Toxoplasma gondii is an intracellular protozoan parasite that can cause meningoencephalitis in infected dogs and cats, while Neospora caninum is a protozoan parasite that can cause neurological disease only in dogs. The life cycles of T. gondii and N. caninum are similar, with cats and dogs as their definitive hosts, respectively.
Host infection occurs in three ways: transplacentally (tachyzoites), via the ingestion of faecally shed oocysts (cats are the definitive hosts and shed oocysts) and/or the ingestion of organisms in intermediate hosts (tachyzoites and bradyzoites). The most common cause of T. gondii infection in dogs and cats is through ingesting tissue from infected intermediate hosts (mice or raw/undercooked meat). In young dogs, N. caninum is normally transmitted vertically in utero, while in adults, infection is often through ingesting infected faeces or muscles.
What are the clinical signs of toxoplasmosis and neosporosis?
Clinical signs of both T. gondii and N. caninum can be acute or chronic and are often present in young or immunocompromised animals. Signs are often reflective of only central nervous system (CNS) disease, although these protozoal parasites can affect multiple organ systems, such as the eyes, lungs and gastrointestinal tract. Neurological signs can include seizures, cranial nerve deficits and cerebellar and neuromuscular signs, as concurrent myopathy may also be present in dogs with protozoal meningoencephalitis. Infection can be present also in the cardiac muscles. Neurological dysfunction is believed to be caused by the intracellular proliferation of tachyzoites.
Animals affected with toxoplasmosis or neosporosis often present with concurrent ophthalmic and neurological signs […] therefore, a thorough ophthalmological examination should be performed
Animals affected with toxoplasmosis or neosporosis often present with concurrent ophthalmic and neurological signs, particularly young dogs and cats. Therefore, a thorough ophthalmological examination should be performed in neurological cases to look for fundic changes and/or uveitis compatible with inflammatory disease.
Protozoal radiculitis is commonly caused by N. caninum in young dogs (although, in the past, this was attributed to T. gondii infections), but can affect dogs at any age. It also has a preference for the lumbosacral spinal nerve roots of young dogs and can cause myelitis and polymyositis.
Affected dogs can be normal at birth, developing an asymmetric paraparesis and plantigrade stance afterwards. A characteristic early sign of disease is progressive rigidity of one or more limbs (genu recurvatum) as the result of myositis and neuritis. Ataxia and a “bunny-hopping” gait may develop along with hyporeflexia and severe muscle atrophy in the pelvic limbs, which can lead to arthrogryposis.
In adult dogs, N. caninum has a predilection for the cerebellum. Thus, a syndrome of the brainstem and cerebellar dysfunctions has been described in dogs affected by necrotising cerebellitis, with symmetrical cerebellar atrophy revealed on magnetic resonance imaging (MRI).
How do we diagnose toxoplasmosis and neosporosis?
A diagnosis of toxoplasmosis or neosporosis relies on proving an active infection through clinical signs and positivity to serology or polymerase chain reaction (PCR) testing and eventual positive response to antiprotozoal treatment. This is because identifying the organisms can be difficult in the living patient. Serum antibodies can confirm infection in affected patients, but an autopsy can confirm the presence of the organism in the lesions, therefore providing a definitive diagnosis.
A diagnosis of toxoplasmosis or neosporosis relies on proving an active infection […] and eventual positive response to antiprotozoal treatment
Solitary or multiple mass lesions can be found on MRI images of the brain of infected animals. In dogs infected with N. caninum,features on an MRI scaninclude:
- cerebellar atrophy
- loss of contrast between grey and white matter
- T2/FLAIR hyperintensities in the cerebellum
- T2 hyperintense material surrounding the cerebellum and extending into the sulci
- meningeal contrast enhancement
Multifocal T2 hyperintense contrast-enhancing parenchymal lesions with associated brain oedema may be seen on MRI scans of cats infected with T. gondii.
Serology and haematology
Immunoglobulin M (IgM) antibodies can be measured for T. gondii, and a positive IgM response suggests active infection even with a negative immunoglobulin G (IgG) response. A fluorescent antibody test can also detect specific antibodies for N. caninum. IgG antibodies against both T. gondii and N. caninum can be measuredin dogs and cats, and there is no cross-reactivity between the antibody tests.
A single positive antibody titre does not establish a definitive diagnosis, as dogs and cats may be exposed to these organisms without developing clinical disease. Only a fourfold increase in serum antibody titres over three to four weeks is supportive of active infection. Dogs with clinical neosporosis have serum titres greater than 1:200, but titres greater than 1:800 can be seen in clinically normal dogs.
Cerebrospinal fluid (CSF) analysis can show mild to moderate inflammation with increased protein concentration and pleocytosis with a mixed population of leucocytes (neutrophils and small or large mononuclear cells with occasional eosinophils).
A presumptive diagnosis of toxoplasmosis is based on positive antibody titres in the CSF, but a positive titre can also be seen in animals previously exposed to the organism. Thus, PCR assays performed on CSF can aid in the antemortem diagnosis of toxoplasmosis and neosporosis.
Serum and CSF anti-Neospora antibody titres are more reliable than serum titres alone. However, evidence of a serum rising titre should be obtained for both infections, especially if there is only an increase of IgG antibodies and not IgM.
Creatine kinase (CK) blood concentrations can be increased in cases of myositis, while electrophysiologic testing can support the suspicion of neuropathy and myopathy. Muscle and nerve biopsies can show the presence of inflammation, bradyzoites in muscles and tachyzoites in the nerves or the CNS.
In a recent study, serum CK and aspartate aminotransferase (AST) activities were significantly increased in dogs with positive serology for N. caninum (Jones and Harcourt-Brown, 2022). Therefore, CK and AST serum activity can be used as a rapid screen for predicting positive serology in dogs with meningoencephalitis caused by N. caninum while waiting for the serology or PCR test results. Treatment can then be started early in these patients, increasing the chances for recovery.
How can we treat toxoplasmosis and neosporosis?
Treatment for toxoplasmosis and neosporosis should be started as soon as possible, as it will increase the chances of recovery. In animals with CNS protozoal infections, treatment with clindamycin (at a dose of 12.5 to 25mg/kg orally or intramuscularly for cats and 10 to 20mg/kg orally or intramuscularly for dogs) and/or trimethoprim/sulphonamide (15 to 30mg/kg) every 12 hours for three to four weeks (up to six as a maximum) is recommended.
Treatment for toxoplasmosis and neosporosis should be started as soon as possible, as it will increase the chances of recovery
Adverse effects of clindamycin can be diarrhoea, vomiting (especially in cats) and reduced appetite. Furthermore, in cases involving ocular forms of disease and with chronically infected animals, clindamycin might not be effective against all organisms in the CNS.
Trimethoprim/sulphonamide can be combined with pyrimethamine (1 mg/kg orally every 24 hours) once the diagnosis has been confirmed. However, cats may develop myelosuppression after more than two weeks of trimethoprim/sulphonamide and pyrimethamine therapy. Therefore, they require folic acid replacement when using this treatment method. Trimethoprim/sulphonamide treatment can be associated with adverse hepatic drug reactions in dogs, and therefore should not be used in dogs with hepatic disease.
What is the prognosis for cats and dogs with toxoplasmosis or neosporosis?
Neurological signs tend to improve with treatment, but they may not resolve completely due to permanent damage caused by the organism
In animals diagnosed with toxoplasmosis or neosporosis infections that cause neurological signs, the prognosis is guarded. Neurological signs tend to improve with treatment, but they may not resolve completely due to permanent damage caused by the organism. If muscle contracture is present, for example, recovery is unlikely. Progression of the disease can be prevented if antiprotozoal treatment is started early in affected animals (especially puppies) showing neurological signs. Relapses are also possible, even with marked improvement or complete remission of the neurological signs.