EPIDEMIOLOGICAL ASPECTS OF FELINE TOXOPLASMOSIS

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INTRODUCTION
Felines (definitive hosts of Toxoplasma gondii) can eliminate fecal oocysts.These are highly infectious parasite forms that evolved to tolerate environmental adversities Cats defecate on soft earth or sand and bury their feces, which can remain in place for months.Cats generally do not present diarrhea during the period of oocysts excretion; hence, unless the cat is ill, little or no fecal residue is adhered to their perianal region.Because of its careful cleaning habits, fecal matter is not found in the pelage of clinically normal animals; therefore the possibility of transmission to humans by the act of touching or petting a cat is minimal or nonexistent.It is important to note that oocysts eliminated by cats, need to be in the extracorporeal environment for at least one day, under particular temperature and humidity conditions, to sporulate and become infective.In this review we aim to provide information on the role of cats take in the cycle of this important zoonosis, suggesting guidelines to the community on how to best avoid human infections.

FELINE TOXOPLASMOSIS
The life cycle of T. gondii was first elucidated in the late 1960s/ early 1970s (Frenkel et al., 1970;Hutchison et al., 1968;Hutchison et al., 1970;Hutchison et al., 1971).These initial works demonstrated the shedding of infective Toxoplasma life forms by cats.Cats can act as definitive (Frenkel et al., 1970) or intermediate host, sheltering the extraintestinal parasite stages (Dubey, 2002;Dubey et al., 1996).T. gondii is transmitted via 3 primary routes: ingestion of tissue cysts, contamination through oocysts from infected cat feces, or congenital infection.

PATHOGENESIS AND DIAGNOSIS
Cats experimentally infected with T. gondii are often asymptomatic: few animals get sick and deaths due to Toxoplasma infection are rare (Omata et al., 1990;Sato et al., 1993).However, close scrutiny of a large number of cats diagnosed with toxoplasmosis (confirmed by histopathology), revealed lung infections (97.7%), neuropathy (96.4%), hepatitis (93.3%), pancreatitis (84.4%), cardiovascular (86.4%) and ophthalmic changes (81.5%) in most cats (Dubey and Carpenter, 1993).Kittens infected during gestation (via the placenta) or through the milk of infected queens can undergo inflammatory processes that affect the liver, lungs and central nervous system.These are clinically displayed as uveitis, lethargy, depression, ascites, encephalitis, hypothermia and sudden death.Experimental infection of pregnant cats with the parasite leads to abortion and high neonatal mortality (Dubey and Hoover, 1977;Dubey et al., 1977;Dubey et al., 1996;Powell et al., 2001;Sakamoto et al., 2009;Sato et al., 1993).In adults with primary or recurrent infection, clinical symptoms are anorexia, lethargy, dyspnea, pneumonia, intermittent fever, emaciation, vomiting, diarrhea, hyperesthesia, stiff gait, lameness, neurological deficits, dermatitis and death (Dubey and Lappin, 2006).Furthermore, T. gondii infections can cause jaundice, cholangitis, ascites, hepatitis and pancreatitis (leading to hepato-biliary compromise) (Harvey and Greeffydd-Jones, 2009;Smart et al., 1973).Under conditions of pancreatitis, there is elevation of serum amylase and lipase as well as reduction in serum calcium (Dubey and Lappin, 2006).Toxoplasmosis can cause tissue impairment, leading to hypoproteinemia, hypo-globulinemia, and increased serum enzymatic activities of alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin and hypergammaglobulinemia (Dubey and Lappin, 2006).In the acute stage of the disease, radiographic examination of the thorax of affected animals can generally detect a diffuse interstitial alveolar pattern with lobar distribution.In severely compromised animals, it is possible to observe a diffuse and homogeneous pattern due to alveolar coalescence.Abdominal radiography of animals severely affected by toxoplasmosis show intestinal masses, increased mesenteric lymph nodes and ascites; whereas ultrasonography frequently show tissue or organ enlargement, suggestive of granuloma formation.Tomography and magnetic resonance imaging are further techniques that can be employed in the clinical to detect damages to the central nervous system of infected animals (Dubey and Lappin, 2006).Toxoplasmosis can also lead to ocular symptoms, caused by parasite invasion of the uveal tract, retina and optic nerve, triggering inflammation with exudative retinal displacement, iridocyclitis, iritis, chorioretinitis, aqueous flare, keratic precipitates, crystalline lens dislocation and glaucoma (Dubey and Lappin, 2006).Ocular symptoms can occur in cats with or without systemic infections.The principal symptoms of acute toxoplasmosis are non-regenerative anemia, leukocytosis with neutrophilia or lymphocytosis, monocytosis and eosinophilia (Dubey and Lappin, 2006) (Dubey and Lappin, 1998).However, the unambiguous confirmation of the diagnosis depends on the isolation of the parasite and positive serodiagnosis (Lapppin, 2004;Carvalho, 2007).Once infected, animals frequently shelter bradyzoites in their tissues, which encourages a long-term humoral immune response.This allows the detection of antibodies against T. gondii by indirect immunofluorescence as well as by direct agglutination test, hemagglutination test and enzyme immunoassay, in diagnosis and epidemiological survey of this zoonosis (Dubey and Lappin, 2006;Zhang, et al., 2000).Anfray et al., (2005)  pyogranulomatous, necrotizing panniculitis, vasculitis and mastitis with clusters of tachyzoites, confirming of the diagnosis by molecular techniques.Dubey and Powell, (2012) reported the occurrence of six million T. gondii oocysts in a fecal sample from a 6-yearold male cat with clinical toxoplasmosis symptoms (lethargy, anorexia, fever and diarrhea) and with positive serology for T. gondii (1:800 by the modified agglutination test).The authors further genotyped the parasites reporting, for the first time, a type I infection in the United States of America (USA).The occurrence of fecal T. gondii oocysts is low as they are released for only one to two weeks during the initial stages of the disease.One method to facilitate the detection of oocysts in the feces of cats and hence provide a parasitological diagnosis is the Sheather method (centrifugal-flotation in sucrose).However, microscopic examination of samples prepared using this method is unable to morphologically distinguish oocysts from the evolutionarily conserved T. gondii, Sarcocystis, Frenkelia and Besnoitia.This discrimination can only be achieved by molecular techniques (Dubey and Lappin, 2006).T. gondii tachyzoites, life form responsible for multiplying the population of parasites in the host, can be detected by cytology of body tissues and fluids samples, such as blood, cerebrospinal fluid, peritoneum and bronchoalveolar lavage samples.The tachyzoites may also be isolated from samples of ascitic fluid or pleural effusion (Brownlee and Sellon, 2001;Dubey and Lappin, 2006).

EPIDEMIOLOGY OF FELINE TOXOPLASMOSIS
Multiple research groups have performed epidemiological studies of feline Toxoplasmosis.In Table 1 we summarize some of the epidemiological studies performed over the last 15 years, with special emphasis to infections on Brazil.Dubey et al. (2004), isolated 37 T. gondii samples from 54 domestic cats from Paraná, in the city of Santa Isabel do Ivaí, during an outbreak of human toxoplasmosis.Most of these isolates, 15 of which were of type I and 22 of type III, were virulent in mice, however, there was no correlation between the tested genotype and virulence.In the same year, Pena et al. (2004) isolated 47 samples of T. gondii from 71 cats in São Paulo, finding that 72.4% of the animals were infected with type I, 25.5% were infected with type III and 2.1% had mixed infection (types I and III).In contrast to the work reported by Dubey (2004), Pena et al., (2004) showed that in mice, Type I parasites had a significantly higher virulence (97% mortality) than type III (42% mortality).Bresciani et al. (2007) conducted studies to investigate the presence of antibodies against T. gondii in cats from the northwestern region of the state of São Paulo, and observed a higher incidence of T. gondii antibodies with aging (probably due to the cumulative exposure to the parasites).Coelho et al. (2011) also performed epidemiological studies of cats infected Bresciani et al., (2016) Archives of Veterinary Science, v.21, n.2, p.01-08, 2016.
with T. gondii and found a strong correlation between disease incidence and factors such as: postnatal infection, diet and presence of rodents in the environment.Sobrinho et al. (2012) investigated concomitant infections with Toxoplasma and Leishmania and found no correlation between the occurrences of either parasite.

TREATMENT AND PROFILAXIS
Clindamycin hydrochloride, administered orally or parenterally, is effective in the treatment of systemic toxoplasmosis and can reduce the elimination of oocysts by cats.It is used toxoplasmosis treatment in animals and humans, and indicated for the treatment of pregnant queens.This drug has good intestinal absorption, is transported through the blood brain barrier and leads to clinical improvement of affected animals within 24 to 48 hours from the onset of treatment.In this time frame, it is possible to observe a return of appetite and normalization of the body temperature.With further treatment, after weeks there are reports of reestablishment of the operation of cranial and spinal nerves, as well as the resolution of polymyositis.Clinical improvement of ocular damage is also described after a week of treatment with clindamycin hydrochloride.However, excessive doses may cause local irritation in the digestive system, with side effects such as anorexia, vomiting and diarrhea (LAPPIN, 2004;(Dubey and Lappin, 2006;Swinger et al., 2009)).Glucocorticoids are generally contraindicated in the treatment of T. gondii infections, since this class of compounds can exacerbate the systemic symptoms of the disease.However, this class of compounds can be advised for the topical treatment (in combination with clindamycin chloride) of ocular lesions (Dubey and Lappin, 2006;Harvey and Greeffydd-Jones, 2009).Clindamycin treatment can also be combined with folic acid supplementation in cases where there is bone marrow compromised by the infection (Dubey and Lappin, 2006).Trimethoprim-sulfametaxol combination therapy is also effective on the treatment of toxoplasmosis, in particular on the treatment of ocular lesions in human (Dubey and Lappin, 2006).In addition to trimethoprim-sulfametaxol, sulfadiazinetrimethoprim combination therapy is also recommended for the control of toxoplasmosis in small animals (Papich, 2009).Barbosa et al.(2012)A simple recommended method to minimize the risk of contamination of cats and humans by Toxoplasma is to discard cat stools daily, as oocysts require at least 24 hours to sporulate and become infectious.It is also important to minimize opportunities for coprophagia by animals, as well as the control of insects and rodents in the environment.
Furthermore, neither humans nor cats should consume raw or undercooked meat or raw milk, and care should be taken to ensure the consumption of clean fruit and vegetable and suitably treated water (Monteiro, 2010).

CONCLUSION
Toxoplasmosis it is a zoonosis of worldwide distribution that causes a range of clinical symptoms, from the absence of any obvious abnormality, to death of the infected host.Thus, diagnosis, treatment and control of toxoplasmosis present a great challenge to the veterinary in a feline clinic.
Although is possible for T. gondii to survive and multiply in the absence of cats, evidence gathered so far indicates that this host is of pivotal importance in the transmission of toxoplasmosis worldwide.Thus, the veterinarian plays a vital role in the control of this disease.