Most cited article - PubMed ID 20608469
Influence of latent toxoplasmosis on the phenotype of intermediate hosts
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: 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
The article is a perspective on utilization of microorganisms and chemosignals in studying human economic behavior. Research in biological roots of economic development has already confirmed that parasitic pressure influenced the creation and development of cultural norms and institutions. However, other effects of microorganisms on human groups and individual decision-making and behavior are heavily understudied. The perspective discusses how parasitic infections, sexually transmitted organisms and microbiota (i.e., "human holobiont") could causally influence risk-seeking behavior, impulsivity, social dominance, empathy, political views and gender differences. As a case study, the parasite Toxoplasma gondii and its influence on economic preferences, personal characteristics and human appearance are examined. I also briefly review how chemosignals influence decision-making, particularly in the social preferences domain. I mention some predictions that arise from the paradigm of economic holobiont for the economic science. The conclusion summarizes limitations of the discussed findings and the stated speculations.
- Keywords
- Toxoplasma gondii, chemosignaling, economics, microbiota, parasites, risk preferences, social preferences, time preferences,
- Publication type
- Journal Article MeSH
The parasite Toxoplasma needs to get from its intermediate hosts, e.g. rodents, to its definitive hosts, cats, by predation. To increase the probability of this occurrence, Toxoplasma manipulates the behavior of its hosts, for example, by the demethylation of promoters of certain genes in the host's amygdala. After this modification, the stimuli that normally activate fear-related circuits, e.g., the smell of a cat in mice, or smell of leopards in chimpanzees, start to additionally co-activate sexual arousal-related circuits in the infected animals. In humans, the increased attraction to masochistic sexual practices was recently observed in a study performed on 36,564 subjects. Here I show that lower rather than higher attraction to sexual masochism and submissiveness among infected subjects is detected if simple univariate tests instead of multivariate tests are applied to the same data. I show and discuss that when analyzing multiple effects of complex stimuli on complex biological systems we need to use multivariate techniques and very large data sets. We must also accept the fact that any single factor usually explains only a small fraction of variability in the focal variable.
- Keywords
- BDSM, Toxoplasmosis, big data, complex systems, epigenetics, manipulation, multivariate statistics, parasitism, sexual behavior, violence,
- Publication type
- Journal Article 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: Past research linked Toxoplasma gondii (TG) infection in humans with neurological and mental disorders (e.g., schizophrenia, Alzheimer's disease and attention disorders), irregularities of the dopaminergic and testosterone system, and increased likelihood of being involved in traffic accidents. METHODOLOGY/PRINCIPAL FINDINGS: We test for an association between TG infection and financial decision-making (DM) using a case-control design in a sample of female Czech students (n = 79). We estimate each subject's risk attitude and loss aversion using an experimental economic task involving real monetary incentives. We find no significant evidence that either measure of decision-making is associated with TG infection. CONCLUSION: We were unable to find evidence of an association between TG infection and financial decision-making in females.
- MeSH
- Adult MeSH
- Financial Management * MeSH
- Rh-Hr Blood-Group System genetics immunology MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Risk-Taking * MeSH
- Decision Making MeSH
- Sex Factors MeSH
- Case-Control Studies MeSH
- Toxoplasmosis complications diagnosis MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Rh-Hr Blood-Group System MeSH
- Rho(D) antigen MeSH Browser
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