Helicobacter Infection

Vol. 19, No. 3 March 1997

V

Small Animal Gastroenterology

Continuing Education Article Refereed Peer Review

Helicobacter Infection FOCAL POINT ★The role of Helicobacter infection in gastrointestinal disease of small animals is being investigated.

KEY FACTS ■ Clinical signs of Helicobacter infection in dogs and cats reportedly include chronic vomiting and diarrhea, inappetence, pica, fever, and polyphagia. ■ Helicobacter mustelae has been linked to gastroduodenal ulceration and adenocarcinoma in ferrets. ■ Laboratory tests are being developed to detect and monitor Helicobacter infection in small animals. ■ Regimens involving antibiotic combinations, bismuth preparations, and acid suppression are used to eradicate Helicobacter infections in humans.

University of Tennessee

Christine C. Jenkins, DVM James R. Bassett, DVM

T

he recognition of the role of spiral bacteria in the pathogenesis of chronic gastritis, gastroduodenal ulceration, and neoplasia in humans and various animal species has spurred many recent studies. Gastric spiral bacteria, formerly assigned to the genus Campylobacter and now to Helicobacter, were first reported to occur in gastric biopsy specimens from dogs in 18891 and from humans in 1938.2 For decades, pathologists questioned the role of these organisms in gastrointestinal disease. Some assumed that spiral organisms were part of the normal gastric flora or were a contaminant of biopsy and autopsy specimens.3 The association of spiral bacteria with gastroduodenal disease in humans was reported by Marshall in 1983.4 Marshall proved an association when he reported the symptoms, endoscopic findings, and histopathologic changes he experienced after ingesting a broth containing spiral bacteria.4 After Marshall’s discovery, further investigation identified the bacteria as Helicobacter pylori.5 H. pylori infection is now recognized as the major cause of chronic gastritis in humans and is implicated as the cause of 60% to 80% of gastric ulcers and 90% of duodenal ulcers in humans.6 Until the recent acceptance of the pathogenicity of Helicobacter in gastritis and gastroduodenal ulcer disease in humans, traditional therapies for gastritis and gastroduodenal ulceration were based on the “no acid–no ulcer” theory. Human peptic ulcer disease was usually treated with antacids, H2-receptor blockers, and/or proton-pump inhibitors to reduce gastric acid and aid in ulcer healing. Because of significantly improved cure rates, gastroenterologists now use antibiotics directed against Helicobacter infection, in addition to acid-inhibition therapy, for the treatment of gastroduodenal ulceration and gastritis in humans.7 Veterinarians are now exploring the role of Helicobacter infection in gastrointestinal disease in veterinary patients. There appears to be a direct association between Helicobacter or similar organisms and gastrointestinal inflammation (and in some cases ulceration) in dogs, cats, cheetahs, and ferrets.8–13 Spiral organisms found in animals are usually a different species of Helicobacter from the H. pylori implicated in human ulcer disease. Not all Helicobacter species cause the same type or degree of gastrointestinal disease, so it would be incorrect to assume that data on H. pylori always apply to the spiral organisms found in small animals. This article gives practicing veterinarians an overview of the numerous publications written about Helicobacter and gastrointestinal disease. Because of the signifi-

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TABLE I Host Range and Pathogenicity of Helicobacter Species Helicobacter Species

Gastrointestinal Infiltrate and Gastric Pathology

Host Species

Zoonotic Potential

H. pylori types I and II

Humans, cats, pigs, and dogs (experimentally)

Lymphoplasmacytic, neutrophilic, eosinophilic; ulceration and gastric carcinoma in humans

Possible

H. acinonyx

Cheetahs (captive)

Severe lymphoplasmacytic, neutrophilic; gland abscess, lymphoid follicles, epithelial erosions

Unknown

H. felis

Cats, dogs, and humans

Lymphoplasmacytic, lymphoid nodules, neutrophilic, eosinophilic

Unknown

H. heilmannii (formerly Gastrospirillium hominis)

Humans, dogs, cats, cheetahs, nonhuman primates, and pigs

Lymphoplasmacytic, neutrophilic, eosinophilic

Possible

H. mustelae

Ferrets

Lymphocytic; carcinoma

Unknown

H. canis

Dogs

Hepatic necrosis

Unknown

H. bizzozeronii

Dogs

Unknown

Unknown

cance of H. pylori in human gastroenterology, most of the information about this genus pertains specifically to H. pylori. Publications addressing clinical findings associated with Helicobacter infection in veterinary patients are limited; however, valuable information has emerged from the search for appropriate animal models for human H. pylori infection.

EPIDEMIOLOGY AND EPIZOOTIOLOGY It is speculated that Helicobacter organisms are normal inhabitants of the stomach of many mammalian species, including dogs,8 cats,9 cheetahs,10,11 ferrets,12,13 pigs,14 humans,5 and nonhuman primates.15 An estimated 20% to 90% of humans are infected with H. pylori; most of these infections are subclinical.16 A recent postmortem survey of 55 random-source cats found Helicobacter-like organisms in 70% of juvenile cats and 97% of adult cats.16 In another study, 82% of 122 dogs and 76% of 127 cats were found by histopathologic evaluation to be infected with Helicobacter-like organisms.17 The exact prevalence in dogs and cats is unknown, but a high percentage may harbor the organisms as commensal inhabitants of the gastric mucosa. Transmission of Helicobacter organisms is suspected to occur by a fecal–oral or oral–oral route.18,19 Fecal–oral transmission is implicated by the higher infection rates in underdeveloped countries, where sanitation may be suboptimal. In these countries, Helicobacter organisms can be cultured from feces of infected children.18 In developed countries, oral–oral transmission may be more

common because the organisms can often be found in saliva from humans with H. pylori infection.19

SPECIES CHARACTERISTICS Helicobacter organisms are gram negative and microaerophilic and have sheathed flagella. They have urease, oxidase, and catalase activity and are motile in gastric mucus. Helicobacter organisms are curved when seen in tissue but appear rodlike, U-shaped, or circular in culture. On histopathologic examination, Helicobacter may appear in the mucus layer of the stomach overlying the mucosal epithelium, may be found closely adhered to surface epithelial cells, or may be seen invading the gastric mucosa. With the use of molecular biology techniques (e.g., 16S ribosomal RNA sequencing [PCR] and DNA hybridization), 13 species in the genus Helicobacter have been definitively identified in animals.20 These species are differentiated by various criteria, including size, morphology, affected hosts, and whether they can be grown in culture. Not all species of Helicobacter are pathogenic, nor have all been shown to induce the same degree or type of pathology in the gastrointestinal tract.18 H. heilmannii and H. felis are the two species most commonly found in dogs and cats. Although the major pathogen in humans is H. pylori, H. heilmannii has also been identified in a small percentage of human ulcer patients. At present, three species of Helicobacter organisms have been identified in the human lower bowel. Table I lists some species of

ROUTES OF INFECTION ■ PATHOGENICITY ■ HOST RANGE

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Helicobacter that have been associated with gastrointestinal inflammation or neoplasia.

PATHOGENICITY The pathogenicity of Helicobacter may result from its unique ability to survive the highly acidic environment of the stomach.6,14,18 Urease is present on the surface of the bacterium and within the cytoplasm. Urease production is an important factor in the organism’s ability to colonize the upper gastrointestinal tract. Urease breaks down urea in gastric juice into ammonia and bicarbonate ions. Ammonia then reacts with water to form ammonium, which increases the pH of the gastric mucus layer surrounding the organism. This buffer effect may extend the life of the organism, thus allowing for its eventual penetration deeper within the mucus surface into a more favorable alkaline environment.21 Urease may be indirectly responsible for some of the damaging effects to the mucosa because ammonia can cause histologic damage and vacuolation in epithelial cells.28 This damage, in combination with the inflammatory response that occurs deep in the mucosa, injures the gastric mucosal barrier and may thus increase the potential for mucosal erosion or ulceration. Helicobacter organisms also disrupt the host’s protective mucus layer, an important component of the gastric mucosal barrier. Helicobacter organisms attach to the mucusproducing cells of the epithelial layer and can affect the release of intracellular mucus into the gastric lumen.22,23 Humans,24 dogs,17 and ferrets with Helicobacter infection have a thinner layer of gastric mucus than do noninfected animals. Exposure to H. pylori lipopolysaccharide changes production of high-molecular-weight mucin to a lowmolecular-weight form with different biochemical processes (e.g., sulfation). Impaired sulfation of mucin has been associated with gastric disease.25 Because mucus normally protects the gastric mucosa, changes in its biochemical properties can predispose to ulceration. H. pylori produces a cytotoxin that can create vacuoles in epithelial cells in vitro26 and possibly in vivo.27 The significance of this cytotoxin is controversial, but 50% to 60% of H. pylori strains express cytotoxic activity in vitro. Some infected humans produce IgG specific for this cytotoxin; this finding implies that the cytotoxin may be significant in vivo. The gene (vac A) for this cytotoxin is present in type I H. pylori. Human patients with duodenal ulcers are always infected by cytotoxinproducing type I bacteria. Another protein (cytotoxin associated gene A [cag A] protein) is a marker for vacuolating toxin effect and is present only when vac A is present. Most humans with duodenal ulcer have antibodies to cag A. Theoretically, these antibodies could be used to screen human patients for duodenal ulcer.

Type I strains of H. pylori may induce mucosal damage by stimulating epithelial cytokine responses.25 Type II H. pylori do not express vac A or cag A. Not all species of Helicobacter need to produce cytotoxin in order to cause gastrointestinal disease. H. mustelae, for example, does not produce cytotoxin despite its association with gastroduodenal ulceration and possible link to gastric adenocarcinoma in ferrets.28 The motility and the helical shape of Helicobacter organisms also play a significant role in pathogenicity because movement through gastric mucus may support colonization.22,29 The Helicobacter organisms that are more motile in mucus have more spirals than do those that adhere to the mucosa.18 Pathogenicity of Helicobacter may correlate with motility because some nonmotile strains cannot colonize gastric epithelium.

Effects on Gastric Function Helicobacter infection may either increase or decrease production of gastric acid by parietal cells. Decreased gastric acid output (hypochlorhydria) has been shown to occur in early Helicobacter infections in several species. The exact mechanisms are unknown, but parietal-cell morphology is abnormal in animals and people with Helicobacter infection. The incidence of hypochlorhydria varies among people with H. pylori infection in different countries. In Japan, the incidence of gastric-acid hyposecretion associated with infection is high; whereas in the United Kingdom, the incidence is very low.30 Meal-stimulated gastrin concentrations are increased in humans and animals with Helicobacter infection. The exact cause of hypergastrinemia is unknown, but studies in rats have shown increased gastrin levels associated with long-term feeding of food containing a high concentration of ammonium. This evidence suggests that ammonia produced as a result of urea breakdown by urease may play a role in hypergastrinemia.31 Reduced levels of somatostatin in the antral mucosa of infected humans have been implicated as a cause of hypergastrinemia because somatostatin regulates gastrin release. Hypergastrinemia increases basal gastric acid secretion in infected humans.30 Basal acid output was three times higher in H. pylori-infected humans with duodenal ulceration than in normal controls.32 Gastrin levels and basal acid outputs return to normal after Helicobacter infection is eradicated.32 Inflammation and Ulcerogenesis Helicobacter infection in humans has been associated with Type B or antral gastritis, which is characterized by chronic inflammation of gastroduodenal tissue.23 Acute or active infection with Helicobacter can

UREASE ■ MUCIN ■ CYTOTOXIN ■ ACID PRODUCTION

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result in neutrophilic infiltration of the gastric mucosa. This initial response is probably induced by bacterial factors or by cytokines (e.g., interleukin-8) involved in inflammation. 25 Lymphoplasmacytic infiltrate and lymphoid nodules are typically observed on histopathologic examination of animals and humans with chronic infection (Figure 1). Typically, inflammatory changes secondary to Helicobacter occur deep in the gastric mucosa—distant from the area of colonization in the gastric mucus.18 As a result of this distant colonization, Helicobacter organisms may be protected from destruction by inflammatory cells and mediators. H. pylori may also avoid destruction by the host’s inflammatory response by its ability to produce superoxide dismutase and catalase—both of which are protective against killing by neutrophils. 18 The role of the inflammatory response in disease pathogenesis is unclear. Damage associated with inflammation in gastroduodenal tissues might be responsible for symptomatic disease, or inflammation might succeed in restraining Helicobacter infection in asymptomatic patients.18,30 In cases of chronic Helicobacter infection, areas of gastroduodenal mucosa distant from high numbers of Helicobacter organisms may be more prone to ulceration than areas where high numbers of Helicobacter are actually found.18,23 In the stom-

Figure 1A

Figure 1B

Figure 1C Figure 1—Gastric biopsy specimens from an 18-year-old cat

with a history of chronic progressive vomiting and hematemesis. The cat was given the diagnosis of Helicobacter-associated gastritis on the basis of a positive urease test and endoscopic biopsy. (A) The superficial lamina propria is expanded by lymphoid infiltrates (H&E, original magnification ×66). (B) Higher magnification reveals marked focal lymphoid infiltrate with displacement and loss of gastric glands (H&E, original magnification ×132). (C) Silver stains show numerous, large, tightly coiled, spiral bacteria (Helicobacter species). (Modified Steiner stain, original magnification ×330; Courtesy of James Dugan, DVM, University of Tennessee)

ach, ulceration occurs more commonly at the transitional zone between normal antral mucosa and normal body mucosa. The mucosa in these areas is believed to be less stable. Ulceration occurs in areas of the duodenum where there are patches of metaplastic mucosa with morphology similar to that of gastric mucus-secreting epithelium.18,23 Metaplastic changes in the duodenal mucosa occur secondary to the presence of gastric acid.

Role in Neoplasia Helicobacter pylori is classified as a group 1 carcinogen because of its association with gastric adenocarcinoma and B-cell lymphoma in humans.33 H. pylori is associated with adenocarcinomas that occur distal to the cardia—including intestinal and diffuse types.34 Epidemiologic evidence supports the association between Helicobacter infection and gastric cancer in humans. In countries with a high prevalence of gastric cancer (e.g., Peru, Columbia, and Mexico), all adults are infected with H. pylori. Also, Helicobacter infection in these countries tends to occur at an earlier age than in countries with a lower incidence of gastric carcinoma.35 Prospective studies in humans suggest that H. pylori infection quadruples the risk of developing gastric cancer in later life. The exact role of Helicobacter in gastric cancer has not been determined despite the establishment of an association. It is speculated that Helicobacter may make the

INFILTRATE ■ INFLAMMATION ■ METAPLASTIC CHANGES ■ ADENOCARCINOMA

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mucosa more susceptible to carcinogens by altering the mucus layer. Helicobacter decreases gastric secretion of ascorbic acid, a known antioxidant, and may thus predispose the mucosa to damage by N-nitrosamines. It is also possible that the bacteria themselves may produce products that cause metaplastic changes in the mucosa.18 The most accepted hypothesis is that chronic inflammation due to Helicobacter infection leads to genetic mutations that result in malignant transformation. These changes, in combination with exposure to dietary mutagens and environmental carcinogens, may lead to the development of neoplasia.35 Helicobacter mustelae has been associated with gastric adenocarcinoma in ferrets. 12,13 Veterinarians are now exploring the role of Helicobacter infection in gastrointestinal malignancies in dogs and cats.

invasive tests (which rely on indirect techniques to detect Helicobacter infecTests using endoscopically tion). Invasive tests include obtained biopsy specimens histologic examination, culture, rapid urease test■ Histopathologic examination—has high ing, and polymerase chain sensitivity and specificity; analysis of multiple reaction (PCR) techniques. biopsy specimens (at least two from each region Noninvasive tests include serology and radiolabeled of the stomach) is recommended to maximize carbon urea breath test chances of detection of the organism. (utilizing either 13C or 14C). ■ Rapid urease testing—can produce results in an Histopathologic examihour or less but sensitivity is only 70% to 90%; nation relies on microscopis often used in conjunction with histopathologic ic visualization of Heliexamination. cobacter-like organisms in gastric tissue. Visual■ Polymerase chain reaction—has high ization of organisms can specificity and sensitivity and can provide be enhanced by the use definitive identification of Helicobacter species of Warthin-Starry silver and strains but has limited availability. stains 37 (Figure 1C). This ■ Culture—is the least sensitive method; test has high sensitivity and some Helicobacter species have not yet been specificity, but false-negative results are possible besuccessfully cultured. cause the distribution of organisms in gastric tissue Serologic and noninvasive tests is often patchy.38–40 Analy■ IgG antibody titers—have high sensitivity and sis of multiple biopsies (at specificity in humans; do not reveal degree of least two from each region of the stomach) is recomgross or histologic gastroduodenal pathology; mended in order to maxititers may not decrease significantly until 6 mize chances of detection months or longer after the infection is eradicated. of the organism.40 ■ Urea breath test—uses a radiolabeled urea Histopathologic examitest meal; highly sensitive and specific, easy to Gastrointestinal Signs nation does not permit perform, and provides results rapidly; useful for Most of the animals and definitive identification of humans with Helicobacter the different Helicobacter monitoring patient response to Helicobacter infection have no clinical species or strains. Morphoeradication therapy. signs or symptoms of dislogic differences between H. pylori and H. heilmanease. Some infected humans nii (the Helicobacter organisms that are known to infect complain of postprandial discomfort, epigastric pain, humans) are pronounced enough, however, to allow heartburn, and dysphagia. Clinical signs reported to ocpresumptive differentiation based on histologic appearcur in dogs and cats include chronic vomiting and diarance. H. heilmannii is larger and more tightly coiled rhea; inappetence, pica, weight loss, fever, and polyphathan H. pylori.37,39,41 gia occur less often.17,36 Hematemesis or melena may be A major advantage of microscopic evaluation of tisobserved if there is concurrent erosive or ulcer disease. sue is that it allows for determination of the extent and DIAGNOSIS severity of inflammatory changes in the gastrointestinal Since the discovery that H. pylori is a major pathogen tract. It also affords the opportunity to evaluate for hisin humans, there have been significant advances in ditologic evidence of neoplasia. agnostics for Helicobacter infections. Diagnostic tests Rapid urease testing is a useful diagnostic tool be(see the box) consist of invasive tests (which require encause Helicobacter organisms are potent producers of urease. The procedure involves incubation of tissue doscopically obtained gastric tissue samples) and nonDiagnostic Tests for Helicobacter Infection

ASCORBIC ACID ■ GENETIC MUTATIONS ■ HISTOPATHOLOGY

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samples in a urea broth containing a pH indicator (phenol red). A color change occurs as urease breaks down urea into ammonia, which raises the pH. The rapidity of the color change may be proportional to the density of Helicobacter organisms.41 Because at least 104 organisms are required for the rapid urease test to produce a positive result, the sensitivity of the test is only 70% to 90%.39,40 Its principal advantage is the rapidity with which test results are obtained (often within 1 hour or less).39,40 Urease testing is often used in conjunction with histopathologic examination. Culture of the organism is the least sensitive method for diagnosis of Helicobacter infection because H. pylori is difficult to cultivate in culture media38,40 and H. heilmanii has never been successfully cultured.36 The advantages of culture are that it permits differentiation of Helicobacter strains and allows for determination of antimicrobial sensitivity.39 The polymerase chain reaction (PCR) technique amplifies a specific segment of the genetic material of Helicobacter organisms. It provides definitive identification of Helicobacter species and strains and has a high sensitivity and specificity.40 PCR is currently performed in only a few centers, which limits its convenience as a diagnostic test. Because tissue samples can only be obtained by endoscopy, noninvasive alternative tests have been developed for the diagnosis of Helicobacter infection. Serologic testing of human serum samples for IgG antibodies to Helicobacter organisms has high sensitivity and specificity.38,42 However, serologic testing does not reveal the degree of gross or histologic gastroduodenal pathology—nor can it identify strain differences among Helicobacter organisms. Serology has limited usefulness in monitoring response to treatment because titers may not decrease significantly until 6 months or longer after the infection is eradicated.38,40 The urea breath test utilizes a urea test meal radiolabeled with 13C or 14C. Breakdown of urea by Helicobacter organisms in the stomach releases radioactive carbon dioxide, which is absorbed into the circulation and exhaled. The exhaled air is sampled, and the level of radioactivity measured. This is a highly sensitive and specific assay. The test is easy to perform, and results are obtained rapidly.40 Unlike serology, it is useful for monitoring patient response to Helicobacter eradication therapy before 6 months after treatment.39,43 One recommended approach in human medicine is to perform invasive testing for initial diagnosis and to use the urea breath test for documenting the eradication of Helicobacter infection. This method allows for initial determination of the degree of gastroduodenal pathology, may make it possible to identify the species

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or strain of Helicobacter, and enables the physician to rule out the possibility of neoplasia or other causes of chronic vomiting. Use of the urea breath test for monitoring the response to treatment helps minimize the number of invasive procedures the patient requires. 43 The eradication of Helicobacter infection should be confirmed at least 4 to 8 weeks after the end of treatment. Earlier testing can yield false-negative results due to temporary suppression of the organism.38,43,44 Currently, diagnostics in veterinary medicine are limited to invasive techniques that require endoscopic or surgical biopsy. In our hospital, we use a combination of urease testing and histopathologic examination of endoscopically obtained gastric biopsy samples. Bacterial culture is not very useful because H. felis is extremely difficult to culture and H. heilmannii has never been cultured. H. mustelae in ferrets is relatively easy to culture in comparison with the Helicobacter species found in dogs and cats.36 Serologic testing has been used successfully to diagnose H. mustelae in ferrets, but no serologic assays have been developed for dogs and cats.36 PCR analysis currently has limited availability and is primarily being used in research centers. Urea breath testing and serologic techniques for Helicobacter diagnosis in dogs are being evaluated at Cornell University.a

TREATMENT The discovery of H. pylori as the major cause of chronic gastritis and one of the major causes of gastroduodenal ulcer disease in humans has changed the focus of antiulcer therapy from inhibition of acid production to eradication of Helicobacter infection. 38,45,46 Ulcers recur in less than 2% of patients after Helicobacter is eradicated but in 50% of patients in whom the organism persists.47 No ideal treatment regimen has been identified, and there is a great deal of controversy as to which regimen should be used. Monotherapy with individual antimicrobials has been ineffective. Combination protocols utilizing multiple drugs have been necessary. Acid-inhibiting drugs (e.g., H 2 -receptor blockers and proton-pump inhibitors) are often included in these protocols.48,49 Bismuth-based compounds (e.g., bismuth subsalicylate or colloidal bismuth subcitrate) are frequently included in multiple-drug regimens. Bismuth accumulates beneath H. pylori cell walls and causes cell lysis. The traditional bismuth-based triple therapy regimens (consisting of bismuth, metronidazole, and either amoxicillin or tetracycline) are associated with high a

Simpson K: Personal communication, College of Veterinary Medicine, Cornell University, Ithaca, NY, 1996.

RAPID UREASE TEST ■ PCR ■ UREA BREATH TEST ■ SEROLOGY

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cure rates (>90% in some studies) in humans.50,51 The development of resistance to metronidazole by H. pylori organisms is resulting in reduced cure rates.50,51 Also, these regimens require multiple daily dosing and are associated with a high frequency of side effects (nausea, vomiting, abdominal pain, and diarrhea), which contributes to patient noncompliance.52–58 Omeprazole is a proton-pump inhibitor that profoundly decreases production of gastric acid. It potentiates the antimicrobial activity of various antibiotics against Helicobacter infections. 49,58 An amoxicillin/omeprazole protocol has shown over 80% cure rates in some studies but much lower success rates in others (as low as 46%).48,51–53,59 This protocol is simple and has a low incidence of side effects.53,57,58 In addition, Helicobacter organisms do not appear to develop resistance to amoxicillin.49,58,60 A combination of omeprazole and clarithromycin (a new acid-stable macrolide similar to erythromycin) is associated with a slightly higher cure rate.61 However, this protocol is considerably more expensive and Helicobacter organisms can develop resistance to clarithromycin.49,57–59 The high number of treatment failures has limited the acceptance of these dual-therapy protocols as the standard of treatment for humans. Newer omeprazole-based triple-therapy regimens have been evaluated and are very promising. A combination of omeprazole, amoxicillin, and tinidazole (a nitroimidazole similar to metronidazole) had an eradication rate of approximately 95%.58 A newer combination of omeprazole, amoxicillin, and clarithromycin achieved a 93% to 94% success rate.48,58 This protocol minimizes the incidence of side effects and the potential for antimicrobial resistance associated with protocols that include nitroimidazoles. 58 The omeprazole-based triple therapies have the advantage that only one week of therapy is required—versus 2 weeks for most Helicobacter-eradication protocols.48,54,58 Little information on the effectiveness of protocols for the eradication of Helicobacter infection in veterinary patients is currently available. A combination of metronidazole, amoxicillin, and bismuth subsalicylate for 3 to 4 weeks is effective in eliminating infection in ferrets.36 A combination of metronidazole, amoxicillin, and famotidine produced marked improvement in clinical signs of Helicobacter infection in over 90% of dogs and cats treated.62 Of the patients evaluated by followup endoscopy, 74% were determined to be Helicobacter negative.62 We have observed marked clinical improvement in many of our canine and feline Helicobacter-infected patients after treatment with an amoxicillin/omeprazole combination. Endoscopic confirmation of the eradica-

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tion of Helicobacter infection has been limited because of owner financial constraints and the need for general anesthesia. The availability of noninvasive tests, such as urea breath testing, would enhance our ability to evaluate the success of Helicobacter-eradication therapy. Further research is needed to evaluate treatment regimens for eradication of Helicobacter infection in veterinary patients.

ZOONOTIC POTENTIAL It has been proposed that Helicobacter infection may be spread to humans by domestic dogs and cats.16,33,62 There have been anecdotal reports of possible transmission of Helicobacter heilmannii to owners who were in close contact with their pets. Other evidence of zoonotic potential is that Helicobacter pylori has been identified in a group of research cats,63 even though cats are more commonly infected with H. felis or H. heilmannii. A recent epidemologic study evaluated H. pylori antibodies in people who owned cats versus people who have no contact with cats.64 Cat owners were at no greater risk of H. pylori infection than the general population. Others suggest that if Helicobacter were transmitted from pet dogs and cats, the incidence of human infections with H. heilmannii and H. felis would be higher because these are the most common species found in dogs and cats. Further investigation into the zoonotic potential of Helicobacter infection is needed before veterinarians can make any definitive recommendations about public health significance. CONCLUSIONS Veterinary gastroenterologists are currently investigating the relevance of Helicobacter infection in veterinary species. These organisms might prove to be an important cause of chronic gastritis and gastrointestinal ulceration in dogs and cats. Because Helicobacter species differ in pathogenicity, however, it would be incorrect to assume that the naturally occurring Helicobacter organisms in dogs and cats have the same pathogenic potential that H. pylori has for humans. It is also probable that host responses to Helicobacter infection differ between species and between individuals. It is likely that most of the Helicobacter infections in dogs and cats, like most of those in humans, are asymptomatic. Treatment would therefore be most warranted for those animals with obvious clinical signs and histopathologic evidence of infection. Noninvasive techniques to monitor Helicobacter infection in animals may soon become available. Such techniques avoid many of the difficulties associated with endoscopic procedures.

ANTIBIOTIC COMBINATIONS ■ TREATMENT PROTOCOLS ■ ERADICATION

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About the Authors Dr. Jenkins is Adjunct Associate Professor of Medicine and Dr. Bassett is a Medicine Resident at the College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee. Dr. Jenkins is a Diplomate of the American College of Veterinary Internal Medicine.

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