Latent Toxoplasmosis Research Articles

Effects of early spontaneous abortions (ESA) and latent toxoplasmosis on Interleukine-23 in women

Cytokines play an important role in intercellular communications, cell growth, differentiation, and immune system modulations. Some of these functions have crucial roles in pregnancy gaining or losing, especially those correlated with T helper 1, T helper 2, and T helper 17 cells. Several studies showed significant variations in Interleukine-23 (IL-23) with Toxoplasma infection. However, little is known about the regulations of this interleukin in the case of early spontaneous abortion (ESA) patients. The present study aimed to evaluate IL-23 to explain the effect of this cytokine on pregnancy gaining or losing with and without toxoplasma infections. Eighty-nine subjects were registered in the current study,16 Toxoplasma infected ESA women, 41 unknown ESA aborted women, 16 healthy pregnant women, and 16 healthy non-pregnant women served as control negative. Detections of anti-Toxoplasma IgG and IL-23 by immunoenzymatic assay (IFA and ELISA, respectively). A significant difference (P = > 0.05) was found in all subjected groups except between Toxoplasmosis ESA and unknown EAS women. The data showed a substantial increase in sera IL-23 in unknown ESA with mean and standard deviation (SD) (13.679±2.461) and Toxoplasma infected women with mean and SD (14.279±4.757) as compared with non-Pregnant women having mean and SD (5.824±1.040) and healthy pregnant women with mean and SD (17.273±6.418). Therefore, this considerable evidence may indicate a role of IL-23 in the development of pregnancy gaining or losing, especially those ESA women.

Congenital Co-infections Among HIV-Exposed Infants Born to Mothers on Antiretroviral Treatment in the United States.

BackgroundMany women living with HIV (WLHIV) are co-infected with cytomegalovirus (CMV), Toxoplasma gondii (T gondii), and/or hepatitis C virus (HCV). The rates of congenital or perinatal transmission of these co-infections are not well defined in the current era, when most WLHIV receive antiretroviral therapy (ART) during pregnancy.MethodsRetrospective review of infants of WLHIV born between 2009–2019. Mothers were screened for antibodies to CMV, T. gondii, and HCV; chronic HCV infection was confirmed using plasma RNA PCR. Infants whose mothers had positive/unknown serostatus were screened for CMV using urine or saliva DNA PCR or culture at ≤3 weeks of life; T. gondii using serology at ≤1 month; and HCV using plasma RNA PCR at ≤6 months and serology at ≥12 months.ResultsThe study included 264 infants from 255 pregnancies in 191 mothers. At delivery, the median (IQR) CD4 count was 569 (406–748) cells/mm3 and plasma HIV load was 0 (0–24) RNA copies/mL. Among 243 infants born to CMV-seropositive (209) or CMV-missed serostatus (25) mothers, 163 (67.1%) were tested for CMV. Four infants had CMV detected, resulting in a rate of congenital infection of 2.5%. Among 65 infants from 54 (21.2%) pregnancies in T. gondii-seropositive women and 8 in women with unknown T. gondii-serostatus, one acquired congenital toxoplasmosis in the setting of acute maternal T. gondii infection. There were no episodes of vertical transmission from mothers with latent toxoplasmosis. Among 18 infants from 13 (5.1%) pregnancies in HCV RNA PCR-positive women and 4 in women with unknown HCV serostatus, there were no congenital or perinatal HCV transmissions.ConclusionsIn a US cohort of pregnant WLHIV on ART, we identified high maternal CMV seroprevalence and a high rate of congenital CMV infection. We did not identify any congenital or perinatal transmissions of T. gondii or HCV among mothers who had latent or chronic infections. Our data support screening pregnant WLHIV and their infants for CMV and suggest that the rates of congenital and perinatal T. gondii and HCV infections among infants born to WLHIV on ART may be lower in the era of effective ART.

Histopathological, Immunohistochemical and Biochemical Studies of Murine Hepatosplenic Tissues Affected by Chronic Toxoplasmosis.

Toxoplasmosis is a serious health problem in humans and animals resulting from obligatory intracellular invasion of reticuloendothelial tissue by Toxoplasma gondii. The profound pathologic effect of toxoplasmosis is confined to nervous tissue, but many other organs, including the liver and spleen, are insulted. Many molecules like caspase-3, CD3, and CD138 are implicated in the tissue immune response in a trial to alleviate hazardous toxoplasmosis impact. This study aimed to investigate the effect of chronic toxoplasmosis on the liver and spleen tissues of mice using biochemical and histopathological techniques and to detect the activity and level of expression of caspase-3, CD3, and CD138 in these tissues using immunohistochemical labeling. Compared with normal control, altered normal histological features accompanied by inflammatory reaction were recorded in hepatosplenic reticuloendothelial tissues in chronically infected mice. The biochemical profile of the liver has been changed in the form of increased liver enzymes, and oxidative stress has been evidenced by elevated nitric oxide (NO) concentration in liver homogenate. The levels of caspase3, CD3, and CD138 were markedly expressed in the liver and spleen of infected mice. Our findings revealed the persistent effect of latent toxoplasmosis on the host's histological architecture, metabolic, and immunological profile, creating a continued challenging host-parasite relationship.

Prevalence and Predictors of Toxoplasma gondii Infection in Psychiatric Inpatients in Fars Province, Southern Iran.

BackgroundPsychiatric patients are at increased risk of exposure to Toxoplasma gondii infection, which may be linked to their living facilities and behaviors. Limited knowledge on the prevalence of T. gondii infection and its associated risk factors in psychiatric patients are available to the international medical communities. Thus, the aim of the current study was to assess seroprevalence of T. gondii and its associated risk factors in psychiatric inpatients in Fars Province, southern Iran.MethodsThis cross-sectional study was carried out on psychiatric patients hospitalized in Ibn Sina Hospital affiliated to Shiraz University of Medical Sciences, Fars Province, southern Iran, March to July 2021. Blood samples were collected from 318 psychiatric patients and assessed for the detection of IgG against T. gondii using enzyme-linked immunosorbent assay (ELISA). Moreover, structured questionnaires were completed for the participants at the time of sampling. Logistic regression analysis was used to assess possible associations between the latent toxoplasmosis and the variables.ResultsThe overall seroprevalence of anti-T. gondii IgG in psychiatric inpatients was 22.3% (71/318; 95% CI = 17.9–27.3). Multivariate analyses revealed that age > 30 years [adjusted odds ratio (AOR) = 2.24, 95% CI = 1.10–4.60, p = 0.03], contact with cats (AOR = 2.52, 95% CI = 1.14–5.58, p = 0.03), raw vegetable consumption (AOR = 3.65, 95% CI = 1.74–7.65, p = 0.001), raw/undercooked meat consumption (AOR = 4.30, 95% CI = 1.47–12.63, p = 0.008), suicide attempt (AOR = 3.77, 95% CI = 1.58–8.97, p = 0.003) and cigarette smoking history (AOR = 0.38, 95% CI = 0.17–0.83, p = 0.02) were independent risk factors for T. gondii infection.ConclusionThe current results demonstrated that contact with cats, raw vegetable consumption and raw/undercooked meat consumption were independent risk factors for T. gondii seropositivity. Moreover, the current study showed significant associations between seropositivity of T. gondii and suicide attempts as well as negative associations between seropositivity of T. gondii and cigarette smoking in psychiatric inpatients using multivariate logistic regression.

Epigenetic Manipulation of Psychiatric Behavioral Disorders Induced by Toxoplasma gondii.

Toxoplasma gondii is known to have a complex life cycle and infect almost all kinds of warm-blooded animals around the world. The brain of the host could be persistently infected by cerebral cysts, and a variety of psychiatric disorders such as schizophrenia and suicide have been reported to be related with latent toxoplasmosis. The infected animals showed fear reduction and a tendency to be preyed upon. However, the mechanism of this “parasites manipulation” effects have not been elucidated. Here, we reviewed the recent infection prevalence of toxoplasmosis and the evidence of mental and behavioral disorders induced by T. gondii and discussed the related physiological basis including dopamine dysregulation and gamma-aminobutyric acid (GABA) pathway and the controversial opinion of the necessity for cerebral cysts existence. Based on the recent advances, we speculated that the neuroendocrine programs and neurotransmitter imbalance may play a key role in this process. Simultaneously, studies in the evaluation of the expression pattern of related genes, long noncoding RNAs (lncRNAs), and mRNAs of the host provides a new point for understanding the mechanism of neurotransmitter dysfunction induced by parasite manipulation. Therefore, we summarized the animal models, T. gondii strains, and behavioral tests used in the related epigenetic studies and the responsible epigenetic processes; pinpointed opportunities and challenges in future research including the causality evidence of human psychiatric disorders, the statistical analysis for rodent-infected host to be more vulnerable preyed upon; and identified responsible genes and drug targets through epigenetics.

Toxoplasmosis impact on prematurity and low birth weight.

BackgroundToxoplasma gondii, one of the most common parasites, causes toxoplasmosis, one of the most frequent zoonotic diseases worldwide. T. gondii infects about one-third of the world’s population. T. gondii infection is generally considered a major risk for spontaneous abortion, prematurity and low birth weight in the animal sphere. Less commonly, a toxoplasma serological profile is correlated with the particular data of delivery. Acute T. gondii infection during pregnancy often leads to spontaneous abortion and/or a severe injury of the eyes, brain, and other structures of the foetus. Latent T. gondii infection of pregnant women could lead to less obvious but important changes during pregnancy, including the end product of pregnancy and the timing of labour. This study aimed to contribute to the current knowledge by comparing serological T. gondii profiles of pregnant women with prematurity and low birth weights of newborns.Material and methodsA retrospective study design was adopted. The study participants included a cohort of 1733 pregnant women who consecutively gave birth to their children and underwent regular antenatal biochemical screening between the 14th and 16th weeks of pregnancy. Prematurity was defined as the liveborn preterm delivery in gestational age of pregnancy <37 weeks. Low birth weight was defined as weight at birth of ≤2499 grams. The complement-fixation test (CFT) provided serological profiles for toxoplasmosis that expresses the overall levels of toxoplasma immunoglobulins of all classes. Enzyme-linked immunosorbent assay (ELISA) tests for IgG and IgM were used simultaneously. IgM positivity helped to differentiate acute from the latent stage of toxoplasmosis. Birth data, especially the week of delivery and fetal weight, were evaluated accordingly.ResultsOf the 1733 pregnant women, 25% were diagnosed as latent toxoplasma positive, and 75% as toxoplasma negative. There were 87 premature deliveries versus 1646 timely births. We observed 88 low birth weights and 1645 normal fetal weights. We found a statistically significant association between latent toxoplasmosis and prematurity, χ2(1) = 5.471, p = .019 and between latent toxoplasmosis and low birth weight of newborns, χ2(1) = 7.663, p = .006. There was a 1.707 times higher risk of prematurity for toxoplasma-positive women, while the risk for low birth weight was 1.861 times higher. The strength of both tests of association was mild. We tested the correlation between the levels of CFT titres and week of delivery and weight of newborns. No association was found between the level of latent toxoplasmosis and the week of delivery and fetal weight.ConclusionLatent toxoplasmosis was associated with premature birth rate and lower birth weight of newborns. The odds of premature delivery was 1.7 and low birth weight 1.9 times higher in women with latent toxoplasmosis compared to toxoplasma negative women. Even though the strength of the association in our large sample is relatively mild, the combination of latent toxoplasmosis with other adverse factors could cause serious harm. Whole CFT and specific IgG levels of latent toxoplasmosis are not linked to the severity of prematurity or low birth weight in newborns.

Behavioral Changes Induced by Latent Toxoplasmosis Could Arise from CNS Inflammation and Neuropathogenesis.

Chronic infection with Toxoplasma gondii, a neurotropic parasite, has been linked to multiple behavioral changes in rodents and humans. The pathogenic mechanisms underlying these correlations are not known. I discuss here from animal studies the distribution of tissue cysts, the constant immune surveillance, the critical role of cyst burden, and the time-dependent consequences, which I believe are crucial to explaining the behavioral changes. In line with the brain-wide distribution of tissue cysts and chronic neuroinflammation, infected mice displayed a broad range of behavioral phenotypes. Many studies suggest that behavioral changes in mice are directly associated with tissue cyst presence or cyst burden and the host immune response. Cyst burden may not exert direct effects; however, the mechanisms causing behavioral and neuropathological changes are potentially the consequence of cyst burden over time, such as the neuroinflammation required to control the reactivation of tissue cysts. The reduction of neuroinflammation has proven that neuropathogenesis and behavioral abnormalities can be reversed, at least partially, in infected mice. Overall, Toxoplasma-induced behavioral changes are likely to be an indirect consequence of the host immune response in a parasite burden-dependent manner.

Estimation of Cyclophilin and Phospholipase Enzyme in Women Infected with Toxoplasmosis.

Toxoplasma gondii, a protozoan parasite with a worldwide distribution, is considered to infect one-third of all humans. many species. The intracellular parasite Toxoplasma gondii causes toxoplasmosis. Numerous physiological abnormalities are documented in toxoplasmosis-infected women. This study aims to demonstrate the connection between cyclophilins, the phospholipase enzyme, and latent toxoplasmosis. The research was carried out between January 2022 and June 2022. out of 150 patients had blood samples drawn, 250 had serum samples drawn from women with toxoplasma gondi infection, and 50 had healthy samples drawn from Hila city, Iraq. To exclude subjects who had any medical disorders, information from the subjects was gathered via an interviewer-managed questionnaire. ELISA was used to examine the serum. Results: About 250 samples from women with infertility were infected with Toxoplasma gondii overall (24%) Enzyme-Linked Immunosorbent Assay was utilized to evaluate the levels of phospholipase and cyclophilin, while automated VIDAS family instruments were employed to determine the qualitative and quantitative anti-Toxoplasma-IgG-tests (ELISA). Since there was a substantial difference in the statistical analysis and a significant difference in the cyclophilin protein, parasite infection changed the quantity of the enzyme phospholipase. This study put forth the theory that toxoplasmosis infection. Our investigation showed that patients with toxoplasma Gondi infection had higher levels of cyclophilins and phospholipase than control subjects.

Toxoplasma gondii infection in HIV-infected pregnant women: epidemiology and risks of mother-to-child transmission.

Toxoplasma gondii (T. gondii) infects approximately one third of the world's population. Globally there are an estimated 13.1 million cases of T. gondii co-infection in HIV-infected people with 87.1% of these individuals living in sub-Saharan Africa. The risk of T. gondii infection in HIV-infected women rises significantly with lower CD4+ T cell counts (particularly under 100 cells/μl). Mother-to-child transmission (MTCT) occurs in approximately 30% of cases of maternal T. gondii infection during pregnancy. The global prevalence of latent toxoplasmosis in HIV-infected pregnant women is 47.5% but the overall risk in HIV-infected mothers of MTCT of T. gondii is however, estimated to be low at < 5%. MTCT in HIV-infected mothers not only occurs due to T. gondii primary infection in pregnancy but also due to reactivation. Infants with congenital toxoplasmosis born to HIV-infected mother may have a more rapid onset and greater dissemination of disease thus having potentially devastating effects. This article discusses the key risks for MTCT of T. gondii infection in HIV-infected mothers as well highlighting the many knowledge gaps for which further study is required.

Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations.

Toxoplasmosis, an infectious zoonotic disease caused by the apicomplexan parasite Toxoplasma gondii (T. gondii), is a major worldwide health problem. However, there are currently no effective options (chemotherapeutic drugs or prophylactic vaccines) for treating chronic latent toxoplasmosis infection. Accordingly, seeking more effective and safer chemotherapeutics for combating this disease remains a long-term and challenging objective. In this paper, we summarize possible molecular biotargets, with an emphasis on those that are druggable and promising, including, without limitation, calcium-dependent protein kinase 1, bifunctional thymidylate synthase-dihydrofolate reductase, and farnesyl diphosphate synthase. Meanwhile, as important components of medicinal chemistry, the binding modes and structure-activity relationship profiles of the corresponding inhibitors were also illuminated. We anticipate that this information will be helpful for further identification of more effective chemotherapeutic interventions to prevent and treat zoonotic infections caused by T. gondii.

Prevalence of toxoplasmosis in patients infected with tuberculosis; a sero-molecular case-control study in northwest Iran

In this study, we investigated the possible association between TB and Toxoplasma gondii infection. One hundred confirmed TB individuals living in northwest Iran were classified into three subgroups; newly diagnosed patients (NTB), old diagnosed patients (OTB) and multidrug resistance patients (MDR-TB). One hundred healthy subjects in the same age and sex distribution were ethnically matched. Sera samples were screened for anti-Toxoplasma antibodies. Nested-PCR was performed by targeting the B1 and GRA6 genes. The frequency of Toxoplasma infection based on IgG titer was 71.1% in the OTB subgroup and 33% in the control group, indicating significant association between Toxoplasma seropositivity and OTB (P = 0.001). According to phylogenetic network, the type I strain of Toxoplasma was identified in the OTB subgroup (10.1%). We concluded that patients with OTB subgroup are at high risk for acquisition of Toxoplasma infection which could reactivate the latent toxoplasmosis.

Is COVID-19 associated with latent toxoplasmosis?

The present study aimed to evaluate the possible association between coronavirus disease 2019 (COVID-19) and latent Toxoplasma gondii infection in a group of patients and healthy individuals. Blood samples were obtained from 269 PCR-positive COVID-19 patients. The serum was separated and tested for the existence of anti-T. gondii antibodies (IgG) using a commercial enzyme-linked immunosorbent assay kit. The prevalence of latent toxoplasmosis between a subgroup of the patients (aged under 55 years old) and COVID-19 negative individuals was compared. Anti-T. gondii antibodies were found in 226/269 (84.0%) patients with COVID-19. Anti-Toxoplasma antibodies were detected in 72/91 (79.1%) cases and 96/123 (78.0%) COVID-19 negative individuals (odd ratio = 1.1; 95% confidence interval: 0.55–2.07, P = 0.85). The median and interquartile range (IQR) of the IgG titer were not statistically significant different between case (97.3 [31.0–133.5]) and control groups (34.4 [13.0–144.5]) (P = 0.10). These findings demonstrated that latent Toxoplasma infection is prevalent amongst the COVID-19 patients. It also did not find any significant association between chronic toxoplasmosis and COVID-19.

Toxoplasmosis is a risk factor for acquiring SARS-CoV-2 infection and a severe course of COVID-19 in the Czech and Slovak population: a preregistered exploratory internet cross-sectional study

BackgroundLatent 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.MethodsA 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.ResultsLogistic 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.ConclusionsToxoplasmosis 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.Graphical abstract

OUTCOMES OF TRANSPLACENTAL TRANSMISSION OF TOXOPLASMA GONDII FROM CHRONICALLY INFECTED FEMALE RED RUFFED LEMURS (VARECIA RUBRA).

Ten red ruffed lemurs (Varecia rubra)-two adult females and their eight offspring-were evaluated in this case series. Two adult females were diagnosed with chronic, latent toxoplasmosis based on serologic testing. The first female lemur had two successive pregnancies. The first pregnancy resulted in transplacental transmission of Toxoplasma gondii. The only surviving offspring was diagnosed with congenital toxoplasmosis based on serologic testing and compatible ophthalmic lesions. The two deceased offspring had disseminated nonsuppurative inflammation and intralesional protozoal organisms consistent with T. gondii, which was confirmed by polymerase chain reaction. The second pregnancy did not result in transplacental transmission. The second chronically infected adult female lemur had one pregnancy that resulted in a single stillborn fetus without evidence of transplacental transmission of T. gondii. Treatment with trimethoprim-sulfamethoxazole and folinic acid was administered to the first adult female and one offspring, but no treatment was given to the second adult female. All surviving lemurs had no further complications associated with toxoplasmosis. This case series demonstrates that chronic, latent infection of reproductive female red ruffed lemurs with T. gondii may result in variable outcomes: (1) transplacental transmission with disseminated fetal infection and stillbirth, (2) transplacental transmission with congenital infection and survival, or (3) lack of transplacental transmission and healthy offspring. Information gained from these cases may help guide recommendations for breeding of this critically endangered species.

Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis

ObjectivesReactivation of latent toxoplasmosis may be life-threatening in haematopoietic stem cell transplant (HSCT) recipients. We conducted an 8-year-long prospective study on the diagnosis and monitoring of reactivated toxoplasmosis in paediatric HSCT recipients. The primary objective was to determine the incidence of reactivated toxoplasmosis in a setting that withholds prophylaxis until engraftment. The second objective was to identify the subgroups of HSCT recipients particularly prone to reactivation who may benefit the most from regular PCR follow-up. MethodsSerological and qPCR screening targeting the Toxoplasma 529 bp gene was performed before HSCT, and continued by weekly monitoring after HSCT for a median time of 104 days. ResultsReactivated toxoplasmosis was diagnosed in 21/104 (20.2%), predominantly in allo- (19/75) and rarely in auto-HSCT (2/29) recipients. Over 50% (14/21) of cases were diagnosed during the first month after HSCT, while awaiting engraftment without prophylaxis. Toxoplasma disease evolved in only three (14.3%, 3/21) patients, all treated by allo-HSCT. Reactivation was more frequent in patients treated for acute lymphoblastic leukaemia (3/27, p 0.03) and especially, in recipients of haploidentical stem cells (10/20, p 0.005). Seronegative status of the donor (where was known) contributed to 75% (12/16) cases of reactivated toxoplasmosis after allo-HSCT. DiscussionThe presented results show that peripheral blood-based qPCR, both before and after HSCT, is a valuable asset for the diagnosis of reactivated toxoplasmosis, whereas the results of serology in recipients should be interpreted with caution. Weekly qPCR monitoring, at least until successful engraftment and administration of prophylaxis, allows for prompt introduction of specific treatment.

Toxoplasmosis: Targeting neurotransmitter systems in psychiatric disorders.

The most common form of the disease caused by Toxoplasma gondii (T. gondii)is latent toxoplasmosis due to the formation of tissue cysts in various organs, such as the brain. Latent toxoplasmosis is probably a risk factor in the development of some neuropsychiatric disorders. Behavioral changes after infection are caused by the host immune response, manipulation by the parasite, central nervous system (CNS) inflammation, as well as changes in hormonal and neuromodulator relationships. The present review focused on the exact mechanisms of T. gondii effect on the alteration of behavior and neurotransmitter levels, their catabolites and metabolites, as well as the interaction between immune responses and this parasite in the etiopathogenesis of psychiatric disorders. The dysfunction of neurotransmitters in the neural transmission is associated with several neuropsychiatric disorders. However, further intensive studies are required to determine the effect of this parasite on altering the level of neurotransmitters and the role of neurotransmitters in the etiology of host behavioral changes.

Rebound of cyst number following discontinuation of guanabenz treatment for latent toxoplasmosis

Toxoplasma gondii is a protozoan parasite that causes opportunistic infection in immunocompromised individuals. The parasite forms latent tissue cysts that are refractory to current treatments and give rise to life-threatening reactivated infection following immune suppression. Previously, we showed that guanabenz sharply reduces brain cyst count in BALB/c mice harboring latent toxoplasmosis; however, whether cyst count would change once drug treatment stopped was not addressed. In the present study, we observed a rebound in brain cysts following the discontinuation of guanabenz or a guanabenz-pyrimethamine combination therapy. The re-expansion of brain cysts was not accompanied by symptoms of acute toxoplasmosis. We also tested whether the rebound in cyst counts could be ameliorated by administering pyrimethamine during or after guanabenz treatment.

Relationship between Latent Toxoplasmosis and Depression in Clients of a Center for Assisted Reproduction.

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.

Latent toxoplasmosis and vitamin D concentration in humans: three observational studies.

Numerous recent studies show that vitamin D deficiency potentiates various chronic physical and psychiatric disorders and diseases. It has been shown that a similar range of disorders is also associated with latent infection with Toxoplasma gondii (Nicolle et Manceaux, 1908). For instance, among cancer, diabetes and schizophrenia patients, we find a higher prevalence of both toxoplasmosis and vitamin D deficiency. Theoretically, therefore, vitamin D deficiency could be the missing link between toxoplasmosis and these disorders. We tested this hypothesis by searching for decreased vitamin D levels in the serum of subjects infected with T. gondii (furthermore called Toxoplasma-infected subjects) in two cross-sectional and one case-control study. Results of the first cross-sectional study (N = 72) suggest that Toxoplasma-infected neurasthenic patients have non-significantly lower levels of calcidiol than Toxoplasma-free patients (study A: P = 0.26 in women, P = 0.68 in men). However, two other studies (study B: N = 400; study C: N = 191) showed a non-significantly higher concentration of vitamin D in Toxoplasma-infected subjects than in Toxoplasma-free subjects both in men (study B: P = 0.70, study C: P = 0.55) and in women (study B: P = 0.64, study C: P = 0.12). Taken together, our preliminary results thus do not support the hypothesis that toxoplasmosis could be associated with vitamin D decrease.

Association between latent toxoplasmosis and fertility parameters of men.

About a third of people in the world are infected with Toxoplasma gondii. This parasite has been found in the reproductive organs and semen of males of many animal species as well as humans. The effects of toxoplasmosis on sperm count, motility and morphology were confirmed in rats. A higher prevalence of toxoplasmosis has been observed in infertile men. On the other hand, no significant effect of infection on semen parameters in men was found in one already published study. To compare the prevalence of toxoplasmosis in men with and without semen pathology and to examine in detail the possible impact of infection on semen volume, sperm count, motility and morphology. The pre-registered cross-sectional study included 669 men who visited the Centre for Assisted Reproduction in Prague from June 2016 until June 2018. The incidence of fertility problems was significantly higher in the 163 Toxoplasma-infected men (48.47%) than in the 506 Toxoplasma-free men (42.29%), τ = 0.049, P=0.029. After correction for multiple tests, we found significantly lower sperm concentration, concentration of progressively motile sperm, and concentration of non-progressively motile sperm in Toxoplasma-positive men than in Toxoplasma-negative men using partial Kendall correlation with age controlled. In addition, toxoplasmosis correlated with sperm quality in smokers but not in non-smokers. Our results suggest that latent toxoplasmosis affects certain semen parameters (sperm count and motility), but does not seem to affect sperm morphology and semen volume. Impairment of semen parameters may be either a side effect of the presence of Toxoplasma gondii in male reproductive organs or a product of manipulation activity of the parasite aimed to increase the efficiency of the sexual route of its transmission. Tobacco smoking also appears to exacerbate the negative impact of toxoplasmosis on semen parameters.