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During pregnancy, primary Toxoplasma gondii infection can cause congenital toxoplasmosis (CT). We described the newborns' outcomes from a multicentre cohort of mothers with seroconversion (SC) at different gestational ages. This retrospective observational study (from 2007 to 2018) was conducted in two Italian referral hospitals: Fondazione IRCCS Policlinico San Matteo in Pavia and Spedali Civili in Brescia. In total, 247 pregnant women were enrolled: seroconversions were enrolled: seroconversions documented as having occurred in the two months preceding pregnancy in 12 cases (4.9%; 95% CI 2.2-7.5%), and during pregnancy in 235 cases (95.1%; 95% CI 92.5-97.8%). SC is defined as the appearance of specific anti-Toxoplasma antibodies (IgM/IgG) during pregnancy in a previously seronegative woman. A total of 56 (22.5%; 95% CI 17.3-27.7%) newborns were lost to follow-up; thus, the outcome of 193 (77.5%; 95% CI 72.3-82.7%) newborns was analyzed. The overall transmission rate of T. gondii infection was 23.8% (95% CI 17.8-29.8%), 0% (95% CI 0.0-11.9%) among the 1st trimester SCs, 12.5% (95% CI 5.6-19.4%) among the 2nd trimester SCs, 53.8% (95% CI 41.7-66.0%) among the 3rd trimester ones. No CT were found in the group of periconceptional infection. Among the infected newborns, clinically manifest cases were 12 (26.1%; 95% CI 13.4-38.8%), including 1 case (2.2%; 95% CI 2.0-6.4%) of stillbirth and 11 symptomatic neonates (23.9%; 95% CI 11.6-36.2%). A total of 83 amniocentesis were performed (33.6%; 95% CI 27.7-39.5%), no complication was recorded and no false positive or false negative results were registered. The results are in line with the fetal risks reported in literature for T. gondii infection during pregnancy, even if at a lower percentage probably due to a prompt treatment.

Congenital toxoplasmosis has a high impact on human disease worldwide, inducing serious consequences from fetus to adulthood. Despite this, there are currently no human vaccines available to prevent this infection. Most vaccination studies against  Toxoplasma gondii  infection used animal models in which the infection was established by exogenous inoculation. Here, we review recent research on potential  T. gondii  vaccines using animal models in which infection was congenitally established. Endeavors in this field have so far revealed that live or subunit vaccines previously found to confer protection against extrinsically established infections can also protect, at least partially, from vertically transmitted infection. Nevertheless, there is no consensus on the more adequate immune response to protect the host and the fetus in congenital infection. Most of the vaccination studies rely on the assessment of maternal systemic immune responses, quantification of parasitic loads in the fetuses, and survival indexes and/or brain parasitic burden in the neonates. More research must be carried out not only to explore new vaccines but also to further study the nature of the elicited immune protection at the maternal-fetal interface. Particularly, the cellular and molecular effector mechanisms at the maternal-fetal interface induced by immunization remain poorly characterized. Deeper knowledge on the immune response at this specific location will certainly help to refine the vaccine-induced immunity and, consequently, to provide the most effective and safest protection against  T. gondii  vertical infection., Competing Interests: The authors declare that the revision work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barros, Teixeira, Vilanova, Correia, Teixeira and Borges.)

Although prenatal diagnosis and prenatal and neonatal therapy of congenital toxoplasmosis are available, there is controversy concerning the effectiveness of prophylaxis to prevent placental transmission. Experimental, parasitological, and clinical data suggest a "window of opportunity" following maternal infection. Among medications active against Toxoplasma gondii, mainly spiramycin (Spy) and pyrimethamine + sulfonamide combinations (P-S) have been evaluated. Results from observational studies suffered treatment bias, since prescriptions differed according to the gestational age at seroconversion, which is the major risk factor for transmission, and many lacked precise timing. Some large retrospective studies found no difference in transmission according to prophylactic treatment, but transmission was lower when treatment started promptly after maternal seroconversion. A few recent studies adjusting for timing of infection observed lower transmission in case of P-S than other or no prophylaxis. In the only randomized controlled trial, transmission was lower with P-S than S (18.5% vs 30%, P = .147); this association was strengthened when the treatment was started within 3 weeks of seroconversion, and the incidence of fetal cerebral ultrasound signs was significantly reduced in the P-S group. Rapid initiation of prophylactic therapy following maternal infection, which is usually asymptomatic, requires systematic screening for maternal seroconversion during pregnancy., (© 2020 John Wiley & Sons, Ltd.)

Toxoplasma gondii infections are common in humans and animals worldwide. The ingestion of food or water contaminated with oocysts excreted by infected cats or ingesting uncooked or undercooked meat containing tissue cysts of T. gondii are the 2 major modes of transmission of T. gondii. Viable T. gondii is more prevalent in pork and lamb than in beef. In the past decade, there have been many articles on the high seroprevalence in cattle, particularly from China. There is a report of an outbreak of acute toxoplasmosis in humans suspected to be linked to the ingestion of Artisan fresh cheese from cow's milk. There are conflicting reports concerning the rate of congenital transmission of T. gondii in cattle, especially from Brazil. In a report from Brazil, viable T. gondii was isolated from the blood of 1 of 60 pregnant cows slaughtered at an abattoir and from 1 fetus. The role of beef in the epidemiology of T. gondii infections is still not clear. Here, we review prevalence, persistence of infection, clinical disease, epidemiology, and public health risks of T. gondii infections in cattle from beef and cow's milk worldwide for the past decade., (© American Society of Parasitologists 2020.)

Toxoplasmosis is a common infection worldwide caused by Toxoplasma gondii , an intracellular parasite. The prevalence of Toxoplasmosis ranges from 17.5% to 69.5% in Turkey. Toxoplasmosis is mostly asymptomatic. It may cause fetal mortality in case of vertical passage. The most common clinical findings in congenital toxoplasmosis are chorioretinitis, hydrocephalus and cerebral calcification. Another group of susceptible patients for Toxoplasma gondii are immunesuppressive patients. Reactivation of a latent infection in the case of immunodeficiency can lead to fatal toxoplasmic encephalitis. Serological diagnostic methods based on the detection of specific antibodies for Toxoplasma gondii are the most commonly used diagnostic methods. However, it may be difficult to interpret the results in pregnant women, neonates, and the patients receiving treatment. It is stated that using more than one method together to improve the reliability of the diagnosis is a more accurate approach. In the prenatal diagnosis of congenital toxoplasmosis, in patients with immunodeficiency, in ocular toxoplasmosis, the polymerase chain reaction is seen as having a higher sensitivity. The aim of this review is to present the general features, diagnostic methods and current approaches in toxoplasma infection, an important public health problem.

In this study, we generated a tkl1 deletion mutant in the Toxoplasma gondii type 1 RH (RHΔ tkl1 ) strain and tested the protective efficacies of vaccination using RHΔ tkl1 tachyzoites against acute, chronic, and congenital T. gondii infections in Kunming mice. Mice vaccinated with RHΔ tkl1 mounted a strong humoral and cellular response as shown by elevated levels of anti- T. gondii -specific IgG, IL-2, IL-12, IFN-γ, and IL-10. All RHΔ tkl1 -vaccinated mice survived a lethal challenge with 1 × 10 3 tachyzoites of type 1 RH or ToxoDB#9 (PYS or TgC7) strain as well as 100 cysts or oocysts of Prugniuad strain. All mock-vaccinated plus infected mice have died. Vaccination also protected against cyst- or oocyst-caused chronic infection, reduced vertical transmission caused by oocysts, increased litter size, and maintained body weight of pups born to dams challenged with 10 oocysts on day 5 of gestation. In contrast, all mock-vaccinated plus oocysts-infected dams had aborted, and no fetus has survived. Vaccinated dams remained healthy postinfection, and their brain cyst burden was significantly reduced compared with mock-vaccinated dams infected with oocysts. In vivo depletion of CD4 + T cells, CD8 + T cells, and B cells revealed that CD8 + T cells are involved in the protection of mice against T. gondii infection. Additionally, adoptive transfer of CD8 + T cells from RHΔ tkl1 -vaccinated mice significantly enhanced the survival of naive mice infected with the pathogenic strain. Together, these data reaffirm the importance of CD8 + T cell responses in future vaccine design for toxoplasmosis and present T. gondii tkl1 gene as a promising vaccine candidate., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Toxoplasma gondii is the etiological agent of toxoplasmosis. Mother-to-child transmission of this parasite can occur during pregnancy. Newborns with congenital toxoplasmosis may develop central nervous system impairment, with severity ranging from subclinical manifestations to death. A proinflammatory/regulated specific immune profile is crucial in the defense against the parasite; nevertheless, its role in the infected pregnant women and the congenitally infected offspring has been poorly explored, and there is still no consensus about its relation to parasite vertical transmission or to severity and dissemination in the congenitally infected newborns. This work aimed to characterize these relations by means of principal component and principal factor analyses. For this purpose, we determined the specific production of the four immunoglobulin G antibody subclasses, cytokines, and lymphocyte proliferation in the T. gondii- infected pregnant women-10 who transmitted the infection to their offspring and seven who did not-as well as in 11 newborns congenitally infected and grouped according to disease severity (five mild and six moderate/severe) and dissemination (four local and seven disseminated). We found that the immune response of nontransmitter women differed from that of the transmitters, the latter having a stronger proinflammatory response, supporting a previous report. We also found that newborns who developed moderate/severe disease presented higher levels of lymphocyte proliferation, particularly of CD8 + and CD19 + cells, a high proportion of tumor necrosis factor α producers, and reduced expression of the immune modulator transforming growth factor β, as opposed to children who developed mild clinical complications. Our results suggest that a distinctive, not regulated, proinflammatory immune response might favor T. gondii vertical transmission and the development of severe clinical manifestations in congenitally infected newborns., (Copyright © 2020 Gómez-Chávez, Cañedo-Solares, Ortiz-Alegría, Flores-García, Figueroa-Damián, Luna-Pastén, Gómez-Toscano, López-Candiani, Arce-Estrada, Bonilla-Ríos, Mora-González, García-Ruiz and Correa.)

Aim: Toxoplasmosis following liver transplant with donor-recipient mismatch is rare, but is often life-threatening. However, there are no data on the frequency of cyst carriage in the liver, nor consensual chemoprophylaxis guidelines. This study aimed at describing frequency and localisation of Toxoplasma cysts in the liver in a mouse model of chronic infection to predict the risk in liver transplantation., Methods: Heart, brain and liver lobes of 21 mice chronically infected with Toxoplasma were collected for DNA extraction and amplification of Toxoplasma gondii rep529 sequence by real-time PCR., Results: Parasite DNA was detected in the liver of 19/21 mice (90.5%), with no preferential anatomical localisation, but with higher parasite loads in the papillary process. Parasite loads in the liver were far lower than in brain and heart. The number of infected lobes was inversely correlated to the total liver weight, but was independent of the brain parasite load and of the parasite strain., Conclusions: The liver is a frequent site of cyst carriage, confirming that transplantation of an organ from a seropositive donor to seronegative recipient is at high risk for acquired toxoplasmosis. Systematic serological screening prior to transplantation and chemoprophylaxis in patients at risk are fully justified., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario., Methodology/principal Findings: We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years., Conclusions/significance: Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.

In human congenital toxoplasmosis the effects of parasite burden and pregnancy time at infection on clinical outcome are well known, but there is controversy regarding the role of Toxoplasma gondii type. Through a systematic review of the literature, we aimed to discern if T. gondii type has a role on clinical outcome in human congenital toxoplasmosis. We built up a database of congenital toxoplasmosis from reports of cases, case series and screening-based cohorts, which had information about parasite type, gestation time at maternal infection and/or clinical outcome in the product. Then, we obtained frequencies for loci used to genotype geographical origin of cases and types found. Also, odds ratios were calculated for association between time of maternal infection or parasite type on outcome. Type II parasites were the most common in Europe, Asia and Africa, while in America there were mainly atypical strains. More newborns with clinical problems were born from mothers infected during the first half of gestation than from those acquiring the parasite after week 24, regardless of parasite genotype (92.9 vs. 16.1 %, OR = 67.9, CI95 25.4-181.6). Type I and atypical parasites were associated with clinical problems as opposed to types II and III, regardless of pregnancy period at infection (86.9 vs. 72.9 %, OR = 2.47, CI95 1.1-5.4). A significant and remarkable tendency of type I parasites to be present during early pregnancy was also observed (94.4 vs. 5.6 %, P < 0.009). In addition to parasite burden and period of gestation, T. gondii genotype seems involved in CT clinical outcome.

This study evaluates whether medical and veterinary students' attitudes toward "One Health" and interprofessional education changed after participating in a joint small group learning exercise focused on risk factors associated with zoonotic disease. A survey was distributed to third-year medical students (n = 98) and second-year veterinary students (n = 140), each with a 95% response rate. Overall, 92% of veterinary students and 73% of medical students agreed or strongly agreed that "One Health" was relevant to their desired specialty. Students from both schools largely agreed that interprofessional education should be a goal of the curriculum for their school, and that interprofessional approaches strengthen their overall education. Students reported increased confidence in their communication skills and improved ability to contribute to One Health collaborative teams. This educational intervention, built around a patient case, focused on a variety of learning objectives including skills (such as communication), knowledge (of zoonotic toxoplasmosis) and attitudes (toward collaborative learning and practice). By sparking an interest in One Health during their early professional education, we sought to encourage a new generation of physicians and veterinarians to adopt a more collaborative spirit to their clinical practice, which will ultimately benefit human, animal and environmental health.

Introduction: There is a paucity of data on the occurrence of congenital toxoplasmosis in children born to mothers dually infected with HIV and Toxoplasma gondii., Objective: To evaluate aspects of the mother-infant pairs associated with vertical transmission of toxoplasmosis in women co-infected with HIV in a referral center for perinatally acquired infections in Belo Horizonte, Brazil., Methods: Descriptive study of HIV vertically exposed children, with congenital toxoplasmosis, followed at a referral center (cohort/Belo Horizonte). Prenatal and post-natal variables for the mother-infant pairs were evaluated. A literature review with no filtering for time and language was performed to identify reports of congenital toxoplasmosis in HIV vertically exposed children., Results: Among 2007 HIV vertically exposed children evaluated in the period from 1998 to 2011, 10 cases of congenital toxoplasmosis were identified (incidence: 0.5%, 95% confidence interval: 0.24-0.91). In searching the literature 22 additional cases in 17 reports were found. Combining the findings of our cohort with other reported cases, 50% (16/32) of congenital toxoplasmosis in HIV vertically exposed children were from Brazil. The cases of congenital toxoplasmosis in HIV vertically exposed children identified in Brazil occurred mainly in the post-Highly Active Antiretroviral Therapy era (p=0.002) and presented a lower death rate (p=0.003) than those from other countries. In the cohort/Belo Horizonte, HIV infection was identified mainly during gestation; T. gondii vertical transmission was observed in pregnant women with CD4(+)>500 cells/mm(3) and latent toxoplasmosis. High rates of ocular lesions (87.5%) and central nervous system involvement (70%) were detected., Conclusions: The risk of vertical transmission of T. gondii in HIV-infected women is low and has been usually associated with maternal immunosuppression and elevated viral load. However, our findings of congenital toxoplasmosis in children born to HIV-infected mothers with latent toxoplasmosis and not immunosuppressed emphasize the need for careful follow-up in these cases., (Copyright © 2014 Elsevier Editora Ltda. All rights reserved.)

Purpose of Review: The management of infection in pregnancy aims mainly at improving the diagnosis and prognosis of congenital infections. Over 400 publications have dealt with this issue over the last 2 years, taking advantage of progress made not only in the epidemiological knowledge of infections but also neonatal treatment and prenatal diagnosis and interventions. The focus remains largely on viral and parasitic infections, namely cytomegalovirus (CMV) and toxoplasmosis, with the appearance of influenza as part of recent and severe outbreaks., Recent Findings: The prevalence of CMV infection is stable. The prediction of foetal infection from primary maternal infection is becoming more accurate and therapeutic approaches are promising, including the development of a vaccine in the near future. The prevalence of toxoplasmosis is decreasing markedly in Europe weakening the effect of preventive measures and questioning the rationale for screening. In addition, the efficacy of prenatal treatment is still under scrutiny, although no appropriate randomized controlled trial (RCT) has been undertaken., Summary: Accurate dating of maternal primary infection is key to prenatal management including foetal and perinatal surveillance and therapy. Heightened prenatal surveillance following influenza infection in early pregnancy is warranted by an apparent increased risk of nonchromosomal congenital malformations in large epidemiological studies, likely as an effect of maternal hyperthermia.

To contribute to the insight into the worldwide population structure of Toxoplasma gondii, we genetically characterized a total of eight strains isolated from intermediate hosts including humans, sheep and pigeons in Serbia. Although parasite DNA was detected in 28.2% (60/213) of the human samples from 162 patients serologically suspected of active toxoplasmosis, as well as in 5/7 seropositive pigeons and in 2/12 seropositive sheep examined, multilocus PCR-RFLP genotyping, using SAG1, 5'SAG2, 3'SAG2, GRA6, 5'GRA7 and 3'GRA7 as markers, was successful in only four human isolates (of which one was isolated from both the bronchoalveolar lavage fluid and blood samples of a single patient), one sheep and three pigeons. Of the eight isolates, five were type II (62.5%), one was type III, one was atypical, and one had a type I allele at GRA6 as the single locus genotyped. Although type II, as elsewhere in Europe, predominated, these results may suggest a higher genetic diversity of T. gondii in Serbia, reflecting local environmental contamination and also the geographical position of the country in South-East Europe., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: Toxoplasma gondii is the most common protozoan parasite in developed nations. Up to 43% of the French population may be infected, depending on eating habits and exposure to cats, and almost one third of the world human's population may be infected. Two types of infection have been described: a congenital form and an acquired form. Although the medical profession treats these latent cases as asymptomatic and clinically unimportant, results of animal studies and recent studies of personality profiles, behavior, and psychomotor performance have led to reconsider this assumption., Preclinical Data: Among rats: parasite cysts are more abundant in amygdalar structures than those found in other regions of the brain. Infection does not influence locomotion, anxiety, hippocampal-dependent learning, fear conditioning (or its extinction) and neophobia in rats. Rats' natural predator is the cat, which is also T. gondii's reservoir. Naturally, rats have an aversion to cat urine, but the parasite suppresses this aversion in rats, thus influencing the infection cycle. Tachyzoites may invade different types of nervous cells, such as neurons, astrocytes and microglial cells in the brain, and Purkinje cells in cerebellum. Intracellular tachyzoites manipulate several signs for transduction mechanisms involved in apoptosis, antimicrobial effectors functions, and immune cell maturation. Dopamine levels are 14% higher in mice with chronic infections. These neurochemical changes may be factors contributing to mental and motor abnormalities that accompany or follow toxoplasmosis in rodents and possibly in humans. Moreover, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro with synergistic activity., Clinical Data: The effects of the parasite are not due to the manipulation in an evolutionary sense but merely due to neuropathological or neuroimmunological effects of the parasite's presence. Toxoplasmosis and schizophrenia: epidemiological studies point to a role for toxoplasmosis in schizophrenia's etiology, probably during pregnancy and early life, this association being congruent with studies in animal models indicating that animal exposures of the developing brain to infectious agents or immune modulating agents can be associated with behavioral changes that do not appear until the animal reaches full maturity. Psychiatric patients have increased rates of toxoplasmic antibodies, the differences between cases and controls being greatest in individuals who are assayed near the time of the onset of their symptoms. The increase of dopamine in the brain of infected subjects can represent the missing link between toxoplasmosis and schizophrenia. Toxoplasmosis and Obsessive Compulsive Disorder (OCD): the seropositivity rate for anti-T. gondii IgG antibodies among OCD patients is found to be significantly higher than the rate in healthy volunteers. Infection of basal ganglia may be implicated in the pathogenesis of OCD among Toxoplasma seropositive subjects. Toxoplasmosis and personality: infected men appear to be more dogmatic, less confident, more jealous, more cautious, less impulsive and more orderly than others. Conversely, infected women seem warmest, more conscientious, more insecure, more sanctimonious and more persistent than others. It is possible that differences in the level of testosterone may be responsible for the observed behavioral differences between Toxoplasma-infected and Toxoplasma-free subjects., Conclusion: In the future two major avenues for research seem essential. On one hand, prospective studies and research efforts must still be carried out to understand the mechanisms by which the parasite induces these psychiatric disorders. On the other hand, it has not yet been demonstrated that patients with positive toxoplasmic serology may better respond to haloperidol's or valproic acid's antiparasitic activity. These results may appear as a major issue in the drug's prescribing choices and explain variability in response to the treatment of patients with schizophrenia that is not explained by the genetic polymorphism., (Copyright © 2012 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: One of the major consequences of pregnant women becoming infected by Toxoplasma gondii is vertical transmission to the fetus. Although rare, congenital toxoplasmosis can cause severe neurological or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies. Prenatal care must include education about prevention of toxoplasmosis. The low prevalence of the disease in the Canadian population and limitations in diagnosis and therapy limit the effectiveness of screening strategies. Therefore, routine screening is not currently recommended., Objective: To review the prevention, diagnosis, and management of toxoplasmosis in pregnancy., Outcomes: OUTCOMES evaluated include the effect of screening on diagnosis of congenital toxoplasmosis and the efficacy of prophylaxis and treatment., Evidence: The Cochrane Library and Medline were searched for articles published in English from 1990 to the present related to toxoplasmosis and pregnancy. Additional articles were identified through references of these articles., Values: The quality of evidence is rated and recommendations made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table)., Benefits, Harms, and Costs: Guideline implementation should assist the practitioner in developing an approach to screening for and treatment of toxoplasmosis in pregnancy. Patients will benefit from appropriate management of this condition., Sponsor: The Society of Obstetricians and Gynaecologists of Canada., Recommendations: 1. Routine universal screening should not be performed for pregnant women at low risk. Serologic screening should be offered only to pregnant women considered to be at risk for primary Toxoplasma gondii infection. (II-3E) 2. Suspected recent infection in a pregnant woman should be confirmed before intervention by having samples tested at a toxoplasmosis reference laboratory, using tests that are as accurate as possible and correctly interpreted. (II-2B) 3. If acute infection is suspected, repeat testing should be performed within 2 to 3 weeks, and consideration given to starting therapy with spiramycin immediately, without waiting for the repeat test results. (II-2B) 4. Amniocentesis should be offered to identify Toxoplasma gondii in the amniotic fluid by polymerase chain reaction (a) if maternal primary infection is diagnosed, (b) if serologic testing cannot confirm or exclude acute infection, or (c) in the presence of abnormal ultrasound findings (intracranial calcification, microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or severe intrauterine growth restriction). (II-2B) 5. Amniocentesis should not be offered for the identification of Toxoplasma gondii infection at less than 18 weeks' gestation and should be offered no less than 4 weeks after suspected acute maternal infection to lower the occurrence of false-negative results. (II-2D) 6. Toxoplasma gondii infection should be suspected and screening should be offered to pregnant women with ultrasound findings consistent with possible TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes, and other) infection, including but not limited to intracranial calcification, microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or severe intrauterine growth restriction. (II-2B) 7. Each case involving a pregnant woman suspected of having an acute Toxoplasma gondii infection acquired during gestation should be discussed with an expert in the management of toxoplasmosis. (III-B) 8. If maternal infection has been confirmed but the fetus is not yet known to be infected, spiramycin should be offered for fetal prophylaxis (to prevent spread of organisms across the placenta from mother to fetus). (I-B) 9. A combination of pyrimethamine, sulfadiazine, and folinic acid should be offered as treatment for women in whom fetal infection has been confirmed or is highly suspected (usually by a positive amniotic fluid polymerase chain reaction). (I-B) 10. Anti-toxoplasma treatment in immunocompetent pregnant women with previous infection with Toxoplasma gondii should not be necessary. (I-E) 11. Women who are immunosuppressed or HIV-positive should be offered screening because of the risk of reactivation and toxoplasmosis encephalitis. (I-A) 12. A non-pregnant woman who has been diagnosed with an acute Toxoplasma gondii infection should be counselled to wait 6 months before attempting to become pregnant. Each case should be considered separately in consultation with an expert. (III-B) 13. Information on prevention of Toxoplasma gondii infection in pregnancy should be made available to all women who are pregnant or planning a pregnancy. (III-C).

The prevention of congenital toxoplasmosis is based on providing information to women, serologic diagnosis and treatment of the infected mother and child. In this article we present the results of 12 years of implementation of a congenital toxoplasmosis prevention program in which we measured the mother's infection incidence rate, the transmission rate and the number and severity of infection in newborns. The study was performed on 12035 pregnant women in the period 2000-2011. The prevalence rate of antibodies against Toxoplasma gondii was 18.33% (2206/12035). Thirty-seven out of 9792 susceptible women presented acute infection and the mother's infection incidence rate was 3.78 per 1000 births. The transplacental transmission rate was 5.4% (2/37). Two newborns presented congenital toxoplasmosis infection, one had no clinical signs while the other presented strabismus and chorioretinitis. Thirty-five infected mothers and the two children with congenital infection were treated. The transmission rates obtained allow consider this prevention program as a valid resource to minimize the impact of congenital toxoplasmosis.

Congenital toxoplasmosis results from the transplacental transmission of the parasite Toxoplasma gondii after a maternal infection acquired in pregnancy. Prevalence of congenital infection ranges from 0.1 to 0.3 per 1000 live births. The maternal-fetal transmission rate increases with gestational age at maternal seroconversion, from less than 15% at 13 weeks of gestation to over 70% at 36 weeks. Conversely, the later the maternal infection, the lower the risk of symptomatic congenital infection (infections acquired during the third trimester are most often asymptomatic at birth). Prenatal diagnosis is currently performed by PCR analysis in amniotic fluid. Antenatal management and treatment vary considerably among countries. In some European countries, maternal infections are detected through serological screening allowing a prompt treatment with spiramycin, which is expected to reduce the risk of vertical transmission. If PCR analysis in amniotic fluid is positive or if maternal infection was acquired in the third trimester of pregnancy, a combination with pyrimethamine and sulphonamide is given until delivery. Benefits of antenatal treatments remain controversial. Infected newborns are prescribed pyrimethamine and sulphonamide for 12 months. Despite antenatal and postnatal treatment, chorioretinitis can occur at any age (prevalence>20% at 10 years of age): long-term ophthalmological follow-up remains necessary., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Acute infections in pregnant women may be transmitted to the fetus and cause severe illness. The purpose of this study was to establish a dedicated surveillance network (DSN) for congenital toxoplasmosis (CT) in Greece, in order to assess the birth prevalence of CT., Methods: A DSN of thirty clinicians was established for reporting CT cases from hospitals throughout Greece. The clinicians were selected on the basis that there was a high possibility the suspected cases would be referred to them from district hospitals or private clinics. Suspected cases of CT were reported on a monthly basis with a zero reporting card during a surveillance period from April 2006 to December 2009. A questionnaire was sent for any suspected case to record information including demographic parameters, clinical signs and symptoms and laboratory results. Serological and molecular confirmation of cases was performed by the Pasteur Hellenic Institute. All newborns suspected of CT received treatment and were serologically and clinically followed up for one year., Results: The monthly response rate reached 100%, although only after reminders sent to 65% of the participant physicians. Sixty-three suspected CT cases were recorded by the DSN during the study period including fourteen confirmed and seven probable cases. Ten cases (47.6%) presented with symptoms at birth. Chorioretinitis was the most prominent manifestation, occurring in five symptomatic CT cases (50%). No other symptoms appeared by the end of the one year clinical follow up. No case was recorded by the existing surveillance system of the Hellenic Center of Disease Control and Prevention (HCDCP) during the same time period. Birth prevalence was estimated at 0.45, 0.51 and 0.51 per 10,000 births for 2007, 2008 and 2009 respectively. The incidence rate of symptomatic CT at birth was estimated at 0.10 cases per 10,000 births per year in Greece (for the period 2007-2009)., Conclusion: The DSN for CT proved to be more sensitive than the classical notification system, easy in application and very efficient in reporting rare diseases such as CT. Similar DSNs could be used to provide useful information on other rare diseases.

Objectives: The objectives of this study were to analyze the association between the classification of toxoplasmosis in the pregnant woman (TP) according to the classification of Lebech et al. and the incidence of congenital toxoplasmosis (CT), also taking into consideration prenatal treatment., Methods: A clinical cohort study of 524 children followed-up until 1 year of age was conducted. Adjusted odds ratios (OR) were estimated by logistic regression., Results: Of 519 pregnant women, 61.3% were not classified due to the incompleteness of hospital records. Among the pregnant women classified as confirmed cases of TP (n=19), the CT risk was six times greater than in the probable/possible group. No case of CT was identified in the group of pregnant women classified as unlikely to have TP. The children with no prenatal treatment (46.2% n=242/524) presented a risk almost three times greater of CT than the treated children (OR 2.77, 95% confidence interval (CI) 1.54-4.97; p=0.001). Complete prenatal treatment was identified as a protecting factor for CT (OR 0.35, 95% CI 0.19-0.65; p=0.001)., Conclusions: A lack or incomplete prenatal treatment was identified as an important risk factor for CT in this study. The proportions of non-classified mothers and children with no prenatal treatment reflect the need to improve prenatal care in Brazil., (Copyright © 2012. Published by Elsevier Ltd.)

Almost uniform protection against congenital toxoplasmosis initiated by inoculations with cysts and oocysts of the parasite was seen in the hamster model, among strains of different genotypes. Because the RH immunization prior to pregnancy has to be controlled with medication for most of the hamsters to survive, and also some congenital transmission of Toxoplasma was observed during the chronic stage of the infection, the hamster is considered less practical than the rat and the BALB/c mouse models. It is concluded that the hamster model closely resembles protection against congenital infection in nature, where most of the pregnant women and ewes that experienced a toxoplasma infection previously, protect their fetuses against an infection with the parasite during pregnancy., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Researchers have learned much concerning the population biology of Toxoplasma gondii over the past 2 decades. It is now apparent that many atypical genotypes exist besides the typical 3 genotypes (type I, type II and type III) first described from samples from Europe and the United States. These genotypes can differ in pathogenicity and transmissibility from the typical genotypes that have been used in the majority of scientific research over the past 70 years. These differences impact much of what we used to believe as facts about congenital toxoplasmosis (CT) and will be important in developing new recommendations for prevention of CT and the monitoring of women at risk for developing CT. The present review highlights new information on T. gondii genotypes and how this information will change the way we convey information about CT to pregnant women, physicians and students.

Reinfection with Toxoplasma gondii is exceptional but can lead to transmission to the fetus when it occurs during pregnancy. We present a case of congenital toxoplasmosis in a young baby born to an immunocompetent mother who had been immunized against toxoplasmosis before pregnancy. The presence of residual IgG-specific antibodies does not always mean an absolute protection against a new toxoplasma infection. During the pregnancy, the patient was advised to follow the hygienic and dietary preventive measures even though the previous test results were consistent with past toxoplasma infection., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Monthly serological screening of non immune pregnant women is recommended for prevention of congenital toxoplasmosis. However, this screening is often interrupted before delivery. We report a case of congenital toxoplasmosis following infection occurring late in pregnancy. This documented case highlights the need for a final routine serological test, 2-3 weeks post-partum for all seronegative pregnant women. In fact, the screening of congenital toxoplasmosis cases allows the early administration of specific treatment that avoids later severe complications such as chorioretinitis., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

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.)

When immunocompetent people become infected with the parasite Toxoplasma gondii, the disease is generally asymptomatic. However, transplacental transmission of T. gondii may lead to severe congenital infection including in utero abortion, foetal death, or neurological or ocular damage of the foetus. France has had a national programme to prevent congenital toxoplasmosis since 1978. However, although estimated seroprevalence in pregnant women has fallen from 84% in the 1960s to 44% in 2003, no reliable data have been available on the annual number of cases of congenital toxoplasmosis or the severity of infection. In 2006, the French National Institute for Public Health Surveillance (Institut de Veille Sanitaire) and the National Reference Centre for Toxoplasmosis recommended that a national laboratory-based surveillance system be used for the surveillance of the disease. In 2007, 31 laboratories reported at least one congenital case through the surveillance system, giving a total of 272 cases. A total of 11 terminations of pregnancy were reported (six abortions and five foetal deaths). Of the live-born cases, 206 were asymptomatic, 28 were symptomatic and seven had a severe form of the disease. As there were 818,700 births in France and French overseas departments in 2007, the overall prevalence of congenital toxoplasmosis observed that year was 3.3 (95% confidence interval (CI): 2.9 to 3.7) per 10,000 live births and the incidence rate of the disease at birth was 2.9 (95% CI: 2.5 to 3.2) per 10,000 live births; the estimated incidence rate of symptomatic congenital toxoplasmosis was 0.34 (95% CI: 0.2 to 0.5) cases per 10,000 live births.

Congenital toxoplasmosis is caused by transplacental contamination of the fetus withToxoplasma gondiifollowing maternal primary infection. The risk of mother-to-child transmission depends on the term of pregnancy at the time of maternal infection. The risk is lower than 5% in the first trimester but can reach 90% in the last days of pregnancy. Inversely, however, fetal disease is more severe when contamination occurs early in pregnancy. The French prevention program officially recommends monthly serological screening of susceptible women during pregnancy and information about hygiene and dietary rules. Prenatal diagnosis of congenital toxoplasmosis is based on a combination of examinations: PCR testing for the parasite in amniotic fluid, mouse inoculation, fetal ultrasonography, and magnetic resonance imaging. Neonatal screening consists of PCR of the placenta, mouse inoculation, detection of specific IgM and IgA in the newborn, ocular fundus examinations by indirect ophthalmoscopy, and transfontanellar ultrasonography. As soon as maternal infection is suspected, preventive treatment with spiramycin begins; the treatment is changed to a combination of pyrimethamine-sulfonamide if fetal infection is proved. Some teams are using this combination as first-line treatment after 30 weeks of gestation, without performing amniocentesis. Recent European multicenter studies raise questions about the effectiveness of prenatal treatment on mother-to-child transmission and on the reduction in the number and severity of fetal sequelae. A randomized controlled trial is required to prove the efficacy of prenatal treatment in general and of specific drugs, in particular. As soon as infection is confirmed, infected children are treated with the pyrimethamine-sulfonamide combination for 12 to 24 months. Recent multicenter studies show that postnatal treatment does not prevent ocular lesions: 5% of treated children had choroiditis lesions at birth, 20% at 5 years, and 30% at 8 years of age. Furthermore no consensus exists about the duration of postnatal treatment (3 months in Denmark versus 12 months in France). A multicenter randomized controlled trial is necessary to assess the efficacy of postnatal treatment and determine its duration. A surveillance system was set up in 2007 by the National Reference Center for Toxoplasmosis to determine the perinatal burden of this infection and to assess the national policy., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Toxoplasma gondii is a parasite of birds and mammals. Cats are the only definitive host and thus the only source of infective oocysts, but other mammals and birds can develop tissue cysts. Although feline infections are typically asymptomatic, infection during human pregnancy can cause severe disease in the fetus. Cat owners can reduce their pets' exposure risk by keeping all cats indoors and not feeding them raw meat. Humans usually become infected through ingestion of oocyst-contaminated soil and water, tissue cysts in undercooked meat, or congenitally. Because of their fastidious nature, the passing of non-infective oocysts, and the short duration of oocyst shedding, direct contact with cats is not thought to be a primary risk for human infection., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Toxoplasmosis is a parasitic zoonosis having worldwide distribution; it infects many human and animal populations and is produced by the parasite Toxoplasma gondii, this being of great importance in contagion of pregnant women since this zoonosis causes illness in the fetus through transplacental infection. A constant mother-foetus infection rate has traditionally been used. Nevertheless, there is evidence of a strong relationship between a mother's gestation week and the moment when a foetus becomes infected. This work describes congenital toxoplasmosis transmission dynamics by using an age-structured model taking a mother's gestational week into account. The model was adapted to a space-time model describing T. gondii dispersion through cats; this provided the amount of parasites in the environment depending on which a pregnant woman would become infected. Simulations were done, varying the amount of parasites and the pregnant mother-inoculum distance. Some parameters related to possible control measures were also varied. Important changes were found when comparing infected pregnant female population patterns, when a constant mother-fetus infection rate was used and when a dependent pregnancy week rate was used. This led to concluding that the gestation week in which the mothers became infected is fundamental in infection being transmitted to their fetuses.

We report the occurrence of congenital toxoplasmosis in three infants born to HIV infected women who had high anti-toxoplasma IgG and negative IgM during pregnancy. We briefly reviewed available literature and discussed the possible transmission mechanisms of congenital toxoplasmosis among HIV infected pregnant women. Serum samples were tested for Toxoplasma gondii IgM and IgG antibodies using commercial enzyme immunoassay and IgG-avidity tests. In the first case, fetal death occurred at 28th week of gestation. In the second case, congenital toxoplasmosis was diagnosis at 6th month of life; and in the third case, an HIV-infected newborn, congenital toxoplasmosis was asymptomatic. These cases point out to the possibility of enhanced maternal-fetal transmission of T. gondii infection by HIV-infected women chronically infected, which may have important public health consequences, considering that increasing frequency of HIV-infection has been observed among women of childbearing age around the world.

We report a preterm infant with congenital HIV-1, CMV, and toxoplasmosis coinfection, whose mother succumbed to probable cerebral toxoplasmosis. Despite repeated neuroimaging, retinal examinations and infant serologic tests, during the first 36 days of life, there was no evidence of congenital toxoplasmosis. However, subsequent tests showed cerebral calcifications, bilateral chorioretinitis, antitoxoplasma IgM antibody, and Toxoplasma gondii DNA in the cerebrospinal fluid by polymerase chain reaction.

Toxoplasma gondii is a highly ubiquitous and prevalent parasite. Despite the cat being the only definitive host, it is found in almost all geographical areas and warm blooded animals. Three routes of transmission are recognised: ingestion of oocysts shed by the cat, carnivory and congenital transmission. In natural populations, it is difficult to establish the relative importance of these routes. This paper reviews recent work in our laboratory which suggests that congenital transmission may be much more important than previously thought. Using PCR detection of the parasite, studies in sheep show that congenital transmission may occur in as many as 66% of pregnancies. Furthermore, in families of sheep on the same farm, exposed to the same sources of oocysts, significant divergent prevalences of Toxoplasma infection and abortion are found between different families. The data suggest that breeding from infected ewes increases the risk of subsequent abortion and infection in lambs. Congenital transmission rates in a natural population of mice were found to be 75%. Interestingly, congenital transmission rates in humans were measured at 19.8%. The results presented in these studies differ from those of other published studies and suggest that vertical transmission may be much more important than previously thought.

Toxoplasma gondii infection during pregnancy may cause severe consequences to the embryo. Current toxoplasmosis treatment for pregnant women is based on the administration of spiramycin or a drug combination as sulphadiazine-pyrimethamine-folinic acid (SPFA) in cases of confirmed fetal infection. However, these drugs are few tolerated and present many disadvantages due to their toxic effects to the host. The aim of this study was to evaluate the effectiveness of different treatments on the vertical transmission of T. gondii, including azithromycin, Artemisia annua infusion, spiramycin and SPFA in Calomys callosus as model of congenital toxoplasmosis. C. callosus females were perorally infected with 20 cysts of T. gondii ME49 strain at the day that a vaginal plug was observed (1st day of pregnancy - dop). Treatment with azithromycin, A. annua infusion, and spiramycin started at the 4th dop, while the treatment with SPFA started at the 14th dop. Placenta and embryonic tissues were collected for morphological and immunohistochemical analyses, mouse bioassay and PCR from the 15th to 20th dop. No morphological changes were seen in the placenta and embryonic tissues from females treated with azithromycin, spiramycin and SPFA, but embryonic atrophy was observed in animals treated with A. annua infusion. Parasites were found in the placenta and fetal (brain and liver) tissues of animals treated with SPFA, A. annua infusion and spiramycin, although the number of parasites was lower than in non-treated animals. Parasites were also observed in the placenta of animals treated with azithromycin, but not in their embryos. Bioassay and PCR results confirmed the immunohistochemical data. Also, bradyzoite immunostaining was observed only in placental and fetal tissues of animals treated with SPFA. In conclusion, the treatment with azithromycin showed to be more effective, since it was capable to inhibit the vertical transmission of T. gondii in this model of congenital toxoplasmosis.

Toxoplasma gondii's importance for humans refers mainly to primary infection during pregnancy, resulting in abortion/stillbirth or congenital toxoplasmosis. The authors sought to evaluate the current global status of T. gondii seroprevalence and its correlations with risk factors, environmental and socioeconomic parameters. Literature published during the last decade on toxoplasmosis seroprevalence, in women who were pregnant or of childbearing age, was retrieved. A total of 99 studies were eligible; a further 36 studies offered seroprevalence data from regions/countries for which no data on pregnancy/childbearing age were available. Foci of high prevalence exist in Latin America, parts of Eastern/Central Europe, the Middle East, parts of south-east Asia and Africa. Regional seroprevalence variations relate to individual subpopulations' religious and socioeconomic practices. A trend towards lower seroprevalence is observed in many European countries and the United States of America (USA). There is no obvious climate-related gradient, excluding North and Latin America. Immigration has affected local prevalence in certain countries. We further sought to recognise specific risk factors related to seropositivity; however, such risk factors are not reported systematically. Population awareness may affect recognition of said risks. Global toxoplasmosis seroprevalence is continuingly evolving, subject to regional socioeconomic parameters and population habits. Awareness of these seroprevalence trends, particularly in the case of women of childbearing age, may allow proper public health policies to be enforced, targeting in particular seronegative women of childbearing age in high seroprevalence areas.

The objective of the research was to test the hamster for a model of transmission of congenital toxoplasmosis. A non-invasive method for the diagnosis of pregnancy in hamsters was designed, with a specificity and a sensitivity of 70.2 and 94.7%, respectively (n=168). Of 32 females with a chronic toxoplasma infection, 3 transmitted Toxoplasma congenitally during their first pregnancy, but not during the subsequent pregnancy. Congenital transmission rates of infections initiated during pregnancy with 2 stages of 2 strains of Toxoplasma were in the range of 33 to 100% of the 76 females inoculated. Only 1 of 17 females transmitted the parasite exclusively via milk. It was concluded that the hamster is a promising species for a model of transmission of congenital toxoplasmosis.

Untreated acute toxoplasmosis among pregnant women can lead to serious sequelae among newborns, including neurological impairment and blindness. In Brazil, the risk of congenital toxoplasmosis (CTox) has not been fully evaluated. Our aim was to evaluate trends in acute toxoplasmosis prevalence from 1998-2005, the incidence of CTox and the rate of mother-to-child transmission (MTCT). A cross-sectional study was undertaken to dentify patients who fit the criteria for acute toxoplasmosis during pregnancy. Exposed newborns were included in a historical cohort, with a median follow-up time of 11 months, to establish definite diagnosis of CTox. Diagnoses for acute infection in pregnancy and CTox were based on European Research Network on Congenital Toxoplasmosis criteria. In 41,112 pregnant women, the prevalence of acute toxoplasmosis was 4.8/1,000 women. The birth prevalence of CTox was 0.6/1,000 newborns [95% confidence interval (CI): 0.4-0.9]. During the follow-up study, 12 additional cases were detected, increasing the CTox rate to 0.9/1,000 newborns (95% CI: 0.6-1.3). Among the 200 newborns exposed to Toxoplasma gondii,there were 37 babies presenting diagnostic criteria of CTox, leading to an MTCT rate of 18.5% (95% CI: 13.4-24.6%). The additional cases identified during follow-up reinforce the need for serological monitoring during the first year of life, even in the absence of evidence of congenital infection at birth.

Prevention of mother-to-child transmission of HIV and Toxoplasma dual infections in the immunocompromised patient remains a healthcare challenge. We report a case of congenital toxoplasmosis resulting from reactivation of latent infection in a severely immunodepressed HIV-infected pregnant woman, who had poor adherence to therapy; this case illustrates the difficulties encountered in management of such a rare condition.

The objective of this study was to refine the rat model of congenital toxoplasmosis. In Fischer rats we found that visualization of spermatozoa in vaginal exudates and the detection of at least 6g body weight increase between days 9 and 12 of pregnancy, allowed the diagnosis and timing of pregnancy with 60% specificity and 84% sensitivity. A dose of 10(4) Toxoplasma gondii bradyzoites or 10(2) T. gondii oocysts of the Prugniaud strain resulted in more than 50% of congenital infection of the rat litters. Transmission of T. gondii via lactation was not detected in rats inoculated with either bradyzoites or oocysts. Bioassays of 51 neonates born from mothers inoculated with bradyzoites (in tissue cysts) and 29 neonates from mothers inoculated with oocysts demonstrated that both liver and lungs can be used for the diagnosis of congenital transmission in this model.

This paper reviews clinical and asymptomatic Toxoplasma gondii infection in humans and other animals in the USA. Seroprevalence of T. gondii in humans and pigs is declining. Modes of transmission, epidemiology and environmental contamination with oocysts on land and sea are discussed.

Toxoplasmosis in pregnancy is usually subclinic or associated with non specific symptoms. Diagnosis and timing of infection are usually based on serological tests. In this short review we tried to summarize the serological patterns we can encounter and to discuss the interpretation of test results.

Toxoplasma gondii is one of the few pathogens that can cross the placenta. Frequency and severity of transmission vary with gestational age. While acquired toxoplasmosis is already well explored, the control of maternal-foetal transmission of the parasite remains almost unknown. This is partly due to inherent inadequacies of animal models. This review summarises the studies which have been undertaken and shows that the mouse is a valuable model despite obvious differences to the human case. The paramount role of the cellular immune response during primary infection has been consistently shown. Surprisingly, IFN-g has a dual role in this process. While its beneficial effects in the control of toxoplasmosis are well known, it also seems to have transmission-enhancing effects within the placenta and can also directly harm the developing foetus. This shows the importance of designing vaccines which protects both mother and foetus. Therefore, it is useful to study the mechanisms of natural resistance against transmission during a secondary infection. In this setting, the process is more complicated, involving cellular, but also humoral components of the immune system. In summary, even if the whole process is far from being elucidated, important insights have been gained so far which will help us to undertake rational vaccine research.

Various critical issues still surround the management of toxoplasmosis in pregnant women and neonates. Although the study of specific antibodies remains an essential parameter for diagnosing materno-fetal infection and establishing time of infection, the method needs to be carefully and critically reviewed due to the distinctive immunological sensitivity of the neonate. We began a retrospective epidemiological study of the pre-natal management of Toxoplasma gondii (TG) infection to evaluate the incidence of congenital toxoplasmosis in children in a southern Italian area (Sicily). 230 children born between 1999 and 2005 to mothers with TG infection during pregnancy enrolled in the G. Di Cristina Children's Hospital of Palermo. Retrospective analysis of the maternal sample established that 150 (65%) of the 230 infants enrolled in the study were born to a mother with probable infection, while the remaining 80 (35%) were born to a mother with definite infection. To date, the results of the neonatal follow-up programme have confirmed the diagnosis of congenital infection in 16 infants (7%); for 43%, diagnosis was made early due to the presence, at birth or in the first month of life, of specific anti-TG IgM. Sequelae were observed in 8/16 infected infants. Sequelae in infected born to mothers with infection in the third trimester opens up the problematic issue of which therapeutic approach to adopt for these women: even without consensus support, a combined regimen of Pyrimethamine-Sulfadiazine could be advocated, even in the absence of prenatal diagnosis. Currently, the best diagnostic strategy involves the sequential or contemporaneous combination of more than one of the currently available methods, as no method on its own can ensure an appropriate level of accuracy.

Toxoplasmosis is a serious disease in humans where it can cause abortion or congenital infection if a women is exposed to disease for the first time during pregnancy. Infection prior to pregnancy normally results in immunity and which is capable of protecting the foetus. Similar observations have been made in the BALB/c mouse indicating the potential of mice for studying congenital disease. Consequently, the mouse has been used to study how mammals balance the opposing needs of maintaining an immunological environment conducive to successful pregnancy while attempting to control a dangerous pathogen. Moreover the mouse has proven useful for testing the potential of a number of vaccine candidates and adjuvants for their ability to prevent congenital infection and/or reduce foetal death and abortion.

The mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. The prenatal and early postnatal diagnosis can only be achieved by serological testing. Serologic tests have different sensitivities, specificities and complexities, so that different tests in more than one blood sample are necessary for the diagnosis. Serological follow-up of the infants should be conducted during the first year of life or until the diagnosis of congenital toxoplasmosis can be ruled out. Treatment recommendations try to reduce the transmission rate and the risk of congenital damage. Congenital toxoplasmosis incidence rate is approximately 5 per 1000 births, but can be reduced to 0.5 per 1000 with an active screening program. The aim of this consensus group was to review the scientific literature on congenital toxoplasmosis and prepare a statement on prevention, diagnosis and treatment that should be implemented in our country.

The first aim of this study was to determine the prevalence of congenital toxoplasmosis in newborn infants treated by the public health system in Porto Alegre, a city in southern Brazil, using neonatal screening for Toxoplasma gondii-specific IgM. The second aim was to investigate whether the cases detected by this approach could have been identified by the prenatal screening for antibodies to T. gondii that was performed in the same population. A fluorometric assay was used to analyse T. gondii-specific IgM in filter paper specimens obtained from newborn infants for routine screening for metabolic diseases. When the specific IgM was positive, serum samples from the infant and the mother were requested for confirmatory serological testing, and the infant underwent clinical examination. Among 10 000 infants screened for T. gondii-specific IgM, seven filter paper samples were positive, and congenital toxoplasmosis was confirmed in six patients. The prevalence of IgM specific for T. gondii was 6/10 000 [95% CI 2/10 000, 13/10 000]. One infected infant had already been identified in the maternity ward before birth, three had been identified by maternal serology at delivery, and two infants with congenital toxoplasmosis were identified solely through neonatal screening. Although four mothers of the patients with congenital toxoplasmosis received prenatal care, and three mothers had one or two serological tests for T. gondii-specific antibodies (one at first trimester, one at first and second trimesters, and the other at second and third trimesters), they were not identified during pregnancy as infected. Neonatal screening identified cases of infection not detected by obtaining only one or two serum samples from pregnant women for T. gondii serology, mainly when infection was acquired and transmitted in late pregnancy. Maternal serology at delivery and neonatal screening were especially useful in the identification of infants with congenital toxoplasmosis when the mother did not receive regular prenatal serological testing or prenatal care.

Infections with Toxoplasma gondii occur worldwide, but are especially prevalent in Europe, South America and Africa. The primary problem for the diagnosis of T. gondii infection is long-lasting IgM-antibodies, thus the presence of T. gondii-specific IgM-antibodies do not necessarily indicate an acute infection. The use of a Toxoplasma-specific IgG-avidity ratio, differentiated Western blots and two-dimensional immunoblots usually resolves diagnostic problems. There is no consensus on the best strategy to control congenital toxoplasmosis. Recent European prospective, but descriptive, studies including a meta-analysis of existing cohorts have found a surprisingly small effect on maternal-fetal transmission and clinical signs in children treated for T. gondii infection diagnosed by pre- and neonatal screening programmes. No randomised studies exist on the treatment of T. gondii infection in pregnant women and newborn children with congenital toxoplasmosis. Atovaquone is the most promising new drug available, but is not yet approved for use in pregnant women and small children.

Infection with Toxoplasma gondii is transmitted to man by infected meat or meat products and by contact with soil or surface water. In theory, prevention by hygienic measures is possible, but this has never been proved to work in practice. Therefore, pre- and postnatal screening has been implemented in several countries aiming at early diagnosis. However, data on the effect of treatment are limited and no randomized, controlled trials have been performed. The risk of T. gondii infection in Europe is declining and studies using historical controls from earlier decades cannot be used for decision making. The screening of pregnant women or neonates makes the assumption that any children diagnosed can be offered an effective treatment. There is an urgent need to test new drugs and demonstrate, using randomized, controlled trials, that the currently used drugs are effective.