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

Statistically, the concentration of antibodies against parasites decreases with the duration of infection. This can result in false-negative outcomes of diagnostic tests for subjects with old infections. When a property of seronegative and seropositive subjects is compared under these circumstances, the statistical tests can detect no difference between these two groups of subjects, despite the fact that they differ. When the effect of the infection has a cumulative character and subjects with older infections are affected to a greater degree, we may even get paradoxical results of the comparison - the seropositive subjects have, on average, a higher value of certain traits despite the infection having a negative effect on those traits. A permutation test for the contaminated data implemented, e.g. in the program Treept or available as a comprehensibly commented R function at https://github.com/costlysignalling/Permutation_test_for_contaminated_data, can be used to reveal and to eliminate the effect of false negatives. A Monte Carlo simulation in the program R showed that our permutation test is a conservative test - it could provide false negative, but not false positive, results if the studied population contains no false-negative subjects. A new R version of the test was expanded by skewness analysis, which helps to estimate the proportion of false-negative subjects based on the assumption of equal data skewness in groups of healthy and infected subjects. Based on the results of simulations and our experience with empirical studies we recommend the usage of a permutation test for contaminated data whenever seronegative and seropositive individuals are compared.

• Keywords
• Case-control studies, Epidemiology, Randomisation tests, Sensitivity, Serology, Specificity, Toxoplasma,
• MeSH
• Biology * methods   MeSH
• Precision Medicine * methods   MeSH
• Humans MeSH
• DNA Mutational Analysis * methods   standards   MeSH
• Sensitivity and Specificity MeSH
• Software * MeSH
• Case-Control Studies MeSH
• Computational Biology methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cytomegalovirus (CMV) is the herpetic virus, which infects 45-100% people worldwide. Many reports suggest that CMV could impair cognitive functions of infected subjects. Here we searched for indices of effects of CMV on infected subjects' intelligence and knowledge. The Intelligence Structure Test I-S-T 2000 R was used to compare IQ of 148 CMV-infected and 135 CMV-free university students. Infected students expressed higher intelligence. Paradoxically, their IQ decreased with decreasing concentration of anti-CMV antibodies, which can be used, statistically, as a proxy of the time passed from the moment of infection in young subjects when the age of subjects is statistically controlled. The paradox of seemingly higher intelligence of CMV infected subjects could be explained by the presence of the subpopulation of about 5-10% CMV-positive individuals in the population of "CMV-negative students". These false negative subjects had probably not only the oldest infections and therefore the lowest concentration of anamnestic antibodies, but also the lowest intelligence among the infected students. Prevalence of CMV infection in all countries is very high, approaching sometimes 90%. Therefore, the total impact of CMV on human intelligence may be large.

• MeSH
• Biomarkers MeSH
• Cytomegalovirus Infections epidemiology   psychology   virology   MeSH
• Cytomegalovirus * MeSH
• Intelligence MeSH
• Intelligence Tests MeSH
• Cognition * MeSH
• Humans MeSH
• Public Health Surveillance MeSH
• Students * MeSH
• Case-Control Studies MeSH
• Models, Theoretical MeSH
• Universities * MeSH
• Health Knowledge, Attitudes, Practice MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Retracted Publication MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH

The protozoan Toxoplasma gondii infects about one-third of the world's population. The consumption of raw meat, contact with cats, contact with soil, and ingestion of food or water contaminated with soil are considered to be the most important sources of infection. Still in most women who were infected during pregnancy, no definitive source of infection is found. In 2014-2016, independent sources of T. gondii infection were searched for by gathering epidemiological data from 1865 (519 infected) responders. Touching garden soil (odds ratio (OR) 3·14, 95% confidence interval (CI) 1·3-6·35), sustaining cat-related injuries (OR 2·16, 95% CI 1·25-3·74), and eating improperly washed root vegetables (OR 1·71, 95% CI 1·02-2·87), but not risky sexual behavior (OR 1·22, 95% CI 0·79-1·90), were the predictors of infection. The seroprevalence of T. gondii infection had been increasing up to ages 35-50 in men and ages 50-54 in women. Past those ages, seroprevalence of toxoplasmosis has been decreasing. This suggests that the natural decrease of anamnestic antibodies concentrations over time leads to positivity-to-negativity seroconversion in many subjects. If this is true, then the prevalence of T. gondii infection in a general population and its potential impacts on public health could be much larger than generally believed.

• Keywords
• Cats, STD, Toxoplasmosis, dogs, pets, risk factors, sexually transmitted diseases, zoonosis,
• MeSH
• Adult MeSH
• Cats MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Prevalence MeSH
• Surveys and Questionnaires MeSH
• Dogs MeSH
• Risk-Taking * MeSH
• Risk Factors MeSH
• Aged MeSH
• Seroepidemiologic Studies MeSH
• Sexual Behavior * MeSH
• Toxoplasma physiology   MeSH
• Toxoplasmosis, Animal epidemiology   parasitology   MeSH
• Toxoplasmosis epidemiology   parasitology   MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Cats MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Dogs MeSH
• Aged MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Slovakia epidemiology   MeSH

BACKGROUND: A recent study performed on 1.3 million patients showed a strong association between being bitten by a cat and probability of being diagnosed with depression. Authors suggested that infection with cat parasite Toxoplasma could be the reason for this association. METHOD: A cross sectional internet study on a non-clinical population of 5,535 subjects was undertaken. RESULTS: The subjects that reported having been bitten by a dog and a cat or scratched by a cat have higher Beck depression score. They were more likely to have visited psychiatrists, psychotherapists and neurologists in past two years, to have been previously diagnosed with depression (but not with bipolar disorder). Multivariate analysis of models with cat biting, cat scratching, toxoplasmosis, the number of cats at home, and the age of subjects as independent variables showed that only cat scratching had positive effect on depression (p = 0.004). Cat biting and toxoplasmosis had no effect on the depression, and the number of cats at home had a negative effect on depression (p = 0.021). CONCLUSIONS: Absence of association between toxoplasmosis and depression and five times stronger association of depression with cat scratching than with cat biting suggests that the pathogen responsible for mood disorders in animals-injured subjects is probably not the protozoon Toxoplasma gondii but another organism; possibly the agent of cat-scratched disease - the bacteria Bartonella henselae.

• MeSH
• Bartonella henselae physiology   MeSH
• Depression microbiology   MeSH
• Cats MeSH
• Humans MeSH
• Multivariate Analysis MeSH
• Cat-Scratch Disease microbiology   MeSH
• Cross-Sectional Studies MeSH
• Dogs MeSH
• Animals MeSH
• Check Tag
• Cats MeSH
• Humans MeSH
• Male MeSH
• Dogs MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: About 30% of people on Earth have latent toxoplasmosis. Infected subjects do not express any clinical symptoms, however, they carry dormant stages of parasite Toxoplasma for the rest of their life. This form of toxoplasmosis is mostly considered harmless, however, recent studies showed its specific effects on physiology, behaviour and its associations with various diseases, including psychiatric disorders such as schizophrenia. Individuals who suffer from schizophrenia have about 2.7 times higher prevalence of Toxoplasma-seropositivity than controls, which suggests that some traits characteristic of schizophrenic patients, including the sex difference in schizophrenia onset, decrease of grey matter density in specific brain areas and modification of prepulse inhibition of startle reaction could in fact be caused by toxoplasmosis for those patients who are Toxoplasma-seropositive. METHODOLOGY/PRINCIPAL FINDINGS: We measured the effect of prepulse inhibition/facilitation of the startle reaction on reaction times. The students, 170 women and 66 men, were asked to react as quickly as possible to a startling acoustic signal by pressing a computer mouse button. Some of the startling signals were without the prepulse, some were 20 msec. preceded by a short (20 msec.) prepulse signal of lower intensity. Toxoplasma-seropositive subjects had longer reaction times than the controls. Acoustic prepulse shorted the reaction times in all subjects. This effect of prepulse on reaction times was stronger in male subjects and increased with the duration of infection, suggesting that it represented a cumulative effect of latent toxoplasmosis, rather than a fading out after effect of past acute toxoplasmosis. CONCLUSIONS: Different sensitivity of Toxoplasma-seropositive and Toxoplasma-seronegative subjects on effect of prepulses on reaction times (the toxoplasmosis-prepulse interaction) suggested, but of course did not prove, that the alternations of prepulse inhibition of startle reaction observed in schizophrenia patients probably joined the list of schizophrenia symptoms that are in fact caused by latent toxoplasmosis.

• MeSH
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Reaction Time MeSH
• Schizophrenic Psychology MeSH
• Schizophrenia immunology   parasitology   physiopathology   MeSH
• Sex Factors MeSH
• Toxoplasma physiology   MeSH
• Toxoplasmosis immunology   parasitology   physiopathology   psychology   MeSH
• Reflex, Startle physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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

BACKGROUND: The purpose of this study was to confirm that women with latent toxoplasmosis have developmentally younger fetuses at estimated pregnancy week 16 and to test four exclusive hypotheses that could explain the observed data. METHODS: In the present retrospective cohort study we analysed by the GLM (general linear model) method data from 730 Toxoplasma-free and 185 Toxoplasma-infected pregnant women. RESULTS: At pregnancy week 16 estimated from the date of the last menstruation, the mothers with latent toxoplasmosis had developmentally younger fetuses based on ultrasound scan (P = 0.014). Pregnancy of Toxoplasma-positive compared to Toxoplasma-negative women was by about 1.3 days longer, as estimated both from the date of the last menstruation (P = 0.015) and by ultrasonography (P = 0.025). CONCLUSION: The most parsimonious explanation for the observed data is retarded fetal growth during the first weeks of pregnancy in Toxoplasma-positive women. The phenomenon was only detectable in multiparous women, suggesting that the immune system may play some role in it.

• MeSH
• Time Factors MeSH
• Adult MeSH
• Cohort Studies MeSH
• Toxoplasmosis, Congenital complications   physiopathology   MeSH
• Humans MeSH
• Linear Models MeSH
• Pregnancy Complications, Parasitic physiopathology   MeSH
• Parity MeSH
• Antibodies, Protozoan analysis   MeSH
• Retrospective Studies MeSH
• Fetal Growth Retardation etiology   physiopathology   MeSH
• Pregnancy MeSH
• Ultrasonography, Prenatal MeSH
• Fetal Development physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antibodies, Protozoan MeSH

Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. The demonstration that latent Toxoplasma infections can alter behavior in rodents has led to a reconsideration of this assumption. When infected human adults were compared with uninfected adults on personality questionnaires or on a panel of behavioral tests, several differences were found. Other studies have demonstrated reduced psychomotor performance in affected individuals. Possible mechanisms by which T. gondii may affect human behavior include its effect on dopamine and on testosterone.

• MeSH
• Cattell Personality Factor Questionnaire * MeSH
• Chronic Disease MeSH
• Adult MeSH
• Humans MeSH
• Toxoplasmosis, Cerebral diagnosis   immunology   parasitology   psychology   MeSH
• Antibodies, Protozoan blood   MeSH
• Psychomotor Performance physiology   MeSH
• Reaction Time MeSH
• Schizophrenic Psychology * MeSH
• Schizophrenia diagnosis   immunology   parasitology   MeSH
• Pregnancy MeSH
• Toxoplasma * immunology   MeSH
• Age Factors MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Antibodies, Protozoan MeSH

The boy-to-girl ratio at birth (secondary sex ratio) is around 0.51 in most populations. The sex ratio varies between societies and may be influenced by many factors, such as stress and immunosuppression, age, primiparity, the sex of the preceding siblings and the socioeconomic status of the parents. As parasite infection affects many immunological and physiological parameters of the host, we analyzed the effect of latent toxoplasmosis on sex ratios in humans. Clinical records of 1,803 infants born from 1996 to 2004 contained information regarding the mother's age, concentration of anti-Toxoplasma antibodies, previous deliveries and abortions and the sex of the newborn. The results of our retrospective cohort study suggest that the presence of one of the most common parasites (with a worldwide prevalence from 20 to 80%), Toxoplasma gondii, can influence the secondary sex ratio in humans. Depending on the antibody concentration, the probability of the birth of a boy can increase up to a value of 0.72, C.I.95 = (0.636, 0.805), which means that for every 260 boys born, 100 girls are born to women with the highest concentration of anti-Toxoplasma antibodies. The toxoplasmosis associated with immunosuppression or immunomodulation might be responsible for the enhanced survival of male embryos. In light of the high prevalence of latent toxoplasmosis in most countries, the impact of toxoplasmosis on the human population might be considerable.

• MeSH
• Humans MeSH
• Sex Ratio * MeSH
• Antibodies, Protozoan blood   MeSH
• Pregnancy immunology   MeSH
• Toxoplasma MeSH
• Toxoplasmosis complications   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Pregnancy immunology   MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antibodies, Protozoan MeSH