Abnormal Development - Toxoplasmosis

Embryology - 2 Dec 2023        Expand to Translate
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Introduction

Toxoplasma tachyzoites

In 2003, the global annual incidence of congenital toxoplasmosis was estimated to be 190,100 cases, equivalent to a burden of 1.20 million disability-adjusted life years. High burdens were seen in South America and in some Middle Eastern and low-income countries.

The causal agent of toxoplasmosis is the protist Toxoplasma gondii (T. gondii). This unicellular eukaryote is a member of the phylum Apicomplexa which includes other parasites responsible for a variety of diseases (malaria, cryptosporidiosis). The diagnosis and timing of an infection are diagnostically based on serological tests. During a period of acute maternal infection, transplacental transmission can occur, and the rate of congenital toxoplasmosis with risk for severe fetal varies from 15 to 68%, depending on gestational age and the transmission rate is highest in the later stages of pregnancy. The congenital disease is characterized by a wide range of clinical manifestations (neural, vision, and systemic involvement). Within the central nervous system infection causes extensive areas of randomly distributed necrosis and ventricular involvement may cause hydrocephalus. Within the eye chorioretinitis occurs, an inflammation of the choroid pigmented vascular coat of the eye. A "bradyzoite" is the term used for the T. gondii dormant stage.

A recent survey identified a low infection knowledge among doctors and nurses providing prenatal care in an endemic region. Some findings suggest that pre-pregnancy immunization against toxoplasmosis may not protect against reinfection by atypical strains.

Historic Embryology

Toxoplasma gondii (toxoplasmosis) was initially described in 1908 in Tunis by Nicolle and Manceaux (1908) and in Brazil by Splendore (1908). Currently every 3 years experts from many areas meet at the ICOCT – IV "International Congress on Congenital Toxoplasmosis" (last held in 2019 Casa Cava, Italy).

Some Recent Findings

Performance of a Toxo IgM prototype assay for the diagnosis of maternal and congenital Toxoplasma infections "Background Testing for anti-Toxoplasma immunoglobulin (Ig)M is of main importance in the context of pregnancy to promptly alert to an acute maternal infection prior to the detection of IgG and to identify infected newborns. Their absence helps exclude a recent maternal infection in the presence of IgG. Methods The performance of a Toxo IgM immunocapture prototype assay (bioMérieux, France) was compared with that of the VIDAS® Toxo IgM and the ARCHITECT® Toxo IgM (Abbott, Germany) assays at Grenoble and Lyon (France). A total of 1446 sera were sampled from (i) 1054 pregnant women found by routine workup to have no infection (n = 843), an acute infection (<4 months) (n = 28) or a chronic infection (>4 months) with residual (n = 120) or no IgM (n = 62); (ii) 50 three-serum panels sampled immediately after a maternal seroconversion; (iii) 242 samples taken in 41 children with a congenital toxoplasmosis (n = 122) and in 40 uninfected children (n = 120). Results In pregnant women, the overall agreement with the VIDAS® assay was 99.23% (CI: 99.16-99.27) and that with the ARCHITECT® assay was 99.14% (CI: 99.07-99.17). Sensitivity of the Toxo IgM prototype assay was 100% (CI: 87.66-100.00) and specificity was 99.64% (98.96-99.93). In acute maternal infections, IgM assays were detected as early with the prototype as with the other two. In the congenitally infected children, IgM were detected on their first sample in 25/40 with the prototype vs. 23/40 with the VIDAS® test. No uninfected child had positive IgM. Conclusion The prototype performed comparably to the ARCHITECT® and VIDAS® Toxo IgM assays for the diagnosis of maternal and congenital toxoplasmosis." Review - Role of Toxoplasma gondii IgG avidity testing in discriminating between acute and chronic toxoplasmosis in pregnancy "Risk of mother-to-child transmission of Toxoplasma gondii (T. gondii) during pregnancy is much greater in women who are exposed to primary T. gondii infection (toxoplasmosis) after conception compared to those who exposed to the infection before conception. Therefore, laboratory tests that help classify recent primary toxoplasmosis are important tools for the management of pregnant women suspected to T. gondii exposure. Detection of Toxoplasma IgM (Toxo IgM) is a sensitive indicator of primary toxoplasmosis, but the indicator specificity is low because sometimes natural IgM antibodies react with Toxoplasma antigens in absence of the infection. Furthermore, Toxo IgM sometimes persists in blood serum for several months or years following the primary infection. In recent decades, Toxo IgG avidity assay has been used as a standard diagnostic technique for a better estimation of the infection acquisition time and identification of the primary T. gondii infection during pregnancy. Avidity is described as the aggregate strength; by which, a mixture of polyclonal IgG molecules react with multiple epitopes of the proteins. This parameter matures gradually within six months of the primary infection. A high Toxo IgG avidity index allows a recent infection (less than four months) to be excluded, whereas a low Toxo IgG avidity index indicates a probable recent infection with no exclusions of the older infections. The current mini review is based on various aspects of T. gondii IgG avidity testing, including a) description of avidity and basic methods used in primary studies on T. gondii IgG avidity and primary infections; b) importance of IgG avidity test in pregnancy; c) result summary of the major studies on use of T. gondii IgG avidity assay in pregnancy; d) brief explanation of the T. gondii IgG avidity values in newborns; e) result summary of the major studies on T. gondii IgG avidity and polymerase chain reaction (PCR); f) discussion of commercially available T. gondii IgG avidity assays, including newer automated assays; and g) current issues and controversies in diagnosis of primary T. gondii infections in pregnancy." Toxoplasma gondii in women of childbearing age and during pregnancy: seroprevalence study in Central and Southern Italy from 2013 to 2017 "Toxoplasmosis is a worldwide health problem. Infection in pregnant women can result in severe fetal morbidity or in subclinical neonatal infection; most subclinical cases develop ocular and neurological sequelae. The purpose of this serological study was to assess the prevalence of Toxoplasma gondii in two populations of women of childbearing age in Siena (Tuscany, Central Italy) and Bari (Apulia, Southern Italy) between 2013 and 2017 and in a group of pregnant women in Bari in 2016-2017. Serum samples were tested for the presence of specific anti-Toxoplasma gondii IgG antibodies by a commercially available ELISA test. The percentage of seropositive subjects in Bari was significantly higher than in Siena (22.4% vs. 12.4%) and an age-related trend was observed. A low prevalence of T. gondii infection (13.8%) was observed among the pregnant women tested. In addition to showing a significant difference between Central and Southern Italy, this study provides updated data on T. gondii seroprevalence in women during childbearing age and pregnancy. The results confirm a trend toward a decrease, especially in younger people and pregnant women."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Developmental Toxoplasmosis | Toxoplasmosis | Toxoplasmosis Necrosis | chorioretinitis

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders "Common infectious pathogens have been associated with psychiatric disorders, self-violence and risk-taking behavior. 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). ...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." Toxoplasmosis and horse meat, france "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." Seroprevalence of TORCH infections in women of childbearing age in Croatia. "During 2005-2009, a seroepidemiological study was carried out in Croatia to define the population susceptible to common TORCH agents among pregnant and non-pregnant women of childbearing age. The IgG seroprevalence was 29.1% forT. gondii, 94.6% for rubella, 75.3% for cytomegalovirus (CMV), 78.7% for herpes simplex virus type 1 (HSV-1), and 6.8% for HSV-2. Acute toxoplasmosis and CMV infection (positive IgM antibodies with low IgG avidity) were documented in 0.25% and 0.09% women, respectively. IgM prevalence was 1.2% for both HSV-1 and HSV-2. None of the participants showed acute rubella infection. Seropositivity to T. gondii and HSV-2 varied significantly between age groups (p = 0.001 and p = 0.036, respectively). Women residing in rural regions showed a significantly higher seroprevalence rate for T. gondii, CMV, and HSV-1 than urban women (T. gondii: 44.0% vs. 25.4%, p < 0.001; CMV: 85.0% vs. 73.1%, p = 0.018; HSV-1: 86.0% vs. 76.4%, p = 0.041)."

Toxoplasmosis Lifecycle

Toxoplasma Tachyzoites

European Congenital Toxoplasmosis Surveillance

See the recent 2008 article.

• Denmark - neonatal screening programme based on neonatal Guthrie card testing for toxoplasma-specific IgM was implemented in 1999 but discontinued on 31 July, 2007.
• France - a surveillance system for congenital toxoplasmosis was initiated in May 2007.
• Germany - congenital toxoplasmosis cases have been notifiable since 2001 implemented under the Protection Against Infection Act.
• Italy - surveillance is confined to a regional programme in the Campania region initiated in 1997.
• Bulgaria, Cyprus, Czech Republic, England and Wales, Estonia, Ireland, Latvia, Lithuania, Malta, Poland, Scotland, and Slovakia - surveillance (congenital or not), as defined by the European Union (symptomatic toxoplasmosis cases serologically confirmed) is considered a notifiable disease and subject to continuous data collection.

Ocular Toxoplasmosis

Clinical episodes of ocular toxoplasmosis can represent either acquire toxoplasmosis after birth or a reactivation of an infection that was acquired in utero.

Ocular toxoplasmosis is the commonest identifiable cause of posterior uveitis.

Links: PubMed Health - Uveitis

References

Reviews

Kim K. (2018). The Epigenome, Cell Cycle, and Development in Toxoplasma. Annu. Rev. Microbiol. , 72, 479-499. PMID: 29932347 DOI.

Montoya JG & Remington JS. (2008). Management of Toxoplasma gondii infection during pregnancy. Clin. Infect. Dis. , 47, 554-66. PMID: 18624630 DOI.

Montoya JG & Liesenfeld O. (2004). Toxoplasmosis. Lancet , 363, 1965-76. PMID: 15194258 DOI.

Jones J, Lopez A & Wilson M. (2003). Congenital toxoplasmosis. Am Fam Physician , 67, 2131-8. PMID: 12776962

Stegmann BJ & Carey JC. (2002). TORCH Infections. Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections. Curr Womens Health Rep , 2, 253-8. PMID: 12150751

Articles

da Silva LB, de Oliveira Rde V, da Silva MP, Bueno WF, Amendoeira MR & de Souza Neves E. (2011). Knowledge of toxoplasmosis among doctors and nurses who provide prenatal care in an endemic region. Infect Dis Obstet Gynecol , 2011, 750484. PMID: 21747644 DOI.

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Search Pubmed: Toxoplasmosis | Maternal Toxoplasmosis

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• NIH PubMed Health Toxoplasmosis | TORCH screen
• ABC Radio The Health Report - Toxoplasmosis Broadcast Monday 30 April 2001
• Queensland Health Topic - Toxoplasmosis
• Cat World toxoplasmosis in cats

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Cite this page: Hill, M.A. (2023, December 2) Embryology Abnormal Development - Toxoplasmosis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Toxoplasmosis

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G