Upregulation of IL-33, CCL2, and CXCL16 levels in Brazilian pregnant women infected by Toxoplasma gondii.

Congenital toxoplasmosis can cause neurological and eye damage, behavioral alterations, or death in fetuses or babies born to Toxoplasma gondii-infected women. Several pieces of evidence suggest that socioeconomic, environmental, and inflammatory patterns linked to the maternal immune response partly drive the pathogenesis of this disease. However, immunoregulation induced by T. gondii infection during gestation is not completely understood. The aim of this study was to assess the association between T. gondii seropositivity and concentrations of plasma markers (CCL2, CXCL16, IL-17, and IL-33) in Brazilian pregnant women. Inflammatory markers were measured by immunoassays in the plasma of 131 pregnant women (13 to 46 years old). The prevalence of T. gondii infections was 45.8% (n = 60) in this population. The concentrations of CCL2, CXCL16, and IL-33 were higher in T. gondii-seropositive than in seronegative pregnant women, while the opposite was observed for IL-17 levels. In IgG+ women, a strong correlation between IL-17 and IL-33 (r = 0.7508, p = 0.0001) and a moderate correlation between CXCL16/IL-17 (r = 0.7319, p = 0.0001) and CXCL16/CCL2 (r = 0.3519, p = 0.0098) was observed. In uninfected women, a strong correlation was found between IL-17 and CXCL16 (r = 0.6779, p = 0.0001) but moderate between IL-17 and IL-33 (r = 0.4820, p = 0.0001). In summary, our data suggest that plasma upregulation of CCL2, CXCL16, and IL-33 might exert a potential protective role in the mother/fetus/parasite axis and, in addition, multiparous women are more likely to be infected with T. gondii than primiparous women.

Association between ocular toxoplasmosis and APEX1 and MYD88 polymorphism.

Ocular toxoplasmosis (OT) is the most common form of posterior uveitis, and in some countries, it is the most frequent cause of visual impairment. Studies demonstrate that the polymorphism in genes involved with the immune response can be related both to the occurrence and to the recurrence of OT. Thus, the present study aimed to analyze the association between OT and the polymorphism of the APEX1 (rs1130409) and MyD88 (rs7744) genes. The studied sample consisted of 48 volunteers with OT and 96 asymptomatic volunteers, but positive for anti - T. gondii IgG (control group). Blood collection was performed for serological analysis (ELISA) and DNA extraction. Genotyping of the polymorphism was performed using real-time PCR. To analyze the association between gene polymorphism and OT, logistic regression was performed. The results showed no association between the MYD88 gene polymorphism and the development of OT. However, a significant association was found between OT and APEX1 gene polymorphism, indicating that individuals expressing polymorphic (GG) or heterozygous (GT) alleles are more likely to develop the disease (P-value = 0.02 and 0.03 respectively). These results suggest that APEX1 (rs1130409) polymorphism is a risk factor for the occurrence of ocular toxoplasmosis in the studied population.

Effect of toxoplasmic infection on the biodistribution of a brain radiopharmaceutical.

Purpose: This study evaluated if Toxoplasma gondii infection and the drug-associated infection modifies the brain radiopharmaceutical Ethylene Cystine Diethylester Dihydrochloride (99mTc-ECD) biodistribution in mice.Materials and methods: A total of 18 mice were divided into 3 groups. Control group (C) received distilled water and 99mTc-ECD; Infected group (I) received T. gondii strain and 99mTc-ECD; Infected and Treated group (IT), in addition to infection, received association of Pyrimethamine and Sulfadiazine and 99mTc-ECD. The T. gondii strain used in this study was TgCkRrRN3. Forty minutes after administration of the 99mTc-ECD, all animals were euthanized, and blood and brain samples were isolated. The counting of the radioactivity percentage per gram of tissue (%ATI/g) was calculated, and statistical analysis was performed by t-test, with a level of significance of p < .05.Results: There was a significant increase in %ATI/g between groups C and I on brain (0.35 ± 0.02 and 0.45 ± 0.04; p = .041) and on blood (0.80 ± 0.09 and 1.14 ± 0.31; p = .049). A significant decrease in %ATI/g occurred between groups C and IT on blood (0.80 ± 0.09 and 0.54 ± 0.08; p = .001) and on brain (0.35 ± 0.02 and 0.22 ± 0.04; p = .049).Conclusions: Combined therapy of anti-Toxoplasma drugs in infected mice reduced the uptake of 99mTc-ECD, probably due to its binding to plasma proteins.

The influence of salt intake on the course of experimental toxoplasmosis in outbred or inbred mouse strains

Many environmental factors contribute to an effective immune response against Toxoplasma gondii (Tg) infection, among which diet is important in triggering the immune response of the host to infection. Emerging reports suggest that salt intake undermines the regulatory mechanisms mediated by innate and adaptive immune cells. Unfortunately, the impact of an Intermediate Salt Diet (ISD) on the pathogenesis and immune response to toxoplasmosis remains unclear. The purpose of this study was to evaluate the susceptibility profile to an ISD (NaCl 2%) of two mouse strains (outbred Swiss and inbred C57BL6) infected by the ME49 strain of Tg. Our data confirm an antagonistic susceptibility to oral Tg infection among the two mouse strains. Sodium intake induced the highest mortality in C57BL6 compared to Swiss mice in the infected groups. A simultaneous ISD with the infection did not induce significant differences in body weight in either mouse strains. Both mouse strains showed an antagonistic response to a sodium intake diet on the number of parasite brain cysts. An increased number of brain cysts in C57BL6 ISD-Tg animals were noted while Swiss ISD-Tg animals presented a decrease in the number of brain cysts compared to NSD-Tg (Normal Salt Diet) for both mouse strains. Furthermore, sodium intake caused a significant reduction in the specific humoral immune response against Tg in inbred C57BL6 mice. Thus, our data reveal that an ISD affects the humoral immune response in the murine model and influences the course of Tg infection.

Occurrence of anti-Toxoplasma gondii antibodies in meat and dairy goat herds in Rio Grande do Norte, Brazil.

Toxoplasmosis is caused by Toxoplasma gondii, which is the main causative agent of abortion in small ruminants. Goats are among the animals that are most susceptible to this protozoon, and the disease that it causes leads to significant economic losses and has implications for public health, since presence of the parasite in products of goat origin is one of the main sources of human infection. Because of the significant economic impact, there is an urgent need to study the prevalence of T. gondii infection among goats in Sertão do Cabugi, which is the largest goat-producing region in Rio Grande do Norte. In the present study, the ELISA assay was used to test 244 serum samples from nine farms, located in four different municipalities in the Sertão do Cabugi region, which is an important goat-rearing region. The results showed that the prevalence of anti-T. gondii antibodies was 47.1% and that there was a significant association between positivity and the variables of age (≥ 34 months), location (Lajes, Angicos and Afonso Bezerra) and farm (all the farms). The avidity test was applied to all the 115 ELISA-positive samples to distinguish between acute and chronic infection. One hundred and three samples (89.6%) displayed high-avidity antibodies, thus indicating that most of the animals presented chronic infection, with a consequent great impact on the development of the goat production system and a risk to human health.

Occurrence of anti-Toxoplasma gondii antibodies in meat and dairy goat herds in Rio Grande do Norte, Brazil / Ocorrência de anticorpos anti-Toxoplasma gondii em rebanhos caprinos de corte e leiteiros do Rio Grande do Norte, Brasil

Toxoplasmosis is caused by Toxoplasma gondii, which is the main causative agent of abortion in small ruminants. Goats are among the animals that are most susceptible to this protozoon, and the disease that it causes leads to significant economic losses and has implications for public health, since presence of the parasite in products of goat origin is one of the main sources of human infection. Because of the significant economic impact, there is an urgent need to study the prevalence of T. gondii infection among goats in Sertão do Cabugi, which is the largest goat-producing region in Rio Grande do Norte. In the present study, the ELISA assay was used to test 244 serum samples from nine farms, located in four different municipalities in the Sertão do Cabugi region, which is an important goat-rearing region. The results showed that the prevalence of anti-T. gondii antibodies was 47.1% and that there was a significant association between positivity and the variables of age (≥ 34 months), location (Lajes, Angicos and Afonso Bezerra) and farm (all the farms). The avidity test was applied to all the 115 ELISA-positive samples to distinguish between acute and chronic infection. One hundred and three samples (89.6%) displayed high-avidity antibodies, thus indicating that most of the animals presented chronic infection, with a consequent great impact on the development of the goat production system and a risk to human health.

A toxoplasmose é causada pelo Toxoplasma gondii, principal agente causador de aborto em pequenos ruminantes. Os caprinos são uns dos animais mais suscetíveis a esse protozoário, levando a perdas econômicas significativas e implicações para a saúde pública, uma vez que a presença do parasito em produtos de origem caprina é uma das principais fontes de infecção humana. Devido ao impacto econômico significativo torna-se urgente estudar a prevalência da infecção, pelo T. gondii, entre caprinos do Sertão do Cabugi, a maior região produtora de caprinos no Rio Grande do Norte. O presente estudo utilizou o ELISA para testar 244 amostras de soro de 9 fazendas, situadas em 4 diferentes cidades na região do Sertão do Cabugi; uma importante região de criação de cabras. Os resultados mostraram uma prevalência de 47,1% para anticorpos anti- T. gondii e uma significativa associação entre a positividade e as variáveis idade (≥ 34 meses), localização (Lajes, Angicos e Afonso Bezerra e propriedade (todas as fazendas). O teste de avidez foi aplicado a todas as 115 amostras positivas pelo ELISA para discriminar entre infecção aguda e crônica. Cento e três amostras (89,6%) apresentaram anticorpos de alta avidez; indicando que a maioria dos animais estavam em infecção crônica, gerando um grande impacto sobre o desenvolvimento do sistema de produção em cabras e um risco para a saúde humana.

In vitro and in vivo antimalarial activity and cytotoxicity of extracts, fractions and a substance isolated from the Amazonian plant Tachia grandiflora (Gentianaceae)

Tachia sp. are used as antimalarials in the Amazon Region and in vivo antimalarial activity of a Tachia sp. has been previously reported. Tachia grandiflora Maguire and Weaver is an Amazonian antimalarial plant and herein its cytotoxicity and antimalarial activity were investigated. Spectral analysis of the tetraoxygenated xanthone decussatin and the iridoid aglyone amplexine isolated, respectively, from the chloroform fractions of root methanol and leaf ethanol extracts was performed. In vitro inhibition of the growth of Plasmodium falciparum Welch was evaluated using optical microscopy on blood smears. Crude extracts of leaves and roots were inactive in vitro. However, chloroform fractions of the root and leaf extracts [half-maximal inhibitory concentration (IC50) = 10.5 and 35.8 µg/mL, respectively] and amplexine (IC50= 7.1 µg/mL) were active in vitro. Extracts and fractions were not toxic to type MRC-5 human fibroblasts (IC50> 50 µg/mL). Water extracts of the roots of T. grandiflora administered by mouth were the most active extracts in the Peters 4-day suppression test in Plasmodium berghei-infected mice. At 500 mg/kg/day, these extracts exhibited 45-59% inhibition five to seven days after infection. T. grandiflora infusions, fractions and isolated substance have potential as antimalarials.