Is Helicobacter A Problem In Cats?

Bob Sherding United States

Helicobacter are curved to spiral-shaped, Gram-negative, microaerophilic, urease-producing, motile bacteria that are tolerant of low pH, allowing them to colonize the stomach. Infection is persistent (months to lifelong) and difficult to eradicate. Pathogenicity varies with species and strain of Helicobacter, and depends on factors in the bacteria such as urease, lipopolysaccharides, cytotoxins, mucinase, lipase, and hemolysin.

Numerous species of Helicobacter infect animals. The H. felis-like group is medium to large Helicobacters (7-10 µm) such as H. felis and Gastrospirillium-like organisms (also known as H. heilmannii). These are the most common Helicobacter species found in cats. Helicobacter pylori (2�4 µm), the major cause of human Helicobacter infection, are much smaller and have only been observed to infect cats on rare occasion. H. pylori is among the most common infections of humans worldwide, second only to Streptococcus mutans that causes dental caries.

Chronic lymphocytic or lympho-follicular gastritis has been associated with Helicobacter infection in cats. Signs of intermittent vomiting may be associated with Helicobacter infections, but many infected cats have no clinical signs despite mild gastritis.

Epidemiology

Various surveys have found a high prevalence of Helicobacter approaching 100% in most shelter and colony cats and 30 to 100% in pet cats. The spiral organisms identified most often in these surveys are the large Helicobacter-like organisms, e.g., H. felis and H. heilmannii. Because of the high prevalence of infection in animals without clinical signs, the clinical significance of gastric Helicobacter-like organisms (GHLO) in cats is uncertain. Helicobacter organisms may be an incidental finding in clinically normal animals, but when they are associated with clinical signs (chronic intermittent vomiting) and gastric mucosal inflammation (lymphocytic gastritis), it is possible that they should be considered potential pathogens and treated.

Transmission is poorly understood; however, GHLO have been found in the vomitus, saliva, and feces of infected animals, and in contaminated surface water. Therefore, transmission probably can be oral-oral, feco-oral, and through food or water contaminated by vomitus, saliva, or feces. Waterborne infection may be important, as Helicobacter spp. is more resistant to chlorination than E. coli. Zoonotic transmission is a potential concern in cats harboring the human variety (H. pylori), but this is considered very rare. A very small percentage of human infections are caused by H. heilmannii, which is similar to the animal organism. Living conditions of group confinement seem to be associated with the highest infection rates in dogs and cats.

Clinical Signs

Because there is poor correlation between the presence of GHLO organisms and the presence of clinical signs or mucosal lesions, the relationship between Helicobacter and gastric disease in cats remains unclear. Signs of intermittent vomiting may be associated with H. felis in cats, but many infected cats have no clinical signs despite histologic evidence of mild gastritis. H. pylori infection in cats is usually subclinical despite persistent colonization (> 7 months) and persistent evidence of mild gastritis lesions. In humans, H. pylori causes chronic gastritis and peptic ulcers and is a cofactor associated with gastric carcinoma and lymphoma. Subclinical infections also are common in humans.

Experimental H. felis infection in cats produces persistent gastric colonization, gastric lymphoid hyperplasia, lymphofollicular gastritis, and seroconversion; however, clinical signs are generally absent and ulcers do not occur. In these studies, experimentally infected cats have been followed for several months post-infection, which may not be long enough to evaluate for full pathogenicity.

Diagnosis

Until the pathogenicity of Helicobacters in cats is better understood, Helicobacter infection should be a consideration in any cat with unexplained chronic intermittent vomiting and lymphocytic gastritis or gastric erosion-ulceration. The methods of diagnosis include rapid noninvasive tests (urease screening breath and blood tests; serology) and tests performed on endoscopically-collected gastric specimens (urease test, cytology, histopathology, electron microscopy, culture, and PCR. PCR and other molecular analyses of gastric biopsies, gastric juice, or culture isolates can be used to diagnose and to identify the species of Helicobacter.

Noninvasive screening tests used in humans include the serum ELISA test for Helicobacter antibodies and the breath test for bacterial urease. The breath test uses oral administration of radiolabelled urea, which is converted by bacterial urease to HCO3, and radiolabelled CO2, which can be measured in expired air. Serologic assays (PCR and ELISA) are currently being evaluated in dogs and cats. In the future, these may simplify identification of Helicobacter carrier animals.

Endoscopy is currently the procedure of choice for procuring specimens for clinical diagnosis of Helicobacter in dogs and cats. Frequent endoscopic findings include a multifocal follicular mucosal pattern, rugal thickening, and punctate hemorrhages. It must be pointed out, however, that Helicobacter organisms are also found in the stomachs of dogs and cats that lack gastric lesions.

The urease screening test is based on the urease-producing characteristics of these bacteria. Mucosal biopsies in urea broth turn the pH indicator a pink color (usually in one to three hours) when urease-producing Helicobacter are present and convert urea to ammonia. False-negative urease test results occur in pyloric biopsies and in animals recently treated with antibiotics, omeprazole, or H2-blockers. False-positives result from other urease-producing bacteria (e.g., Proteus).

The ability to identify Helicobacter in cytology or biopsy specimens may relate to the presence of a prominent mucus layer on the gastric mucosa. Gastric mucosal brush and impression smear cytology stained with Diff-Quik or Gram stain is excellent for demonstrating the presence of motile spiral bacteria. Histopathologic findings in gastric biopsies include lymphocytic gastritis, prominent lymphoid follicles, atrophy, fibrosis, and erosions. With routine microscopy, spiral bacteria are seen in the glands, surface mucus, and in some cases within gastric parietal cells. Warthin-Starry silver staining increases the visibility of spiral bacteria in gastric biopsies. Gastric specimens can also be evaluated by culture, PCR, and electron microscopy.

To culture Helicobacter, gastric mucosa is inoculated onto Brucella agar plates containing 10% rabbit blood and Skirrow's supplement and incubated at 37 C in 10% CO2 for four to five days. A swab is rubbed over the surface of the plates, streaked on blood agar, and incubated for an additional three days for detection of light growth. The criteria used for identification of resulting colonies as Helicobacter sp. include colony morphology; Gram-negative staining; ultrastructure; production of urease, oxidase, and catalase; obligate microaerophilic growth; polyacrylamide gel electrophoresis; and DNA restriction endonuclease analysis. The H. heilmannii-like bacteria of unproven pathogenicity (which are most common in dogs and cats) are rarely culturable.

Treatment

The dilemma is whether to treat or ignore Helicobacter. Helicobacter may be an incidental finding in clinically normal animals, but when infection is associated with clinical signs (chronic intermittent vomiting) and gastric mucosal inflammation (lymphocytic gastritis), treatment could be a consideration. Hundreds of clinical trials with various drug combinations have been reported for treating human Helicobacter infection. The most effective regimens produce > 90% eradication rates using combinations of antibiotics and an acid control drug (potentiated triple therapy) for at least two weeks. In all species, eradication of Helicobacter is extremely unpredictable and can only be confirmed if follow-up evaluations are done many weeks following treatment. One suggested oral treatment protocol for Helicobacter in cats includes a combination of clarithromycin (Biaxin; 5 mg/kg q12h PO), amoxicillin (20 mg/kg q8h PO), and omeprazole (Prilosec; 0.7-1.0 mg/kg q24h PO) for two to three weeks. A less expensive protocol uses a combination of amoxicillin (20 mg/kg q8h PO), metronidazole (10 mg/kg q8h PO), and famotidine (Pepcid; 0.5-1.0 mg/kg q24h PO) for two to three weeks, but this might be slightly less effective.

A clinical study of amoxicillin-metronidazole-famotidine combination (Magne M: Proc ACVIM, 1995) in 63 dogs and 20 cats diagnosed with Helicobacter gastritis by endoscopic biopsy and urease testing found that signs improved in 90% and the eradication rate was 74% based on follow-up evaluation at three to four weeks following treatment. However, other studies have shown that eradication is unpredictable and delayed recurrence (recrudescence or reinfection) after treatment is common. In experimental H. pylori infection in six cats, a combination of amoxicillin, metronidazole, and omeprazole produced apparent resolution based on negative PCRs at two and four weeks post-treatment, but PCRs became positive again at six weeks post-treatment indicating return of infection.