Global epidemiology and spatial distribution of Toxoplasma gondii in goats: Protocol for a systematic review and Bayesian hierarchical meta-analysis.

BACKGROUND: Toxoplasma gondii, a cosmopolitan protozoan parasite causes toxoplasmosis in humans and many species of domestic and wild animals. T. gondii instigates significant economic losses in sheep and goat farming industry and can lead to abortion, stillbirth, congenital malformations and neonatal losses. The objective of this protocol is to evaluate worldwide seroprevalence of T. gondii exposure in goats using Bayesian hierarchical meta-analysis and geographic information system (GIS). METHODS: A comprehensive literature search will be conducted using search engines, including Web of Science, ScienceDirect, Scopus, PubMed, ProQuest, EMBASE, PROSPERO Register and, Google Scholar without date and language restrictions. The authors search for cross-sectional studies that determine the seroprevalence of T. gondii in goats. Two reviewers will independently screen, selected studies; also, they will extract data, and assess the risk of bias. In case(s) of disagreement, a consensus will be reached with the help of a third author. The Bayesian hierarchical meta-analysis will use to estimate country and worldwide true seroprevalence of T. gondii, which is consist of the sensitivity and specificity of the applied serological assays. The obtained data will be used to identify country-level risk factors associated with T. gondii exposure using GIS in the ArcGIS software. DISCUSSION: The systematic review produced from this protocol will provide the true prevalence rate and spatial distribution T. gondii exposure in goats both regionally and globally using Bayesian hierarchical and GIS analysis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020107928.

Protective efficacy by a novel multi-epitope vaccine, including MIC3, ROP8, and SAG1, against acute Toxoplasma gondii infection in BALB/c mice.

Toxoplasma gondii is an intracellular apicomplexan parasite, which can cause a serious infectious disease in pregnant women and immunocompromised individuals. Therefore, the development of a polyvalent vaccine consisting of all stages of the parasite life cycle using the epitopes from tachyzoites, bradyzoites, and sporozoites is likely to be required for complete protective immunity. In this study, we designed protein vaccine candidate based on the prediction of specific epitopes (i.e., B cell and T cell) from three Toxoplasma gondii antigens. The MRS protein (MIC3: 30-180, ROP8: 85-185, and SAG1: 85-235) was expressed in Escherichia coli, and purification was performed using a HisTrap HP column and then we evaluated immunogenicity and protective property in BALB/c mice. Seventy-two mice were randomly divided into six groups, including three vaccinations (i.e., MRS, MRS-Freund, and MRS-Calcium Phosphate Nanoparticles (MRS-CaPNs)) and three control (i.e., Phosphate-buffered saline, Freund, and CaPNs) groups. All groups were immunized three times via subcutaneous injection within three-week intervals. In the vaccination groups, the BALB/c mice were injected with 20 µg of MRS protein for the first time and 10 µg of MRS for the next two times. Antibodies, cytokines, and splenocytes proliferation in the immunized mice were assayed using the enzyme-linked immunosorbent assay. Protective efficacy was analyzed by challenging the immunized mice with T. gondii of RH strain. Antibody, cytokine, and lymphocyte proliferation assays showed that the mice immunized with MRS induced stronger humoral and T helper type 1 cell-mediated immune responses, compared to the control mice. However, co-immunization with adjuvants (i.e., Freund and CaNPs) resulted in impaired immune responses. Effective protection against the parasite achieved an increase in survival time in the immunized mice, especially in the MRS-CaNPs group. The obtained results of the present study demonstrated that multi-epitope protein vaccination, MRS, is a potential strategy against toxoplasmosis infection. In addition, the vaccine co-delivered with CaPNs could provide an important key for vaccine candidate to control T. gondii infection.

Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta-analysis.

The World Health Organization has reported an annual global suicide rate of 14.5 per 100,000 people. On the other hand, it is estimated that approximately one-third of the global population are infected with Toxoplasma gondii (T. gondii) parasite. It is widely assumed that microbial pathogens, such as T. gondii, are probably associated with affective and behavioural modulation. The present article aimed to assess the proposed role of toxoplasmosis in raising the risk of suicidal ideation (SI) and suicide attempts (SA) using the available epidemiological data. Seven major electronic databases and the Internet search engine Google were searched for all the studies published between the 1st of January 1950 and 31st of October 2019. The heterogeneity and the risk of bias within and across studies were assessed. Following data extraction, pooled odds ratios (ORs) with 95% confidence interval (CI) across studies were calculated using the random-effects models. A total number of 9,696 articles were screened and 27 studies were regarded as eligible in our systematic review (SI with five papers and 22 papers on SA). A significant association was detected between antibodies against T. gondii with TA (ORs = 1.57; 95% confidence interval [CI] 1.23-2.00, p = .000). Exploration of the association between T. gondii and SA yielded a positive effect of seropositivity for IgG antibodies but not IgM. Despite the limited number of studies, a statistical association was detected between suicidal behaviours and infection with latent T. gondii.

A systematic review of Toxoplasma gondii genotypes and feline: Geographical distribution trends.

Toxoplasma gondii (T. gondii) is well known for its ability to virtually infect all warm-blooded vertebrates. Although felines as the definitive hosts have an important role in the epidemiology of toxoplasmosis, there are few descriptions of genetic diversity in the world. The present review study aimed to describe the population structure of T. gondii in these animal species. For the purpose of the study, five English language databases reporting data on T. gondii genotyping in cats were searched within March-June 2019. This study is registered on the site of CAMARADES-NC3Rs (15-Jan-2018). The searching process resulted in the inclusion of 50 reports published from 1992 to June 2019. The data revealed that 47,390 samples were genotyped into 662 T. gondii DNA/isolates. Globally, atypical genotypes were predominant (47.7%, n = 316); in addition, Type II clonal strains were the second most common genotype (37%, n = 244). These results suggested an epidemic population structure in America and Asia, and a clonal population structure in Europe and Africa. Genotype #3 was found to be dominant in Africa, Europe and Oceania continents. Furthermore, genotypes #9 and #5 were prevalent in Asia and America, respectively. Additionally, genotypes #2, #3, #5 and #20 were common genotypes in domestic and sylvatic cycles from family Felidae. Collectively, this systematic review indicated a large degree of genetic diversity and circulation of mouse-virulent T. gondii strains in this family. However, further studies are necessary to better understand the population structure of T. gondii in these animal species and determine the significance of their features.

Is Toxoplasma gondii a potential risk factor for Alzheimer's disease? A systematic review and meta-analysis.

Toxoplasmosis is a major public health concern due to neurotropic nature and role in the development of mental and behavioral disorders. Alzheimer's disease (AD) is an important nervous disease that results in the reduction of the amount of beta-amyloid plaque deposition and irreversible loss of neurons in the brain. Although a few studies evaluated the association between AD and toxoplasmosis, the present study as a systematic review and meta-analysis of published studies investigated the possible association between Toxoplasma gondii (T. gondii) and AD. A systematic literature search was conducted using seven electronic databases from the inception to 25th of November 2018 with no restriction of language that looked at toxoplasmosis (as an exposure) and AD (as a disease). The random effect model was used to determine the total odds ratio (OR) and total p-value. Generally, eight studies containing 3239 subjects (360 patients and 2879 controls) met the eligibility criteria. Then, eight articles were used for meta-analysis with respect to inclusion and exclusion criteria. The results of the meta-analysis (random effect model) showed a common OR of 1.53 (95% CI: 1.07-2.18). Despite the fact that there was no evidence of publication bias (P = 0.079) using formal statistical test, the visual inspection of the funnel graph suggested that the observed effect was fueled mainly by three studies with large effects (and large standard errors). Moreover, the file-drawer effect (i.e. publishing mainly studies with positive results) might play a role in the phenomenon. Results of this meta-analytic study suggested that T. gondii can be considered a risk factor for the development of AD and exacerbation of its symptoms. However, the number of published relevant studies is still relatively low, and the risk of the presence of publication bias is relatively high. Therefore, the investigation of the clinically important question of the possible association between toxoplasmosis and AD definitively deserves further attention.

Is there any association between Toxoplasma gondii infection and depression? A systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental disorders; however, the relationship between T. gondii infection and depressive disorder is unclear. Regarding this, the present systematic review and meta-analysis was conducted to investigate the scientific evidence regarding the potential association between major depression disorder (MDD) and Toxoplasma infection. METHODS: For the purpose of the study, the articles related to the subject of interest were systematically searched in seven electronic databases. Special attention was given to the studies examining T. gondii seropositivity level in depressed patients and controls. RESULTS: The search process resulted in the identification of a total of 30 publications meeting the inclusion criteria and published up to April 2018 for the systematic review. Furthermore, 29 studies met the inclusion criteria to be entered into meta-analysis. Our meta-analysis involved the review of cross-sectional studies including 1657 depressed patients and 19565 individuals as controls and case-control studies entailing 1311 depressed cases and 6015 controls without depression. 1582 depressed people participated in cross-sectional studies whose results were reported as odds ratio (OR). In addition, the total number of participants was 15068 in this type of studies. Statistical analysis indicated that the pooled OR of the risk of anti-T. gondii IgG antibody in depressed individuals in case-control and cross-sectional studies was 1.15 (95% confidence interval (CI): 0.95-1.39). CONCLUSIONS: As the findings of the reviewed articles indicated, toxoplasmosis is not a risk factor for MDD. However, it is necessary to perform further research to clarify the detailed association between T. gondii and dysthymia or mild and moderate depression. Furthermore, it is recommended to better investigate the effect of antibody titers on the relationship between depression and T. gondii infection.

Congenital toxoplasmosis among Iranian neonates: a systematic review and meta-analysis.

Toxoplasmosis is a serious zoonotic disease that can lead to abortion and congenital disorders and has a widespread global distribution in humans and animals. The objective of this review was to investigate the incidence of toxoplasmosis in Iranian neonates in order to obtain a comprehensive assessment of the overall situation of the disease for use in developing future interventions. Original studies investigating the incidence of Toxoplasma gondii infections in Iranian neonates were systematically searched in a number of English-language and Persian-language electronic databases. The search process resulted in the inclusion of a total of 11 studies in the systematic review, 10 of which were entered into the meta-analysis. The reviewed articles included 2,230 Iranian neonates investigated through January 1, 2018. Based on the retrieved studies, the overall weighted incidence rates of toxoplasmosis in the Iranian neonatal population and neonates with suspected congenital toxoplasmosis were estimated to be 0.64% (95% confidence interval [CI], 0.31 to 1.09) and 4.10% (95% CI, 2.68 to 5.77), respectively, using a fixed-effects model. The findings of the reviewed studies demonstrate that the incidence of toxoplasmosis is high in Iranian neonates. Accordingly, it can be concluded that toxoplasmosis is a serious public health concern that has been ignored by the Ministry of Health. Therefore, it is essential to perform further studies, in addition to implementing screening and detection programs, using standardized methods to estimate the incidence of toxoplasmosis in Iran and to determine its associated risk factors.

Relationship between toxoplasmosis and obsessive compulsive disorder: A systematic review and meta-analysis.

BACKGROUND: A few studies investigated the relationship between toxoplasmosis and mental disorders, such as obsessive compulsive disorder (OCD). However, the specific nature of the association between Toxoplasma gondii (T. gondii) infection and OCD is not yet clear. The aim of this study was to collect information on the relationship between OCD and toxoplasmosis and assess whether patients with toxoplasmosis are prone to OCD. METHODS: For the purpose of this study, 6 major electronic databases and the Internet search engine Google Scholar were searched for the published articles up to July 30th, 2018 with no restriction of language. The inverse variance method and the random effect model were used to combine the data. The values of odds ratio (OR) were estimated at 95% confidence interval (CI). RESULTS: A total of 9 case-control and 3 cross-sectional studies were included in our systematic review. However, 11 of these 12 articles were entered into the meta-analysis containing 9873 participants, out of whom 389 were with OCD (25.96% positive for toxoplasmosis) and 9484 were without OCD (17.12% positive for toxoplasmosis). The estimation of the random effect model indicated a significant common OR of 1.96 [95% CI: 1.32-2.90]. CONCLUSION: This systematic review and meta-analysis revealed that toxoplasmosis could be as an associated factor for OCD (OR = 1.96). However, further prospective investigations are highly recommended to illuminate the underlying pathophysiological mechanisms of T. gondii infection in OCD and to better investigate the relationship between OCD and T. gondii infection.

Is Toxoplasma gondii playing a positive role in multiple sclerosis risk? A systematic review and meta-analysis.

Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii with a globally widespread distribution. The aim of this systematic review and meta-analysis was to characterize the association between T. gondii infection and multiple sclerosis (MS). The data were systematically collected from the English electronic databases up to April 2017. The research process resulted in the identification of five studies related to the subject of interest entailing 669 MS patients and 770 controls. The pooled prevalence rates of T. gondii infection in the MS patients and controls were estimated as 32.4% (95% CI: 27.4-38.6) and 39.1% (95% CI: 29.1-50.5), respectively. By random effect model, the combined odds ratio was 0.72 (95% CI: 0.49-1.06) with P = .0961. Although this meta-analysis study showed a lower seroprevalence of T. gondii in the MS patients as compared with that in the control group, no significant association was found between toxoplasmosis and MS disease. Further investigations are recommended to determine the detailed association between MS patients and T. gondii infection.

Toxoplasmosis seroprevalence in rheumatoid arthritis patients: A systematic review and meta-analysis.

BACKGROUND: Toxoplasmosis is a cosmopolitan infection caused by an intracellular obligatory protozoan, Toxoplasma gondii. Infection to this parasite in immunocompetent patients is usually asymptomatic, but today it is believed that the infection can be a risk factor for a variety of diseases, including rheumatoid arthritis (RA). RA is an autoimmune disease and the most common type of inflammatory arthritis that is a major cause of disability. The aim of this systematic review and meta-analysis was to address the association between RA and toxoplasmosis in light of the available research. METHODS: Based on the keywords, a systematic search of eight databases was conducted to retrieve the relevant English-language articles. Then, the studies were screened based on the inclusion and exclusion criteria. The random effect model was used to calculate the odds ratio (OR) using forest plot with 95% confidence interval (CI). RESULTS: Overall, 4168 Individual, extracted from 9 articles were included for systematic review evaluation, with 1369 RA patients (46% positive toxoplasmosis) and 2799 individuals as controls (21% positive toxoplasmosis). Then, eight articles (10 datasets) were used for meta-analysis (1244 rheumatoid arthritis patients and 2799 controls). By random effect model, the combined OR was 3.30 (95% CI: 2.05 to 5.30) with P < 0.0001. CONCLUSION: Although toxoplasmosis could be considered as a potential risk factor for rheumatoid arthritis, more and better quality studies are needed to determine the effect of T. gondii infection on induction or exacerbation of RA. Our study was registered at the International Prospective Register of Systematic Reviews (PROSPERO; code: CRD42017069384).