Association between infection with Toxoplasma gondii and psychiatric disorders.

Toxoplasmosis is one of the world's most prevalent zoonoses. The causative agent, Toxoplasma gondii (Nicolle et Manceaux, 1908) is a facultative heteroxenic, polyxenic apicomplexan protist. There are several potential pathways of transmission within and between host species. Most infections with T. gondii result from close contact with pets/cats, ingestion of tissue cysts in undercooked meat of infected animals, and oocysts from food or water contaminated by feline faeces. Recently, epidemiological studies have shown that T. gondii infection plays a prominent role in the pathogenesis of several psychiatric disorders. This report reviews the association between T. gondii infection and patients with psychiatric disorders, particularly schizophrenia, depressive disorders and bipolar disorders.

Global prevalence of Toxoplasma gondii infection in the aborted fetuses and ruminants that had an abortion: A systematic review and meta-analysis.

Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan protozoan that can cause reproductive losses in ruminants across the world. Therefore, a meta-analysis was conducted to estimate the worldwide prevalence of T. gondii infection in the aborted fetuses and stillbirths of sheep, goat, and cattle. Moreover, it attempted to evaluate the prevalence rate of T. gondii infection in ruminants that had abortions using serological methods. Based on the keywords, a systematic search of six databases was conducted to retrieve cross-sectional articles in English-language. Data were synthesized to calculate the overall prevalence of T. gondii infection worldwide using the random-effects model with a 95 % confidence interval (CI). Moreover, the present study includes sensitivity analysis, publication bias test, and quality assessment of the studies. The final analyses included 37, 19, and 8 studies conducted on sheep (4383 aborted fetuses and stillbirths as well as 1940 abortive sheep), goat (248 aborted fetuses and stillbirths and 533 abortive goats), and cattle (460 aborted fetuses and stillbirths and 165 abortive cattle). The overall prevalence rates of T. gondii infection in aborted fetuses and stillbirths globally were 42 % (95 % CI: 17 %-67 %), and 31 % (95 % CI: 11 %-51 %) using molecular methods for sheep and goats, as well as 16 % (95 % CI: 11 %-22 %) and 27 % (95 % CI: 1 %-54 %) using serological tests for sheep and goats, respectively. In addition, the overall prevalence rates of T. gondii infection in sheep and goats that had abortions were 56 % (95 % CI: 35 %-76 %) and 50 % (95 % CI: 6 %-94 %), respectively. These analyses could not be performed in cattle due to the small number of studies and the small number of animals under study. According to the high prevalence of T. gondii infection in sheep and goats that had an abortion, T. gondii could be a potential factor of causing reproductive failures in ruminants worldwide. So, effective control measures and strategies are needed to reduce the rate of abortion in sheep and goats as well as reduce the economic damage to the livestock industry.

Prior Toxoplasma Gondii Infection Ameliorates Liver Fibrosis Induced by Schistosoma Japonicum through Inhibiting Th2 Response and Improving Balance of Intestinal Flora in Mice.

Schistosomiasis is an immunopathogenic disease in which a T helper (Th) cell type 2-like response plays vital roles. Hepatic fibrosis is its main pathologic manifestations, which is the leading cause of hepatic cirrhosis. Co-infections of Schistosoma japonicum (Sj) with other pathogens are frequently encountered but are easily ignored in clinical studies, and effective therapeutic interventions are lacking. In this study, we explored the effect of Toxoplasma gondii (Tg) prior infection on Th1/Th2 response, community shifts in gut microbiome (GM), and the pathogenesis of schistosomiasis in murine hosts. Mice were prior infected with Tg before Sj infection. The effects of co-infection on Th1/Th2 response and hepatic fibrosis were analyzed. Furthermore, we investigated this issue by sequencing 16S rRNA from fecal specimens to define the GM profiles during co-infection. Tg prior infection markedly reduced the granuloma size and collagen deposit in livers against Sj infection. Prior infection promoted a shift toward Th1 immune response instead of Th2. Furthermore, Tg infection promoted the expansion of preponderant flora and Clostridiaceae was identified as a feature marker in the GM of the co-infection group. Redundancy analysis (RDA)/canonical correspondence analysis (CCA) results showed that liver fibrosis, Th1/Th2 cytokines were significantly correlated (P < 0.05) with the GM compositions. Tg infection inhibits hepatic fibrosis by downregulating Th2 immune response against Sj infection, and further promotes the GM shifts through "gut-liver axis" in the murine hosts. Our study may provide insights into potential anti-fibrosis strategies in co-infection individuals.

Molecular Diagnosis and Pathological Study of Toxoplasma gondii in Aborted Caprine and Ovine Fetuses in Borderline of Iran-Iraq.

BACKGROUND: Infection with the protozoan parasite Toxoplasma gondii is widely prevalent in animals and humans. In goats and sheep this infection has a high economic impact as it causes abortions and lamb losses. Although there are several studies reporting seroprevalence in small ruminants in Iran, molecular-based information is scarce. PURPOSE: This study aimed to screen caprine and ovine aborted fetuses for T. gondii infection by PCR and histopathology. METHODS: Brains of 121 aborted fetuses (10 caprine and 111 ovine) were collected from different parts of the Kordestan province, bordering with Iraq. Gestational age and the general status of each fetus such as freshness, autolysis, mummification and presence of macroscopic lesions in the fetus and foetal membranes was recorded. Individual brain tissues of fetuses were subjected to nested-PCR targeting the B1 gene, and histopathological sections prepared from brains were examined microscopically. RESULTS: PCR results revealed T. gondii-associated abortion in one caprine and nine ovine fetuses (8.3%). Microscopically, pathological lesions included non-purulent meningitis associated with gliosis, focal necrosis, and occasionally tissue cyst. CONCLUSION: This paper reports for the first time T. gondii-associated abortion in goats in Iran. As organs from aborted fetuses do not necessarily show lesions, molecular confirmation is the unique diagnostic method and should be used in situations of an abortion epidemic.

Transcriptomic analysis of reproductive damage in the epididymis of male Kunming mice induced by chronic infection of Toxoplasma gondii PRU strain.

BACKGROUND: Some researchers have reported that Toxoplasma gondii can cause serious reproductive impairment in male animals. Specifically, T. gondii destroy the quality of sperm in the epididymis, which affects their sexual ability. However, among such studies, none have investigated the male reproductive transcriptome. Therefore, to investigate the relationship between T. gondii and sperm maturation, we infected mice with T. gondii prugniaud (PRU) strain and performed transcriptome sequencing of the epididymis. RESULTS: Compared with the control group, 431 upregulated and 229 downregulated differentially expressed genes (DEGs) were found (P-value < 0.05, false discovery rate (FDR) < 0.05 and |log2 (fold change)| ≥ 1). According to results of a bioinformatics analysis, Gene Ontology (GO) function is divided into three categories: cellular component, molecular function and biological process. Upon performing GO analysis, we found that some DEGs correlated with an integral part of membrane, protein complex, cell surface, ATP binding, immune system process, signal transduction and metabolic process which are responsible for the epididymal injury. DEGs were mapped to 101 unique KEGG pathways. Pathways such as cytokine-cytokine receptor interaction, glycolysis/gluconeogenesis and apoptosis are closely related to sperm quality. Moreover, Tnfsf10 and spata18 can damage the mitochondria in sperm, which decreases sperm motility and morphology. CONCLUSIONS: We sequenced the reproductive system of male mice chronically infected with T. gondii, which provides a new direction for research into male sterility caused by Toxoplasma infection. This work provides valuable information and a comprehensive database for future studies of the interaction between T. gondii infection and the male reproductive system.

Coxiella burnetii associated with BVDV (Bovine Viral Diarrhea Virus), BoHV (Bovine Herpesvirus), Leptospira spp., Neospora caninum, Toxoplasma gondii and Trypanosoma vivax in reproductive disorders in cattle.

This is a cross-sectional study to assess the presence of antibodies in ruminants against selected pathogens associated with reproductive disorders in cattle in four Brazilian states, including the zoonotic agent Coxiella burnetii. The used tests were Virus Neutralization Assay for IBR and BVD, Microscopic Agglutination Test for Leptospira spp., Indirect Fluorescent Antibody Test (IFAT) for C. burnetii and Toxoplasma gondii, and Enzyme-Linked Immunosorbent Assay for Neospora caninum and Trypanosoma vivax. Seropositivity for C. burnetii was 13.7% with titers from 128 to 131,072; 57.8% for BoHV-1, with titers between 2 and 1,024; 47.1% for BVDV-1a, with titers from 10 to 5,120; 89.2% for N. caninum; 50% for T. vivax; and 52.0% for Leptospira spp., with titers between 100 to 800 (the following serovars were found: Tarassovi, Grippotyphosa, Canicola, Copenhageni, Wolffi, Hardjo, Pomona and Icterohaemorrhagiae); 19.6% for T. gondii with titer of 40. This is the first study that has identified C. burnetii in cattle associated with BoHV and BVDV, N. caninum, Leptospira spp., T. gondii and T. vivax. Thus, future studies should be conducted to investigate how widespread this pathogen is in Brazilian cattle herds.

Treatment with Bumped Kinase Inhibitor 1294 Is Safe and Leads to Significant Protection against Abortion and Vertical Transmission in Sheep Experimentally Infected with Toxoplasma gondii during Pregnancy.

Previous studies on drug efficacy showed low protection against abortion and vertical transmission of Toxoplasma gondii in pregnant sheep. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. Here, we present the safety and efficacy of BKI-1294 treatment (dosed orally at 100 mg/kg of body weight 5 times every 48 h) initiated 48 h after oral infection of sheep at midpregnancy with 1,000 TgShSp1 oocysts. BKI-1294 demonstrated systemic exposure in pregnant ewes, with maximum plasma concentrations of 2 to 3 µM and trough concentrations of 0.4 µM at 48 h after each dose. Oral administration of BKI-1294 in uninfected sheep at midpregnancy was deemed safe, since there were no changes in behavior, fecal consistency, rectal temperatures, hematological and biochemical parameters, or fetal mortality/morbidity. In ewes infected with a T. gondii oocyst dose lethal for fetuses, BKI-1294 treatment led to a minor rectal temperature increase after infection and a decrease in fetal/lamb mortality of 71%. None of the lambs born alive in the treated group exhibited congenital encephalitis lesions, and vertical transmission was prevented in 53% of them. BKI-1294 treatment during infection led to strong interferon gamma production after cell stimulation in vitro and a low humoral immune response to soluble tachyzoite antigens but high levels of anti-SAG1 antibodies. The results demonstrate a proof of concept for the therapeutic use of BKI-1294 to protect ovine fetuses from T. gondii infection during pregnancy.

Schistosoma mansoni Coinfection Attenuates Murine Toxoplasma gondii-Induced Crohn's-Like Ileitis by Preserving the Epithelial Barrier and Downregulating the Inflammatory Response.

Background and aims: Mice orally infected with T. gondii develop Crohn's disease (CD)-like enteritis associated with severe mucosal damage and a systemic inflammatory response, resulting in high morbidity and mortality. Previously, helminthic infections have shown therapeutic potential in experimental colitis. However, the role of S. mansoni in T. gondii-induced CD-like enteritis has not been elucidated. Our study investigated the mechanisms underlying T. gondii-induced ileitis and the potential therapeutic effect of S. mansoni coinfection. Methods: C57BL/6 mice were infected by subcutaneous injection of cercariae of the BH strain of S. mansoni, and 7-9 weeks later, they were orally infected with cysts of the ME49 strain of T. gondii. After euthanasia, the ileum was removed for histopathological analysis; staining for goblet cells; immunohistochemistry characterizing mononuclear cells, lysozyme expression, apoptotic cells, and intracellular pathway activation; and measuring gene expression levels by real-time PCR. Cytokine concentrations were measured in the serial serum samples and culture supernatants of the ileal explants, in addition to myeloperoxidase (MPO) activity. Results:T. gondii-monoinfected mice presented dense inflammatory cell infiltrates and ulcerations in the terminal ileum, with abundant cell extrusion, apoptotic bodies, and necrosis; these effects were absent in S. mansoni-infected or coinfected animals. Coinfection preserved goblet cells and Paneth cells, remarkably depleted in T. gondii-infected mice. Densities of CD4- and CD11b-positive cells were increased in T. gondii- compared to S. mansoni-infected mice and controls. MPO was significantly increased among T. gondii-mice, while attenuated in coinfected animals. In T. gondii-infected mice, the culture supernatants of the explants showed increased concentrations of TNF-alpha, IFN-gamma, and IL-17, and the ileal tissue revealed increased expression of the mRNA transcripts for IL-1 beta, NOS2, HMOX1, MMP3, and MMP9 and activation of NF-kappa B and p38 MAPK signaling, all of which were counterregulated by S. mansoni coinfection. Conclusion:S. mansoni coinfection attenuates T. gondii-induced ileitis by preserving mucosal integrity and downregulating the local inflammatory response based on the activation of NF-kappa B and MAPK. The protective function of prior S. mansoni infection suggests the involvement of innate immune mechanisms and supports a conceptually new approach to the treatment of chronic inflammatory diseases, including CD.

Coxiella burnetii associated with BVDV (Bovine Viral Diarrhea Virus), BoHV (Bovine Herpesvirus), Leptospira spp, Neospora caninum, Toxoplasma gondii and Trypanosoma vivax in reproductive disorders in cattle / Coxiella burnetii associada ao BVDV (Vírus da Diarreia Viral Bovina), BoHV (Vírus do Herpes Bovino), Leptospira spp, Neospora caninum, Toxoplasma gondii e Trypanosoma vivax em distúrbios reprodutivos em bovinos

Abstract This is a cross-sectional study to assess the presence of antibodies in ruminants against selected pathogens associated with reproductive disorders in cattle in four Brazilian states, including the zoonotic agent Coxiella burnetii. The used tests were Virus Neutralization Assay for IBR and BVD, Microscopic Agglutination Test for Leptospira spp., Indirect Fluorescent Antibody Test (IFAT) for C. burnetii and Toxoplasma gondii, and Enzyme-Linked Immunosorbent Assay for Neospora caninum and Trypanosoma vivax. Seropositivity for C. burnetii was 13.7% with titers from 128 to 131,072; 57.8% for BoHV-1, with titers between 2 and 1,024; 47.1% for BVDV-1a, with titers from 10 to 5,120; 89.2% for N. caninum; 50% for T. vivax; and 52.0% for Leptospira spp., with titers between 100 to 800 (the following serovars were found: Tarassovi, Grippotyphosa, Canicola, Copenhageni, Wolffi, Hardjo, Pomona and Icterohaemorrhagiae); 19.6% for T. gondii with titer of 40. This is the first study that has identified C. burnetii in cattle associated with BoHV and BVDV, N. caninum, Leptospira spp., T. gondii and T. vivax. Thus, future studies should be conducted to investigate how widespread this pathogen is in Brazilian cattle herds.

Resumo Este é um estudo transversal para avaliar a presença de anticorpos em ruminantes contra patógenos selecionados e associados a distúrbios reprodutivos em bovinos de quatro estados brasileiros, incluindo o agente zoonótico Coxiella burnetii. Os testes utilizados foram Teste de Vírus-Neutralização para BoHV e BVDV, teste de Aglutinação Microscópica para Leptospira spp., Reação de Imunofluorescência Indireta for C. burnetii e Toxoplasma gondii, e Ensaio de Imunoabsorção Enzimática para Neospora caninum e Trypanosoma vivax. A soropositividade para C. burnetii foi de 13,7% com títulos de 128 a 131.072; 57,8% para BoHV-1, com títulos entre 2 a 1.024; 47,1% para BVDV-1a, com títulos de 10 a 5.120; 89,2% para N. caninum; 50% para T. vivax; e 52,0% para Leptospira spp., com títulos entre 100 a 800 (sorovares encontrados: Tarassovi, Grippotyphosa, Canicola, Copenhageni, Wolffi, Hardjo, Pomona e Icterohaemorrhagiae) 19,6% para T. gondii com título de 40. Este é o primeiro estudo que evidencia a participação de C. burnetii em bovinos associada ao Vírus da Rinotraqueíte bovina infecciosa e da diarreia viral bovina, N. caninum, Leptospira spp., T. gondii e T. vivax em bovinos. Desta forma, futuros estudos devem ser conduzidos a fim de investigar o quão disseminado se encontra este patógeno em rebanhos bovinos brasileiros.

Rhodococcus equi pVAPN type causing pneumonia in a dog coinfected with canine morbillivirus (distemper virus) and Toxoplasma gondii.

Canine morbillivirus (previously, canine distemper virus, CDV) is a highly contagious infectious disease-causing agent that produces immunosuppressive infections and multiple clinical signs. Canine toxoplasmosis is an opportunistic disease characterized by enteric, pulmonary, and neuromuscular signs that might be confused with CDV-induced infections. Rhodococcus equi is a Gram-positive intracellular facultative bacterium that is also opportunistic in nature, and causes pyogranulomatous infections in humans and multiple host animals, although canine rhodococcosis is rare or unrecognized. The pathogenicity of R. equi is intimately related to the presence of plasmid-encoded virulence-associated proteins (Vap). Three host-adapted virulence plasmid types of R. equi have been recognized: the circular pVAPA and pVAPB are associated with equine and porcine strains, respectively, and the recently detected linear pVAPN virulence plasmid is related to bovine isolates. Nevertheless, data regarding the detection of host-adapted virulence plasmid types of R. equi isolated from companion animals are scarce. This report describes a case of an uncommon coinfection due to R. equi, T. gondii and CDV, which was diagnosed in a pet dog with respiratory distress. In this case, CDV most likely induced immunosuppression, which facilitated opportunistic infections by R. equi and T. gondii. The analysis of the virulence profile of R. equi revealed the novel pVAPN plasmid type, initially related to bovine strains. This is the second report of the bovine-associated pVAPN type in a pet dog, with an unusual coinfection with T. gondii and CDV. These findings represent a public health concern due to the close contact between pet animals and their owners, particularly because the pVAPN plasmid type was recently detected in people with HIV/AIDS from the same geographical region.

Reproductive disorders in does experimentally infected by Toxoplasma gondii / Distúrbios reprodutivos em cabras experimentalmente infectadas por Toxoplasma gondii

The aim of this study was to describe the reproductive disorders related to experimental infection by artificial insemination with semen contaminated with Toxoplasma gondii of four goats in the chronic phase of the infection. In the end of the study, the does were submitted to necropsy, and PCR and histopathological evaluations were performed. Among infected does that exhibited embryonic loss, two were in anestrus and two exhibited repeated estrus. One of the latter animals exhibited clinical signs of estrus at seven-day intervals, whereas the other had a 21-day estrous cycle. However, both does were naturally mated on subsequent natural estrous and were not able to get pregnant until the end of the experiment (90 d). Two of the goats exhibited abnormalities in the ultrasound examinations, one of which was an ovarian cyst, while the other was a hydrosalpinx, both of which were confirmed in the post-mortem examination. The main microscopic injuries in this group were neutrophilic infiltration of the lungs, interstitial glomerulonephritis and neutrophilic infiltration of the liver. T. gondii DNA was found in the organs (heart and brain) of three does. In conclusion, does infected with Toxoplasma gondii in semen at the time of artificial insemination display reproductive disorders in the chronic phase of infection that might be associated with toxoplasmosis.

Objetivou-se descrever os distúrbios reprodutivos associados à infecção experimental por Toxoplasma gondii através da inseminação artificial com sêmen contaminado em quatro cabras no estágio crônico da infecção. As características do trato reprodutor foram avaliadas através de ultrassonografia transretal, visando o diagnóstico gestacional ou de desordens reprodutivas, após a infecção experimental. Ao final do experimento, os animais foram necropsiados e avaliações histopatológicas e PCR foram realizados. Dentre os animais infectados que exibiram mortalidade embrionária, duas apresentaram anestro e duas apresentaram repetição de estro, sendo que destas uma apresentou intervalos entre estros reduzido (sete dias) e outra em intervalo regular (21 dias). Todavia, ambas foram submetidas a monta natural durante os estros naturais subsequentese não foi confirmada gestação até o final do experimento (90 dias). Duas cabras exibiram alterações nos exames de ultrassonografia, sendo identificadas um cisto ovariano, e uma hidrossalpinge, ambas confirmadas no exame post-mortem. As principais lesões microscópicas nesse grupo foram infiltração neutrofílica dos pulmões, glomerulonefrite intersticial e infiltração neutrofílica do fígado. O DNA de T. gondii foi encontrado nos órgãos (coração e cérebro) de três cabras. Em conclusão, cabras infectadas comsêmen contendoT. gondii no momento da inseminação artificial apresentam distúrbios reprodutivos na fase crônica da infecção que podem estar associados à toxoplasmose.

Distúrbios reprodutivos em cabras experimentalmente infectadas por Toxoplasma gondii / Reproductive disorders in does experimentally infected by Toxoplasma gondii

Objetivou-se descrever os distúrbios reprodutivos associados à infecção experimental por Toxoplasma gondii através da inseminação artificial com sêmen contaminado em quatro cabras no estágio crônico da infecção. As características do trato reprodutor foram avaliadas através de ultrassonografia transretal, visando o diagnóstico gestacional ou de desordens reprodutivas, após a infecção experimental. Ao final do experimento, os animais foram necropsiados e avaliações histopatológicas e PCR foram realizados. Dentre os animais infectados que exibiram mortalidade embrionária, duas apresentaram anestro e duas apresentaram repetição de estro, sendo que destas uma apresentou intervalos entre estros reduzido (sete dias) e outra em intervalo regular (21 dias). Todavia, ambas foram submetidas a monta natural durante os estros naturais subsequentes e não foi confirmada gestação até o final do experimento (90 dias). Duas cabras exibiram alterações nos exames de ultrassonografia, sendo identificadas um cisto ovariano, e uma hidrossalpinge, ambas confirmadas no exame post-mortem. As principais lesões microscópicas nesse grupo foram infiltração neutrofílica dos pulmões, glomerulonefrite intersticial e infiltração neutrofílica do fígado. O DNA de T. gondii foi encontrado nos órgãos (coração e cérebro) de três cabras. Em conclusão, cabras infectadas com sêmen contendo T. gondii no momento da inseminação artificial apresentam distúrbios reprodutivos na fase crônica da infecção que podem estar associados à toxoplasmose.

The aim of this study was to describe the reproductive disorders related to experimental infection by artificial insemination with semen contaminated with Toxoplasma gondii of four goats in the chronic phase of the infection. In the end of the study, the does were submitted to necropsy, and PCR and histopathological evaluations were performed. Among infected does that exhibited embryonic loss, two were in anestrus and two exhibited repeated estrus. One of the latter animals exhibited clinical signs of estrus at seven-day intervals, whereas the other had a 21-day estrous cycle. However, both does were naturally mated on subsequent natural estrous and were not able to get pregnant until the end of the experiment (90 d). Two of the goats exhibited abnormalities in the ultrasound examinations, one of which was an ovarian cyst, while the other was a hydrosalpinx, both of which were confirmed in the post-mortem examination. The main microscopic injuries in this group were neutrophilic infiltration of the lungs, interstitial glomerulonephritis and neutrophilic infiltration of the liver. T. gondii DNA was found in the organs (heart and brain) of three does. In conclusion, does infected with Toxoplasma gondii in semen at the time of artificial insemination display reproductive disorders in the chronic phase of infection that might be associated with toxoplasmosis.

Outbreak of toxoplasmosis in four squirrel monkeys (Saimiri sciureus) in Japan.

Toxoplasma gondii is a protozoan parasite that causes fatal disease in New World monkeys. Several reports have described outbreaks of toxoplasmosis in squirrel monkeys. Here, we report the death of four squirrel monkeys in a captive colony from acute toxoplasmosis, one of which developed toxoplasmosis about 1 year after the initial outbreak. Serum anti-T. gondii antibody was detected by a latex agglutination test in the animals, and one presented seropositive before clinical signs were observed. Macroscopically, the lungs were severely affected and three animals showed pulmonary edema. Microscopically, interstitial pneumonia was observed in all animals. In the liver and heart, multifocal mononuclear cell infiltration with necrosis was detected. Parasite loading tended to be higher in the lungs, liver and heart than in the spleen, kidney and brain. The parasite was isolated from the brain of one animal and this isolate showed type II restriction patterns in the SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2 and PK1 genes of T. gondii and type I restriction patterns in the L358 and Apico genes by PCR-Restriction Fragment Length Polymorphism analysis. The clinical signs were reduced in mice infected with this isolate compared with those infected with reference type II strain PLK in a bioassay. To our knowledge, this is the first report of isolation of the parasite from squirrel monkeys in Japan and offers the opportunity for genomic and pathogenic analyses to aid our understanding of acute toxoplasmosis.

A case of pulmonary toxoplasmosis resembling multiple lung metastases of nasal lymphoma in a cat receiving chemotherapy.

An 11-year-old cat presented with nasal discharge and lacrimation and was diagnosed with nasal lymphoma. Although the cat showed favorable progression after undergoing chemotherapy, CT imaging demonstrated enlarged pulmonary nodules caused by Toxoplasma gondii. Following the cessation of chemotherapy, the cat was prescribed clindamycin hydrochloride for toxoplasmosis treatment; however, the cat developed kidney lymphoma and died. No T. gondii organisms were observed in the whole body necropsy specimens. It is known that immunocompromised human patients, including those who undergo chemotherapy, are considered at risk for toxoplasmosis. However, the risk of developing toxoplasmosis in cats undergoing chemotherapy is currently unknown. Findings from this case report suggest that cats with chemotherapy-resistant pulmonary masses might have a T. gondii infection rather than metastatic disease.

Toxoplasma gondii infection triggers chronic cachexia and sustained commensal dysbiosis in mice.

Toxoplasma gondii is a protozoan parasite with a predation-mediated transmission cycle between rodents and felines. Intermediate hosts acquire Toxoplasma by eating parasite cysts which invade the small intestine, disseminate systemically and finally establish host life-long chronic infection in brain and muscles. Here we show that Toxoplasma infection can trigger a severe form of sustained cachexia: a disease of progressive lean weight loss that is a causal predictor of mortality in cancer, chronic disease and many infections. Toxoplasma cachexia is characterized by acute anorexia, systemic inflammation and loss of 20% body mass. Although mice recover from symptoms of peak sickness, they fail to regain muscle mass or visceral adipose depots. We asked whether the damage to the intestinal microenvironment observed at acute time points was sustained in chronic infection and could thereby play a role in sustaining cachexia. We found that parasites replicate in the same region of the distal jejunum/proximal ileum throughout acute infection, inducing the development of secondary lymphoid structures and severe, regional inflammation. Small intestine pathology was resolved by 5 weeks post-infection. However, changes in the commensal populations, notably an outgrowth of Clostridia spp., were sustained in chronic infection. Importantly, uninfected animals co-housed with infected mice display similar changes in commensal microflora but never display symptoms of cachexia, indicating that altered commensals are not sufficient to explain the cachexia phenotype alone. These studies indicate that Toxoplasma infection is a novel and robust model to study the immune-metabolic interactions that contribute to chronic cachexia development, pathology and potential reversal.

Molecular and serological prevalence of Toxoplasma gondii and Anaplasma spp. infection in goats from Chongqing Municipality, China.

Toxoplasmosis and anaplasmosis are severe zoonotic diseases, the former caused by Toxoplasma gondii and the latter by Anaplasma spp. In the present study, 332 goat blood samples were randomly collected from Chongqing Municipality, China to screen for T. gondii and Anaplasma spp. We used a polymerase chain reaction (PCR) to detect DNA, and enzyme-linked immunosorbent assay (ELISA) to test for T. gondii antibodies. The prevalence of T. gondii and Anaplasma spp. was 38% and 35% respectively by PCR, and 42% for T. gondii antibodies by ELISA. The co-infection rate by T. gondii and Anaplasma was 13%, where the two predominant pathogens co-infecting were Anaplasma phagocytophilum + A. bovis (10%), followed by T. gondii + A. phagocytophilum (9.64%). While co-infection by three pathogens varied ranging from 1.81% to 5.72%, less than 1% of goats were found to be positive for four pathogens. This is the first investigation of T. gondii and Anaplasma spp. infection in goats from Chongqing.

Protozoal coinfection in horses with equine protozoal myeloencephalitis in the eastern United States.

BACKGROUND: Infection by 2 or more protozoa is linked with increased severity of disease in marine mammals with protozoan encephalitis. HYPOTHESIS/OBJECTIVES: To assess whether horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona also have evidence of infection with Neospora hughesi or Toxoplasma gondii. We hypothesized that horses with EPM would be more likely than horses with cervical vertebral stenotic myelopathy (CVSM) to be positive for antibodies to multiple protozoan parasites. ANIMALS: One hundred one horses with neurologic disease: 49 with EPM and 52 with CVSM. METHODS: Case review. Archived serum and cerebrospinal fluid (CSF) from 101 horses were examined. Inclusion criteria included neurologic disease, antemortem or postmortem diagnosis of EPM or CVSM, and availability of serological results or archived samples for testing. Additional testing for antibodies was performed on serum for T. gondii, as well as serum and CSF for N. hughesi. RESULTS: Horses with EPM were more likely than horses with CVSM to have positive immunologic results for S. neurona on serum (95.9% versus 76.9%, P = .0058), CSF (98.0% versus 44.2%, P < .00001), and serum : CSF titer ratio (91.8% versus 0%, P < .00001). Positive results for Neospora and Toxoplasma were uncommon, with total seroprevalence rates of 12.9% and 14.9%, respectively. The proportions of EPM cases testing positive for Neospora and Toxoplasma (16% and 12%) were not different from the proportions of CVSM cases testing positive (10% and 17%, P = .31 and .47, respectively). CONCLUSION: Results do not indicate an important role for protozoal coinfection in EPM in the eastern United States.

First description of clonal lineage type II (genotype #1) of Toxoplasma gondii in abortion outbreak in goats.

The purpose of this study was to perform genotypic characterization and to evaluate the virulence of Toxoplasma gondii obtained from aborted fetuses in an abortion outbreak in goats from northeastern Brazil. Brain samples from 32 fetuses were submitted to mouse bioassay for T. gondii isolation. Two isolates were obtained and subjected to genotypic characterization. Isolate virulence was evaluated using murine model in different doses (from 105 to 101 tachyzoites/mL). In genotyping, both isolates were classified as clonal lineage type II (genotype #1 ToxoDB) and showed to be virulent for mice. This is the first description of genotype #1 in cases of goat abortion, showing the circulation of virulent T. gondii isolate producing reproductive disorders in pregnant goat.

Toxoplasma Co-infection Prevents Th2 Differentiation and Leads to a Helminth-Specific Th1 Response.

Nematode infections, in particular gastrointestinal nematodes, are widespread and co-infections with other parasites and pathogens are frequently encountered in humans and animals. To decipher the immunological effects of a widespread protozoan infection on the anti-helminth immune response we studied a co-infection with the enteric nematode Heligmosomoides polygyrus in mice previously infected with Toxoplasma gondii. Protective immune responses against nematodes are dependent on parasite-specific Th2 responses associated with IL-4, IL-5, IL-13, IgE, and IgG1 antibodies. In contrast, Toxoplasma gondii infection elicits a strong and protective Th1 immune response characterized by IFN-γ, IL-12, and IgG2a antibodies. Co-infected animals displayed significantly higher worm fecundity although worm burden remained unchanged. In line with this, the Th2 response to H. polygyrus in co-infected animals showed a profound reduction of IL-4, IL-5, IL-13, and GATA-3 expressing T cells. Co-infection also resulted in the lack of eosinophilia and reduced expression of the Th2 effector molecule RELM-ß in intestinal tissue. In contrast, the Th1 response to the protozoan parasite was not diminished and parasitemia of T. gondii was unaffected by concurrent helminth infection. Importantly, H. polygyrus specific restimulation of splenocytes revealed H. polygyrus-reactive CD4+ T cells that produce a significant amount of IFN-γ in co-infected animals. This was not observed in animals infected with the nematode alone. Increased levels of H. polygyrus-specific IgG2a antibodies in co-infected mice mirrored this finding. This study suggests that polarization rather than priming of naive CD4+ T cells is disturbed in mice previously infected with T. gondii. In conclusion, a previous T. gondii infection limits a helminth-specific Th2 immune response while promoting a shift toward a Th1-type immune response.

CCR5 Is Involved in Interruption of Pregnancy in Mice Infected with Toxoplasma gondii during Early Pregnancy.

Toxoplasmosis can cause abortion in pregnant humans and other animals; however, the mechanism of abortion remains unknown. C-C chemokine receptor type 5 (CCR5) is essential for host defense against Toxoplasma gondii infection. To investigate the relationship between CCR5 and abortion in toxoplasmosis, we inoculated wild-type and CCR5-deficient (CCR5-/-) mice with T. gondii tachyzoites intraperitoneally on day 3 of pregnancy (embryonic day 3 [E3]). The pregnancy rate decreased as pregnancy progressed in infected wild-type mice. Histopathologically, no inflammatory lesions were observed in the fetoplacental tissues. Although wild-type mice showed a higher parasite burden at the implantation sites than did CCR5-/- mice at E6 (3 days postinfection [dpi]), T. gondii antigen was detected only in the uterine tissue and not in the fetoplacental tissues. At E8 (5 dpi), the embryos in infected wild-type mice showed poor development compared with those of infected CCR5-/- mice, and apoptosis was observed in poorly developed embryos. Compared to uninfected mice, infected wild-type mice showed increased CCR5 expression at the implantation site at E6 and E8. Furthermore, analyses of mRNA expression in the uterus of nonpregnant and pregnant mice suggested that a lack of the CCR5 gene and the downregulation of tumor necrosis factor alpha (TNF-α) and CCL3 expression at E6 (3 dpi) are important factors for the maintenance of pregnancy following T. gondii infection. These results suggested that CCR5 signaling is involved in embryo loss in T. gondii infection during early pregnancy and that apoptosis is associated with embryo loss rather than direct damage to the fetoplacental tissues.