Over the past three turbulent decades, research has profoundly reshaped our understanding of chronic Toxoplasma gondii infection-traditionally regarded as harmless in immunocompetent individuals-unveiling its surprising impact on human health, performance, and behavior. This review emphasizes the effects of chronic Toxoplasma infection on physical and mental health, cognitive performance, and behavioral changes, highlighting key findings from studies investigating these domains, with a particular focus on both ultimate and proximate mechanisms underlying the observed effects. To this end, the primary focus will be on human studies; however, animal model studies will also be thoroughly considered when necessary and appropriate, to provide context and additional important information. Research demonstrates that chronic Toxoplasma infection may contribute to a broad spectrum of physical health issues. Ecological studies have revealed correlations between toxoplasmosis prevalence and increased morbidity and mortality from various conditions, including cardiovascular diseases, neurological disorders, and certain cancers. Large-scale cross-sectional studies have further shown that infected individuals report a higher incidence of numerous health complaints and diagnosed diseases, suggesting a significant impact on overall physical well-being. In addition to physical health, lifelong Toxoplasma infection (subclinical toxoplasmosis) has been implicated in cognitive impairments and behavioral changes. Studies have reported associations between infection and poorer performance in areas such as reaction time, processing speed, working memory, and executive function. Many of these behavioral changes likely relate to worsened health and a shift towards a "fast life history strategy." These cognitive deficits can have significant implications for daily functioning and performance. Furthermore, the role of Toxoplasma infection in the development or exacerbation of mental health disorders has been extensively investigated. Meta-analyses, ecological studies, and large-scale observational studies have demonstrated associations between Toxoplasma infection and an increased risk of disorders such as schizophrenia and obsessive-compulsive disorder. While the precise mechanisms underlying these associations remain under investigation, research suggests that neuroinflammation and alterations in neurotransmitter systems are likely to play a role. Far from being harmless, subclinical toxoplasmosis is increasingly recognized as a hidden factor influencing human health, behavior, and cognitive performance-with implications that extend well beyond the individual to public health at large. Further research is warranted to elucidate the complex interplay between Toxoplasma infection, host physiology, and the development of various physical, cognitive, behavioral, and mental health conditions.

• Keywords
• OCD, RhD, Rhesus D antigen, autism, evolution, intelligence, manipulation hypothesis, mental health, parasite, schizophrenia, subclinical toxoplasmosis, testosterone,
• Publication type
• Journal Article MeSH
• Review MeSH

Toxoplasma gondii (Nicolle et Manceaux, 1908), an intracellular parasite that causes toxoplasmosis, infects a third of the human population. Latent toxoplasmosis has been linked to altered immune responses, including elevated proinflammatory cytokines. In early pregnancy, the immune system adapts to balance inflammation and foetal tolerance. This study assessed whether pregnant women in the first trimester infected with Toxoplasma gondii have different cytokine levels than uninfected women. This study also examined whether women with discordant test results for toxoplasmosis represent a distinct group or a mixed group composed of infected women with unusually low levels of anti-Toxoplasma antibodies and uninfected women with high levels of cross-reacting antibodies. We measured 18 cytokines (IL-1β, IL-1ra, IL-2, IL-4, IL-7, IL-9, IL-17A, Eotaxin, FGF basic, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α) in 78 pregnant women, classified as Toxoplasma-positive, Toxoplasma-negative or Toxoplasma-discordant (negative by IgG ELISA, positive by complement fixation test [CFT]). Using exploratory factor analysis, we identified two factors, the first explaining 29.6% and the second 24.9% of the total variability in cytokine concentrations. Toxoplasma-positive women scored significantly higher in the second factor, primarily associated with cytokines linked to Th1-driven inflammation and cellular immunity. Specifically, these women exhibited elevated levels of IL-1β, IL-1ra, IL-2, FGF basic and PDGF-BB compared to Toxoplasma-negative women. This finding suggests that pregnant women with latent toxoplasmosis experience some degree of chronic inflammation. Additionally, our results indicate that Toxoplasma-discordant women are likely Toxoplasma-negative individuals with detectable anti-Toxoplasma IgM antibodies. However, as this study focused on pregnant women, further research is necessary to validate these conclusions in broader populations.

• Keywords
• Toxoplasma gondii, cytokines, immunity, pregnancy,
• MeSH
• Cytokines blood   MeSH
• Adult MeSH
• Latent Infection * MeSH
• Humans MeSH
• Young Adult MeSH
• Pregnancy Complications, Parasitic * immunology   diagnosis   MeSH
• Antibodies, Protozoan blood   MeSH
• Serologic Tests MeSH
• Pregnancy MeSH
• Toxoplasma immunology   MeSH
• Toxoplasmosis * diagnosis   immunology   MeSH
• Inflammation * immunology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytokines MeSH
• Antibodies, Protozoan MeSH

Humans infected by Toxoplasma gondii express no specific symptoms but manifest higher incidence of many diseases, disorders and differences in personality and behavior. The aim of this study was to compare the political beliefs and values of Toxoplasma-infected and Toxoplasma-free participants. We measured beliefs and values of 2315 responders via an online survey (477 Toxoplasma-infected) using the Political Beliefs and Values Inventory (PI34). This study showed Toxoplasma-infected and Toxoplasma-free participants of our cross-sectional study differed in three of four factors of PI34, scoring higher in Tribalism and lower in Cultural liberalism and Anti-Authoritarianism. We found sex differences in political beliefs associated with Toxoplasma infection. Infected women scored higher in tribalism and lower in cultural liberalism, compared with the Toxoplasma-free control group, while infected men scored higher in economic equity. These results fit with sexual differences in behavior and attitude observed after toxoplasmosis infection. Controlling for the effect of worse physical health and mental health had little impact, suggesting that impaired health did not cause these changes. Rather than adaptation to prevalence of parasites, as suggested by parasite-stress theory, the differences might be side-effects of long-term mild inflammatory reaction. However, to get clear picture of the mild inflammation effects, more research focused on different infectious diseases is needed.

• Keywords
• Toxoplasma gondii, infectious diseases, manipulation hypothesis, parasite threat, pathogen avoidance, political beliefs, stress,
• MeSH
• Humans MeSH
• Personality MeSH
• Cross-Sectional Studies MeSH
• Sexual Behavior MeSH
• Toxoplasma * MeSH
• Toxoplasmosis * complications   epidemiology   parasitology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Latent toxoplasmosis, i.e. a lifelong infection with the protozoan parasite Toxoplasma gondii, affects about a third of the human population worldwide. In the past 10 years, numerous studies have shown that infected individuals have a significantly higher incidence of mental and physical health problems and are more prone to exhibiting the adverse effects of various diseases. METHODS: A cross-sectional internet study was performed on a population of 4499 (786 Toxoplasma-infected) participants and looked for factors which positively or negatively affect the risk of SARS-CoV-2 infection and likelihood of a severe course of COVID-19. RESULTS: Logistic regression and partial Kendall correlation controlling for sex, age, and size of the place of residence showed that latent toxoplasmosis had the strongest effect on the risk of infection (OR = 1.50) before sport (OR = 1.30) and borreliosis (1.27). It also had the strongest effect on the risk of severe course of infection (Tau = 0.146), before autoimmunity, immunodeficiency, male sex, keeping a cat, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease. Toxoplasmosis augmented the adverse effects of other risk factors but was not the proximal cause of the effect of cat-keeping on higher likelihood of COVID infection and higher severity of the course of infection because the effect of cat-keeping was also observed (and in particular) in a subset of Toxoplasma-infected respondents (Tau = 0.153). Effects of keeping a cat were detected only in respondents from multi-member families, suggesting that a cat could be a vector for the transmission of SARS-CoV-2 within a family. CONCLUSIONS: Toxoplasmosis is currently not considered a risk factor for COVID-19, and Toxoplasma-infected individuals are neither informed about their higher risk nor prioritised in vaccination programs. Because toxoplasmosis affects a large segment of the human population, its impact on COVID-19-associated effects on public health could be considerable.

• Keywords
• COVID-19, Cat, Pets, Risk factors, SARS-CoV-2, Symptoms, Zoonosis,
• MeSH
• COVID-19 epidemiology   parasitology   physiopathology   MeSH
• Incidence MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• Risk Factors MeSH
• Social Media * MeSH
• Severity of Illness Index MeSH
• Toxoplasma immunology   pathogenicity   MeSH
• Toxoplasmosis complications   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Slovakia epidemiology   MeSH

Latent infection of the globally spread parasite Toxoplasma gondii in humans has been associated with changes in personality and behavior. Numerous studies have investigated the effect of toxoplasmosis on depression, but their results are inconsistent. Our study focused on the effect of latent toxoplasmosis on depression in men and women in association with their fertility. In 2016-2018, we recruited clients (677 men and 664 women) of the Center for Assisted Reproduction and asked them to complete a standardized Beck Depression Inventory-II. In women without fertility problems, we found higher depression scores in Toxoplasma-positive than in Toxoplasma-negative (p = 0.010, Cohen's d = 0.48). Toxoplasma-positive infertile men, on the other hand, had lower depression scores than Toxoplasma-negative infertile men (p ≤ 0.001, Cohen's d = 0.48). Our results are consistent with the previously described effects of latent toxoplasmosis, which seem to go in opposite directions regarding the effect on personality and behavior of men and women. Our results could be explained by gender-contrasting reactions to chronic stress associated with lifelong infection. This suggests that due to gender differences in the impact of latent toxoplasmosis, future studies ought to perform separate analyses for women and men.

• Keywords
• Beck Depression Inventory, Toxoplasma gondii, depression score, fertility,
• Publication type
• Journal Article MeSH

Several recent studies have demonstrated the association of cat-related injuries with major depression and with depressiveness in the general population. It was suggested that cat-scratch disease, the infection with the bacterium Bartonella henselae, can be responsible for the observed association. However, no direct evidence for the role of the Bartonella infection in this association has been published until now. In this preregistered case-controls study performed on 250 healthy subjects tested earlier for the presence of anti-Toxoplasma IgG antibodies, we searched for the positive association between presence of anamnestic anti-Bartonella IgG antibodies and depressiveness measured with Beck II inventory, depression subscale of neuroticism measured with N-70 questionnaire, and self-reported health problems. We found that that Bartonella seropositivity was positively correlated with Beck depression only in Toxoplasma-seronegative men and negatively correlated with health in Toxoplasma-seronegative women. Bartonella seropositivity expressed protective effects against Toxoplasma seropositivity-associated increased neuroticism in men while Toxoplasma-seropositivity expressed protective effects against Bartonella seropositivity-associated health problems in women. A comparison of the patterns of association of mental and physical health problems with Bartonella seropositivity and with reported cat-related injury suggests that different factor, possibly infection with different pathogen transmitted by cat related-injuries than the B. henselae, is responsible for the observed association of cat related-injuries with depressiveness and major depression. The existence of complex interactions between Bartonella seropositivity, Toxoplasma seropositivity, and sex also suggest that the effect of symbionts on the host's phenotype must by always studied in the context of other infections, and separately for men and women.

• Keywords
• Bartonella, Toxoplasma, animal-related injuries, bartonellosis, cat-scratch disease, depressiveness, major depression, toxoplasmosis,
• Publication type
• Journal Article MeSH

A relationship between latent toxoplasmosis and the immune system during HIV disease is poorly understood. Therefore, the aim of this follow-up study was to characterize immunological parameters in HIV-infected patients with latent toxoplasmosis and noninfected individuals. A total of 101 HIV-infected patients were enrolled in the study. The patients were classified into two groups based on anti-Toxoplasma gondii antibodies: a group of 55 toxoplasma-positive persons (TP) and a group of 46 toxoplasma-negative persons (TN). Absolute counts of several lymphocyte subsets decreased in the TP group, namely, T cells (p = 0.007), B cells (p = 0.002), NK cells (p = 0.009), CD4 T cells (p = 0.028), and CD8 T cells (p = 0.004). On the other hand, the percentage of CD8 T cells expressing CD38 and HLA-DR significantly increased during the follow-up in the TP group (p = 0.003, p = 0.042, resp.) as well as the intensity of CD38 and HLA-DR expression (MFI) on CD8 T cells (p = 0.001, p = 0.057, resp.). In the TN group, analysis of the kinetics of immunological parameters revealed no significant changes over time. In conclusion, the results suggest that latent T. gondii infection modulates the immune response during HIV infection.

• MeSH
• Cytokines immunology   MeSH
• Adult MeSH
• HIV Infections immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphocytes immunology   MeSH
• AIDS-Related Opportunistic Infections immunology   MeSH
• Immunity, Innate immunology   MeSH
• Toxoplasmosis immunology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH

BACKGROUND: Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. METHODS: Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). CONCLUSIONS: Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

• MeSH
• Autoimmune Diseases epidemiology   etiology   MeSH
• Autoantibodies blood   immunology   MeSH
• Adult MeSH
• Thyroid Hormones blood   MeSH
• Immunoglobulin G blood   immunology   MeSH
• Pregnancy Complications epidemiology   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Thyroid Diseases epidemiology   etiology   MeSH
• Antibodies, Protozoan blood   immunology   MeSH
• Cross-Sectional Studies MeSH
• Risk Factors MeSH
• Pregnancy MeSH
• Toxoplasmosis complications   diagnosis   MeSH
• Pregnancy Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Autoantibodies MeSH
• Thyroid Hormones MeSH
• Immunoglobulin G MeSH
• Antibodies, Protozoan MeSH

BACKGROUND: Rhesus-positive and rhesus-negative persons differ in the presence-absence of highly immunogenic RhD protein on the erythrocyte membrane. This protein is a component of NH(3) or CO(2) pump whose physiological role is unknown. Several recent studies have shown that RhD positivity protects against effects of latent toxoplasmosis on motor performance and personality. It is not known, however, whether the RhD phenotype modifies exclusively the response of the body to toxoplasmosis or whether it also influences effects of other factors. METHODOLOGY/PRINCIPAL FINDINGS: In the present cohort study, we searched for the effects of age and smoking on performance, intelligence, personality and self-estimated health and wellness in about 3800 draftees. We found that the positive effect of age on performance and intelligence was stronger in RhD-positive soldiers, while the negative effect of smoking on performance and intelligence was of similar size regardless of the RhD phenotype. The effect of age on four Cattell's personality factors, i.e., dominance (E), radicalism (Q(1)), self-sentiment integration (Q(3)), and ergic tension (Q(4)), and on Cloninger's factor reward dependency (RD) was stronger for RhD-negative than RhD-positive subjects, while the effect of smoking on the number of viral and bacterial diseases was about three times stronger for RhD-negative than RhD-positive subjects. CONCLUSIONS: RhD phenotype modulates the influence not only of latent toxoplasmosis, but also of at least two other potentially detrimental factors, age and smoking, on human behavior and physiology. The negative effect of smoking on health (estimated on the basis of the self-rated number of common viral and bacterial diseases in the past year) was much stronger in RhD-negative than RhD-positive subjects. It is critically needed to confirm the differences in health response to smoking between RhD-positive and RhD-negative subjects by objective medical examination in future studies.

• MeSH
• Adult MeSH
• Phenotype MeSH
• Intelligence genetics   MeSH
• Smoking genetics   MeSH
• Rh-Hr Blood-Group System genetics   metabolism   MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Personality genetics   MeSH
• Military Personnel * MeSH
• Psychomotor Performance * MeSH
• Toxoplasmosis genetics   MeSH
• Age Factors MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Rh-Hr Blood-Group System MeSH
• Rho(D) antigen MeSH Browser

BACKGROUND: About 30% of the population worldwide are infected with the protozoan parasite Toxoplasma gondii. Latent toxoplasmosis has many specific behavioral and physiological effects on the human organism. Modified reactivity of the immune system has been suggested to play a key role in many of these effects. For example, the immunosuppression hypothesis explains the higher probability of the birth of male offspring observed in Toxoplasma-positive humans and mice by the protection of the (more immunogenic) male embryos against abortion. METHODS: Here we searched for indices of immunosuppression in Toxoplasma-positive subjects by comparing clinical records of immunology outpatients. RESULTS: Our cohort study showed that the male patients with latent toxoplasmosis had decreased and the Toxoplasma-positive women had increased leukocyte, NK-cell and monocyte counts in comparison with controls. The B-cell counts were reduced in both Toxoplasma-positive men and women. The difference between Toxoplasma-positive and Toxoplasma-negative subjects diminished with the decline of the specific Toxoplasma antibody titre (a proxy for the length of infection), which is consistent with the observed decreasing strength of the effect of latent toxoplasmosis on human reproduction. The prevalence of toxoplasmosis in 128 male patients was unusually low (10.9%) which contrasted with normal prevalence in 312 female patients (23.7%) and in general population Prague (20-30%). CONCLUSIONS: Latent toxoplasmosis has immunomodulatory effects in human and probably protects men against some classes of immunopathological diseases. The main limitation of the present study was the absence of the data on the immunoreactivity of immune cells subpopulations. Therefore further studies are needed to search for indices of immunosuppression in human using more specific markers.

• MeSH
• Asymptomatic Diseases * MeSH
• Adult MeSH
• Immune Tolerance * MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Mice MeSH
• Prospective Studies MeSH
• Toxoplasma immunology   MeSH
• Toxoplasmosis immunology   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH