Ocular Outcome of Brazilian Patients With Congenital Toxoplasmosis.

BACKGROUND: Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis. We aimed to describe the ocular outcome and factors that may influence the visual prognosis of these patients. METHODS: Cohort of patients with confirmed congenital toxoplasmosis seen between 1996 and 2017 in Porto Alegre, southern Brazil. RESULTS: Seventy-seven patients were included, of which 65 (85.5%) were identified by routine screening. Median age at the end of the follow-up was 10 years (minimum 2, maximum 25). Retinochoroiditis was present in 55 patients (71.4%). New retinochoroidal lesions developed after the first year of life in 77.8% of the patients who began treatment after the fourth month of life, compared with 35.2% among those treated before 4 months of life (relative risk = 0.45, 95% confidence intervals: 0.27-0.75, P = 0.02) and 33.3% among those treated before 2 months of life (relative risk = 0.42, 95% confidence intervals: 0.25-0.72, P = 0.01). There was a peak incidence of new retinochoroidal lesions between 4 and 5 years and another peak between 9 and 14 years, the latter only among girls. Thirty-four patients with retinochoroiditis were followed up for 10 years or more, and the school performance was appropriate in 28 (82.4%). CONCLUSIONS: The high incidence of new retinochoroidal lesions during the follow-up period indicates the importance of long-term follow-up of patients with congenital toxoplasmosis. Initiating treatment within the first 4 months of life, especially within the first 2 months, was a protective factor against the later development of retinochoroiditis. Despite the usual favorable prognosis, the high morbidity of congenital toxoplasmosis in Brazil was confirmed.

Visual Outcomes in Presumed Congenital Foveal Toxoplasmosis.

PURPOSE: Congenital macular lesions attributed to toxoplasmosis may limit potential visual acuity. The appearance and location of these scars may cause physicians to overlook associated amblyopia. This study reviews the visual outcomes and benefits of amblyopia therapy in children with foveal toxoplasmosis scars. DESIGN: Retrospective observational case series. METHODS: Setting: Single center. PATIENT POPULATION: Children with presumed foveal toxoplasmosis scars who underwent amblyopia treatment. MAIN OUTCOME MEASURE: Charts were reviewed for amblyopia treatment, fundus photographs, optical coherence tomography (OCT), and visual acuity. RESULTS: Median age at presentation was 2.8 years and median follow-up was 6.2 years. Occlusion therapy was undertaken in 9 patients. Median duration of occlusion therapy was 1.7 years. Six patients improved with occlusion therapy (average 4.6 lines gained on optotype acuity). Final visual acuity ranged from 20/25 to 20/250, with 6 of 8 patients better than 20/80. OCT confirmed macular scars in 5 patients, with varying degrees of foveal architecture disruption. CONCLUSION: Despite the striking appearance of the lesions in patients with presumed foveal toxoplasmosis, visual potential may be better than expected. The appearance of the lesions is not always predictive of visual outcome. A trial of occlusion therapy to treat amblyopia should be initiated in these patients to ensure that they reach their maximal visual potential.

Effect of congenital toxoplasmosis on the encoding of speech in infants.

OBJECTIVE: To investigate the effect of congenital toxoplasmosis (CTP) on the Frequency-Following Response (FFR) in infants. STUDY DESIGN: 11 infants diagnosed with CTP and 12 healthy infants with no risk indicators for hearing impairment, aged 29-90 days old. All infants underwent an FFR neurophysiological assessment. The test stimulus was the syllable [da], 40 ms in duration, which was monaurally presented to the right ear at an intensity of 80 dBnHL. Absolute latencies and amplitudes of the V, A, C, D, E, F, and O waves, the slope (µV/ms) and measure between onset (A) and offset (O), were compared between the two groups. RESULTS: Infants with CTP had increased latency of FFR waves V, A, E, F, and O, and decreased amplitude for waves A and F. They also showed a reduction in A-O slope and a higher latency difference between onset (A) and offset (O). CONCLUSION: The neurophysiological responses of Frequency-Following Response can be influenced by congenital toxoplasmosis. Since, the CTP showed prolongation of the V, A, E, F and O waves and decrease of the amplitude for waves A and F.

Study of brainstem auditory evoked potentials in early diagnosis of congenital toxoplasmosis / Estudo dos potenciais auditivos de tronco encefálico na toxoplasmose congênita diagnosticada precocemente

Abstract Introduction: Congenital toxoplasmosis is an infectious disease with high prevalence in tropical countries. It is characterized by neurological, ophthalmological and auditory sequelae. Objective: The aim of this study was to evaluate and describe the brainstem auditory evoked potential in infants aged 1-3 months diagnosed with congenital toxoplasmosis and to compare them with infants of the same age group without the infection. Methods: This is an observational, analytical and cross-sectional study in which brainstem auditory evoked potential was investigated in infants with congenital toxoplasmosis. The following audiological exams were performed: transient-evoked otoacoustic emissions, clinical and automatic brainstem auditory evoked potential. Results: 100 children participated in the study, but the final sample consisted of 76 children. Of the 37 children with toxoplasmosis included in the study, 28 completed the neurological imaging evaluation, and of these, 3 (10.7%) showed an altered neurological examination. At the brainstem auditory evoked potential assessment, two children without toxoplasmosis and 10 children with congenital toxoplasmosis had results suggestive of alterations in the brainstem auditory pathway maturation. Conclusion: 10 (27%) children were identified with a possible unilateral alteration in the electrophysiological assessment. There was a 5-fold higher risk for a child between 1 and 3 months of age with toxoplasmosis to have an altered brainstem auditory evoked potential compared to a child of the same age range without the infection.

Resumo Introdução: A toxoplasmose congênita é uma doença infecciosa com grande prevalência nos países tropicais. Caracteriza-se por sequelas neurológicas, oftalmológicas e auditivas. Objetivo: O objetivo desse estudo foi avaliar e descrever o potencial evocado auditivo de tronco encefálico em bebês de 1 a 3 meses diagnosticados com toxoplasmose congênita e comparar com bebês de mesma faixa etária sem a infecção. Metódo: Trata-se de um estudo observacional, analítico e transversal, no qual foi realizada a pesquisa do potencial evocado auditivo de tronco cerebral em lactentes com toxoplasmose congênita. Foram realizados os exames audiológicos: emissões otoacústicas evocadas por estímulo transiente, potencial auditivo de tronco encefálico clínico e automático. Resultados: Participaram do estudo 100 crianças, porém a amostra final foi constituída por 76. Das 37 crianças com toxoplasmose incluídas no estudo, 28 completaram a avaliação neurológica de imagem e, dessas, três (10,7%) apresentaram exame neurológico alterado. Na avaliação do potencial evocado auditivo de tronco encefálico, duas crianças sem toxoplasmose e 10 com toxoplasmose congênita apresentaram resultado sugestivo de alteração no processo maturacional da via auditiva de tronco encefálico. Conclusão: Foram identificadas 10 (27%) crianças com possível alteração unilateral na avaliação eletrofisiológica e um risco cinco vezes maior de uma criança entre um e três meses com toxoplasmose apresentar alteração no potencial evocado auditivo de tronco encefálico quando comparada com uma criança da mesma faixa de idade sem a infecção.

Study of brainstem auditory evoked potentials in early diagnosis of congenital toxoplasmosis.

INTRODUCTION: Congenital toxoplasmosis is an infectious disease with high prevalence in tropical countries. It is characterized by neurological, ophthalmological and auditory sequelae. OBJECTIVE: The aim of this study was to evaluate and describe the brainstem auditory evoked potential in infants aged 1-3 months diagnosed with congenital toxoplasmosis and to compare them with infants of the same age group without the infection. METHODS: This is an observational, analytical and cross-sectional study in which brainstem auditory evoked potential was investigated in infants with congenital toxoplasmosis. The following audiological exams were performed: transient-evoked otoacoustic emissions, clinical and automatic brainstem auditory evoked potential. RESULTS: 100 children participated in the study, but the final sample consisted of 76 children. Of the 37 children with toxoplasmosis included in the study, 28 completed the neurological imaging evaluation, and of these, 3 (10.7%) showed an altered neurological examination. At the brainstem auditory evoked potential assessment, two children without toxoplasmosis and 10 children with congenital toxoplasmosis had results suggestive of alterations in the brainstem auditory pathway maturation. CONCLUSION: 10 (27%) children were identified with a possible unilateral alteration in the electrophysiological assessment. There was a 5-fold higher risk for a child between 1 and 3 months of age with toxoplasmosis to have an altered brainstem auditory evoked potential compared to a child of the same age range without the infection.

Congenital Toxoplasmosis: A Review.

Acute infection of toxoplasmosis during pregnancy is detrimental to the developing fetus. In the United States, approximately 1 in 10,000 live births are affected by congenital toxoplasmosis. Although multifactorial in etiology, maternal infection is primarily attributed to the consumption of contaminated meat or water. Infection and transmission to the fetus may result in devastating neurologic impairment. Screening methods for all pregnant women should be implemented in routine prenatal care. This article will highlight the inherent dangers of congenital toxoplasmosis, while including general care of the fetus for prevention of transmission, medical management, and long-term outcomes.

Functional echocardiography in the fetus with non-cardiac disease.

We describe the hemodynamic changes observed in fetuses with extra cardiac conditions such as intrauterine growth restriction, tumors, twin-twin transfusion syndrome, congenital infections, and in fetuses of mothers with diabetes. In most fetuses with mild extra cardiac disease, the alterations in fetal cardiac function remain subclinical. Cardiac function assessment has however helped us to achieve a better understanding of the pathophysiology of these diseases. In fetuses at the more severe end of the disease spectrum, functional echocardiography may help in guiding clinical decision-making regarding the need for either delivery or fetal therapy. The growth-restricted fetus represents a special indication for routine cardiac function assessment, as in utero hemodynamic changes may help optimize the timing of delivery. Moreover, in intrauterine growth restriction, the altered hemodynamics causes cardiovascular remodeling, which can result in an increased risk of postnatal cardiovascular disease.

Toxoplasma gondii: the effects of infection at different stages of pregnancy on the offspring of mice.

Congenital toxoplasmosis can cause fetal damage in humans and domestic animals. This study was focused on the effects of Toxoplasma gondii (Prugniaud strain) infection at different stages of pregnancy on the offspring of mice. Results showed that newborn mice from all infected groups were significantly lower in weight than those from the control group but significant difference was not found among these groups at day 60 after birth. The survival rate of the offspring from the group of mice infected at the earlier stage of pregnancy was significantly lower than those of infected and control groups. The positive offspring (with cysts found in their brain tissues) born from the mice infected at the earlier and intermediate stages of pregnancy showed a shorter latency and greater number of errors in the step-through passive avoidance test than those born from the mice infected at the late stage of pregnancy, the control group and the negative offspring from the infected groups. The number of cysts in the brain tissue was significantly higher in the offspring born from the groups of mice infected at the earlier and intermediate stages of pregnancy than those from the group of mice infected at the late stage of pregnancy. In addition, our results indicated that a high congenital transmission rate (90%) occurred in this NIH mouse model. In conclusion, the earlier and intermediate maternal infection of T. gondii can result in severe congenital toxoplasmosis, exhibiting conditions such as stillbirth or non-viability, and learning or memory capability damage in this mouse model. These results not only provide useful data for better understanding the effects of T. gondii infection on the offspring of mice infected at different stages of pregnancy but also for better consideration of the effect of this infection on other mammalian hosts including humans.

Longer pregnancy and slower fetal development in women with latent "asymptomatic" toxoplasmosis.

BACKGROUND: The purpose of this study was to confirm that women with latent toxoplasmosis have developmentally younger fetuses at estimated pregnancy week 16 and to test four exclusive hypotheses that could explain the observed data. METHODS: In the present retrospective cohort study we analysed by the GLM (general linear model) method data from 730 Toxoplasma-free and 185 Toxoplasma-infected pregnant women. RESULTS: At pregnancy week 16 estimated from the date of the last menstruation, the mothers with latent toxoplasmosis had developmentally younger fetuses based on ultrasound scan (P = 0.014). Pregnancy of Toxoplasma-positive compared to Toxoplasma-negative women was by about 1.3 days longer, as estimated both from the date of the last menstruation (P = 0.015) and by ultrasonography (P = 0.025). CONCLUSION: The most parsimonious explanation for the observed data is retarded fetal growth during the first weeks of pregnancy in Toxoplasma-positive women. The phenomenon was only detectable in multiparous women, suggesting that the immune system may play some role in it.

Cellular and molecular physiopathology of congenital toxoplasmosis: the dual role of IFN-gamma.

Toxoplasma gondii is one of the few pathogens that can cross the placenta. Frequency and severity of transmission vary with gestational age. While the control of acquired toxoplasmosis is already well explored, the control of materno-foetal transmission of the parasite remains almost unknown. This is partly due to the lack of an animal model to study this process. 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 has been shown by several experiments. However, IFN-gamma 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 and can also directly harm the developing foetus. The ultimate goal of these studies is to develop a vaccine 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 both cellular and 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.

Risk of visual impairment in children with congenital toxoplasmic retinochoroiditis.

PURPOSE: Reliable information is needed to counsel parents of children with congenital toxoplasmosis regarding the long-term risk of visual impairment resulting from ocular toxoplasmosis. DESIGN: Prospective cohort study of children with congenital toxoplasmosis identified by prenatal or neonatal screening. METHODS: After three years of age, ophthalmologists reported the site of retinochoroidal lesions and visual acuity and parents reported visual impairment. An ophthalmologist predicted the child's vision based on the last retinal diagram. Selection biases were minimized by prospective enrollment and data collection, high rates of follow-up, and exclusion of referred cases. RESULTS: Two hundred and eighty-one of 284 infected children who underwent ophthalmic examinations were followed up to a median age of 4.8 years. One in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole. In children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23). Analyses based on affected eyes showed that 42% (29/69) had a posterior pole lesion, of which just more than half (15/29, 52%) had normal vision, as did 84% (16/19) of eyes with a peripheral lesion alone. Vision predicted by the ophthalmologist was moderately sensitive (59%) but overestimated impairment associated with posterior pole lesions. Of 44 children with information on acuity, four (9%) had bilateral visual impairment worse than 6/12 Snellen. CONCLUSIONS: Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye.

[Study on the development of fetus and infant congenitally infected by Toxoplasma gondii and intervention].

Toxoplasma gondii infection during pregnancy can result in abortion, premature delivery, fetal death, deformity, and impact the physical and intellectual development of the newborns. This is an investigation on the consequences of pregnancy in Toxoplasma gondii-infected women, the development of their babies, and the effect of pyrimethamine treatment during 1990-1996 in Baoding City.

Toxoplasmose congênita / Congenital toxoplasmosis

Toxoplasmose é causada por infecção pelo parasita protozoário Toxoplasma gondii. Foram revisados aspectos da fisiopatologia da toxoplasmose congênita. As manifestações da toxoplasmose congênita no feto ou neonato são imprevisíveis, variando desde o óbito intra-uterino, retardo mental, convulsões, cegueira, hidrocefalia e coriorretinite até lesões menos severas, em que as manifestações da toxoplasmose congênita podem não ser aparentes até a segunda ou terceira décadas de vida. Testes sorológicos são utilizados para o diagnóstico da infecção aguda na gestante e na criança. A terapêutica mais utilizada e, provavelmente, mais efetiva é a combinação de pirimetamina, sulfadiazina e ácido folínico.

Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii. Some aspects of the physiopathology of the congenital toxoplasmosis were revised. Manifestations of congenital toxoplasmosis in the fetus and the newborn are unpredictable. They range from intra-uterine death, mental retardation, seizures, blindness, hydrocephalia and chorioretinitis to less severe lesions in which manifestations of congenital toxoplasmosis may not become apparent until the second or third decades of life. Serological tests are used to diagnose acute infection in pregnant women or in children. The most commonly used therapeutic regimen, and probably the most effective, is the combination of pyrimethamine with sulfadiazine and folinic acid.

Usefulness of quantitative polymerase chain reaction in amniotic fluid as early prognostic marker of fetal infection with Toxoplasma gondii.

OBJECTIVE: Our purpose was to evaluate Toxoplasma gondii concentration in amniotic fluid (AF) samples as a prognostic marker of congenital toxoplasmosis. STUDY DESIGN: A retrospective study was carried out in 88 consecutive AF samples from 86 pregnant women, which were found positive by prospective polymerase chain reaction (PCR) testing. Parasite AF concentrations were estimated by real-time quantitative PCR and analyzed in relation to the clinical outcome of infected fetuses during pregnancy and at birth, taking into account the gestational age at maternal infection. RESULTS: A significant negative linear regression was observed between gestational age at maternal infection and T gondii DNA loads in AF. After adjusting for time at maternal seroconversion by multivariate analysis, higher parasite concentrations were significantly associated with a severe outcome of congenital infection (odds ratio [OR]=15.38/log (parasites/mL AF) [95% CI=2.45-97.7]). CONCLUSION: PCR quantification of T gondii in AF can be highly contributive for early prognosis of congenital toxoplasmosis. Maternal infections acquired before 20 weeks with a parasite load greater than 100/mL of AF have the highest risk of severe fetal outcome.

Precocious puberty: an endocrine manifestation in congenital toxoplasmosis.

We reviewed retrospectively seven children with congenital toxoplasmosis and precocious puberty. All seven showed very high levels of LH (25.2-155.0 IU/ml) and FSH (7.1-38.2) upon stimulation with GnRH. Three of them showed low GH response to an insulin tolerance test. All the children had severe mental retardation. We emphasize that children with congenital toxoplasmosis should have their hypothalamopituitary function evaluated even in subclinical situations that could be responsible for endocrinological disturbances such as precocious puberty.

Effect of Toxoplasma gondii infection kinetics on trophoblast cell population in Calomys callosus, a model of congenital toxoplasmosis.

This work evaluated the kinetics of events that occur in the placenta of Calomys callosus after Toxoplasma gondii infection. Animals on the first day of pregnancy (dop) and virgin nonpregnant females were perorally infected with 20 cysts of T. gondii strain ME49. After 100 days of infection, the virgin animals were mated and received an additional 20 cysts on the first dop. The placentas and the embryos from both acutely and chronically infected animals were analyzed up to day 20 of pregnancy by morphological and immunocytochemical assays. Noninfected and infected animals exhibited placenta with normal morphology. From the seventh dop and infection onwards, liver and spleen cells of the infected animals contained several parasitophorous vacuoles. On the 13th day, the maternal blood present at the placental blood spaces contained T. gondii-infected leukocytes. Infected placental cells were only seen on the 15th dop, being the trophoblast giant cells, the first cell type to contain signs of the parasite internalization, followed by labyrinth zone cells 24 h later and spongiotrophoblast cells only after the 19th dop. Fetal liver and brain were infected by T. gondii concomitantly to the labyrinth cell infection. No signals of infection were observed on placentas and embryos from chronically infected animals. Therefore, considering the sequence of events leading to the infection of the various organs, it could be hypothesized that the placenta is infected later on during pregnancy, which may be related to the defense roles played by this structure. However, trophoblast giant cells are unable to completely stop the progression of T. gondii infection towards the fetal tissues. C. callosus was demonstrated to be a suitable experimental model to study the dynamics of congenital toxoplasmosis.

[Prevention of congenital toxoplasmosis in France. Risk assessment. Results and perspectives of prenatal screening and newborn follow up]. / La prévention de la toxoplasmose congénitale en France. Evaluation des risques. Résultats et perspectives du dépistage anténatal et du suivi du nouveau-né.

In France, a national program for the prevention of congenital toxoplasmosis has been set up 25 years ago. This program is here presented and discussed in details. It is based on a decision tree well defined, with pre and/or per gravidic serological screening with several different tests, completed, if necessary, by ultrasounds examinations of the fetus, biomolecular tests (PCR) on amniotic fluid, and by clinical, biological, and radiological surveillance of neo-nates. The purpose of this prevention program is to: 1/identify nonimmune young women and limit their contamination risk during pregnancy by appropriate counseling on hygiene and diet; 2/screen and treat per gravidic toxoplasmosis as early as possible so as to prevent or limit transmission to the fetus and its consequences. 3/in utero diagnose and treat infestation of the fetus; 4/diagnose and treat asymptomatic congenital toxoplasmosis in neonates, to prevent risks of reactivation and late complications, especially ocular. Such a prevention program has a cost validated by the prevalence of acquired toxoplasmosis in adults in France (over 50% of the population) and by the yearly incidence of congenital toxoplasmosis (at least 0.1% of births according to the best hypothesis). These 6 to 700 congenital toxoplasmosis cases per year may be compared to the 6 to 7,000 per gravidic seroconversions which could lead to fetal contamination if no preventive measures are taken. Nevertheless, as it is often the case in the field of prevention, it is very difficult to statistically assess the efficacy of this program even though several arguments show that it allows to eliminate the most serious toxoplasmosis, sources of serious handicaps at birth, and to limit the frequency of late complications (especially retino-choroiditis) of asymptomatic infections in neonates. The position of European countries varies as to prevention of congenital toxoplasmosis. Some countries (Austria, Belgium) have national prevention programs similar to the French one, whereas others have set up only limited programs or set up no systematic prevention. These differences may be accounted for by the different frequencies of toxoplasmic risk. It seems mandatory to forget all dogmatism and not to stick to a strictly statistical approach for a disease with not only medical but also social and human consequences.

Bax-induced apoptosis not demonstrated in the congenital toxoplasmosis in mice.

A prominent neuropathological change observed in a murine model of congenital toxoplasmosis is cerebral cortical hypoplasia. In the early embryonic life of toxoplasmosis mice, the number of apoptotic cell observed in cerebral cortex is increased, indicating that increased number of apoptotic cells might relate to the pathogenetic mechanism of the cortical hypoplasia. Immunohistochemical expression of apoptosis-related factors, Bcl-2 and Bax has been studied in fetal murine brains infected with toxoplasma and in controls. Paraffin sections of the fetal brains on embryonic day (ED) 10, 12, 14, 16 and 18 were applied for the immunostains of Bcl-2 and Bax. Totally, 47 experimental animals (ED10: n=8, ED12: n=6, ED14: n=12, ED16: n=6, ED18: n=15) and 48 control animals (ED10: n=6, ED12: n=8, ED14: n=9, ED16: n=9, ED18: n=16) were examined. Bcl-2 positive cells were detected on ED10, whereas Bax positive cells appeared on ED14. No difference of Bcl-2 and Bax expression between toxoplasmosis and control groups was detected, suggesting that there is no clear relation between Bax-induced apoptosis and cortical dysplasia in congenital toxoplasmosis.