Use of Natural Models to Save Cats with Upper Respiratory Tract Disease or Diarrhea
Center for Companion Animal Studies, Veterinary Teaching Hospital, Colorado State University, Fort Collins, CO, USA
There are many infectious diseases of cats that result in significant clinical manifestations of disease. Those agents that result in upper respiratory tract infections (URI) with resultant sneezing, nasal discharges and conjunctivitis are some of the most common. For example, feline herpesvirus 1 infections have been detected in over 90% of cats housed in shelters (Veir et al. 2008). Other common causes of URI in cats include feline calicivirus, Bordetella bronchiseptica, Chlamydia felis, and Mycoplasma spp. Cats with clinical signs of disease are often not adoptable and treatment of the cases can be expensive. Infectious causes of diarrhea are also common in cats and diarrhea can delay adoption or lead to owner relinquishment of their cats. Common infectious agents associated with diarrhea in cats include Cryptosporidium spp., Cystoisospora spp., Giardia spp., Tritrichomonas foetus (blagburni), and Clostridium spp. Some of these infectious agents also potentially infect humans (zoonoses). Thus, it is important to resolve clinical signs of disease in cats with signs or URI or diarrhea.
There are many ways to acquire research data on treatment of infectious diseases. In some countries, cats bred for research purposes that are housed in barrier facilities to avoid prior exposure to the infectious agent to be studied can be purchased and then inoculated with the infectious disease agent. This pathway is commonly followed for vaccine efficacy studies that require strict, controlled circumstances. For some infectious agents, treatment studies can be performed on experimentally infected cats bred for research. FHV-1 is a notable example as this agent is an effective primary pathogen resulting in predictable disease manifestations. However, other infectious agents are less pathogenic and it can be difficult to study treatments in experimentally infected cats. For example, specific pathogen-free kittens that are inoculated with Giardia Assemblage F or Cryptosporidium felis generally do not develop diarrhea, making it impossible to gather clinical efficacy data of treatment. There are other disadvantages to performing research studies using purpose-bred cats, most notably the need to purchase and make healthy cats sick. Thankfully for some infectious agents, the illness is transient and purpose-bred cats can be adopted after the project ends. In addition, studying cats with clinical signs of URI or diarrhea in the field have other cofactors relating to illness which are impossible to replicate in experimental infection studies which makes detection of positive results powerful. Because of the problems associated with experimental cat studies, many researchers including those in the Center for Companion Animal Studies have emphasized use of natural models in infectious disease research.
In this lecture, I will present examples of infectious disease research involving naturally infected, animal shelter cats. Using these cats, it is optimal to perform positive control studies where all are administered a treatment with a reasonable expectation for success and then the groups compared to see if the treatments are equivalent or if one is superior. The obvious benefits include those to the individual cat (resolution of illness) and to the shelter (conservation of shelter resources because the study pays for everything). But even more importantly is that if the data is collected in a controlled fashion and ultimately published, many more cats around the world can benefit from the work. Several examples will be presented in lecture; the following are two notable examples.
New treatments for URI in cats are greatly needed. When drug companies develop new products, proving efficacy is very important for the drug label as well as to provide information about other uses of the product after it is launched. Recently, the veterinary quinolone, pradofloxacin (Veraflox, Bayer Animal Health) was marketed in some countries. We completed a study of cats with upper respiratory disease complex that had two major objectives: to identify organisms associated with feline rhinitis in a natural setting and to compare the efficacy and safety of pradofloxacin and amoxicillin for the treatment of suspected bacterial rhinitis in cats residing in a humane society (Spindel et al. 2008). Forty humane society cats with suspected bacterial upper respiratory infections were studied. Nasal discharges were collected for performance of infectious disease diagnostic tests prior to random placement into one of three treatment groups. Cats were administered amoxicillin at 22 mg/kg q12h, pradofloxacin at 5 mg/kg q24h, or pradofloxacin at 10 mg/kg q24h; all drugs were administered by mouth. Cats failing to initially respond to either pradofloxacin protocol were crossed to the amoxicillin protocol and cats that failed amoxicillin were crossed to one of the two pradofloxacin protocols.
The organisms most frequently isolated or amplified by polymerase chain reaction assays (PCR) pretreatment were feline herpesvirus-1 (75%), Mycoplasma species (62.5%), Bordetella species (47.5%), Staphylococcus species (12.5%) and Streptococcus species (10.0%).
The initial treatment was amoxicillin for 15 cats, pradofloxacin at 5 mg/kg for 13 cats, and pradofloxacin at 10 mg/kg for 12 cats. Of the amoxicillin-treated cats, clinical signs resolved in 10 cats (66.7%) and five cats were switched to pradofloxacin (10 mg/kg for one cat and 5 mg/kg for 4 cats), after which clinical signs resolved in 4. Of the pradofloxacin-treated cats (5 mg/kg), clinical signs resolved in 10 cats (76.9%) and 3 cats were switched to amoxicillin after which clinical signs resolved in all 3. Of the pradofloxacin-treated cats (10 mg/kg), clinical signs resolved in 11 cats (91.7%) and one cat was switched to amoxicillin after which clinical signs resolved. Overall, 73.7% of amoxicillin-treated cats resolved and 83.3% of pradofloxacin-treated cats resolved. Drug toxicity was not noted and all cats were reported to tolerate the administration of the drug. We concluded in the manuscript that pradofloxacin can be a safe, efficacious therapy for some cats with suspected bacterial upper respiratory infections (Spindel 2008).
The Center for Companion Animal Studies has recently worked extensively with the Purina Veterinary Diets® probiotic, Enterococcus faecium SF-68 (FortiFlora®) which is marketed in some countries. This probiotic has been shown to stabilize the gastrointestinal microbiota and to increase immune functions in kittens (Veir et al. 2007). In a recent study, we hypothesized that cats housed in an animal shelter and fed SF68 would have decreased episodes of diarrhea and improved fecal scores compared to untreated cats in the same environment (Bybee et al. 2011). The cats were all fed a standardized species-appropriate diet and cats in one room were supplemented daily with FortiFlora® and cats in the alternate room were supplemented daily with a placebo. Otherwise, management of the rooms was identical for the duration of the study. To reduce risk of a room influence on the results of the study, the room in which cats were being supplemented with FortiFlora® was switched after 1 month, with a 1-week washout period to lessen the possibility that SF68 surviving in the environment could influence the results of the study. During the study, routine shelter cleaning and disinfection protocols were followed. Prior to cleaning the rooms each morning, feces in the cage of each cat was scored by an investigator blinded to the treatment groups using the Purina Fecal Scoring System for Dogs and Cats. Feces with a score of 4–7 (indicating mild to severe diarrhea) were collected and transported to Colorado State University for infectious disease testing which included microscopic examination for parasite eggs, cysts and oocysts after zinc sulfate centrifugation flotation and immunofluorescent antibody testing (IFA) for Cryptosporidium oocysts and Giardia cysts (Merifluor® Cryptosporidium/Giardia, Meridian Bioscience, Inc., Cincinnati, OH). The percentages of cats with diarrhea lasting 2 days or longer were calculated over the course of the study and the presence of parasites was included as a covariate. Significance was defined as p < 0.05.
The percentage of cats with diarrhea lasting a minimum of 2 days was 7.7% for the probiotic group and 20.7% for the placebo group. This result was significantly different (p = 0.0297), suggesting that administration of SF68 to cats housed in shelters may lessen the numbers of days with diarrhea. As this was a short-term study, this effect was likely a result of probiotic influences on intestinal flora rather than systemic immune enhancement.
1. Bybee SN, Scorza AV, Lappin MR. Effect of the probiotic Enterococcus faecium SF68 on presence of diarrhea in cats and dogs housed in an animal shelter. J Vet Intern Med. 2011;25:856.
2. Spindel ME, Veir JK, Radecki SV, Lappin MR. Evaluation of pradofloxacin for the treatment of feline rhinitis. J Feline Med Surg. 2008;10:472.
3. Veir JK, Ruch-Gallie R, Spindel ME, Lappin MR. Prevalence of selected infectious organisms and comparison of two anatomic sampling sites in shelter cats with upper respiratory tract disease. J Feline Med Surg. 2008;10:551.
4. Veir JV, Knorr R, Cavadini C, Sherrill SJ, Benyacoub J, Satyaraj E, Lappin MR. Effect of supplementation with Enterococcus faecium (SF68) on immune functions in cats. Vet Ther. 2007;8:229.