Helicobacter ISSN 1523-5378

doi: 10.1111/j.1523-5378.2012.00975.x

REVIEW ARTICLE
Epidemiology and Diagnosis of Helicobacter pylori Infection
Ante Tonkic,* Marija Tonkic,† Philippe Lehours‡ and Francis Mégraud‡
*Division of Gastroenterology, Department of Internal Medicine, University Hospital Split, School of Medicine, University of Split, Split, Croatia,
†
Department of Clinical Microbiology, University Hospital Split, School of Medicine, University of Split, Split, Croatia, ‡INSERM U853, and Université
Bordeaux Segalen, Laboratoire de Bactériologie, Bordeaux, France

Keywords
Prevalence, incidence, endoscopy, histology,
culture, molecular tests, urea breath test,
stool antigen test, serology.
Reprint requests to: Francis Mégraud, INSERM
U853, Laboratoire de Bactériologie, Hôpital
Pellegrin, 33076 Bordeaux Cedex, France.
E-mail: francis.megraud@chu-bordeaux.fr
Abstract
Medline, PubMed and the Cochrane databases were searched on epidemiol-
ogy and diagnosis of Helicobacter pylori for the period of April 2011–March
2012. Several studies have shown that the prevalence of H. pylori infection
is decreasing in adults and children in many countries. Various diagnostic
tests are available, and most of them have high sensitivity and specificity.
The Maastricht IV/Florence consensus report states that the urea breath test
using 13C urea remains the best test to diagnose H. pylori infection. Among
the stool antigen tests, the ELISA monoclonal antibody test is recommended.
All these tests were used, either as a single diagnostic test or in combination,
to investigate H. pylori infection among different populations throughout the
world. Of particular interest, current improvements in high-resolution endo-
scopic technologies enable increased diagnostic accuracy for the detection of
H. pylori infection, but none of these techniques, at present, are specific
enough for obtaining a real-time diagnosis of H. pylori infection.

and was higher among those born overseas as well as

Epidemiology
In the context of a decreased trend in Helicobacter pylori
prevalence, a number of studies were performed on
adults and children, both in developed and developing
countries (Table 1). The main tool used was serology,
but in a few studies, urea breath tests (UBT) or stool
antigen tests (SAT) were used.
In the United States, seroprevalence was performed
on adults participating in the continuous National
Health and Nutrition Examination Survey (1999–2000).
The age standardized prevalence was high among His-
panic and African Americans compared to non-Hispanic
whites. A significant decrease from the previous survey
(1988–1991) was only observed in the non-Hispanic
white population [1]. A prevalence study conducted in
204 volunteer blood donors in Nassau (Bahamas) esti-
mated a global prevalence of 58% for H. pylori infec-
tion, that is, comparable to other Caribbean territories
[2]. In Australia, a nationwide study including 1355
subjects showed a lower prevalence of H. pylori infec-
tion than in other developed countries. H. pylori infec-
tion varied significantly with age (ranging from 5 to
32% for those aged <40 and >70 years, respectively)
in the lowest socioeconomic areas [3].
In Europe, H. pylori prevalence is still higher in the
eastern than in the western countries. A serological sur-
vey carried out in 2318 patients presenting themselves
at the emergency ward of Magdeburg hospital (former
East Germany) had an overall prevalence of 44.4%
(43.3% of them with anti-CagA antibodies). A signifi-
cant drop in seroprevalence was noted for those born
after 1980 (<30 years of age) in the area. This can be
explained by the housing program that was developed
in the 1970s in this region allowing an improvement of
the socioeconomic conditions [4].
A population-based study was designed in Denmark
in primary care where 36,629 dyspeptic patients per-
formed UBT at home at the discretion of their general
practitioner, from 2003 to 2009. The prevalence was
approximately 20% and declined over time during the
course of the study, mainly between 2004 and 2007.
Prevalence was higher for those older than 45 years
than for the younger ones [5]. In Belgium, the analysis
of data from 22,612 dyspeptic patients over two decades
(1988–2007) showed a global prevalence of 37.7%, as
determined by culture; the prevalence was lower in

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H. pylori epidemiology & diagnosis Tonkic et al.

Table 1 Prevalence of Helicobacter pylori infection observed in studies published in 2011 (adults)

Country (city) Year specimen collection Number Method Prevalence (%) Authors

USA 1999–2000 4145 Serology 30.7 Grad et al. [1]

Bahamas 204 Serology 58 Carter et al. [2]
Australia 2002–2005 1355 Serology 15.5 Pandeya et al. [3]
Germany (Magdeburg) 2009–2010 2318 Serology 44.4 Wex et al. [4]
Denmark (Jutland)a 2003–2009 36,629 UBT 20.1 Dahlerup et al. [5]
Belgium (Brussels)b 1988–2007 22,612 Culture 37.7 Miendje Deyi et al. [6]
Israel 2007–2008 1466 Serology 45.2 Muhsen et al. [7]
China (Northern) 798 Serology 54.5 Guo et al. [8]
China (Shandong) 2008–2012 1637 Serology 35.5 Wang et al. [9]
Pakistan (Islamabad) 2009–2010 516 UBT 74.4 Rasheed et al. [10]

UBT, urea breath test.

a
Dyspeptic patients consulting a general practitioner.
b
Dyspeptic patients consulting a gastroenterologist.

Western European patients than in North African
patients with a significant decrease from 1988 to 2007:
36.2 and 15.2% for the former and 71.7 and 40% for
the latter [6].
In Israel, the age-adjusted H. pylori seroprevalence
was 45.2% for Jewish participants. A difference was
found according to age, as usual, but also from the
region of the world from which participants originated
(higher prevalence in Asia – Africa – South America
than in North America – Western Europe – Australia)
[7].
In northern China, the seroprevalence in 798
healthy adults was 54.5% [8]. In the littoral region of
Shandong, also in China, the seroprevalence in the
normal adult population was 35.9%. They found a
lower level in alcohol consumers with normal liver
function tests (27%) [9]. The highest prevalence among
the studies published this year was found in 516
asymptomatic individuals from Pakistan (74.4%) [10].
Using a combination of diagnostic tests (histology,
serology, UBT, and rapid urease test (RUT)), Matsuo T
et al. showed among 3161 gastric cancer cases diag-
nosed from 1996 to 2010 in Japan, only 21 were truly
H. pylori negative. This low prevalence of H. pylori-neg-
ative gastric cancer cases was also correlated with path-
ological characteristics different from common gastric
cancer cases [11].
H. pylori serology alone usually does not show a
strong association between the presence of H. pylori
antibodies and gastric cancer. For this reason, some
authors looked at CagA antibodies that are supposed to
persist for longer periods of time after curing the infec-
tion by antibiotic treatment, or spontaneous clearance
during the progression of atrophy. In a nested Euro-
pean case–control study from the Eurogast-EPIC
project, Gonzalez et al. [12] showed by using immuno-
blot detecting CagA antibodies that nearly, all noncar-
dia-gastric cancer cases were indeed H. pylori positive,
with an odds ratio three times higher than that
obtained by ELISA.
Detection of anti-CagA antibodies combined with
H. pylori ELISA, urease test, and histology was also used
to determine H. pylori infection in Russian and eastern
Siberian populations carrying a different risk of gastric
cancer. Tsukanov et al. [13] showed that H. pylori
infection is high in these populations, but ethnic groups
with a similar prevalence of CagA antibodies had a dif-
ferent prevalence of intestinal metaplasia (IM) and inci-
dence of gastric cancer, indicating other host-related
and/or environmental factors.
Several surveys have been carried out in children.
They are presented in Table 2. To obtain insight into
the natural history of H. pylori infection, Queiroz et al.
followed up a cohort of 133 Brazilian children from a
low-income community using UBT. The prevalence of
H. pylori infection was 53.4% at baseline and 64.7%
8 years later. Among them, 6.0% had lost the infection,
while 17.3% became infected [14]. Risk factors for
H. pylori infection were a high number of children in
the household and male gender.
There is now evidence that H. pylori infection is
declining in both developed and developing countries.
This was clearly shown using UBT in a retrospective
study (2002–2009) performed on 1030 children from
Buenos Aires. The authors found a prevalence of
41.2% for the period of 2002–2004, dropping to 26.0%
in the triennium 2007–2009 [15].
H. pylori antigen detection using monoclonal SAT
was also used in a prospective study conducted among
231 Israeli Arab children. The incidence of H. pylori

2 © 2012 Blackwell Publishing Ltd, Helicobacter 17 (Suppl. 1): 1–8

Tonkic et al. H. pylori epidemiology & diagnosis

Table 2 Prevalence of Helicobacter pylori infection observed in studies published in 2011 (children)

Country (City) Recruitment Year Number Method Prevalence (%) Authors

Germany (Leipzig) School children 2006 1905 UBT 6.5 Bauer et al. [59]
The Netherlands Asthma cohort 2005–2006 545 Serology 9 den Hoed et al. [60]
Portugal (Lisbon) Asymptomatic children 2002–2003 844 SAT 31.6 Oleastro et al. [61]
Israel Various symptoms 2000–2001 575 Arabs Serology 45.6 Muhsen et al. [16]
584 Jews 25.2
Argentina Gastrointestinal symptoms 2007–2009 254 UBT 24.7 Janjetic et al. [15]
(Buenos Aires)
Uganda (Kampala) Malaria cohort 2004–2005 200 Serology 63 Gupta et al. [62]
Ethiopia Population-based cohort 2008–2009 646 SAT 41 Amberbir et al. [63]

SAT, stool antigen tests; UBT, urea breath tests.

infection was 33.3%, and the mean age of acquisition
was 14 months. As already described, low socioeco-
nomic status and low paternal education were identi-
fied among others as risk factors [16].
Finally, using a combination of diagnostic tests
(RUT, culture, and histology), Llanes et al. [17] found
an H. pylori prevalence of 30.8% among 133 con-
secutive Cuban children with upper gastrointestinal
symptoms.
H. pylori infection can be transmitted orally. Using
PCR detection in dental plaques of 35 children (4–
14 years) and 45 family members (mothers and/or
fathers), the bacterium was identified in 40% of
infected children and in most family members as well
[18]. This study showed the presence of the bacterium
in the subgingival dental plaque which could be a res-
ervoir contributing to the intrafamilial transmission.
Diagnosis
It is important to note that the 4th Maastricht Consen-
sus Report in which diagnostic methods are considered
was published this year [19].
Invasive Tests
Endoscopy
The emergence of high-resolution endoscopic technolo-
gies enables the improvement of diagnostic accuracy for
the detection of H. pylori infection and its associated
lesions. The most promising high-resolution imaging
technologies include high-resolution microendoscopy,
optical coherence tomography, endocytoscopy, and
confocal laser endoscopy [20, 21]. None of these tech-
niques allowing “optical biopsies” are widely available
nor specific enough at present for obtaining a real-time
diagnosis of H. pylori infection.
A study of 300 patients in Japan showed that con-
ventional narrow-band imaging (NBI) has a good corre-
lation with the histopathologic severity of H. pylori
gastritis. Five different histopathologic grades of
H. pylori gastritis (gastric atrophy, IM, infiltration by
inflammatory cells, and density of H. pylori infection)
were recognized among the different NBI mucosal
patterns [22].
Kawamura et al. [23] indicated that a magnifying
endoscopy with NBI clearly revealed micromorphologi-
cal differences that correspond to the histologic and
endoscopic findings among patients with different
H. pylori-associated diseases.
Confocal laser endomicroscopy can be used as a
functional imaging technique to detect mucosal barrier
defects in patients with H. pylori infection and IM [24].
Furthermore, endocytoscopy is a safe and effective new
endoscopic imaging technique for obtaining in vivo his-
tology and guided biopsies with a high diagnostic accu-
racy. Endocytoscopy enables microscopic imaging at a
1400-fold magnification, allowing the analysis of muco-
sal structures at the cellular level, as well as the in vivo
detection of H. pylori [25]. Currently evolving func-
tional and molecular-targeted imaging technologies are
of potential importance in the field of real-time diagno-
sis of H. pylori infection [26, 27].
Histology
Histology is considered to be the gold standard in the
direct diagnosis of H. pylori gastritis [19]. Currently, the
conventional Giemsa staining is the most widely used
technique, and immunostaining further increases sensi-
tivity and specificity [28].
However, some host factors may affect the accuracy
of histopathology for H. pylori detection. Therefore, the
Maastricht IV Consensus Report has recommended that
if possible, proton pump inhibitors (PPI) should be

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H. pylori epidemiology & diagnosis
stopped for 2 weeks before performing histology [19].
It is well known that bleeding decreases the sensitivity
of H. pylori diagnostic tests in patients with peptic ulcer
bleeding, but Choi et al. [29] determined that histology
is quite a reliable test, regardless of the presence of
bleeding. Furthermore, a meta-analysis by Tian et al.
[30] showed that histology had a higher sensitivity and
specificity than the UBT and the RUT for the diagnosis
of H. pylori infection after a partial gastrectomy.
Peptide nucleic acid-FISH is a genotypic method for
detecting the clarithromycin resistance of H. pylori,
based on fluorescent in situ hybridization [31]. The set
of probes targeting the point mutations responsible for
clarithromycin resistance was applied to H. pylori sus-
pensions, and it showed 100% sensitivity and specific-
ity (95% CI, 79.9–100 and 95% CI, 71.6–100,
respectively) [31].
Rapid Urease Test
The RUT has an accuracy of >90% in the detection of
H. pylori infection, and a positive RUT is sufficient to
initiate eradication treatment [19]. RUT is relatively
inexpensive, and it provides rapid results. In the case of
an active ulcer bleeding, the sensitivity of RUT may be
reduced [29].
Koumi et al. [32], in a prospective study, proved
that a faster urease test (H. pylori Quick test; Biohit,
Helsinki, Finland) is more cost-effective than the CLO
test. Furthermore, Li et al. [33] showed that gastric
biopsy specimens stored in the RUT gel for 30 days can
still be used to confirm the diagnosis of an H. pylori
infection and test for clarithromycin susceptibility.
Culture
According to the Maastricht IV Consensus Report,
H. pylori culture and antibiotic susceptibility testing
should be performed if primary resistance to clarithro-
mycin exceeds 20% in a given geographical area [19].
Furthermore, after the first eradication failure, culture
should be considered in all regions before providing
second-line treatment [19].
Some factors like peptic ulcer bleeding may affect
the tests for H. pylori detection. Culture and three other
tests (RUT, histology, and anti-CagA IgG) were per-
formed under such circumstances [34]. The sensitivity
of the biopsy specimen’s culture, histology, and RUT
was 86.4, 68.2, and 65.9%, respectively, and the speci-
ficity was 100, 75, and 77.8%, respectively, indicating
that culture was the best method for the detection of
H. pylori in bleeding patients with peptic ulcer bleeding
after nonsteroidal anti-inflammatory drug consumption.
4 © 2012 Blackwell Publishing Ltd, Helicobacter 17 (Suppl. 1): 1–8
Tonkic et al.
Contrary to these findings, other authors concluded
that bleeding decreased the sensitivity of H. pylori tests
in patients with peptic ulcer, especially RUT and cul-
ture, while histology was found to be the most reliable
test regardless of the presence of bleeding [29].
As the decreased density of H. pylori in atrophic gas-
tritis may lead to a low sensitivity of the tests, Sudraba
et al. [35] evaluated the accuracy of histology, RUT,
culture, UBT, and serology (IgG/IgA) in such condi-
tions. Culture, histology, and UBT turned out to be the
three best tests in such cases.
Serum or blood derivatives are used as supplements
for the isolation of H. pylori on nutrient-rich media.
These supplements often require frozen storage and can
be unstable with a risk of drop in the quality level. The
study of Hutton et al. demonstrated the growth of
H. pylori in solid and liquid media containing a highly
purified, lipid-rich bovine serum albumin called Albu-
MAX II® (Gibco BRL, Grand Island, NY, USA). Growth
was comparable to the growth obtained on blood agar
or liquid media with serum and higher than on media
containing b-cyclodextrin [36]. The effect of another
compound, cholesterol, as a substitute for serum or
cyclodextrin, was demonstrated to be a valuable option
for the supplementation of media for the H. pylori
growth [37].
Despite the fact that H. pylori has been considered a
microaerophilic bacterium, research was undertaken to
evaluate its growth profile, morphology, intracellular
pH, and energy metabolism under a range of O2 levels
with or without 10% O2. Park et al. [38] concluded,
unlike previous reports, that H. pylori may indeed be a
capnophilic aerobe whose growth is promoted by atmo-
spheric oxygen levels in the presence of 10% O2. Sur-
prisingly, two mucoid H. pylori strains featuring rapid
growth under microaerobic and aerobic conditions and
high resistance to the antimicrobials tested were
recently isolated from gastric biopsies after 24 hours
incubation [39]. It is assumed that the production of
exopolysaccharide could serve as a physical barrier to
reduce oxygen diffusion into the bacterial cell and the
uptake of antibiotics.
Molecular methods
Because the isolation of H. pylori is demanding and
time-consuming and the resistance to antimicrobials is
rising, molecular methods are a good alternative for the
detection of H. pylori in clinical specimens and for the
detection of mutations leading to resistance, especially
to macrolides and fluoroquinolones. PCR and real-time
PCR are the most frequently used methods. A study
from Spain has shown that real-time PCR improves
Tonkic et al.
H. pylori detection in patients with peptic ulcer bleeding
[40]. They selected 52 histology-negative formalin-fixed
paraffin-embedded biopsy specimens obtained during
peptic ulcer bleeding episodes and found that among
them, 42 were false negatives.
Performing real-time PCR requires expensive equip-
ment. A new PCR format derived from standard PCR
called “dual priming oligonucleotide” (DPO)-PCR was
developed and used in H. pylori and macrolide resis-
tance detection [41]. DPO-PCR is a multiplex PCR assay
that increases the specificity and sensitivity of detection
when compared to conventional PCR because nonspe-
cific binding sites are blocked and imperfect primer
annealing is eliminated. DPO-PCR can be performed in
any standard thermocycler. Lehours et al. investigated
the capability of the DPO-PCR kit Seeplex ClaR®-
H. pylori ACE detection, (Seegene, Seoul, Korea) to
detect both H. pylori and two types of point mutation
causing clarithromycin resistance (A2142G and
A2143G) on 127 gastric biopsies [42] in comparison
with standard phenotypic tests and an in-house real-
time fluorescence resonance energy transfer (FRET)-
PCR. The sensitivity of DPO-PCR and real-time
FRET-PCR was 97.7 and 100%, and specificity was 83.1
and 80.7%, respectively, indicating the interest of this
method.
Miendje Deyi et al. [43] evaluated the performance
and usefulness of a multiplex PCR followed by hybrid-
ization on a strip, the Genotype® HelicoDR kit (Hain
LifeScience, Nehren, Germany), for the detection of
H. pylori and for the determination of resistance to clar-
ithromycin and fluoroquinolones in gastric biopsies
obtained from 128 patients. This kit proved to be prom-
ising for practical use because of its excellent sensitivity,
speed, and ability to detect infections with multiple
strains. Compared to the culture-based method, the
performance of HelicoDR in detecting fluoroquinolone
resistance was, however, lower than that of clarithro-
mycin resistance. The authors emphasized the necessity
of adapting the probes to the local prevalence of muta-
tions, in particular in detecting new GyrA mutations
that are not included in the kit.
After the improvement of DNA extraction methods
from stool samples, a stool real-time PCR assay
(H. pylori ClariRes assay; Ingenetix, Vienna, Austria) is
now available as the only noninvasive test allowing
H. pylori detection and clarithromycin susceptibility
testing. In Brazil, H. pylori DNA from gastric biopsies
and stool specimens from 217 dyspeptic children were
extracted with the QIAampDNA stool mini kit (Qiagen,
Valencia, CA, USA). The sensitivity and specificity of
the test were 69 and 100% for the detection of H. pylori
and 83.3 and 100% for the detection of clarithromycin
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H. pylori epidemiology & diagnosis
resistance, respectively. This assay proved to be appro-
priate for H. pylori clarithromycin susceptibility testing,
particularly in populations with a high clarithromycin
resistance [44].
The same stool PCR assay was useful and effective
as a noninvasive approach for H. pylori susceptibility
testing in tailored treatments in children [45]. Results
showed that it was as effective as culture.
Another application of a stool PCR assay is as a non-
invasive method for genotyping H. pylori. Several arti-
cles tackled this topic [46, 47].
Indian authors have developed a quantitative real-
time PCR (Q-PCR) assay to determine the levels of the
H. pylori DNA within human gastric mucosa [48]. They
used the ureC gene (one copy per bacterium) as the tar-
get. This technique is easy to perform and allows for
the rapid determination and quantification of H. pylori,
which can be used for monitoring the treatment out-
come.
One of the presumed reasons why infection with
H. pylori is persistent and difficult to eradicate is the
colonization of individual hosts by multiple H. pylori
genotypes. In the study of Ren et al. [49], a modified
randomly amplified polymorphic DNA (RAPD) method
was used to study the diversity of H. pylori in individu-
als, using primary culture isolates instead of passaged
culture isolates. The results showed that the incidence
of multiple colonization was 99%, which is significantly
higher than in other reports. A higher number of RAPD
genotypes within a single host (up to five genotypes)
were observed as the disease developed or became
more serious. The results of this study suggest that
investigating primary culture isolates better reflects the
H. pylori diversity in individuals. However, different
genotypes in a given patient may have originated from
a single ancestral strain.
Noninvasive Tests
13
C urea breath test
The 13C UBT is a widely available test with a diagnostic
accuracy of >95% [28]. UBT is widely available because
breath samples are easy to collect and can even be sent
by mail to a central laboratory for analysis. Further-
more, UBT is useful for epidemiological studies, before
endoscopy and especially for assessing the efficacy of
eradication regimens.
In a population-based study previously cited, Dahl-
erup et al. evaluated the use of a UBT that was per-
formed by patients themselves at home as part of a
test-and-treat strategy to investigate the prevalence of
H. pylori in patients using a UBT for the first time.
5
H. pylori epidemiology & diagnosis
There were only 1.6% errors in collection indicating
that this strategy can be used [5]. Schmilovitz-Weiss
et al. [50] in a retrospective multicenter chart review
study established that the Breath ID System (Exalenz,
Modi'in, Israel) used in diagnosing H. pylori infection
can safely shorten the test duration by an average of
10–13 minutes without a loss in sensitivity or specificity.
Urea breath test is an accurate test for diagnosing
H. pylori infection in patients with an intact stomach,
but the sensitivity and specificity of the UBT in patients
after a partial gastrectomy are variable because of the
lower bacterial load. Wardi et al. evaluated the Breath
ID in such patients and established that this continuous
UBT had a better positive predictive value than RUT
(0.62 and 0.35, respectively). The negative predictive
value was high for both methods, 0.92 and 0.95,
respectively [51].
The 13C UBT has shown a variable level of accuracy
in the pediatric population. In a meta-analysis, Leal
et al. [52] confirmed that the 13C UBT is less accurate
for the diagnosis of H. pylori infection in young chil-
dren.
Stool antigen tests
The monoclonal SAT are suitable and widely available
tests for the primary as well as for post-treatment diag-
nosis of H. pylori infection [19].
The applicability of a rapid office-based stool test
(Rapid TPAg) using monoclonal antibodies against cata-
lase was evaluated by Shimoyama et al. in 102 patients
who received H. pylori eradication therapy. The overall
accuracy of rapid TPAg and UBT to determine H. pylori
eradication was 98.0 and 96.0%, respectively. The anti-
genicity of stool sample suspensions was preserved for
7 days in the collection devices [53].
Although rapid in-office polyclonal tests in general
are reputed to have a low level of accuracy, data indi-
cate that it could be different for a new in-office SAT.
The efficacy of the polyclonal enzyme immunoassay
(EZ-STEP H. pylori; Dinona, Seoul, Korea) was evalu-
ated on stools of 515 patients. Choi et al. established
that its performance was comparable to that of histol-
ogy, RUT, and UBT, with an accuracy of 93.6–95.9%.
This new SAT still gave a strong diagnostic performance
in the setting of the progression of atrophic gastritis and
IM and in patients over 40 years old [54].
To investigate the effect of a PPI treatment on a
SAT, Kodama et al. evaluated the TestMate pylori
enzyme immunoassay® (Kyowa Hakko Kirin Co. Ltd,
Tokyo, Japan). In this study, the SAT was as sensitive
as the UBT, making it a useful and reliable diagnostic
method, even during PPI administration [55].
6 © 2012 Blackwell Publishing Ltd, Helicobacter 17 (Suppl. 1): 1–8
Tonkic et al.
The systematic review and meta-analysis conducted
by Leal et al. [56] established that stool ELISA using
monoclonal antibodies is an efficient noninvasive test
for the diagnosis of H. pylori infection in children.
Antibody-based tests (serology)
Serological testing is the most widely available test for
the detection of H. pylori with a relatively high negative
predictive value [19, 28]. Furthermore, serology is the
only test that is not affected by local changes in
the stomach that could lead to false-negative results in
the other tests. Furthermore, in patients treated with
PPIs, if it not possible to stop them for at least 2 weeks,
a validated IgG serology test (ELISA) may be used. This
is the case in the setting of ulcer bleeding, as well as
the recent use of antimicrobial and antisecretory drugs
[19].
Serum pepsinogen testing is clinically useful for the
prediction of gastric preneoplastic conditions in
H. pylori-infected persons [57]. H. pylori serology com-
bined with the detection of serum pepsinogen I/II ratio
and gastrin 17 (G17) offers the possibility of a “serologi-
cal” biopsy. CagA was positively associated with a
decrease in serum PG1 and PGI/II ratio [58]. This sero-
logical assessment of gastric atrophy is, however, only
adequate for subjects at risk of an intestinal type of gas-
tric cancer [58].
Conclusion
In conclusion, at present, there is no single test that
can be considered as the gold standard for the diagnosis
of H. pylori infection. The selection of the most suitable
diagnostic test depends on the clinical circumstances as
well as on their availability and cost. Further data are
needed to evaluate current invasive and noninvasive
tests in an attempt to improve their diagnostic accu-
racy.
Acknowledgements and Disclosures
Competing interests: the authors have no competing
interests.
References
1 Grad YH, Lipsitch M, Aiello AE. Secular trends in Helicobacter
pylori seroprevalence in adults in the United States: evidence
for sustained race/ethnic disparities. Am J Epidemiol
2012;175:54–9.
2 Carter FP, Frankson T, Pintard J, Edgecombe B. Seroprevalence
of Helicobacter pylori infection in adults in the Bahamas. West
Indian Med J 2011;60:662–5.
Tonkic et al.
3 Pandeya N, Whiteman DC. Prevalence and determinants of He-
licobacter pylori sero-positivity in the Australian adult commu-
nity. J Gastroenterol Hepatol 2011;26:1283–9.
4 Wex T, Venerito M, Kreutzer J, Gotze T, Kandulski A, Malfer-
theiner P. Serological prevalence of Helicobacter pylori infection
in Saxony-Anhalt, Germany, in 2010. Clin Vaccine Immunol
2011;18:2109–12.
5 Dahlerup S, Andersen RC, Nielsen BS, Schjodt I, Christensen
LA, Gerdes LU, et al. First-time urea breath tests performed at
home by 36,629 patients: a study of Helicobacter pylori preva-
lence in primary care. Helicobacter 2011;16:468–74.
6 Miendje Deyi VY, Vanderpas J, Bontems P, Van den Borre C,
De Koster E, Cadranel S, et al. Marching cohort of Helicobacter
pylori infection over two decades (1988–2007): combined effects
of secular trend and population migration. Epidemiol Infect
2011;139:572–80.
7 Muhsen K, Cohen D, Spungin-Bialik A, Shohat T. Seropreva-
lence, correlates and trends of Helicobacter pylori infection in the
Israeli population. Epidemiol Infect 2011;140:1207–14.
8 Guo X, Zhao BH, Zhang MX. Risk factors of Helicobacter pylori
infection among adults in northern China. Hepatogastroenterology
2011;58:306–10.
9 Wang MY, Yue JY, Zhang YX, Liu XD, Gao XZ. Helicobacter
pylori infection in asymptomatic HBV carriers, alcohol users and
normal adult population in Shandong Province, China. Clin Res
Hepatol Gastroenterol 2011;35:560–2.
10 Rasheed F, Ahmad T, Bilal R. Frequency of Helicobacter pylori
infection using 13C-UBT in asymptomatic individuals of Bara-
kaho, Islamabad, Pakistan. J Coll Physicians Surg Pak
2011;21:379–81.
11 Matsuo T, Ito M, Takata S, Tanaka S, Yoshihara M, Chayama
K. Low prevalence of Helicobacter pylori-negative gastric cancer
among Japanese. Helicobacter 2011;16:415–9.
12 Gonzalez CA, Megraud F, Buissonniere A, Lujan Barroso L, Ag-
udo A, Duell EJ, et al. Helicobacter pylori infection assessed by
ELISA and by immunoblot and noncardia gastric cancer risk in
a prospective study: the Eurgast-EPIC project. Ann Oncol
2012;23:1320–4.
13 Tsukanov VV, Butorin NN, Maady AS, Shtygasheva OV, Amel-
chugova OS, Tonkikh JL, et al. Helicobacter pylori infection,
intestinal metaplasia, and gastric cancer risk in eastern Siberia.
Helicobacter 2011;16:107–12.
14 Queiroz DM, Carneiro JG, Braga-Neto MB, Fialho AB, Fialho
AM, Goncalves MH, et al. Natural history of Helicobacter pylori
infection in childhood: eight-year follow-up cohort study in an
urban community in northeast of Brazil. Helicobacter
2012;17:23–9.
15 Janjetic MA, Goldman CG, Barrado DA, Cueto Rua E, Balcarce
N, Mantero P, et al. Decreasing trend of Helicobacter pylori infec-
tion in children with gastrointestinal symptoms from Buenos
Aires, Argentina. Helicobacter 2011;16:316–9.
16 Muhsen K, Jurban M, Goren S, Cohen D. Incidence, age of
acquisition and risk factors of Helicobacter pylori infection among
Israeli Arab infants. J Trop Pediatr 2012;58:208–13.
17 Llanes R, Millan LM, Escobar MP, Gala A, Capo V, Feliciano O,
et al. Low prevalence of Helicobacter pylori among symptomatic
children from a hospital in Havana, Cuba. J Trop Pediatr
2012;58:231–4.
18 Tsami A, Petropoulou P, Kafritsa Y, Mentis YA, Roma-
Giannikou E. The presence of Helicobacter pylori in dental
plaque of children and their parents: is it related to their peri-
odontal status and oral hygiene? Eur J Paediatr Dent
2012;12:225–30.
© 2012 Blackwell Publishing Ltd, Helicobacter 17 (Suppl. 1): 1–8
H. pylori epidemiology & diagnosis
19 Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon
AT, Bazzoli F, et al. Management of Helicobacter pylori infection
–the Maastricht IV/Florence Consensus Report. Gut
2012;61:646–64.
20 Omori T, Kamiya Y, Tahara T, Shibata T, Nakamura M,
Yonemura J, et al. Correlation between magnifying narrow
band imaging and histopathology in gastric protruding/or
polypoid lesions: a pilot feasibility trial. BMC Gastroenterol
2012;12:17.
21 Shukla R, Abidi WM, Richards-Kortum R, Anandasabapathy S.
Endoscopic imaging: how far are we from real-time histology?
World J Gastrointest Endosc 2011;3:183–94.
22 Alaboudy AA, Elbahrawy A, Matsumoto S, Yoshizawa A.
Conventional narrow-band imaging has good correlation with
histopathological severity of Helicobacter pylori gastritis. Dig Dis
Sci 2011;56:1127–30.
23 Kawamura M, Abe S, Oikawa K, Terai S, Saito M, Shibuya D,
et al. Topographic differences in gastric micromucosal patterns
observed by magnifying endoscopy with narrow band imaging.
J Gastroenterol Hepatol 2011;26:477–83.
24 Ji R, Zuo XL, Yu T, Gu XM, Li Z, Zhou CJ, et al. Mucosal
barrier defects in gastric intestinal metaplasia: in vivo
evaluation by confocal endomicroscopy. Gastrointest Endosc
2012;75:980–7.
25 Neumann H, Fuchs FS, Vieth M, Atreya R, Siebler J, Kiesslich
R, et al. Review article: in vivo imaging by endocytoscopy. Ali-
ment Pharmacol Ther 2011;33:1183–93.
26 Kiesslich R, Goetz M, Hoffman A, Galle PR. New imaging tech-
niques and opportunities in endoscopy. Nat Rev Gastroenterol
Hepatol 2011;8:547–53.
27 Zhang JG, Liu HF. Functional imaging and endoscopy. World J
Gastroenterol 2011;17:4277–82.
28 Braden B. Diagnosis of Helicobacter pylori infection. BMJ
2012;344:e828.
29 Choi YJ, Kim N, Lim J, Jo SY, Shin CM, Lee HS, et al. Accu-
racy of diagnostic tests for Helicobacter pylori in patients with
peptic ulcer bleeding. Helicobacter 2012;17:77–85.
30 Tian XY, Zhu H, Zhao J, She Q, Zhang GX. Diagnostic perfor-
mance of urea breath test, rapid urea test, and histology for He-
licobacter pylori infection in patients with partial gastrectomy: a
meta-analysis. J Clin Gastroenterol 2012;46:285–92.
31 Cerqueira L, Fernandes RM, Ferreira RM, Carneiro F, Dinis-
Ribeiro M, Figueiredo C, et al. PNA-FISH as a new diagnostic
method for the determination of clarithromycin resistance of
Helicobacter pylori. BMC Microbiol 2011;11:101.
32 Koumi A, Filippidis T, Leontara V, Makri L, Panos MZ. Detec-
tion of Helicobacter pylori: a faster urease test can save resources.
World J Gastroenterol 2011;17:349–53.
33 Li Y, Rimbara E, Thirumurthi S, Trespalacios A, Reddy R, Sa-
bounchi S, et al. Detection of clarithromycin resistance in Heli-
cobacter pylori following noncryogenic storage of rapid urease
tests for 30 days. J Dig Dis 2012;13:54–9.
34 Manguso F, Riccio E, de Nucci G, Aiezza ML, Amato G,
Degl’Innocenti L, et al. Helicobacter pylori infection in bleeding
peptic ulcer patients after non-steroidal antiinflammatory drug
consumption. World J Gastroenterol 2011;17:4509–16.
35 Sudraba A, Daugule I, Rudzite D, Funka K, Tolmanis I, Eng-
strand L, et al. Performance of routine Helicobacter pylori tests in
patients with atrophic gastritis. J Gastrointestin Liver Dis
2011;20:349–54.
36 Hutton ML, Kaparakis-Liaskos M, Ferrero RL. The use of Albu-
MAX II((R)) as a blood or serum alternative for the culture of
Helicobacter pylori. Helicobacter 2012;17:68–76.
7
H. pylori epidemiology & diagnosis
37 Jimenez-Soto LF, Rohrer S, Jain U, Ertl C, Sewald X, Haas R.
Effects of cholesterol on Helicobacter pylori growth and virulence
properties in vitro. Helicobacter 2012;17:133–9.
38 Park SA, Ko A, Lee NG. Stimulation of growth of the human
gastric pathogen Helicobacter pylori by atmospheric level of oxy-
gen under high carbon dioxide tension. BMC Microbiol
2011;11:96.
39 Siavoshi F, Saniee P, Atabakhsh M, Pedramnia S, Tavakolian
A, Mirzaei M. Mucoid Helicobacter pylori isolates with fast
growth under microaerobic and aerobic conditions. Helicobacter
2012;17:62–7.
40 Ramirez-Lazaro MJ, Lario S, Casalots A, Sanfeliu E, Boix L,
Garcia-Iglesias P, et al. Real-time PCR improves Helicobacter
pylori detection in patients with peptic ulcer bleeding. PLoS
ONE 2011;6:e20009.
41 Woo HY, Park DI, Park H, Kim MK, Kim DH, Kim IS, et al.
Dual-priming oligonucleotide-based multiplex PCR for the
detection of Helicobacter pylori and determination of clarithro-
mycin resistance with gastric biopsy specimens. Helicobacter
2009;14:22–8.
42 Lehours P, Sifre E, Megraud F. DPO multiplex PCR as an alter-
native to culture and susceptibility testing to detect Helicobacter
pylori and its resistance to clarithromycin. BMC Gastroenterol
2011;11:112.
43 Miendje Deyi VY, Burette A, Bentatou Z, Maaroufi Y, Bontems
P, Lepage P, et al. Practical use of GenoType(R) HelicoDR, a
molecular test for Helicobacter pylori detection and susceptibility
testing. Diagn Microbiol Infect Dis 2011;70:557–60.
44 Scaletsky IC, Aranda KR, Garcia GT, Goncalves ME, Cardoso
SR, Iriya K, et al. Application of real-time PCR stool assay
for Helicobacter pylori detection and clarithromycin sus-
ceptibility testing in Brazilian children. Helicobacter 2011;16:
311–5.
45 Vecsei A, Innerhofer A, Graf U, Binder C, Giczi H, Hammer K,
et al. Helicobacter pylori eradication rates in children upon sus-
ceptibility testing based on noninvasive stool polymerase chain
reaction versus gastric tissue culture. J Pediatr Gastroenterol Nutr
2011;53:65–70.
46 Sicinschi LA, Correa P, Bravo LE, Peek RM Jr, Wilson KT, Loh
JT, et al. Non-invasive genotyping of Helicobacter pylori cagA,
vacA, and hopQ from asymptomatic children. Helicobacter
2012;17:96–106.
47 Markovska R, Boyanova L, Yordanov D, Gergova G, Mitov I.
Helicobacter pylori oipA genetic diversity and its associations with
both disease and cagA, vacA s, m, and i alleles among Bulgarian
patients. Diagn Microbiol Infect Dis 2011;71:335–40.
48 Shukla SK, Prasad KN, Tripathi A, Ghoshal UC, Krishnani N,
Nuzhat H. Quantitation of Helicobacter pylori ureC gene and its
comparison with different diagnostic techniques and gastric his-
topathology. J Microbiol Methods 2011;86:231–7.
49 Ren L, Liao YL, Song Y, Guo Y, Mao XH, Xie QH, et al.
High frequency variations of Helicobacter pylori isolates in indi-
vidual hosts in a Chinese population. Int J Infect Dis 2012;16:
e358–63.
50 Schmilovitz-Weiss H, Sehayek-Shabat V, Eliakim R, Skapa E,
Avni Y, Shirin H. Applicability of a short/rapid 13C-urea breath
8 © 2012 Blackwell Publishing Ltd, Helicobacter 17 (Suppl. 1): 1–8
Tonkic et al.
test for Helicobacter pylori: retrospective multicenter chart review
study. BMC Gastroenterol 2012;12:8.
51 Wardi J, Shalev T, Shevah O, Boaz M, Avni Y, Shirin H. A
rapid continuous-real-time 13C-urea breath test for the detec-
tion of Helicobacter pylori in patients after partial gastrectomy. J
Clin Gastroenterol 2012;46:293–6.
52 Leal YA, Flores LL, Fuentes-Panana EM, Cedillo-Rivera R, Tor-
res J. 13C-urea breath test for the diagnosis of Helicobacter pylori
infection in children: a systematic review and meta-analysis.
Helicobacter 2011;16:327–37.
53 Shimoyama T, Sawaya M, Ishiguro A, Hanabata N, Yoshimura
T, Fukuda S. Applicability of a rapid stool antigen test, using
monoclonal antibody to catalase, for the management of Heli-
cobacter pylori infection. J Gastroenterol 2011;46:487–91.
54 Choi J, Kim CH, Kim D, Chung SJ, Song JH, Kang JM, et al.
Prospective evaluation of a new stool antigen test for the detec-
tion of Helicobacter pylori, in comparison with histology, rapid
urease test, (13)C-urea breath test, and serology. J Gastroenterol
Hepatol 2011;26:1053–9.
55 Kodama M, Murakami K, Okimoto T, Fukuda Y, Shimoyama
T, Okuda M, et al. Influence of proton pump inhibitor treat-
ment on Helicobacter pylori stool antigen test. World J Gastroen-
terol 2012;18:44–8.
56 Leal YA, Cedillo-Rivera R, Simon JA, Velazquez JR, Flores LL,
Torres J. Utility of stool sample-based tests for the diagnosis of
Helicobacter pylori infection in children. J Pediatr Gastroenterol
Nutr 2011;52:718–28.
57 Toyoda K, Furusyo N, Ihara T, Ikezaki H, Urita Y, Hayashi J.
Serum pepsinogen and Helicobacter pylori infection-a Japanese
population study. Eur J Clin Microbiol Infect Dis 2012 Feb 22
[Epub ahead of print].
58 Bornschein J, Selgrad M, Wex T, Kuester D, Malfertheiner P.
Serological assessment of gastric mucosal atrophy in gastric
cancer. BMC Gastroenterol 2012;12:10.
59 Bauer S, Krumbiegel P, Richter M, Richter T, Roder S, Rolle-
Kampczyk U, et al. Influence of sociodemographic factors on
Helicobacter pylori prevalence variability among schoolchildren
in Leipzig, Germany. A long-term follow-up study. Cent Eur J
Public Health 2011;19:42–5.
60 den Hoed CM, Vila AJ, Holster IL, Perez-Perez GI, Blaser MJ,
de Jongste JC, et al. Helicobacter pylori and the birth cohort
effect: evidence for stabilized colonization rates in childhood.
Helicobacter 2011;16:405–9.
61 Oleastro M, Pelerito A, Nogueira P, Benoliel J, Santos A, Cabral
J, et al. Prevalence and incidence of Helicobacter pylori Infection
in a healthy pediatric population in the Lisbon area. Helicobacter
2011;16:363–72.
62 Gupta V, Perez-Perez GI, Dorsey G, Rosenthal PJ, Blaser MJ.
The seroprevalence of Helicobacter pylori and its relationship to
malaria in Ugandan children. Trans R Soc Trop Med Hyg
2012;106:35–42.
63 Amberbir A, Medhin G, Erku W, Alem A, Simms R, Robinson
K, et al. Effects of Helicobacter pylori, geohelminth infection and
selected commensal bacteria on the risk of allergic disease and
sensitization in 3-year-old Ethiopian children. Clin Exp Allergy
2011;41:1422–30.