J Vet Intern Med 2000;14:125–133
Helicobacter Infection in Dogs and Cats: Facts and Fiction
Reto Neiger and Kenneth W. Simpson
The discovery of the spiral bacterium Helicobacter pylori and its causative role in gastric disease in humans has brought a dramatic
change to gastroenterology. Although spiral bacteria have been known for more than a century to infect the stomachs of dogs and
cats, recent research has been conducted mainly in the wake of interest in H. pylori. H. pylori has not been found in dogs and
only very rarely in cats and zoonotic risk is minimal. A variety of other Helicobacter spp. can infect the stomach of pets; however,
their pathogenic role is far from clear, and they have a small but real zoonotic potential. The prevalence of gastric Helicobacter
spp. in dogs and cats is high, irrespective of clinical signs, and as in human medicine, mode of transmission is unclear. The
relationship of Helicobacter spp. to gastric inflammation in cats and dogs is unresolved, with inflammation, glandular degeneration,
and lymphoid follicle hyperplasia accompanying infection in some but not all subjects. Circulating anti-Helicobacter immunoglobulin G antibodies have been detected in 80% of dogs with naturally acquired infection and most dogs and cats with experimental
infection. The gastric secretory axis is similar in infected and uninfected cats and dogs and no relationship of infection to gastrointestinal ulcers has been found. Differences in the pathogenicity of Helicobacter spp. are apparent, because infection with H pylori
is associated with a more severe gastritis than infection with other Helicobacter spp. in both cats and dogs. Rapid urease test,
histopathology, and touch cytology are all highly accurate invasive diagnostic tests for gastric Helicobacter-like organisms in dogs
and cats, whereas culture and polymerase chain reaction are the only means to identify them to the species level. Urea breath and
blood tests or serology can be used to diagnose Helicobacter spp. noninvasively in dogs and cats. Most therapeutic studies in pets
have not shown long-term eradication of Helicobacter spp. Whether this is due to reinfection or recrudescence has not been
established.
Key words: Canine; Epidemiology; Feline; Review; Scanning electron microscopy; Spiral organisms; Therapy.
R
ecognition and treatment of Helicobacter pylori has
greatly simplified the management of chronic ulcer
disease in humans. Since isolation of H pylori in 1983,1 it
has become clear that H pylori infection is associated with
a chronic superficial gastritis in all infected humans, can
cause peptic ulcers, and is a cofactor for the development
of gastric carcinoma and lymphoma.1–3 The presence of spiral bacteria in the stomachs of animals has been known for
more than a century,4–6 and gastric spiral organisms have
been documented in dogs, cats,7–16 ferrets, monkeys, cheetahs, pigs, cows, predatory cats, and foxes, among other
species.17 To date, relatively little attention has been paid
to the pathogenicity of species other than H pylori and the
consequences of a Helicobacter infection in healthy and
sick animals is far from clear. Danger exists that information gathered in H pylori-infected humans will be directly
applied to veterinary patients without consideration of differences in Helicobacter spp. and the response of nonhuman hosts. This review summarizes our current knowledge
of gastric Helicobacter spp. infection in dogs and cats
Species Characteristics
Helicobacter spp. are gram-negative, microaerophilic,
curved to spiral-shaped, motile bacteria that, along with
Campylobacter and Arcobacter, belong to a distinct phylum
From the Department of Small Animal Medicine and Surgery, Royal
Veterinary College, University of London, North Mymms, Hertfordshire, UK (Neiger); and the Department of Clinical Sciences, College
of Veterinary Medicine, Cornell University, Ithaca, NY (Simpson).
Reprint requests: Reto Neiger, Dr. med. vet. PhD, The Royal Veterinary College, University of London, Hawkshead Lane, North
Mymms, Hatfield, Hertfordshire AL9 7TA, UK; e-mail: rneiger@
rvc.ac.uk.
Submitted March 4, 1999; Revised August 10, 1999; Accepted October 5, 1999.
Copyright q 2000 by the American College of Veterinary Internal
Medicine
0891-6640/00/1402-0002/$3.00/0
within the class Proteobacteria of the eubacteria: the rRNA
superfamily VI.18 In addition to the stomach, they are found
in the intestine and liver of various animal species.17 To
date 31 organisms with typical characteristics of Helicobacter species have been described; however, many names
commonly used have not been properly validated, thus
causing confusion as to the taxonomic status of these bacteria.19 Most gastric Helicobacter-like organisms (GHLO)
found in dogs and cats are large spiral organisms (0.5 3
5–10 mm) and cannot be distinguished by light microscopy.
Early reports describing GHLO were based on electron microscopic morphologic criteria.14 However, because bacterial morphology varies in vivo and in vitro,15,20 electron
microscopic appearance is not a definitive means of distinguishing different GHLO. Taxonomic classification of Helicobacter spp. relies mainly on the determination of their
16S rRNA and 23S rRNA sequence and DNA hybridization
or on culture with conventional phenotype testing.19–21
To date H felis, H bizzozeronii, H salomonis, ‘‘Flexispira
rappini,’’ H bilis, and ‘‘H heilmannii’’ have been reported
from the stomach of dogs,15,20,22 whereas H felis, H pametensis, H pylori, and ‘‘H heilmannii’’ have been reported
from the stomach of cats.12,20,23 Large tightly spiraled
GHLO in the human gastric mucosa were described soon
after the discovery of H pylori and were initially named
‘‘Gastrospirillum hominis.’’24 The 1st large GHLO cultured
was named H felis because of its isolation from a cat stomach,25 but it can also be found in dogs15,20,22,26,27 and human
patients.28 It has sparsely distributed periplasmic fibers appearing singly or in groups of 2, 3, or 4 on the crest of the
helical body (Fig 1). Two other GHLO have been cultured
from the dog stomach, namely H bizzozeronii, an organism
without periplasmic fibers,16 and H salomonis, with a shorter and thicker cell body.29 A bacterium entwined with periplasmic fibers that seem to cover the entire surface of the
organisms has also been found in the stomach of dogs.14,15
It is closely related to the genus Helicobacter and is classified as ‘‘F rappini.’’ Uncultured large gastric spiral or-
126
Neiger and Simpson
Fig 1. Scanning electron microscopy of a Helicobacter felis from a canine gastric biopsy. Multiple flagellae are visible at both poles as well as
a single periplasmic fiber on the crest of the helical body (courtesy of Dr M. Stoffel, Veterinary Anatomy, Bern, Switzerland).
ganisms that lack periplasmic fibrils or have a small fiber
in the valley of the helical body (Fig 2) are perhaps the
most common GHLO found in cats and dogs.12,22,30 By comparison of their 16S rRNA sequence these organisms are
considered members of the genus Helicobacter and some
were subsequently named ‘‘H heilmannii’’ in honor of the
German pathologist Konrad Heilmann.31 Only recently 1
‘‘H heilmannii’’ strain was isolated in Denmark and typed
based on its 16S rRNA sequence.32
H pylori, which was isolated from laboratory cats,23 is
much smaller (0.5 3 1.5–3 mm), curved or S-shaped, and
easily distinguished by light microscopy (Fig 3). Unexpectedly, H pylori strain ATCC 43504 resembles morphologically, when grown on blood agar plates, H pylori,
whereas when grown in broth media, the morphologic appearance resembles that of ‘‘H heilmannii.’’33 Other Helicobacter spp. such as H pametensis and H bilis have been
sporadically reported in the stomach of dogs and cats.12,34
Although mixed gastric infections with 2 or more Helicobacter spp. have been reported in dogs,11,14,20,22 others have
demonstrated competitive exclusion after 1 Helicobacter
sp. has colonized the stomach.35 Similarly, H salomonis
originally present in the stomach of 6-week-old puppies
were suppressed by an experimental infection with H bizzozeronii.36
In addition to the gastric Helicobacter spp., an increasing
number of intestinal and hepatic Helicobacter spp. have
been described. H cinaedi, H fenneliae, and ‘‘F rappini’’
have been isolated from the feces from dogs and
cats,14,17,37,38 ‘‘H colifelis’’ was described in a kitten with
severe diarrhea,39 and H canis was found in dogs with and
without diarrhea as well as in the liver of a dog with multifocal necrotizing hepatitis.40 The pathogenicity of these
nongastric Helicobacter spp. in dogs and cats is similarly
unclear at the moment.
Epidemiology
Gastric Helicobacter-like organisms are highly prevalent
in cats and dogs, with 86% of random-source cats,10,41 100%
of random-source dogs,42 90–100% of clinically healthy pet
cats,12,13,20,30 67–100% of clinically healthy pet dogs,15,20,22,43,44
and 100% of laboratory beagles and shelter dogs infected.15,42,45 GHLO have also been demonstrated in gastric biopsies from 57–76% of cats8,9,44 and 61–95% of dogs8,9,43,44
presented for the investigation of recurrent vomiting. Living
conditions seem an important factor because most studies
using shelter or colony dogs or cats have a higher prevalence than studies using pets.15 Age may also play a role,
because young animals may be less often colonized than
adults,10, although this is controversial.7,8,12 Cats as young
as 6 weeks were infected based on the 13C-urea breath test
(Neiger, personal communication) and 10 of 10 cats ,6
months old were densely colonized with H pylori (Simpson,
Helicobacter Infection in Dogs and Cats
127
Fig 2. Scanning electron microscopy of multiple Helicobacter heilmannii from a canine gastric biopsy. A small fiber is present in the valley of
the helical body and multiple flagellae are found at both poles (courtesy of Dr M. Stoffel, Veterinary Anatomy, Bern, Switzerland).
personal communication). Interestingly, Yamasaki and coworkers44 found a lower prevalence in sick compared to
healthy pets. Possible explanations for this finding could be
the recent use of antibiotics in sick animals or perhaps a
protective immune response.
The prevalence of GHLO in dogs and cats also depends
on the techniques employed to detect Helicobacter spp. In
research studies using several diagnostic tests or including
a test of high sensitivity, such as impression smears or polymerase chain reaction (PCR), a higher prevalence is noted.12,13,15,22,43 Few reports cited above mentioned the prevalence of specific Helicobacter spp. in the stomach of cats
and dogs. Recently, in Swiss cats positive for GHLO only
‘‘H heilmannii’’ was identified.12 In a study of 95 dogs, 21
strains of H bizzozeronii, 8 strains of H felis, 8 strains of
H salomonis, and 2 strains of ‘‘F rappini’’-like organisms
were isolated,20 whereas among other species, 12 strains of
‘‘H heilmannii’’ were found in 65 Swiss dogs by PCR.22
The precise mode of transmission of Helicobacter is unclear. A fecal–oral spread is hypothesized by some, because
H pylori can be cultured from human and cat feces, and
suboptimal sanitary conditions in underdeveloped countries
might favor such a transmission.46,47 Oral–oral spread is hypothesized by others, because H pylori can be found in the
saliva of infected humans and the spouses of infected people have a higher prevalence.46 Although gnotobiotic dogs
experimentally infected with H pylori and H felis transmit-
ted the organism to uninfected dogs,48,49 H felis- and ‘‘H
heilmannii’’-positive mice did not transmit the infection to
naive mice, suggesting that oral–oral transmission in vomiting puppies is more likely than fecal–oral spread in coprophageous mice.50 However, the recent isolation of H pylori from surface water in the United States and Sweden51,52
suggests that water-borne infection is likely to be an important route, particularly when considering that H pylori
is more resistant to chlorination than is Escherichia coli.
Finally, H salomonis can be transmitted from the dam to
puppies during the lactation period.36
Pathogenicity
In human patients extensive evidence exists implicating
H pylori in the pathogenesis of chronic superficial gastritis.
Eradication of H pylori by antimicrobial therapy cures gastritis and the titer of anti-H pylori antibodies decreases with
time. A plethora of reports have shown many putative
mechanisms by which H pylori alters gastric physiology,46,53,54 including the induction of gastric inflammation, by
the disruption of the gastric mucosal barrier (disrupting
phospholipases, secreting vacuolating cytotoxins, inducing
apoptosis, and so on), or by altering the gastric secretory
axis (by decreasing somatostatin release, inducing hypergastrinemia, diminishing the responsiveness of parietal
cells, and so on). H pylori infection in humans has been
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Neiger and Simpson
Fig 3. Light microscopic picture (Warthin Starry stain) from the stomach of a cat infected with Helicobacter pylori. The bacteria, which are
seen in the mucous overlying the mucosa, have the typical comma or S-shaped appearance and are 2–3 mm long.
associated with the production of the proinflammatory cytokines interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis
factor-alpha (TNF-a).55,56 The production of these proinflammatory cytokines has been linked to alterations in gastrin, somatostatin, and acid secretion, and the genesis of
gastritis and ulceration.55,57,58
Infection with Helicobacter spp. also predisposes humans to the development of gastric cancer.2,3,59 The precise
mechanism of carcinogenesis is unclear, but it may involve
the induction of nitric oxide synthetase by proinflammatory
cytokines with subsequent NO production and nitrosamine
formation.60 It may also involve a decrease in apoptosis
relative to cell proliferation.61
Disease may be defined as tissue injury or clinical manifestation.62 This fundamental statement is important, because the relationship of Helicobacter spp. to gastric inflammation in cats and dogs is unresolved, with inflammation or glandular degeneration accompanying infection
in some but not all subjects.7–9,11,12,44 In dogs with naturally
acquired helicobacteriasis, mild gastritis with infiltration of
lymphocytes and plasma cells have been commonly observed.7,8,15,22 Enlarged canaliculi and pyknotic parietal cells
have also been reported.11 Interestingly, in a recent study,
glandular degeneration was more frequent in the fundi of
dogs and cats with GHLO than without GHLO, but gastric
fibrosis and lymphycytic–plasmacytic enteritis were similar.44
Histologic findings in infected as well as uninfected cats
vary from a normal gastric mucosa to mild or moderate
chronic gastritis.7,12,13,30 A correlation between the presence
of GHLO and the extent of histopathologic changes was
demonstrated in 1 study.9 Moreover, Happonen and coworkers7 found lymphocyte aggregates only in GHLO-positive cats, which also had more lymphocytes in the fundus
and corpus than GHLO-negative cats. A more severe gastritis characterized by marked lymphoid follicular hyperplasia and infiltration of neutrophils and eosinophils has
been observed in cats with H pylori infection.23,63
Factors that must be considered when trying to interpret
the results of studies performed in dogs and cats include
the source of the animals, presence or absence of clinical
signs, methodologies used to confirm infection status, and
the criteria used to examine histopathologic sections. In
several studies dogs and cats were selected on the basis of
gastrointestinal signs,8,9,43,44 whereas in others, all animals
were asymptomatic.7,10–12,15,30 Thus, drawing a relationship
between GHLO colonization and symptoms is difficult.
Multiple studies have evaluated gastric histopathology
and have described the type and degree of inflammatory
cells, lymphoid follicles, and glandular alterations; however, the lack of standardized criteria to define histologic
changes makes comparison between different studies impossible at worst or cumbersome at best. The high prevalence of infection in dogs and cats also makes finding a
suitable negative control group difficult. Furthermore, because most studies have used only limited diagnostic tests
Helicobacter Infection in Dogs and Cats
with limited sensitivity, comparisons of colonized to noncolonized animals may have been inaccurate. Finally, the
presence of multiple species complicates the investigation
of pathogenicity.20,22
In addition to determining the presence of specific Helicobacter species, it is apparent that an effective study of
the pathogenicity of Helicobacter spp. in dogs and cats will
require us to step beyond the assessment of mucosal pathology with a light microscope to investigate the cellular,
immunologic, and functional consequences of infection. In
dogs with naturally acquired Helicobacter spp. infection, a
variety of secretory function tests such as unstimulated gastric pH, fasting, postprandial, and bombesin-stimulated
plasma gastrin levels, as well as pentagastric-stimulated
maximal acid output and titratable acidity were similar
when compared to a specific-pathogen-free (SPF), Helicobacter-free control group.64 The question of clinical manifestation still must be taken into consideration.
Experimental Studies
Relatively few experimental studies of Helicobacter infection have been conducted in dogs and cats. Gnotobiotic
dogs have been experimentally infected with H pylori49 and
H felis,48 SPF dogs with H felis,65 and SPF cats with H
pylori and H felis.63,66 Only recently conventional 4- to 6month-old Beagle puppies were experimentally infected
with a mouse-adapted H pylori strain.67 All gnotobiotic
dogs (n 5 5 in both studies) showed a chronic gastritis after
4 weeks of infection with H pylori and H felis and an increase in fasting gastric pH was reported in 4 of 10 dogs
after infection.48,49 In contrast, SPF dogs showed no relationship of H felis infection to gastric inflammation after 6
months.65 Blinded evaluation of gastric biopsies from those
dogs revealed mild gastric inflammation and lymphoid follicles in both infected and uninfected dogs. No correlation
was found between the number of organisms observed and
the degree of gastric inflammation or number of lymphoid
follicles. The gastric secretory axis, assessed by fasting and
meal-stimulated plasma gastrin, mucosal gastrin and somatostatin immunoreactivity, fasting gastric pH, and pentagastrin-stimulated gastric acid secretion was similar in
both infected and uninfected dogs. This study in SPF dogs
also showed that fasting gastric pH was not a reliable indicator of gastric secretory function.65 H pylori infection in
conventional puppies resulted in vomiting and loose stool
shortly after inoculation. After 1 week of infection these
dogs showed a marked polymorphonuclear leukocyte infiltration in the lamina propria, which over the next few
weeks changed to a chronic follicular gastritis with the
presence of small lymphoplasmacytic aggregates and lymphoid follicles and only scattered neutrophilic granulocytes.
Additionally, IL-8 was detected immunohistochemically after the 1st and 2nd week of infection in areas of the stomach
where neutrophil transcytosis was most pronounced and became undetectable in biopsies taken from week 8 onwards,
when neutrophilic infiltration was much less prominent than
in the early phase of infection.67
In SPF cats infected with 2 different H pylori strains
(cytoxin-associated protein cagA present or absent) chronic
gastritis was observed 4 to 7 months after infection.63,66
129
Multifocal lymphoplasmacytic follicles were prominent in
the antrum and body of infected cats. Five SPF Helicobacter-free cats were studied before and for 1 year after inoculation with H felis.68 Four SPF uninfected cats served
as controls. Lymphoid follicular hyperplasia, atrophy, and
fibrosis were observed primarily in the pylorus of infected
cats. Mild mononuclear inflammation was detected in both
infected and uninfected cats, but was more extensive in
infected cats, with inflammation throughout the stomach,
and cardia gastritis observed only in infected cats. Eosinophilic infiltrates were observed only in infected cats.68 No
upregulation of antral mucosal IL-1a, IL-1b, or TNF-a was
detected by reverse transcription-PCR in any cats. The gastric secretory axis, assessed by fasting plasma gastrin and
pentagastrin-stimulated gastric acid secretion, was similar
in both infected and uninfected cats.68
Seroconversion was observed in all of these studies. H
felis- and H pylori-infected gnotobiotic dogs had fairly rapid and uniform seroconversion 3 weeks after infection,
whereas H felis-infected SPF dogs showed more gradual
and variable seroconversion over the 6-month period of infection.48,49,65 The serologic responses observed in SPF dogs
are similar to those in SPF cats infected with H pylori and
H felis, where some cats did not seroconvert until 6 months
after infection and had titers 2- to 15-fold greater than baseline.65,66,68
Diagnosis
Diagnostic tests consist of invasive tests (rapid urease
test, histopathology, touch cytology, culture, PCR, electron
microscopy), which require an endoscopically taken biopsy
sample, and noninvasive tests (urea breath and blood tests,
serology).12,22,69
Invasive Tests
The rapid urease test is based on the production of urease
by almost all gastric Helicobacter spp.20 A gastric biopsy
is incubated in urea broth containing phenol red as a pH
indicator. As urease breaks down urea into ammonia, the
pH rises and a color change occurs. Other urease-producing
bacteria in the stomach (eg, Proteus spp. in coprophagic
beagles) can give a false positive reading, whereas patchy
distribution or rare urease-negative Helicobacter spp. can
yield false-negative results.70,71 Diagnosis in pets is obtained
normally within 1–3 hours. In humans, the rapidity of the
color change is somewhat proportional to a H pylori colonization.72
Histopathology relies on the observation of Helicobacter
organisms in gastric biopsy tissue. Special staining such as
silver stains,12,15 Giemsa,8,9 or toluidine blue,7 will enhance
the visibility of GHLO when colonization density is low.
Because of the patchy distribution, several biopsies from
antrum, corpus, and cardia should be evaluated. H pylori
induces in human patients a moderate to severe chronic–
active gastritis characterized by a persistent active granulocytic inflammatory response.46 Only recently has a similar
visual analogue scale for canine gastric biopsy specimens
been introduced, making comparison between various studies possible.43
Touch cytology with Gram or Diff Quika staining is a
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Neiger and Simpson
simple, rapid, and sensitive diagnostic test for diagnosing
infection with GHLO.12,13,22,43,73 However, the extent of a
concurrent gastritis or lymphoid follicular hyperplasia can
not be evaluated.
Bacteriologic culture of all Helicobacter spp. is cumbersome20 and the designation ‘‘H heilmannii’’-like organism
has been suggested for uncultured Helicobacter spp. without periplasmic fibers.30 Only recently, several Helicobacter
spp. were isolated from 51% of GHLO-positive dogs and
identification was performed by standardized conventional
phenotypic tests as well as by whole-cell protein profiling.20
Dot-blot DNA hybridization12,22 or PCR15 of positive culture
isolates are other means of Helicobacter species identification. Positive culture is the only possibility to determine
antimicrobial sensitivity.
PCR of DNA extracted from a biopsy specimen or from
gastric juice permits diagnosis as well as identification of
the Helicobacter species.12,15,22,42,74 Primers are mostly derived from either the urease gene or from the 16S rRNA
gene. PCR products can subsequently be cloned and sequenced or analyzed by restriction fragment length polymorphism to identify the species and strain.75
Electron microscopy has been advocated to differentiate
Helicobacter species on the basis of typical morphologic
criteria.14–16,76 Five cultured canine Helicobacter spp. could
be differentiated based on transmission and scanning electron microscopy.77 However, other studies showed that cultured Helicobacter spp. may lose their typical in vivo morphologic characteristics.15,20,33
For the diagnosis of naturally acquired Helicobacter infection in dogs and cats, rapid urease test, histopathology,
and touch cytology are highly accurate.12,22,43 When colonization density is low, impression smears and PCR seem
more accurate than modified Steiner stain and rapid urease
test.65,70 Multiple biopsies should always be acquired, not
only from fundus, but also from the cardia and antrum–
pylorus area, because of the patchy distribution of gastric
Helicobacter spp. Because of this pattern and the requirement of a gastric biopsy, less-invasive methods of diagnosing infection are clearly needed. In humans, noninvasive
diagnosis of H pylori has been achieved using serology or
the urea breath test. The former is largely used as screening
test, whereas the latter test is also used to confirm eradication after treatment.
Noninvasive Tests
Serology by enzyme-linked immunosorbent assay
(ELISA) or immunoblotting is used extensively as a diagnostic tool in human clinics and for epidemiologic studies.
The most accurate ELISA test kits are based on a variety
of semipurified antigens derived from H pylori and measure
circulating immunoglobulin G (IgG) in serum. IgG or IgA
can also be measured in the gastric fluid.46 In addition to
diagnosing an infection, immunoblotting has been used to
define the immunogenic moieties of H pylori or to investigate equivocal ELISA test results. Serodiagnosis in dogs
and cats represents a challenge, because they can harbor
several Helicobacter species.15,20,22 A recent study evaluated
immunoblotting and ELISA in serum samples from naturally infected dogs and from uninfected SPF dogs.42 Kinetic
ELISA results and number of bands per lane on a immunoblotting test were significantly higher for samples from
infected dogs than in uninfected dogs. Serology has limited
usefulness as an aid in demonstrating therapeutic success
in human patients, because titers may not decrease for 6
months or more after the infection has been cleared,46 although recent studies in humans show that a drop in antibody titers is consistent with eradication.78
The urea breath and blood tests use urea labeled with
isotopically stable 13C or radioactive 14C. Urease produced
by Helicobacter spp. cleaves ingested labeled urea to ammonia. The released labeled C atoms are absorbed into the
circulation and exhaled. Exhaled air is collected and with
13
C-urea the ratio of 13CO2 to 12CO2 is measured by mass
spectrometry, whereas the amount of radioactive CO2 is
analyzed with 14C-urea.79 The ratio of 13CO2 to 12CO2 can
also be measured in a blood sample.46 The 13C-urea breath
and blood test has been evaluated in cats12 and dogs.70 Because the urea breath test demonstrates the actual Helicobacter colonization, it is the preferred noninvasive method
to document a successful eradication in humans and animals. However, proton pump inhibitors and histamine H2receptor antagonists decrease the urease activity of Helicobacter spp., so the time of testing after antibiotic and
antisecretory usage is important.80,81 A gap of at least 2–5
days after cessation of therapy should be maintained. Furthermore, low levels of colonization might persist for many
months and may be missed by early testing.70,82
Therapy
Guidelines of the European Study Group of H pylori infection and the American National Institutes of Health state
that all patients with peptic ulcers and a H pylori infection
should be treated. No therapy is recommended for H pyloriinfected asymptomatic human patients.83 A plethora of clinical trials using different antimicrobial treatments have been
conducted to assess their ability to eradicate H pylori in
humans. An acid-secretory inhibitor drug-potentiated tripletherapy for 2 weeks (eg, clarithromycin, amoxicillin, bismuth plus ranitidine) or double-therapy for 1 week (eg,
metronidazole or amoxicillin, clarithromycin plus omeprazole or lansoprazole) show eradication rates of .90% in
human patients.
Whether antimicrobial therapy should be instituted in domestic pets with gastritis or ulcer disease is presently unknown. In a preliminary uncontrolled treatment trial use of
a combination of amoxicillin, metronidazole, and famotidine resulted in clinical improvement in .90% of 63 dogs
and cats colonized with GHLO and 74% of 19 dogs and
cats reexamined by gastroscopy were GHLO negative.84
Unfortunately, the diagnostic tests used and the time
elapsed between end of therapy and control endoscopy
were not reported. Only few controlled, randomized, blind
therapeutic studies in dogs and cats have been published.
In naturally infected dogs treatment with amoxicillin, metronidazole, and famotidine for 2 weeks was highly successful when evaluated 3 days after therapy, but 28 days
later GHLO were present and the urea breath test was positive in most dogs again.70 Similar results were observed in
naturally infected cats treated either with azithromycin, tin-
Helicobacter Infection in Dogs and Cats
idazole, bismuth, and ranitidine or with clarithromycin,
metronidazole, bismuth, and ranitidine for 4 or 7 days when
evaluated by urea breath test.82 After 3 weeks of amoxicillin, metronidazole, and omeprazole, cats with H pylori infection were culture negative, but 5 out of 6 cats were positive in a species-specific PCR in dental plaque, saliva, or
gastric fluid samples.74 All these studies indicate the difficulty of eradicating Helicobacter spp. in dogs and cats. In
most studies, whether antibiotic failure was due to reinfection or recrudescence was unclear. However, in 1 recent
preliminary study in dogs infected by GHLO, a 80% eradication rate after a 1-week triple therapy was reported as
controlled 30 days after therapy with urea breath test, rapid
urease test, and histology.85
Public Health Implication
Because of the discovery of cats harboring H pylori in a
research colony23,86 as well as in China87 and according to
preliminary data also in France,88 cats may be a potential
natural reservoir of H pylori and could pose a zoonotic risk.
In epidemiologic studies, H pylori-positive farm workers
showed significant more contact with cats than with other
animals.89 However, 2 studies evaluating H pylori antibodies in cat owners and comparing them to humans without
contact to cats showed no increased risk in the 1st population.90,91 A preliminary study in veterinarians was equally
negative for an increased risk of acquiring a H pylori infection from pets.92 Finally, isolation of H pylori from stray
and pet cats has not been possible in various studies,12,40,42
suggesting that H pylori infection in cats may be an anthroponosis—an animal infection with a human pathogen.93
The discovery of H pylori in surface water has shifted the
possibility of direct transmission from pets even further.52
Several reports in human patients have assumed a possible zoonotic transmission of large GHLO from dogs or
cats.94,95 Only recently, an identical ‘‘H heilmannii’’ organism identified by PCR and urease-B gene sequencing has
been found in a patient and 1 of his cats.75 The possible
risk of transmission of large GHLO to human patients is
rather small, considering the greater than 90% prevalence
in dogs and cats and the rare (,0.5%) occurrence in humans. Notwithstanding, proper hygienic control is necessary to keep the risk to a minimum.
Conclusion
Prevalence of gastric Helicobacter species in healthy or
sick client-owned dogs and cats is .70%. The pathogenic
role of GHLO has not been clearly established. Compared
to uninfected dogs, infected dogs have increased glandular
degeneration, circulating anti-Helicobacter antibodies, and
a variable increase in lymphoid follicles, but similar gastric
secretory function and mononuclear inflammation. The evidence to support a role for Helicobacter in gastritis in cats
is somewhat stronger than in dogs, where a relationship of
infection to glandular degeneration, lymphoid follicle hyperplasia, and mononuclear inflammation has been demonstrated. No abnormalities of gastric function have been
detected in cats infected with H felis and H pylori. The
species of Helicobacter may be important in regard to pathogenicity, because cats with H pylori infection develop
131
more severe gastritis than those with H felis or H heilmannii.
The clinician must carefully consider other causes of gastrointestinal signs in dogs and cats, such as dietary intolerance, parasitic or bacterial enteritis, or inflammatory bowel disease, before incriminating Helicobacter as the cause.
At the authors’ institutions treatment for GHLO is undertaken only in patients with clinical signs and biopsy-confirmed gastritis and Helicobacter infection. Treatment is
then instituted with a 2-week course of 2 antibiotics, mostly
amoxicillin and metronidazole or clarithromycin, with or
without an antisecretory drug, such as a proton-pump inhibitor or a H2-receptor antagonist. The authors’ opinion is
that well-controlled, blinded, prospective multicenter studies are required to elucidate the pathogenic role of GHLO
in cats and dogs with gastrointestinal signs and gastritis.
Footnote
Diff Quik, Dade, Düdingen, Switzerland
a
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