RESUMEN
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.
Asunto(s)
Coroiditis/prevención & control , Toxoplasmosis Congénita/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Antimaláricos/uso terapéutico , Coroiditis/diagnóstico , Coroiditis/etiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pirimetamina/uso terapéutico , Calidad de Vida , Sulfonamidas/uso terapéutico , Toxoplasmosis Congénita/complicaciones , Toxoplasmosis Congénita/diagnóstico , Resultado del TratamientoRESUMEN
Tests commonly used for routine determination of anti-Toxoplasma gondii immunoglobulin G (IgG) antibodies show a high level of consistency. However, considerable variations between commercial screening tests are still observed in detecting antibodies present at low concentrations, leading to a number of discrepant and/or equivocal results. It is therefore important to use a reference test to confirm borderline results. In this study, we evaluated the use of a new qualitative test based on Western blot analysis--the LDBio-Toxo II IgG test--as a confirmatory test for at-risk patients. The study was performed retrospectively, using 569 serum samples with "low-positive" (2 to 32 international units) anti-Toxoplasma IgG levels from 375 patients. These samples were either sera collected during the routine screening of pregnant women, from patients with unrelated infections, or from immunocompromised patients or sequential sera taken from pregnant women with acquired Toxoplasma infection or from their newborns during follow-up. The LDBio-Toxo II IgG test was compared to several commercial tests commonly used for anti-Toxoplasma IgG screening. The Sabin-Feldman dye test was used as a reference test. In this study, the results of the LDBio-Toxo II IgG test appeared to be consistent with those of the dye test; the LDBio-Toxo II IgG test had a specificity of 100% and a sensitivity of 99.2%. Our findings suggest that the LDBio-Toxo II IgG test is a useful serological tool in cases in which the presence or absence of Toxoplasma antibodies needs to be reliably determined, for example, for the follow-up of pregnant women and their newborns or for subjects with immune deficiencies following human immunodeficiency virus infection, hematological malignancies, or transplantation.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Western Blotting/métodos , Inmunoglobulina G/sangre , Toxoplasma/inmunología , Toxoplasmosis/diagnóstico , Adulto , Animales , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Retinochoroiditis is the main complication of congenital toxoplasmosis. Its risk factors have rarely been investigated and were the object of this study. METHODS: A retrospective study was conducted on 300 infants with congenital toxoplasmosis born between July 1, 1996 and December 31, 2002 and treated with pyrimethamine and sulfonamide for at least 12 months. Results of eye tests were collected up to 24 months. Risk factors associated with first retinochoroiditis were identified by univariate then multivariate analyses (Cox model). RESULTS: One hundred forty-nine boys and 151 girls were included. Maternal infection dated from the first trimester in 34 cases, the second in 97 cases, and the last in 169 cases. At birth, 22 infants had cerebral calcifications. During the first 2 years of life, first retinochoroiditis was diagnosed in 36 infants (12%). In multivariate analysis, 3 factors were significantly associated with first retinochoroiditis before the age of 2 years: a delay of >8 weeks between maternal seroconversion and first treatment [hazard ratio, 2.54; 95% confidence interval (CI), 1.14-5.65], female gender (hazard ratio, 2.02; 95% CI, 1.01-4.1), and cerebral calcifications at birth (hazard ratio, 4.3; 95% CI, 1.9-10). There was no correlation between gestational age at the time of maternal infection and risk for retinochoroiditis. CONCLUSIONS: A delay of >8 weeks between maternal seroconversion and the beginning of treatment, female gender, and especially cerebral calcifications are risk factors for retinochoroiditis during the first 2 years of life in infants treated for congenital toxoplasmosis.
Asunto(s)
Coroiditis/epidemiología , Toxoplasmosis Congénita/complicaciones , Encéfalo/patología , Calcinosis , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Análisis Multivariante , Pirimetamina/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Estadística como Asunto , Sulfonamidas/uso terapéutico , Factores de Tiempo , Toxoplasmosis Congénita/tratamiento farmacológicoRESUMEN
OBJECTIVE: We wished to investigate the prognosis of children infected with Toxoplasma gondii during the first trimester of pregnancy and whose ultrasound findings were entirely normal, in order to find out whether congenital toxoplasmosis did or did not justify termination of pregnancy if there was no fetal abnormality on ultrasound. STUDY DESIGN: A prospective and retrospective study was carried out by 12 French centers who enrolled 36 children infected with T. gondii during the first trimester of pregnancy and whose ultrasound examinations showed no anomaly. The outcome of these children after the age of 12 months (mean 50 months, range 12-144 months) was analyzed. RESULTS: Of the 36 infected children, 28 (78%) presented subclinical toxoplasmosis. Only specific IgG antibodies persisted after 1 year. The principal manifestation in 7 children (19%) was chorioretinitis without major vision loss. Their intellectual development was entirely normal. One child (3%) developed severe congenital toxoplasmosis. CONCLUSION: Since 97% of children infected with toxoplasmosis during the first trimester of pregnancy are asymptomatic or only slightly affected, we believe that in such circumstances termination of pregnancy is not indicated. However, appropriate treatment is essential and prenatal ultrasound examinations should be free of any anomaly.
Asunto(s)
Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Parasitarias del Embarazo , Efectos Tardíos de la Exposición Prenatal/parasitología , Toxoplasmosis Congénita/complicaciones , Animales , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Embarazo , Primer Trimestre del Embarazo , Pronóstico , Pirimetamina/uso terapéutico , Sulfonamidas/uso terapéutico , Toxoplasmosis Congénita/diagnóstico por imagen , Toxoplasmosis Congénita/tratamiento farmacológico , Ultrasonografía PrenatalAsunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Antiprotozoarios/administración & dosificación , Quimioprevención/métodos , Pirimetamina/administración & dosificación , Sulfadiazina/administración & dosificación , Toxoplasmosis Cerebral/prevención & control , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/administración & dosificación , Recuento de Linfocito CD4 , Quimioterapia Combinada/métodos , Humanos , Insuficiencia del Tratamiento , Carga ViralRESUMEN
There are often discrepancies when using different methods to measure anti-Toxoplasma gondii IgG levels in patient samples. The diagnostic performance of a chemiluminescent immunoassay (CLIA) and an enzyme-linked fluorescent assay (ELFA) used as confirmatory tests for samples identified as positive or equivocal by an electrochemiluminescent immunoassay (ECLIA) were examined. Cut-off values were those stated by the manufacturer, and Western blot was used to confirm the results of all methods. All samples identified as positive by ECLIA (n=93) were confirmed as positive by Western blot, as were 14 of the 28 samples identified as equivocal. When these 121 samples were retested, the sensitivities of CLIA and ELFA were 64.4% and 73.8%, respectively. Both methods exhibited a specificity of 100%. This study confirms that the results obtained from the different immunoassays are not comparable, and neither CLIA nor ELFA should be used to confirm ECLIA results, which should instead be confirmed by methods such as Western blot or Sabin-Feldman dye test.
Asunto(s)
Anticuerpos Antiidiotipos/sangre , Anticuerpos Antiprotozoarios/sangre , Inmunoglobulina G/inmunología , Toxoplasma/inmunología , Toxoplasmosis/diagnóstico , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Humanos , Mediciones Luminiscentes/métodos , Sensibilidad y Especificidad , Toxoplasmosis/inmunologíaRESUMEN
This retrospective study proposes a new reading of immunoblotting (IB) in the diagnosis of congenital toxoplasmosis. Our findings demonstrate that a three-IgM-band association at 75, 90, and 100 kDa called the IgM triplet increases the sensitivity to 95.8% when combined with prenatal and serological neonatal tests.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos , Immunoblotting/métodos , Toxoplasma/inmunología , Toxoplasmosis Congénita/diagnóstico , Antígenos de Protozoos/química , Femenino , Humanos , Inmunoglobulina M/sangre , Recién Nacido , Peso Molecular , Embarazo , Estudios Retrospectivos , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Toxoplasma/químicaRESUMEN
Six agglutination tests for detecting Toxoplasma gondii-specific antibodies (immunoglobulin G or M) in serum were performed and compared. In total, 599 sera were examined using direct and indirect agglutination assays. Sensitivity varied from 93.7% to 100% and specificity from 97.1% to 99.2%. In a selected population with interfering diseases, the percentage of false positives ranged from 4.3% to 10.9%. Although an overall agreement of 100% was found for chronic toxoplasmosis, sensitivity for the detection of confirmed acute toxoplasmosis ranged from 86.4% to 97.3%. Regarding the large variability in terms of the performance of the 6 assays, tests based on the hemagglutination principle were found to be better than the other agglutination tests for all the panels evaluated, meaning that they could be used as qualitative or semiquantitative low-cost screening assays.
Asunto(s)
Pruebas de Aglutinación/métodos , Toxoplasmosis/diagnóstico , Anticuerpos Antiprotozoarios/sangre , Errores Diagnósticos/estadística & datos numéricos , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Toxoplasma/inmunologíaRESUMEN
Detection and treatment of acute toxoplasmosis during pregnancy can avoid severe disease of the fetus. In this context, assessment of anti-Toxoplasma IgG avidity has been shown to exclude recent infection. The Elecsys Toxo IgG and IgM assays (Roche Diagnostics) have been validated for screening pregnant women and a new assay, Elecsys Toxo IgG Avidity, was recently developed. Our aims were to investigate the performance characteristics of this new avidity assay and explore whether additional information can be provided by avidity assays. The Elecsys assay was compared with the Vidas (bioMérieux) and Architect (Abbott) Avidity assays using two sets of serum samples (n = 291 and n = 255). The rate of general agreement between the Elecsys and Vidas assays was 74%, and that between the Elecsys and Architect assays was 83%. For 11% of the serum samples, avidity was high with the Vidas assay and within the gray zone with the Elecsys assay. None of the assays detected high-avidity antibodies in serum taken <4 months after infection. Avidity values of >90% were exclusively reported in sera taken >9 months after infection by the Elecsys and Architect assays. Almost all avidities of <19% with the Elecsys assay and <17% with the Architect assay corresponded to sera taken <3 and <2 months after infection, respectively. The Elecsys IgG Avidity assay can be used to exclude recent infection. New ways of interpreting the avidity result are also suggested: very high or low values could exclude infections within the last 9 months or help to confirm a recent infection, respectively. However, these potential interpretations require further investigation.
Asunto(s)
Anticuerpos Antiprotozoarios/inmunología , Afinidad de Anticuerpos , Inmunoglobulina G/inmunología , Toxoplasma/inmunología , Toxoplasmosis/diagnóstico , Femenino , Humanos , Inmunoensayo/métodos , Inmunoglobulina M/inmunología , Embarazo , Factores de TiempoRESUMEN
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.
Asunto(s)
Toxoplasmosis Congénita/tratamiento farmacológico , Antiprotozoarios/uso terapéutico , Coccidiostáticos/uso terapéutico , Femenino , Francia , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Tamizaje Masivo , Vigilancia de la Población , Embarazo , Diagnóstico Prenatal , Pirimetamina/uso terapéutico , Espiramicina/uso terapéutico , Sulfonamidas/uso terapéutico , Toxoplasmosis Congénita/transmisiónRESUMEN
OBJECTIVE: To provide clinicians with information about the accuracy of real-time polymerase chain reaction (PCR) analysis of amniotic fluid for the prenatal diagnosis of congenital Toxoplasma infection. METHODS: This was a prospective cohort study of women with Toxoplasma infection identified by prenatal screening in three centers routinely carrying out real-time PCR for the detection of Toxoplasma gondii in amniotic fluid. The data available were gestational age at maternal infection, types and dates of maternal treatment, results of amniocentesis and neonatal work-up and definitive infectious status of the child. We estimated sensitivity, specificity and positive and negative predictive values both overall and per trimester of pregnancy at the time of maternal infection. RESULTS: Polymerase chain reaction analysis was carried out on amniotic fluid for 261 of the 377 patients included (69%). It was accurate with the exception of four negative results in children who were infected. Overall sensitivity and negative predictive value were 92.2% (95% confidence interval [CI] 81-98%) and 98.1% (95% CI 95-99.5%), respectively. There was no significant association with the trimester of pregnancy during which maternal infection occurred. Specificity and positive predictive values of 100% were obtained for all trimesters. CONCLUSION: Real-time PCR analysis significantly improves the detection of T. gondii on amniotic fluid. It provides an accurate tool to predict fetal infection and to decide on appropriate treatment and surveillance. However, postnatal follow-up remains necessary in the first year of life to fully exclude infection in children for whom PCR results were negative. LEVEL OF EVIDENCE: III.
Asunto(s)
Líquido Amniótico/parasitología , Reacción en Cadena de la Polimerasa , Diagnóstico Prenatal , Toxoplasma/aislamiento & purificación , Toxoplasmosis Congénita/diagnóstico , Amniocentesis , ADN Protozoario/análisis , Femenino , Enfermedades Fetales/diagnóstico , Humanos , Recién Nacido , Masculino , Valor Predictivo de las Pruebas , Embarazo , Complicaciones Parasitarias del Embarazo/diagnóstico , Sensibilidad y EspecificidadRESUMEN
We report the genotyping analysis of Toxoplasma gondii isolates in samples collected from 88 immunocompromised patients, along with clinical and epidemiological data. Most of these samples were collected in France during the current decade by the Toxoplasma Biological Resource Center. Lack of specific anti-Toxoplasma treatment, pulmonary toxoplasmosis, and involvement of multiple organs were the 3 main risk factors associated with death for this patient group. Genotyping results with 6 microsatellite markers showed that type II isolates were predominant among patients who acquired toxoplasmic infection in Europe. Non-type II isolates included 13 different genotypes and were mainly collected from patients who acquired toxoplasmosis outside Europe. Type III was the second most common genotype recovered from patients, whereas type I was rare in our population. Three nonarchetypal genotypes were repeatedly recovered from different patients who acquired the infection in sub-Saharan Africa (genotypes Africa 1 and Africa 2) and in the French West Indies (genotype Caribbean 1). The distribution of genotypes (type II vs. non-type II) was not significantly different when patients were stratified by underlying cause of immunosuppression, site of infection, or outcome. We conclude that in immunocompromised patients, host factors are much more involved than parasite factors in patients' resistance or susceptibility to toxoplasmosis.
Asunto(s)
Huésped Inmunocomprometido , Toxoplasma/genética , Toxoplasmosis/parasitología , Animales , Encefalitis/complicaciones , Encefalitis/mortalidad , Encefalitis/parasitología , Francia/epidemiología , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Enfermedades Pulmonares Parasitarias/complicaciones , Enfermedades Pulmonares Parasitarias/mortalidad , Enfermedades Pulmonares Parasitarias/parasitología , Toxoplasma/clasificación , Toxoplasmosis/complicaciones , Toxoplasmosis/mortalidadRESUMEN
BACKGROUND: Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute. METHODS AND FINDINGS: In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting. CONCLUSIONS: These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Colágeno Tipo II/genética , Epigénesis Genética , Toxoplasmosis Congénita/genética , Encéfalo/patología , Estudios de Cohortes , Ojo/patología , Impresión Genómica , Genotipo , Humanos , Desequilibrio de Ligamiento , Toxoplasmosis Congénita/patología , Resultado del TratamientoRESUMEN
The reactivation of an uncommon type I/III recombinant-genotype Toxoplasma gondii strain resulted in unusually severe encephalitis and chorioretinitis associated with a cerebral salt wasting syndrome in an African human immunodeficiency virus patient. This observation suggests an influence of the parasite genotype on disease expression in immunocompromised patients.
Asunto(s)
ADN Protozoario/genética , Infecciones por VIH/complicaciones , Toxoplasma/clasificación , Toxoplasma/genética , Toxoplasmosis Cerebral/parasitología , Animales , Antiprotozoarios/uso terapéutico , Encéfalo/parasitología , Encéfalo/patología , Coriorretinitis/tratamiento farmacológico , Coriorretinitis/parasitología , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Toxoplasma/aislamiento & purificación , Toxoplasmosis Cerebral/tratamiento farmacológicoRESUMEN
The diagnosis of disseminated toxoplasmosis in a 14-year-old allogeneic bone marrow recipient with graft-versus-host disease was determined by the detection of Toxoplasma gondii tachyzoites in sputum smears. Sputum analysis is a valuable alternative in the clinical assessment of pulmonary toxoplasmosis, especially when conventional invasive techniques are not practicable.
Asunto(s)
Enfermedades Pulmonares Parasitarias/diagnóstico , Esputo/parasitología , Toxoplasma/aislamiento & purificación , Toxoplasmosis/diagnóstico , Adolescente , Animales , Trasplante de Médula Ósea/efectos adversos , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Humanos , Enfermedades Pulmonares Parasitarias/parasitología , Microscopía/métodos , Coloración y Etiquetado/métodos , Toxoplasma/crecimiento & desarrollo , Toxoplasmosis/parasitología , Trasplante Homólogo/efectos adversosRESUMEN
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.