levoleucovorin and Toxoplasmosis--Congenital

Topics: Abortion, Spontaneous; Adult; Animals; Diagnosis, Differential; Eye Diseases; Female; Humans; Hypersensitivity; Infant, Newborn; Inflammation; Leucovorin; Male; Prednisone; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Sulfadiazine; Syphilis; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular; Tuberculosis

Between December 1981 and May 1991, 44 infants and children with congenital toxoplasmosis were referred to our study group. A uniform approach to evaluation and therapy was developed and is described herein along with the clinical characteristics of these infants and children. In addition, case histories that illustrate especially important clinical features or previously undescribed findings are presented. Factors that contributed to the more severe disabilities included delayed diagnosis and initiation of therapy; prolonged, concomitant neonatal hypoxia and hypoglycemia; profound visual impairment; and prolonged, uncorrected increased intracranial pressure with hydrocephalus and compression of the brain. Years after therapy was discontinued, three children developed new retinal lesions (without loss of visual acuity when therapy for Toxoplasma gondii was initiated promptly), and three children experienced a new onset of afebrile seizures. Most remarkable were the normal developmental, neurological, and ophthalmologic findings at the early follow-up evaluations of many--but not all--of the treated children despite severe manifestations, such as substantial systemic disease, hydrocephalus, microcephalus, multiple intracranial calcifications, and extensive macular destruction detected at birth. These favorable outcomes contrast markedly with outcomes reported previously for children with congenital toxoplasmosis who were untreated or treated for only 1 month.

Topics: Animals; Calcinosis; Chemistry, Pharmaceutical; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Feasibility Studies; Humans; Infant; Leucovorin; Magnetic Resonance Imaging; Neutropenia; Physical Examination; Pilot Projects; Prenatal Care; Pyrimethamine; Spiramycin; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis, Cerebral; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular; Treatment Outcome

We investigated the prevalence of ocular abnormalities in infants vertically exposed to Toxoplasma gondii infection during an outbreak in Santa Maria City, Brazil.. Consecutive case series.. A total of 187 infants were included.. The infants were recruited from January 2018 to November 2019. All mothers were screened for syphilis and human immunodeficiency virus before delivery. Toxoplasmosis infection was confirmed in all mothers and infants based on the presence of serum anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies. All infants underwent an ophthalmologic examination; ocular abnormalities were documented using a wide-field digital imaging system. Neonatal cranial sonography or head computed tomography was performed in 181 infants, and the cerebrospinal fluid (CSF) was screened for anti-T. gondii IgG and IgM antibodies in 159 infants. Peripheral blood samples from 9 infants and their mothers were analyzed for the presence of T. gondii DNA by real-time polymerase chain reaction.. Ocular abnormalities associated with congenital toxoplasmosis.. A total of 187 infants were examined. Twenty-nine infants (15.5%) had congenital toxoplasmosis, of whom 19 (10.2%) had ocular abnormalities, including retinochoroiditis in 29 of 38 eyes (76.3%), optic nerve abnormalities in 5 eyes (13.2%), microphthalmia in 1 eye (2.6%), and cataract in 2 eyes (5.3%). Bilateral retinal choroidal lesions were found in 10 of 19 infants (52.6%). Nine eyes of 6 infants had active lesions, with retinal choroidal cellular infiltrates at the first examination. Thirteen (7.2%) of 181 infants screened presented with cerebral calcifications. Eighty-three percent of the screened infants were positive for anti-T. gondii IgG and negative for IgM antibodies in the CSF. Congenital toxoplasmosis was higher in mothers infected during the third pregnancy trimester, and maternal treatment during pregnancy was not associated with a lower rate of congenital toxoplasmosis.. High prevalence rates of clinical manifestations were observed in infants with congenital toxoplasmosis after a waterborne toxoplasmosis outbreak, the largest yet described. Cerebral calcifications were higher in infants with ocular abnormalities, and maternal infection during the third pregnancy trimester was associated with a higher rate of congenital toxoplasmosis independent of maternal treatment.

Topics: Antibodies, Protozoan; Antiprotozoal Agents; Disease Outbreaks; DNA, Protozoan; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunoglobulin G; Immunoglobulin M; Infant, Newborn; Leucovorin; Male; Pregnancy; Prevalence; Pyrimethamine; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular; Ultrasonography

Congenital toxoplasmosis (CT) is a parasitic disease that causes serious fetal and neonatal harm or death. In countries that do not have antenatal screening programs, the initiation of CT treatment relies on a postnatal diagnosis. Until recently, diagnosis was based on clinical signs and immunoglobulin seropositivity, which is fraught with difficulty. In these cases, diagnosis was often delayed or treatment, which carries risk, started empirically. We highlight the use of polymerase chain reaction to diagnose a case of congenital toxoplasmosis, allowing early treatment and justifying the treatment burden.

Topics: Antiprotozoal Agents; DNA, Protozoan; Drug Therapy, Combination; Early Diagnosis; Electroencephalography; Humans; Infant; Leucovorin; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Pyrimethamine; Spinal Puncture; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular; Ultrasonography

Topics: Antiprotozoal Agents; Brain; Calcinosis; Female; Humans; Infant; Leucovorin; Pyrimethamine; Sulfadiazine; Tomography Scanners, X-Ray Computed; Toxoplasma; Toxoplasmosis, Congenital

To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants.. Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year..   Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.4-8.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age.. The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.

Topics: Antibodies, Protozoan; Antiprotozoal Agents; Brazil; Humans; Immunoglobulin M; Infant; Infant, Newborn; Leucovorin; Neonatal Screening; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital

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.

Topics: Adult; Antiprotozoal Agents; Child, Preschool; Drug Therapy, Combination; Early Diagnosis; Female; Humans; Infant; Leucovorin; Male; Mass Screening; Pregnancy; Pregnancy Complications, Parasitic; Pyrimethamine; Sulfadiazine; Toxoplasmosis; Toxoplasmosis, Congenital

The study objective was to determine plasma concentration of pyrimethamine in 24 infants aged 1-5 months, treated for congenital toxoplasmosis. Pyrimethamine was used in a single daily dose at an amount of 0.35-0.98 mg/kg daily, with sulfadiazine (50-100 mg/kg/day) in divided doses 2-3 times a day, and folinic acid given twice a week (7.5 mg). This regimen was continued for 2-6 months, then Fansidar was administered. Pyrimethamine concentration in plasma was measured using high-performance liquid chromatography method (HPLC). A total of 70 tests were performed. Concentration of pyrimethamine ranged from 0.01 to 1.2 microg/ml. In 14 children (58 tests) the concentration of pyrimethamine achieved therapeutic value. In 7 patients (8 tests) the concentration was below therapeutic level, and in 3 patients (4 tests) above therapeutic level. In 11/24 (46%) children transient moderate neutropenia was observed. Modification of therapy was necessary in 12 patients. Monitoring of pyrimethamine concentration in plasma improves safety and effectiveness of the therapy and is useful in obtaining correct individual dose of the drug. Neutropenia is the most common side-effect of pyrimethamine observed even when using the recommended dose.

Topics: Antiprotozoal Agents; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Infant; Leucovorin; Male; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Congenital

This paper reports on the national neonatal screening programme for congenital toxoplasmosis (CT) in Denmark conducted from 1999 to 2007, including background, basis for initiation of screening, methods, results, and finally reasons for the discontinuation of the screening.. A nationwide screening was conducted at Statens Serum Institut, including >98% newborns, and using filter paper eluates (Guthrie card, PKU card) obtained from newborns 5-10 days old. These were analysed for Toxoplasma gondii-specific antibodies (IgM), and if positive, then IgM (ISAGA). Confirmatory serology was performed on children and their mothers (IgM, IgG, IgA, dye test) where infection was suspected, and children with suspected or confirmed CT initiated a 3-month treatment regimen with pyrimethamine, sulfadiazine and folinic acid supplements. Selective cohorts were followed with regard to developmental and clinical outcome.. A total of 100 children were diagnosed with CT in the screening period, and only 2 cases were detected outside of the screening programme. CT prevalence was 1.6 per 10,000 live-born infants. Follow-up studies showed new retinochoroidal lesions in affected children despite treatment.. Screening was terminated August 2007, after it became apparent that no benefit of treatment could be shown. CT was evaluated using a Danish adaptation of the Uniform Screening Panel (ACMG), showing CT as an unlikely candidate for screening today. Whereas results might be comparable with other low-endemic countries with similar strains of T. gondii, neonatal screening and treatment might offer different results in regions with either high prevalence or different strains of T. gondii.

Topics: Antibodies, Protozoan; Antiprotozoal Agents; Child; Child, Preschool; Denmark; Drug Administration Schedule; Drug Therapy, Combination; Humans; Immunoglobulin M; Infant; Infant, Newborn; Leucovorin; National Health Programs; Neonatal Screening; Predictive Value of Tests; Prevalence; Program Development; Program Evaluation; Pyrimethamine; Sulfadiazine; Time Factors; Toxoplasma; Toxoplasmosis, Congenital; Treatment Outcome

Topics: Choroidal Neovascularization; Drug Therapy, Combination; Fluorescein Angiography; Humans; Infant; Leucovorin; Male; Pyrimethamine; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasmosis, Congenital

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.

Topics: Animals; Antibodies; Artemisia annua; Azithromycin; DNA, Protozoan; Drug Therapy, Combination; Embryo, Mammalian; Female; Immunohistochemistry; Infectious Disease Transmission, Vertical; Leucovorin; Mice; Placenta; Plant Extracts; Polymerase Chain Reaction; Pregnancy; Pyrimethamine; Sigmodontinae; Spiramycin; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital

To determine the incidence of new chorioretinal lesions in patients with congenital toxoplasmosis who were treated throughout their first year of life.. Prospective longitudinal observation of a cohort.. One hundred thirty-two children were studied as part of the longitudinal observation.. One hundred thirty-two children were treated during their first year of life with pyrimethamine, sulfadiazine, and leucovorin. They had eye examinations at prespecified intervals.. New chorioretinal lesions on fundus examination and fundus photographs.. The mean age (+/- standard deviation) is 10.8+/-5.1 years (range, 0.2-23). One hundred eight children have been evaluated for new chorioretinal lesions. Thirty-four (31%; 95% confidence interval, 23%-41%) of 108 children developed at least one chorioretinal lesion that was previously undetected. These occurred at varying times during their follow-up course. Fifteen children (14%) developed new central lesions, and 27 (25%) had newly detected lesions peripherally. Ten (9%) had more than one occurrence of new lesions developing, and 13 (12%) had new lesions in both eyes. Of those who developed new lesions, 14 children (41%) did so at age 10 or later.. New central chorioretinal lesions are uncommon in children with congenital toxoplasmosis who are treated during their first year of life. This finding contrasts markedly with earlier reports in the literature for untreated children or those treated for only 1 month near birth, in whom new lesions were much more prevalent (>/=82%). Our observation that 14 (41%) of the 34 children with new chorioretinal lesions had occurrences when they were 10 years or older indicates that long-term follow-up into the second decade of life is important in assessing the efficacy of treating toxoplasmosis during infancy.

Topics: Adolescent; Adult; Antiprotozoal Agents; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Incidence; Infant; Leucovorin; Longitudinal Studies; Male; Prospective Studies; Pyrimethamine; Recurrence; Retinal Diseases; Sulfadiazine; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular

To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis.. Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed.. In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions.. In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.

Topics: Adolescent; Adult; Antiprotozoal Agents; Cataract; Cataract Extraction; Child; Child, Preschool; Drug Therapy, Combination; Humans; Incidence; Infant; Leucovorin; Pyrimethamine; Sulfadiazine; Toxoplasmosis, Congenital

Congenital toxoplasmosis usually results from acquired infection in non-immune pregnant women. However, severely HIV-infected women with a latent Toxoplasma infection can transmit the parasite as a result of reactivation. We report a case of toxoplasmic reactivation in an HIV-infected woman with moderate immunosuppression resulting in a severe congenital toxoplasmosis.

Topics: Adult; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Female; Fetal Blood; HIV Infections; Humans; Immunocompromised Host; Infant, Newborn; Infectious Disease Transmission, Vertical; Leucovorin; Male; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Complications, Parasitic; Pyrimethamine; Recurrence; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Congenital; Vitamin B Complex

The reactivity values of Toxoplasma gondii ROP2, GRA4, and GRA7 recombinant antigens (rAgs) were analyzed by immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) in 23 congenitally infected (I) and 36 noninfected (NI) infants. The reactivity values observed from the serum samples of I versus NI infants for each recombinant protein were 91% versus 67% for rROP2 (P = .05), 86% versus 29% for rGRA4 (P < .001), and 56% versus 11% for rGRA7 (P = .003). The follow-up showed that serum samples from NI infants became negative for specific IgG at 5.8 months (95% confidence interval [CI], 4.9-6.7) using a commercial assay; meanwhile, by specific recombinant protein ELISA, the samples became negative at 3.7 months with rROP2 (95% CI, 2.8-4.6), at 1.3 months with rGRA4 (95% CI, 0.8-1.8), and at 0.9 months with rGRA7 (95% CI, 0.5-1.3). Kinetic analysis also showed that serum samples from group I presented different IgG-profiles among rAgs. The rROP2 IgG profile was similar to that of the commercial assay, whereas rGRA4 and rGRA7 profiles showed a gradual decrease along the period of the study. The potential of the utility of rAgs to develop a diagnostic system that discriminates congenitally I infants from NI is discussed.

Topics: Aging; Animals; Antibody Formation; Antigens, Protozoan; Antiprotozoal Agents; Gene Expression Regulation; Humans; Immunoglobulin G; Infant; Infant, Newborn; Kinetics; Leucovorin; Pyrimethamine; Recombinant Proteins; Sensitivity and Specificity; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital

The clinical management of perinatal toxoplasmosis involves a gynaecologist during pregnancy and a neonatologist after delivery. Then, in the absence of a uniform approach, early evaluation of infected infants requires a thorough long-term follow-up also in asymptomatic children, who have to be observed for at least one year due to unpredictable sequelae in later life. We retrospectively analyzed pregnancy management of 54 women with certain infection from Toxoplasma gondii (TG) and prospectively enrolled their infants to compare prenatal management with postnatal clinical outcome. All mothers with seroconversion for TG infection were from the Palermo area and were retrospectively analyzed, whereas their newborns referred to G. Di Cristina Children Clinical Hospital between 1999-2004 were prospectively enrolled in a 48-month follow-up. Timing of infection was dated for 24 women (45%) to the first trimester, 18 (33%) to the second and 12 (22%) the third. The maternal-fetal transmission rate was 17.2%. Prenatal diagnosis from amniotic fluid was performed in 25/54 pregnant subjects and showed positive results in 6. Despite diagnosis of TG infection, 9 women were untreated and only 2 with positive amniocentesis received combined therapy. 10/55 enrolled infants were infected and half of them were preterm and/or SGA at birth. None showed peculiar signs of TG at birth but 4 had abnormalities during the follow-up. 9/10 infected children were born to mothers who had undergone neither amniocentesis nor combined therapy.. Our work confirms the difficulty of applying standardized therapeutic protocol for TG infection during pregnancy. The asymptomatic course of TG infection at birth confirms the importance of an instrumental long-term follow-up to identify typical TG lesion to prevent sequelae.

Topics: Adolescent; Adult; Amniocentesis; Animals; Antibodies, Protozoan; Antiprotozoal Agents; Chorioretinitis; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrocephalus; Immunoglobulin G; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Small for Gestational Age; Infectious Disease Transmission, Vertical; Italy; Leucovorin; Male; Prednisone; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy Trimesters; Prenatal Care; Prospective Studies; Pyrimethamine; Retrospective Studies; Spiramycin; Sulfadiazine; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Cerebral; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular

Topics: Antimalarials; Drug Combinations; Female; Follow-Up Studies; Humans; Leucovorin; Neutropenia; Pregnancy; Prenatal Care; Pyrimethamine; Sulfadoxine; Toxoplasmosis, Congenital; Vitamin B Complex

Topics: Animals; Antibodies, Protozoan; Antiprotozoal Agents; Chorioretinitis; DNA, Protozoan; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunoglobulin G; Infant; Leucovorin; Panuveitis; Pyrimethamine; Retina; Retinal Detachment; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular

We report a female patient with congenital toxoplasmosis who presented with hydrops fetalis and cerebral abnormalities, detected on fetal ultrasound. Following prenatal treatment, the hydrops fetalis resolved and at four months of age she has normal growth and development. This case emphasizes the potential good prognosis in cases with congenital toxoplasmosis detected and treated prenatally.

Topics: Adult; Amniocentesis; Animals; Antiprotozoal Agents; Cordocentesis; DNA, Protozoan; Echoencephalography; Female; Gestational Age; Humans; Hydrops Fetalis; Leucovorin; Pregnancy; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital; Ultrasonography, Prenatal

To evaluate different laboratory tests used to diagnose congenital toxoplasmosis in the neonatal period.. A retrospective multicenter study of 294 pregnant women who experienced seroconversion for Toxoplasma gondii and subsequently delivered live-born infants. Fetal infection was assessed via specific IgM and IgA antibodies (cord and neonatal blood) and detection of T gondii in placenta and cord blood by mouse inoculation.. Ninety-three (32%) of the 294 infants were congenitally infected. The sensitivity of IgA in cord blood and in neonatal blood was 64% and 66%; the sensitivity of IgM was 41% and 42%, respectively. Mouse inoculation of the placenta and cord blood had sensitivities of 45% and 16%. Positive results of the serologic tests in congenitally infected children correlated significantly with the gestational age at the time of maternal infection but was not significantly influenced by the administration of specific antiparasitic treatment during pregnancy.. Specific T gondii IgA antibody is a more sensitive test than IgM for detecting congenital toxoplasmosis in the neonatal period. The overall specificity is better for serologic tests performed on neonatal blood than for those on cord blood. Neonatal screening with IgM or IgA antibodies will not detect the majority of children with congenital toxoplasmosis when the maternal infection occurred before the 20th week of pregnancy.

Topics: Anti-Bacterial Agents; Female; Gestational Age; Humans; Infant, Newborn; Leucovorin; Pregnancy; Pregnancy Complications, Parasitic; Retrospective Studies; Sensitivity and Specificity; Spiramycin; Toxoplasmosis, Congenital

To describe a case of severe congenital toxoplasmosis because of inadequate surveillance of a seronegative pregnant woman and to evaluate the usefulness of different microbiological diagnostic methods after birth.. We applied serology, DNA amplification by one-tube semi-nested PCR, cell culture and mice inoculation analysis.. Anti. T. gondii serology was useful for the diagnosis of congenital toxoplasmosis. PCR analysis of neonate cerebrospinal fluid and peripheral blood were positive, and yielded negative results after a few days of specific treatment. Cellular culture and mice inoculation yielded negative results.. Our results suggest that serology and PCR are useful methods for the diagnosis of toxoplasmosis in newborns. Prenatal toxoplasmosis screening and suitable follow up of the seronegative pregnant women are necessary to prevent cases of severe infection in our area.

Topics: Acute Disease; Administration, Topical; Adult; Animals; Anti-Inflammatory Agents; Antibodies, Protozoan; Antiprotozoal Agents; Blood; Brain; Cerebrospinal Fluid; Chorioretinitis; Dexamethasone; Female; Glucocorticoids; Humans; Infant, Newborn; Leucovorin; Male; Methylprednisolone; Mice; Neonatal Screening; Ophthalmic Solutions; Polymerase Chain Reaction; Pregnancy; Pyrimethamine; Random Amplified Polymorphic DNA Technique; Sulfadiazine; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular

The purpose of this study was to determine the clinical and immunological outcome of 78 children with congenital toxoplasmosis treated with the pyrimethamine-sulfadoxine combination between 1980 and 1997.. Children were divided into 3 groups according to the initial duration of treatment (always including folinic acid, 5 mg/week by mouth), as follows: pyrimethamine (1.25 mg/kg every 15 d) + sulfadoxine (25 mg/kg every 15 d) for 12 months (Group 1, 47 children), or for 24 months, with or without prenatal therapy (respectively, Group 2, 19 children, and Group 3, 12 children).. Chorioretinitis occurred in 23% of these 78 children. Four children had unilateral blindness, 1 had mild epileptic fits and 1 had psychomotor retardation. The lowest rate of sequelae were in Groups 2 and 3. Immunological rebounds, generally without clinical repercussions, occurred frequently (90% of cases on average) during, or more often after therapy, regardless of the treatment duration. Treatment was always well tolerated.. Our current treatment strategy for congenital toxoplasmosis consists of a 24-month course of pyrimethamine-sulfadoxine (Fansidar) combined with folinic acid (Lederfoline). If the prenatal diagnosis is positive, we also prescribe this treatment to the mother until delivery. This combination offers satisfactory compliance, adequate serum concentrations, and good preventive efficacy.

Topics: Adolescent; Antimalarials; Child; Child, Preschool; Chorioretinitis; Drug Administration Schedule; Drug Combinations; Follow-Up Studies; Humans; Infant; Infant, Newborn; Leucovorin; Pyrimethamine; Sulfadoxine; Toxoplasmosis, Congenital

To determine the natural history of intracranial calcifications in infants with treated congenital toxoplasmosis.. Between January 1982 and March 1994, cranial computed tomography was performed in 56 infants with treated congenital toxoplasmosis when they were newborns and approximately 1 year old. Locations and sizes of intracranial calcifications were noted.. Forty newborns had intracranial calcifications. By 1 year of age, calcifications diminished or resolved in 30 (75%) and remained stable in 10 (25%) of these treated infants. Ten (33%) of the 30 infants whose calcifications diminished versus seven (70%) of the 10 infants with stable calcifications received less intensive antimicrobial treatment than the other treated infants. In contrast, a small number of infants who were untreated or treated 1 month or less had intracranial calcifications that increased or remained stable during their 1st year of life.. Diminution or resolution of intracranial calcifications was an unexpected and remarkable finding in infants with treated, congenital toxoplasmosis, consonant with their improved neurologic functioning.

Topics: Anti-Infective Agents; Brain; Calcinosis; Follow-Up Studies; Humans; Infant; Infant, Newborn; Leucovorin; Pyrimethamine; Sulfadiazine; Time Factors; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral; Toxoplasmosis, Congenital

Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae.. In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment.. Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three).. Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae.

Topics: Antibodies, Protozoan; Central Nervous System Diseases; Follow-Up Studies; Humans; Immunoglobulin G; Immunoglobulin M; Infant, Newborn; Leucovorin; Neonatal Screening; Pyrimethamine; Retinal Diseases; Spiramycin; Sulfadiazine; Toxoplasmosis, Congenital

Pyrimethamine levels in sera, cerebrospinal fluid (CSF), and ventricular fluid were measured by using reversed-phase high-pressure liquid chromatography. The specimens were from 37 infants receiving pyrimethamine for treatment of suspect or proven congenital toxoplasmosis. Pyrimethamine half-life in serum was 64 +/- 12 h when determined by study of terminal-phase kinetics of samples obtained from nine babies. This half-life was significantly different (P = 0.008) from the pyrimethamine half-life (33 +/- 12 h) determined by terminal-phase kinetics for two babies of the same age taking phenobarbital. Serum pyrimethamine levels at various intervals after dosages of pyrimethamine were also lower for infants receiving phenobarbital. Levels measured in sera from babies taking the same dose of pyrimethamine throughout their first year of life did not appear to vary significantly over time or at different ages (P greater than 0.05). Mean +/- standard deviation serum levels 4 h after a pyrimethamine dose were 1.297 +/- 0.54 micrograms/ml for babies taking 1 mg of pyrimethamine per kg of body weight daily and 0.7 +/- 0.26 microgram/ml for babies taking 1 mg/kg each Monday, Wednesday, and Friday. Levels in CSF were approximately 10 to 25% of concomitant levels in serum. Serum folate levels for infants who took 0.64 to 1.7 mg leukovorin per kg ranged from 33 to 663 ng/ml. To determine whether the levels of pyrimethamine in serum and CSF of treated infants were in a range that affected the most virulent, rapidly replicating, and standard laboratory strain of Toxoplasma gondii, effects of various concentrations of pyrimethamine and sulfadiazine on replication of T. gondii in vitro were assessed. The levels of the antimicrobial agents effective in vitro were in the range of levels of pyrimethamine achieved in sera and CSF. Although folinic acid could inhibit the therapeutic effect of pyrimethamine and sulfadiazine in vitro, inhibition was noted only at levels (> or = 4,800 ng/ml) that were considerably higher than the folate levels found in the treated infants' sera.

Topics: Chromatography, High Pressure Liquid; Humans; Infant; Infant, Newborn; Leucovorin; Phenobarbital; Pyrimethamine; Toxoplasmosis, Congenital

Topics: Acute Disease; Adult; Animals; Antibodies, Protozoan; Drug Therapy, Combination; Female; Fetal Blood; Humans; Immunoglobulin G; Infant, Newborn; Leucovorin; Pregnancy; Prenatal Diagnosis; Pyrimethamine; Spiramycin; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital

Comparisons of lymphocyte surface phenotypes and functions were made among 25 pediatric patients with congenital toxoplasmosis (ages 1 month to 5 years) and 24 uninfected babies, a baby with postnatally acquired infection, and 6 uninfected, 7 recently infected, and 6 chronically infected adults. Percentages of lymphocytes with B1, T11, T3, T4, T8, T6, B4, Ia, NKH phenotypes and T4 to T8 ratios of infected and uninfected babies were the same (p greater than 0.05). Lymphocytes from congenitally infected babies had lower blastogenic responses (mean stimulation index [SI] = 5) to Toxoplasma lysate antigens (TLA) than lymphocytes from adult control groups with recent and chronic infection (Mean SIs = 32, 72; p less than 0.001). Compared to infected adults, congenitally infected children had similar or greater responses to concanavalin A (mean SIs = 94; 118, 76, p greater than 0.05) and in mixed leukocyte culture (mean SIs = 63; 22, 26, p greater than 0.05). For symptomatic babies, low blastogenic response to TLA correlated with more severe disease at presentation (p = 0.002). Lymphocyte blastogenic responses to TLA were increased for most children when they were older than 15 months, but responses remained less than adult levels for 9 of the 17 older children studied. There was no correlation between concomitant serum pyrimethamine levels and lymphocyte blastogenic responses to TLA. Pyrimethamine and sulfonamide treatment in vitro and in vivo did not alter lymphocyte response to TLA. Lymphocytes from congenitally infected babies failed to produce either gamma interferon or Interleukin 2 when cultured with TLA. In contrast, they produced these lymphokines when cultured with concanavalin A or phytohemagglutinin. Specific deficits in cell-mediated immune responses to TLA may account for the significant organ damage that occurs in infants and children with congenital toxoplasmosis.

Topics: Adult; Animals; Antigens, Protozoan; Child, Preschool; Concanavalin A; Humans; Infant; Interferon-gamma; Interleukin-2; Leucovorin; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Phenotype; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Congenital

The pyrimethamine-sulfadoxine combination, active against acute toxoplasmosis in the mouse, was administered to 24 children with congenital toxoplasmosis in doses of 500 mg sulfadoxine and 25 mg pyrimethamine per 20 kg bodyweight once every fortnight. The drug appeared to be as effective as other sulfonamide-pyrimethamine combinations. It was generally well tolerated and was withdrawn in only 3 patients on account of minor side-effects. Giving pyrimethamine-sulfadoxine together with folinic acid is a much simpler treatment of congenital toxoplasmosis than the usual ones.

Topics: Child, Preschool; Drug Combinations; Female; Humans; Infant; Leucovorin; Male; Pyrimethamine; Sulfadoxine; Sulfanilamides; Toxoplasmosis, Congenital

Topics: Abortion, Spontaneous; Abortion, Therapeutic; Female; Humans; Infant; Infant, Newborn; Leucovorin; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Congenital

Topics: Adult; Bone Marrow; Bone Marrow Diseases; Female; Humans; Leucovorin; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Thrombocytopenia; Time Factors; Toxoplasmosis; Toxoplasmosis, Congenital

Topics: Diagnosis, Differential; Eye; Female; Humans; Leucovorin; Prednisone; Pregnancy; Pregnancy Complications, Infectious; Pyrimethamine; Sulfadiazine; Toxoplasmosis; Toxoplasmosis, Congenital; Toxoplasmosis, Ocular