Talk:Abnormal Development - Toxoplasmosis

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Cite this page: Hill, M.A. (2019, August 17) Embryology Abnormal Development - Toxoplasmosis. Retrieved from


Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders

Brain Behav Immun. 2019 Jan 29. pii: S0889-1591(18)30699-8. doi: 10.1016/j.bbi.2019.01.026. [Epub ahead of print]

Burgdorf KS1, Trabjerg BB2, Pedersen MG3, Nissen J4, Banasik K5, Pedersen OB6, Sørensen E4, Nielsen KR7, Larsen MH4, Erikstrup C8, Bruun-Rasmussen P5, Westergaard D5, Thørner LW4, Hjalgrim H9, Paarup HM10, Brunak S5, Pedersen CB3, Torrey EF11, Werge T12, Mortensen PB3, Yolken RH13, Ullum H4.

BACKGROUND: Common infectious pathogens have been associated with psychiatric disorders, self-violence and risk-taking behavior. METHODS: This case-control study reviews register data on 81,912 individuals from the Danish Blood Donor Study to identify individuals who have a psychiatric diagnosis (N = 2591), have attempted or committed suicide (N = 655), or have had traffic accidents (N = 2724). For all cases, controls were frequency matched by age and sex, resulting in 11,546 participants. Plasma samples were analyzed for immunoglobulin G (IgG) antibodies against Toxoplasma gondii and cytomegalovirus (CMV). RESULTS: T. gondii was detected in 25·9% of the population and was associated with schizophrenia (odds ratio [OR], 1·47; 95% confidence interval [CI], 1·03-2·09). Accounting for temporality, with pathogen exposure preceding outcome, the association was even stronger (IRR, 2·78; 95% CI, 1·27-6·09). A very weak association between traffic accident and toxoplasmosis (OR, 1·11; 95% CI, 1·00-1·23, p = 0.054) was found. CMV was detected in 60·8% of the studied population and was associated with any psychiatric disorder (OR, 1·17; 95% CI, 1·06-1·29), but also with a smaller group of neurotic, stress-related, and somatoform disorders (OR, 1·27; 95% CI, 1·12-1·44), and with attempting or committing suicide (OR, 1·31; 95% CI, 1·10-1·56). Accounting for temporality, any psychiatric disorder (IRR, 1·37; 95% CI, 1·08-1·74) and mood disorders (IRR, 1·43; 95% CI, 1·01-2·04) were associated with exposure to CMV. No association between traffic accident and CMV (OR, 1·06; 95% CI, 0·97-1·17) was found. CONCLUSIONS: This large-scale serological study is the first study to examine temporality of pathogen exposure and to provide evidence of a causal relationship between T. gondii and schizophrenia, and between CMV and any psychiatric disorder. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: Antibodies; Cytomegalovirus; Infection; Parasite, psychiatric disorders; Serology; Suicide; Toxoplasma gondii; Toxoplasmosis; Traffic accidents PMID: 30685531 DOI: 10.1016/j.bbi.2019.01.026


The Epigenome, Cell Cycle, and Development in Toxoplasma

Annu Rev Microbiol. 2018 Sep 8;72:479-499. doi: 10.1146/annurev-micro-090817-062741. Epub 2018 Jun 22.

Kim K1,2.

Toxoplasma gondii is a common veterinary and human pathogen that persists as latent bradyzoite forms within infected hosts. The ability of the parasite to interconvert between tachyzoite and bradyzoite is key for pathogenesis of toxoplasmosis, particularly in immunocompromised individuals. The transition between tachyzoites and bradyzoites is epigenetically regulated and coupled to the cell cycle. Recent epigenomic studies have begun to elucidate the chromatin states associated with developmental switches in T. gondii. Evidence is also emerging that AP2 transcription factors both activate and repress the bradyzoite developmental program. Further studies are needed to understand the mechanisms by which T. gondii transduces environmental signals to coordinate the epigenetic and transcriptional machinery that are responsible for tachyzoite-bradyzoite interconversion. KEYWORDS: bradyzoite; chromatin; differentiation; epigenetics; parasite; tachyzoite PMID: 29932347 DOI: 10.1146/annurev-micro-090817-062741


Toxoplasmosis and horse meat, france

Emerg Infect Dis. 2011 Jul;17(7):1327-8.

Pomares C, Ajzenberg D, Bornard L, Bernardin G, Hasseine L, Darde ML, Marty P. Source Universite de Nice-Sophia Antipolis-Inserm U895, Nice, France. Abstract To the Editor: Toxoplasma gondii parasites are obligate intracellular apicomplexans that can infect virtually all warm-blooded animals; felids are definitive hosts. The most common sources of human infection are ingestion of tissue cysts in undercooked meat or of food or water contaminated with oocysts shed by felids and transplacental transmission. Acquired toxoplasmosis in immunocompetent humans is frequently asymptomatic but is associated with cervical or occipital lymphadenopathy in approximately 10% of patients. Severe or fatal outcomes for immunocompetent patients have been attributed to the virulence of specific T. gondii genotypes (1). We describe 3 cases of toxoplasmosis caused by atypical strains probably acquired by from ingestion of raw horse meat imported from Canada and Brazil.

PMID: 21762609

First colombian multicentric newborn screening for congenital toxoplasmosis

PLoS Negl Trop Dis. 2011;5(5):e1195. Epub 2011 May 31.

Gómez-Marin JE, de-la-Torre A, Angel-Muller E, Rubio J, Arenas J, Osorio E, Nuñez L, Pinzon L, Mendez-Cordoba LC, Bustos A, de-la-Hoz I, Silva P, Beltran M, Chacon L, Marrugo M, Manjarres C, Baquero H, Lora F, Torres E, Zuluaga OE, Estrada M, Moscote L, Silva MT, Rivera R, Molina A, Najera S, Sanabria A, Ramirez ML, Alarcon C, Restrepo N, Falla A, Rodriguez T, Castaño G. Source Grupo GEPAMOL, Centro de Investigaciones Biomédicas, Universidad del Quindio, Armenia, Colombia.


AIMS: To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern).

MATERIALS AND METHODS: We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life.

RESULTS: 61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city.

CONCLUSIONS: Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis.

PMID: 21655304

High level of soluble HLA-G in amniotic fluid is correlated with congenital transmission of Toxoplasma gondii

Clin Immunol. 2011 Feb;138(2):129-34. Epub 2010 Dec 24.

Robert-Gangneux F, Gangneux JP, Vu N, Jaillard S, Guiguen C, Amiot L. Source Laboratoire de Parasitologie, Faculté de Médecine et Centre Hospitalier Universitaire de Rennes, Rennes, France. Abstract The expression of human leukocyte antigen (HLA)-G on cytotrophoblast cells contributes to maternal-fetal tolerance. Soluble forms of HLA-G (sHLA-G) can be detected in amniotic fluid (AF) and a decrease of sHLA-G is known to be correlated to fetal loss. In this work we investigated the role of sHLA-G in the transplacental passage of the protozoan parasite Toxoplasma gondii, responsible for congenital toxoplasmosis in about 30% of fetuses when primary infection (PI) occurs during pregnancy. We determined the sHLA-G concentration in 61 AF from women with PI and 24 controls. Our results showed higher sHLA-G levels in AF from PI than in controls (p<0.001). Moreover sHLA-G level from congenitally infected fetuses (n=12) was higher than in fetus in whom congenital infection was ruled out (n=49, p<0.05). These data suggest that sHLA-G could participate in immunomodulation necessary to avoid fetal loss due to Toxoplasma infection, but that over-expression could favor congenital transmission.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 21185786

Knowledge of Toxoplasmosis among Doctors and Nurses Who Provide Prenatal Care in an Endemic Region

Infect Dis Obstet Gynecol. 2011;2011:750484. Epub 2011 May 18.

da Silva LB, de Oliveira Rde V, da Silva MP, Bueno WF, Amendoeira MR, de Souza Neves E. Source Laboratório de Doenças Febris Agudas, Instituto de Pesquisa Clínica Evandro Chagas, Fiocruz, Avenida Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil.


Congenital toxoplasmosis is a potentially severe infection and its prevention is most often based on serological screening in pregnant women. Many cases could be prevented by simple precautions during pregnancy. Aiming to assess the knowledge about toxoplasmosis among professionals working in antenatal care in a high prevalent region, a questionnaire was administered to 118 obstetric nurses and physicians attending at primary care units and hospitals. The questionnaire was self-completed and included questions on diagnosis, clinical issues, and prevention. Only 44% of total answers were corrected. Lower scores were observed among those with over 10 years of graduation, working in primary care units, and nurses. Errors were mainly observed in questions of prevention and diagnosis. As congenital toxoplasmosis is a mother-to-child (MTC) transmitted disease, early diagnosis and treatment can prevent serious and irreversible fetal damage. Thus, doctors and nurses who provide prenatal care must be appropriately trained on prophylactic, diagnostic, and clinical aspects of toxoplasmosis. The authors suggest that measures should be taken for continuing education regarding toxoplasmosis in pregnancy.

PMID: 21747644

Discovering disease associations by integrating electronic clinical data and medical literature

PLoS One. 2011;6(6):e21132. Epub 2011 Jun 23.

Holmes AB, Hawson A, Liu F, Friedman C, Khiabanian H, Rabadan R. Source Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.


Electronic health record (EHR) systems offer an exceptional opportunity for studying many diseases and their associated medical conditions within a population. The increasing number of clinical record entries that have become available electronically provides access to rich, large sets of patients' longitudinal medical information. By integrating and comparing relations found in the EHRs with those already reported in the literature, we are able to verify existing and to identify rare or novel associations. Of particular interest is the identification of rare disease co-morbidities, where the small numbers of diagnosed patients make robust statistical analysis difficult. Here, we introduce ADAMS, an Application for Discovering Disease Associations using Multiple Sources, which contains various statistical and language processing operations. We apply ADAMS to the New York-Presbyterian Hospital's EHR to combine the information from the relational diagnosis tables and textual discharge summaries with those from PubMed and Wikipedia in order to investigate the co-morbidities of the rare diseases Kaposi sarcoma, toxoplasmosis, and Kawasaki disease. In addition to finding well-known characteristics of diseases, ADAMS can identify rare or previously unreported associations. In particular, we report a statistically significant association between Kawasaki disease and diagnosis of autistic disorder.

PMID: 21731656


Evaluation of Toxoplasma gondii placental transmission in BALB/c mice model

Exp Parasitol. 2009 Oct;123(2):168-72. Epub 2009 Jun 27.

Pezerico SB, Langoni H, Da Silva AV, Da Silva RC. Source Universidade Estadual Paulista, Botucatu, SP, Brazil.


Toxoplasma gondii infection is common worldwide and highly important to pregnant women as it can be transmitted to the fetus via the placenta. This study aimed at evaluating the prevention of placental transmission in two different strains after chronic infection with each one of the strains. A BALB/c mice model was inoculated 30days before breeding (immunization) and re-infected 12 and 15days after pregnancy (challenge). Seven experimental groups were assayed: G1: ME49-immunization (type II), M7741-challenge (type III); G2: M7741-immunization, ME49-challenge; G3, ME49-immunization; G4: M7741-immunization; G5: ME49-challenge; G6: M7741-challenge; G7: saline solution inoculation. Serology, mouse bioassay, PCR and RLFP of the uterus, placenta and fetus were performed to determine the congenital transmission of the strains challenged after chronic infection. IgG T. gondii antibodies were detected in G1, G2, G3 and G4, but not in G5, G6 and G7. All animals of G5 and G6 were IgM-positive. Congenital infection was not detected by bioassay and PCR. Nonetheless, placentas from G3 and G4 resulted positive but no corresponding fetal infection was detected. G1 and G2 did not show the genotype of the strain challenged during pregnancy, only those of chronic infection. Thus, the chronically infected BALB/c mice showed no re-infection after inoculation with another strain during pregnancy. Further studies with different parasite loads and different mice lineages are needed.

PMID: 19563804


Comparison of two DNA targets for the diagnosis of Toxoplasmosis by real-time PCR using fluorescence resonance energy transfer hybridisation probes

BMC Infect Dis. 2003 May 2;3:7.

Reischl U, Bretagne S, Krüger D, Ernault P, Costa JM. Source Institute of Medical Microbiology and Hygiene, University Hospital Regensburg, Franz-Josef-Straubeta-Allee 11, D-93053 Regensburg, Germany.


BACKGROUND: Toxoplasmosis is an infectious disease caused by the parasitic protozoan Toxoplasma gondii. It is endemic worldwide and, depending on the geographic location, 15 to 85% of the human population are asymptomatically infected. Routine diagnosis is based on serology. The parasite has emerged as a major opportunistic pathogen for immunocompromised patients, in whom it can cause life-threatening disease. Moreover, when a pregnant woman develops a primary Toxoplasma gondii infection, the parasite may be transmitted to the fetus and cause serious damage. For these two subpopulations, a rapid and accurate diagnosis is required to initiate treatment. Serological diagnosis of active infection is unreliable because reactivation is not always accompanied by changes in antibody levels, and the presence of IgM does not necessarily indicate recent infection. Application of quantitative PCR has evolved as a sensitive, specific, and rapid method for the detection of Toxoplasma gondii DNA in amniotic fluid, blood, tissue samples, and cerebrospinal fluid.

METHODS: Two separate, real-time fluorescence PCR assays were designed and evaluated with clinical samples. The first, targeting the 35-fold repeated B1 gene, and a second, targeting a newly described multicopy genomic fragment of Toxoplasma gondii. Amplicons of different intragenic copies were analyzed for sequence heterogeneity.

RESULTS: Comparative LightCycler experiments were conducted with a dilution series of Toxoplasma gondii genomic DNA, 5 reference strains, and 51 Toxoplasma gondii-positive amniotic fluid samples revealing a 10 to 100-fold higher sensitivity for the PCR assay targeting the newly described 529-bp repeat element of Toxoplasma gondii.

CONCLUSION: We have developed a quantitative LightCycler PCR protocol which offer rapid cycling with real-time, sequence-specific detection of amplicons. Results of quantitative PCR demonstrate that the 529-bp repeat element is repeated more than 300-fold in the genome of Toxoplasma gondii. Since individual intragenic copies of the target are conserved on sequence level, the high copy number leads to an ultimate level of analytical sensitivity in routine practice. This newly described 529-bp repeat element should be preferred to less repeated or more divergent target sequences in order to improve the sensitivity of PCR tests for the diagnosis of toxoplasmosis.

PMID: 12729464