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

In this article, I recount the journey of discovering the effects of latent toxoplasmosis on human psychology, behaviour, morphology, and health as I observed it from the closest perspective over the past 30+ years, during which our laboratory has been intensely focused on this research. I trace how we moved from the initial observations of differences between infected and uninfected individuals in certain personality traits to the systematic study of similar differences in behaviour, both in the laboratory and in everyday life, as well as in physiological and even morphological traits. This eventually led us to investigate the causal relationships behind these observed associations and their molecular basis. I describe some of the unexpected discoveries our research revealed - whether it was the impact of toxoplasmosis on the human sexual index, the prenatal and postnatal development, the sexual preferences and behaviour, the modulatory effect of blood Rh factor on toxoplasmosis, or the discovery of sexual transmission of toxoplasmosis. In exploring whether the toxoplasmosis-associated effects were merely side effects of an ongoing latent infection, we gradually uncovered that seemingly asymptomatic toxoplasmosis has profound (and certainly not positive) effects on the mental and physical health of infected individuals. The article also includes three separate boxes that discuss some key methodological challenges we encountered along the way, such as how to distinguish the effect of infection from mere statistical association, or how to differentiate parasitic manipulation from a simple side effect.

• Keywords
• Rh factor, Toxoplasma, behaviour, chronic toxoplasmosis, dopamine, manipulation, mental health, morbidity, parasite., personality, physical health, schizophrenia, sex ratio, testosterone,
• MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Sexual Behavior MeSH
• Toxoplasmosis * psychology   physiopathology   parasitology   MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH

BACKGROUND: Toxoplasmosis is becoming a global health hazard as it infects 30-50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. AIMS OF THE STUDY: The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. METHODS AND FINDINGS: Prevalence data published between 1995-2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. CONCLUSIONS: The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research.

• MeSH
• Asymptomatic Diseases epidemiology   MeSH
• Accidents, Traffic statistics & numerical data   MeSH
• Gross Domestic Product MeSH
• Internationality * MeSH
• Quality-Adjusted Life Years MeSH
• Humans MeSH
• Prevalence MeSH
• Suicide statistics & numerical data   MeSH
• Seroepidemiologic Studies MeSH
• Toxoplasmosis blood   epidemiology   mortality   transmission   MeSH
• Humidity MeSH
• Geography MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

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

The immunosuppression hypothesis suggests that the increased sex ratio in mice and women with latent toxoplasmosis, retarded embryonic growth in the early phases of pregnancy, prolonged pregnancy of Toxoplasma-infected women, and increased prevalence of toxoplasmosis in mothers of children with Down syndrome can be explained by the presumed immunosuppressive effects of latent toxoplasmosis. Here, we searched for indices of immunosuppression in mice experimentally infected with Toxoplasma gondii. Our results showed that mice in the early phase of latent infection exhibited temporarily increased production of interleukin (IL)-12 and decreased production of IL-10. In accordance with the immunosuppression hypothesis, the mice showed decreased production of IL-2 and nitric oxide and decreased proliferation reaction (synthesis of DNA) in the mixed lymphocyte culture in the early and also in the late phases of latent toxoplasmosis. Since about 30% of the world population are latently infected by T. gondii, the toxoplasmosis-associated immunosuppression might have serious public health consequences.

• MeSH
• Asymptomatic Infections * MeSH
• Immune Tolerance * MeSH
• Interleukin-10 metabolism   MeSH
• Interleukin-12 metabolism   MeSH
• Humans MeSH
• Lymphocytes immunology   MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Nitric Oxide metabolism   MeSH
• Cell Proliferation MeSH
• Reproduction physiology   MeSH
• Toxoplasma immunology   MeSH
• Toxoplasmosis complications   immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Interleukin-10 MeSH
• Interleukin-12 MeSH
• Nitric Oxide MeSH