Difference between revisions of "Toxoplasmosis - Cat and Dog"

From WikiVet English
Jump to navigation Jump to search
 
(59 intermediate revisions by 2 users not shown)
Line 1: Line 1:
==Description==
+
{{OpenPagesTop}}
 
+
==Introduction==
''Toxoplasma gondii'' is an obligate, intracellular coccidian parasite that is capable of infecting most mammals including man. Cats and other Felidae are the definitive host for ''T. gondii'', and all other mammals are intermediate hosts. ''Toxoplasma gondii'' has three infectious stages: 1) sporozoites; 2) an actively reproducing stage called tachyzoites; and 3) slowly multiplying bradyzoites. Tachyzoites and bradyzoites are found in tissue cysts, whereas sporozoites are containted within oocysts, which are excreted in the faeces. This means that the protozoa can be transmitted by ingestion of oocyst-contaminated food or water, or by consumption of infected tissue. Transplacental infection is also possible.
+
[[Image:Toxoplasmosis Life Cycle.jpg|thumb|right|300px| Life cycle of ''Toxoplasma gondii''. Source: Wikimedia Commons; Author: LadyofHats (2010)]]
 
 
===Life Cycle===
 
[[Image:Toxoplasmosis Life Cycle.jpg|thumb|right|300px|Life cycle of ''Toxoplasma gondii''. Source: Wikimedia Commons; Author: LadyofHats (2010)]]
 
In the naive definitive host, ''Toxoplasma gondii'' undergoes an enteroepithelial life cycle. Cats become infected by ingesting intermediate hosts containing tissue cysts, which release their bradyzoites in the gastrointestinal tract when the wall is digested. Bradyzoites then penetrate the small intestinal epithelium and produce five types of schizonts, which then give rise to merozoites. Male and female gamonts are formed from merozoites, which fertilise to form a macrogamont. A wall forms aroung the macrogamont to produce an oocyst, which is passed in the faeces approximately three days after ingestion of the tissue cyst. Initially, these oocysts are unsporulated and are therefore not infectious, but after 1 to 5 days sporulation occurs to produce two sporocysts, each with four infectious sporozoites. This sporulation is dependent on temperature and aeration, and sporocysts can remain viable in the environment for up to 18 months even if exposed to high or freezing temperatures and low humidity. As cats generally develop immunity to ''T. gondii'' after the initial infection, they will only shed oocysts once in their lifetime.
 
 
 
When other, non-feline, carnivores (such as dogs) consume tissue cysts or oocysts from cat faeces, ''Toxoplasma gondii'' initiates extraintestinal replication. This process is the same for all hosts, and does not vary with the form of the parasite ingested. Bradyzoites and sporozoites, from cysts and oocysts respectively, are released in the intestine and infect the intestinal epithelium where they replicate. This produces tachyzoites, which are lunate in shape, about 6 microns in diameter and possess the ability to multiply in almost any cell type. The infected cell ruptures to release tachyzoites which then disseminate via blood and lymph to infect other tissues. Tachyzoites then replicate intracellularly and, if the cell does not burst, they eventually encyst and persist for the life of the host. Tissue cysts readily form in the CNS, muscles and visceral organs.
 
 
 
===Transmission===
 
 
 
Although any of the three life stages described above can infect warm-blooded vertebrates, most infections are acquired following the ingestion of sporozoites or bradyzoites, as tachyzoites are easily inactivated in the gastric environment. As cats rarely practice coprophagy, infection is usually acquired through the ingestion of infected intermediate hosts such as rodents. Dogs tend to consume food or water contaminated with oocysts from cat faeces.
 
 
[[Image:Toxoplasmosis Tissue Cyst.jpg|thumb|right|200px| Toxoplasma tissue cyst. Source: Wikimedia Commons; Author: Marvin 101 (2008)]]  
 
[[Image:Toxoplasmosis Tissue Cyst.jpg|thumb|right|200px| Toxoplasma tissue cyst. Source: Wikimedia Commons; Author: Marvin 101 (2008)]]  
If a pregnant queen  is naive to ''Toxoplasma gondii'' at the time of ingestion, transplacental infection can occur. The outcome of this depends on the stage of gestation. Infection during the first trimester usually has severe consequences, such as stillbirth or abortion; infection during the second or third trimesters are more likely to give rise to an infected foetus. Kittens infected neonatally commonly show interstitial pneumonia, necrotising hepatitis, myocardidits, non-suppurative encephalits and uveitis on post-mortem examination<Sup>1</sup>.
 
  
===Pathogenesis===
+
Toxoplasmosis is caused by ''[[Toxoplasma gondii]]'' infection. Its life cycle is described in the pathogen page, ''[[Toxoplasma gondii]]''.
  
The outcome of primary infection depends on the immune status of the host, as well as the location of and degree of injury caused by tissue cysts. Primary infection normally results in chornic disease, where tissue cysts form but clinical signs are not normally apparent. In immunodeficient animals, or in animals with concurrent illness, chronic infections may become symptomatic as the organism is allowed to proliferate. Acute primary infection in these animals can, rarely, prove fatal.  
+
==Pathogenesis==
 +
The outcome of primary infection depends on the immune status of the host, as well as the location of and degree of injury caused by tissue cysts. Primary infection normally results in chronic disease, where tissue cysts form but clinical signs are not normally apparent. In immunodeficient animals, or in animals with concurrent illness, chronic infections may become symptomatic as the organism is allowed to proliferate. Acute primary infection in these animals can, rarely, prove fatal.  
  
The mechanism of clinical disease in chronic toxoplasmosis is not fully understood, but may be related to low-level tachyzoite replication, or intermittent antigenaemia and parasitemia<sup>2</sup> have been detected in experimentally
+
The mechanism of clinical disease in chronic toxoplasmosis is not fully understood, but may be related to low-level tachyzoite replication, or intermittent antigenaemia and parasitemia<sup>2</sup>. The pathogenesis of disease could also be associated with immunological reactions against the organism through formation and deposition of immune complexes, and delayed hypersensitivity reactions<sup>3</sup>.
inoculated cats (Burney and others 1999). The pathogenesis of disease could also be associated with immunological reactions against the organism through formation and deposition of immune complexes, and delayed hypersensitivity reactions<sup>4</sup>.
 
  
 
==Signalment==
 
==Signalment==
 +
Cats more commonly show clinical disease than dogs. Male cats are predisposed, and the average age of the feline toxoplasmosis patient is 4 years (range: 2 weeks to 16 years)<sup>4</sup>.  There are no breed predilections.
  
Cats more commonly show clinical disease than dogs. Male cats are predisposed, and the average age of the feline toxoplasmosis patient is 4 years (range: 2 weeks to 16 years)<sup>3</sup>.  There are no breed predilections.
+
==Clinical Signs==
 +
Clinical signs are determined by the site and extent of organ damage by tachyzoites, and may be acute or chronic. Acute signs manifest at the time of initial infection, whereas chronic signs are associated with reactivation of encysted infection during times of immunocompromise.  
  
==Diagnosis==
+
In '''cats''', disease is most severe in transplacentally infected kittens, which may be stillborn or die before weaning. Those that survive are anorexic and lethargic, with a pyrexia that does not respond to antibiotics. The lungs, liver or CNS may be necrosed, leading to signs such as dyspnoea, respiratory noise, icterus, ascites and neurological signs. Kittens infected neonatally commonly show interstitial pneumonia, necrotising hepatitis, myocardidits, non-suppurative encephalits and uveitis on post-mortem examination<Sup>1</sup>.
===Clinical Signs===
 
  
Clinical signs are determined by the site and extent of organ damage by tachyzoites, and may be acute or chronic. Acute signs manifest at the time of initial infection, whereas chronic signs are associated with reactivation of encysted infection during times of immunocompromise.  
+
Cats infected post-natally most commonly display gastrointestinal and/or respiratory signs. Again, animals may be anorexic and lethargic, with an antibiotic non-responsive fever. Vomiting, diarrhoea, icterus or abdominal effusion may be apparent, and the cat may lose weight. Ocular signs such as uveitis, iritis and detachment of the retina are also common. Neurologic signs are seen in less than 10% of patients <sup>4</sup> and may present as circling, torticollis, anisocoria, seizures, blindness or in-coordination. Signs progress rapidly in patients suffering acute disease, in whom respiratory and/or CNS involvement is common. Chronic infections tend to follow a slower course.
  
In cats, disease is most severe in transplacentally infected kittens, which may be stillborn or die before weaning. Those that survive are anorexic and lethargic, with a pyrexia that does not respond to antibiotics. The lungs, liver or CNS may be necrosed, leading to signs such as dyspnoea, respiratory noise, icterus, ascites and neurological signs. Cats infected post-natally most commonly display gastrointestinal and/or respiratory signs. Again, animals may be anorexic and lethargic, with an antibiotic non-responsive fever. Vomiting, diarrhoea, icterus or abdominal effusion may be apparent, and the cat  may lose weight. Ocular signs such as uveitis, iritis and detachment of the retina are also common. Neurologic signs are seen in less than 10% of patients <sup>3</sup> and may present as circling, torticollis, anisocoria, seizures, blindness or inco-ordination. Signs progress rapidly in patients suffering acute disease, in whom respiratory and/or CNS involvement is common. Chronic infections tend to follow a slower course.
+
In young '''dogs''', ''Toxoplasma gondii'' infection is usually generalised, causing fever, weight loss and anorexia. Dyspnoea, diarrhoea and vomiting may also be seen. Older animals more commonly experience localised infections which are primarily associated with the neural and muscular systems. When neurological signs are seen, they usually reflect diffuse inflammation of the CNS. For example, dogs might suffer seizures, ataxia, paresis or muscle weakness. Although cardiac involvement occurs, this is not normally clinically significant. Ocular changes are rare, but are similar to those described in cats.
 
 
In young dogs, ''Toxoplasma gondii'' infection is usually generalised, causing fever, weight loss and anorexia. Dyspnoea, diarrhoea and vomiting may also be seen. Older animals more commonly experience localised infections which are primarily associated with the neural and muscular systems. When neurological signs are seen, they usually reflect diffuse inflammation of the CNS. For example, dogs might suffer seizures, ataxia, paresis or muscle weakness. Although cardiac involvement occurs, this is not normally clinically significant. Ocular changes are rare, but are similar to those described in cats.
 
  
 
===Laboratory Tests===
 
===Laboratory Tests===
 +
Demonstration of ''Toxoplasma gondii'' in the tissues with associated inflammation is required for the definitive diagnosis of clinical toxoplasmosis. For example, tachyzoites may be seen in blood, cerebrospinal fluid, peritoneal and pleural effusions, aqueous humour or transtracheal washes from clinically ill animals. ''Toxoplasma gondii'' may also be detected in these samples using PCR, tissue culture or animal inoculation techniques<sup>1</sup>. These methods may be employed on tissue biopsies too, as well as examination under haematoxylin and eosin or immunohistochemical staining. Immunohistochemistry is preferred to H&E because it is specific for ''T. gondii''. Demonstration of the organism is often most easily achieved post-mortem, as the size of the sample is not restrictive to the likelihood of seeing ''T.gondii''. In the absence of demonstration of ''Toxoplasma gondii'' in the tissues or fluids ante-mortem, there is no one specific test to diagnose toxoplamosis. However, a combination of various diagnostic procedures can be used to build a presumptive diagnosis. 
  
Routine haematology, biochemistry and urinalysis show no changes specific for toxoplasmosis. However, during ''T. gondii'' infection, several features may be seen and could be suggestive. For haematology, these might include: non-regenerative anaemia, neutrophilic leucocytosis, lymphocytosis, monocytosis, neutropenia or eosinophilia. Biochemical profiles could show increased creatine kinase, ALT, SAP, bilirubin and total protein, and proteinuria and bilirubinuria may be revealed by urinalysis.<sup>1</sup>
+
Firstly, clinical signs should be suggestive of toxoplasmosis, despite variation in the presentation of disease between individuals. Although no pathognomic changes for toxoplasmosis are seen on routine haematology, biochemistry and urinalysis, certain results are often seen in ''T. gondii'' infection. For example, most cats show a mild non-regenerative anaemia, and 50% of patients are initially leukopenic due to [[lymphopenia]]. [[Neutropenia]] may occur in conjunction with lymphopenia, and leukocytosis may occur during recovery<sup>4</sup>. Most patients also show and increase in creatine kinase, ALT, SAP, and hypoalbuminaemia is also common<sup>1, 4</sup>. 25% of cats show hyperbilirubinemia and [[icterus]], and [[Pancreatitis|pancreatitis]] may cause low to low normal serum calcium. A mild proteinuria and bilirubinuria are often revealed by urinalysis.
  
CYTOLOGY AND CEREBROSPINAL FLUID
+
Demonstration of antibodies in serum is indicative of exposure to ''T. gondii'', but does not necessarily show active infection. This could be overcome by testing for ''T. gondii'' antigen or immune complexes, but these methods are currently only available to researchers. Several techniques are commercially available for detection of antibody, including [[ELISA testing|ELISA]], [[Immunofluorescence|immunofluorescent antibody testing]], Sabin-Feldmann dye test, and [[Agglutination|agglutination tests]]. Although these tests are theoretically able to detect all classes of immunoglobulin against ''Toxoplasma gondii'' in many species, it seems that feline serum positive for IgM only often reads as a false negative<sup>5, 6</sup>. Therefore, careful interpretation is necessary, particularly since the IgM antibody class appears to correlate more closely to clinical disease than IgG<sup>7</sup>. IgG antibody persists at high levels for at least six years after infection, and so a single IgG measurement is not particularly useful for clinical diagnosis. A rising IgG titre may be more suggestive of active toxoplasmosis: however, IgG is not produced until 2-3 weeks post-infection which may be too late to be useful in acute cases, and many animals with chronic toxoplasmosis will not be assayed until IgG is already at its maximal titre. A more practically useful form of serology is examination of IgM in aqueous humour or cerebrospinal fluid. IgM, in contrast to IgG and IgA, has only been detected in the aqueous humour and CSF of cats with clinical disease <sup>5, 6</sup>. Therefore, an IgM titre of above 1:64 is highly suggestive of recent or active ''T. gondii'' infection.
ANALYSIS
 
In a series of cats with suspected CNS toxoplasmosis,
 
cerebrospinal fluid (CSF) protein levels ranged from
 
normal to 149 mg/% and nucleated cell counts from less
 
than 5 to 28 cells/,l (M. R. Lappin, unpublished data).
 
Small mononuclear cells were the predominant white
 
blood cells. Cytological examination may reveal tachyzoites
 
in blood, CSF, transtracheal wash fluids, peritoneal
 
effusions and pleural effusions from clinically ill
 
animals.
 
FAECAL EXAMINATION
 
T gondii oocysts are 10 x 12 ,um in size and can be
 
demonstrated microscopically in feline faeces following
 
0 2 4 6 8 12 16 20 26 34
 
Weeks after inoculation
 
Temporal appearance of
 
T gondii-specific IgM, IgG
 
and IgA antibodies in the
 
serum of experimentally
 
flotation using solutions with a specific gravity of 1-18. inoculated cats
 
Oocysts of the non-pathogenic coccidians Hammondia
 
hammondi and Besnoitia darlingi cannot be distinguished
 
microscopically from those of T gondii; definitive diagnosis
 
relies on laboratory animal inoculation. Most cats
 
with clinical toxoplasmosis have completed the oocyst
 
shedding period and so the diagnostic utility of faecal
 
examination is limited. However, due to the potential
 
zoonotic risk, a faecal examination should be performed
 
for any cat with clinical signs referable to toxoplasmosis.
 
SEROLOGY
 
T gondii-specific antibodies, antigens and immune
 
complexes have been detected in the serum of cats
 
(Lappin 1996). Tests for antigens and immune complexes
 
are currently only available in research laboratories
 
and so will not be discussed further.
 
Antibodies can be detected using a range of techniques
 
that are commercially available, including ELISA,
 
immunofluorescent antibody, western blot immunoassay,
 
Sabin-Feldmann dye test, and a variety of agglutination
 
tests. ELISA, immunofluorescent antibody assay
 
and western blot immunoassay have been adapted to
 
detect IgM, IgG and IgA antibody responses (see graph
 
above).
 
A latex agglutination assay and an indirect haemagglutination
 
assay are also available commercially. These
 
assays, which can be used with serum from multiple
 
species, theoretically detect all classes of immunoglobulin
 
directed against T gondii. However, these assays rarely
 
detect antibody in feline serum samples positive only for
 
IgM (Lappin 1996, Dubey and Lappin 1998). A combination
 
of modified agglutination tests using formalin-fixed
 
and acetone-fixed tachyzoites can be used to accurately
 
predict recent infection, but the assays are not commercially
 
available.
 
Using ELISA, approximately 80 per cent of healthy,
 
experimentally infected cats have detectable T gondiispecific
 
IgM in serum within two to four weeks of inoculation
 
with T gondii; the titres are generally negative
 
again by 16 weeks post-infection. Persistent IgM titres
 
(>16 weeks) have been documented commonly in cats
 
coinfected with FIV and in cats with ocular toxoplasmosis.
 
In some chronically infected cats, IgM can be detected
 
again after repeat inoculation with T gondii, primary
 
inoculation with the Petaluma isolate of FIV, and administration
 
of glucocorticoids. Because of these findings,
 
IgM titres cannot accurately predict when a cat is
 
InPractice i NOVEMBER/DECEMBER 1999 583
 
shedding oocysts or if a cat has clinical toxoplasmosis.
 
However, detectable IgM titres were present in the
 
serum of 93-3 per cent of cats in one study of clinical
 
toxoplasmosis, while IgG titres were only detected in
 
60 per cent (Lappin and others 1989). Hence, the IgM
 
antibody class appears to correlate more closely to clinical
 
disease than IgG.
 
T gondii-specific IgG can be detected by ELISA in
 
serum in the majority of healthy, experimentally inoculated
 
cats within three to four weeks of infection (Lappin
 
1996, Dubey and Lappin 1998). IgG antibody titres can
 
be detected for at least six years after infection (Dubey
 
1995); since the organism probably persists for life, IgG
 
antibodies probably do as well. Single, high IgG titres do
 
not necessarily suggest recent or active infection -
 
healthy cats commonly have titres of above 10,000 six
 
years after experimental induction of toxoplasmosis. The
 
demonstration of an increasing IgG titre can document
 
recent or active disease but, in experimentally infected
 
cats, the time span from the first detectable positive IgG
 
titre to the maximal IgG titre is approximately two to
 
three weeks. Many cats with sublethal clinical toxoplasmosis
 
have chronic, mild clinical signs and may not be
 
evaluated serologically until their IgG antibody titres
 
have reached their maximal values. In humans and cats
 
with reactivation of chronic toxoplasmosis, IgG titres
 
rarely increase.
 
Western blot immunoassay can be used to determine
 
the T gondii antigens recognised by humoral immune
 
responses. Transplacentally infected kittens could be distinguished
 
from T gondii-naive kittens with antibodies in
 
serum from colostrum ingestion by comparing antigen
 
recognition patterns between the queen and kittens.
 
AQUEOUS HUMOUR AND CSF ANTIBODY
 
AND DNA MEASUREMENT
 
Detection of T gondii-specific antibodies produced by the
 
eyes or CNS can be used to document clinical toxoplasmosis.
 
While IgG and IgA class antibodies are produced
 
transiently by the eyes and CNS of healthy cats after
 
experimental inoculation, IgM has only been detected in
 
the aqueous humour or CSF of cats with clinical disease
 
(Lappin 1996, Dubey and Lappin 1998). Most cats with
 
local production of T gondii-specific antibodies in aqueous
 
humour have responded to the administration of anti-
 
Toxoplasma drugs, suggesting that aqueous humour antibody
 
testing can aid in the diagnosis of clinical ocular
 
toxoplasmosis in cats (Lappin and others 1992b).
 
T gondii DNA has been detected in the aqueous
 
humour of cats with uveitis by polymerase chain reaction
 
(PCR) (Lappin and others 1996). However, the
 
organism is also detected occasionally in the aqueous
 
humour of cats without uveitis and so positive results do
 
not provide a definitive diagnosis of clinical toxoplasmosis
 
(Burney and others 1998).
 
DEMONSTRATION OF T GONDII IN TISSUES
 
In addition to using cytology to demonstrate T gondii
 
tachyzoites, PCR, tissue culture and animal inoculation
 
techniques can be used to detect the organism in whole
 
blood, aqueous humour or CSF. Tissue biopsy sections
 
can be assessed for the presence of T gondii by haematoxylin
 
and eosin (H&E) staining, immunohistochemical
 
staining, PCR, cell culture or animal inoculation.
 
Immunohistochemical staining procedures are superior
 
to H&E staining because they are specific for T gondii
 
(see figure on page 580). It may be difficult to document
 
the organism in the tissues of some clinically ill cats
 
because of the small sections of tissue evaluated
 
histopathologically and because the pathogenesis of disease
 
in some may be immune-mediated. This appears to
 
be particularly true for the ophthalmic form of the disease
 
in cats.
 
DIAGNOSIS OF CLINICAL FELINE
 
TOXOPLASMOSIS
 
Definitive diagnosis of clinical feline toxoplasmosis
 
requires demonstration of the organism in the tissues in
 
association with inflammation. This is usually achieved
 
at necropsy in cats with overwhelming tachyzoite replication.
 
Occasionally, a definitive diagnosis of clinical
 
feline toxoplasmosis is made antemortem by demonstrating
 
bradyzoites or tachyzoites in tissues or effusions.
 
Since T gondii-specific antibodies can be detected in
 
the serum, CSF and aqueous humour of normal animals,
 
as well as those with clinical signs of disease, it is not
 
possible to make an antemortem diagnosis of clinical
 
toxoplasmosis based on these tests alone. However, a
 
presumptive antemortem diagnosis of clinical feline
 
toxoplasmosis may be based on the following combination
 
of findings:
 
* Demonstration of antibodies in serum, aqueous
 
humour or CSF (documents exposure to T gondii);
 
* Demonstration of an IgM titre of above 1:64 or a
 
fourfold or greater increase in IgG titre, or the documentation
 
of local antibody production or DNA in aqueous
 
humour or CSF (suggests recent or active infection);
 
* Clinical signs of disease referable to toxoplasmosis;
 
* Exclusion of other common aetiologies;
 
* Positive response to appropriate treatment (see
 
below).
 
  
Diagnosis is made by biologic, serologic, or histologic methods, or by some combination of the above. Clinical signs of toxoplasmosis are nonspecific and are not sufficiently characteristic for a definite diagnosis. Antemortem diagnosis may be accomplished by indirect hemagglutination assay, indirect fluorescent antibody assay, latex agglutination test, or ELISA. IgM antibodies appear sooner after infection than IgG antibodies but generally do not persist past 3 mo after infection. Increased IgM titers (>1:256) are consistent with recent infection. In contrast, IgG antibodies appear by the fourth week after infection and may remain increased for years during subclinical infection. To be useful, IgG titers must be measured in paired sera from the acute and convalescent stages (3-4 wk apart) and must show at least a 4-fold increase in titer. Additionally, CSF and aqueous humor may be analyzed for the presence of tachyzoites or anti- T  gondii  antibodies. Postmortem, tachyzoites may be seen in tissue impression smears. Additionally, microscopic examination of tissue sections may reveal the presence of tachyzoites or bradyzoites. T  gondii  is morphologically similar to other protozoan parasites and must be differentiated from Sarcocystis  spp  (in cattle), S neurona  (in horses), and Neospora  caninum  (in dogs).
+
''T. gondii'' oocysts may be demonstrated in cat faeces. This diagnostic procedure is not of value in dogs, since as intermediate hosts they do not produce oocysts. Oocysts are roughly 10x12 microns in size and can be seen microscopically following a flotation technique. It is not possible to visibly differentiate between ''Toxoplasma'' oocysts and those from other, non-pathogenic coccidia such as ''Hammondia hammondi'' and ''Besnoitia darlingi'': laboratory animal innoculation is necessary for this. Unfortunately, most cats with clinical toxoplasmosis have already finished shedding oocysts, and so faecal examination is of little use as a stand-alone diagnostic test. However, it will evaluate the zoonotic risk posed by cats showing signs of toxoplasmosis.
  
 
===Diagnostic Imaging===
 
===Diagnostic Imaging===
 
 
Radiographs of the thorax in pulmonic toxoplasmosis commonly show patchy alveolar and interstitial pulmonary patterns, but pleural effusions are rare<sup>1</sup>. Abdominal radiographs can show a variety of changes, including hepatomegaly, pertitoneal effusions, lymphadenopathy, intestinal masses, or pancreatitis (seen as reduced contrast in the right cranial quadrant)<sup>1,3</sup>. Myelography, CT or MRI can detect mass lesions in cats with CNS involvement.
 
Radiographs of the thorax in pulmonic toxoplasmosis commonly show patchy alveolar and interstitial pulmonary patterns, but pleural effusions are rare<sup>1</sup>. Abdominal radiographs can show a variety of changes, including hepatomegaly, pertitoneal effusions, lymphadenopathy, intestinal masses, or pancreatitis (seen as reduced contrast in the right cranial quadrant)<sup>1,3</sup>. Myelography, CT or MRI can detect mass lesions in cats with CNS involvement.
  
 
===Pathology===
 
===Pathology===
 +
On post-mortem examination, necrotic foci of up to 1cm diameter can affect many organs. Most commonly, these foci are found in the liver, pancreas, mesenteric lymph nodes, lungs and brain<sup>4</sup>. Ulcers and granulomas may also be seen on the stomach and small intestine.
 +
 +
Biopsy or post-mortem histopathology can reveal tissue cysts containing tachyzoites.
 +
 
==Treatment==
 
==Treatment==
 +
The toxoplasmosis patient does not usually require hospitalisation, unless they are suffering severe disease or cannot maintain adequate nutrition or hydration unaided. Patients showing neurological signs should also be confined and monitored.
  
The toxoplasmosis patient does not usually require hospitalisation, unless they are suffering severe disease or cannot maintain adqequate nutrition or hydration unaided. Patients showing neurological signs should also be confined and monitored.
+
Supportive care should be given to cats and dogs with clinical toxoplasmosis as required. The specific treatment for ''Toxoplasma gondii'' infection is '''clindamycin'''. Treatment should generally be given for four weeks, but should continue for at least two weeks after clinical signs have disappeared. Side effects can include acute vomiting and diarrhoea, but stopping treatment for a day or so before reintroducing the drug usually resolves this. Alternatively, a trimethoprim-potentiated sulphonamide may be used for 4 weeks. This is useful in animals where clindamycin is not tolerated or is ineffective in treating CNS toxoplasmosis. Trimethoprim-sulphonamides can cause depression, anaemia, leukopenia and thrombocytopenia, so a complete blood cell count should be performed every two weeks to monitor this. Macrolides such as spiramycin, azithromycin and clarithromycin may also be effective against toxoplamosis, but have not yet been evaluated in cats and dogs. In toxoplasma-induced uveitis, intraocular inflammatory reactions can cause lens luxation and glaucoma, and so animals with uveitis should be prescribed topical glucocorticoids in addition to clindamycin or potentiated sulphonamides.  
  
 +
Animals should be re-examined two days after commencement of treatment, when clinical signs should begin to resolve. If this is not the case, an alternative anti-''Toxoplasma'' drug should be considered. At two weeks, uveitis should be completely resolved, and neurological deficits should show improvement. Two weeks after the owner reports clinical recovery, the animal should be re-examined for a third time, and a decision made as to discontinuation of treatment. It should be noted that some neuromuscular changes may not fully resolve, due to permanent CNS damage.
  
'''Prevention'''
+
Toxoplasmosis may be '''prevented''' through dietary and behavioural modifications. Cats and dogs should not be fed raw meat or animal products or unpasteurised milk. They should also not be permitted to hunt birds or rodents, and access to food-producing animals should be restricted.
*Cat
 
**Impossible if cat is allowed outdoors due to hunting
 
**If kept indoors, only canned food should be fed and vermin controlled
 
**ELISA to check if seropositive
 
  
For animals other than humans, treatment is seldom warranted. Sulfadiazine (15-25 mg/kg) and pyrimethamine (0.44 mg/kg) act synergistically and are widely used for treatment of toxoplasmosis. While these drugs are beneficial if given in the acute stage of the disease when there is active multiplication of the parasite, they will not usually eradicate infection. These drugs are believed to have little effect on the bradyzoite stage. Certain other drugs, including diaminodiphenylsulfone, atovaquone, and spiramycin are also used to treat toxoplasmosis in difficult cases. Clindamycin is the treatment of choice for dogs and cats, at 10-40 mg/kg and 25-50 mg/kg respectively, for 14-21 days.
+
==Zoonosis==
 +
Toxoplasmosis in cats, who shed infectious oocysts, poses a considerable zoonotic threat. An animal with a positive antibody titre is not necessarily a danger to man, since most of these animals are chronically infected and have ceased to shed oocysts. A naive animal, however, is at risk of becoming infected and shedding oocysts in its faeces - this constitutes a zoonotic threat. Toxoplasmosis in pregnant women can be associated with disastrous consequences, and so contact with cats excreting oocysts, cat litter and raw meat should be avoided. Other humans should take hygienic precautions, such as washing hands, keeping litter trays covered, washing vegetables before cooking to remove oocysts from contaminated soil and wearing gloves while gardening.
  
==Zoonosis==
+
For more information on toxoplasmosis in man, please see [[Toxoplasmosis - Human]].
T  gondii  is an important zoonotic agent. In some areas of the world, up to 60% of the human population have serum IgG titers to T  gondii  and are likely to be persistently infected. Toxoplasmosis is a major concern for people with immune system dysfunction (eg, people infected with human immunodeficiency virus). In these individuals, toxoplasmosis usually presents as meningoencephalitis and results from the emergence of T  gondii  from tissue cysts located in the brain as immunity wanes rather than from primary T  gondii  infection. Toxoplasmosis is also a major concern for pregnant women because tachyzoites can migrate transplacentally and cause birth defects in human fetuses. Infection of women with T  gondii  may occur after ingestion of undercooked meat or accidental ingestion of oocysts from cat feces. To prevent infection, the hands of people handling meat should be washed thoroughly with soap and water after contact, as should all cutting boards, sink tops, knives, and other materials. The stages of T  gondii  in meat are killed by contact with soap and water. T  gondii  organisms in meat can also be killed by exposure to extreme cold or heat. Tissue cysts in meat are killed by heating the meat throughout to 67°C or by cooling to -13°C. Toxoplasma  in tissue cysts are also killed by exposure to 0.5 kilorads of gamma irradiation. Meat of any animal should be cooked to 67°C before consumption, and tasting meat while cooking or while seasoning should be avoided. Pregnant women should avoid contact with cat litter, soil, and raw meat. Pet cats should be fed only dry, canned, or cooked food. The cat litter box should be emptied daily, preferably not by a pregnant woman. Gloves should be worn while gardening. Vegetables should be washed thoroughly before eating because they may have been contaminated with cat feces.
 
At present there is no vaccine to prevent toxoplasmosis in humans.
 
  
 
==Prognosis==
 
==Prognosis==
 +
Within 2-3 days of clindamycin or trimethoprim-sulphonamide administration, most clinical signs should begin to resolve and the prognosis is good. However, anti-''Toxoplasma'' drugs are unlikely to completely eradicate the organism from the host, and so recurrences are common. Ocular and CNS toxoplasmosis respond more slowly to therapy and carry a worse prognosis. Some neuromuscular signs may be persistent due to permanent nervous damage. Animals with hepatic or pulmonary disease have a poor prognosis.
 +
 +
{{Learning
 +
|literature search = [http://www.cabdirect.org/search.html?q=%28title%3A%28%22toxoplasma+gondii%22%29+OR+title%3A%28toxoplasmosis%29%29+AND+od%3A%28cats%29+ Toxoplasmosis in cats publications]
 +
}}
 +
 
==Links==
 
==Links==
 +
<big>'''[[Toxoplasmosis - Sheep|Ovine Toxoplasmosis]]'''
 +
 +
'''[[Toxoplasmosis - Human|Human Toxoplasmosis]]'''</big>
  
 
*[http://www.vet.cornell.edu/fhc/brochures/toxo.html Cornell College of Veterinary Medicine Toxoplasmosis Factsheet]
 
*[http://www.vet.cornell.edu/fhc/brochures/toxo.html Cornell College of Veterinary Medicine Toxoplasmosis Factsheet]
Line 241: Line 74:
 
#Lappin, M (1999) Feline toxoplasmosis. ''In Practice'', '''21(10)''', 578-589.
 
#Lappin, M (1999) Feline toxoplasmosis. ''In Practice'', '''21(10)''', 578-589.
 
#Burney, D P et al (1999) Detection of Toxoplasma gondii parasitemia in experimentally inoculated cats. ''Journal of Parasitology'', '''85'''.
 
#Burney, D P et al (1999) Detection of Toxoplasma gondii parasitemia in experimentally inoculated cats. ''Journal of Parasitology'', '''85'''.
 +
#Dubey, J P (2005) Toxoplasmosis in cats and dogs. ''Proceedings of the World Small Animal Veterinary Association 2005''.
 
#Tilley, L.P. and Smith, F.W.K.(2004)'''The 5-minute Veterinary Consult (Fourth Edition)''' ''Blackwell Publishing''.
 
#Tilley, L.P. and Smith, F.W.K.(2004)'''The 5-minute Veterinary Consult (Fourth Edition)''' ''Blackwell Publishing''.
#Dubey, J P (2005) Toxoplasmosis in cats and dogs. ''Proceedings of the World Small Animal Veterinary Association 2005''.
+
# Lappin, M R (1996) Feline toxoplasmosis: interpretation of diagnostic test results. ''Seminars in Veterinary Medicine and Surgery'', '''11''', 154-160.
 +
# Dubey, J P and Lappin, M R (1998) Toxoplasmosis and neosporosis. In '''Infectious Diseases of the Dog and Cat''', ''W B Saunders'', 493-503.
 +
#Lappin, M R et al (1989) Clinical feline toxoplasmosis: serologic diagnosis and therapeutic management of 15 cases. ''Journal of Veterinary Internal Medicine'', '''3''', 139-143.
 
#Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
 
#Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
#Fisher, M () Endoparasites in the dog and cat: 2. Protozoa. ''In Practice'', '''24(3)''', 146-153.
+
#Fisher, M (2002) Endoparasites in the dog and cat: 2. Protozoa. ''In Practice'', '''24(3)''', 146-153.
 +
#Quinn, P J and McCraw, B M (1972) Current status of toxoplamsa and toxoplasmosis: A review. '' The Canadian Veterinary Journal'', '''13(11)''', 247-262.
 +
 
 +
 
 +
{{review}}
  
 +
{{OpenPages}}
  
[[Category:Tissue_Cyst_Forming_Coccidia]][[Category:Cat]]
+
[[Category:Reproductive Diseases - Cat]][[Category:Cardiac Diseases - Cat]][[Category:Respiratory Diseases - Cat]][[Category:Neurological Diseases - Cat]][[Category:Alimentary Diseases - Cat]]
[[Category:To_Do_-_Lizzie]]
+
[[Category:Expert_Review]]
 +
[[Category:Respiratory Diseases - Dog]][[Category:Neurological Diseases - Dog]][[Category:Musculoskeletal Diseases - Dog]]
 +
[[Category:Zoonoses]]
 +
[[Category:Cardiology Section]]

Latest revision as of 17:31, 17 October 2013


Introduction

Life cycle of Toxoplasma gondii. Source: Wikimedia Commons; Author: LadyofHats (2010)
Toxoplasma tissue cyst. Source: Wikimedia Commons; Author: Marvin 101 (2008)

Toxoplasmosis is caused by Toxoplasma gondii infection. Its life cycle is described in the pathogen page, Toxoplasma gondii.

Pathogenesis

The outcome of primary infection depends on the immune status of the host, as well as the location of and degree of injury caused by tissue cysts. Primary infection normally results in chronic disease, where tissue cysts form but clinical signs are not normally apparent. In immunodeficient animals, or in animals with concurrent illness, chronic infections may become symptomatic as the organism is allowed to proliferate. Acute primary infection in these animals can, rarely, prove fatal.

The mechanism of clinical disease in chronic toxoplasmosis is not fully understood, but may be related to low-level tachyzoite replication, or intermittent antigenaemia and parasitemia2. The pathogenesis of disease could also be associated with immunological reactions against the organism through formation and deposition of immune complexes, and delayed hypersensitivity reactions3.

Signalment

Cats more commonly show clinical disease than dogs. Male cats are predisposed, and the average age of the feline toxoplasmosis patient is 4 years (range: 2 weeks to 16 years)4. There are no breed predilections.

Clinical Signs

Clinical signs are determined by the site and extent of organ damage by tachyzoites, and may be acute or chronic. Acute signs manifest at the time of initial infection, whereas chronic signs are associated with reactivation of encysted infection during times of immunocompromise.

In cats, disease is most severe in transplacentally infected kittens, which may be stillborn or die before weaning. Those that survive are anorexic and lethargic, with a pyrexia that does not respond to antibiotics. The lungs, liver or CNS may be necrosed, leading to signs such as dyspnoea, respiratory noise, icterus, ascites and neurological signs. Kittens infected neonatally commonly show interstitial pneumonia, necrotising hepatitis, myocardidits, non-suppurative encephalits and uveitis on post-mortem examination1.

Cats infected post-natally most commonly display gastrointestinal and/or respiratory signs. Again, animals may be anorexic and lethargic, with an antibiotic non-responsive fever. Vomiting, diarrhoea, icterus or abdominal effusion may be apparent, and the cat may lose weight. Ocular signs such as uveitis, iritis and detachment of the retina are also common. Neurologic signs are seen in less than 10% of patients 4 and may present as circling, torticollis, anisocoria, seizures, blindness or in-coordination. Signs progress rapidly in patients suffering acute disease, in whom respiratory and/or CNS involvement is common. Chronic infections tend to follow a slower course.

In young dogs, Toxoplasma gondii infection is usually generalised, causing fever, weight loss and anorexia. Dyspnoea, diarrhoea and vomiting may also be seen. Older animals more commonly experience localised infections which are primarily associated with the neural and muscular systems. When neurological signs are seen, they usually reflect diffuse inflammation of the CNS. For example, dogs might suffer seizures, ataxia, paresis or muscle weakness. Although cardiac involvement occurs, this is not normally clinically significant. Ocular changes are rare, but are similar to those described in cats.

Laboratory Tests

Demonstration of Toxoplasma gondii in the tissues with associated inflammation is required for the definitive diagnosis of clinical toxoplasmosis. For example, tachyzoites may be seen in blood, cerebrospinal fluid, peritoneal and pleural effusions, aqueous humour or transtracheal washes from clinically ill animals. Toxoplasma gondii may also be detected in these samples using PCR, tissue culture or animal inoculation techniques1. These methods may be employed on tissue biopsies too, as well as examination under haematoxylin and eosin or immunohistochemical staining. Immunohistochemistry is preferred to H&E because it is specific for T. gondii. Demonstration of the organism is often most easily achieved post-mortem, as the size of the sample is not restrictive to the likelihood of seeing T.gondii. In the absence of demonstration of Toxoplasma gondii in the tissues or fluids ante-mortem, there is no one specific test to diagnose toxoplamosis. However, a combination of various diagnostic procedures can be used to build a presumptive diagnosis.

Firstly, clinical signs should be suggestive of toxoplasmosis, despite variation in the presentation of disease between individuals. Although no pathognomic changes for toxoplasmosis are seen on routine haematology, biochemistry and urinalysis, certain results are often seen in T. gondii infection. For example, most cats show a mild non-regenerative anaemia, and 50% of patients are initially leukopenic due to lymphopenia. Neutropenia may occur in conjunction with lymphopenia, and leukocytosis may occur during recovery4. Most patients also show and increase in creatine kinase, ALT, SAP, and hypoalbuminaemia is also common1, 4. 25% of cats show hyperbilirubinemia and icterus, and pancreatitis may cause low to low normal serum calcium. A mild proteinuria and bilirubinuria are often revealed by urinalysis.

Demonstration of antibodies in serum is indicative of exposure to T. gondii, but does not necessarily show active infection. This could be overcome by testing for T. gondii antigen or immune complexes, but these methods are currently only available to researchers. Several techniques are commercially available for detection of antibody, including ELISA, immunofluorescent antibody testing, Sabin-Feldmann dye test, and agglutination tests. Although these tests are theoretically able to detect all classes of immunoglobulin against Toxoplasma gondii in many species, it seems that feline serum positive for IgM only often reads as a false negative5, 6. Therefore, careful interpretation is necessary, particularly since the IgM antibody class appears to correlate more closely to clinical disease than IgG7. IgG antibody persists at high levels for at least six years after infection, and so a single IgG measurement is not particularly useful for clinical diagnosis. A rising IgG titre may be more suggestive of active toxoplasmosis: however, IgG is not produced until 2-3 weeks post-infection which may be too late to be useful in acute cases, and many animals with chronic toxoplasmosis will not be assayed until IgG is already at its maximal titre. A more practically useful form of serology is examination of IgM in aqueous humour or cerebrospinal fluid. IgM, in contrast to IgG and IgA, has only been detected in the aqueous humour and CSF of cats with clinical disease 5, 6. Therefore, an IgM titre of above 1:64 is highly suggestive of recent or active T. gondii infection.

T. gondii oocysts may be demonstrated in cat faeces. This diagnostic procedure is not of value in dogs, since as intermediate hosts they do not produce oocysts. Oocysts are roughly 10x12 microns in size and can be seen microscopically following a flotation technique. It is not possible to visibly differentiate between Toxoplasma oocysts and those from other, non-pathogenic coccidia such as Hammondia hammondi and Besnoitia darlingi: laboratory animal innoculation is necessary for this. Unfortunately, most cats with clinical toxoplasmosis have already finished shedding oocysts, and so faecal examination is of little use as a stand-alone diagnostic test. However, it will evaluate the zoonotic risk posed by cats showing signs of toxoplasmosis.

Diagnostic Imaging

Radiographs of the thorax in pulmonic toxoplasmosis commonly show patchy alveolar and interstitial pulmonary patterns, but pleural effusions are rare1. Abdominal radiographs can show a variety of changes, including hepatomegaly, pertitoneal effusions, lymphadenopathy, intestinal masses, or pancreatitis (seen as reduced contrast in the right cranial quadrant)1,3. Myelography, CT or MRI can detect mass lesions in cats with CNS involvement.

Pathology

On post-mortem examination, necrotic foci of up to 1cm diameter can affect many organs. Most commonly, these foci are found in the liver, pancreas, mesenteric lymph nodes, lungs and brain4. Ulcers and granulomas may also be seen on the stomach and small intestine.

Biopsy or post-mortem histopathology can reveal tissue cysts containing tachyzoites.

Treatment

The toxoplasmosis patient does not usually require hospitalisation, unless they are suffering severe disease or cannot maintain adequate nutrition or hydration unaided. Patients showing neurological signs should also be confined and monitored.

Supportive care should be given to cats and dogs with clinical toxoplasmosis as required. The specific treatment for Toxoplasma gondii infection is clindamycin. Treatment should generally be given for four weeks, but should continue for at least two weeks after clinical signs have disappeared. Side effects can include acute vomiting and diarrhoea, but stopping treatment for a day or so before reintroducing the drug usually resolves this. Alternatively, a trimethoprim-potentiated sulphonamide may be used for 4 weeks. This is useful in animals where clindamycin is not tolerated or is ineffective in treating CNS toxoplasmosis. Trimethoprim-sulphonamides can cause depression, anaemia, leukopenia and thrombocytopenia, so a complete blood cell count should be performed every two weeks to monitor this. Macrolides such as spiramycin, azithromycin and clarithromycin may also be effective against toxoplamosis, but have not yet been evaluated in cats and dogs. In toxoplasma-induced uveitis, intraocular inflammatory reactions can cause lens luxation and glaucoma, and so animals with uveitis should be prescribed topical glucocorticoids in addition to clindamycin or potentiated sulphonamides.

Animals should be re-examined two days after commencement of treatment, when clinical signs should begin to resolve. If this is not the case, an alternative anti-Toxoplasma drug should be considered. At two weeks, uveitis should be completely resolved, and neurological deficits should show improvement. Two weeks after the owner reports clinical recovery, the animal should be re-examined for a third time, and a decision made as to discontinuation of treatment. It should be noted that some neuromuscular changes may not fully resolve, due to permanent CNS damage.

Toxoplasmosis may be prevented through dietary and behavioural modifications. Cats and dogs should not be fed raw meat or animal products or unpasteurised milk. They should also not be permitted to hunt birds or rodents, and access to food-producing animals should be restricted.

Zoonosis

Toxoplasmosis in cats, who shed infectious oocysts, poses a considerable zoonotic threat. An animal with a positive antibody titre is not necessarily a danger to man, since most of these animals are chronically infected and have ceased to shed oocysts. A naive animal, however, is at risk of becoming infected and shedding oocysts in its faeces - this constitutes a zoonotic threat. Toxoplasmosis in pregnant women can be associated with disastrous consequences, and so contact with cats excreting oocysts, cat litter and raw meat should be avoided. Other humans should take hygienic precautions, such as washing hands, keeping litter trays covered, washing vegetables before cooking to remove oocysts from contaminated soil and wearing gloves while gardening.

For more information on toxoplasmosis in man, please see Toxoplasmosis - Human.

Prognosis

Within 2-3 days of clindamycin or trimethoprim-sulphonamide administration, most clinical signs should begin to resolve and the prognosis is good. However, anti-Toxoplasma drugs are unlikely to completely eradicate the organism from the host, and so recurrences are common. Ocular and CNS toxoplasmosis respond more slowly to therapy and carry a worse prognosis. Some neuromuscular signs may be persistent due to permanent nervous damage. Animals with hepatic or pulmonary disease have a poor prognosis.


Toxoplasmosis - Cat and Dog Learning Resources
CABICABI logo.jpg
Literature Search
Search for recent publications via CAB Abstract
(CABI log in required)
Toxoplasmosis in cats publications


Links

Ovine Toxoplasmosis

Human Toxoplasmosis

References

  1. Lappin, M (1999) Feline toxoplasmosis. In Practice, 21(10), 578-589.
  2. Burney, D P et al (1999) Detection of Toxoplasma gondii parasitemia in experimentally inoculated cats. Journal of Parasitology, 85.
  3. Dubey, J P (2005) Toxoplasmosis in cats and dogs. Proceedings of the World Small Animal Veterinary Association 2005.
  4. Tilley, L.P. and Smith, F.W.K.(2004)The 5-minute Veterinary Consult (Fourth Edition) Blackwell Publishing.
  5. Lappin, M R (1996) Feline toxoplasmosis: interpretation of diagnostic test results. Seminars in Veterinary Medicine and Surgery, 11, 154-160.
  6. Dubey, J P and Lappin, M R (1998) Toxoplasmosis and neosporosis. In Infectious Diseases of the Dog and Cat, W B Saunders, 493-503.
  7. Lappin, M R et al (1989) Clinical feline toxoplasmosis: serologic diagnosis and therapeutic management of 15 cases. Journal of Veterinary Internal Medicine, 3, 139-143.
  8. Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition) Merial
  9. Fisher, M (2002) Endoparasites in the dog and cat: 2. Protozoa. In Practice, 24(3), 146-153.
  10. Quinn, P J and McCraw, B M (1972) Current status of toxoplamsa and toxoplasmosis: A review. The Canadian Veterinary Journal, 13(11), 247-262.




Error in widget FBRecommend: unable to write file /var/www/wikivet.net/extensions/Widgets/compiled_templates/wrt675b55020bb926_05688848
Error in widget google+: unable to write file /var/www/wikivet.net/extensions/Widgets/compiled_templates/wrt675b550210f8c4_21326408
Error in widget TwitterTweet: unable to write file /var/www/wikivet.net/extensions/Widgets/compiled_templates/wrt675b5502153a11_81006531
WikiVet® Introduction - Help WikiVet - Report a Problem