There has been a recent trend in developed countries such as the UK, of feeding dogs and cats raw meat-based diets (Waters, 2017). Investigations of the nutritional value of such diets have suggested that they pose the risk of nutrient imbalances and vitamin deficiencies (Freeman and Michel, 2001; Freeman et al, 2013; Lenox et al, 2015). A topic often discussed is the risk to human and animal health from contamination or infection of raw meat with parasites and zoonotic bacteria, including antimicrobial-resistant bacteria.
Surveillance of Salmonella spp. in pet diets by the Animal and Plant Health Agency in the UK has shown that raw meat diets are 20 times more likely to be positive for Salmonella spp. than processed diets (Animals and Plant Health Agency, 2018). In Brazil, dogs fed raw meat-based diets were 30 times more likely to be positive for Salmonella than dogs on processed diets. Some of the serovars that were isolated are commonly associated with human salmonellosis, and 88% of the isolates were resistant to at least one of the seven classes of antimicrobials tested (Viegas et al, 2020).
Case description:
Clinical presentation
A five-month-old female entire French Bulldog was referred to a specialist veterinary hospital for investigations of acute vomiting, diarrhoea and pyrexia. She was up to date with regular vaccines and prevention against internal and external parasites (Bravecto, MSD Animal Health; and Milprazon, KRKA UK Ltd). She was fed a commercially available poultry-based raw meat diet. She lived with another dog, who was fed a commercial dry diet and was clinically healthy. As the dog was deaf, she was always walked on the lead under strict supervision.
On presentation, the patient was dull, her mucous membranes were pink and dry, respiratory rate was 52 breaths per minute, heart rate was 115 beats per minute, and rectal temperature was 40.3°C. Pulses were of good quality and synchronous. Dehydration was estimated at 7%. Thoracic auscultation and palpation of peripheral lymph nodes were unremarkable. There was moderate abdominal pain diffusely. She weighed 5.2 kg, with a body condition score of 4/9.
Investigations
Haematology showed a mild non-regenerative normocytic normochromic anaemia, monocytosis and eosinopenia, compatible with systemic inflammation (Table 1). There was also a severe thrombocytopenia at 10 x 10^9/l, which was confirmed by blood smear evaluation and persisted for 9 days. The neutrophils showed moderate toxic changes and bacilli were engulfed by poorly preserved leukocytes (Figure 1).
| Result | Reference interval | SI units | |
|---|---|---|---|
| Red blood cells | 4.2 | 5.6–8.4 | × 10^12/l |
| Haematocrit | 26.0 | 37.3–61.7 | % |
| Haemoglobin | 9.1 | 13.1–20.5 | g/dl |
| Mean corpuscular volume | 61.9 | 61.6–73.5 | fL |
| Mean corpuscular haemoglobin concentration | 35.0 | 21.2–25.9 | g/dl |
| Reticulocytes | 19.7 | 10–110 | K/ul |
| White blood cells | 12.4 | 2.9–11.6 | × 10^9/l |
| Neutrophils | 8.8 | 2.9–11.6 | × 10^9/l |
| Monocytes | 1.2 | 0.2–1.1 | × 10^9/l |
| Eosinophils | 0.03 | 0.06–1.2 | × 10^9/l |
| Basophils | 0.01 | 0.0–0.1 | × 10^9/l |
| Platelets | 10 | 148–484 | × 10^9/l |
Biochemistry (Table 2) identified hypoalbuminaemia (15.5 g/l, reference interval 26–35 g/l), likely a combination of intestinal loss and negative acute phase response; and mild total hypocalcaemia, presumably caused by a reduction in protein-bound calcium. Alkaline phosphatase was markedly elevated (1289 U/l, reference interval 20–60 U/l), potentially because of raised endogenous glucocorticoids, growth in a young animal and as a result of cholestasis, the latter supported by the mild elevation in bile acids and cholesterol. Mild hypokalaemia was suspected to be the result of reduced dietary intake and loss through vomiting and diarrhoea. Prothrombin time and activated partial thromboplastin time were within reference interval.
| Result | Reference interval | SI units | |
|---|---|---|---|
| Total protein | 54.9 | 58–73 | g/l |
| Albumin | 15.5 | 26–35 | g/l |
| Globulin | 39.4 | 18–37 | g/l |
| Alanine aminotransferase | 27 | 21–102 | U/l |
| Alkaline phosphatase | 1289 | 20–60 | U/l |
| Bile acids | 29 | 0–10.5 | umol/l |
| Bilirubin | 3.3 | 0–6.8 | umol/l |
| Cholesterol | 7.6 | 3.8–7 | mmol/l |
| Triglycerides | 1.14 | 0.57–1.14 | mmol/l |
| Urea | 3.5 | 1.7–7.4 | mmol/l |
| Creatinine | 41 | 22–115 | umol/l |
| Total calcium | 2.16 | 2.3–3 | mmol/l |
| Phosphate | 1.6 | 0.9–2 | mmol/l |
| Sodium | 148 | 144–160 | mmol/l |
| Potassium | 3.2 | 3.5–5.8 | mmol/l |
| Chloride | 114 | 109–122 | mmol/l |
| Glucose | 5 | 3–5 | mmol/l |
| Prothrombin time | 12 | 11–14 | seconds |
| Activated partial thromboplastin time | 81 | 60–93 | seconds |
Urine analysis was unremarkable and with no proteinuria identified. A faecal Parvovirus antigen test (SNAP Parvo Test, IDEXX) and serology for tick-borne diseases that could cause thrombocytopenia (Borrelia burgdorferi, Anaplasma spp. and Ehrlichia spp.) (SNAP 4Dx Plus, IDEXX) were negative.
Faecal parasitology and an antigen-based Giardia test (SNAP Giardia Test, IDEXX) were negative. Faecal culture was positive for Campylobacter coli, and negative for Salmonella spp. and Yersinia spp. The faecal sample was collected two days after antimicrobial therapy had started, as this was the first time the animal had defaecated since admission.
Abdominal ultrasound identified a fluid-filled, hypomotile small intestine throughout its length consistent with a functional ileus. Additionally, there were mildly enlarged jejunal and mesenteric lymph nodes, which were considered normal for a puppy. Thoracic radiographs and echocardiography were performed to exclude a focus of infection outside the gastrointestinal tract and both were unremarkable.
The left jugular vein was shaved and prepared for aseptic blood collection. Five millilitres of blood were obtained and injected aseptically into a blood culture bottle (Oxoid Signal Blood Culture System, Thermo Fisher Scientific). The needle on the syringe was replaced, and the stopper of the blood culture bottle was cleaned with alcohol before the blood was inoculated. The culture bottle was incubated at 37°C for 48 hours. Blood culture was positive for Salmonella gallinarum, as identified by VITEK®2 (Biomerieux Diagnostics) at a veterinary referral laboratory. The sample was sent to the Scottish Microbiology Reference Laboratories, which confirmed the species and serovar using whole genome sequencing.
Treatment
The animal was treated with fluid therapy to correct dehydration initially, then to address maintenance requirements as well as ongoing losses. Additionally, the dog received maropitant (Prevomax, Dechra; 1 mg/kg intravenously every 24 hours) for an anti-emetic effect, methadone (Comfortan, Dechra; 0.2 mg/kg intravenously every 4–6 hours) for analgesia, fenbendazole (Panacur, MSD Animal Health; 50 mg/kg orally every 24 hours for 5 days) to treat potentially unidentified parasites on faecal parasitology, and amoxicillin-clavulanate (Augmentin, GlaxoSmithKline UK; 20 mg/kg intravenously every 8 hours) for septicaemia.
The pyrexia persisted for a further 24 hours and owing to the lack of clinical response, marbofloxacin was commenced (Marbocyl, Vetoquinol; 5 mg/kg intravenously every 24 hours). Within 12 hours, the pyrexia resolved and the dog's mentation and abdominal comfort improved. Treatment was continued with marbofloxacin (Marbocyl P, Vetoquinol; 3.7 mg/kg orally every 24 hours for 16 days) and paracetamol (Paracetamol Oral Suspension, Crescent; 13 mg/kg orally every 12 hours for 4 days).
Outcome
The patient had no further vomiting or diarrhoea following admission. Marked thrombocytopenia (<5 x 10^9/l) persisted for 9 days, although the patient did not show any clinical signs of petaechiation or haemorrhage.
On day 9 of hospitalisation, the platelet count normalised (198 × 10^9/l; reference interval 148–484 × 10^9/l) and the dog was discharged on oral marbofloxacin. At this point, serum C-reactive protein was measured to allow for a more objective decision on when to stop the antimicrobial, as the volumes necessary for reliable blood cultures and the animal's size were deemed to be limiting factors. The value was elevated at 21.5 mg/l (reference interval < 5 mg/l).
One week later, the animal returned to the primary veterinary surgeon for clinical examination with haematology, albumin and C-reactive protein measurements obtained. All clinical parameters and blood results were within normal limits, with the C-reactive protein levels below the limit of detection. Owing to the complete clinical response, marbofloxacin was stopped and the dog has remained asymptomatic since.
Discussion
Raw meat is claimed by some to be a more natural diet for dogs and cats, with proposed health benefits for the teeth, skin, behavioural disorders and an extensive range of infectious, inflammatory, neoplastic and endocrine diseases (Freeman et al, 2013; BARF World, 2020; Natures Menu, 2020). Aside from improved faecal quality in some studies (Glasgow et al, 2002; Sandri et al, 2017; Animals and Plant Health Agency, 2018), the other proposed health benefits of feeding raw meat-based diets are anecdotal, and there are no controlled studies supporting these statements (Hamper et al, 2017; Davies et al, 2019). Feeding raw meat-based diets may answer a psychological desire among owners to improve their pet's health and care for them, through a route that is simple and easy to understand, compared with more complex and confusing interventions advised by veterinary health professionals (Freeman et al, 2013).
Investigations of the nutritional value of raw meat-based diets have proposed nutrient imbalances and vitamin deficiencies (Freeman and Michel, 2001; Freeman et al, 2013; Lenox et al, 2015). While commercial raw meat-based diets may meet European pet food industry standards, they are commonly formulated without evaluation in feeding trials (Mehlenbacher et al, 2012; Waters, 2017). It is not known whether the raw meat fed to the dog reported in this article was nutritionally balanced for a puppy. One of the paramount concerns regarding raw meat-based diets is the growing number of peer-reviewed publications showing that they carry substantially higher numbers of pathogens, some of which have the potential to cause life-threatening illness in both animals and humans.
Parasites that have been shown to be potentially harboured in raw meat include Toxoplasma gondii (Lopes et al, 2008; Coelho et al, 2011; Freeman et al, 2013; van Bree et al, 2018), Sarcocystis (van Bree et al, 2018), Neospora caninum, Isospora spp, Cryposporidium parvum, Giardia, Echinococcus spp, and Taenia spp (LeJeune and Hancock, 2001; Macpherson, 2005; Silva and Machado, 2016; Davies et al, 2019). The risk to human health or livestock from pets shedding some of these organisms has been well characterised, but objective data on the role of raw meat-based diets with respect to infection by these organisms is limited.
In contrast with the sparse data on the association between raw meat-based diets and parasitic infection, zoonotic bacteria have often been cultured from raw meat directly, or from the faeces shed by the pets that are fed these diets. These include Salmonella spp (Weese and Rousseau, 2006; Finley et al, 2008; Mehlenbacher et al, 2012; Hellgren et al, 2019), Escherichia coli spp (Strohmeyer et al, 2006; Freeman et al, 2013; Byrne et al, 2018; van Bree et al, 2018), Campylobacter spp, Clostridium perfringens, Clostridium difficile (Hellgren et al, 2019; Viegas et al, 2020), Listeria monocytogenes (Nemser et al, 2014; Angelo et al, 2016; van Bree et al, 2018), Yersinia enterocolitica (Bucher et al, 2008), and Brucella spp (Frost et al, 2017). A recent study has also identified a large number of cats with gastrointestinal lesions caused by Mycobacterium bovis, all of which were fed raw meat from a single reputable raw meat-based diet manufacturer (O'Halloran et al, 2018).
Another emerging concern is the isolation of antimicrobial-resistant bacteria from commercial raw diets, including extended-spectrum beta-lactamase Escherichia coli (Wedley et al, 2017; van Bree et al, 2018), AmpC-positive Enterobacteriaceae (Schmidt et al, 2015; Baede et al, 2015; 2017) and multi-resistant strains of Salmonella (Morley et al, 2006; Leonard et al, 2015; Viegas et al, 2020).
Salmonellosis is a food-borne disease of massive public health significance. It is estimated to cause illness in over 20 million people, and death in 150 000 people per year worldwide. There is a great concern regarding the increasing number of antimicrobial-resistant Salmonella strains (Angelo et al, 2016; Saha et al, 2020). Analysis of commercial raw diets for pets have shown Salmonella contamination in proportions ranging from 7% (Strohmeyer et al, 2006; Hellgren et al, 2019) to 21% (Finley et al, 2008; van Bree et al, 2018) in the USA and Europe. Processed pet diets can also be contaminated with Salmonella, but this is 20 times less likely than with raw diets (Animals and Plant Health Agency, 2018).
The dog reported here was infected with Salmonella gallinarum. Considering the animal's lifestyle, which was predominantly indoors and closely supervised when walked on a lead, the other in-contact dog not displaying clinical signs, and the fact Salmonella gallinarum is host-specific to poultry, it is suspected that this infection originated from the raw poultry meat the animal was fed. Dogs may be infected with Salmonella from contaminated food and water, but Salmonella gallinarum is found almost exclusively in poultry. Unfortunately, we were not able to definitively confirm the source of Salmonella gallinarum as a sample of the diet was not available to submit for culture, which we recognise as a major limitation. The relevance of the positive culture of Campylobacter coli is uncertain, as we have no evidence that it originated from the patient's diet or that it caused disease. Several studies have shown that healthy dogs can carry Campylobacter spp., which raises questions regaring the pathogenic role of these organisms in dogs (Duijvestijn et al, 2016; Leahy et al, 2017).
The blood culture technique followed manufacturer recommendations. In the largest study of dogs with suspected bacteraemia performed to date (n=939 dogs), positive blood cultures were obtained from only 15% of dogs and none were positive for Salmonella spp. Only 4% of dogs had blood culture performed from two or three different sites (Greiner et al, 2008).
The decision to treat the patient with a fluoroquinolone antibiotic was based on the previous lack of response to a lower-tier antimicrobial and the recommendation in human medicine to use fluoroquinolones in severe salmonellosis while pending sensitivity results (Crump et al, 2015). Fluoroquinolones are also advised in septicaemia caused by Salmonella in dogs (Greene, 2011). As the dog was septic, a dose at the higher end of the recommended range was chosen (Plumb, 2018). The risk of arthropathy in a growing animal and the off-licence use of a dose above manufacturer's recommendations were discussed with the owner, who consented to these given that the potential benefits were felt to outweigh the risks.
A definitive cause for this dog's thrombocytopenia was not confirmed, although immune-mediated destruction was considered to be most likely and was presumed to be associated with infection. Immune-mediated destruction of platelets has been reported in dogs with a variety of infections (Cortese et al, 2009; Jo'neill et al, 2010; Chirek et al, 2018; França et al, 2018). Platelet-bound antibody testing can confirm that the thrombocytopenia is immune-mediated in origin. However, the test is not readily available and cannot distinguish between primary and secondary immune-mediated destruction (O'Marra et al, 2011). Hence, diagnosis of immune-mediated thrombocytopenia is based on a persistent low count (less than 35x10^9/l) and exclusion of other causes of thrombocytopenia (Botsch et al, 2009). As there was no evidence of gross haemorrhage with this patient, and coagulation times were within reference interval, microthrombi formation secondary to disseminated intravascular coagulation was unlikely, but it cannot be fully excluded as a source of thrombocytopenia. Specific treatment for thrombocytopenia was not required in this dog, with platelet count normalisation coinciding with improved clinical signs following the institution of marbofloxacin.
The owner of this dog appeared unaware of the potential risks associated with raw meat-based diets. A recent study has confirmed that 99% of owners that feed their pets these diets believe it does not pose a health risk to themselves; and 88% of owners believe it does not pose a health risk to their pets either (Viegas et al, 2020). There are several ways through which owners can become infected with bacteria contaminating the raw meat they feed to their pets. This can happen through contact with an infected pet, direct contact with the food when preparing a meal, through ingestion of cross-contaminated human food, or via contact with contaminated surfaces in the house (Overgaauw et al, 2009; Lambertini et al, 2016). Salmonella, for example, can persist in food bowls of pets fed a raw meat diet for at least several days at room temperature, even after cleaning with soap or bleach, or after washing the bowls in the dishwasher (Weese and Rousseau, 2006). Dogs can shed Salmonella for several days after a single meal of contaminated raw meat; and the shedding may continue for up to 8 months if the dog is fed contaminated raw meat over a prolonged period of time (Lefebvre et al, 2008).
Conclusions
This is the first report of septicaemia associated with Salmonella gallinarum, with secondary severe thrombocytopenia, in a dog fed a commercially available raw meat diet. It was not possible to confirm whether the Salmonella originated from the raw meat, as a sample of the diet was not available to submit for culture. This report discusses the risks that raw feeding may pose to pets and their owners, as well as the lack of knowledge surrounding this matter. It is important to better communicate with pet owners about the potential risks and at the very least, veterinarians should advise careful handling of the raw meat and of the faeces of pets that are raw fed. From a clinical perspective, this case also highlights the importance of obtaining a dietary history in those patients where systemic infections are suspected, to aid in the clinical decision-making process.