[Toxoplasmosis in the practice of a neurologist]. / Toksoplazmoz v praktike nevrologa.

Toxoplasmosis is a zoonotic protozoal disease characterized by a chronic course, polymorphism of clinical manifestations, predominant damage to the central nervous system, organs of vision, liver and lungs. The causative agent of the disease is the obligate intracellular parasite Toxoplasma gondii, which circulates widely in the external environment and has a large circle of intermediate hosts. Toxoplasmosis is classified by the method of infection (congenital or acquired), by pathogenesis (acute or chronic), by manifestation (latent or with the manifestation of symptoms). According to the state of the human immune system, the disease can occur without immunodeficiency, while the patient has a chronic lifelong carrier, and with immunodeficiency. People with HIV most commonly present with cerebral toxoplasmosis. The article presents a case of the development of toxoplasmosis in a patient in the absence of a burdened history.

First description of congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2: a case report.

BACKGROUND: Congenital toxoplasmosis can be associated with serious clinical consequences from fetus to adulthood. Hence, early detection is required to minimize severe sequelae through appropriate therapy. We describe the first case of a congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2 and the challenging serological diagnosis of the disease in this context. CASE PRESENTATION: A Caucasian boy was born at 27 weeks 2 days of gestation by cesarean section due to maternal COVID-19-related respiratory failure. Postpartum serological screening of the mother revealed a previously unrecognized active Toxoplasma gondii infection. The premature child initially tested negative for anti- Toxoplasma gondii immunoglobulin A and M antibodies 1, 2 and 4 weeks after birth, whereas immunoglobulin G antibodies were only weakly positive with no evidence of child-specific production. Neither neurological nor ophthalmological abnormalities were detected. Approximately 3 months after birth, serological testing indicated a congenital toxoplasmosis by presence of immunoglobulin A and M, in combination with a child-specific immunoglobulin G synthesis. Additionally, cerebrospinal fluid was tested positive for Toxoplasma gondii DNA. Although no clinical manifestations of congenital toxoplasmosis were detected, an antiparasitic therapy was initiated to minimize the risk of late sequelae. There were no hints for a transplacental transmission of severe acute respiratory syndrome coronavirus 2. CONCLUSION: This case raises the awareness of possible coinfections with the risk of transplacental transmission in cases of maternal coronavirus disease 2019. The report emphasizes the need for screening vulnerable patients for toxoplasmosis in general and especially in the context of pregnancy. It becomes evident that prematurity can complicate the serological diagnosis of congenital toxoplasmosis due to a delayed antibody response. Repeated testing is recommended to carefully monitor children at risk and especially those with a history of preterm birth.

Is latent Toxoplasma gondii infection associated with the occurrence of schizophrenia? A case-control study.

INTRODUCTION: Neurotropic pathogens such as Toxoplasma gondii (T. gondii) which result in chronic infections in the brain are associated with mental illnesses. In view of this, a growing body of literature has revealed the possible interaction of schizophrenia and T. gondii infection. METHOD: A case-control study was conducted from February 2018 to January 2019 among 47 Schizophrenia patients and 47 age and sex-matched controls. Data was collected using a structured questionnaire. Serum was used for serological analysis of anti-T. gondii IgG and IgM antibodies through chemiluminescent immunoassay. Proportions and mean with standard deviations (SD) were used as descriptive measures and variables with p-values <0.05 were considered as statistically significant and independently associated with schizophrenia. RESULT: The mean ages of schizophrenia patients and controls were 29.64 ± 5.8 yrs and 30.98 ± 7.3 yrs, respectively. We found that 81.9% (77/94) of the study subjects had a positive anti-T. gondii IgG antibody. While the difference is statistically insignificant, schizophrenic patients have a marginally higher seroprevalence of toxoplasmosis than controls (87.2% vs 80.9%; p = 0.398). Schizophrenia cases who live in homes with soil floors have a significantly higher T. gondii infection as compared to those who live in homes with cement/ceramic floors (90.9% vs 33.3%; p = 0.004). Furthermore, there was a significantly lower T. gondii infection among schizophrenic cases who were taking antipsychotic medication for more than three yrs (79.3% vs 100.0%, p = 0.039). On the other hand, among all study subjects who have T. gondii infection, subjects who are addicted to khat and alcohol were about seven times more likely to develop schizophrenia (71.4% vs 47.7%, OR = 7.13, p = 0.024). CONCLUSION: Our data is not sufficient to show a significant positive correlation between T. gondii infection and schizophrenia. For study subjects with T. gondii infection, addiction to khat and alcohol is one of the risk factors for schizophrenia.

[Effects of Toxoplasma gondii infection on mouse and human uterine natural killer cells].

OBJECTIVE: To examine the effects of Toxoplasma gondii infection on the proportion, quantity, differentiation and function of mouse and human uterine natural killer cells (uNK cells), so as to explore the role of uNK cells in abortion of early pregnancy caused by T. gondii infection. METHODS: Pregnant mice were injected intraperitoneally with T. gondii tachyzoites on day 6.5 of pregnancy, and the abortion mouse model caused by T. gondii infections was constructed. Mouse uterine lymphocytes were isolated on day 9.5 of pregnancy. Human uterine lymphocytes were isolated from fresh human decidual specimens after abortion in normal early pregnancy and co-cultured with tachyzoites of the T. gondii RH strain for 48 h at T. gondii/uterine lymphocytes ratios of 0.5:1, 1:1 and 2:1. The phenotypes of mouse uNK cells (CD122, NK1.1, DX5) and human uNK cells (CD3, CD56, CD11b, CD27) and the expression of intracellular cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by flow cytometry. Mouse and human uNK cells were sorted by magnetic beads, and the cytotoxicity of uNK cells was tested using the lactate dehydrogenase (LDH) release assay at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1 with mouse or human uNK cells as effector cells and mouse YAC-1 cells or human K562 cells as target cells. RESULTS: On day 9.5 of pregnancy, the mouse abortion rate was significantly higher in the infected group than that in the control group (83.02% vs. 3.51%; χ2 = 71.359, P < 0.001). Significantly lower absolute number of uNK cells [(4 547 ± 1 610) cells/mouse vs. (8 978 ± 3 339) cells/mouse; U = 2.000, P < 0.05], lower NK1.1 expression on uNK cell surface [(74.53 ± 8.37)% vs. (93.00 ± 1.11)%; U = 0.000, P < 0.05], higher proportion of NK1.1-DX5-cells [(20.10 ± 8.03)% vs. (5.04 ± 0.68)%; U = 0.000, P < 0.05], lower proportion of NK1.1+ DX5+ cells [(21.70 ± 12.48)% vs. (45.75 ± 2.26)%; U = 0.000, P < 0.05] and higher IFN-γ expression [(16.74 ± 1.36)% vs. (8.13 ± 1.90)%; U = 0.000, P < 0.05] were detected in the infected group than in the control group, while no significant difference was seen in TNF-α expression between the two groups [(67.98 ± 9.20)% vs. (52.93 ± 10.42)%; U = 2.000, P > 0.05]. The mouse uNK cells showed a strong cytotoxicity in the infected group, and the cytotoxicity gradually increased with the effector/target cell ratio. The cytotoxicity of uNK cells against YAC-1 cells was 2.30%, 4.32%, 8.12% and 12.65% in the infected group and 1.21%, 1.63%, 2.51% and 3.22% in the control group at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1, respectively. Following co-culture of human uterine lymphocytes and tachyzoites of the T. gondii RH strain for 48 h, the proportion [TOX 2:1 group vs. control group: (6.61 ± 1.75)% vs. (17.48 ± 4.81)%; F = 7.307, P < 0.01], and absolute number of human uNK cells in uterine lymphocytes of human uNK cells in uterine lymphocytes [TOX 2:1 group vs. control group: (12 104 ± 5 726) cells/well vs. (65 285 ± 21 810) cells/well; H = 11.540, P < 0.01] were significantly lower in the infected group than in the control group. A lower proportion of CD56brightCD16- NK cells [TOX 2:1 group vs. control group: (25.25 ± 5.90)% vs. (36.03 ± 4.51)%; F = 3.213, P > 0.05] and higher proportion of CD56dimCD16+ NK cells [TOX 2:1 group vs. control group: (11.15 ± 2.15)% vs. (7.09 ± 2.24)%; F = 2.992, P > 0.05] were detected in uNK cells in the infected group than in the control group, and the ratio of CD56brightCD16- cells/CD56dimCD16+ cells was significantly lower in the infected group than in the control group [TOX2:1 group vs. control group: (2.37 ± 0.92) vs. (5.58 ± 2.39); H = 8.228, P < 0.05]. In addition, the proportion of CD11b+CD27- cells in human uNK cells was significantly higher in the infected group than in the control group [TOX 2:1 group vs. control group: (30.28 ± 6.91)% vs. (17.48 ± 4.67)%; H = 6.556, P < 0.05], while no significant differences were found between the two groups in terms of IFN-γ [TOX 2:1 group vs. control group: (14.13 ± 1.28)% vs. (15.19 ± 1.64)%; F = 1.639, P > 0.05] or TNF-α expression [TOX 2:1 group vs. control group: (54.76 ± 10.02)% vs. (50.33 ± 3.67)%; F = 0.415, P > 0.05]. Human uNK cells presented a strong cytotoxicity in the infected group, and the cytotoxicity gradually increased with the effector/target cell ratio. The cytotoxicity of human uNK cells against K562 cells was 11.90%, 28.11%, 49.91% and 73.35% in the infected group and 12.21%, 21.63%, 33.51% and 48.22% in the control group at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1, respectively. CONCLUSIONS: T. gondii infection presents diverse effects on the differentiation and secretion ability of mouse and human uNK cells. However, T. gondii infection causes a reduction in the absolute number and enhances the cytotoxicity of both mouse and human uNK cells.

Toxoplasma gondii infection as a risk factor for osteoporosis: a case-control study.

BACKGROUND: More than one-third of the total world population is infected by Toxoplasma gondii (T. gondii). T. gondii has been linked to various diseases, such as cancer, mental disorders, type 2 diabetes mellitus (T2DM), etc. However, the effects of T. gondii infection on the risk of osteoporosis are unclear. Our study aimed to uncover evidence to determine whether patients exposed to T. gondii have an increased or decreased risk of osteoporosis in people with abnormal bone mineral density (BMD) by using case-control study. METHODS: A total of 729 patients, including 316 osteopenia and 413 osteoporosis patients of Han Chinese ancestry were selected in the study. Their blood samples were collected and the levels of specific IgG antibodies against T. gondii were measured using ELISA assay. We obtained some information about the patients from the medical record that included demographic indexes and clinical data. A logistic regression analysis was used to evaluate the effects of T. gondii infection on femur osteoporosis, lumbar osteoporosis and compound osteoporosis. Potential interaction was analyzed using multifactor dimensionality reduction software 1.0.0 (MDR 1.0.0). RESULTS: 113 positive patients with T. gondii infections have been detected, including 80 cases of osteoporosis and 33 cases of osteopenia, the infection rates of T. gondii were 19.37% (80/413) and 10.44% (33/316), respectively. The patients with T.gondii infections were at a 2.60 times higher risk of suffering from compound osteoporosis than those without T. gondii infections (OR = 2.60, 95% CI 1.54-4.39, P < 0.001), but not associated with femur osteoporosis (OR = 1.01, 95% CI 0.43-2.34, P = 0.989) and lumbar osteoporosis (OR = 0.84, 95% CI 0.34-2.07, P = 0.705) after adjusting for the covariates. Moreover, a significantly higher risk of compound osteoporosis in the individuals with all two factors (T. gondii infection, Female) was observed compared with reference group (without T. gondii infection, male) under the interaction model (OR = 11.44, 95%CI = 5.44-24.05, P < 0.001). And the individuals with all two factors (T. gondii infection, over 70 years) exhibited a 8.14-fold higher possibility of developing compound osteoporosis compared with reference group (without T. gondii infection, under 70 years) (OR = 8.14, 95% CI 3.91-16.93, P < 0.001). We further stratified by age and sex, and found that women with T. gondii infection was more likely to develop compound osteoporosis than those without infection(OR = 3.12, 95% CI 1.67-5.81, P < 0.001), but we not found the association between T. gondii infection and compound osteoporosis in males (OR = 1.36, 95% CI 0.37-4.94, P = 0.645). CONCLUSIONS: T. gondii infection is a risk factor for osteoporosis, especially compound osteoporosis. Meanwhile, it is very necessary for patients with osteoporosis to further diagnose and treat T. gondii infection, especially women.

Exploring the Association Between Latent Toxoplasma gondii Infection and COVID-19 in Hospitalized Patients: First Registry-Based Study.

PURPOSE: This study aimed to determine the possible association between Toxoplasma gondii infection and COVID-19 outcomes among 133 patients with an RT-PCR-positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hospitalized at Imam Khomeini Hospital, Sari, Mazandaran Province, northern Iran, during August to November 2020. METHODS: A questionnaire was used to collect baseline data from the patients who were registered to the Iranian National Registry Center for Toxoplasmosis (INRCT). Also, blood samples were taken from each patient for detecting anti-T. gondii antibodies and T. gondii DNA using enzyme-linked immunosorbent assay (ELISA) and conventional-PCR methods, respectively. Variables related to the COVID-19 severity and outcomes were indicated based on multiple multinomial logistic regression models. RESULTS: Of 133 patients enrolled in the INRCT with COVID-19 through RT-PCR, 50 (37.59%), 52 (39.1%), and 31 (23%) suffered from mild, moderate, and severe COVID-19, respectively. 57.1% of the patients who died had severe COVID-19, while among those with other outcomes, only 18.60% had severe COVID-19 (P < 0.05). Anti-T. gondii IgG was detected in 109/133 (81.95%) patients, which was not statistically significant (P > 0.05). Among those with negative and positive anti-T. gondii IgG, 2 (8.30%) and 29 (26.60%) had severe COVID-19, respectively (P > 0.05). T. gondii DNA and anti-T. gondii IgM were not found in any of the patients. Moreover, all deaths occurred in those with moderate or severe COVID-19 and a positive anti-T. gondii IgG. CONCLUSION: To our knowledge, this is the first registry-based study concerning T. gondii infection among patients with COVID-19. Our data show the high rate of latent T. gondii infection among COVID-19 with different severity. However, there is no significant relationship between latent T. gondii infection and COVID-19 severity and outcomes. Thus, conducting multicenter studies in different geographic regions of the world could offer a better understanding of this relationship.

Serum levels of C-reactive protein and ferritin in COVID-19 patients infected with Toxoplasma gondii.

During infection, T. gondii disseminates by the circulatory system and establishes chronic infection in several organs. Almost third of humans, immunosuppressed individuals such as HIV/AIDS patients, cancer patients, and organ transplant recipients are exposed to toxoplasmosis. Therefore, the study aimed to investigate the possibility that Toxoplasma infection could be a risk factor for COVID-19 patients and its possible correlation with C-reactive protein and ferritin. Overall 220 patients referred to the Al Furat General Hospital, Baghdad, Iraq were enrolled from 2020-2021. All serum samples were tested for T. gondii immunoglobulins (IgG and IgM) antibodies, C-reactive protein and ferritin levels. In patients with COVID-19, the results revealed a high positivity percentage for anti-Toxoplasma IgG. In COVID-19 patients infected with T. gondii, the C-reactive protein and ferritin levels were higher than the controls. The ferritin level was high in COVID-19 patients infected with toxoplasmosis compare with COVID-19 patient without toxoplasmosis in different gender and age while the level of CRP had no significant differences in COVID-19 patient with or without toxoplasmosis. These finding suggest that the incidental rate of toxoplasmosis could be considered as an indication to the high risk of COVID-19.

Hijacking of host mitochondria by Toxoplasma gondii and SARS-CoV-2.

Mitochondria regulate energy production, cell cycle, and immune signaling. Li et al. recently reported that Toxoplasma gondii induces the shedding of mitochondrial outer membrane to promote its growth. Intriguingly, the hijacking of host mitochondria has been shown to play an essential role in the pathogenesis of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Treatment of a full-thickness macular hole and retinal detachment secondary to toxoplasma chorioretinitis that developed shortly after COVID-19: A case report.

Although ocular toxoplasmosis is usually a self-limiting infection, it can lead to severe reduction in visual acuity due to intense vitreous inflammation or involvement of posterior segment structures. Depending on the severity of intraocular inflammation, serious complications, including epiretinal membrane or retinal detachment may develop. In this paper, we aim to present a case that complicated by both a full-thickness macular hole and retinal detachment secondary to toxoplasmosis chorioretinitis that developed shortly after the novel coronavirus disease (COVID-19) and discuss our treatment approach. After the patient was diagnosed based on a routine ophthalmological examination, fundus imaging, and serological examination, functional and anatomical recovery was achieved through systemic antibiotherapy and vitreoretinal surgery. Full-thickness macular hole and retinal detachment are rare complications of ocular toxoplasmosis. However, there are only few publications in the literature concerning these complications and their surgical treatment. In this case report, we demonstrated the success of vitreoretinal surgery combined with antibiotic therapy on the posterior segment complications of ocular toxoplasmosis.

Seroprevalence of Toxoplasma gondii, Rubella, Group A Streptococcus, CMV and HSV-1 in COVID-19 Patients with Vitamin D Deficiency.

<b>Background and Objective:</b> In recent years, respiratory tract viral infections have caused many pandemics that impact the whole world. To investigate the seropositivity of <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> in recovered COVID-19 patients and correlate these findings with vitamin D levels. <b>Materials and Methods:</b> A total of 417 COVID-19 patients with diarrhoea were enrolled in this study. Vitamin D and seroprevalence for <i>Toxoplasma gondii</i>, rubella, CMV, HSV-1 and group A <i>Streptococcus</i> were evaluated and correlated. <b>Results:</b> It was found that recent infection in COVID-19 patients with HSV-1, rubella, <i>Toxoplasma</i> and CMV, respectively. IgG was detected indicating the development of adaptive immunity with all microbes. <b>Conclusion:</b> Current study detected a correlation between vitamin D levels and HSV-1 and no correlation between this infection and vitamin D deficiency with the other microbes.

The role of polyspecific T-cell exhaustion in severe outcomes for COVID-19 patients having latent pathogen infections such as Toxoplasmagondii.

Various categories of coronavirus disease 19 (COVID-19) patients have exhibited major mortality rate differences and symptoms. Some papers have recently explained these differences in mortality rates and symptoms as a consequence of this virus infection acting in synergy with one or more latent pathogen infections in some patients. A latent pathogen infection likely to be involved in millions of these patients is the protozoan parasite Toxoplasma gondii, which infects approximately one third of the global human population. However, other papers have concluded that latent protozoan parasite infections can reduce the severity of viral infections. The aims and purposes of this paper include providing explanations for the contradictions between these studies and introducing a significant new category of T-cell exhaustion. Latent pathogens can have different genetic strains with great differences in their effects on a second pathogen infection. Furthermore, depending on the timing and effectiveness of drug treatments, pathogen infections that become latent may or may not later induce immune cell dysfunctions, including T-cell exhaustion. Concurrent multiple pathogen T-cell exhaustion is herein called "polyspecific T-cell exhaustion."

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.

The link between Toxoplasma gondii infections and higher mortality in COVID-19 patients having schizophrenia.

A strong link between schizophrenia and a higher mortality rate from SARS-CoV-2 infections has been reported for schizophrenia patients, with a mortality odds ratio (OR) of 2.67 compared to normal patients, after adjustment of the OR for age, sex, race and extra risk factors. In addition, an extensive number of papers have reported a very strong link between schizophrenia and Toxoplasma gondii infections. A meta-analysis of 38 studies of links between schizophrenia and T. gondii antibody seroprevalence resulting from previous infections indicated that the likelihood of T. gondii infection in schizophrenia patients was 2.7 times higher than the general population. In other words, the meta-analysis indicated that schizophrenia patients had an odds ratio of 2.7 of T. gondii infection compared to the general population. This indicates that compared to the general population, schizophrenia patients have virtually the same odds ratio for having a T. gondii infection and for mortality from a COVID-19 infection. This suggests that T. gondii infections, directly or indirectly, have a relationship with higher mortality in COVID-19 patients having schizophrenia. This conclusion would also apply to the general population.

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.

BACKGROUND: Latent toxoplasmosis, i.e. a lifelong infection with the protozoan parasite Toxoplasma gondii, affects about a third of the human population worldwide. In the past 10 years, numerous studies have shown that infected individuals have a significantly higher incidence of mental and physical health problems and are more prone to exhibiting the adverse effects of various diseases. METHODS: A cross-sectional internet study was performed on a population of 4499 (786 Toxoplasma-infected) participants and looked for factors which positively or negatively affect the risk of SARS-CoV-2 infection and likelihood of a severe course of COVID-19. RESULTS: Logistic regression and partial Kendall correlation controlling for sex, age, and size of the place of residence showed that latent toxoplasmosis had the strongest effect on the risk of infection (OR = 1.50) before sport (OR = 1.30) and borreliosis (1.27). It also had the strongest effect on the risk of severe course of infection (Tau = 0.146), before autoimmunity, immunodeficiency, male sex, keeping a cat, being overweight, borreliosis, higher age, or chronic obstructive pulmonary disease. Toxoplasmosis augmented the adverse effects of other risk factors but was not the proximal cause of the effect of cat-keeping on higher likelihood of COVID infection and higher severity of the course of infection because the effect of cat-keeping was also observed (and in particular) in a subset of Toxoplasma-infected respondents (Tau = 0.153). Effects of keeping a cat were detected only in respondents from multi-member families, suggesting that a cat could be a vector for the transmission of SARS-CoV-2 within a family. CONCLUSIONS: Toxoplasmosis is currently not considered a risk factor for COVID-19, and Toxoplasma-infected individuals are neither informed about their higher risk nor prioritised in vaccination programs. Because toxoplasmosis affects a large segment of the human population, its impact on COVID-19-associated effects on public health could be considerable.

An Open-Source Toolkit To Expand Bioinformatics Training in Infectious Diseases.

As access to high-throughput sequencing technology has increased, the bottleneck in biomedical research has shifted from data generation to data analysis. Here, we describe a modular and extensible framework for didactic instruction in bioinformatics using publicly available RNA sequencing data sets from infectious disease studies, with a focus on host-parasite interactions. We highlight lessons learned from adapting this course for virtual learners during the coronavirus disease 2019 (COVID-19) pandemic.