Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

BACKGROUND: We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. CASE PRESENTATION: A two-month-old male had a twin in utero who disappeared between the 7th and the 14th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. CONCLUSIONS: We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Prognosis of Fetal Parenchymal Cerebral Lesions without Ventriculomegaly in Congenital Toxoplasmosis Infection.

OBJECTIVE: To evaluate the neurodevelopmental and ocular outcome of a continuous retrospective series of fetal toxoplasmosis infections for which prenatal ultrasound (US) follow-up revealed abnormal cerebral findings without associated ventriculomegaly. MATERIALS AND METHODS: We retrospectively reviewed all cases of proven fetal Toxoplasma gondii infection with fetal cerebral anomalies at US examination without significant ventriculomegaly (≥10 mm) evaluated in our center over a 5-year period. US and magnetic resonance imaging findings were collected. The neurodevelopmental and ocular outcomes of the cases were studied. RESULTS: Nine fetuses were included. Hyperechogenic foci of the cerebral parenchyma were isolated in five cases. Among those, four children had normal neurological development. Amblyopia was detected in on case. Hyperechogenic foci were associated with other anomalies of cerebral parenchyma in three cases among which two children had normal neurological development. Termination of pregnancy was performed in three cases: one case within the context of severe maternal schizophrenia with isolated hyperechogenic foci, one case where hyperechogenic foci were associated with extensive lesions of the white matter, and one case for severe fetal hydrops. CONCLUSION: The neurological prognosis of cerebral hyperechogenic lesions without ventriculomegaly in fetal toxoplasmosis infection may be favorable. The risk of ocular damage however remains high and unpredictable in the prenatal period.

[DRESS complicated by hemophagocytic lymphohistiocytosis in an infant treated for congenital toxoplasmosis]. / DRESS compliqué d'un syndrome d'activation macrophagique chez un nourrisson traité pour une toxoplasmose congénitale.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe disease that may be complicated by hemophagocytic lymphohistiocytosis but this is rarely described in children. PATIENTS AND METHODS: We report the case of a 5-week old infant hospitalized in a pediatric intensive care unit for hemophagocytic lymphohistiocytosis with prolonged fever, splenomegaly, cytopenia, fibrinogen≤1.5g/L, ferritin≥500µg/L, and soluble IL-2 receptor≥2400U/mL. As a result of the presence of a diffuse skin rash, eosinophilia and multiple organ failure that started three weeks after the initiation of a congenital toxoplasmosis treatment, association with DRESS was suggested. DISCUSSION: Exposure to sulfadiazine remains the main factor leading to DRESS in this case. This is probably the trigger event, secondarily complicated by hemophagocytic lymphohistiocytosis, although in our case the diagnosis was made subsequently. The unfortunately poor outcome of this association is probably exacerbated in fragile patients such as young infants. CONCLUSION: Clinicians should be aware of the possibility of DRESS of every early onset associated with hemophagocytic lymphohistiocytosis linked to a treatment started during the neonatal period to avoid any delay in care that might adversely affect the prognosis.

Patterns of Hydrocephalus Caused by Congenital Toxoplasma gondii Infection Associate With Parasite Genetics.

Four anatomical patterns of hydrocephalus secondary to congenital Toxoplasma gondii infection were identified and characterized for infants enrolled in the National Collaborative Chicago-based Congenital Toxoplasmosis Study. Analysis of parasite serotype revealed that different anatomical patterns associate with Type-II vs Not-Exclusively Type-II strains (NE-II) (P = .035).

Toxoplasmosis and pregnancy.

Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most Canadians? Answer Low prevalence of the infection, high cost associated with testing, low sensitivity of screening tests, false-positive test results, and limitations of treatment effectiveness are all cited as reasons for not routinely screening for T gondii infection in Canada. Currently, screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region. Congenital toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies.

[Congenital toxoplasmosis with ocular involvment--case report]. / Toxoplasmoza Folezz congenitala (afectare oftalmologica)--caz clinic.

Two thirds of the congenital toxoplasmosis cases describe minimal or inapparent symptoms present at birth, being diagnosed from a psychomotor retard. The forms of chorioretinitis may be described by repeated outbursts in the first years of life. Chorioretinitis or focal necrotizing retinitis usually develops in a bilateral way, being progressive and leading to blindness. Usually there is only one focal inflammatory beginning at the edge of a pigmented scar and the local inflammatory process may extend through successive spikes in other regions of the retina. Active chorioretinitis is expressed clinically by a blurred misty eyesight, with the advent of scotomas, photophobia, and if the macula is involved, the loss of the central eyesight may occur. In this paper I present the patient R.A., 6 years old from Constanta who is hospitalized in the Clinic of Infectious Diseases for investigations and treatment continuity because positive IgG Toxoplasma was previously found. The child has spastic quadriplegia and profound mental retardation.

Congenital Toxoplasmosis and Long-term Outcomes

Objective: Congenital toxoplasmosis (CT) can have severe early and late sequelae in children. In this study, we aimed to evaluate the demographic, clinical, treatment characteristics of patients diagnosed with congenital Toxoplasma infection and to highlight the long-term complications of the patients. Methods: Patients with CT were included in this study who were followed between 2010 and 2022 in Cukurova University Medical Faculty Hospital. Demographic, clinical and treatment characteristics were searched retrospectively. In the diagnosis of maternal and CT, Toxoplasma IgM, IgG, IgG avidity, T. gondii polymerase chain reaction tests were used along with clinical and symptoms. Results: Eighteen children (two twins) with CT and their mothers (n=16) were included in the study. Median age was 1 month. Ten (55.5%) of the children were male. CT diagnosis was made during pregnancy in 7 mothers (resulting in 8 babies) and postnatally in 9 mothers (resulting in 10 babies). The mothers of 5 (31.1%) babies with CT received spiramycin treatment during pregnancy. Three (60%) of 5 pregnant women who received spiramycin were diagnosed in the first trimester, 4 (80%) of the babies did not have any sequale and only 1 (20%) had microphthalmia. Ocular involvement was the most common presentation of the disease occured in 10 patients (55.5%), hydrocephalus and intracranial calcification developed in five patients (27.7%). Hearing loss developed in 2 (11.1%) patients. During the follow-up period, seizures developed in 3 patients (16.6%), microcephaly in 2 patients (11.1%), and neurodevolopmental retardation in 7 patients (38.8%), two of the patients had severe mental retardation. One (5.5%) patient with hydrocephalus died at 36 months of age due to complications after ventriculoperitoneal shunt application. Conclusion: In our study, we observed severe sequelae in vision, hearing, and neurodevelopmental aspects in children diagnosed with CT at birth and during follow-ups. Early diagnosis and treatment of infants, along with the detection of Toxoplasma infection during pregnancy, are essential in preventing severe sequelae that may arise due to CT.

The global burden of congenital toxoplasmosis: a systematic review.

OBJECTIVE: To estimate the global burden of congenital toxoplasmosis (CT), which results from infection of pregnant women with Toxoplasma gondii. METHODS: The authors systematically searched 9 major databases for published and unpublished sources and established direct contact with the authors of source materials. Searches were country-specific. To be included, studies had to report on the incidence of CT, on positivity to Toxoplasma-specific IgM in infants and pregnant women (including seroconversion results) or on positivity to Toxoplasma-specific IgG in the general population. Various modelling techniques were used, depending on the country-specific data available, to estimate the CT incidence and burden in each country. These data were then synthesized into an estimate of the global incidence of CT and of the global burden of CT in disability-adjusted life years (DALYs). FINDINGS: The global annual incidence of congenital toxoplasmosis was estimated to be 190,100 cases (95% credible interval, CI: 179,300-206,300). This was equivalent to a burden of 1.20 million DALYs (95% CI: 0.76-1.90). High burdens were seen in South America and in some Middle Eastern and low-income countries. CONCLUSION: Congenital toxoplasmosis poses a substantial burden of poor health globally. Toxoplasmosis should be included in future updates of the global burden of disease and the corresponding data should be used to support public health interventions to reduce disease burden.

A pilot study using residual newborn dried blood spots to assess the potential role of cytomegalovirus and Toxoplasma gondii in the etiology of congenital hydrocephalus.

BACKGROUND: Congenital hydrocephalus is a condition characterized by accumulation of cerebrospinal fluid in the ventricles of the brain. Prenatal infections are risk factors for some birth defects. This pilot study investigated whether residual dried blood spots (DBS) could be used to assess infections as risk factors for birth defects by examining the associations between prenatal infection with Toxoplasma gondii (T. gondii) or cytomegalovirus (CMV) with congenital hydrocephalus. METHODS: Case-infants with hydrocephalus (N=410) were identified among live-born infants using birth defects surveillance systems in California, North Carolina, and Texas. Control-infants without birth defects were randomly selected from the same geographic areas and time periods as case-infants (N=448). We tested residual DBS from case- and control-infants for T. gondii immunoglobulin M and CMV DNA. When possible, we calculated crude odds ratios (cORs) and confidence intervals (CIs). RESULTS: Evidence for prenatal T. gondii infection was more common among case-infants (1.2%) than control-infants (0%; p=0.11), and evidence for prenatal CMV infection was higher among case-infants (1.5%) than control-infants (0.7%; cOR: 2.3; 95% CI: 0.48, 13.99). CONCLUSIONS: Prenatal infections with T. gondii and CMV occurred more often among infants with congenital hydrocephalus than control-infants, although differences were not statistically significant. This pilot study highlighted some challenges in using DBS to examine associations between certain infections and birth defects, particularly related to reduced sensitivity and specimen storage conditions. Further study with increased numbers of specimens and higher quality specimens should be considered to understand better the contribution of these infections to the occurrence of congenital hydrocephalus.

A potential association between Toxoplasma gondii infection and schizophrenia in mouse models.

Schizophrenia is a serious neuropsychiatric disease of uncertain etiology, which causes human mental disorder and affects about 1% of the population. In recently years, some studies showed that some cases of schizophrenia may be associated with Toxoplasma gondii infection. In order to investigate a potential association between Toxoplasma infection and schizophrenia, we investigated the relative clinical symptom of schizophrenia such as learning and memory capability, depression and stereotypy to find some useful information by behavioral test in mouse models. Our results demonstrated that mice from Toxoplasma infection and MK-801 administration (as the model of schizophrenia) were impaired in learning and memory capability, and they had more serious depression and stereotypy compared with the control mice, especially the mice from congenital Toxoplasma infection. In addition, our results clearly showed that the number of cysts in brain tissue of congenital Toxoplasma infection mice was significantly low than in acquired Toxoplasma infected mice. Collectively, these results suggested a potential association between Toxoplasma infection and schizophrenia.

Is the incidence of congenital toxoplasmosis declining?

Prenatal infection with the protozoan parasite Toxoplasma gondii can cause congenital toxoplasmosis (CT), an often fatal or lifelong-disabling condition. Several studies of human populations have reported temporal decreases in seroprevalence, suggesting declining CT incidence. However, the consistency of this trend among diverse populations remains unclear, as does its implication for prenatal screening programmes, the major intervention against CT. Using temporally resolved data on the seroprevalence of T. gondii in various countries, we discuss how the parasite's changing epidemiology may affect trends in CT incidence in varying and counterintuitive ways. We argue that parasite stage-specific serology could be helpful for understanding underlying causes of secular changes in seroprevalence. Furthermore, we highlight the importance of updating cost-effectiveness estimates of screening programmes, accounting for neuropsychiatric sequelae.

Atovaquone ameliorate gastrointestinal toxoplasmosis complications in a pregnancy model.

BACKGROUND: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis. MATERIAL/METHODS: Programmed pregnant mice were i.p. infected with 50-2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications. RESULTS: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and severe hepatitis (score 3.6±0.01 on scale 0--normal to 4--severe) with influx of inflammatory and plasma cells, multinucleated dysplastic hepatocytes and necrosis. In addition, dams expressed mild to severe pancreatitis with mononuclear cell invasion, loss of islets and necrosis. This was consistent with splenomegaly (X3 Fold), and massive infiltration of epithelioid cells and loss of germinal structure. Colon became significantly shortened in length (p<0.01) with semi-normal content. Pathological manifestation included, shortening of crypts with numerous microabscess formations, infiltration of lymphocytes, and macrophages. The severe clinical complications led to abortion (50%), early birth (25%) or still birth (25%) consistent with the high dose of Tachyzoites inoculation. Atovaquone treatment partially but significantly protected the dams from the severity of hepatitis, splenomegaly, colitis, myocarditis, and pain related responses as well as fetal demise. CONCLUSIONS: This is a valuable model for therapeutic evaluation of feto-maternal Toxoplasmosis and gastrointestinal complications. Atovaquone protects dams and their fetuses against some infectious/inflammatory aspects of the disease.

Congenital ocular toxoplasmosis in consecutive siblings.

Toxoplasma gondii infection can cause ocular manifestations after acquired and congenital disease. We report two cases of symptomatic congenital toxoplasmosis with ocular involvement in non-twin siblings, with a 2-year interval between pregnancies. Vertical transmission of toxoplasmosis in successive pregnancies, which was once considered impossible, is now found to be plausible even in immunocompetent subjects.

A Systematic Review to Evaluate a Possible Association Between Congenital Toxoplasmosis and Preterm Labor.

BACKGROUND: Congenital toxoplasmosis (CT) is a widespread infection in several countries, and it is defined as an infection of a fetus, newborn, or infant under 1 year of age. Moreover, it represents a thread to pregnant women globally. The objective of our study is to evaluate a potential association between prematurity and CT and whether intrauterine transmission impacts gestational length during pregnancy. METHODS: PubMed, Cochrane Library and Google Scholar databases were searched from 1950 to 2019. Case-control studies, retrospective, and prospective cohort studies were eligible. Seven studies were included from a total of 314. The Newcastle-Ottawa scale was used to establish the quality of the articles included. RESULTS: Based on our review, an association between CT and preterm labor was not established, which may reflect heterogeneity in screening, treatments administered, and differing reported incidences of CT across continents over 69 years. A multicenter prospective cohort study powered to investigate a potential association is indicated. CONCLUSION: Further studies are needed including multicenter prospective cohort studies powered to investigate key clinical associations such as vertical transmission and preterm birth.

[Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention]. / Toxoplasmose congénitale : comparaison randomisée de stratégies de prévention des rétinochoroïdites.

In France, children with confirmed congenital toxoplasmosis receive a treatment for a period of 12 to 24 months. Such prolonged treatment may generate potentially severe risks, in particular hematologic and cutaneous. Our objective is to compare the effectiveness of two therapeutic strategies on the prevention of retinochoroiditis by a randomized, non-inferiority, open-label, parallel study including 486 children, 3 to 6 months of age with a non-severe form of congenital toxoplasmosis. Following randomization, pyrimethamine-sulphonamide treatment is initiated for a period of three months, followed by a treatment with Fansidar(®) for 9 months, or therapeutic abstention. Follow-up visits during a two-year period will include an examination of the eye, a blood test, and questionnaires to evaluate the children's quality of life and their parents' anxiety. Confirming the non-inferiority of the effectiveness of a short-term treatment will improve the quality of life of parents and children.

Bilateral ocular involvement in congenital toxoplasmosis: A case report and literature review.

We report a case of neuro-ophthalmological complications of congenital toxoplasmosis, a parasitic infection caused by Toxoplasma gondi. Its congenital form occurs either as a primary infection or as reactivation of the same due to immunosuppression during pregnancy. With an incidence rate of 1.5/1000 live births, this disease is an important cause of visual loss from chorio-retinal lesions in >82%. Recent studies have shown that treatment given in utero and in the first year of life can reduce ophthalmological complications.

Hearing brain evaluated using near-infrared spectroscopy in congenital toxoplasmosis.

Congenital toxoplasmosis (CT) is a known cause of hearing loss directly caused by Toxoplasma gondii. Hearing loss might result from sensory, neural, or sensorineural lesions. Early treated infants rarely develop hearing loss, but retinochoroidal lesions, intracranial calcifications and hydrocephalus are common. In this study, we aimed to evaluate the brain evoked hemodynamic responses of CT and healthy infants during four auditory stimuli: mother infant directed speech, researcher infant directed speech, mother reading and researcher recorded. Children underwent Transitionally Evoked Otoacoustic Emission Auditory Testing and Automated Brainstem Auditory Response tests with normal auditory results, but with a tendency for greater latencies in the CT group compared to the control group. We assessed brain hemodynamics with functional near-infrared spectroscopy (fNIRS) measurements from 61 infants, and we present fNIRS results as frequency maps of activation and deactivation for each stimulus. By evaluating infants in the three first months of life, we observed an individual heterogeneous brain activation pattern in response to all auditory stimuli for both groups. Each channel was activated or deactivated in less than 30% of children for all stimuli. There is a need of prospective studies to evaluate if the neurologic or auditory changes course with compromise of children outcomes.

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.