Between 1995 and 1999, a total of 24 (12 male, 12 female) wild-caught Pallas’ cats (Otocolobus manul) were imported into North America from Russia and Mongolia to establish a founder population of this small-sized felid species. Over the past 5 years, breeding of these Pallas’ cats has resulted in the birth of 45 kittens in 13 litters; however, more than 50% of these kittens have died within 4 months of birth. In almost all kittens subjected to necropsy, the cause of death has been attributed to infection with the protozoal parasite Toxoplasma gondii. As a consequence of toxoplasmosis, only eight of the 24 potential Pallas’ cat founders have surviving offspring in the captive population, with many of the original wild-caught cats approaching reproductive senescence (based on reproductive patterns derived from studbook data). If Pallas’ cats are to be maintained in captivity as a self-sustaining, genetically viable population, then it is imperative that preventive and treatment modalities be established for reducing neonatal losses caused by toxoplasmosis.
One promising new drug, diclazuril, is marketed as an oral anticoccidial agent in Europe, Canada, and South Africa and has proven very effective in a number of domestic species for prevention and treatment of coccidiosis. Diclazuril also has been effective in mice for both prophylaxis and treatment of acute toxoplasmosis. Although diclazuril has established efficacy and a wide margin of safety in other species, there are no published reports of this drug being tested in any felid species. Therefore, the objectives of the present study were to (1) assess the relative toxicity of diclazuril when administered at prophylactic dosages to neonatal domestic cats and (2) begin evaluating the safety and efficacy of diclazuril for preventing and treating toxoplasmosis in neonatal Pallas’ cats.
For drug evaluation in domestic cats, adult queens in the Cincinnati Zoo Center for Research of Endangered Wildlife (CREW) research colony were monitored daily for behavioral estrus and then naturally mated to one of two proven breeder males. Three females became pregnant, subsequently giving birth to a total of 13 viable kittens. Ten kittens were randomly assigned to one of two treatment groups (diclazuril or control). Beginning at 3 days after birth and then every 3 days until 8 weeks of age, kittens were treated orally either with diclazuril (1 mg/kg body weight; Vecoxan, Janssen Animal Health, United Kingdom; 2.5 mg diclazuril/ml) or distilled water (0.4 ml/kg). Blood samples were collected from each kitten beginning at 10 days of age and then weekly thereafter to assess hematologic parameters. Every 3 days, kittens were weighed and measured to monitor body growth. Domestic cat data were evaluated using repeated measures ANOVA.
For initial drug assessment in Pallas’ cats, neonates were treated with diclazuril at two institutions (Cincinnati Zoo and Botanical Garden and the Oakhill Center for Rare & Endangered Species). For evaluation of prophylaxis, five kittens in one healthy litter were treated with diclazuril (1 mg/kg PO) beginning at 7 days after birth and then every 7 days until 12 weeks of age. Two of these kittens were hand-raised whereas the other three kittens remained with the dam throughout the study. To evaluate effectiveness as a treatment option, one kitten with suspected congenital toxoplasmosis was treated daily with diclazuril (10 mg/kg PO) beginning on the first day after birth. This kitten was the only surviving offspring from a litter of six (four stillborn kittens with the fifth kitten dying approximately 12 hours after birth) that were born to a dam with a previous history of in utero toxoplasmosis transmission.
Our preliminary results suggest that diclazuril is safe to administer at low dosages to neonatal domestic cats. Through 3 weeks of age, mean (± SEM) body weight (diclazuril, 460 ± 85 g; control, 406 ± 30 g) and crown rump length (diclazuril, 22.6 ± 1.0 cm; control, 22.5 ± 0.6 cm) did not differ (p>0.05) between treatment groups. Hematologic assessment revealed no differences (p>0.05) over time in white or red blood cell counts or hematocrit values. Biochemical profiles also did not differ (p>0.05), with similar values for serum enzymes (alanine transferase, aspartate transferase, alkaline phosphatase), total bilirubin, cholesterol, total protein, blood urea nitrogen (BUN), BUN/creatinine ratio and glucose levels. In Pallas’ cats, neonatal studies have just been initiated (as of April 2001) and complete findings will not be available until mid-2001. To date, the five kittens receiving diclazuril prophylaxis appear to remain healthy whereas the single kitten receiving diclazuril as treatment for acute toxoplasmosis continues to survive and gain weight slowly (after 7 days of treatment). In conclusion, diclazuril appears to have no adverse effects when administered at a prophylactic dosage every 3 days to newborn felids. Furthermore, we anticipate that our ongoing studies may establish this drug as an effective preventive or treatment option to help reduce the devastating impact of toxoplasmosis on Pallas’ cat conservation efforts.
The authors greatly appreciate the assistance of Dr. Mark Campbell, Cincinnati Zoo and Botanical Garden and John Aynes, Oakhill Center for Rare & Endangered Species, with this study.