20 Aug 2012
Luca Motta
Job TitleLuca Motta discusses the many variables attributed to this condition, and describes the approaches to preventing and treating it
Neospora caninum is a protozoan that may cause neurological signs in dogs. In naturally infected dogs, the predominant route of transmission is considered to be transplacental. With respect to neural and muscular tissues, parasite-containing lesions are found in the muscles, heart, brain, spinal cord, nerve roots, and retina. The clinical sign that should arouse suspicion of neosporosis in puppies less than six months old is ascending paresis/paralysis of the limbs. Older dogs may become ill from reactivation of a chronic subclinical infection. They often have signs of multifocal central nervous system (CNS) involvement. Demonstrating serum antibodies to N caninum can help confirm the diagnosis of neosporosis. Tachyzoites may be found in aspirates or smears from any parasitised tissue or body f luid. Magnetic resonance imaging may help in the diagnosis of CNS and muscle lesions in course of the neosporosis. Puppies that develop severe signs in two to three days are less likely to improve than dogs with more chronic signs. In adult dogs with acute lower motor neuron paralysis and/or CNS involvement, early treatment may be successful. In dogs, N caninum can be transmitted repeatedly through successive litters and this tendency should be considered when planning the breeding of Neospora infected bitches.
NEOSPORA caninum is a protozoan of the phylum Apicomplexa. Under a light microscope, its tachyzoites and tissue cysts (Figure 1) resemble those of Toxoplasma gondii.
The domestic dog or the coyote is the definitive host, and sheds the oocysts following ingestion of N caninum-infected tissues. The shedding period appears to be short (about five days) but, in some instances, has been documented up to four months.
Experimental transmission in dogs has been produced by oral or parenteral administration of Neospora cysts. Large numbers of oocysts are detected after feeding dogs infected tissues from cattle, the natural intermediate host. Dogs infected with sporulated oocysts of N caninum are not able to shed oocysts in faeces. The life cycle and modes of transmission of the parasite are still not completely understood.
In naturally infected dogs, the predominant route of transmission is considered to be transplacental. It may be that the chronically infected bitch develops parasitaemia during gestation, which spreads transplacentally to the fetus. Successive litters from the same subclinically infected dam may be born infected. The majority of – but not all – puppies in a litter have clinical manifestations. Other pups may carry the infection subclinically with reactivation (Figure 2). Reactivation of infection, causing cutaneous, neural, or muscular disease, has occurred following immunosuppressive illnesses or administration of modified live virus vaccines, cytotoxic agents or glucocorticoids.
Naturally occurring infections in dogs have been found throughout the world. Seroprevalence of clinically healthy dogs is usually much less than 20 per cent, but much greater than the prevalence of clinical illness, suggesting subclinical infections. Purebred dogs have been prevalent in published case reports.
In infected carnivores, tachyzoites are found within macrophages, polymorphonuclear cells, spinal fluid neural, and and other cells of the body. Cell necrosis occurs after rapid intracellular replication of tachyzoites. Tissue cysts are found mainly in the brain, spinal cord, peripheral nerves and retina, and occasionally in muscles (Figures 3, 4 and 5).
The clinical sign that should arouse suspicion of neosporosis in puppies less than six months old is ascending paresis/paralysis of the limbs.
Signs are often noticed at three to nine weeks of age. The pelvic limbs are more severely affected than the thoracic limbs. Paralysis progresses to rigid contracture of muscles (especially the quadriceps femoris) of affected limbs, which may lead to severe arthrogryposis (Figures 6, 7, 8, 9 and 10). This is a result of the muscle fibrosis secondary to the lower motor neuron damage and myositis. In some pups, joint deformation may develop. Cervical weakness, dysphagia, megaoesophagus, head tilt and, ultimately, death may occur. In some dogs, the progression may become static.
Older dogs most likely become ill from reactivation of a chronic subclinical infection. They often have signs of multifocal central nervous system (CNS) involvement, with or without polymyositis. Less common manifestations result from myocarditis, dermatitis, pneumonia, or multifocal dissemination. Neurological signs associated with CNS neosporosis include tetraparesis that can progress to paralysis, appendicular muscular atrophy, masticatory muscle myositis, head tilt, seizures, cerebellar ataxia, brainstem signs, myoglobinuria and trigeminal neuropathy (Table 1). Death from diffuse CNS or muscle inflammation can occur in dogs of any age. Some puppies do not develop intracranial neurological signs. They can survive for months with hand feeding and care, but remain paralysed with associated complications.
Routine haematological tests and serum biochemistry are not useful in supporting a diagnosis of neosporosis, and may reveal increased creatine kinase (CK), aspartate amino transferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) activities.
Cerebrospinal fluid (CSF) abnormalities have included mild increases in protein concentration and nucleated cell count. Lymphocytes, monocytes and macrophages, neutrophils and eosinophils may be found in the CSF. CSF analysis may also reveal tachyzoites, and CSF results can be within refer ence limits. CSF polymerase chain reaction (PCR) testing can help in diagnosing active CNS N caninum infection.
Electromyographic abnormalities may be observed, including fibrillation potentials, positive sharp waves and repetitive discharges (Figure 11). Motor and sensory nerve conduction velocities may be reduced in the most severely affected limbs, but they are often within the reference range.
Demonstrating serum and CSF antibodies to N caninum can help in confirming the diagnosis of neosporosis. Assays have included indirect fluorescent antibody test (IFA), enzyme-linked immunosorbent assay (ELISA), immunoprecipitation and multiplex PCR. Serum immunofluorescence assay (IFA) titre results can vary between laboratories – however, in some reference laboratories, values of 1: 50 or greater are considered positive, and values are often greater than 1: 800. Antibodies to N caninum may also be found in CSF samples, although at lower titres than in serum.
Positive titres can exist in previously exposed dogs that may be infected, but they remain non-symptomatic, with values of 1: 800 or greater, for years. Occasionally, animals with histologically confirmed infections have low titre results.
A study aiming to evaluate occurrences of antibodies against N caninum and Toxoplasma gondii in 147 dogs with neurological signs revealed 11.5 per cent were seropositive for N caninum, 21 per cent for T gondii and 2.7 per cent for both protozoa. Serum titration on the positive animals showed that 54.8 per cent and 41.2 per cent had titres equal to or more than 1: 200 against T gondii and N caninum, respectively. This study shows that inclusion of serological tests for neosporosis and toxoplasmosis is recommended in diagnosing neurological diseases in dogs. Tachyzoites can be found in aspirates or smears from any parasitised tissue or body fluid.
Biopsy of affected muscle is potentially a valuable antemortem test that may yield a definitive diagnosis when organisms are detected. The author recommends serology and CSF-PCR for the diagnosis of active N caninum infection.
Advanced diagnostic imaging may help in diagnosing CNS and muscle lesions in the course of neosporosis. The presence of bilaterally symmetrical cerebellar atrophy and loss of contrast between cerebellar grey and white matter on magnetic resonance imaging (MRI) is a common finding in adult dogs. Contrast enhancement of the affected cerebellar meninges and meninges surrounding the brainstem may be seen, especially in acute cases. MRI lesions have been rarely detected in the masticatory muscles, and in the corona radiata of the occipital lobe.
With respect to neural and muscular tissues, parasite-containing lesions are found in the muscles, heart, brain, spinal cord, nerve roots and retina.
Nonsuppurative encephalomyelitis, polyradiculoneuritis, ganglionitis, myositis (of all striated muscles) and myofibrosis are the predominant histological findings. Polyradiculoneuritis is a more typical feature of infection in pups. Parasites are most consistently found in the cerebrum, regardless of the clinical presentation. Cerebellar cortical necrosis, atrophy and inflammation may be found in adult dogs.
Information on effective therapy for neosporosis is limited. However, drugs used in therapy for toxoplasmosis should be tried early in the course of illness. Clindamycin, sulfadiazine and pyrimethamine alone or in combination have been administered to treat canine neosporosis.
In puppies, clinical improvement is not likely in the presence of muscle contracture or rapidly advancing paralysis. Puppies that develop severe signs in two to three days are less likely to improve than dogs with more chronic signs (more than three weeks between onset of signs and examination).
To reduce the chance of illness, all dogs in an affected litter should be treated as soon as the diagnosis is made in one littermate. Older (more than 16 weeks) puppies and adult dogs respond better to treatment. In adult dogs with acute lower motor neuron paralysis from myositis, early treatment may be successful because scar contracture is less common. Myositis and cerebellitis have responded to therapy with a combination of clindamycin, trimethoprim, sulfadiazine and pyrimethamine.
No drugs are known to prevent transplacental transmission. Clindamycin i s effective in suppressing the replication and dissemination of tachyzoites, but does not appear to be effective against encysted bradyzoites.
In dogs, N caninum can be transmitted repeatedly through successive litters and litters of their progeny.
This tendency should be considered when planning the breeding of Neospora-infected bitches. Dogs should not be fed uncooked meat, especially beef or aborted materials. They should be prevented from defaecating in feed troughs, watering sources, pastures or livestock-holding pens where cattle are housed. No vaccine has been developed to prevent neosporosis.
The zoonotic potential of N caninum is unknown. There is no direct evidence the organism can infect people, although serologic evidence suggests that people are exposed to the organism. In examining sera from 76 women with a history of abortions, none had detectable serum antibodies to the parasite.
A study used 1,029 sera collected from presumably healthy individuals in an area in which N caninum infection of dairy cattle was known to be endemic. Only 6.7 per cent of patients had titres of 1: 100 by IFA testing. The infection of healthy individuals by N caninum may follow a course similar to that of T gondii, where the vast majority of infections are asymptomatic.
• Not all drugs mentioned are licensed for use in dogs.
Luca Motta
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