Helicobacter pylori infection is the most common cause of chronic gastritis and peptic ulceration in humans.
Helicobacter pylori infection is the most common cause of chronic gastritis and peptic ulceration in humans. It is also associated with an increased risk of gastric lymphoma and adenocarcinoma. Spiral bacteria were described in 1896 in humans and several animal species. They were "rediscovered" in 1983 when they were reported to cause of peptic ulceration in humans. Helicobacter pylori is a microaerophilic curved spiral gram negative organism with 4 flagella. The bacterium lives in gastric mucus, can attach to epithelial cells, and may penetrate intercellular junctions. High bacterial urease concentration cleaves urea to produce ammonia, which helps to neutralize the acid environment surrounding the bacterium. The immune system does not result in removal of the organisms; without treatment infection is life-long. Some studies have shown as many as 90% of people are infected with H. pylori. Luckily, most infections are not associated with clinical signs. Diagnosis can be made with serology, cytology of gastric mucus, culture of biopsies, histopathology of biopsies with H&E or silver stains, C-13 or C-14 labeled urea breath tests, or rapid urease tests. Many treatments have been studied, but the gold standard to which they are all compared to is omeprazole, ampicillin or tetracycline, metronidazole, and bismuth for 2 weeks.
Many species of spiral bacteria have been identified in dogs and cats: H. felis, H. pylori, and H Heilmannii (formerly called Gastrospirillum hominis), H. Salomonis, and H. bizzozeronii are the most common. Experimentally, infection has been established in both dogs and cats and lymphoid follicular gastritis developed. However, in these experimental studies, clinical signs were absent or very mild. Several surveys of laboratory, shelter, and pet populations (with and without GI signs) have shown a very high prevalence rate in dogs and cats, nearing 100% in some studies. Peptic ulceration is very rare in dogs and cats, demonstrating the pathophysiologic difference between H. pylori and the spiral bacteria commonly found in dogs and cats. Little is known about the effects of treatment of dogs and cats with chronic vomiting and Helicobacter spp. infection. At the present time there are many unanswered questions regarding Helicobacter in dogs and cats. Some questions include: 1) What is the relationship between Helicobacter and dogs and cats with chronic gastritis and vomiting? 2) What is the optimal treatment to eradicate the organism? 3) After treatment, is reinfection or recrudescence a common occurrence in dogs and cats? 4) What factors can help predict if a dog or cat with chronic gastritis and Helicobacter would benefit from treatment for Helicobacter? 5) Does Helicobacter have a role in other diseases such as gastric cancer and inflammatory bowel disease?
Because of the potential pathophysiologic relationship between Helicobacter spp. in dogs and cats and chronic gastritis and vomiting, the author has treated clinical cases for Helicobacter. In some cases, treatment has resulted in resolution or improvement in clinical signs. Until additional studies about Helicobacter in dogs and cats are available, it seems prudent to at least determine if spiral bacteria are present in dogs and cats with chronic vomiting, during gastroscopic examination or exploratory celiotomy. Spiral bacteria can be identified in gastric biopsy or brush cytology specimens, or indirectly identified by rapid urease testing of gastric mucosal samples. Obtaining results from histologic evaluation of biopsy samples requires 24-72 hours. Results of rapid urease tests and gastric brush cytology are available much sooner.
The least expensive and most practical diagnostic method of the 3 commonly used tests, that also has the quickest turnaround time, is gastric brush cytology. After completion of the endoscopic examination and collection of biopsy samples from the duodenum and stomach, a brush cytologic specimen can be collected. A guarded cytology brush is passed through the endoscope's biopsy channel into the gastric body along the greater curvature. The cytology brush is extended from the sheath, and gently rubbed along the mucosa from the antrum towards the fundus, along the greater curvature. Hemorrhagic areas associated with previous biopsy sites should be avoided. The brush is retracted into the protective sheath and withdrawn from the endoscope. The brush is extended from the sheath, gently rubbed across several glass microscope slides, which are air died, and stained with a rapid Wright stain.a The slide is examined under 100x oil immersion. Areas with numerous epithelial cells and large amounts of mucus are initially viewed. If present, the spiral bacteria are easily seen. They are usually at least as long as the diameter of a red blood cell and their classic spiral shape is obvious (Figure 3). The author examines at least 10 oil immersion fields on 2 slides before the specimen is considered negative. Unlike diagnostic tests that involve using a single (or several) small biopsy samples, brush cytology gathers surface mucus and epithelial cells from a much larger area, increasing the chances for identification of bacteria. Brush cytology was found to be more sensitive than urease testing or histopathological examination of gastric tissues in identifying Helicobacter organisms in dogs and cats.
The rapid urease test detects the presence of bacterial urease, produced by the Helicobacter spp., in a gastric biopsy sample. A commercially available test, the CLOtest®b, is utilized in the author's clinic. Individual tests cost approximately $6.00. The test consists of an agar gel with urea and a pH indicator, phenol red, placed within a small plastic well. The tests should be kept refrigerated prior to use. A biopsy sample obtained from the angularis incisura of the stomach is pushed into the gel. The test is maintained at room temperature and examined frequently for a 24-hour period. If bacterial urease is present, urea will be hydrolyzed to ammonia, which will change the pH of the gel. The color of the gel will turn from yellow to magenta. The rate at which the gel changes color is proportional to the number of Helicobacter spp. present. When large numbers of bacteria are present in the biopsy sample, the rapid urease test quickly changes color, often within 15-30 minutes. If the color of the gel has not changed within 24 hours, the test is interpreted as negative. Because of false positives and negatives, the cost of the tests, the turn around time for test results (especially if negative), and the ease and reliability of brush cytology, the author feels that the rapid urease test is the least valuable of the 3 commonly utilized methods of diagnosis in my clinic.
Histopathologic identification of Helicobacter spp. within gastric biopsy samples, utilizing hematoxylin and eosin (H&E) or special stains, has a specificity of 100% and a sensitivity of greater than 90% in studies in humans. Because of the patchy distribution of organisms within the stomach, examination of samples from multiple gastric locations will increase sensitivity. In my clinic, samples from the pylorus, angularis incisura, gastric body along the greater curvature, and the cardia are routinely examined. Spiral bacteria can be seen within the mucus covering the surface epithelium, within the gastric pits, glandular lumen, and the parietal cells (Figures 4A and 4B). In cats, bacteria have been identified submucosally within gastric lymphoid follicles. Spiral bacteria associated with the mucosal surface or within gastric pits are relatively easy to detect with routine H&E staining of tissues. However, if the distribution of bacteria favors gastric glands and glandular epithelial cells, bacteria are much more readily detected with a silver technique. Therefore, if bacteria are not identified with H&E staining, a modified Steiners Silver stain is used. Because of similarities in morphologic characteristics it is not possible to identify specific species using routine histologic staining techniques. Besides the identification of Helicobacter, histopathologic evaluation of biopsy samples allows assessment of underlying inflammation (Figure 5) or neoplasia, which may be the cause of the animal's clinical signs.
I have completed recently a clinical study comparing 2 treatments for Helicobacter in dogs. Dogs with chronic vomiting for at least 2 weeks, with Helicobacter spp. identified in gastric biopsy samples and gastritis, with or without inflammatory bowel disease, were entered into the study. The diagnostic workup included a CBC, biochemical profile, UA, fecal examination, abdominal ultrasonography, gastroduodenoscopy with mucosal biopsy, gastric cytology, and CLO test. Dogs with systemic diseases, gastric foreign bodies, gastric / duodenal neoplasia, pyloric hypertrophy, or Physaloptera infection were not eligible for the study. Dogs were randomly assigned to receive either triple therapy (amoxicillin 15 mg/kg, metronidazole 10 mg/kg, and Pepto Bismol tablets [(<5 kg; 0.25 tablet, 5-9.9 kg; 0.5 tablet, 10-24.9 kg; 1.0 tablet, and >25 kg; 2.0 tablets]) or quadruple therapy (triple therapy plus famotidine 0.5 mg/kg). All drugs were given BID for 2 weeks. Owners kept a daily diary of clinical signs and endoscopy was repeated 4 weeks and 6 months after treatment was completed. Results of the study have not yet been published but have been reported in abstract form. Six months after completing either therapy, approximately 40% of dogs had gastric biopsy specimens that were negative for Helicobacter. There was no difference between the 2 treatments in the percentage of dogs that remained negative. Both treatments reduced the frequency of vomiting by approximately 85%. Dogs that were negative for Helicobacter had a greater reduction in vomiting frequency that those that were positive.
Because of the high rate of treatment failure in this study after 6 months, I have been investigating the use of clarithromycin based protocols; clarithromycin (7.5 mg/kg BID), in combination with amoxicillin (15 mg/kg BID) or omeprazole (0.7mg/kg SID). This study is ongoing, but preliminary data 4 weeks after completion of therapy is very encouraging for the clarithromycin and amoxicillin combination.
It will take many controlled clinical studies before we can understand the potential role of Helicobacter in dogs and cats with chronic gastritis, and can answer many of the questions I have proposed. Although treatment of Helicobacter offers another, and very different, therapeutic route for animals with chronic gastritis, we must remember that a direct cause and effect relationship between Helicobacter and chronic gastritis has not yet been established in dogs or cats. Failure of a patient to rapidly respond to antimicrobial treatment suggests that something besides Helicobacter is causing the chronic gastritis and vomiting.
• 6 year old, MN, Shetland sheepdog
• Vomiting 1x / q48H for 2 years
• Yellow foam, twigs
• Vomiting associated with abdominal contractions
• Normal appetite, no diarrhea
• Present diet: Purina EN, fruits and vegetables
• HW: Filarabits plus
Regurgitation or vomiting (circle one)
o No likely rule outs
o Dietary indiscretion
o Chronic gastritis
o Inflammatory bowel disease
o Gastric foreign body
• CBC, biochemical profile, UA (anesthesia workup)
• ± abdominal ultrasound
• ± abdominal radiograph
• ± upper GI barium series
• exploratory laparotomy
Diagnostic results / diagnosis
• CBC, biochemical profile, UA - normal
• Endoscopy - mucosal follicles, superficial erosions, granular duodenum, CLO pos
• Histopathology - gastritis, IBD, spiral bacteria
• Triple therapy- amoxicillin, metronidazole, Pepto Bismol BID x 14 days
• Continue EN, avoid table food
• FU 6 weeks - vomited 3x, normal endoscopy, normal histopathology, CLO neg, silver stain neg
• FU 6 months - Vomited 4 times, added fruits, cheese, dog treats, and hot dog! • Endoscopy - stomach contained grass and bird seed, CLO neg, histopathology normal
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