Gastric Helicobacter-like Infections

CHAPTER 49

Gastric Helicobacter-like Infections Jane E. Sykes and Stanley L. Marks

Overview of Helicobacter Infections in Dogs and Cats First Described: 1881 by Rappin (France),1 who observed ­spiral bacteria in a dog’s stomach; the association between H. pylori infection and disease in humans was made in 1983 by Warren and Marshall (Australia).2 Cause: Various species of non–H. pylori helicobacters, rarely H. pylori in cats (gram-negative spiral-shaped bacteria that belong to the family Helicobacteraceae) Primary Mode of Transmission: Fecal-oral and oral-oral transmission proposed, possibly water-borne. Transmission through contact with vomitus may also occur. Affected Hosts: Humans and a variety of other animals are colonized by helicobacters; an association with disease is clearest for humans and ferrets Geographic Distribution: Worldwide Major Clinical Signs (Dogs and Cats): Possibly chronic vomiting (gastric helicobacters) or diarrhea (intestinal helicobacters), although evidence for a causative role in disease is weak Differential Diagnoses: Dietary indiscretion, gastrointestinal foreign body, chronic pancreatitis, inflammatory bowel disease, food-responsive enteropathy, eosinophilic fibrosing gastritis (cats), bilious vomiting syndrome, gastrointestinal neoplasia (lymphoma, mast cell neoplasia, gastric adenocarcinoma), chronic infiltrative infectious diseases of the gastrointestinal tract (including feline infectious peritonitis, mycobacteriosis, canine cryptococcosis, pythiosis), hypoadrenocorticism, hyperthyroidism, toxins (including drugs), gastric helminthiasis (e.g., P ­ hysaloptera and Ollulanus spp.) Human Health Significance: Dogs and cats may be a source of human infection with non–H. pylori helicobacters that have been associated with gastritis, gastroduodenal ulceration, and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in humans.

Etiology and Epidemiology Helicobacter spp. are flagellate, gram-negative, microaerophilic, curved to spiral-shaped motile bacteria. They are grouped into gastric, hepatic, and intestinal Helicobacter species, with intestinal species residing primarily in the large intestine.3,4 In humans, gastric Helicobacter spp. are an important cause of gastritis and gastroduodenal ulceration and increase the risk

for development of gastric adenocarcinoma and lymphoma. In contrast, the extent to which Helicobacter spp. cause disease in dogs and cats is not fully understood, and newly discovered organisms in dogs and cats have drawn most attention in regard to their zoonotic potential.5 Helicobacter pylori, the type organism, is the most important species infecting humans. H. pylori infection is extremely rare in cats and has only been identified in one colony of cats to date.6 It has not been described in dogs. Dogs and cats are generally infected with gastric non–H. pylori helicobacters (also referred to as gastric helicobacter-like organisms, or GHLOs).5 These are much larger than H. pylori (5 to 10 µm long versus 1.5 to 3 µm long for H. pylori), and species cannot be differentiated from one another based on their light or electron microscopic appearance alone (Figure 49-1). The nomenclature of non–H. pylori helicobacters is complicated. Species identified in dogs and cats are listed in Table 49-1.4,7-16 Before their genetic characterization, non–H. pylori helicobacters were originally referred to as ­“Gastrospirillum hominis” and later “Helicobacter heilmannii.” Subsequent analysis of multiple gene sequences from a variety of “H. heilmannii” from dogs and cats has revealed that “H. heilmannii” is not one but a group of organisms that includes H. felis, H. bizzozeronii, H. salomonis, and an organism that has been confusingly named H. heilmannii. These organisms have also been implicated in human disease, albeit less commonly than H. pylori.5 Depending on the study, between 60% and 100% of dogs and cats carry non–H. pylori helicobacters, and gastric Helicobacter spp. can be found in apparently healthy animals and dogs and cats without signs of vomiting.5,17-22 H. felis infection has been associated with gastric pathology in dogs in some studies23 but not others.24 Dogs and cats are probably colonized shortly after birth, as a result of fecal-oral and oral-oral ­transmission.25 Transmission through contact with vomitus may also occur. Water-borne transmission may play a role in spread of H. pylori to humans.26 Shelter and colony dogs and cats may have a higher prevalence of colonization, most likely due to the close ­proximity of animals to one another. One Helicobacter species may be able to suppress the presence of another, so that dogs and cats are primarily colonized with a single species, although in some animals, the simultaneous presence of multiple species has been found.27-30 The organisms have a remarkable ability to survive the low pH of the stomach, which they resist by living deep in the mucus glands of the stomach and through production of the enzyme urease. The urease catalyzes the hydrolysis of urea to carbon dioxide and ammonia, which raises the pH of the organism’s milieu. In dogs and cats, the organisms are also found within the canaliculi and the cytoplasm of parietal cells.25,30,31

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SECTION 2  Bacterial Diseases

A

B

FIGURE 49-1  Structure of gastric Helicobacter species. Note the terminal bunches of flagellar filaments. A, Helicobacter pylori. B, Gastric helicobacter-like organism.

TABLE 49-1 Helicobacter Species Identified in Dogs, Cats, and Humans4,7-16 Species

Location

Host

H. bizzozeronii H. salomonis H. cynogastricus H. heilmannii H. felis H. pametensis H. baculiformis H. pylori “Flexispira rappini” H. bilis H. cinaedi H. fennelliae “H. colifelis” H. marmotae H. canis

Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach Stomach, intestine Stomach, intestine Intestine Intestine Intestine Intestine Intestine, liver

Dog, humans Dog Dog Dog, cat, humans Dog, cat, humans Cat Cat Cat Dog, cat Dog, cat Dog, cat Dog, cat Cat Cat Dog, cat, humans

concurrently.31 Experimental and natural infection of dogs and cats with non–H. pylori helicobacters has been associated with chronic lymphoplasmacytic gastritis and lymphoid follicular hyperplasia. Gastroduodenal ulceration and marked alterations in the gastric acid secretory axis, as occur in humans, have not been observed in dogs and cats.24,33,34 However, not all animals infected with non–H. pylori helicobacters have histopathologic evidence of gastritis, and no correlation has been observed between the severity of gastric pathology and the degree of colonization by helicobacters. More severe gastritis with marked lymphoid follicular hyperplasia and neutrophilic inflammatory infiltrates has been reported in cats and acutely in puppies experimentally infected with H. pylori.35,36 The puppies developed gastrointestinal signs, including vomiting and loose stool, shortly after inoculation. It is possible that the degree of bacterial invasion and gastritis in dogs and cats varies with the infecting H ­ elicobacter species or even strain.30 In humans, gastric pathology has been associated with possession of a number of pathogenicity genes by H. pylori, including cagA (cytotoxinassociated gene A), vacA (vacuolating cytotoxin), and iceA (induced by contact with epithelium).37 The degree of vacuolating cytotoxin production can also vary among strains.38 In human patients, H. pylori infection has been well associated with gastric low-grade, B-cell, mucosa-associated lymphoid tissue (MALT) lymphoma. Eradication of H. pylori achieves complete remission in some patients with H. pylori–positive early-stage gastric MALT lymphoma.39 One study suggested a possible association between Helicobacter spp. infection and gastric lymphoma in cats,40 but additional studies are required to determine the role of Helicobacter spp. infection in feline gastric disease. Non–H. pylori helicobacters have been detected in the hepatobiliary system of cats with neutrophilic cholangitis41 and lymphocytic cholangitis,42 although this may reflect ascending bacterial infection secondary to an underlying disease process. H. canis was detected in the liver of a 2-month-old puppy with multifocal necrotizing hepatitis that had acute weakness and vomiting, and died within hours.43 H. canis was also detected in a colony of Bengal cats with diarrhea, but its role as a causative agent was uncertain.44 Abundant organisms that genetically resembled H. canis were detected microscopically throughout the large intestine of a 2-month-old kitten with severe diarrhea, vomiting, dehydration, weight loss, and inappetence.3 In one study, the presence of heavy colonic infection with enterohepatic Helicobacter spp. infection in a group of laboratory dogs was associated with the presence of mucosal atrophy and fibrosis, and a possible role of Helicobacter spp. infection in canine inflammatory bowel disease was suggested.29

Clinical Features

Diagnosis

Signs and Their Pathogenesis

Microbiologic Testing

The majority of dogs and cats infected with Helicobacter spp. show no clinical signs. Helicobacter infection of some dogs and cats has been hypothesized to cause chronic intermittent vomiting, inappetence, pica, belching, weight loss, fever, and polyphagia.31 Unfortunately, strong evidence that supports an association with such disease in dogs and cats is lacking. Clinical signs in some animals with biopsy-confirmed infection resolve following specific therapy for gastric helicobacter infection,31-33 although the results of one study were difficult to interpret because an elimination diet was administered

Clinical diagnosis of Helicobacter infection in dogs and cats has most commonly been based on histopathology, cytology, rapid urease testing, and, to a lesser extent, PCR on gastric biopsies (Table 49-2). Other tests such as the urea breath and blood tests, fecal PCR, and serologic tests are primarily used in human patients and in the research arena.

Diagnosis Using Cytology and Histopathology

Spiral organisms can be readily detected in touch impression smears of gastric tissue obtained following biopsy or necropsy,

CHAPTER 49  Gastric Helicobacter-like Infections

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TABLE 49-2 Diagnostic Assays Available for Gastric Helicobacter Infection in Dogs and Cats* Assay

Specimen Type

Target

Performance

Bacterial isolation

Gastric biopsies

Helicobacter organisms

Can take up to 10 days. Low sensitivity for non–H. pylori helicobacters, which can be difficult to culture. Patchy distribution may also lead to false negatives. Allows ­typing and antimicrobial susceptibility testing.

Cytology

Impression smears of ­gastric biopsies or ­cytology brush ­specimens

Helicobacter organisms

Rapid and sensitive, but false negatives can occur. Patchy distribution may also lead to false negatives. Does not provide information on inflammatory or architectural changes in underlying tissue.

Histopathology

Gastric biopsies

Helicobacter organisms

Less sensitive than cytologic examination. Patchy ­distribution may also lead to false negatives. Use of silver stains increases sensitivity when organism ­numbers are low. ­Allows determination of associated gastric ­histopathology.

Rapid urease testing

Gastric biopsies

Helicobacter urease

Rapid and very sensitive. Patchy distribution and low ­organism loads may lead to false negatives. Very rare false positives with other urease-producing organisms.

PCR

Gastric biopsies

Helicobacter DNA

Rapid (within hours); can be highly sensitive and specific. Sequence analysis can determine the species involved. Primarily used on a research basis.

Serology

Serum

Antibodies to Helicobacter spp.

Moderate sensitivity in dogs and cats. Results do not ­correlate well with gastric histopathology and do not ­always correlate with active infection. Primarily used in research settings.

Urea breath and blood testing

Breath, blood

Radiolabeled carbon dioxide derived from the activity of Helicobacter urease

Requires specialized detection equipment. Although ­sensitive, false negatives may occur, such as following acid suppression. In dogs and cats, has been primarily used in research settings to date.

*For all tests, positive results do not imply that Helicobacter is the cause of disease.

after staining with Gram or Diff Quik stains (Figure 49-2). A cytology brush can also be used to obtain a specimen during endoscopy. Several biopsies or brush specimens may need to be evaluated from different regions of the stomach (fundus, cardia, antrum/pylorus) when the distribution of organisms is patchy. When organism burdens are high, the organisms can be detected using histopathology, which allows assessment of concurrent gastric pathology (Figures 49-3 and 49-4). The use of silver stains (such as Warthin-Starry stain or Steiner stain), Giemsa, or toluidine blue stain, as well as immunostaining, dramatically increases sensitivity for organism detection (see Figures 49-3, C, and 49-4, C).45

Bacterial Isolation

Isolation of gastric helicobacters is difficult and has low sensitivity. Growth typically requires incubation on selective media in microaerobic conditions for 5 to 10 days. Isolation is advantageous in research settings because it allows subsequent identification of the organism using conventional biochemical testing, whole-cell protein profiling, and DNA analysis.21,46 It also allows antimicrobial susceptibility testing, which has recently been recommended before treating humans for H. pylori infection because of the increasing prevalence of antimicrobial resistance.47 Resistance to antimicrobials has also

been documented in non–H. pylori helicobacters isolated from dogs and cats.48

Rapid Urease Testing

The rapid urease test involves incubating a gastric biopsy in a urea broth that contains the pH indicator phenol red. If gastric helicobacters are present, helicobacter urease breaks down the urea; with the release of ammonia, a rise in pH and a color change occur. The change in color can occur within 1 to 3 hours, although the broth is generally incubated at room temperature for 24 hours. The test is very sensitive, but false-negative results can occur if the distribution within the stomach is patchy or if organism loads are low. False-positive results have rarely been reported when other urease-producing bacteria are present in the stomach, such as Proteus spp.

Detection of Helicobacter DNA

PCR assays have been extensively used to detect Helicobacter species in tissues on a research basis, including those from dogs and cats. Sequence analysis of the PCR products can allow identification of the Helicobacter species present. Fluorescent in situ hybridization (FISH) has also been used to detect, localize, and identify Helicobacter species infection in tissues from dogs and cats.4,32,40,49

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SECTION 2  Bacterial Diseases

FIGURE 49-2  Spiral-shaped gastric Helicobacter-like organisms visible in a Diff Quik–stained smear (arrows) of a gastric biopsy from a 2-year-old male neutered Cavalier King Charles spaniel with chronic vomiting and regurgitation for which no other cause was apparent (1000× magnification).

Serology

A variety of serum ELISA and immunoblotting assays have been used in humans to detect antibodies and screen for H. pylori infection, and some can be used to some extent to monitor the success of therapy.50,51 Serologic assays have been used on a research basis to noninvasively detect non–H. pylori ­helicobacter infection in dogs and cats, in some studies demonstrating ­moderate sensitivity and good specificity.52-54

Urea Breath and Blood Testing

Diagnosis and monitoring of the extent of H. pylori infection in human patients can also be accomplished noninvasively using urea breath and blood testing, which involves oral administration of urea containing 14C or the stable isotope 13C. After ingestion, the labeled urea is converted to ammonia by ­Helicobacter urease, and the released carbon is absorbed systemically, where it can be measured in the blood. Subsequently, the labeled carbon dioxide is exhaled and can be measured in the breath. Acid suppression interferes with test results by decreasing H ­ elicobacter urease activity, and so testing is generally performed several days after discontinuing treatment. False positives can also occur.55 Urea breath and blood testing has been used with success in dogs,56 and breath testing has been used in cats20,57 both before and following specific treatment for Helicobacter infection.

Stool Antigen Assays

Assays that detect H. pylori antigen in feces have been used in human patients,55 but their use in dogs and cats has not been described.

Pathologic Findings Infection with non–H. pylori helicobacters in dogs and cats has primarily been associated with chronic lymphocytic or lymphoplasmacytic gastritis, with lymphoid follicular hyperplasia (see Figures 49-3, A, and 49-4, A), although the extent of inflammation varies dramatically from absent to severe.19,58,59 An eosinophilic inflammatory component has been described in

some cats.58 Neutrophil and eosinophil infiltrates can accompany mononuclear inflammation in some cats infected with H. pylori.58,60 Organisms may be found in the ­superficial mucus and crypts, and sometimes within parietal cells see Figures 49-3 and 49-4). Histopathologic findings in a cat infected with an intestinal helicobacter included large numbers of densely packed spiral bacteria covering the intestinal mucosa and present within the crypts, and minimal inflammatory changes. Hepatic changes in a dog with H. canis infection consisted of randomly distributed and coalescing hepatocellular necrosis with associated ­neutrophilic and mononuclear infiltrates.43

Treatment and Prognosis Whether antimicrobial treatment should be used for ­Helicobacter infections in dogs and cats is unknown. Humans with H. pylori infections are typically treated with a ­combination of a proton pump inhibitor, amoxicillin, and clarithromycin, with or without bismuth subsalicylate. Treatment of humans is reserved for symptomatic individuals; the development of antimicrobial resistance by H. pylori is increasingly of concern.61 Treatment should be reserved for dogs and cats with gastrointestinal signs that have no other identifiable cause of illness, after a diagnosis of gastritis and Helicobacter infection has been confirmed using biopsy. A 2-week course of combination therapy with ­antimicrobials and a proton pump inhibitor or an H2 antagonist does not reliably eliminate gastric helicobacters in dogs and cats, although clinical signs often resolve.33,56,62,63 Reinfection can occur in some animals after treatment. This theory is underscored by a study of 20 dogs that were naturally infected with Helicobacter spp. and treated with triple therapy ­(clarithromycin, amoxicillin, and lansoprazole) for 7 days. The dogs were then randomized into a control group kept in isolation, and an experimental group, which was placed in contact with Helicobacter-positive dogs for 60 days. Triple therapy was effective in 100% of the dogs; however, recurrence of infection occurred in 80% of dogs in

CHAPTER 49  Gastric Helicobacter-like Infections

A

A

B

B

C

C

FIGURE 49-3  Histopathology of the stomach of a 2-year-old female spayed Maltese terrier with chronic vomiting and regurgitation. A, Lymphoid follicular nodules. The remaining lamina propria is infiltrated by small numbers of eosinophils, neutrophils, lymphocytes, and plasma cells. H&E stain, 40× magnification. B, Large numbers of spiralshaped bacteria are visible in the superficial mucous and gastric glands. H&E stain, 1000× magnification. C, Agyrophilic intralesional spiral-shaped bacteria within the gastric glands. Warthin-Starry stain, 1000× magnification.

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FIGURE 49-4  Histopathology of the stomach of a 14-year-old male neutered domestic shorthair that was infected with FIV and was euthanized because of squamous cell carcinoma. Gastrointestinal signs were not reported. A, Severe, chronic, lymphofollicular gastritis. H&E stain, 40× magnification. B, Abundant fine, spiral-shaped bacteria were visualized in the superficial mucous and within parietal cells (arrows). H&E stain. C, Warthin-Starry stain showing intracellular agyrophilic spiral-shaped bacteria (arrows); 1000x magnification.

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TABLE 49-3 Antimicrobials Used with Success to Treat Helicobacter spp. Infection in Dogs and Cats Drug

Dose (mg/kg)

Interval Duration Route (hours) (days)

Metronidazole

10-15

PO

12

14-21

Amoxicillin

22

PO

12

14-21

Bismuth subsalicylate

0.22 mL/kg

PO

6-8

14-21

Clarithromycin

5-10

PO

12

14-21

Omeprazole

0.7-1.0

PO

24

14-21

Famotidine

0.5-1.0

PO

12

14-21

The first three drugs are administered as a combination. Alternatively, clarithromycin can be combined with amoxicillin and administered with either omeprazole or famotidine. Bismuth compounds should be avoided in cats. Omeprazole should be given on an empty stomach 30 minutes before a meal.

the experimental group, and in none of the dogs in the control group after 60 days.64 A 3-week course of amoxicillin, metronidazole, and bismuth subsalicylate (Table 49-3) cleared gastric helicobacters in dogs and cats, with resolution of vomiting, but histopathologic evidence of gastritis did not resolve.32 Metronidazole could be substituted with clarithromycin.21 One study showed that concurrent use of an H2 antagonist in dogs did not change outcome.33 This is consistent with the lack of abnormalities in the gastric acid secretory axis in dogs infected with non–H. pylori helicobacters.24,34

Immunity and Vaccination Gastric helicobacters persist in the stomach despite a vigorous humoral immune response. Research has been underway to develop an effective vaccine for H. pylori infection in humans, and a variety of H. pylori antigens induce protection in healthy human volunteers or mouse models.65 No vaccine is available for Helicobacter infection in dogs and cats, and a greater understanding of the role of gastric helicobacters in canine and feline disease will be required in order to assess the need for effective vaccines against these organisms.

Public Health Aspects At least 50% of the world’s human population is infected with H. pylori, although the prevalence of infection has decreased in developed countries.66 In the Western world, 1% to 10% of people develop gastroduodenal ulceration as a result of chronic H. pylori infection. A smaller percentage of infected people (<3%) develop gastric adenocarcinoma or MALT lymphoma in association with infection. Duodenal ulceration results from increased gastrin release in response to H. pylori–induced ­gastric antral inflammation. Factors that influence outcome are not well understood, but an individual’s immune response to

FIGURE 49-5  Endoscopic image of lymphoid follicular gastritis in a 2-year-old ­maltese terrier with chronic vomiting and regurgitation that was associated with the presence of large numbers of gastric helicobacter like-organisms. Note the ‘goose pimple’ appearance of the mucosa. the organism, as well as the possession of virulence factors by H. pylori strains, appears to play an important role.66 Eradication of infection using antimicrobial therapy can cure gastroduodenal ulceration and MALT lymphoma, but gastric adenocarcinoma generally persists despite treatment.67 Although H. pylori has been documented to infect a colony of cats, infection of cats with this species is extremely rare, and exposure to pets is not a risk factor for H. pylori infection in humans. Non–H. pylori gastric helicobacter infection is uncommon in humans compared with H. pylori infection. Nevertheless, these helicobacters have also been associated with chronic active gastritis, gastroduodenal ulceration, and MALT ­lymphomas in people. Disease is generally less severe than that caused by H. pylori.5 Clinical signs in humans may be absent or consist of nausea, epigastric pain, vomiting, hematemesis, heartburn, and decreased appetite. Treatment with triple antibiotic therapy and bismuth subsalicylate can resolve infection and gastritis. Pets have been suggested as a source of these helicobacters for humans,5,7,68-71 and close contact with dogs and cats is a risk factor for infection.72 Licking has been suggested as a mode of transmission, based on the presence of non–H. pylori helicobacter DNA in the oral cavity of dogs.25 Pigs play an even more important role in zoonotic ­transmission of non–H. pylori gastric helicobacters, the swine helicobacter H. suis being the most prevalent ­species ­identified in humans.5 Intestinal helicobacters found in dogs and cats, especially H. cinaedi, have been associated with enteric disease and ­bacteremia in immunocompromised humans.73 The relative role of dogs and cats in transmission of these organisms to humans is unknown. Nosocomial spread of H. cinaedi was suggested among immunocompromised humans in one report.74

CHAPTER 49  Gastric Helicobacter-like Infections

CASE EXAMPLE Signalment: “Mochi,” a 2-year-old female spayed Maltese terrier from Dixon, CA

History: Mochi had been vomiting and regurgitating

intermittently since she was 1 year of age. As a puppy, the owner (a veterinary student) reported intermittent episodes of “burping.” The vomiting occurred 2 to 5 times throughout the day and was not associated with eating, drinking, or exercise. The vomitus usually consisted of brown fluid with no recognizable food particles. Dietary changes that included a digestible elimination diet containing a novel, single protein source followed by a fat-restricted prescription diet had not resulted in improvement in her clinical signs. Therapy with cisapride (3 mg PO q8h) and famotidine (2.5 mg PO q24h) or omeprazole (3.5 mg PO q24h) resulted in only slight improvement in the frequency of vomiting. Her appetite was appropriate, and there had been no weight loss or diarrhea. She primarily lived indoors with one cat. She was up to date on vaccinations, which included those for rabies, distemper, parvovirus, and canine adenovirus.

Physical Examination:

Body Weight: 3 kg General: Bright, alert and responsive, hydrated, nervous. Ambulatory on all 4 limbs. T = 100.4°F (38.0°C), HR = 120 beats/min, RR = 28 breaths/min, mucous membranes pink and moist, CRT = 1 s. Integument, Eyes, Ears, Nose, and Throat: No clinically significant abnormalities were noted. Musculoskeletal: The dog’s body condition score was 4/9 with symmetrical muscling. Cardiovascular, Respiratory, and Lymph Nodes: No clinically significant abnormalities were noted. Gastrointestinal and Genitourinary: Abdominal palpation was unremarkable. “Burping” behavior was observed in the room, which occurred without any prodromal signs or abdominal effort. Lip-smacking behavior occurred immediately afterwards. Rectal examination was normal.

Laboratory Findings:

CBC:

HCT 46.5% (40%-55%) MCV 64.4 fL (65-75 fL) MCHC 35.9 g/dL (33-36 g/dL) WBC 5700 cells/µL (6000-13,000 cells/µL) Neutrophils 3112 cells/µL (3000-10,500 cells/µL) Lymphocytes 1830 cells/µL (1000-4000 cells/µL) Monocytes 257 cells/µL (150-1200 cells/µL) Eosinophils 479 cells/µL (0-1500 cells/µL) Platelets 277,000/µL (150,000-400,000 platelets/µL).

Serum Chemistry Profile:

Sodium 147 mmol/L (145-154 mmol/L) Potassium 4.4 mmol/L (3.6-5.3 mmol/L) Chloride 111 mmol/L (108-118 mmol/L) Bicarbonate 23 mmol/L (16-26 mmol/L) Phosphorus 5.3 mg/dL (3.0-6.2 mg/dL) Calcium 10.6 mg/dL (9.7-11.5 mg/dl)

471

BUN 22 mg/dL (5-21 mg/dL) Creatinine 1.1 mg/dL (0.3-1.2 mg/dL) Glucose 95 mg/dL (64-123 mg/dL) Total protein 5.7 g/dL (5.4-7.6 g/dL) Albumin 4.0 g/dL (3.0-4.4 g/dL) Globulin 1.7 g/dL (1.8-3.9 g/dL) ALT 42 U/L (19-67 U/L) AST 45 U/L (19-42 U/L) ALP 52 U/L (21-170 U/L) GGT < 3 U/L (0-6 U/L) Cholesterol 241 mg/dL (135-361 mg/dL) Total bilirubin 0.2 mg/dL (0-0.2 mg/dL). Urinalysis: SGr 1.040, pH 7.0, no protein, glucose, or ketones, trace hemoprotein, 0-1 WBC/HPF, 0-1 RBC/HPF, moderate lipid droplets. Serum Pancreatic Lipase Immunoreactivity: <30 µg/L (reference range 0-200 µg/L)

Imaging Findings:

Abdominal Radiographs: A moderate amount of gas was

identified within multiple small intestinal loops, but an obstructive pattern was not identified. Thoracic Radiographs: The cardiopulmonary structures were within normal limits. A small amount of gas was visualized within the esophagus on the left lateral projections. Esophagram: Unremarkable study. Abdominal Ultrasound: No abnormalities were identified. Gastroduodenoscopy: Gross findings were suggestive of diffuse lymphoid follicular hyperplasia, with a mild “goose pimple” appearance to the gastric mucosa (Figure 49-5). Multiple biopsies of all regions of the stomach and multiple duodenal biopsies were obtained and submitted for histopathology. Histopathology: Stomach: Moderate, lymphofollicular, eosinophilic, and lymphoplasmacytic gastritis with intralesional spiral bacteria (see Figure 49-3). Duodenum: Mild, chronic, lymphofollicular, eosinophilic, and lymphoplasmacytic duodenitis and ileitis. Jejunum: Diffuse, mild, eosinophilic, and lymphoplasmacytic enteritis. Diagnosis: Chronic gastritis associated with Helicobacter spp. infection; mild eosinophilic and lymphoplasmacytic enteritis. Treatment: Treatment for the Helicobacter infection was initiated with metronidazole (30 mg PO q12h), amoxicillin (60 mg PO q12h), and bismuth subsalicylate for 2 weeks. The owner reported almost complete resolution of the vomiting following treatment, but signs returned after treatment was discontinued, and an additional course of treatment was instituted. Treatment with a fat-restricted prescription diet was continued. The frequency of vomiting then decreased to once a week. Comments: Whether the Helicobacter spp. infection in this dog contributed to clinical signs or was an incidental finding in a dog with underlying enteritis was not clear. The failure to respond to multiple diet changes, including an elimination diet, and the dramatic response to triple therapy supported a possible role for Helicobacter spp. infection, or a diagnosis of antibiotic-responsive gastroenteropathy that was unrelated to Helicobacter spp. infection.

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SECTION 2  Bacterial Diseases

SUGGESTED READING Haesebrouck F, Pasmans F, Flahou B, et  al. Gastric helicobacters in domestic animals and nonhuman primates and their significance for human health. Clin Microbiol Rev. 2009;22(2):202-223.

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