Update in Helicobacter Infection
World Small Animal Veterinary Association World Congress Proceedings, 2009
Alicia Valdés, DVM, MSc
Assistant Professor Department of Clinical Sciences, University of Chile

Although discovered at the end of the 19th century, gastric spiral organisms have been ignored by gastroenterologists, until the isolation of Helicobacter pylori from the human stomach in 1984 by Marshall and Warren. Compelling evidence established H. pylori as the primary cause of chronic active gastritis and peptic ulceration in humans and determined this organism as a major risk factor in the development of gastric adenocarcinoma and malignant mucosa-associated lymphoid tissue (MALT) lymphoma.

A small proportion (approximately 0.25-1.7%) of patients suffering from gastritis, peptic ulcers, and gastric cancer are diagnosed with gastric helicobacter-like bacteria other than H. pylori. These bacteria are commonly referred to as "Helicobacter heilmannii"-like organisms (HHLO) and are characterized by their long tightly coiled morphology. These spiral organisms have been described in the gastric mucosae of cats and dogs since the 19th century and are considered common inhabitants of the gastric mucosal niche.

Recent polyphasic taxonomy studies involving various isolates revealed at least three different species belonging to the genus Helicobacter, namely, Helicobacter felis, Helicobacter bizzozeronii, and Helicobacter salomonis; these species are both phenotypically and phylogenetically highly related. Confirmation of these molecular data came with the isolation and subsequent identification of a H. bizzozeronii strain from H. heilmannii infected patients. For the first time, conclusive evidence was provided that at least some of the human organisms categorized as "H. heilmannii" represent established Helicobacter species, and are possibly transmitted through animals.

Nevertheless, the prevalence and the role of the different non-pylori Helicobacter species possibly included in the "H. heilmannii" complex hitherto is unclear. The main problem encountered in this field of research is the difficulty to obtain pure cultures of these bacteria from either humans or animals, due to their extremely fastidious culture requirements, together with the lack of sensitive and specific diagnostic methods and poor availability of research material. This seriously hampers the exploration and collection of new epidemiologic data.

Morphologically, it is not difficult to differentiate H. heilmannii from the other non-spiral gastric organisms including H. pylori. However, as a variety of large gastric spiral organisms such as H. felis, H. salomonis, and H. bizzozeronii, although very rarely identified in human stomach, are indistinguishable from H. heilmannii on routine light microscopy, 16S rDNA sequencing or fluorescence in situ hybridization (FISH) with specific probes are required for more definitive identification.

A polymerase chain reaction (PCR) assay for the simultaneous detection of H. bizzozeronii, H. salomonis, and H. felis in cats and dogs, referred to as "pet carnivore helicobacters", is available. Also, 16S rDNA-based PCR assays that enable the specific detection of gastric Helicobacter species originating from pigs ("Candidatus H. suis") and cattle ("Candidatus H. bovis") have been developed.

Human patients with H. heilmannii infection show chronic gastritis similar to H. pylori-associated gastritis. However, the neutrophilic activity and mononuclear cell infiltration would be significantly low in cases of H. heilmannii-associated gastritis compared to H. pylori-associated gastritis. It has been described that H. heilmannii does not predominantly contact with gastric epithelial cells in contrast to H. pylori: these different localization of H. heilmannii may be related with mild neutrophilic infiltration.

The neutrophilic infiltration has been regarded to represent the activity of H. pylori gastritis with a close relation to the Helicobacter density, which also plays an important role in epithelial damage; however, such findings would be not evident in H. heilmannii-associated gastritis.

The distinctive histologic features of H. heilmannii-associated gastritis mentioned by the previous reports included the followings: absence of epithelial damage, lymphocytic exudation into gastric foveolae, mild inflammatory activity, infrequent acquired MALT, and infrequent intestinal metaplasia.

Dubois et al. were the first investigators who reported Gastrospirillum hominis-like organisms (GHLO) frequently invading and damaging parietal cells of monkeys. H. heilmannii organisms invaded into parietal cells accompanied by cellular changes, and it seems to be one of the characteristic histologic findings of H. heilmannii-associated gastritis.

The association between H. pylori and gastric MALT lymphoma is well established: H. pylori can be demonstrated in the gastric mucosa of most cases of gastric MALT lymphoma. O'Rourke et al. have shown that up to 25% of H. heilmannii-infected mice develop gastric MALT lymphomas.

Treatment strategies for H. heilmannii infection for human patients have not yet been fully determined. However, effective eradication with common anti-Helicobacter therapy involving proton pump inhibitors and combinations of antibiotics has been reported.

In dogs, Leib et al (2007) administered a triple therapy consisted of amoxicillin 15 mg/kg, metronidazole 10 mg/kg, and 262-mg bismuth subsalicylate tablets a on a scale based on body weight (< 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). In the same investigation another group of dogs received a quadruple therapy consisted of famotidine, 0.5 mg/kg, added to triple therapy. All medications were given PO q12h for 2 weeks. The eradication rate of gastric Helicobacter spp was similar in both treatment groups (75%) at 4 weeks after completion of therapy. These results indicate that the addition of famotidine, for acid suppression, was not more effective than triple therapy alone.

In conclusion, in human patients H. heilmannii-associated gastritis is uncommon and milder than H. pylori-associated gastritis, but may be noteworthy with respect to the development of MALT lymphoma. In dogs and cats, H. heilmannii is present in healthy and gastritis animals, and that is the reason for many research studies that actually try to understand the clinical significance of H. heilmannii infection in human and animal stomachs.


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Speaker Information
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Alicia Valdés, DVM, MSc
Department of Clinical Sciences
University of Chile

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