Cross-sectional study to investigate the seroprevalence and risk factors of Toxoplasma gondii among women attending the antenatal clinic in Namwala, Zambia.

BACKGROUND: Toxoplasmosis is a zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii). It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to undesirable pregnancy outcomes such as congenital malformations, miscarriage, premature birth and stillbirth. This study investigated the seroprevalence of T. gondii infection among pregnant women attending the antenatal clinic at Namwala District Hospital in Southern Zambia. METHODS: This was a cross-sectional study where blood was collected, and the serum was tested for Toxoplasma IgG and IgM. A questionnaire was administered to participants on demographic characteristics and risk factors. Data were entered in Microsoft Excel and exported to STATA version 14 for analysis. RESULTS: A total of 401 women were enrolled in the study from 3 March to 5 August 2021. The seroprevalence of Toxoplasma IgG was 4.2% (n=17), while the seroprevalence of Toxoplasma IgM was 0.7% (n=3). The median age was 27 (IQR: 24-30) years, and a larger proportion had primary-level education (n=223, 55.6%). The majority (81.6%) of the women were married. None of the risk factors investigated in this study were significant for T. gondii infection. CONCLUSION: There was a low seroprevalence of T. gondii infection among pregnant women in the Namwala district of Southern Province, Zambia, and regular screening may not be warranted in this population. Continued research on toxoplasmosis is recommended to understand its epidemiology across Zambia.

Neuroserpin, IL-33 and IL-17A as potential markers of mild symptoms of depressive syndrome in Toxoplasma gondii-infected pregnant women.

Introduction: Depressive syndrome (DS) is a common complication during pregnancy and the postpartum period, and is triggered by multiple organic/genetic and environmental factors. Clinical and biochemical follow-up is essential for the early diagnosis and prognosis of DS. The protozoan Toxoplasma gondii causes infectious damage to the fetus during parasite primary-infection. However, in long-term infections, pregnant women develop immune protection to protect the fetus, although they remain susceptible to pathological or inflammatory effects induced by T. gondii. This study aimed to investigate plasma inflammatory biomarkers in pregnant women seropositive and seronegative for T. gondii, with diagnoses of minor and moderate/severe DS. Methods: Pregnant women (n=45; age=18-39 years) were recruited during prenatal care at health centers in Ouro Preto, Minas Gerais, Brazil. Participants were asked to complete a socio-demographic questionnaire to be submitted to well-standardized DS scale calculators (Beck Depression Inventory Questionnaire, Edinburgh Postnatal Depression Scale, and Major Depressive Episode Module). Additionally, 4 mL of blood was collected for plasma neuroserpin, CCL2, IL-17A, and IL-33 analysis. Results: Pregnant volunteers with chronic T. gondii contact were all IgG+ (44%; n=21) and exhibited increased plasma IL-33, IL-17A, and neuroserpin levels, but not CCL2, compared to uninfected pregnant women. Using Beck's depression inventory, we observed an increase in plasma IL-17A and IL-33 in women with T. gondii infeCction diagnosed with mild DS, whereas neuroserpin was associated with minor and moderate/severe DS. Discussion: Our data suggest a close relationship between DS in pregnant women with chronic T. gondii infection and neurological conditions, which may be partially mediated by plasma neuroserpin, IL-33, and IL-17A levels.

Serum signature of antibodies to Toxoplasma gondii, rubella virus, and cytomegalovirus in females with bipolar disorder: A cross-sectional study.

BACKGROUND AND AIM: Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association. METHODS: Antibody seropositivity of IgM and IgG to T gondii, rubella virus, and CMV of females with BD and controls was extracted based on medical records from January 2018 to January 2023. Family history, type of BD, onset age, and psychotic symptom history were also collected. RESULTS: 585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50). LIMITATIONS: Absence of male evidence and control of socioeconomic status and environmental exposure. CONCLUSIONS: Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed.

Toxoplasma gondii infection and high levels of IgE are associated to erythema nodosum leprosy (ENL).

Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), the major cause of irreversible neuropathy in leprosy, which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. Leprosy remains persistently endemic in our region where it predominantly affects lowest socioeconomic conditions people, as Toxoplasma gondii infection in the municipality studied. Previously, we have shown T. gondii coinfection as a risk marker for leprosy, mainly in its severe form. This present study assessed whether T. gondii infection is also a risk factor for leprosy reactions and the predictive value of immunoglobulin production prior to development of leprosy reactions. Patients with leprosy (n = 180), co-infected or not with T. gondii, had their serum investigated for levels of IgA, IgE, IgG1, IgG2, IgG3 and IgG4 anti-PGL-1 by ELISA prior to development of leprosy reactions. The serologic prevalence for T. gondii infection was 87.7% in leprosy reaction patients reaching 90.9% in those with ENL. The leprosy reaction risk increased in T. gondii seropositive individuals was two-fold ([OR] = 2.366; 95% confidence interval [CI 95%]: 1.024-5.469) higher than those seronegative, and considering the risk of ENL, this increase was even more evident (OR = 6.753; 95% CI: 1.050-72.85) in coinfected individuals. When evaluated the prediction of anti-PGL-1 immunoglobulin levels for development of leprosy reactions in patients coinfected or not with T. gondii, only the increase IgE levels were associated to occurrence of reactional episodes of leprosy, specifically ENL type, in patients coinfected with T. gondii, compared to those not coinfected or no reaction. Thus, the immunomodulation in co-parasitism T. gondii-M. leprae suggest increased levels of IgE as a biomarker for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.

In silico study to explore the mechanism of Toxoplasma-induced inflammation and target therapy based on sero and salivary Toxoplasma.

We aimed to assess salivary and seroprevalence of Toxoplasma immunoglobulins in risky populations and evaluate drug docking targeting TgERP. A cross-sectional study was conducted in Alexandria University hospitals' outpatient clinics. 192 participants were enrolled from September 2022 to November 2023. Anti-Toxoplasma IgG and IgM were determined in serum and saliva by ELISA. An in-Silico study examined TgERP's protein-protein interactions (PPIs) with pro-inflammatory cytokine receptors, anti-inflammatory cytokine, cell cycle progression regulatory proteins, a proliferation marker, and nuclear envelope integrity-related protein Lamin B1. Our findings revealed that anti-T. gondii IgG were detected in serum (66.1%) and saliva (54.7%), with 2.1% of both samples were positive for IgM. Salivary IgG had 75.59% sensitivity, 86.15% specificity, 91.40% PPV, 64.40% NPP, 79.17% accuracy and fair agreement with serum IgG. On the other hand, the sensitivity, specificity, PPV, NPV, and accuracy in detecting salivary IgM were 75.0%, 99.47%, 75.0%, 99.47%, and 98.96%. AUC 0.859 indicates good discriminatory power. Examined synthetic drugs and natural products can target specific amino acids residues of TgERP that lie at the same binding interface with LB1 and Ki67, subsequently, hindering their interaction. Hence, salivary samples can be a promising diagnostic approach. The studied drugs can counteract the pro-inflammatory action of TgERP.

Seroprevalence and sociodemographic characteristics of Toxoplasma gondii infection in patients with psychiatric disorders in Malaysia.

Toxoplasma gondii is a neurotropic protozoan parasite that affects neuronal processing in the brain. This study aimed to investigate the prevalence of T. gondii infection in psychiatric disorder patients. We also investigated the potential association between sociodemographic, clinical manifestation, and behavior of Toxoplasma-seropositive patients with psychiatric disorders. Commercial ELISAs (IgG, IgM, and IgG avidity) using serum and PCR using buffy coat were performed on samples from 54 individuals in each of the following groups: patients diagnosed with depressive disorder, bipolar disorder, and schizophrenia, as well as psychiatrically healthy subjects (control group). They were recruited from the Hospital Universiti Sains Malaysia in Kelantan, Malaysia. Of 54 patients with depressive disorder, 24/54 (44.4 %) were seropositive for IgG, and four (16.7 %) were IgG+/IgM+. Among the latter, a high avidity index indicating a past infection was observed in half of the samples (50.0 %), and the other half (50.0 %) showed a low avidity index, indicating a possible recent infection. Meanwhile, 30/54 (55.6 %) patients with bipolar disorder were seropositive for IgG+, five (16.7 %) were IgG+/IgM+, and four of them had a high avidity index, and one had a low avidity index. Patients with schizophrenia showed 29/54 (53.7 %) seropositive for IgG, two of them (6.9 %) were IgG+/IgM+; one of latter had a high avidity index, and one had a low avidity index. Of 54 people in the control group, 37.0 % (20/54) were seropositive for T. gondii IgG antibodies. However, no significant difference was observed in seroprevalence between the control group and each patient group. No PCR-positive results were documented. A Chi-Square and multiple logistic regression showed that age (p = 0.031), close contact with cats/pets (p = 0.033) and contact with soil (p = 0.012) were significantly associated with Toxoplasma seropositivity in patients with psychiatric disorders. Additional research is needed to elucidate the causal relationships and underlying mechanisms.

Correlation between toxoplasmosis and schizophrenia in Egyptian patients and its impact on dopamine serum levels.

Toxoplasma gondii, a parasite infecting around one-third of the global population, has been linked to neurological disorders like schizophrenia. Abnormal dopamine levels are linked to the pathophysiology of schizophrenia, but their association remains unclear. This study aimed to investigate the relationship between T. gondii seroprevalence and dopamine serum levels in schizophrenic patients in Egypt. This case-control study included 93 patients diagnosed with schizophrenia and 93 individuals as controls. T. gondii seroprevalence was determined using an enzyme-linked immunosorbent assay (ELISA). Dopamine serum levels were measured using ELISA. Sociodemographic and clinical characteristics were also collected. The study found a higher prevalence of T. gondii IgG antibodies in patients with schizophrenia (68 %) compared to controls (46.2 %). Contact with cats, sausage consumption, and undercooked meat were identified as possible risk factors associated with T. gondii infection. The mean level of serum dopamine was significantly (P < 0.001) higher in patients with schizophrenia (115.3 Pg/ml ±31.8) compared to the control group (75.02 Pg/ml ±26.5). The study found that schizophrenic patients with T. gondii seropositivity had significantly higher dopamine serum levels (mean=145.2 ± 32.1 pg/ml) than those without T. gondii seropositivity (mean=122.5 ± 29.7 pg/ml) (p = 0.001). Logistic regression analysis revealed that T. gondii seropositivity was a significant predictor of increased dopamine serum levels in schizophrenic patients (odds ratio=3.4, 95 % confidence interval=1.8-6.4, p < 0.001). The study suggests that T. gondii seroprevalence may increase dopamine serum levels in Egyptian schizophrenic patients, potentially contributing to dopamine dysregulation in schizophrenia, but further research is needed to confirm these findings and investigate the underlying mechanisms.

Population-based cohort study of Toxoplasma gondii P22 antibody positivity correlation with anxiety.

BACKGROUND: Accumulating evidence suggests that latent infection with Toxoplasma gondii (T. gondii) is associated with a variety of neuropsychiatric and behavioral conditions. This research aims to explore the potential correlation between T. gondii antibody positivity and neuropsychiatric disorders through a comprehensive prospective cohort study. METHODS: The cohort study utilized the UK Biobank database to recruit 8814 individuals with no prior diagnosis of neuropsychiatric disorders. Cox proportional hazards models were employed to investigate the associations between T. gondii P22 antibody seropositivity (P22+) and the development of various types of neuropsychiatric disorders. RESULTS: Of the population, 14.65 % tested positive for T. gondii P22 antibody. The presence of T. gondii P22 antibody showed a slight inverse association with epilepsy (HR: 0.28; 95 % CI: 0.10-0.77), while it was positively associated with an increased risk of developing anxiety disorders (HR: 1.38; 95 % CI: 1.04-1.83). LIMITATIONS: The study sample consisted mostly of white British individuals aged 40 to 69 years old. Although we adjusted for potential confounders, there may be other unmeasured and residual confounding factors that could have influenced our reported associations. CONCLUSIONS: The findings suggested an increased risk of anxiety and potential evidence of epilepsy associated with T. gondii P22+. However, our analysis did not reveal an increased risk of several other neuropsychiatric conditions including Alzheimer's disease, dementia, substance abuse disorders, depression, and neurodegenerative disorders, associated with P22 antibody seropositivity.

Association between Toxoplasma gondii and gestational diabetes with regard to serum leptin and tumor necrosis factor alpha, a preliminary study.

Gestational diabetes (GDM), the onset of any degree of glucose intolerance during pregnancy, increases a wide range of adverse health outcomes for both the mother and the fetus. The aim of the present study was to evaluate the association of Toxoplasma gondii infection with GDM in a case-control study with regard to the levels of leptin and tumor necrosis factor alpha (TNF-α) as two inflammatory biomarkers. Fifty-one pregnant diabetic cases and 109 controls were selected from a prenatal care clinic of a general hospital in Shiraz, southern Iran during July-November 2020. Cases and controls were similar in age, gestational age and number of parturitions. The presence of IgG antibodies against T. gondii, and serum concentrations of leptin and TNF-α were determined by ELISA. Anti-Toxoplasma antibodies were detected in 25 subjects (15.6 %, 95 % CI: 9.9-21.3). Nine (18 %) diabetic cases were infected with Toxoplasma compared to 16 (15 %) healthy controls (P = 0.63). Level of leptin was higher (P = 0.07) while TNF-α was lower in diabetic cases compared to healthy controls (P = 0.08). When subjects were classified according to the combination of GDM and T. gondii, leptin was significantly lower in healthy (non-diabetic, non-infected) subjects compared to diabetics (P = 0.026), and TNF-α was higher in healthy subjects compared to Toxoplasma-infected diabetics (P = 0.032). These findings can be interpreted as both comorbidities being individually associated with increasing serum leptin and decreasing TNF-α concentrations, with modifying effects on each other. The present study opens a new perspective on GDM and its complex pathophysiological mechanism. Future research in this area is needed to better understand the underlying pathway for the development of GDM and the role of T. gondii and inflammatory biomarkers.

A systematic review and meta-analysis of the validation of serological methods for detecting anti-Toxoplasma gondii antibodies in humans and animals.

Toxoplasma gondii is a paradigmatic zoonotic parasite from the One Health perspective, since it is broadly distributed and virtually infects all warm-blooded species. A wide variety of serological techniques have been developed to detect T. gondii infection in humans and animals. Our aim was to describe and compare the main characteristics of these serological tests and validation processes and to critically analyze whether these tests meet the standards required to ensure an accurate serological diagnosis. The current systematic review and meta-analysis included 134 studies that were published from 2013 to 2023. QUADAS 2 tool was used to evaluate the quality of the included studies. A total of 52 variables related to the characteristics of the techniques and analytical and diagnostic validation parameters were studied. A wider panel of tests was developed for humans, including techniques exclusively developed for humans that involve costly equipment and the measurement of different Ig isotypes that are considered biomarkers of congenital toxoplasmosis. Studies conducted in humans frequently employed commercial techniques as reference tests, measured different immunoglobulin isotypes with a predominance for IgG (>50%) and discriminated between acute and chronic infections. In animals, the most commonly used reference techniques were in-house tests, which almost exclusively detected IgG. Common limitations identified in a large number of studies were some misunderstandings of the terms "gold standard" and "reference test" and the absence of information about the negative and positive control sera used or the exact cutoff employed, which were independent of the quality of the study. There is a lack of analytical validation, with few evaluations of cross-reactivity with other pathogens. Diagnostic odds ratio values showed that indirect ELISA based on native or chimeric antigens performed better than other tests. The reproducibility of serological test results in both humans and animals is not guaranteed due to a lack of relevant information and analytical validation. Thus, several key issues should be considered in the future, including interlaboratory ring trials.

Retrospective study of toxoplasmosis prevalence in pregnant women in Benin and its relation with malaria.

BACKGROUND: Globally distributed with variable prevalence depending on geography, toxoplasmosis is a zoonosis caused by an obligate intracellular protozoan parasite, Toxoplasma gondii. This disease is usually benign but poses a risk for immunocompromised people and for newborns of mothers with a primary infection during pregnancy because of the risk of congenital toxoplasmosis (CT). CT can cause severe damage to fetuses-newborns. To our knowledge, no study has been conducted in sub-Saharan Africa on toxoplasmosis seroprevalence, seroconversion and CT in a large longitudinal cohort and furthermore, no observation has been made of potential relationships with malaria. METHODS: We performed a retrospective toxoplasmosis serological study using available samples from a large cohort of 1,037 pregnant women who were enrolled in a malaria follow-up during the 2008-2010 period in a rural area in Benin. We also used some existing data to investigate potential relationships between the maternal toxoplasmosis serological status and recorded malaria infections. RESULTS: Toxoplasmosis seroprevalence, seroconversion and CT rates were 52.6%, 3.4% and 0.2%, respectively, reflecting the population situation of toxoplasmosis, without targeted medical intervention. The education level influences the toxoplasmosis serological status of women, with women with little or no formal education have greater immunity than others. Surprisingly, toxoplasmosis seropositive pregnant women tended to present lower malaria infection during pregnancy (number) or at delivery (presence) and to have lower IgG levels to Plasmodium falciparum Apical Membrane Antigen 1, compared to toxoplasmosis seronegative women. CONCLUSIONS: The high toxoplasmosis seroprevalence indicates that prevention against this parasite remains important to deploy and must be accessible and understandable to and for all individuals (educated and non-educated). A potential protective role against malaria conferred by a preexisting toxoplasmosis infection needs to be explored more precisely to examine the environmental, parasitic and/or immune aspects.

Association between lymphadenopathy after toxoplasmosis seroconversion in pregnancy and risk of congenital infection.

The aim of the study was to describe the pregnancy outcome of a large cohort of women with toxoplasmosis seroconversion in pregnancy and to investigate the relation between maternal lymphadenopathy and risk of congenital toxoplasmosis (CT). This was a retrospective study involving women with confirmed toxoplasmosis seroconversion in pregnancy between 2001 and 2017. Women were clinically evaluated for lymphadenopathy and classified as follows: lymphadenopathy absent (L-) or lymphadenopathy present (L+). The mothers were treated and followed-up according to local protocol, and neonates were monitored at least for 1 year in order to diagnose CT. A total of 218 women (one twin pregnancy) were included in the analysis. Pregnancy outcome was as follows: 149 (68%) of children not infected, 62 (28.3%) infected, 4 (1.8%) first trimester termination of pregnancy, 2 (0.9%) first trimester miscarriages, and 3 (1.4%) stillbirths (of which one already counted in the infected cohort). 13.8% of women were L+ , and they were nearly three times more likely to have a child with CT compared to L- women (aOR, 2.90; 95%CI, 1.28-6.58). Moreover, the result was still statistically significant when the analysis was restricted to 81 children whose mothers were clinically examined and received treatment within 5 weeks from estimated time of infection. In conclusion, there is a positive association between L+ status in pregnant women, and risk of CT also confirmed when restricting the analysis to women with early diagnosis of seroconversion and treatment. This data could be very useful in counselling pregnant women with toxoplasmosis seroconversion and lead to direct a more specific therapeutic and diagnostic protocol.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort.

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler's virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 - 5010) and identified three genome-wide signals (P < 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections.

The Role and Function of Regulatory T Cells in Toxoplasma gondii-Induced Adverse Pregnancy Outcomes.

Infection with Toxoplasma gondii (T. gondii) during the pregnant period and its potentially miserable outcomes for the fetus, newborn, and even adult offspring continuously occur worldwide. People acquire infection through the consumption of infected and undercooked meat or contaminated food or water. T. gondii infection in pregnant women primarily during the gestation causes microcephaly, mental and psychomotor retardation, or death. Abnormal pregnancy outcomes are mainly associated with regulatory T cell (Treg) dysfunction. Tregs, a special subpopulation of T cells, function as a vital regulator in maintaining immune homeostasis. Tregs exert a critical effect on forming and maintaining maternal-fetal tolerance and promoting fetal development during the pregnancy period. Forkhead box P3 (Foxp3), a significant functional factor of Tregs, determines the status of Tregs. In this review, we summarize the effects of T. gondii infection on host Tregs and its critical transcriptional factor, Foxp3.

Association of Toxoplasma gondii Seropositivity With Cognitive Function in Healthy People: A Systematic Review and Meta-analysis.

Importance: The parasite Toxoplasma gondii has been associated with behavioral alterations and psychiatric disorders. Studies investigating neurocognition in people with T gondii infection have reported varying results. To systematically analyze these findings, a meta-analysis evaluating cognitive function in healthy people with and without T gondii seropositivity is needed. Objective: To assess whether and to what extent T gondii seropositivity is associated with cognitive function in otherwise healthy people. Data Sources: A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A systematic search of PubMed, MEDLINE, Web of Science, PsycInfo, and Embase was performed to identify studies from database inception to June 7, 2019, that analyzed cognitive function among healthy participants with available data on T gondii seropositivity. Search terms included toxoplasmosis, neurotoxoplasmosis, Toxoplasma gondii, cognition disorder, neuropsychological, and psychomotor performance. Study Selection: Studies that performed cognitive assessment and analyzed T gondii seroprevalence among otherwise healthy participants were included. Data Extraction and Synthesis: Two researchers independently extracted data from published articles; if needed, authors were contacted to provide additional data. Quantitative syntheses were performed in predefined cognitive domains when 4 independent data sets per domain were available. Study quality, heterogeneity, and publication bias were assessed. Main Outcomes and Measures: Performance on neuropsychological tests measuring cognitive function. Results: The systematic search yielded 1954 records. After removal of 533 duplicates, an additional 1363 records were excluded based on a review of titles and abstracts. A total of 58 full-text articles were assessed for eligibility (including reference list screening); 45 articles were excluded because they lacked important data or did not meet study inclusion or reference list criteria. The remaining 13 studies comprising 13 289 healthy participants (mean [SD] age, 46.7 [16.0] years; 6586 men [49.6%]) with and without T gondii seropositivity were included in the meta-analysis. Participants without T gondii seropositivity had favorable functioning in 4 cognitive domains: processing speed (standardized mean difference [SMD], 0.12; 95% CI, 0.05-0.19; P = .001), working memory (SMD, 0.16; 95% CI, 0.06-0.26; P = .002), short-term verbal memory (SMD, 0.18; 95% CI, 0.09-0.27; P < .001), and executive functioning (SMD, 0.15; 95% CI, 0.01-0.28; P = .03). A meta-regression analysis found a significant association between older age and executive functioning (Q = 6.17; P = .01). Little suggestion of publication bias was detected. Conclusions and Relevance: The study's findings suggested that T gondii seropositivity was associated with mild cognitive impairment in several cognitive domains. Although effect sizes were small, given the ubiquitous prevalence of this infection globally, the association with cognitive impairment could imply a considerable adverse effect at the population level. Further research is warranted to investigate the underlying mechanisms of this association.

High performance of a novel point-of-care blood test for Toxoplasma infection in women from diverse regions of Morocco.

Point-of-care (POC) testing for Toxoplasma infection has the potential to revolutionize diagnosis and management of toxoplasmosis, especially in high-risk populations in areas with significant environmental contamination and poor health infrastructure precluding appropriate follow-up and preventing access to medical care. Toxoplasmosis is a significant public health challenge in Morocco, with a relatively heavy burden of infection and, to this point, minimal investment nationally to address this infection. Herein, we analyse the performance of a novel, low-cost rapid test using fingerstick-derived whole blood from 632 women (82 of whom were pregnant) from slums, educational centres, and from nomad groups across different geographical regions (i.e. oceanic, mountainous) of Morocco. The POC test was highly sensitive and specific from all settings. In the first group of 283 women, sera were tested by Platelia ELISA IgG and IgM along with fingerstick whole blood test. Then a matrix study with 349 women was performed in which fingerstick - POC test results and serum obtained by venipuncture contemporaneously were compared. These results show high POC test performance (Sensitivity: 96.4% [IC95 90.6-98.9%]; Specificity: 99.6% [IC95 97.3-99.9%]) and high prevalence of Toxoplasma infection among women living in rural and mountainous areas, and in urban areas with lower educational levels. The high performance of POC test confirms that it can reduce the need for venipuncture and clinical infrastructure in a low-resource setting. It can be used to efficiently perform seroprevalence determinations in large group settings across a range of demographics, and potentially expands healthcare access, thereby preventing human suffering.

Limited Impact of the Inhibitory Receptor TIGIT on NK and T Cell Responses during Toxoplasma gondii Infection.

Resistance to the parasite Toxoplasma gondii is mediated by NK and T cell production of IFN-γ, but the failure to contract this response can lead to severe T cell-dependent immunopathology. Although the cytokines IL-10 and IL-27 prevent immune hyperactivity during toxoplasmosis, inhibitory receptors, expressed by NK and T cells, are also implicated in this process. The inhibitory receptor TIGIT is expressed on NK and T cells and competes with the costimulatory receptor CD226 for binding of the ligand CD155. During toxoplasmosis, the activation of NK and T cells is associated with increased expression of CD226 and TIGIT, whereas DCs express increased levels of CD155. To determine if the loss of TIGIT impacts NK and T cell activities, wild-type and TIGIT knockout mice were infected with T. gondii During the acute stage of infection, wild-type and TIGIT knockout mice had comparable parasite burdens and similar NK and T cell responses. Likewise, during the chronic phase of this infection, the loss of TIGIT did not affect the magnitude or phenotype of the T cell response nor the ability to control pathogen load. These data suggest that during toxoplasmosis, despite upregulation of relevant ligands, TIGIT signaling does not limit NK and T cell activities. Thus, TIGIT-independent mechanisms dominate the restraint of the immune response during toxoplasmosis.

Type 1 conventional dendritic cell fate and function are controlled by DC-SCRIPT.

The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of DC lineage diversity, its genetic basis is not fully understood. The transcription factor DC-SCRIPT is expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8 (interferon regulatory factor 8)-dependent cDC1, whereas cDC2 numbers increased marginally. The residual DC-SCRIPT-deficient cDC1s had impaired capacity to capture and present cell-associated antigens and to secrete IL-12p40, two functional hallmarks of this population. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8 Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.