Tritrichomonas 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).
It has been found all over the world, but the widespread use of artificial insemination in breeding cattle has led to the virtual elimination of this organism from the cattle population in many countries including the UK and much of Europe.
Infection in catsThere have been a number of studies, initially from the USA, but now from numerous countries throughout the world, that have demonstrated that T foetus is an important cause of diarrhoea in cats. It can infect and colonise the large intestine, and can cause prolonged and intractable diarrhoea.
Studies have shown that this parasite mainly causes colitis (large bowel diarrhoea) resulting in increased frequency of defecation, semi-formed to liquid faeces, and sometimes fresh blood or mucous in the faeces. With severe diarrhoea the anus may become inflamed and painful, and in some cases the cats may develop faecal incontinence. Although cats of all ages can develop diarrhoea, it is most commonly seen in young cats and kittens, the majority being under 12 months of age. Most of the affected cats come from rescue shelters and pedigree breeding colonies. Abdominal ultrasound examination may show corrugation of the large bowel and local lymphadenopathy. Colonic biopsies from affected cats typically show mild to severe inflammatory changes with 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 with the mucosa. Although the diarrhoea may be persistent and severe, most affected cats are otherwise well, and show no significant weight loss.
Infection is most commonly seen in colonies of cats and multicat households, where the organism is presumably spread between cats by close and direct contact. While there is no direct evidence of spread from other species or spread via food or water, it has been shown to survive for several hours or even days in faeces, and can survive passage through the intestinal tracts of slugs. They can also survive for minutes to hours in cat urine, wet cat food and water. Studies in the US and UK have shown an overall prevalence of 10-15% in pet cats, rising to 31% of cats at a US cat show and 30% in UK faecal samples from cats with diarrhoea. Young pedigree cats (particularly Siamese and Bengal) have been shown to be more likely to be infected in the UK. Overall, studies suggest that this is an important, common, and previously unrecognised cause of diarrhoea in cats, with infection most likely where there is a high density of cats sharing the same environment.
While T foetus is known to be a significant cause of reproductive disease in cattle (infertility, abortion and endometritis), its role in causing reproductive disease in cats is still unclear. There is one report of a cat from Norway that came from a T foetus-infected household and developed pyometra (which was found to contain T foetus organisms). The cat may have been predisposed to the infection by having received six weeks of oral contraceptive (medroxyprogesterone acetate). It has also been suggested that tom cats may be able to harbour the infection in their prepuce. However, a recent paper USA failed to detect T foetuswithin the reproductive tracts of cats living in T foetus-infected catteries.
DiagnosisAssessment of the cats faeces for the presence of T foetus can be made using a number of different methods (see below for more details); (i) looking for moving parasites in fresh faecal smears (ii) using a specific culture system or (iii) by detection of T foetus DNA using PCR. The different methods have differing sensitivities: in one study direct smears were positive in 5/36 cases, culture in 20/36, and PCR in 34/36 cases; PCR is by far the most sensitive test, but even this can be hampered by intermitted shedding of the parasite. Diagnosis of T foetus infection is usually straightforward. The organism exists in the intestine as small, motile trophozoites, and these can be detected under the microscope. For optimum results, fresh faeces should be examined, and if any mucous has been passed with the faeces this is the most likely place to find the organisms. Smears of faeces/mucous 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 appear a little bit 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’. Examination of multiple smears and multiple faecal 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, 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. Two other diagnostic tests are available which are both more sensitive and specific for this organism. Firstly, the organism can be cultured from faecal 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 faeces (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 faeces 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 was available from Capital Diagnostics in Edinburgh (0131 535 3145) but its high prevalence of false negatives (due to the parasite dying in the cold UK postal system) means that it is not recommended as PCR is far more sensitive. The most sensitive and specific test is a PCR (polymerase chain reaction) test – a sophisticated test that can detect the presence of the genetic material of the organism. This is an extremely sensitive test that is available in the UK and US from a number of laboratories (please see below).
PrognosisCurrent information suggests 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 diarrhoea took an average of nine months, with occasional cats having diarrhoea persisting for more than two years, and rarely for life. 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 diarrhoea.
TreatmentSince the diarrhoea usually resolves over time, and is often more of an inconvenience than being associated with significant illness, it may not be necessary to treat all cats. Using a simple highly digestible diet or a high fibre diet and/or probiotics or synbiotics may result in improved faecal consistency, and this may be sufficient to control the clinical signs in some cats. Unfortunately, most studies on 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 and metronidazole. The use of a variety of different antimicrobial drugs has been reported to improve faecal consistency during therapy of infected cats, possibly because of interaction between T. foetus and the bacteria normally present in the intestine, and/or other concurrently carried enteric pathogens. However, such antibiotic use is not recommended as it may ultimately prolong the shedding of the organism, and does not resolve the underlying problem.
A study by Dr Jody Gookin at the North Carolina State University (who has performed most of the work on this infection in cats) identified that ronidazole and tinadazole (antibiotics similar but not the same as metronidazole) have some efficacy against T. foetus infection in cats (JVIM, 2006;20:536; Am J Vet Res, 2007; 68:1085), and that ronidazole is more effective than tinadazole. Ronidazole appears to be relatively safe, although a small number of 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. However, ronidazole is not licensed for use in cats; it should only be used with caution and with informed, signed, owner consent. Initial studies suggested that a dose of 30-50mg/kg once to twice daily for two weeks is capable of both resolving clinical signs and potentially eradicating T. foetus but it can also be associated with neurological side effects, plus occasional lethargy and/or vomiting. Therefore, we now recommend 20-30mg/kg once daily for two weeks, which should be reduced for young kittens or cats with hepatopathy to 10mg/kg once daily for two weeks. To ensure that each kitten receives the correct dose, and so reduce the risk of side effects, it is important to weigh the kittens prior to ordering the reformulated capsules. The bitterness of the powder means that it must be placed in capsules prior to administration. For the same reason it is important not to split tablets or open capsules and sprinkle the contents on food. In addition to treating with ronidazole, we recommend giving a probiotic or a synbiotic for four weeks starting on the same day as the ronidazole treatment. Our pilot study using Protexin Pro-Kolin Enterogenic™ in conjunction with ronidazole resulted in significantly fewer recurrences.
Recurrences: Unfortunately, T. foetus in some cats can be resistant to ronidazole therapy, so clinical signs recur following treatment. If this occurs, rule out possible co-infections as it has been shown that T. foetus-infected cats frequently carry a number of other potential faecal pathogens. Only if recurrence occurs despite giving a concurrent probiotic or a synbiotic, and after ruling out other potential infections, then consider repeating ronidazole treatment, but at a higher dose. Infected catteries: Once T. foetus has been identified in a cat from a cattery, many breeders want to treat all the cats in the cattery (particularly if a number of them have diarrhoea) in the hope that they can clear the infection from the cattery. Unfortunately, at standard ronidazole dosages, T. foetus is not always cleared from an individual cat, although the number of parasites is reduced to such a low level that the diarrhoea resolves and the cat usually clears the rest of the parasites with time. This means that even if you were to treat all the cats in a cattery, there is a reasonable chance that the infection will not be removed. In addition, ronidazole is not a licenced product, and there is a low but potential risk of toxicity. Because of these factors, the treatment of asymptomatic cats is not recommended. However, many breeders are choose to pursue this course of action. If this is the case, ensure the breeder fully understands the situation and have them sign an informed consent form. Obtaining ronidazole: Ronidazole is not licensed for use in cats, and its availability will vary in different countries. Preparations of ronidazole suitable for use in cats may not be widely available, but may be obtained from licensed compounding pharmacists (including Nova Laboratories and Summit Veterinary Pharmaceuticals in the UK). Care should be exercised in the use of ronidazole, as there are very few studies of its use in cats, and long-term studies in other species have suggested some potential toxicity concerns (in many countries its use in food-producing animals has been banned to minimise human exposure). Careful handling of the drug is therefore advised. It should never be given to pregnant queens (or queens about to be put to stud): it appears teratogenic and may result in a number of severe defects. Anyone handling ronidazole should wear gloves (especially if they are a woman of reproductive age).
Can T. foetus infect people?Very rare cases of T. foetus infection have been reported in immunosuppressed humans, where it can even cause systemic infection. As a precaution against infection, people in contact with infected cats are advised to take basic hygiene precautions to avoid ingesting the parasite. These precautions will also help to prevent the spread of the infection to other cats, and prevent humans from being infected with other infections that the cat may carry. Suitable hygiene precautions include:
Washing hands thoroughly after handling cat faeces
Washing hands thoroughly after cleaning cat litter trays, whether the cat has diarrhoea or not
Cat scratches or bites should always be washed immediately with soap and water. Seek medical attention as soon as possible if signs of infection appear, such as redness, pain or swelling.
Persons with a weakened immune system should not handle their cat’s faeces or litter box; they are advised to wash their hands after handling their cats, and they are advised not to keep cats that have persistent diarrhoea. If their cat develops diarrhoea it should be fully investigated and if found to be infected with T. foetus it should be treated with ronidazole and then re-tested, or (at least temporarily) re-homed until the infection has resolved.
In addition, there have also been reports of T. foetus infection in puppies. For further information on T. foetus infection in cats, visit:http://www.icatcare.org/ For veterinary surgeons seeking further discussion, contact Danièlle Gunn-Moore: email Danielle.Gunn-Moore@ed.ac.uk. Tel: 44 (0)131 650 7650 Fax: 44 (0)131 650 7652.
T. foetus PCR:In the UK this is available from Capital Diagnostics, SAC Veterinary Science Division, Bush Estate, Penicuik, Midlothian, EH26 0QE: Tel. 0131 535 3145). A real-time quantitative PCR (QPCR) assay is now available at Langford Veterinary Services Diagnostic Laboratories at the University of Bristol, Langford House, Langford, Bristol, BS40 5DU. Tel: +44 (0)117 928 9412 Fax: +44 (0)117 928 9613 Email: firstname.lastname@example.org. Further details on the test and submission forms can be found on http://www.langfordvets.co.uk/lab_pcrnews.htm. IDEXX 8-way cat diarrhoea panel tests for T. foetus plus other potential pathogens. Carmichael Torrance have also just stated offering this PCR: email@example.com. In the US samples can be submitted to the College of Veterinary Medicine, North Caroline State University (USA) for this test – information on this is available at:www.cvm.ncsu.edu/mbs/gookin_jody.htm.
Acknowledgements Thanks to Dr Andy Sparkes, Ellie Mardell and Kirsty Wood who were involved with the initial preparation of this paper.
References and further readingDahlgren SS, Gjerde B, Pettersen HY (2007) First record of naturalTritrichomonas foetus infection of the feline uterus. Journal of Small Animal Practice 48:654-657 Foster DM, Gookin JL, Poore MF, Stebbins ME, Levy MG (2004) Outcome of cats with diarrhoea and Tritrichomonas foetus infection. Journal of the American Veterinary Medical Association 225:888-892 Gookin JL, Breitschwerdt EB, Levy MG, Gager RB (1999) Diarrhoea associated with trichomoniasis in cats. Journal of the American Veterinary Medical Association 215:1450-1454 Gookin JL, Birkenheuer AJ, Breitschwerdt EB, Levy MG (2002) Single-tube nested PCR for detection of Tritrichomonas foetus in feline faeces. Journal of Clinical Microbiology 40:4126-4130 Gookin JL, Copple CN, Papich MG, Poore MW, Stauffer SH, Birkenheuer AJ, Twedt DC, Levy M (2006) Efficacy of ronidazole for treatment of felineTritrichomonas foetus infection. Journal of Veterinary Internal Medicine 20: 536-543 Gookin JL, Foster DM, Poore MF, Stebbins ME, Levy MG (2003b) Use of a commercially available culture system for diagnosis of Tritrichomonas foetusinfection in cats. Journal of the American Veterinary Medical Association222:1376-1379 Gookin JL, Levy MG, Law JM, Papich MG, Poore MF, Breitschwerdt EB (2001) Experimental infection of cats with Tritrichomonas foetus. American Journal of Veterinary Research 62:1690-1697 Gookin JL, Stebbins ME, Adams E, Burlone K, Fulton M, Hochel R, Talaat M, Poore M, Levy MG (2003a) Prevalence and risk of T foetus infection in cattery cats (Abstract).Journal of Veterinary Internal Medicine 17:380 Gookin JL, Stebbins ME, Hunt E, Bulone K, Fulton M, Hochel R, Talaat M, Poore M, Levy MG (2004) Prevalence and risk factors for feline Tritrichomonas foetusand Giardia infection. Journal of Clinical Microbiology 42:2707-2710 Gookin JL, et al. (2005) Molecular characterisation of tritrichomonads from faeces of dogs with diarrhoea. J Parasitology, 91(4): 939-43 Gookin JL, Stauffer SH, Coccaro MR, Poore MF, Levy MG, Papich MG (2007) Efficacy of tinidazole for treatment of cats experimentally infected with Tritrichomonas foetus. Am J Vet Res 68(10):1085-8. Gookin JL, Stauffer SH, Dybas D, Cannon DH (2010) Documentation of the in vivo and in vitro aerobic resistnace of feline Tritrichomonas foetus isolates to ronidazole. JVIM 24: 1003-1007 Gray SG, Hunter SA, Stone MR, Gookin JL (2010) Assessment of reproductive tract disease in cats at risk for Tritrichomonas foetus infection.Am J Vet Res.71(1):76-81. Grey SG, Hunter SA, Stone MR, Gookin JL. Assessment of reproductive tract disease in cats at risk for enteric Tritrichomonas foetus infection. Abstract 111, Proceedings of the ACVIM Congress, 2009, pp718. Grellet A, Bickel T, Polack B, et al. Prevalence of Tritrichomonas foetus in puppies from French breeding kennels. Proceedings of the ECVIM 2010, Toulouse. Gunn-Moore, DA, McCann, TM, Reed, N, Simpson, KE, Tennant, B. (2007) Prevalence of Tritrichomonas foetus infection in cats with diarrhoea in the UK. JFMS 9: 214-218 Gunn-Moore DA, Tennant B. (2007) Tritrichomonas foetus in cats in the UK. Vet Rec. 160(24): 850-851 Hale S. Norris JM, Slapeta J (2009) Prolonged resilience of Tritrichomanas foetusin cat faeces at ambient temperature. Vet Parasitol 166: 60-65 Kather EJ, Marks SL, Kass PH. (2007) Determination of the in vitro susceptibility of feline tritrichomonas foetus to 5 antimicrobial agents. J Vet Intern Med.;21(5):966-70) Levy MG, Gookin JL, Poore M, Birkenheuer AJ, Dykstra MJ, Litaker RW (2003)Tritrichomonas foetus and not Pentatrichomonas hominis is the etiologic agent of feline trichomonal diarrhoea. Journal of Parasitology 89:99-104 Manning K (2010) Update on the diagnosis and management of Tritrichomanas foetus infections in cats. Topics in Comapnion Animal Medicine 25(3): 145-148 Mardell EJ, Sparkes AH. (2006) Chronic diarrhoea associated withTritrichomanas foetus infection in a British cat. Veterinary Record 158,765-766 Romatowski J (2000) Pentatrichomonas hominis infection in four kittens. Journal of the American Veterinary Medical Association 216:1270-1272 Rosado TW, Specht A, Marks SL. (2007) Neurotoxicosis in 4 cats receiving ronidazole. J Vet Intern Med 21(2):328-31 Rosypal AC, Ripley A, Stockdale Walden HD, Blagburn BL, Grant DC, Lindsay DS (2012) Survival of a feline isolate of Tritrichomanas foetus in water, cat urine, cat food and cat litter. Vet Parasitol 185: 279-281 SAC (SAC Veterinary Services) Monthly Report (2007); available onlinewww.sac.ac.uk/consultancy/veterinary/publications/monthlyreports/2007 :Veterinary Record 161(16): 544-546 Van der Saag M, McDonell D, Slapeta J. (2011) Cat genotype Tritrichomanas foetus survives passage through the alimentary tract of two common slug species. Vet Parasitology 177: 262-266 Zalonis CA, Pillay A, Secor W et al. (2011) Rare case of trichomonal peritonitis. Emerg Inf Dis 17(7):1312-1313