the
natural history of Helicobacter pylori
infection in children. Arch Med Res
2000; 31: 431–69.
6. Peterson WL GDY. Helicobacter pylori.
In: Feldman Sleiseneger MH, ed.
Sleiseneger and Ford Trans
Gastrointestinal and Liver Disease:
Pathophysiology, Diagnosis,
Management, 8th ed. Philadelphia, PA:
WB Saunders Company, 2006;
732–49.
7. Xu XH, Liu FL, Zhang SH, Zhao JS, Shi
J. Analysis on Helicobacter pylori
infection and its related diseases in
1442 children in Tianjin city. Chin J E
pidemiol 2000; 21: 100–2.
8. Zhang DH, Zhou LY, Lin SR, et al.
Recent changes in the prevalence of
Helicobacter pylori infection among
children and adults in high- or low-
incidence regions of gastric cancer in
China. Chin Med J (Engl) 2009; 122:
1759–63.
9. Kori M, Goldstein E, Granot E.
Helicobacter pylori infection in young
children detected by a monoclonal stool
antigen immunoassay. Pediatr Infect Dis
J 2009; 28: 157–9.
10. Rowland M, Daly L, Vaughan M,
Higgins A, Bourke B, Drumm B. Age-
specific incidence of Helicobacter pylori.
Gastroenterology 2006; 130: 65–72; quiz
211.
11. Goodman KJ, O’rourke K, Day RS,
et al. Dynamics of Helicobacter pylori
infection in a US-Mexico cohort during
the first two years of life. Int J
Epidemiol 2005; 34: 1348–55.
12. Segal I, Otley A, Issenman R, et al. Low
prevalence of Helicobacter pylori
infection in Canadian children: a cross-
sectional analysis. Can J Gastroenterol
2008; 22: 485–9.
Aliment Pharmacol Ther 2015; 42: 1019–1026
ª 2015 John Wiley & Sons Ltd
Prevalence and risk factors of H. pylori in children
13. Kimang’a AN, Revathi G, Kariuki S,
Sayed S, Devani S. Helicobacter pylori:
prevalence and antibiotic susceptibility
among Kenyans. S Afr Med J 2010;
100:
53–7.
14. Eusebi LH, Zagari RM, Bazzoli F.
Epidemiology of Helicobacter pylori
infection. Helicobacter 2014; 19(Suppl.
1): 1–5.
15. Calvet X, Ram
ırez L
azaro MJ, Lehours
P, M
egraud F. Diagnosis and
epidemiology of Helicobacter pylori
infection. Helicobacter 2013; 18(Suppl.
1): 5–11.
16. Tonkic A, Tonkic M, Lehours P,
M
egraud F. Epidemiology and diagnosis
of Helicobacter pylori infection.
Helicobacter 2012; 17(Suppl. 1): 1–8.
17. Wong BC, Lam SK, Wong WM, et al.
Helicobacter pylori eradication to prevent
gastric cancer in a high-risk region of
China: a randomized controlled trial.
JAMA 2004; 291: 187–94.
18. Dohil R, Hassall E. Peptic ulcer disease
in children. Bailliere’s Best Practice &
Research. Clin Gastroenterol 2000; 14:
53–73.
19. Koletzko S, Jones NL, Goodman KJ,
et al. Evidence-based guidelines from
ESPGHAN and NASPGHAN for
Helicobacter pylori infection in children.
J Pediatr Gastroenterol Nutr 2011; 53:
230–43.
20. Malfertheiner P, Megraud F, O’Morain
CA, et al. Management of Helicobacter
pylori infection – the Maastricht IV/
Florence Consensus Report. Gut 2012;
61: 646–64.
21. Malaty HM, El-Kasabany A, Graham
DY, et al. Age at acquisition of
Helicobacter pylori infection: a follow-
up study from infancy to adulthood.
Lancet 2002; 359: 931–5.
22. S
ykora J, Siala K, Varvarovsk
a J,
Pazdiora P, Pomahacov
a R, Huml M.
Epidemiology of Helicobacter pylori
infection in asymptomatic children: a
prospective population-based study
from the Czech Republic. Application
of a monoclonal-based antigen-in-stool
enzyme immunoassay. Helicobacter
2009; 14: 286–97.
23. Oleastro M, Pelerito A, Nogueira P,
et al. Prevalence and incidence of
Helicobacter pylori infection in a
healthy pediatric population in the
Lisbon area. Helicobacter 2011; 16:
363–72.
24. Rothenbacher D, Bode G, Brenner H.
Dynamics of Helicobacter pylori infection
in early childhood in a high-risk group
living in Germany: loss of infection
higher than acquisition. Aliment
Pharmacol Ther 2002; 16: 1663–8.
25. Haruma K. Trend toward a reduced
prevalence of Helicobacter pylori
infection, chronic gastritis, and gastric
cancer in Japan. Gastroenterol Clin
North Am 2000; 29: 623–31.
26. Bures J, Kop
acov
a M, Koupil I, et al.
Epidemiology of Helicobacter pylori
infection in the Czech Republic.
Helicobacter 2006; 11: 56–65.
27. Elitsur Y, Dementieva Y, Rewalt M,
Lawrence Z. Helicobacter pylori
infection rate decreases in symptomatic
children: a retrospective analysis of
13 years (1993-2005) from a
gastroenterology clinic in West
Virginia. J Clin Gastroenterol 2009; 43:
147–51.
28. Kawakami E, Machado RS, Ogata SK,
Langner M. Decrease in prevalence of
Helicobacter pylori infection during
a 10-year period in Brazilian
children. Arq Gastroenterol 2008; 45:
147–51.
29. Azevedo NF, Huntington J, Goodman
KJ. The epidemiology of Helicobacter
pylori and public health implications.
Helicobacter 2009; 14(Suppl. 1): 1–7.
30. Fock KM, Ang TL. Epidemiology of
Helicobacter pylori infection and gastric
cancer in Asia. J Gastroenterol Hepatol
2010; 25: 479–86.
31. Fock KM, Dhamodaran S TE. Is H.
pylori genotypes significant in Asian
patients with gastric cancer and GERD?
Gut 2006; 55: A258.
32. Jais M, Barua S. Seroprevalence of anti
Helicobacter pylori IgG/IgA in
asymptomatic population from Delhi.
J Commun Dis 2004; 36: 132–5.
33. Perez-Perez GI, Taylor DN, Bodhidatta
L, et al. Seroprevalence of Helicobacter
pylori infections in Thailand. J Infect
Dis 1990; 161: 1237–41.
34. Rahman R, Asombang AW, Ibdah JA.
Characteristics of gastric cancer in
Asia.World J Gastroenterol 2014; 20:
4483–90.
35. Chen J, Bu XL, Wang QY, Hu PJ, Chen
MH. Decreasing seroprevalence of
Helicobacter pylori infection during
1993-2003 in Guangzhou, southern
China. Helicobacter 2007; 12: 164–9.
36. Weyermann M, Rothenbacher D,
Brenner H. Acquisition of Helicobacter
pylori infection in early childhood:
independent contributions of infected
mothers, fathers, and siblings. Am J
Gastroenterol 2009; 104: 182–9.
37. Brown LM. Helicobacter pylori:
epidemiology and routes of
transmission. Epidemiol Rev 2000; 22:
283–97.
38. Heuberger F, Pantoflickova D, Gassner
M, et al. Helicobacter pylori infection in
Swiss adolescents. Prevalence and risk
1025
Z. Ding et al.
factors. Eur J Gastroenterol Hepatol
2003;15: 179–83.
39. Malcolm CA, Mackay WG, Shepherd
A, Weaver LT. Helicobacter pylori in
children is strongly associated with
poverty. Scott Med J 2004; 49: 136–8.
40. Daniel M, Miria G. Helicobacter pylori
infection in children from Northeast
Argentina: seroprevalence and its
relation with nutritional status and
socio-sanitary conditions. Inf Emerg
2002; 4: 24–9.
41. Rodrigues MN, Queiroz DM, Bezerra
Filho JG, Pontes LK, Rodrigues RT,
Braga LL. Prevalence of Helicobacter
pylori in children from an urban
community in north-east Brazil and
risk factors for infection. Eur J
Gastroenterol Hepatol 2004; 16: 201–5.
42. Mansour-Ghanaei F, Yousefi Mashhour
M, Joukar F, Sedigh M, Bagher-Zadeh
AH, Jafarshad R. Prevalence of
Helicobacter pylori infection among
children in Rasht, Northern Iran.
Middle East Journal of Digestive
Diseases (MEJDD) 2009; 1: 84–8.
43. Megraud F. Comparison of non-
invasive tests to detect Helicobacter
pylori infection in children and
adolescents: results of a multicenter
European study. J Pediatr 2005; 146:
198–203.
44. Kivi M, Tindberg Y, S€ orberg M, et al.
Concordance of Helicobacter pylori
1026
strains within families. J Clin Microbiol
2003; 41: 5604–8.
45. Osaki T, Okuda M, Ueda J, et al.
Multilocus sequence typing of DNA
from faecal specimens for the analysis
of intra-familial transmission of
Helicobacter pylori. J Med Microbiol
2013; 62: 761–5.
46. Yokota SI, Konno M, Fujiwara SI, et al.
Intrafamilial, preferentially mother-to-
child and intraspousal, Helicobacter
pylori infection in Japan determined by
mutilocus sequence typing and random
amplified polymorphic DNA
fingerprinting. Helicobacter 2015;
in press. doi: 10.1111/hel.12217.
47. Andrew J, Marsden B, Brown D, Wong
VS, Wood E, Kelsey M. Comparison of
three-stool antigen tests for Helicobacter
pylori detection. Clin Pathol 2003; 56:
769–71.
48. Braden B, Posselt HG, Ahrens P, Kitz
R, Dietrich CF, Caspary WF. New
immunoassay in stool provides an
accurate noninvasive diagnosis method
for Helicobacter pylori screening in
children. Pediatrics 2000; 106: 115–7.
49. Konstantopoulos N, R€ ussmann H,
Tasch C, et al. Evaluation of the
Helicobacter pylori stool antigen test
(HpSA) for detection of Helicobacter
pylori infection in children. Am J
Gastroenterol 2001; 96: 677–83.
50. Gisbert JP, Pajares JM. Diagnosis of
Helicobacter pylori by stool antigen
determination: a systematic review. Am
J Gastroenterol 2001; 96: 2829–38.
51. Koletzko S, Konstantopoulos N,
Bosman D, et al. Evaluation of a
monoclonal enzyme immunoassay for
detection of Helicobacter pylori antigen
in stool from children. Gut 2003; 52:
804–6.
52. Schwarzer A, Lottspeich C, Russmann
H, Ossiander G, Koletzko S. Evaluation
of a novel rapid one-step monoclonal
chromatographic immunoassay for
detection of Helicobacter pylori in stool
from children. Eur J Clin Microbiol
Infect Dis 2007; 26: 475–80.
53. Calvet X, Lario S, Ram
ırez-L
azaro MJ,
et al. Accuracy of monoclonal stool tests
for determining cure of Helicobacter
pylori infection after treatment.
Helicobacter 2010; 15: 201–5.
54. World Gastroenterology Organisation.
World Gastroenterology Organisation
Global Guideline: Helicobacter pylori in
developing countries. J Clin
Gastroenterol 2011; 45: 383–8.
55. Yan SK, Lin QS, Song YH, Wang SQ.
Detection of Helicobacter pylori stool
antigen by non-invasive enzyme
immunoassay. Chin Med Sci J 2003; 18:
218–21.
Aliment Pharmacol Ther 2015; 42: 1019–1026
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