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

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

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

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

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

BACKGROUND: Toxoplasma, a protozoan parasite of cats, infects many species of intermediate and paratenic hosts, including about one-third of humans worldwide. After a short phase of acute infection, the tissue cysts containing slowly dividing bradyzoites are formed in various organs and toxoplasmosis proceeds spontaneously in its latent form. In immunocompetent subjects, latent toxoplasmosis was considered asymptomatic. However, dozens of studies performed on animals and humans in the past twenty years have shown that it is accompanied by a broad spectrum of specific behavioural, physiological and even morphological changes. In human hosts, the changes often go in the opposite direction in men and women, and are mostly weaker or non-existent in Rh-positive subjects. METHODS: Here, we searched for the indices of lower endurance of the infected subjects by examining the performance of nearly five hundred university students tested for toxoplasmosis and Rh phenotype in two tests, a weight holding test and a grip test. RESULTS: The results confirmed the existence of a negative association of latent toxoplasmosis with the performance of students, especially Rh-negative men, in these tests. Surprisingly, but in an accordance with some already published data, Toxoplasma-infected, Rh-positive subjects expressed a higher, rather than lower, performance in our endurance tests. DISCUSSION: Therefore, the results only partly support the hypothesis for the lower endurance of Toxoplasma infected subjects as the performance of Rh-positive subjects (representing majority of population) correlated positively with the Toxoplasma infection.

• MeSH
• Physical Endurance * MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M blood   MeSH
• Rh-Hr Blood-Group System blood   MeSH
• Humans MeSH
• Young Adult MeSH
• Antibodies, Protozoan blood   MeSH
• Hand Strength * MeSH
• Toxoplasma immunology   MeSH
• Toxoplasmosis physiopathology   MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Immunoglobulin G MeSH
• Immunoglobulin M MeSH
• Rh-Hr Blood-Group System MeSH
• Antibodies, Protozoan 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: Latent toxoplasmosis, a lifelong infection with the protozoan Toxoplasma gondii, has cumulative effects on the behaviour of hosts, including humans. The most impressive effect of toxoplasmosis is the "fatal attraction phenomenon," the conversion of innate fear of cat odour into attraction to cat odour in infected rodents. While most behavioural effects of toxoplasmosis were confirmed also in humans, neither the fatal attraction phenomenon nor any toxoplasmosis-associated changes in olfactory functions have been searched for in them. PRINCIPAL FINDINGS: Thirty-four Toxoplasma-infected and 134 noninfected students rated the odour of urine samples from cat, horse, tiger, brown hyena and dog for intensity and pleasantness. The raters were blind to their infection status and identity of the samples. No signs of changed sensitivity of olfaction were observed. However, we found a strong, gender dependent effect of toxoplasmosis on the pleasantness attributed to cat urine odour (p = 0.0025). Infected men rated this odour as more pleasant than did the noninfected men, while infected women rated the same odour as less pleasant than did noninfected women. Toxoplasmosis did not affect how subjects rated the pleasantness of any other animal species' urine odour; however, a non-significant trend in the same directions was observed for hyena urine. CONCLUSIONS: The absence of the effects of toxoplasmosis on the odour pleasantness score attributed to large cats would suggest that the amino acid felinine could be responsible for the fatal attraction phenomenon. Our results also raise the possibility that the odour-specific threshold deficits observed in schizophrenia patients could be caused by increased prevalence of Toxoplasma-infected subjects in this population rather than by schizophrenia itself. The trend observed with the hyena urine sample suggests that this carnivore, and other representatives of the Feliformia suborder, should be studied for their possible role as definitive hosts in the life cycle of Toxoplasma.

• MeSH
• Mental Disorders chemically induced   epidemiology   MeSH
• Cats MeSH
• Humans MeSH
• Urine chemistry   MeSH
• Odorants * MeSH
• Olfaction Disorders chemically induced   epidemiology   MeSH
• Sex Factors MeSH
• Toxoplasmosis complications   MeSH
• Animals MeSH
• Check Tag
• Cats MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't 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

BACKGROUND: Recently, a negative association between Toxoplasma-infection and novelty seeking was reported. The authors suggested that changes of personality trait were caused by manipulation activity of the parasite, aimed at increasing the probability of transmission of the parasite from an intermediate to a definitive host. They also suggested that low novelty seeking indicated an increased level of the neurotransmitter dopamine in the brain of infected subjects, a phenomenon already observed in experimentally infected rodents. However, the changes in personality can also be just a byproduct of any neurotropic infection. Moreover, the association between a personality trait and the toxoplasmosis can even be caused by an independent correlation of both the probability of Toxoplasma-infection and the personality trait with the third factor, namely with the size of living place of a subject. To test these two alternative hypotheses, we studied the influence of another neurotropic pathogen, the cytomegalovirus, on the personality of infected subjects, and reanalyzed the original data after the effect of the potential confounder, the size of living place, was controlled. METHODS: In the case-control study, 533 conscripts were tested for toxoplasmosis and presence of anti-cytomegalovirus antibodies and their novelty seeking was examined with Cloninger's TCI questionnaire. Possible association between the two infections and TCI dimensions was analyzed. RESULTS: The decrease of novelty seeking is associated also with cytomegalovirus infection. After the size of living place was controlled, the effect of toxoplasmosis on novelty seeking increased. Significant difference in novelty seeking was observed only in the largest city, Prague. CONCLUSION: Toxoplasma and cytomegalovirus probably induce a decrease of novelty seeking. As the cytomegalovirus spreads in population by direct contact (not by predation as with Toxoplasma), the observed changes are the byproduct of brain infections rather than the result of manipulation activity of a parasite. Four independent lines of indirect evidence, namely direct measurement of neurotransmitter concentration in mice, the nature of behavioral changes in rodents, the nature of personality changes in humans, and the observed association between schizophrenia and toxoplasmosis, suggest that the changes of dopamine concentration in brain could play a role in behavioral changes of infected hosts.

• MeSH
• Cytomegalovirus Infections complications   immunology   psychology   MeSH
• Adult MeSH
• Humans MeSH
• Personality physiology   MeSH
• Exploratory Behavior physiology   MeSH
• Antibodies, Protozoan blood   MeSH
• Antibodies, Viral blood   MeSH
• Case-Control Studies MeSH
• Toxoplasmosis complications   immunology   psychology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antibodies, Protozoan MeSH
• Antibodies, Viral MeSH