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Toxoplasmosis in Indo-Pacific humpbacked dolphins (Sousa chinensis), from Queensland.

OBJECTIVE: To describe the clinical signs, gross pathology, serology, bacteriology, histopathology, electron microscopy and immunohistochemistry findings associated with toxoplasmosis in four Indo-Pacific humpbacked dolphins (Sousa chinensis) that stranded in Queensland in 2000 and 2001. DESIGN: Clinical assessment, gross necropsy, and laboratory examinations. PROCEDURE: Necropsies were performed on four S. chinensis to determine cause of death. Laboratory tests including serology, bacteriology, histopathology and transmission electron microscopy were done on the four dolphins. Immunohistochemistry was done on the brain, heart, liver, lung, spleen and adrenal gland from various dolphins to detect Toxoplasma gondii antigens. RESULTS: Necropsies showed all of four S. chinensis that stranded in Queensland in 2000 and 2001 had evidence of predatory shark attack and three were extremely emaciated. Histopathological examinations showed all four dolphins had toxoplasmosis with tissue cysts resembling T. gondii in the brain. Tachyzoite stages of T. gondii were detected in the lungs, heart, liver, spleen and adrenal gland, variously of all four dolphins. Electron microscopy studies and immunohistochemistry confirmed the tissues cysts were those of T. gondii. All four dolphins also had intercurrent disease including pneumonia, three had peritonitis and one had pancreatitis. CONCLUSION: Four S. chinensis necropsied in Queensland in 2000 and 2001 were found to be infected with toxoplasmosis. It is uncertain how these dolphins became infected and further studies are needed to determine how S. chinensis acquire toxoplasmosis. All four dolphins stranded after periods of heavy rainfall, and coastal freshwater runoff may be a risk factor for T. gondii infection in S. chinensis. This disease should be of concern to wildlife managers since S. chinensis is a rare species and its numbers appear to be declining.

Animals↗

[A case of toxoplasmosis with dermatomyositis].

We report a case of dermatomyositis (DM) in a 15-year-old female with toxoplasmosis after ingestion of raw bovine liver. Facial erythema and cervical lymphadenopathy preceded myalgia and muscle weakness of the extremities. The diagnostic criteria of DM was fulfilled because of symmetrical and proximal dominant muscle weakness, elevation of myogenic enzyme (CPK, GOT, LDH, myoglobin, aldorase), myogenic pattern of electromyogram, skeletal muscle biopsy showing interstitial myositis with mild destruction of muscle fiber, and facial erythema. Immunological findings showed IgG anti-toxoplasma antibody to be 1340 IU/ml and IgM to be 7.0 (Cut off index 0.7), suggesting acute toxoplasmosis. Treatment with prednisolone for DM and acetylspiramycin for toxoplasmosis was successful. Toxoplasmosis should be considered as a possibility in patients with myositis.

Adolescent↗

Paradoxical effect of clindamycin in experimental, acute toxoplasmosis in cats.

Cats were experimentally inoculated parenterally with the ME49 strain of Toxoplasma gondii to characterize the efficacies of two different dosages of orally administered clindamycin hydrochloride in the treatment of ocular toxoplasmosis. Concentrations of clindamycin hydrochloride at levels previously suggested to be inhibitory to T. gondii replication in vitro were achieved in the serum and aqueous humor but not in the cerebrospinal fluid. Antibiotic therapy, initiated 7 days after inoculation, resulted in no significant difference in the morphometric severity of ocular posterior segment lesions compared with that in the control groups. Treatment appeared to blunt T. gondii-specific immunoglobulin M production but had no significant effect on immunoglobulin G titers. Paradoxically, clindamycin administration was associated with increased morbidity and mortality from hepatitis and interstitial pneumonia, which are characteristic of generalized toxoplasmosis. Serum tumor necrosis factor alpha activity was detected at moderate levels in all groups of cats and correlated with the severity of clinical disease. The results of the study suggest that clindamycin, when administered at this specific time interval following inoculation, does not ameliorate ocular lesions and has a detrimental effect on the clinical course of acute, experimental toxoplasmosis in cats. The factors responsible for and the relevance of this detrimental effect to naturally occurring toxoplasmosis in humans and pet cats were not clear from the study but may relate to an antibiotic-associated decrease in the antitoxoplasmic activity of phagocytic cells responsible for the control of T. gondii.

Acute Disease↗

Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme-linked immunofiltration assay immunological profiles and anti-Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies.

Diagnostic strategies for congenital toxoplasmosis have changed profoundly in recent years. Immunological diagnostic methods, long considered disappointing, can now be used at a very early stage. Over a 3-year period, 1,050 infants at risk of congenital toxoplasmosis (born to 1,048 mothers infected during pregnancy) were monitored for a minimum of 12 months and a maximum of 7 years. More than 6,000 serum specimens were analyzed by comparative mother-infant immunological profiles (CIPs) based on an enzyme-linked immunofiltration assay (ELIFA) and an immunocapture method for the detection of specific immunoglobulin M (IgM) and IgA. IgG antibodies were also titrated. One hundred three cases of congenital toxoplasmosis were demonstrated. The CIP-ELIFA method had a better diagnostic yield (sensitivity, 90%) than specific IgM and/or IgA detection by immunocapture assay (sensitivity, 77%). By using a combination of these tests, congenital infection was diagnosed in the first month and the first 3 months of life in 90 and 94% of infants with toxoplasmosis, respectively, with a specificity of 99.8% and a positive predictive value of 99% at 8 months of age. This dual diagnostic approach (ELIFA and IgM-IgA immunocapture) is highly efficient and has important implications for therapy. Indeed, early postnatal diagnosis based on objective evidence enables therapy with pyrimethamine-sulfadoxine to be started immediately for 24 months, while spiramycin (which used to be given preventively for 9 to 12 months to all infants at risk) can be stopped after the first 3 months of life.

Animals↗

Determination of genotypes of Toxoplasma gondii strains isolated from patients with toxoplasmosis.

To determine the genotypes of Toxoplasma gondii strains associated with human toxoplasmosis, we developed a sensitive approach for typing parasites grown from clinical samples by short-term in vitro culture. A newly described nested PCR assay was capable of amplifying genomic DNA from as few as five parasites in the presence of host tissues. Typing was based on DNA polymorphisms at the SAG2 locus, encoding tachyzoite surface antigen p22. Restriction fragment length polymorphisms in PCR-amplified SAG2 products were used to classify strains into one of the three major lineages of T. gondii. This approach was successfully used to determine the genotypes of 68 of 72 samples that had been previously isolated from patients with congenital, cerebral, and disseminated toxoplasmosis. Type II strains of T. gondii were found in a majority of the samples, accounting for 55 (81%) of the 68 toxoplasmosis cases. In contrast, type I and III strains were found in only 7 (10%) and 6 (9%) of the 68 cases, respectively. The results of this study support the previous finding that type II strains are most often associated with human toxoplasmosis. Nested PCR analysis at the SAG2 locus provides rapid assignment of T. gondii to a specific genotype that should be useful in analyzing a variety of clinical samples.

AIDS-Related Opportunistic Infections↗

Use of fluorescence resonance energy transfer hybridization probes to evaluate quantitative real-time PCR for diagnosis of ocular toxoplasmosis.

Toxoplasma gondii infection is an important cause of chorioretinitis in Europe and the United States. Ophthalmological examination and a good clinical response to adequate therapy mainly support ocular toxoplasmosis diagnosis. However, clinical diagnostic may be difficult in some atypical cases. In these cases, laboratory confirmation, based on detection of local specific antibodies and parasite DNA by conventional PCR, is therefore important to confirm the disease etiology. More recently, real-time PCR has been developed to improve prenatal congenital toxoplasmosis diagnosis. We therefore examined the diagnostic value of quantitative real-time PCR for the detection of T. gondii in aqueous humor samples, associated with quantification of human beta-globin to control sample quantitative quality, by using a double fluorescence resonance energy transfer hybridization probes system with a double fluorescence reading. Of the 23 the clinically toxoplasmosis suspect patients, 22 showed serological evidence of exposure to Toxoplasma; one had a serological profile indicative of active infection. The analysis of paired aqueous humor and serum samples revealed an intraocular antibody production in 9 of 23 cases (39.1%). The quantitative real-time PCR revealed positive and high parasite numbers and high Toxoplasma/human genome ratios in three cases. Furthermore, PCR was the only positive confirmatory test in two cases (11.1%). None of the patients included in the control group (n = 7) had evidence of either local specific antibody production or T. gondii DNA detection, suggesting a good relative assay specificity. On the whole, quantitative real-time PCR appears to be useful for diagnosing atypical ocular toxoplasmosis presentations.

Adolescent↗

Genotyping of Toxoplasma gondii by multiplex PCR and peptide-based serological testing of samples from infants in Poland diagnosed with congenital toxoplasmosis.

Toxoplasma gondii has a clonal population genetic structure with three (I, II, and III) lineages that predominate in North America and Europe. Type II strains cause most cases of symptomatic human infections in France and the United States, although few other regions have been adequately sampled. Here we determined the parasite genotype in amniotic fluid and cerebrospinal fluid samples from congenital toxoplasmosis cases in Poland. Nineteen confirmed congenital cases of toxoplasmosis were analyzed, including both severe and asymptomatic cases. The genotype of parasite strains causing congenital infection was determined by direct PCR amplification and restriction fragment length polymorphism analysis. Nested multiplex PCR analysis was used to type four independent polymorphic markers. The sensitivity of multiplex nested PCR was >/=25 parasites/ml in amniotic fluid and cerebral spinal fluid samples. Parasite DNA was successfully amplified in 9 of 19 samples (eight severely affected and one asymptomatic fetus). Only genotype II parasites were identified as the source of T. gondii infection based on restriction fragment length polymorphism analysis. Strains causing congenital infections were also typed indirectly based on detection of antibodies to strain-specific peptides. Serotyping indicated that 12 of 15 cases tested were caused by type II strains and these positives included both symptomatic and asymptomatic infections. Overall, the combined analysis indicated that 14 of the cases were caused by type II strains. Our results are consistent with the hypothesis that parasite burden is associated with severity of congenital toxoplasmosis and indicate that serological testing provides a promising method for genotypic analysis of toxoplasmosis.

Amniotic Fluid↗

Unusual ocular presentation of acute toxoplasmosis.

Four patients with toxoplasmosis are reported with unusual presenting ocular lesions. One patient had an active lesion that appeared to involve the optic nerve as well as focal toxoplasmosis chorioretinitis at the macula. A second patient had a pale optic nerve in association with the classical chorioretinal scars of toxoplasmosis. The third patient had toxoplasmosis chorioretinitis of the macula with subretinal neovascularisation. The fourth patient had a branch artery occlusion complicating acute retinitis.

Acute Disease↗

Immunoblotting can help the diagnosis of ocular toxoplasmosis.

AIMS: To determine whether IgG immunoblotting can improve the diagnosis of ocular toxoplasmosis. METHODS: Samples of serum were tested from patients with ocular lesions that could be caused by toxoplasmosis. All such samples from Scotland and Northern Ireland are usually referred to the Scottish Toxoplasma Reference Laboratory. From questionnaires filled out by the clinicians, two groups of sera were identified: ocular toxoplasmosis (active and quiescent), n = 54 (group 1); and eye disease as a result of other causes, n = 36 (group 2). Control groups were made up of sera from patients with no eye disease and a normal dye test result (< or = 125 IU/ml), n = 16 (group 3); and toxoplasma seronegative, cytomegalovirus (CMV) positive, and herpes simplex virus (HSV) positive sera (group 4), n = 18. RESULTS: Immunoblots with an active pattern could be identified (IgG antibodies against at least four antigens with molecular weight of 6, 20, 22, 23, 25, and 36 kDa). Significantly more of this pattern was found in group 1 (33 of 54; 61.1%) compared with group 2 (nine of 36; 25%) or group 3 (six of 16; 37.5%). Within group 1, significantly more sera with an active pattern had dye test results > or = 65 IU/ml compared with those without. More sera from patients < 30 years of age were found with the active pattern in group 1 compared with group 2. No group 4 sera had active immunoblot patterns. CONCLUSIONS: The immunoblot result adds more support to the diagnosis of ocular toxoplasmosis. In cases where the clinical diagnosis is difficult, immunoblots are particularly indicated; if negative, other causes of eye disease should be sought.

Adult↗

Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring.

OBJECTIVE: The authors examined the relationship between maternal antibody to toxoplasmosis and the risk of schizophrenia and other schizophrenia spectrum disorders in offspring. Toxoplasmosis is known to adversely affect fetal brain development. METHOD: In a nested case-control design of a large birth cohort born between 1959 and 1967, the authors conducted serological assays for Toxoplasma antibody on maternal serum specimens from pregnancies giving rise to 63 cases of schizophrenia and other schizophrenia spectrum disorders and 123 matched comparison subjects. Toxoplasma immunoglobulin (Ig)G antibody was quantified by using the Sabin-Feldman dye test. The Ig titers were classified into three groups: negative (<1:16) (reference), moderate (1:16-1:64), and high (> or =1:128). RESULTS: The adjusted odds ratio of schizophrenia/schizophrenia spectrum disorders for subjects with high maternal Toxoplasma IgG antibody titers was 2.61 (95% confidence interval=1.00-6.82). There was no association between moderate Toxoplasma Ig antibody titers and the risk of schizophrenia/spectrum disorders. CONCLUSIONS: These findings suggest that maternal exposure to toxoplasmosis may be a risk factor for schizophrenia. The findings may be explained by reactivated infection or an effect of the antibody on the developing fetus. Given that toxoplasmosis is a preventable infection, the findings, if replicated, may have implications for reducing the incidence of schizophrenia.

Adult↗

An outbreak of toxoplasmosis in farmed mink (Mustela vison S.).

A large Wisconsin mink (Mustela vison) farm experienced an outbreak of toxoplasmosis in the spring of 1999 following an outbreak of canine distemper during the previous fall. Major clinical signs for pregnant females included reduced feed consumption, abortions, and stillborn kits; kits < or =3 weeks old experienced ataxia and mortality. Of 7,800 females, 1,976 (26%) lost their entire litter either from abortion or neonatal mortality. Kit mortality from 7 days to 3 weeks of age was 3,300, and overall kit mortality attributed to the toxoplasmosis outbreak was 10,408. Six neonatal mink kits, 12 3-week-old kits, and 2 adult female mink were submitted to the University of Minnesota Veterinary Diagnostic Laboratory for diagnostic workup. Gross postmortem lesions were limited to empty stomachs (12 of 12 kits) and pale livers (4 of 12 kits) for the 3-week-old kits. Major microscopic lesions included interstitial pneumonia, encephalitis, encephalomalacia, and myocarditis. Toxoplasmosis was diagnosed by microscopic lesions, microscopic lesion distribution, and the detection of Toxoplasma gondii tachyzoites by immunohistochemistry. This is the first detailed report of an outbreak of toxoplasmosis in mink in the United States.

Abortion, Veterinary↗

Toxoplasmosis serology: an efficient hemagglutination procedure to detect IgG and IgM antibodies.

In search of an efficient but simple, low cost procedure for the serodiagnosis of Toxoplasmosis, especially suited for routine laboratories facing technical and budget limitations as in less developed countries, the diagnostic capability of Hematoxo, an hemagglutination test for toxoplasmosis, was evaluated in relation to a battery of tests including IgG- and IgM-immunofluorescence tests, hemagglutination and an IgM-capture enzymatic assay. Detecting a little as 5 I.U. of IgG antitoxoplasma antibodies, Hematoxo showed a straight agreement as to reactivity and non-reactivity for the 443 non-reactive and the 387 reactive serum samples, included in this study. In 23 cases presenting a serological pattern of acute toxoplasmosis and showing IgM antibodies, Hematoxo could detect IgM antibodies in 18, indicated by negativation or a significant decrease in titers as a result of treating samples with 2-mercapto-ethanol. However, a neat increase in sensitivity for IgM specific antibodies could be achieved by previously removing IgG from the sample, as demonstrated in a series of acute toxoplasmosis sera. A simple procedure was developed for this purpose, by reconstituting a lyophilized suspension of Protein A--rich Staphylococcus with the lowest serum dilution to be tested. Of low cost and easy to perform, Hematoxo affords not only a practical qualitative procedure for screening reactors and non-reactors, as in prenatal services, but also quantitative assays that permit to titrate antibodies as well as to identify IgM antibodies.

Animals↗

An estimation of the frequency of gestational toxoplasmosis in the Brazilian Federal District.

Acute infections by the protozoan Toxoplasma gondii during pregnancy (gestational toxoplasmosis) are known to cause serious health problems to the fetus (congenital toxoplasmosis). In Brasília, there have been few studies on the incidence of toxoplasmosis. This report summarizes a retrospective study performed on 2,636 selected pregnant women attended by the public health system of Guará, a satellite-city of Brasília. In this survey, 17 cases of gestational toxoplasmosis were detected; 15 of which were primary maternal infection and the remaining 2 were consistent with secondary maternal infection. These results suggest an annual seroconversion rate of 0.64 percent (90 percent confidence interval: 0.38, 0.90).

Animals↗

Prenatal study of fetal endocardial hyperrefringence and its relation to maternal toxoplasmosis.

OBJECTIVE: To compare a group of fetuses whose mothers had acute or recent toxoplasmosis with a group of fetuses whose mothers had no systemic disease, analyzing the presence of changes in endocardial refringence. METHODS: This study assessed 91 fetuses of mothers diagnosed with acute or recent toxoplasmosis, detected by seroconversion or the presence of elevated IgM and IgG titers, confirmed through the IgM-capture ELISA. They were compared with a control group comprising 182 fetuses selected from a low-risk population participating in a prenatal screening program for heart diseases. RESULTS: No significant difference was observed between the mean gestational (29.2+/-4.6 weeks; 29.2+/-4.6 weeks) and maternal (25.7+/-6.7 years; 26+/-5.4 years) ages in the 2 groups. Areas of endocardial hyperechogenicity were observed in 69 fetuses whose mothers had toxoplasmosis (75.8%) and in only 6 fetuses of the control group (3.3%) (P<0.001). In 52 patients of the group studied (75.4%), endocardial hyperrefringence was diffuse, and, in 17 (24.3%), it was focal. In the control group, focal distribution was observed in 5 fetuses (83.3%). CONCLUSION: The prenatal echocardiographic image of focal or diffuse endocardial hyperrefringence is more prevalent in pregnancies with maternal toxoplasmosis than in the healthy ones, and an association between fetal endocardial hyperechogenicity and maternal disease exists.

Acute Disease↗

A comparative study of congenital toxoplasmosis between public and private hospitals from Uberlândia, MG, Brazil.

The main purpose of the present study was to examine if there is difference in terms of incidence rates of congenital toxoplasmosis among populations assisted in public and private hospitals from Uberlândia, state of Minas Gerais, Brazil. A total of 805 serum samples from cord blood were collected, being 500 from public hospital and 305 from private hospital, and all patients answered a questionnaire about pregnancy and newborns. An indirect enzyme linked immunosorbent assay (ELISA) was performed to detect IgG antibodies to Toxoplasma gondii and the positive samples were retested to verify the presence of specific IgM and IgA antibodies in a capture ELISA. We found significant differences among data from both hospitals with respect to maternal age, origin city, gestational age, number of visits to physicians during pregnancy, type of delivery, and birth weight. Seroprevalence of IgG antibodies against T. gondii for patients from public and private hospitals was 57.6% and 41.9% respectively, and this difference was statistically significant (P < 0.0001). In addition, the frequency of congenital toxoplasmosis measured by the presence of IgM and/or IgA antibodies toward T. gondii was exclusively located in samples from public hospital (0.8%), and no positive sample was seen in private hospital (0%). Considering that almost all babies suffering from congenital toxoplasmosis, if undiagnosed and untreated, will develop visual or neurological impairments by adulthood, the results presented herein emphasized the importance to accomplish screening programs for toxoplasmosis during pregnancy, particularly in the public hospitals, due to the expressive rate of congenital disease showed in the patients attended at these centers.

Animals↗

[Toxoplasmosis: occurrence of antibodies antitoxoplasma gondii and diagnosis].

UNLABELLED: Toxoplasmosis is a zoonosis of broad geographic distribution, being an opportunist infection mainly in AIDS patients. The incidence of serum antibodies of the type anti-Toxoplasma gondii is variable and growing according the different age groups. The laboratory test for the diagnostic of this disease, include the exam of the pathologic species as well as immunologic tests. Although the serum tests have limitations, they are still utilized in the Clinical Analysis laboratories. To improve the congenital toxoplasmosis diagnosis in AIDS patients, the polymerase chain reaction (PCR) and Nested-PCR have been utilized alternatively. PURPOSES: To focus the occurrence of toxoplasmosis, considering the different techniques and shapes of point of views in the serological analysis. METHODS: The antibodies (Ac) anti-Toxoplasma gondii of 2994 patients from the Santa Catarina Federal University Hospital, in the period from February 28, 1996 to July 28, 1998 were evaluated. This evaluation was accomplished by the Immunofluorescency Indirect reaction, which was confirmed by the ELISA method. RESULTS: The results showed that 41.91% of the patients had the antibodies anti-Toxoplasma gondii. From this total we concluded that 0.87% of these patients had the IgM in different titles which can be or not classified in the acute phase of the disease. This study demonstrates that the incidence of toxoplasmosis in our orment is relatively high. It shows too that in the identification of the acute process of the disease, the serologic tests can be added to a more sensible and specific techniques that allows the evidentiation of the microorganism thus contributing to a better diagnosis.

Animals↗

Current recommendations and future prospects in the treatment of toxoplasmosis.

Toxoplasma infection is highly prevalent throughout the world and causes disease in diverse populations. Effective treatment regimens are available for each clinical entity of toxoplasma, but problems of incomplete clinical efficacy, drug potency, drug safety, and length of treatment remain. No well-controlled clinical trials in humans have been performed to evaluate the efficacy and safety of treatment. Primary treatment of toxoplasmosis is with the synergistic combination of pyrimethamine and sulphonamide. This is considered the treatment of choice for severe disease, disease in immunocompromised patients, and congenital toxoplasmosis. Spiramycin, a macrolide antibiotic, is frequently used alone or alternately with pyrimethamine and sulphonamide for pregnant women with the acute acquired infection to prevent congenital toxoplasmosis. Clindamycin is used frequently to treat acute flares of toxoplasmic chorioretinitis and as second-line therapy for toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome (AIDS). Inadequacies in the treatment of toxoplasmosis in immunosuppressed patients, exemplified by experience with AIDS patients, should provide the impetus for well-designed trials to find and evaluate more potent and better-tolerated agents. Classes of new drugs that have been investigated and show some promise include: (a) macrolides (roxithromycin, azithromycin); (b) folic acid antagonists (piritrexim and trimetrexate), and (c) purine analogues (arprinocid). Immunomodulators have attracted interest, and interferon-gamma alone and in combination with roxithromycin is effective in murine models. Interleukin-2 is also effective in the murine model.

Animals↗

Use of a multiplex polymerase chain reaction assay in the antemortem diagnosis of toxoplasmosis and neosporosis in the central nervous system of cats and dogs.

OBJECTIVE: To develop a multiplex polymerase chain reaction (PCR) assay for the detection of Toxoplasma gondii and Neospora caninum DNA in canine and feline biological samples. SAMPLE POPULATION; Biological samples from 7 cats with systemic (n = 4) or CNS (3) toxoplasmosis, 6 dogs with neospora- or toxoplasma-associated encephalitis, and 11 animals with nonprotozoal disease. PROCEDURE: Primers for T gondii, N caninum, and the canine ferritin gene (dogs) or feline histone 3.3 gene (cats) were combined in a single PCR assay. The DNA was extracted from paraffin-embedded brain tissue, CSF, or skeletal muscle. The PCR products with positive results were cloned, and sequence identity was confirmed. RESULTS: Of 7 cats and 4 dogs with immunohistochemical or serologic evidence of toxoplasmosis, PCR results were positive for all cats and 3 dogs for T gondii, and positive for T gondii and N caninum for 1 dog. Another dog had negative PCR results for both parasites. Of 2 dogs with immunohistochemical or serologic evidence of neosporosis, PCR results were positive for 1 for N caninum and positive for the other for T gondii. All negative-control samples yielded negative results for T gondii and N caninum on the PCR assay. CONCLUSIONS AND CLINICAL RELEVANCE: Standard tests for toxoplasmosis or neosporosis associated with the CNS rely on serologic, histologic, or immunohistochemical analysis and can be difficult to interpret. The multiplex PCR assay with built-in control reactions could be a complementary clinical tool for the antemortem diagnosis of toxoplasmosis or neosporosis associated with the CNS.

Animals↗