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

BackgroundMost Toxoplasma gondii infections in humans are considered foodborne, but the relative importance of the various routes of infection is largely unknown. Consumption of green produce contaminated with T. gondii oocysts has been identified as a possible source.AimWe aimed to estimate the occurrence and prevalence of T. gondii oocysts in commercially available ready-to-eat (RTE) salad mixes in 10 European countries.MethodsA real-time PCR-based method for oocyst detection was developed and optimised by two laboratories and validated in an interlaboratory test. This detection method and a harmonised sampling strategy were applied in a multi-country study. Multivariable logistic regression was used to investigate risk factors for oocyst contamination of RTE salad.ResultsThe real-time PCR method had a detection limit of 10 oocysts per 30 g of salad. We collected 3,329 RTE salad samples (baby leaf and cut leaf mixes) from October 2021 to September 2022. The prevalence of T. gondii oocyst contamination was 4.1% (95% confidence interval (CI): 3.4-4.8%; n = 3,293). In multivariable regression analysis, winter season, sampling and packaging of salad in Northern Europe and production of salad in Western Europe were associated with detection of T. gondii, with no statistically significant differences between salad types.ConclusionWe estimated the prevalence of T. gondii oocysts in RTE leafy green salads using a validated and standardised procedure to assess the potential risk for human infection; highlighting the need to address this risk at each critical point of the salad production chain.

• Keywords
• Europe, Leafy greens, Toxoplasma gondii, harmonisation, oocysts, ready-to-eat salads, ring-trial,
• MeSH
• Food Contamination * analysis   MeSH
• Real-Time Polymerase Chain Reaction * methods   MeSH
• Humans MeSH
• Oocysts isolation & purification   MeSH
• Food Parasitology * methods   MeSH
• Prevalence MeSH
• Toxoplasma * isolation & purification   genetics   MeSH
• Toxoplasmosis * epidemiology   MeSH
• Vegetables * parasitology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe epidemiology   MeSH

Latent infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) has been repeatedly correlated with behavioural and physiological changes in both humans and animals. While classically regarded as a parasite transmitted via ingestion or vertical (transplacental) transmission, accumulating evidence suggests that sexual transmission may also contribute to its epidemiology. This review explores the hypothesis that some behavioural effects of toxoplasmosis - especially those related to attraction, sexual activity, and mate choice - may have evolved to facilitate sexual transmission of the parasite. We summarise findings from animal models and human studies that show modified sexual preferences, altered sexual activity, enhanced attractiveness in infected individuals, and elevated prevalence of T. gondii in groups exhibiting high sexual activity or non-traditional sexual behaviour patterns. Particular attention is given to the role of testosterone, which may mediate both behavioural changes and reproductive consequences, such as shifts in offspring sex ratios and fertility outcomes. Direct detection of the parasite in semen and evidence of transmission through insemination in non-human species further support the plausibility of this route. The observed behavioural effects may also intersect with mechanisms previously thought to enhance predation risk, such as altered fear responses to felid odours. Taken together, these findings point to the possibility that sexual transmission, while likely secondary in humans, may have played a more substantial role in the evolutionary history and current ecology of T. gondii than previously appreciated. This perspective also provides an alternative interpretative framework for understanding the broad spectrum of phenotypic changes associated with latent toxoplasmosis. Further interdisciplinary research is required to clarify the relative contribution of sexual transmission to the parasite's life cycle and to assess its implications for public health and theory of host-parasite coevolution.

• Keywords
• manipulation, parasite manipulation., review, sexual behaviour, sexually transmitted diseases, testosterone, toxoplasmosis,
• MeSH
• Host-Parasite Interactions * MeSH
• Humans MeSH
• Sexual Behavior MeSH
• Toxoplasma * physiology   MeSH
• Toxoplasmosis * transmission   parasitology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review 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

PURPOSE: Toxoplasma gondii is one of the most widespread parasites in the human population globally. Several modes of its transmission have been proposed: some are well-researched and confirmed, others remain unconfirmed. One unconfirmed hypothesis pertains to potential transmission of Toxoplasma gondii via oral sex (fellatio) in humans. A recent study found tissue cysts in the semen of men with latent toxoplasmosis. Therefore, we aimed to test the hypothesis of Toxoplasma gondii transmission through oral sex experimentally. METHODS: Eighty-two laboratory mice were orally administered semen samples from 41 men with latent toxoplasmosis. These semen samples were examined for the presence of Toxoplasma gondii DNA using PCR. RESULTS: We detected Toxoplasma gondii DNA in three of the 41 semen samples from men with latent toxoplasmosis. Oral administration of semen samples to laboratory mice did not result in parasite transmission. CONCLUSION: We have not demonstrated the transmission of Toxoplasma to mice by oral exposure to semen from infected men. While this does not conclusively rule out the possibility of such transmission in humans, the results suggest that, if it does occur, this mode of transmission is likely infrequent.

• Keywords
• Ejaculate, Fellatio, Latent toxoplasmosis, Parasitic disease, Sexual transmission, Sperm,
• MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• DNA, Protozoan genetics   MeSH
• Semen * parasitology   MeSH
• Toxoplasma * MeSH
• Toxoplasmosis * transmission   parasitology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DNA, Protozoan MeSH

One-third of humanity harbors a lifelong infection with Toxoplasma gondii, and probably about 80% are infected with human cytomegalovirus (CMV). This study aims to delineate the associations between toxoplasmosis and cognitive abilities and compare these to the associations with CMV. We evaluated the cognitive performance of 557 students, who had been examined for Toxoplasma and CMV infections, using intelligence, memory, and psychomotor tests. The results indicated cognitive impairments in seropositive individuals for both pathogens, with variations in cognitive impact related to sex and the Rh factor. Specifically, Toxoplasma infection was associated with lower IQ in men, whereas CMV was predominantly associated with worse performance by women when testing memory and reaction speeds. Analysis of the antibody concentrations indicated that certain Toxoplasma-associated cognitive detrimental effects may wane (impaired intelligence) or worsen (impaired reaction times) over time following infection. The findings imply that the cognitive impairments caused by both neurotropic pathogens are likely due to pathological changes in the brain rather than from direct manipulative action by the parasites.

• Keywords
• Rh factor, behavior, cognition, cytomegalovirus, intelligence, manipulation hypothesis, memory, parasite, psychomotor performance, toxoplasmosis,
• MeSH
• Cytomegalovirus Infections * immunology   epidemiology   MeSH
• Cytomegalovirus * immunology   MeSH
• Adult MeSH
• Cognition * MeSH
• Rh-Hr Blood-Group System immunology   MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Cross-Sectional Studies MeSH
• Sex Factors MeSH
• Toxoplasma * immunology   MeSH
• Toxoplasmosis * psychology   immunology   epidemiology   complications   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Rh-Hr Blood-Group System 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