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Tritrichomonas foetus infection
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Introduction
  • Tritrichomonas foetus is a protozoan parasite that has been traditionally identified as a cause of reproductive disease in cattle (infertility, abortion and endometritis); while it has been found all over the world, the widespread use of artificial insemination has led to its virtual elimination from cattle in many countries, including the UK and much of Europe.
  • T. foetus has recently been shown to be an important cause of prolonged and intractable large bowel diarrhea in cats.


Presenting signs
  • T. foetus infection mainly causes colitis Colitis (large bowel diarrhea) with increased frequency of defecation, semi-formed to liquid foul-smelling feces, sometimes with fresh blood or mucus in the feces. With severe diarrhea the anus may become inflamed and painful, and in some cases the cats may develop fecal incontinence.
  • Although the diarrhea Diarrhea: parasites may be persistent and severe, most affected cats are otherwise well, and do not show significant weight loss. However, occasional deaths have occurred in young kittens, probably resulting from secondary bacterial sepsis.


Acute presentation
  • Acute onset of large bowel diarrhea (see above).


Geographic incidence
  • The infection has so far only been confirmed in cats in the USA, UK and Germany. However, the infection is known to be present world wide in cattle.
  • In the USA, using PCR diagnostics, 31% of cats at a pedigree cat show were found to be infected. Using the same diagnostics, in the UK, ~10% of cats with diarrhea were found to be infected.


Age predisposition
  • Although cats of all ages can be infected and develop diarrhea, clinical disease is seen most commonly in young cats and kittens, the majority being under 12 months of age.


Sex predisposition
  • None noted.


Breed predisposition
  • Most of the clinically affected cats have come from rescue shelters and pedigree breeding colonies. Anecdotally, in the UK, Bengal Bengal and Maine Coon Maine Coon breeds appear to be over-represented. However, this probably occurs because these breeds are more likely to be kept in very large groups and to have cats imported from the USA (where the infection is more prevalent), than relating to a breed predisposition.


Public Health considerations
  • The infection has occasionally been seen in immuno-suppressed humans, but as yet, there have been no indications of zoonotic spread from cats.


Cost considerations
  • The cost of investigation, treatment and loss of revenue from unsold kittens can be significant.


Special risks (e.g. anesthetic)
  • None.
Pathogenesis Top

Etiology
  • T. foetus is a microscopic single-celled flagellated protozoan parasite that has traditionally been identified as a cause of reproductive disease in cattle (infertility, abortion and endometritis). In cats, T foetus infects and colonizes the small and large intestine, and can cause prolonged and intractable large-bowel diarrhea.


Predisposing factors
General
  • Although cats of all ages can be affected with diarrhea, it is seen most commonly in young cats and kittens, the majority being under 12 months of age. Most of the affected cats have come from rescue shelters and pedigree breeding colonies.


Pathophysiology
  • In cats, T foetus can infect and colonize the small and large intestines, but it is the colon where it can cause lymphocytic-plasmocytic (and also neutrophilic) inflammation; resulting in increased frequency of defecation, and the production of semi-formed to liquid feces, sometimes with fresh blood or mucus.


Timecourse (incubation, duration)
  • While experimental infection can result in diarrhea within a few days, many cats can be asymptomatic carriers. Once clinical signs occur they can be waxing and waning, spontaneously resolve or, occasionally, result in intractable diarrhea that can last for up to 2 years.


Epidemiology (population dynamics)
  • In a study in the USA, 31% of cats at a cat show were identified as being infected with T foetus, suggesting that this may be an important, common, and previously unrecognized cause of diarrhea in cats.
  • Infection is most commonly seen in colonies of cats and multicat households, where the organism is believed to be spread between cats by close and direct contact.

Diagnosis Top

Presenting problems
  • Chronic large bowel diarrhea (see above).


Client history
  • Multicat, often pedigree cat, household with multiple cases of large bowel diarrhea.


Clinical signs
  • Chronic large bowel diarrhea (see above).


Diagnostic investigation
  • Diagnosis of T foetus infection is usually quite straightforward using fecal analysis (see below).
  • Colonic endoscopy Colonoscopy typically revealed inflammatory change, which is usually seen as a lymphocytic-plasmocytic infiltrate on histopathological examination.
  • Abdominal ultrasound Ultrasonography: GI system examination may show corrugation of the large bowel and local lymphadenopathy.

Definitive Diagnostic features
  • The organism exists in the intestine as small, motile trophozoites, and these can be detected under the microscope. For optimum results, fresh feces Fecal examination for parasites should be examined, and if any mucus has been passed with the feces this is the most likely place to find the organisms.  Smears of feces/mucus diluted with some saline can be made on a microscope slide. A cover slip can be pressed over the smear and then the slide can be examined under x200 and x400 magnification. In most clinically affected cats, large numbers of the small motile organisms can be seen they look a little like microscopic tadpoles with very short tails (!), and have an undulating membrane that runs over the length of the body. Their movement is described as 'jerky, forward motion' Tritrichomonas foetus video.
  • Examination of multiple smears and multiple fecal samples will improve the detection of the organism. Rectal swabs can also be examined for the organism - a cotton swab can be inserted into the anus and rotated over the colonic mucosa - this is then withdrawn and a smear made on a microscope slide which is again diluted with saline and examined as above. The organism needs to be distinguished from Giardia Giardia spp, another protozoan parasite, but with Giardia infection the trophozoites tend to be far fewer in number, they are binucleate with a concave ventral 'sucker', and do not exhibit the same forward motion as T foetus. If a cat has received recent antibiotic therapy, this can suppress the number of T foetus trophozoites shed, and can make the diagnosis more difficult. In such cases, more sensitive diagnostic techniques may be preferable.
  • The organism can be cultured from fecal samples using a system developed for diagnosis in cattle. The 'In PouchTM TF' test (BioMed Diagnostics, Oregon, USA) uses a liquid culture system in a sterile plastic pouch. The pouch can be inoculated with 0.05g of feces (about half the size of a small pea). The pouches are incubated at room temperature and can be examined microscopically for the motile organisms every two days for 12 days. This test is more sensitive than direct examination of feces and helpful for detecting infections where direct smears are negative.  Giardia, and other similar organisms will not grow in this specific culture medium. In the UK, this system is available from Capital Diagnostics in Edinburgh (0131 535 3145), however, posting the pouches back to the laboratory in cold weather can lead to false negatives as the parasites die in the cold.
  • PCR (polymerase chain reaction) PCR (Polymerase chain reaction) can detect the presence of the genetic material of the organism. This is an extremely sensitive and specific test. In the UK samples can be submitted to Capital Diagnostics in Edinburgh (0131 535 3145), while in the USA they can be sent to the College of Veterinary Medicine, North Carolina State University (USA) - information on this is available at: www.cvm.ncsu.edu/mbs/gookin_jody.htm.


Gross autopsy findings
  • Few affected kittens die, however, when they do they have severe colitis, regional lymphadenopthy, and typically have evidence of sepsis Shock: septic.


Histopathology findings
  • Colonoscopy may reveal inflamed thickened friable mucosa, plus or minus mucus and blood.
  • Colonic biopsies from affected cats typically show mild to severe inflammatory changes with predominantly infiltration of lymphocytes and plasma cells - a pattern commonly seen with other infectious agents and with inflammatory bowel disease. However, the parasites may be seen in close association to the mucosa and deep within the colonic crypts.


Differential diagnosis
  • Giardia spp. infection, coccidiosis (Isospora Isospora felis), Cryptosporidium spp. infection Cryptosporidium spp, inflammatory bowel disease Inflammatory bowel disease: overview, other infectious or dietary causes of colitis in cats.

Treatment Top
Initial symptomatic treatment
  • Feeding either a simple highly digestible diet or a high fiber diet may result in improved fecal consistency, and this alone may allow sufficient control of clinical signs in some cases.
  • Unfortunately, most studies into the treatment of T. foetus infection in cats have been unrewarding. The organism is resistant to most traditionally used anti-protozoal drugs such as fenbendazole Fenbendazole and metronidazole Metronidazole, and while the use of a variety of different antimicrobial drugs Therapeutics: antimicrobial drug has been reported to improve fecal consistency during therapy of infected cats, this is probably because of an interaction between T. foetus and the bacteria that are normally present in the intestine. Random antibiotic use is not recommended as it may ultimately prolong the shedding of the organism, and does not resolve the underlying problem.
  • As the diarrhea typically resolves over time, and is often more of an inconvenience than being associated with significant adverse effects in affected cats, it may not be necessary or advisable to treat all affected cats with ronidazole (see below for the potential side-effects of this drug). 


Standard treatment
  • A recent study by Dr Jody Gookin at the North Carolina State University identified that ronidazole (an antibiotic similar but not the same as metronidazole) may have good efficacy against T. foetus infection in cats (JVIM, 2006 20,536-543). 
  • From limited studies ronidazole appears to be relatively safe in cats, although some patients have developed neurological signs, eg twitching and seizures, which have resolved on stopping the drug. The neurological signs are similar to those seen in some kittens, or cats with liver disease, when they are given standard or high doses of metronidazole.
  • Initial studies suggested that a dose of 30-50 mg/kg once to twice daily for two weeks is capable of both resolving clinical signs and potentially eradicating the T. foetus. However, keeping to the lower end of the dose is advisable (30 mg/kg), as is reducing it even further for young kittens, or cats with hepatopathy; (10 mg/kg once to twice daily for two weeks). The bitterness of the powder means that it must be placed in capsules prior to administration*.
    warning.jpg Ronidazole is not licensed for use in cats; it should only be used with caution and with informed, signed, owner consent.
  • Ronidazole (10% powder preparation) is commonly used to treat trichomoniasis in birds (eg pigeons). However, it is not available in this form in the UK, and the consistency of the 10% formulation is difficult to guarantee. Therefore, permission has been gained from the Veterinary Medicines Directorate (VMD) to use 100% pure chemical grade ronidazole to treat T. foetus infected cats. This is the form that is now used in the USA. In the UK it can be obtained from G W Cartwright, Orffa UK Ltd, PO Box 113, Northallerton, DL6 1YH, UK; Tel. 01609 772 881; Fax. 01609 78 941; Mobile. 07850 663 463. While the VMD have agreed to use of this chemical in these cats, they strongly recommend that detailed records are maintained and that no cat is treated without first obtaining informed, signed, owner consent. In addition, data should be compiled on all potential adverse effects: send case information on any potential adverse effects to Danielle.Gunn-Moore@ed.ac.uk.
  • Care should be exercised in the use of ronidazole; there are very few studies of its use in cats, and long-term studies in other species have suggested potential toxicity concerns (and in many countries its use in food-producing animals has been banned to minimize human exposure). Careful handling of the drug is therefore advised; and vets should seek further information before considering treatment (Danielle.Gunn-Moore@ed.ac.uk). 
    *Empty gelatine capsule are available from most veterinary drug suppliers, and the small end of a size 4 capsule holds ~90mg of pure ronidazole. Reformulation into capsules can be performed by Nova Laboratories, Tel: 0116 223 0099, but the packet of ronidazole must be sent to them un-opened with a copy of the Certificate of Analysis and a signed named-animal prescription.


Monitoring
  • While being treated with ronidazole cats should be carefully monitored for signs of neurological disorder, eg lethargy, tremors, ataxia, seizures, coma, etc. If these occur, treatment with ronidazole should be stopped immediately.


Subsequent management

Treatment
  • No other medial treatments are currently available. However, dietary manipulation can still be undertaken (eg feeding either a simple highly digestible diet or a high fiber diet may improve fecal consistency).
  • Observe for recurrence of large bowel diarrhea.

Monitoring
  • Observe for recurrence of large bowel diarrhea.

Prevention Top
Control
  • Improve hygiene. Perhaps, only introduce (import) cats into a T.foetus-negative cattery once they have also been tested negative.


Prophylaxis
  • None recommended at present.


Group eradication
  • Not recommended at present as ronidazole is currently only available as a pure chemical, not a drug, there are no products licensed for use in cats, and side-effects from the use of pure ronidazole appear to be quite common.

Sequelae Top
Prognosis
  • Current information suggests that the long-term prognosis for infected cats is good, and that they will eventually overcome the infection.  However, this is a slow process - in one study of infected cats, resolution of the diarrhea took an average of nine months, with occasional cats having diarrhea persisting for more than two years, while in others it resolved after two months. It appears that most infected cats continue to shed low levels of the organism in their faeces for many months after the resolution of the diarrhea.


Expected response to treatment
  • Treatment with ronidazole typically resolves the diarrhea rapidly. Where ronidazole treatment is not undertaken, affected cats may show waxing and waning clinical signs, but most resolve with time. Feeding a simple highly digestible diet or a high fibre diet may improve fecal consistency.


Reasons for treatment failure
  • While some cases may appear to be resistant to ronidazole, it is probably more likely that the cats are being re-infected by other cats from within their colony (remember that asymptomatic carriers are common).

Sources Top
Publications
Refereed papers
  • Recent references from PubMed.
  • Mardell E J, Sparkes A H (2006) Chronic diarrhoea associated with Tritrichomanas foetus infection in a British cat. Vet Rec 158 (22), 765-766 PubMed
  • Gookin J L, Copple C N, Papich M G, Poore M W, Stauffer S H, Birkenheuer A J, Twedt D C, Levy M (2006) Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection. JVIM 20,  536-543 PubMed.
  • Foster D M, Gookin J L, Poore M F, Stebbins M E, Levy M G (2004) Outcome of cats with diarrhoea and Tritrichomonas foetus infection.  JAVMA 225, 888-892 PubMed.
  • Gookin J L, Stebbins M E, Hunt E, Bulone K, Fulton M, Hochel R, Talaat M, Poore M, Levy M G (2004) Prevalence and risk factors for feline Tritrichomonas foetus and Giardia infection.  J Clin Microbiol 42, 2707-2710 PubMed
  • Levy M G, Gookin J L, Poore M, Birkenheuer AJ, Dykstra M J, Litaker R W (2003) Tritrichomonas foetus and not Pentatrichomonas hominis is the etiologic agent of feline trichomonal diarrhoea.  J Parasitol 89, 99-104.
  • Gookin J L, Foster D M, Poore M F, Stebbins M E, Levy M G (2003) Use of a commercially available culture system for diagnosis of Tritrichomonas foetus infection in cats. JAVMA 222, 1376-1379 PubMed.
  • Gookin J L, Birkenheuer A J, Breitschwerdt E B, Levy M G (2002) Single-tube nested PCR for detection of Tritrichomonas foetus in feline faeces. J Clin Microbiol 40, 4126-4130 PubMed.
  • Gookin J L, Levy M G, Law J M, Papich M G, Poore M F, Breitschwerdt E B (2001) Experimental infection of cats with Tritrichomonas foetus.  Am J Vet Res 62, 1690-1697 PubMed.
  • Romatowski J (2000) Pentatrichomonas hominis infection in four kittens.  JAVMA 216, 1270-1272.
  • Gookin J L, Breitschwerdt E B, Levy M G, Gager R B (1999) Diarrhea associated with trichomoniasis in cats.  JAVMA 215, 1450-1454.

Other sources of information


Vetstream contributor(s)
  • Jody L Gookin DVM PhD DipACVIM, Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
  • Danielle Gunn-Moore BSc BVM&S PhD MACVSc MRCVS RCVS Specialist in Feline Medicine, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Hospital for Small Animals, Easter Bush Veterinary Centre, Roslin, Midlothian EH25 9RG, UK.

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Bengal
Colitis
Colonoscopy
Cryptosporidium spp
Diarrhea: parasites
Fecal examination for parasites
Fenbendazole
Giardia spp
Inflammatory bowel disease: overview
Isospora felis
Maine Coon
Metronidazole
PCR (Polymerase chain reaction)
Shock: septic
Therapeutics: antimicrobial drug
Ultrasonography: GI system
Tritrichomonas foetus video
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