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M Wallon

Publications and source records attributed to M Wallon.

At least 19 recordsLinked to original sources

Impact of spiramycin treatment and gestational age on maturation of Toxoplasma gondii immunoglobulin G avidity in pregnant women.

The objective of the present study was to investigate the maturation of immunoglobulin G (IgG) avidity after Toxoplasma gondii seroconversion during pregnancy and the factors that affect IgG avidity over time. The study used 309 serum samples from 117 women and a multiple linear mixed regression analysis to show the patterns of variation of IgG avidity throughout gestation. The IgG avidity ratios and the patterns of their evolution with time were quite diverse among the women and were statistically heterogeneous (P = 0.011); however, the trend was toward a statistically significant increase (P < 0.0001). On average, a 1.0167-fold increase was observed for each additional gestational week after the putative date of infection. At 12 weeks after putative infection (the expected IgG avidity maturation time), the mean avidity ratio was 16.6% (95% confidence interval, 15.4 to 17.9%). At all times, the avidity ratio remained significantly heterogeneous among the women (P < 0.05); for 95% of them, that ratio ranged from 7.8 to 35.3% at 12 weeks after putative infection. Maternal age at the putative time of infection did not influence the maturation of IgG avidity. However, on average, a 1.009-fold decrease (P = 0.03) in that avidity was observed for each additional week of gestational age before infection and a 1.03-fold increase (P = 0.0003) was observed for each additional week of delay to the onset of spiramycin treatment. The rate of increase in the avidity ratio was lower if infection occurred late in pregnancy and higher if the delay to treatment was long. This information cannot allow accurate determination of the delay since the time of infection. The present results provide support for interpretation of the assay and caution against overinterpretation.

Animals↗

Delayed maturation of immunoglobulin G avidity: implication for the diagnosis of toxoplasmosis in pregnant women.

The low avidity of immunoglobulin G has been reported to be a useful marker of recent infection with Toxoplasma. Several investigators, however, have published discrepant result on the maturation of avidity over time. The aim of this study was to analyse persistent low avidity of immunoglobulin G in immunocompetent individuals and in pregnant women and how it could interfere in the flowchart of antenatal diagnosis of toxoplasmosis in the latter group. An international literature search was conducted together with a retrospective study of a hospital database. Eleven publications that met the inclusion criteria reported delayed maturation of avidity at a frequency ranging from 0 to 66.6% of the patients. Examination of those publications demonstrated an important heterogeneity in the type of assay used, the calculation of avidity, the cutoff above which avidity was considered to be elevated, and the delay since infection after which indices are expected to be high. In the hospital database, persistent low avidity was found even after a median follow-up period of 6 years. Different factors could interfere with maturation of avidity, such as variations between individuals, the assay system used, and, possibly, the treatment administered. The results of this study clearly demonstrate that, in a pregnant woman, an acute infection cannot be reliably diagnosed solely on the basis of low avidity of immunoglobulin G. Further investigations and standardization of assays are urgently needed. Estimation of the time of infection remains difficult, especially in cases in which the samples are drawn late in pregnancy; the final estimate must be based on several tests repeated at intervals of weeks.

Animals↗

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Journal Article↗

[Congenital ocular toxoplasmosis--ocular manifestations and prognosis after early diagnosis of infection].

BACKGROUND: Congenital toxoplasmosis (CT) is the most frequently encountered congenital infection. The aim of the present review is to report about the long-term outcome of functional and morphological manifestations after an early confirmation of the diagnosis. PATIENTS AND METHODS: We report on a cohort of patients with serologically confirmed CT, born between 1988 and 2001, who were followed up prospectively at a single centre (Institute of Parasitology, Hôpital de la Croix Rousse, University of Lyon). All patients underwent regular ophthalmological, parasitological and paediatric controls on a half-yearly or annual basis. Ocular manifestations were documented and visual acuity was assessed as far as was possible. RESULTS: 1,506 seroconversions were diagnosed during pregnancy, and 327 of the live-born offspring were seropositive for CT. At the end of the study period, ocular manifestations occurred in 79 of the children (24 %), and in 7 cases (9 %) they were discovered during the first month of life. In 72 of the patients (91 %), the ocular manifestations developed between 1 and 151 months (median follow-up time: 6.3 +/- 3.7 years; range: 0.5 - 14 years) under medical treatment for the first year of life. At the end of the study period, information regarding visual acuity was available for 66 patients. In 55 of these (83 %), visual acuity was normal in both eyes, and in 11 (17 %), it was reduced below 0.5. In 1 child, both eyes were functionally affected, one severely. CONCLUSION: CT may not become manifest ocularly until after a decade, which underlines the necessity for long-term ophthalmological monitoring of the infected individuals. In our patients, the prognostic outcome after therapy for the first year of life was better than that reported in the literature. This favourable outcome may serve as a basis for patient counselling.

Adolescent↗

Comparative diagnostic performance of two commercial rapid tests for malaria in a non-endemic area.

In the study reported here, the diagnostic performance of two new rapid tests for the diagnosis of malaria was evaluated in symptomatic patients in a non-endemic area. Of 557 consecutive patients, 109 (19.6%) had documented malaria. For the NOW ICT MALARIA P.f./P.v. (Binax, Portland, ME, USA) and OptiMAL IT (Diamed, Cressier, Switzerland) tests, respectively, sensitivity values were 96.3% and 79.8% (P-value, 0.0001), and specificity values were 98.8% and 98.4%. The NOW ICT test did not detect two of 80 Plasmodium falciparum infections, and it generated false-positive results for five patients. The OptiMAL IT test failed to detect ten of the P. falciparum infections, and it generated seven false-positive results. The results suggest that these rapid diagnostic tests for malaria may be useful, but they cannot replace microscopic examination of blood films.

Adolescent↗

Duration of the IgM response in women acquiring Toxoplasma gondii during pregnancy: implications for clinical practice and cross-sectional incidence studies.

We followed up a cohort of 446 toxoplasma-infected pregnant women to determine the median and variability of the duration of positive toxoplasma-IgM (immunoglobulin M) results measured by an immunofluorescence test (IFT) and an immunosorbent agglutination assay (ISAGA). IgM antibodies were detected for longer using the ISAGA test [median 12.8 months, interquartile range (IQR) 6.9-24.9] than the IFT (median 10.4, IQR 7.1-14.4), but the variability between individuals in the duration of IgM positivity was greatest for the ISAGA test. IgM-positive results persisted beyond 2 years in a substantial minority of women (27.1% ISAGA, 9.1% IFT). Variation in the duration of the IgM response measured by ISAGA and IFT limit their usefulness for predicting the timing of infection in pregnant women. However, measurement of IgM and IgG antibodies in a cross-sectional serosurvey offers an efficient method for estimating the incidence of toxoplasma infection.

Adult↗

Cellular immunity to Toxoplasma gondii in congenitally infected newborns and immunocompetent infected hosts.

The aim of this study was to determine the frequency of anergy to Toxoplasma gondii in congenitally infected newborns and immunocompetent infected individuals. Specific anergy to Toxoplasma has been reported previously, especially in cases of congenital toxoplasmosis. Whole blood from 592 immunocompetent patients with suspected toxoplasmosis was cultured in the presence of soluble Toxoplasma antigen for 7 days. Activated T lymphocytes were detected by flow cytometry. In patients over 1 year of age, the percentage of soluble Toxoplasma antigen-stimulated T cells expressing the interleukin-2 receptor CD25 was higher in infected patients than in uninfected subjects (40.0+/-18.3% vs. 1.8+/-2.0%, P<0.0001). No differences were detected between seroconverters, i.e. those with recent rises in IgM and IgG antibodies, and those with acquired or congenital toxoplasmosis. Similar results were observed when congenitally infected ( n=38) and uninfected ( n=89) children under 1 year of age were compared (17.6+/-9.2% vs. 3.0+/-4.9%, P<0.0001). The sensitivity and specificity values of CD25 detection for diagnosis of congenital toxoplasmosis in infants were 95% and 89%, respectively, at a threshold value of 7% above control culture. The results show that specific cellular immunity is detectable in virtually all Toxoplasma-infected patients, including newborns. Detection of CD25 constitutes a simple, sensitive and specific test for diagnosis of congenital toxoplasmosis.

Animals↗

Prognostic factors for the long-term development of ocular lesions in 327 children with congenital toxoplasmosis.

The aim of this study was to identify the high-risk factors associated with the development of ocular lesions in a large cohort of children with congenital toxoplasmosis (CT), irrespective of their gestational age at the time of maternal infection. Children were managed according to a standardized protocol and monitored for up to 14 years at the Croix-Rousse Hospital, Lyon, France. Cox model and a flexible regression, spline-based method were used for the analysis. During a median follow-up time of 6 years, 79 of the 327 children (24%) had at least one retinochoroidal lesion. No bilateral impairment of visual acuity was observed. The risk of a child developing ocular disease was higher not only when mothers were infected early during pregnancy, which was expected, but also when CT was diagnosed prior to or at the time of birth, when non-ocular manifestations were present at baseline and when birth was premature.

Adolescent↗

[Toxoplasma infections in early pregnancy: consequences and management].

OBJECTIVE: To assess the consequences for the fetus of maternal toxoplasma infection acquired during the first 8 weeks of gestation and to set guidelines on how to manage these maternal infections. METHODS: Data were prospectively analyzed on 360 pregnancies followed-up in our department due to a toxoplasma infection during the 8 first weeks of pregnancy. Estimates of the risk of fetal infection were based on all cases, including those which could not be followed up until infection was ruled out or confirmed. Severity of infection was estimated based on ultrasound findings during pregnancy, neonatal and long-term postnatal clinical, neurological and ophthalmologic work up. RESULTS: Out of the 360 included women, 336 gave birth to a live born child: 7 (2%) were infected, 302 (90%) were free of infection and follow-up was insufficient to conclude about the 27 (8%) remaining infants. The estimated risk of fetal infection ranged between 2 and 10% based on live born children and between 3 and 14% when the 24 interrupted pregnancies were included. At their last clinical evaluation at 70 months of age, all 7 children, including the 2 who had inactive peripheral eye lesions and the one who had a unique intracranial calcification were free of any ophthalmologic or neurological impairment. CONCLUSION: Our study confirms that in the event of a maternal infection during the first 8 weeks of pregnancy the risk of fetal infection is low and results mainly in a spontaneous termination of pregnancy. Future parents should be assured that conversely to a common opinion, the prognosis of congenital toxoplasmosis in live-born children is good. For these early maternal infections as for those acquired later, we recommend immediate treatment with spiramycin, monthly ultrasound surveillance, amniocentesis and treatment with pyrimethamine and sulphamides if the PCR is positive. Abortion should be restricted to cases with ultrasound lesions

Amniocentesis↗

[Evaluation of prevention strategies for congenital toxoplasmosis: a critical review of medico-economic studies].

BACKGROUND: Congenital toxoplasmosis (CT) may lead to serious neurological or sensory consequences. A serological screening of women at risk of acquiring toxoplasmosis became mandatory in France, first during the visit before wedding (1978), then during the visit for pregnancy declaration (1985) and at last with a monthly follow-up during pregnancy since 1992. The efficacy and the profitability of the program was never assessed, in spite of the modification of the epidemiological context. However medico-economical studies were conducted in countries in which no prevention program for CT was available to determine the interest of an antenatal screening similar to the French one or of other prevention strategies. METHODS: Eight studies comparing at least two strategies were selected. Methodologies used in those studies were analyzed by two independent readers with the help of a standardized scale. A score was calculated for each study. RESULTS: Each study analyzed suffered from methodological limitations, in particular concerning the estimation of antenatal treatment efficacy, which could lead to invalidate their conclusion. The most reliable studies in regard to methodological guidelines, that is with the higher score, concluded that antenatal screening was not contributive. However, they could not be transposed directly in the present French situation, because of the difference of the epidemiological and economical context. CONCLUSIONS: Given the difficulty to obtain a clear conclusion, it seems necessary to perform a rigorous decision analysis to identify the more effective and acceptable program in terms of human and financial costs for preventing congenital toxoplasmosis.

Cost-Benefit Analysis↗

[Congenital toxoplasmosis. Transitory negative serology].

OBJECTIVES: Toxoplasmosis serology may become temporarily negative in children with congenital toxoplasmosis, leading to a risk of misdiagnosis and inadequate surveillance. The purpose of our work was to better understand the time course of toxoplasmosis serology which has not been studied specifically and to propose practical recommendations. PATIENTS AND METHODS: We conducted a prospective study in 217 children born with congenital toxoplasmosis between January 1988 and December 1997. Clinical, ophthalmological and serology data were collected every three months during their first year of life then every six months until three years of age and every year thereafter for all patients. Negative serology was defined as the absence of IgG at indirect immunofluorescence and ELISA (enzyme linked immunosorbent assay) and by the absence of IgM at ISAGA (immunosorbent agglutination assay). RESULTS: During the mean follow-up of 66 +/- 33 months (range 12-126 months), 33 children (15%) presented a period where the toxoplasmosis serology (ELISA and indirect immunofluorescence) was negative for a transient period reaching a mean 5 months. The dye test was performed in 25 of these children and was negative in 6 (24%). Among the negative conversions observed at routine testing, 73% occurred in children taking pyrimethamine/sulfadoxin therapy and the others occurred a mean 11.7 months after interruption of treatment. There was a positive association between maternal treatment and transient seronegativity in the cases where the maternal contamination had occurred during the first 2 trimesters of pregnancy. The serology became positive again in 30 of the 33 children (91%) and in 22 children there was a rebound. At last follow-up, the 3 other children still had negative serology (mean duration 35 months, range 3-62 months). CONCLUSION: Transient negative toxoplasmosis serology is a frequent phenomenon in children with congenital toxoplasmosis. Although the underlying pathophysiological mechanism remains unknown, it is crucial to avoid questioning the initial diagnosis of congenital toxoplasmosis and to continue regular routine monitoring.

Child↗

Serological rebound in congenital toxoplasmosis: long-term follow-up of 133 children.

UNLABELLED: Although serological rebound is common in infants with congenital toxoplasmosis, clinical recommendations for management, in particular the need for additional treatment, vary. The goals of our retrospective cohort study in 133 consecutive children with congenital toxoplasmosis were to estimate the incidence and duration of the rebounds, identify predictive factors, assess the long-term risk of eye lesions and the need for treatment. We first estimated the incidence and duration of rebounds and identified predictive factors using an univariate analysis and a Cox model modified to include time-dependent variables. Two cohort studies were then conducted to compare the incidence density of secondary eye lesions in children who had a rebound versus no rebound, and among children who had a rebound after initial therapy, in those who received an additional course of treatment and in those who did not. Of the 133 children, 93 (70%) had at least one rebound during a mean follow-up of 95 months. Of those with one rebound diagnosed after initial treatment, 33 received an additional 3-month course of pyrimethamine/sulphadoxine and 48 were not treated. Intracranial calcification at birth was associated with an increased relative risk (RR) of rebound (RR = 2.601; P = 0.03), and treatment with pyrimethamine/sulphadoxine between 2 and 12 months of age with a decreased risk (RR = 0.3; P = 0.0845), whereas age of pregnancy at maternal infection, type of treatment during pregnancy and sex were not found to be predictive factors. There was no difference in incidence densities of secondary eye lesions in children without rebound (7/3,367 child-months) compared to those with at least one rebound (22/9,609 child-months) (RR = 1.10; 95% CI: 0.47-2.58), and, among the 81 children who had one rebound diagnosed after initial treatment, in those who received an additional course of treatment and in those who did not (RR = 0.72; 95% CI: 0.30-1.72). CONCLUSION: serological rebound is common in children with congenital toxoplasmosis but, due to the risk and constraints, an additional course of treatment and more ophthalmological surveillance than currently practiced do not seem warranted.

Animals↗

Prenatal diagnosis using polymerase chain reaction on amniotic fluid for congenital toxoplasmosis.

OBJECTIVE: To evaluate sensitivity, specificity, and predictive values of a prenatal amniotic fluid (AF) polymerase chain reaction (PCR) test for diagnosis of congenital toxoplasmosis. METHODS: A multicenter prospective study was done on 271 women with proved primary Toxoplasma infection during pregnancy and who had amniocentesis for prenatal diagnosis by PCR. Live-born infants were eligible for analysis only if a serologic follow-up could assess a definitive infection status. RESULTS: Of the 270 evaluable cases, 75 were congenitally infected, 48 of whom had a positive PCR at prenatal diagnosis. Overall sensitivity of PCR on AF was estimated at 64% (95% confidence interval [CI] 53.1%, 74.9%), negative predictive value of 87.8% (95% CI 83.5%, 92.1%), whereas specificity and positive predictive value were 100% (95% CIs 98%, 100% and 92.3%, 100%, respectively). Among cases with congenital toxoplasmosis, there were no significant differences between those with positive or negative PCR with regard to median gestational age at maternal infection, interval between maternal infection and amniocentesis, or duration of treatment before amniocentesis. However, sensitivity of PCR was found to be significantly higher for maternal infections that occurred between 17 and 21 weeks' gestation (P <.02). CONCLUSION: A negative PCR of AF cannot rule out congenital infection. In this case, continuation of treatment with spiramycin combined with ultrasonographic follow-up and postnatal follow-up are warranted. Our results also suggest presumptive treatment combining pyrimethamine and sulfonamides in case of maternal infection occurring late in pregnancy.

Adult↗

Ecological comparison of the risks of mother-to-child transmission and clinical manifestations of congenital toxoplasmosis according to prenatal treatment protocol.

We compared the relative risks of mother-to-child transmission of Toxoplasma gondii and clinical manifestations due to congenital toxoplasmosis associated with intensive prenatal treatment in Lyon and Austria, short term treatment in 51% of Dutch women, and no treatment in Danish women. For each cohort, relative risks were standardized for gestation at seroconversion. In total, 856 mother-child pairs were studied: 549 in Lyon, 133 in Austria, 123 in Denmark and 51 in The Netherlands. The relative risk for mother-to-child transmission compared to Lyon was 1.24 (95% CI: 0.88, 1.59) in Austria; 0.59 (0.41, 0.81) in Denmark; and 0.65 (0.37, 1.01) in The Netherlands. Relative risks for clinical manifestations compared with Lyon (adjusted for follow-up to age 3 years) were: Austria 0.19 (0.04, 0.51); Denmark 0.60 (0.13, 1.08); and The Netherlands 1.46 (0.51, 2.72). There was no clear evidence that the risk of transmission or of clinical manifestations was lowest in centres with the most intensive prenatal treatment.

Anti-Bacterial Agents↗

Effect of prenatal treatment on mother to child transmission of Toxoplasma gondii: retrospective cohort study of 554 mother-child pairs in Lyon, France.

BACKGROUND: The aim of prenatal serological screening for toxoplasmosis is to identify and treat maternal infection as soon as possible in order to prevent transmission of the parasite to the fetus. However, despite widespread provision of prenatal toxoplasma screening across Europe, the effectiveness of prenatal treatment is uncertain. The study aimed to determine the effect of the timing and type of prenatal treatment on mother to child transmission of Toxoplasma gondii. METHOD: A cohort of 554 infected pregnant women were identified in Lyon, France between 1987 and 1995 and their children were followed to determine congenital infection status. We determined the effect of prenatal treatment on transmission by examining the effect of the delay between maternal seroconversion and start of treatment. We also compared the effect of the type of treatment and no treatment on the risk of mother to child transmission. Analyses were adjusted for gestation at maternal seroconversion. RESULTS: Compared to treatment within 4 weeks from seroconversion, the adjusted odds ratios (OR) for mother to child transmission after a treatment delay of 4-7 weeks was 1.29 (95% CI : 0.61, 2.73) and after more than 8 weeks, 1.44 (95% CI : 0.60, 3.31). The adjusted OR associated with spiramycin alone compared with pyrimethamine-sulfadiazine treatment was 0.91 (95% CI : 0.45, 1.84) and the OR for no treatment compared with pyrimethamine-sulfadiazine treatment was 1.06 (95% CI : 0.37, 3.03). CONCLUSIONS: The authors hypothesize that the absence of an effect of prenatal treatment is due to transmission before the start of treatment.

Adult↗

Options for the pharmacotherapy of toxoplasmosis during pregnancy.

Toxoplasmosis infection during pregnancy can cause stillbirths, severe mental retardations or ocular disorders that can also occur later in life and have a potential to relapse. As the disease is generally asymptomatic, diagnosis relies on serological tests. Primary prevention intends to prevent the infection of the fetus, while secondary prevention aims at reducing the severity of sequelae. Preventive attitudes regarding congenital toxoplasmosis differ according to countries. In Austria and France, a nationwide programme based on the screening of seronegative pregnant women and the treatment of all seroconversions has been implemented. The UK and Norway have rejected such a screening due to the lack of evidence of its efficacy. A review of published studies showed that no randomised controlled trials have been conducted. The only available data come from retrospective studies and are methodologically flawed. The impact of chemotherapy on primary and secondary prevention still needs to be assessed. This lack of evidence results in conflicting attitudes that increase the anxiety already raised in pregnant women and doctors by the occurrence of a maternal toxoplasmosis during pregnancy. Before making any change in preventative strategy, it is of utmost importance to increase our knowledge on treatment efficacy through proper randomised trials of existing drugs and of new potentially active compounds.

Antiprotozoal Agents↗

Treatments for toxoplasmosis in pregnancy.

BACKGROUND: Toxoplasmosis is a widespread parasitic disease and usually causes no symptoms. However, infection of pregnant women may cause congenital infection, resulting potentially in mental retardation and blindness in the infant. OBJECTIVES: The objective of this review was to assess whether or not treating toxoplasmosis in pregnancy reduces the risk of congenital toxoplasma infection and improves infant outcomes. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. An electronic search was performed using the key words 'congenital and toxoplasmosis' on the following databases: MEDLINE (1966-07/1997), Embase (1993-07/1997), Pascal (French) (1990-1997), Biological Abstracts (1993-1995) and the Cochrane Controlled Trials Register. There was also contact with experts in the field, including those in the European Research Network on Congenital Toxoplasmosis. SELECTION CRITERIA: Randomised controlled trials of antibiotic treatment versus no treatment of pregnant women with proven or likely acute Toxoplasma infection, with outcomes in the children reported. We also inspected relevant reports of less robust experimental studies in which there were (non randomly allocated) control groups, although it was not planned to include such data in the primary analysis. DATA COLLECTION AND ANALYSIS: Reports of possibly eligible studies were scrutinised by two investigators. MAIN RESULTS: Out of the 2591 papers identified, none met the inclusion criteria. REVIEWER'S CONCLUSIONS: Despite the large number of studies performed over the last three decades we still do not know whether antenatal treatment in women with presumed toxoplasmosis reduces the congenital transmission of Toxoplasma gondii. Screening is expensive, so we need to evaluate the effects of treatment, and the impact of screening programmes. In countries where screening or treatment is not routine, these technologies should not be introduced outside the context of a carefully controlled trial.

Female↗