Cytauxzoonosis in Indiana, USA: a case series of cats infected with Cytauxzoon felis (2018-2022).

CASE SERIES SUMMARY: This case series describes six cases involving seven cats naturally infected with Cytauxzoon felis in Indiana, USA. Medical records were retrospectively reviewed and all available information on signalment, history, clinical and diagnostic findings, treatment, outcome and pathology was reported. Cats infected with C felis were domestic shorthairs, were aged between 2 and 9 years and all but one of the cats were male. The seven infected cats originated from five counties in southwestern Indiana. Six of seven cats were found to have acute cytauxzoonosis based on clinical signs, gross pathologic lesions, observation of C felis in tissues and/or detection of C felis DNA. One cat was identified as a subclinical survivor cat with no known clinical history of cytauxzoonosis. RELEVANCE AND NOVEL INFORMATION: The reported cases are the first confirmed reports of acute and chronic cytauxzoonosis in cats from Indiana and document an expansion in the range of C felis. Veterinary practitioners in Indiana should consider infection with C felis as a differential diagnosis for cats that present with fever, inappetence, lethargy, depression, dehydration, dyspnea, hemolytic crisis, anorexia or icterus. Administration of approved acaricides to cats currently offers the best protection and control against C felis infection.

What is known about Tritrichomonas foetus infection in cats? / O que sabemos sobre a infecção por Tritrichomonas foetus em gatos?

Abstract Tritrichomonas foetus is a parasite that has been definitively identified as an agent of trichomonosis, a disease characterized by chronic diarrhea. T. foetus colonizes portions of the feline large intestine, and manifests as chronic and recurrent diarrhea with mucus and fresh blood, which is often unresponsive to common drugs. Diagnosis of a trichomonad infection is made by either the demonstration of the trophozoite on a direct fecal smear, fecal culture and subsequent microscopic examination of the parasite, or extraction of DNA in feces and amplification by the use of molecular tools. T. foetus is commonly misidentified as other flagellate protozoa such as Giardia duodenalis and Pentatrichomonas hominis. Without proper treatment, the diarrhea may resolve spontaneously in months to years, but cats can remain carriers of the parasite. This paper intends to serve as a source of information for investigators and veterinarians, reviewing the most important aspects of feline trichomonosis, such as trichomonad history, biology, clinical manifestations, pathogenesis, world distribution, risk factors, diagnosis, and treatment.

Resumo Tritrichomonas foetus é um parasito que foi identificado definitivamente como agente de tricomoníase, caracterizada por diarreia crônica. T. foetus coloniza porções do intestino grosso dos felinos e se manifesta como uma diarreia crônica e recorrente, com muco e sangue, geralmente irresponsiva às drogas comumente usadas no tratamento. O diagnóstico da infecção por tricomonadídeos é feito pela demonstração de trofozoítos no exame direto de fezes frescas, cultura fecal e subsequente exame microscópico ou extração do DNA do parasito na amostra fecal e amplificação, utilizando-se técnicas moleculares. T. foetus é comumente confundido com outros protozoários flagelados, como Giardia duodenalis e Pentatrichomonas hominis. Sem tratamento adequado, a diarreia pode cessar espontaneamente em meses ou anos, porém os gatos podem permanecer portadores do parasito. Esse artigo pretende servir como fonte de informação para pesquisadores e veterinários, revisando os mais importantes aspectos da tricomoníase felina, como histórico, biologia, manifestações clínicas, patogênese, distribuição mundial, fatores de risco, diagnóstico e tratamento.

Therapeutic uses of metronidazole and its side effects: an update.

OBJECTIVE: Metronidazole is an antibiotic widely used in different medical conditions such as trichomoniasis, amoebiasis, and giardiasis among others. Its use has been associated with toxicity; however, it is not well characterized. In this review, we discuss the different therapeutic uses of metronidazole and its side effects in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information, original research articles, clinical trials, and reviews were collected from PubMed to know the state of the art of the different therapeutic uses of metronidazole and the reported side effects. RESULTS: Metronidazole was used by the first time in 1959, to treat an infection caused by Trichomonas vaginalis; subsequently, new therapeutic properties were discovered. Nowadays, Metronidazole is used to treat infections caused by Bacteroides, Fusobacteria and Clostridia, rosacea, oral and dental infections, bone and joint infections, gynecologic infections, endocarditis, septicemia, and respiratory tract infections. It also can be used to treat Crohn´s disease or even like prophylaxis, before surgical procedures. Metronidazole is well tolerated with mild to moderate side effects such as nausea, abdominal pain, and diarrhea. Nevertheless, serious neurotoxicity, optic neuropathy, peripheral neuropathy, and encephalopathy have been reported in rare cases. Their genotoxic effects observed in animal models are controversial in humans. CONCLUSIONS: The therapeutic use of metronidazole had increased worldwide. Even though it is widely used, metronidazole has been associated with neurotoxicity and genotoxicity; however, its side effects are not well established. Conversely, its veterinary use is restricted in some countries because of its tumor association. Subsequently, further studies are needed to discover the secure use of metronidazole and describe new usages for this drug.

Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine.

Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.

The conundrum of feline Trichomonosis.

Practical relevance: Trichomonosis of the large intestine of the cat was described as a cause of chronic diarrhea over 20 years ago. The trichomonad was identified as Tritrichomonas foetus, with a genotype that is distinct from venereal T foetus of cattle. Clinical challenges: Despite multiple means for diagnosis of the infection, including light microscopy, protozoal culture and PCR amplification using species-specific primers, tests with even greater sensitivity are needed. Feline trichomonosis is resistant to all commonly used antiprotozoal drugs. Ronidazole is currently the only drug demonstrated to be effective in eliminating the infection from cats; however, this drug has a narrow safety margin and clinical resistance is increasingly recognized. The more we learn about trichomonosis in cats, the more complicated and controversial the infection has become, ranging from what we should call the organism to whether we should even bother trying to treat it. Global importance: Feline trichomonosis is recognized to occur worldwide and is regarded as one of the most common infectious causes of colitis in the domestic cat. The infection is widespread in catteries and shelters; and, while remission of diarrhea may occur over time, persistence of the infection is common. Evidence base: This review provides a comprehensive examination of what is currently known about feline trichomonosis and pinpoints areas, based on the authors' opinion, where further research is needed.

Comparative transcriptomics reveals striking similarities between the bovine and feline isolates of Tritrichomonas foetus: consequences for in silico drug-target identification.

BACKGROUND: Few, if any, protozoan parasites are reported to exhibit extreme organ tropism like the flagellate Tritrichomonas foetus. In cattle, T. foetus infects the reproductive system causing abortion, whereas the infection in cats results in chronic large bowel diarrhoea. In the absence of a T. foetus genome, we utilized a de novo approach to assemble the transcriptome of the bovine and feline genotype to identify host-specific adaptations and virulence factors specific to each genotype. Furthermore, a subset of orthologs was used to characterize putative druggable targets and expose complications of in silico drug target mining in species with indefinite host-ranges. RESULTS: Illumina RNA-seq reads were assembled into two representative bovine and feline transcriptomes containing 42,363 and 36,559 contigs, respectively. Coding and non-coding regions of the genome libraries revealed striking similarities, with 24,620 shared homolog pairs reduced down to 7,547 coding orthologs between the two genotypes. The transcriptomes were near identical in functional category distribution; with no indication of selective pressure acting on orthologs despite differences in parasite origins/host. Orthologs formed a large proportion of highly expressed transcripts in both genotypes (bovine genotype: 76%, feline genotype: 56%). Mining the libraries for protease virulence factors revealed the cysteine proteases (CP) to be the most common. In total, 483 and 445 bovine and feline T. foetus transcripts were identified as putative proteases based on MEROPS database, with 9 hits to putative protease inhibitors. In bovine T. foetus, CP8 is the preferentially transcribed CP while in the feline genotype, transcription of CP7 showed higher abundance. In silico druggability analysis of the two genotypes revealed that when host sequences are taken into account, drug targets are genotype-specific. CONCLUSION: Gene discovery analysis based on RNA-seq data analysis revealed prominent similarities between the bovine and feline T. foetus, suggesting recent adaptation to their respective host/niche. T. foetus represents a unique case of a mammalian protozoan expanding its parasitic grasp across distantly related host lineages. Consequences of the host-range for in silico drug targeting are exposed here, demonstrating that targets of the parasite in one host are not necessarily ideal for the same parasite in another host.

Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats.

Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.

Antiparasitic and immunomodulatory effect of innovative treatments against Myxobolus sp. infection in Diplodus puntazzo.

The potential antiparasitic and immunomodulatory effect of three treatments against myxosporean parasites on the innate immune system of sharpsnout sea bream (Diplodus puntazzo) was investigated. Fish naturally infected with Myxobolus sp. (Bivalvulida/Platysporina), a histozoic parasite mainly affecting the renal interstitial tissue, were treated by oral administration of a combination of salinomycin with amprolium, Origanum essential oil or fumagillin in a small-scale field trial. Various leucocyte functions influenced by myxosporean infection were examined in order to determine treatment effects on leucocyte immunocompetence of treated fish. One month post treatment all drugs caused a significant decrease in prevalence and intensity of infection in comparison to untreated, infected fish. The effect was most prominent in salinomycin with amprolium treated fish, which 1-month post treatment contained either no cysts at all or a few spores free in melanomacrophage centres revealing almost total elimination of the parasite and the antiparasitic action of the treatment. There was no histopathological evidence of drug toxicity. Antiparasitic action was accompanied by a significant enhancement of phagocytic activity demonstrated by ingestion of large numbers of latex beads and the secretion of high levels of reactive nitrogen intermediates by phagocytes in vitro. Complete restoration of the diminished mitogenic responses and serum lysozyme secretion was also detected in salinomycin with amprolium-treated fish compared to untreated, infected fish. These data suggest that salilomycin with amprolium may be a promising treatment for myxosporean infections in intensively cultured warm-water fish, exhibiting action partially via the enhancement of host, innate immune functions and leading to parasite elimination.

Efficacy and toxicity of orally administrated anti-coccidial drugs for innovative treatments of Myxobolus sp. infection in Puntazzo puntazzo.

This study tested drugs and therapeutic compounds to determine effective commercial treatment for fishes infected with myxosporeans. Two series of shore-based experiments and 1 field trial were performed. For the shore-based experiments we used Puntazzo puntazzo (ca. 20 g weight) with kidneys infected with Myxobolus sp. Initially, 6 different doses of Fumagillin, 2 doses of Toltrazuril, and 1 dose of Amprolium, ESB3 and Salinomycin were tested. In the second shore-based experiment, infected fish were treated with Origanum essential oils, Toltrazuril with propylene glycol, Amprolium, and a combination of Salinomycin 12% + Amprolium (SA). In the field trial, P. puntazzo (ca. 165 g) infected with the parasite were treated with SA, Origanum essential oils and Fumagillin. In all trials, the drugs were added to the feed and administered according to the selected regimen. Their efficacy was evaluated in terms of mortality (acceptable level was <3%), pathology and prevalence rate of Myxobolus sp. Lesions were observed only in fish treated with Fumagillin and Toltrazuril. Pathology due to treatment with Fumagillin was observed only at doses > 6 mg kg(-1) body wt for 6 wk in the interstitial renal tissue, where slight inflammation arose. The highest dose tested (25 mg kg(-1)) also produced necrosis in the interstitial tissue, degeneration of the epithelial cells of the tubules and a reduction in melanomacrophage centre numbers. The SA combination proved the most effective treatment for Myxobolus sp. infection of P. puntazzo as (1) the therapeutic regimen and commercial product was not toxic and (2) a significant reduction occurred in the prevalence rate.

Gill infection of Leporinus macrocephalus Garavello & Britski, 1988 (Osteichthyes: Anostomidae) by Henneguya leporinicola n. sp. (Myxozoa: Myxobolidae). Description, histopathology and treatment

Piauçus (Leporinus macrocephalus), were raised in 300 m2 ponds (density of 10 fish/m2) presenting asphyxia signals and daily mortality of 27 fishes. Specimens with 8-cm total body length, were collected for necropsy. Mucus of body surface and pieces of organs were collected and examined microscopically, in wet mounts, stained or in histological sections. The smears examination showed the presence of several spores in the secondary lamellae of the gill filaments, identified as Henneguya leporinicola n.sp (Myxozoa: Myxobolidae). Histopathological study showed epithelial hyperplasia and fulfilling of the spaces between the secondary lamellae, congestion and telangiectasia sinusoidal. It was also observed hyperplasia of the goblet cells and several cysts of parasite with 70.3 microns diameter. Such cysts were situated among the secondary lamellae, covered or not by the hyperplasic epithelium. With this diagnostic, three applications of formalin solution 10 ml/m3 were carried out. Fifteen days after that, fish were examined again to ascertain whether the treatment was efficient on disease caused by the protozoa. The tissue alterations present in the gills after the treatment were just a moderate sinusoidal congestion and a slight epithelial hyperplasia on the base of the secondary lamellae.

Gill infection of Leporinus macrocephalus Garavello & Britski, 1988 (Osteichthyes: Anostomidae) by Henneguya leporinicola n. sp. (Myxozoa: Myxobolidae). Description, histopathology and treatment.

Piauçus (Leporinus macrocephalus), were raised in 300 m2 ponds (density of 10 fish/m2) presenting asphyxia signals and daily mortality of 27 fishes. Specimens with 8-cm total body length, were collected for necropsy. Mucus of body surface and pieces of organs were collected and examined microscopically, in wet mounts, stained or in histological sections. The smears examination showed the presence of several spores in the secondary lamellae of the gill filaments, identified as Henneguya leporinicola n.sp (Myxozoa: Myxobolidae). Histopathological study showed epithelial hyperplasia and fulfilling of the spaces between the secondary lamellae, congestion and telangiectasia sinusoidal. It was also observed hyperplasia of the goblet cells and several cysts of parasite with 70.3 microns diameter. Such cysts were situated among the secondary lamellae, covered or not by the hyperplasic epithelium. With this diagnostic, three applications of formalin solution 10 ml/m3 were carried out. Fifteen days after that, fish were examined again to ascertain whether the treatment was efficient on disease caused by the protozoa. The tissue alterations present in the gills after the treatment were just a moderate sinusoidal congestion and a slight epithelial hyperplasia on the base of the secondary lamellae.

Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy.

Three weak, recumbent neonatal foals with skin lesions, including a thin wooly coat, were born to mares being treated for equine protozoal myeloencephalitis. Mares received sulfadiazine or sulfamethoxazole-trimethoprim, pyrimethamine, folic acid, and vitamin E orally. Foals were anemic, leukopenic, azotemic, hyponatremic, and hyperkalemic. Serum folate concentrations in the 3 foals and 2 mares were lower than those reported in the literature for clinically normal brood mares. Treatment was unsuccessful. For each foal, necropsy revealed lobulated kidneys with thin cortices and a pale medulla, and the spleen and thymus were small. Histologic examination revealed marked epidermal necrosis without inflammatory cells, thin renal cortices, renal tubular nephrosis, lymphoid aplasia, and bone marrow aplasia and hypoplasia. These observations indicate that oral administration of sulfonamides, 2,4-diaminopyrimidines (pyrimethamine with or without trimethoprim), and folic acid to mares during pregnancy is related to congenital defects in newborn foals.