Interventions and observations associated with survival of orphaned shelter kittens undergoing treatment for diarrhea

Abstract

Objectives

The objective of this study was to identify significant associations between treatment interventions and survival of orphaned shelter kittens with diarrhea.

Methods

Orphaned kittens admitted to a large open-intake municipal animal shelter and entering a volunteer foster care provider network between April 2016 and July 2017 were studied. Individual orphaned kittens for which the care provider sought examination by shelter veterinarians because of clinical signs of diarrhea were included. Treatments administered were recorded and their association with kitten survival to adoption or transfer to a rescue partner was statistically examined.

Results

A total of 1718 orphaned kittens were fostered, among which 220 kittens (12.8%) from 118 different litters were presented for evaluation of diarrhea. A total of 172 (78.2%) kittens underwent treatment for their diarrhea, among which 153 (89.0%) survived to adoption or transfer to a rescue partner and 19 (11.0%) died or were humanely euthanized. Kittens with diarrhea that were ⩾4 weeks of age were 24.8 times more likely to survive (95% confidence interval [CI] 6.8–89.8; P <0.0001). While controlling for age, kittens that received a vitamin and mineral supplement were 12.8 times more likely to survive (95% CI 3.1–52.5; P = 0.0004) than kittens with diarrhea that did not receive the supplement. Treatment with subcutaneous fluids, penicillin G, tube feeding, a probiotic containing Enterococcus faecium SF68, ponazuril or metronidazole did not statistically significantly increase the survival of kittens with diarrhea.

Conclusions and relevance

Age ⩾4 weeks and treatment of diarrhea with a vitamin and mineral supplement favorably improves survival of orphaned kittens to adoption. Application of these findings are likely to improve the health and welfare of this population and contribute to a refinement in use of shelter resources.

Introduction

Cat overpopulation is a welfare challenge in most communities, with an estimated 180 million kittens born each year in the USA. ¹ There are approximately 30–40 million outdoor unowned and feral cats in the USA and it is estimated that these community cats are responsible for 80% of the kittens that are born annually. ¹ During the reproductive season, orphaned kittens are ‘rescued’ from out-of-doors by caring citizens and enter an estimated 3500 brick-and-mortar USA animal shelters at alarming rates. While the exact statistics are unknown, many kittens fostered will die or be euthanized because of severe illness before they reach 8 weeks of age. In one published report, 78% of free-roaming kittens disappeared or died by 6 months of age. ²

Diarrhea is one of the most common health problems of kittens and the majority of deaths of orphaned kittens are associated with clinical signs or post-mortem evidence of gastrointestinal disease.^2–9 Infectious causes of diarrhea, mainly feline panleukopenia virus (FPV) infection, accounts for over half of the deaths of shelter kittens. ³ While there are numerous other causes of diarrheal disease in kittens, diagnostic testing of orphaned kittens is infrequent owing to limited shelter resources. Consequently, orphaned kittens that develop diarrhea are often treated empirically for intestinal bacterial, protozoal or parasitic infections, and are commonly provided supportive care in the form of probiotics, vitamin supplements, subcutaneous fluids or assisted feeding. Given the high morbidity, mortality, labor and resource requirements associated with management of diarrheal disease in orphaned kittens, it is surprising that there are no published studies examining the impact of treatment interventions on survival outcome in this population. Identification of life-saving treatment approaches would be of immediate benefit to the health and welfare of orphaned kittens and the thousands of shelters across the USA tasked to care for them.

A long-term goal of kitten welfare strategies is to improve survival of orphaned kittens by identifying life-saving empirical treatment(s) for kittens with diarrhea. As a step toward that goal, the objective of this study was to identify significant associations between prescribed or preferred treatment interventions and survival outcome of orphaned kittens with diarrhea. The study was undertaken at a large, open-intake municipal animal shelter serving a population of 1 million citizens and having a seasonal caseload of 1831 kittens. The results of this study suggest that kittens receiving a vitamin and mineral supplement for treatment of diarrhea were seven times more likely (95% confidence interval [CI] 2.3–20.6; P <0.001) to survive to adoption or transfer to a rescue partner than were kittens not treated with the supplement.

Materials and methods

Kitten population

This study was conducted at the Wake County Animal Center (WCAC), which serves approximately one million citizens residing in Wake County, North Carolina. Approximately 300 orphaned kittens enter the shelter per month during the reproductive season (May–September) and there are generally 150–200 kittens in foster care during the summer months most years. In this study, all kittens were unowned, <12 weeks of age and <0.9 kg (2 lb) body weight, and relinquished to the WCAC between April 2016 and July 2017. Each kitten was assigned an individual identification/medical record number and tracked using a web-based shelter software program (ShelterBuddy, http://www.shelterbuddy.com).

Upon entry into the shelter, all kittens were administered a single oral dose of ponazuril paste (30 mg/kg; Marquis [15% w/w ponazuril]; Boehringer Ingelheim) and pyrantel pamoate (11 mg/kg; Pyrantel Pamoate Suspension [50 mg/ml]; Columbia Laboratories) and topical administration of (Selamectin Revolution [Selamectin]; Zoetis Parsippany) for treatment of endo- and ectoparasites. Kittens that were estimated to be ⩾4 weeks of age and ⩾0.45 kg were vaccinated by subcutaneous injection with feline viral rhinotracheitis, calicivirus and panleukopenia antigen (Nobivac: Feline 1-HCP; Intervet Merck Animal Health Division).

Kittens estimated to be <3 weeks of age were offered a milk replacer (KMR; PetAg) via bottle. Kittens estimated to be >3 weeks of age were trained to eat a slurry of high-quality canned kitten food (Science Diet Cat Food; Hill’s Pet Nutrition) mixed with water or milk replacer. Once kittens were weaned onto solid food they were offered a free choice of canned kitten food and dry kibble. The type of canned food fed varied with the inventory of a donated stock of commercially available canned food marketed for kittens. All kittens were housed in a dedicated room within the shelter and transferred as soon as possible (average 2–3 days) to the home of a volunteer foster care provider. ¹⁰

Case selection

Any kitten for which the foster care provider requested an examination by the WCAC veterinary team because of clinical signs of diarrhea was included in the study. Kittens were evaluated for appetite by offering warm canned food during the examination and via discussion of clinical history with the foster care provider. Kittens were weighed at the time of examination and the age, sex, number of kittens in the litter and treatments administered were recorded using a Microsoft Excel spreadsheet.

Diagnostic testing

Kittens underwent fecal testing for diarrheal pathogens at the discretion of the shelter veterinarian based on factors such as severity of clinical signs and availability of resources needed for testing. Kittens that exhibited severe clinical illness such as marked weight loss, dehydration, anorexia and lethargy were tested for feline panleukopenia virus (SNAP Parvo; IDEXX Laboratories) ¹¹ prior to treatment. Fecal flotation was performed by trained veterinary assistants using sodium nitrate solution (Fecasol; Vetoquinol USA) with a standard float time of 10 mins followed by microscopic examination for the presence of parasite ova. Testing for the presence of Giardia species antigen in feces was performed using a commercial assay (Giardia Antigen Test Kit; IDEXX Laboratories).

Treatment

Kittens were treated according to a general diarrhea protocol consisting of ponazuril paste (Marquis [15% w/w ponazuril]; Boehringer Ingelheim) administered at a dose of 50 mg/kg PO q24h for 3 days, a liquid vitamin and mineral supplement (Hi-Vite Drops; Vetoquinol USA) dosed at 0.1 ml/lb of body weight PO q24h for 3 days, and a probiotic supplement (Fortiflora; Nestle Purina PetCare) mixed in a small amount of canned cat food every 12 h for 5 days (see Appendix 1 in the supplementary material). Additional treatments were administered at the veterinarian’s discretion based on the clinical condition of the kitten. These treatments included subcutaneous lactated Ringer’s solution (Lactated Ringer’s Injection, USP; Hospira) at 11 ml/kg body weight, oral metronidazole (Metronidazole Benzoate Suspension; RoadRunner Compounded) solution at 25 mg/kg PO q24h for 5 days, and subcutaneous penicillin G procaine (Pro-Pen-G 300,000 units/ml; Bimeda) at 60,000 units/kg. A small subset of kittens also received tube feeding.

Statistical analyses

Continuous data (age, body weight, number of kittens in litter) were described as median and range or interquartile range (IQR). Differences between groups were examined for statistical significance using the Mann–Whitney rank sum test. Categorical data (sex, appetite, testing performed, treatment provided, and outcome) were described in percentages. Differences in percentages between groups were examined for statistical significance using χ² tests with calculation of odds ratio and 95% CIs using a commercially available software program (SigmaStat; Systat Software). Kitten outcome was designated as survivor if the kitten survived to the time of adoption or transfer to a rescue partner organization. Kitten outcome was designated as non-survivor if the kitten died while in foster care or illness severity warranted humane euthanasia. A P value <0.05 was considered significant.

A backward elimination logistic regression model was conducted with variables positively associated with survival and all possible interaction terms were tested using a statistical software program (SAS). The entry criteria for the model was α = 0.3 for selection of entry and α = 0.35 for stay. If no interaction terms were statistically significant, a reduced model was built.

Results

Study population

From April 2016 to July 2017, 3250 kittens were admitted to the WCAC, of which 1718 were fostered at the WCAC or in residences of trained community foster care volunteers. Among kittens in the foster care program, 220 kittens (12.8%) from 118 different litters were examined by the WCAC veterinary team for a chief complaint of diarrhea. Kittens ranged in age from 3 to 12 weeks (median 6 weeks) and weighed between 0.14 and 1.6 kg (median 1.13 kg). Litter size ranged from one to six kittens (median three kittens). Appetite was described as good in 146/220 (66.4%) kittens and poor in 74/220 (33.6%) kittens.

Diagnostic testing

At the time of veterinary evaluation, 109/220 (49.5%) kittens had some form of fecal testing performed. Testing for parvovirus antigen (SNAP Parvo) was performed on feces from 125/220 (56.8%) kittens. Performance of testing for parvovirus antigen (SNAP Parvo) was significantly biased toward the group of kittens that died or were euthanized (n = 53/67; 79%) compared with kittens that survived (n = 72/153; 47.0%)(P <0.0001, χ²). A total of 42/125 (33.6%) tested kittens were positive for parvovirus antigen (SNAP Parvo). The majority of parvovirus antigen-positive kittens (n = 38/42; 90%) died or were humanely euthanized prior to any treatment due to severe diarrhea. The remaining four kittens that tested positive for fecal parvovirus antigen were from three different litters and underwent treatment. Two of the treated, parvovirus-antigen-positive kittens survived and two were humanely euthanized.

Testing for Giardia species antigen (Giardia Antigen Test Kit) was performed on feces from 20/220 (9.1%) kittens. Performance of testing for Giardia species antigen was not biased toward the group of kittens that died or were euthanized (n = 5/67; 7%) vs kittens that survived (n = 15/153; 9.8%). A total of 5/20 (25%) tested kittens were positive for Giardia species antigen. Kittens that died or were euthanized were no more likely to test positive for Giardia species infection than kittens that survived.

Testing for parasitic ova (Fecasol) was performed on feces from 53/220 (24.1%) kittens. Performance of testing for parasitic ova was biased toward the group of kittens that ultimately survived (n = 48/153; 31.4%) vs kittens that died or were euthanized (n = 5/67; 7%) (P = 0.0002 χ²). Of kittens tested for fecal parasitic ova, 13/53 (25%) kittens tested positive for coccidia (10 kittens) or roundworm (three kittens) ova. Kittens that died or were euthanized were no more likely to test positive for coccidia, or roundworm infection than kittens that survived.

Factors associated with treatment outcome

Of the 220 kittens that presented for diarrhea, 67 (30.4%) kittens ultimately died or were humanely euthanized because of their illness (supplementary material: Figure 1). Forty-eight of these kittens died or were euthanized owing to the severity of clinical signs prior to receiving any treatment, including 38 kittens that tested positive for fecal parvovirus antigen.

A total of 172 (78.2%) kittens underwent treatment for their diarrhea. Of the kittens undergoing treatment for their diarrhea, 153 (89.0%) survived to adoption or transfer to a rescue partner and 19 (11.0%) died or were humanely euthanized. Kittens that sur-vived remained in foster care for a median of 35 days (range 1–103 days) prior to adoption or transfer to a rescue partner, while kittens that did not respond to treat-ment died or were euthanized within a median of 6 days (range 1–22 days) following the initial diagnosis of diarrhea (P <0.001 Kruskal–Wallis ANOVA on ranks). Kittens that survived were significantly greater in age (median 7 weeks, IQR 6–9 weeks) at time of treatment for diarrhea than were kittens that died (median 4 weeks, IQR 3–7 weeks; P <0.001 Mann–Whitney Rank Sum). Of the kittens that underwent treatment for their diarrhea, factors associated with increased odds of survival included a good appetite (odds ratio [OR] 2.7, 95% CI 0.94–8.0; P = 0.063), age ⩾4 weeks (OR 16, 95% CI 5.4–47.8; P <0.0001) and body weight ⩾1 kg (OR 5.4, 95% CI 2.0–14.6; P = 0.001).

Kittens with diarrhea that received a vitamin and mineral supplement (Hi-Vite Drops) were seven times more likely to survive (95% CI 2.3–20.6; P <0.001) than kittens with diarrhea that did not receive the supplement (Table 1, Figure 1). Kittens with diarrhea that survived were significantly less likely to have received treatment with subcutaneous fluids (Lactated Ringer’s Injection, USP) (OR 0.12; 95% CI 0.04–0.34; P <0.001), penicillin G (Pro-Pen-G 300,000 units/ml) (OR 0.043; 95% CI 0.013–0.14; P <0.001) or tube feeding (OR 0.107; 95% CI 0.02–0.57; P = 0.015) compared with kittens with diarrhea that died or were euthanized. There was no association between treatment with a probiotic containing Enterococcus faecium SF68 (Fortiflora), ponazuril (Marquis) or metronidazole (Metronidazole Benzoate Suspension) and survival outcome of kittens with diarrhea.

Table 1

Odds ratio for survival to adoption or transfer to a rescue partner of 172 kittens ⩽12 weeks of age that developed diarrhea and underwent treatment while under foster care

Treatment administered	Number (%) of kittens treated (n = 172)	OR	95% CI	P value (χ2)
Vitamin and mineral supplement*	153 (89.0)	6.9	2.3–20.6	<0.001
Probiotic †	142 (82.5)	1.7	0.55–5.0	0.55
Ponazuril	138 (80.2)	1.0	0.31–3.2	0.78
Subcutaneous fluids	52 (30.2)	0.12	0.039–0.34	<0.001
Penicillin G	17 (9.9)	0.043	0.013–0.14	<0.001
Metronidazole	16 (9.3)	0.49	0.13–1.9	0.54
Tube feeding	6 (3.5)	0.107	0.02–0.57	0.015

*

Hi-Vite Drops; Vetoquinol USA

†

Fortiflora; Nestle Purina PetCare

OR = odds ratio; CI = confidence interval

Figure 1

Survival outcome and numbers of kittens that did or did not receive a vitamin and mineral supplement for treatment of diarrhea

Administration of the vitamin and mineral supplement (Hi-Vite Drops) was examined together with the variables of age ⩾4 weeks, weight ⩾1 kg and appetite (good) in a backward elimination logistic regression model. No statistically significant interaction terms were identified among the variables in the model. Both age ⩾4 weeks (OR 24.7; 95% CI 6.8–89.8; P <0.0001) and vitamin and mineral supplementation (OR 12.8; 95% CI 3.1–52.5; P = 0.0004), while controlling for age, were identified as independent predictors of survival.

Discussion

Diarrhea is one of the most common and deadly clinical conditions diagnosed in orphaned kittens; however, the specific prevalence and mortality of diarrhea in this population is unknown. In this study, diarrhea was severe enough to prompt specific examination by shelter veterinarians in 12.8% of orphaned kittens. This percentage is apt to underestimate the true prevalence of diarrhea as kittens were prophylactically treated for common causes of diarrhea (ie, coccidiosis and intestinal parasites) prior to placement in foster care. Among kittens examined for diarrhea, 22% died or were euthanized without treatment, the majority of which were diagnosed with FPV infection based on severity of clinical signs in combination with positive results of a fecal parvovirus antigen assay. These findings agree with results of prior studies in identifying FPV as a prevalent cause of death in this population. ³

In this study, we focused on the 78% of orphaned kittens (n = 172) with diarrhea that underwent some form of treatment, with the aim to identify interventions associated with kitten survival and therefore improved animal welfare. Our study is the first to define a mortality rate of 11% among this subpopulation of orphaned kittens.

Importantly, we identified that kittens with diarrhea that received a commercially available oral vitamin and mineral supplement (Hi-Vite Drops) were seven times more likely to survive than kittens that did not receive the supplement. Although it is possible that the supplement was given preferentially to kittens that were more likely to survive, the majority of kittens (90%) in the study received the supplement, and other treatments having a high prevalence of use in this population (eg, probiotic Enterococcus faecium SF68 [Fortiflora]) were not significantly associated with survival. The WCAC began using the vitamin and mineral supplement in treatment protocols for orphaned kittens with diarrhea based on anecdotal feedback from foster care volunteers that the supplement hastened recovery. Because the supplement contains many vitamins, minerals and micronutrients, it is not possible to determine which ingredient or ingredients might be responsible for the improved outcome of these kittens. It is interesting that the probiotic used in this study also contained some vitamins, minerals and micronutrients but was not positively associated with survival. This suggests unique ingredients or their concentrations in the vitamin and mineral supplement compared with the probiotic may have been more responsible for the survival effect.

Cats have unique nutritional needs due to their carnivorous digestive strategy, which relies on nutritional factors obtained directly from the tissue of other animals. ¹² It is possible that the supplement provided an essential micronutrient that promoted survival of these kittens. In particular, cats require a continuous source of amino acids (especially arginine) to sustain function of the urea cycle, require exogenous vitamin A, D and niacin, and have a higher requirement for thiamine compared with dogs.^12–14 Each of these particular vitamins was present in the vitamin and mineral supplement used in this study, but not contained in the probiotic. While commercial kitten foods should be replete with these micronutrients, the requirements of kittens with diarrhea is unknown. At a minimum the supplement provided a direct source of vitamins and minerals via oral syringe. Given the morbidity and mortality of diarrhea in kittens and significant survival benefit of treatment with the vitamin and mineral supplement used in this study, further evaluation of the vitamin status of kittens appears warranted and may identify additional or more specific treatment approaches for this population.

An additional finding in this study was a lack of association between survival of orphaned kittens with diarrhea and treatment with a probiotic containing E faecium SF68 (Fortiflora). Other studies have shown that shelter cats fed E faecium SF68 were less likely to have diarrhea lasting ⩾2 days than untreated controls. ¹⁵ However, a more recent study of weanling kittens ¹⁶ did not identify any improvement in fecal scores of kittens receiving E faecium SF68 vs placebo. Whether E faecium SF68 influenced the severity or duration of diarrhea in orphaned kittens in this study is unknown; however, it did not influence the overall outcome variable of survival.

Other treatments that were not associated with survival of orphaned kittens with diarrhea included administration of ponazuril or metronidazole. Ponazuril is specifically indicated for treatment of coccidiosis. ¹⁷ All kittens in this study received ponazuril and salamectin for treatment of coccidiosis and intestinal helminths, respectively, prior to entry into foster care. Consequently, kittens with intestinal parasites were likely under-represented in the population of kittens treated for diarrhea in this study. This is supported by our finding that the prevalence of coccidiosis or intestinal helminths in orphaned kittens with diarrhea that had feces examined by flotation in this study was only 19% and 6%, respectively. Therefore, a lack of survival benefit of treatment with ponazuril should not be interpreted as a lack of efficacy of ponazuril, or a low pathogenicity of coccidiosis in orphaned kittens. Metronidazole is reported to be effective in reducing anaerobic bacteria in the duodenum of cats ¹⁸ and is effective for the treatment of Giardia species infections. ¹⁹ Based on the limited number of kittens (n = 20) that had feces tested for Giardia species antigen, it would be difficult to estimate a prevalence of infection of kittens in this study. Metronidazole was prescribed uncommonly to kittens with diarrhea in this study and therefore its lack of association with survival should be interpreted with caution.

Several treatments administered to orphaned kittens with diarrhea were significantly associated with decreased odds of survival. These included treatment with subcutaneous fluids, procaine penicillin G and tube feeding. It is likely that these associations reflect a selection bias for administration of these medications to kittens with the most severe clinical signs of dehydration, possible sepsis and anorexia.

While not the main purpose of this study, we also examined kitten-related variables for association with survival in the treated population. Kittens that survived were significantly older in age at time of treatment for diarrhea than were kittens that died (median 7 weeks vs 4 weeks). Factors associated with significantly increased odds of survival in treated kittens included a good appetite and body weight >1 kg. These data support our clinical experience that older and larger kittens with a normal appetite are better able to withstand the negative effects of diarrhea. When tested in a logistic regression model, both age ⩾4 weeks and treatment with the vitamin and mineral supplement were independently identified as associated with survival.

Several limitations to this study are worth discussion. Not all kittens underwent fecal diagnostic testing and the testing performed was limited in scope to detection of fecal parvovirus antigen, Giardia species antigen and parasitic ova. This reflects both the difficulty of obtaining a sufficient amount of feces from kittens with diarrhea to perform a meaningful analysis and conscientious use of limited shelter resources. The tests that were chosen for use may not be the gold standard for diagnosis of the target pathogens, cannot be used to predict that a diagnosed pathogen is responsible for diarrhea and suffer from limitations in sensitivity or specificity.^20–22 Importantly, it was not the purpose of this study to document specific causes of diarrhea. Results of these fecal tests did allow a crude estimation of the prevalence of Giardia species and coccidia infection in the treated kitten population, which provided some insight into the impact, or lack thereof, of treatment intervention for these infections (ie, metronidazole and ponazuril).

Another limitation of this study is an under-representation of orphaned kittens that tested positive for FPV that underwent treatment. There was a bias for greater FPV testing and an increased prevalence of positive test results among kittens that died or were euthanized prior to receiving treatment. We speculate that a greater severity of diarrhea prompted greater testing and higher likelihood of positive FPV test results in these kittens. Not all kittens in the treatment group were tested for FPV and therefore any role of the infection in influencing mortality in those kittens is unknown. Given the grave impact of FPV on survival of orphaned kittens, studies identifying all infected individuals and treatments associated with increased survival in this population are needed. Unfortunately, the risk of infectious disease spread within the shelter precluded the WCAC from housing or treating sick kittens with positive test results for fecal parvoviral antigen. Kittens that are diagnosed with FPV while in foster care may undergo outpatient treatment if it is considered a humane option. This was the case with four orphaned kittens in foster care that developed diarrhea and underwent treatment in this study.

An additional limitation to this study was the lack of standardization or accounting of diets fed to the foster kittens and therefore inability to determine any impact of diet on survival. Recent studies have demonstrated a dramatic influence of post-weaning diet (canned vs kibble) on the intestinal bacterial community composition of kittens. Interestingly, genes involved in vitamin biosynthesis, metabolism and transport were significantly enriched in the metagenomes of kittens fed a canned diet. ²³ A prospective study examining the influence of diet on vitamin homeostasis and survival of kittens with diarrhea is warranted. Unfortunately, many shelters in the USA rely on donated pet food and commercial kitten diets chosen at the discretion of foster care providers.

A final limitation to this study was that it did not score the severity of diarrhea or examine the influence of treatment on the severity of diarrhea in these kittens. To support their welfare, kittens were treated primarily on an outpatient basis and daily fecal scoring was not considered to be within the scope or purpose of the study. It is fair to assume that the majority of kittens that failed to survive in this study did so for reasons related to their failure to respond to treatment for diarrhea rather than some unrelated cause. Failure to respond to treatment for diarrhea is supported by the short time interval between diagnosis of diarrhea and death or euthanasia of the non-survivor kittens.

Conclusions

This study has identified a 12.8% incidence of diarrhea in orphaned kittens that had previously received prophylactic treatment for coccidiosis and intestinal parasites. In kittens with diarrhea that underwent some form of treatment, the mortality was 11%. Treatment of diarrheic kittens with a vitamin and mineral supplement was associated with a significant increase in odds of survival to adoption or transfer to a rescue partner, thereby improving the welfare of these individual animals. These findings support use of a vitamin and mineral supplement in treatment protocols for orphaned kittens with diarrhea and suggest a need for additional studies to determine the vitamin and mineral status of kittens in this population.

Supplemental Material

Appendix A

Manufacturer-listed analysis of content of the vitamin and mineral supplement and probiotic used in this study

Supplemental Material

Supplementary Figure 1

Flow diagram for outcome of 220 orphaned shelter kittens undergoing treatment for diarrhea