Helicobacter spp

From Felipedia

Helicobacter spp, cultured from gastric mucosa

Multiple spiral organisms, Helicobacter felis, are seen in the mucus layer of this feline gastric mucosal biopsy. Some spirochetal organisms may also be found in the antral mucus glands and within canaliculi of perietal cells

Helicobacter spp are common Spirochete bacteria that colonize the stomach of cats, and a leading cause of feline gastric ulceration. Spontaneous gastric perforation has been reported in cats, but does not necessarily involve Helicbacter spp infection and may be caused by other factors such as long-term NSAID use (e.g. Meloxicam).

Although first discovered in 1889, little was known of their importance until the 1980s when a causal relationship was hypothesized with gastric/duodenal ulceration and neoplasia in humans.

It is know realised that Helicobacter spp are associated with chronic gastritis in cats as well as other variant spirochetes (such as Borrelia burgdorferi and Flexispira spp) being intimated in lymphoma, pancreatitis and cholangiohepatitis in cats.

Helicobacter spp are gram-negative, microaerophilic, curved to spiral motile bacteria that inhabit the stomach and to a lesser degree, the intestine and liver of cats. They break down urea into ammonia and bicarbonate and thus create a less acidic microenvironment in order to survive. The overall prevalence rates of Helicobacter are high in both cats (80-100%) and humans (20-100%, with higher rates in older people and in poorer countries). Most Helicobacter infections are not associated with clinical signs. Nevertheless, these bacteria have the potential to cause disease. The main species in cats are:

• Helicobacter pylori - humans, cats
• Helicobacter canis - dogs, cats
• Helicobacter heilmannii - cats, dogs, humans
• Helicobacter felis - cats, dogs, humans
• Helicobacter cinaedi -cats, dogs, humans

Clinical signs

• Gastritis & gastroenteritis

H. pylori is of special note because it is shown to cause significant disease in people and has been confirmed as causing disease in cats. In a recent study, gastric samples were collected from 23 cats; 18 with no clinical signs, and 5 that had chronic vomiting. Samples were assessed microscopically for epithelial changes, as well as by PCR for the organism. The bacteria were detected in 20 of the 23 cats, four of which were from the cats experiencing chronic vomiting. No correlation was found between gastric inflammation and level of Helicobacter spp colonization. Helicobacter colonization was associated with increased epithelial proliferation in the stomach; thus, the authors postulate, it could contribute to gastric cancers^[1].

A few reports exist of Helicobacter spp being isolated from cats with diarrhoea. The first report was of H. colifelis being grown from the lower intestinal tract of a cat^[2]. Another report describes H. canis cultured from feces of four Bengal cats^[3]. These were from a cattery with 20 other cats, 75% of which had episodic diarrhoea that was characterised as being watery, mucoid and/or blood tinged. However, other potential gastrointestinal pathogens (such as Clostridium spp) also were cultured from these cats, and some of the nondiarrhoeic cats were found to have H. canis in their feces as well. Therefore, cause and effect is hard to ascribe. Finally, a Flexispira rappini-like organism (a type of Helicobacter spp) was grown from a 4-month-old kitten that died of haemorrhagic enteritis^[4]. Coinfections with Helicobacter and Campylobacter spp may be more common than suspected, and distinguishing between these two genera can be difficult. PCR is necessary to characterise isolates accurately.

• Pancreatitis

Autoimmune pancreatitis is a recently defined disease in humans and accounts for 4.6-6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjogren's syndrome. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized^[5].

• Lymphosarcoma

There is now a good causal link between H. pylorus infection in cats and development of gastric and SI lymphoma^[6].

• Cholangiohepatitis

Infection with Helicobacter spp. is increasingly linked with hepatobiliary inflammation and neoplasia in people and in a variety of animals. A recent study identified Helicobacter deoxyribonucleic acid in 2/32 cats with cholangiohepatitis and 1/13 cats with noninflammatory liver disease. Deoxyribonucleic acid sequences of hepatic Helicobacter species were distinct from those found in the stomach and are broadly consistent with those identified in cat intestine and bile, and hepatobiliary disease in people and rodents^[7].

Although reports of clinical symptoms in cats are limited, possible signs include chronic vomiting, weight loss, abdominal pain, borborygmus (gas gurgles) and diarrhoea. The differential diagnosis should include those of chronic vomiting and possibly diarrhoea. In humans, it appears that Helicobacter infection may predispose to gastric cancer (Helicobacter infection represents a 400% increase risk of developing gastric carcinoma). Cats, however, get infected with different Helicobacter species and the same association with cancer in this species has not been made^[8].

The mode of transmission of Helicobacter is uncertain. It is unknown whether animals transmit infection to people, or vice versa. Faecal-oral transmission is also suspected because Helicobacter has been identified in the faeces.

Diagnosis

There are a number of ways to determine if a cat's chronic gastrointestinal problem is being complicated by Helicobacter infection.

1. Biopsy - While it is possible to miss Helicobacter if only certain areas of the stomach are colonized, biopsy is by far the most accurate test. This method not only detects the infection but also assesses the degree of inflammation and checks for cancer. Biopsy is by mucosal (endoscopic) or full-thickness (laparotomy) of multiple areas of the stomach.
2. Rapid Urease Test - Some gastroenterologists will keep a special broth handy during the biopsy procedure. A spare tissue sample can be dropped in the broth and incubated for an hour. The presence of urease, the enzyme that creates Helicobacter's protective bicarbonate layer, induces a colour change in the solution. In this way, Helicobacter can be detected in an hour rather than after the 2 days it takes to obtain biopsy results.
3. PCR Testing - This especially sensitive DNA testing can be used but is only available in a few centres.
4. Blood Testing - antibodies against Helicobacter can be detected but their levels take months to decline even after the Helicobacter organism is long gone. This limits the usefulness of such testing.
5. Breath Testing - A useful test for humans where a radio-isotope labelled meal is fed and the patient's breath is tested for Helicobacter metabolites. This form of testing is easy to use for monitoring the eradication of Helicobacter plus it is non-invasive. In humans, Helicobacter eradication is usually confirmed 4-8 weeks after treatment has been completed. This test has not been adopted for clinical use in animals at this stage.

Treatment

There are many medication combinations used to treat Helicobacter (dosages in feline patients are usually transcribed from humans).

1. Primary therapeutics are based on dual antibiotic therapy. Give any two of the following for 3 weeks: Amoxicillin (20mg/kg PO bid2), azithromycin (5mg/kg PO oid), clarithromycin (5mg/kg PO bid), doxycycline (5mg/kg PO bid), metronidazole (12.5 mg/kg PO bid), tetracycline (20mg/kg PO tid)

Amoxicillin

1. Secondary therapeutics based on antacid therapy. One of the following: famotidine (0.5mg/kg PO bid), ranitidine (2.5-3.5 mg/kg PO bid), cimetidine (10 mg/kg PO tid), or omeprazole (0.7 mg/kg PO oid).

High eradication rates are achieved in humans. Most animals are asymptomatic and do not require therapy. Initial therapy in animals suspected to have clinical disease has seemed to be successful in limited reports; however, response rates have not been evaluated in the long term, and recurrence of infection has been identified. It is not known whether recurrence represents persistent infection, reinfection, or recrudescence.

References

1. ↑ Norsworthy et al (2003) The Feline Patient: essentials of diagnosis and treatment. Lippincott Williams and Wilkins, Baltimore. USA
2. ↑ Foley, JE et al (1998) Identification of a novel enteric Helicobacter species in a kitten with severe diarrhoea. J Clin Microbiol 36:908-912
3. ↑ Foley, JE et al (1999) Isolation of Helicobacter canis from a colony of Bengal cats with endemic diarrhoea. J Clin Microbiol 37:3271-3275
4. ↑ Kipar, A et al (2001) Fatal gastrointestinal infection with Flexispira rappini-like organisms in a cat. J Vet Med 48:357-365
5. ↑ Guarneri, F et al (2005) Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry? J Cell Mol Med. 2005 Jul-Sep;9(3):741-4
6. ↑ Parsonnet J., Friedman G.D., Vandersteen D.P., Chang Y., Vogelman J.H., Orentreich N. & Sibley R.K. (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325:1127–1131
7. ↑ Greiter-Wilke, A., et al (2006) Association of Helicobacter with cholangiohepatitis in cats. J Vet Intern Med. Jul-Aug;20(4):822-7
8. ↑ August, JR (2006) Consultations in feline internal medicine. Vol. 5. Elsevier Saunders, USA