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Congenital toxoplasmosis is sometimes difficult to diagnose clinically and histologically, since it can present in diversified forms. The present report deals with a rare type of toxoplasma infection that resulted in a stillborn with hydrops fetales and extensive fetal placental calcification. The direct toxoplasma immunofluorescence test was of great value in the diagnosis.
Pre- and neonatal screening for congenital toxoplasmosis rests upon the assumption that treatment is beneficial on either acute symptoms or in preventing later reactivation. Postpartum treatment of congenital toxoplasmosis with sulfadiazine and pyrimethamine has remained almost unchanged for 50 years. More recently, sulfadiazine has been substituted by sulfadoxine, which has a much longer half-life and provides a basis for a dose schedule with higher compliance. Newer drugs with potential effects against Toxoplasma gondii, such as azithromycin, atovaquone and clindamycin, require further evaluation in animal models and human studies. No randomized controlled trials have ever been conducted. The available studies are either observational studies of groups of referred patients or observational studies with historical controls accrued over many years, often decades. Pre- and neonatal screening for congenital toxoplasmosis is performed on more than two million pregnant women every year in Europe, North and South America at the estimated cost of more than 500 million annually. The benefit needs to be documented by a prospective, placebo-controlled randomized study, which needs to be organized and financed by the countries performing nationwide, universal screening programs.
We present serologic results on 26 patients with congenital toxoplasmosis and on 22 of their mothers. The infection was severe (central nervous system involvement) in 12 patients, 12 had only ocular manifestations, and two were asymptomatic. The dye test results were positive on all specimens, and were positive at a titer of 1:1,024 or higher if collected from patients younger than 2 years of age. The complement-fixation test (CFT) results were positive on all specimens from patients younger than 2 years of age and on 69% of specimens collected from older patients. These serologic results are contrasted with those obtained on two control groups: (1) 46 uninfected infants followed up after birth because of substantial antibody titers in their mothers during pregnancy; and (2) 190 infants and children tested because toxoplasmosis was tentatively included in the differential diagnosis of the current illness. In both control groups the positive results on the CFT were limited almost exclusively to cord blood specimens or specimens collected during the first 2 weeks of life. Lower CFT titers in follow-up specimens suggested that the antibodies were maternal in origin. These two tests are valuable in providing laboratory support for the diagnosis of congenital toxoplasmosis, particularly the test for the comparatively short-lived complement-fixing antibody.
Congenital toxoplasmosis secondary to maternal primary infection acquired late during pregnancy is generally asymptomatic at birth. We report a case of a newborn infant whose mother had been infected between the 27th and the 33rd week of gestation. No treatment had been given during gestation. The infant had a disseminated form of toxoplasmosis with hepatosplenomegaly, pneumonitis, purpura, hepatitis. On the third day of life, he developed shock. The patient died early despite therapy. Septic shock is unusual in congenital toxoplasmosis, although it has been described in immunocompromised patients, notably in patients infected with the human immunodeficiency virus.
Almost all babies suffering from congenital toxoplasmosis, if undiagnosed and untreated, will develop visual or neurological impairments by adulthood. The aim of this study was to investigate the occurrence of congenital toxoplasmosis in two hospitals from Uberlândia, Brazil. A total of 805 serum samples of cord blood were collected, 500 from public hospital and 305 from private hospital, and all patients answered a questionnaire about pregnancy and newborns. ELISA was accomplished to detect IgG antibodies to Toxoplasma gondii and positive sera were re-tested to verify specific IgM and IgA antibodies in a capture ELISA. Seroprevalence of IgG antibodies against T. gondii was 51.6 per cent in the hospitals, while the frequency of congenital toxoplasmosis was 0.5 per cent, with specific IgM and/or IgA antibodies. The main clinical alteration was chorioretinitis (an inflammatory process of the retina and uveal tract). The high seroprevalence in this population and expressive rate of congenital disease show the requirement of screening programmes for toxoplasmosis during pregnancy.
Four cases of congenital toxoplasmosis with hydranencephaly are reported. The anatomic lesions are the consequence of ischemic necrosis and foetal hydrocephalus. The risk of such lesions is highest during the second trimester of pregnancy. The preventive steps against congenital toxoplasmosis are recalled.
Congenital toxoplasmosis was evaluated in Wistar and Holtzman rats using two strains of Toxoplasma gondii isolated in Brazil. Pregnant rats were inoculated by subcutaneous or intraperitoneal routes with 10(6) or 8 x 10(6) tachyzoites of N strain (virulent for mice) and by subcutaneous or oral routes with 10(2) or 1.2 x 10(3) cysts of P strain (avirulent for mice). The tissues of rat pups born from these rats were bioassayed for T. gondii infection. T. gondii was not observed in the pups born from rats inoculated with N strain. In the animals inoculated with P strain, congenital toxoplasmosis occurred in 22.8% (Wistar rats inoculated with 10(2) cysts by the subcutaneous route), 11.4% (Wistar rats inoculated with 10(2) cysts by the oral route), 21.2% (Wistar rats inoculated with 1.2 x 10(3) cysts by the oral route) and 2.9% of fetal infection (Holtzman rats inoculated with 10(2) cysts by the oral route). None of the pups born from chronically infected mother were infected with T. gondii.
The central nervous system is often affected in patients with congenital toxoplasmosis. However, hypothalamo-pituitary dysfunction has rarely been reported in children with congenital toxoplasmosis, and no case with prolonged fever of central origin has been documented so far. We describe a newborn with congenital toxoplasmosis who presented with fever due to hypothalamo-pituitary dysregulation and combined hypothalamo-pituitary deficiencies consisting of central diabetes insipidus, hypothyroidism and ACTH deficiency.
Immunocapture assays ISAGA PLUS IgA/IgM (bioMérieux) and IgE ISAGA were used to determine their usefulness in the diagnosis of acquired and congenital toxoplasmosis. Specific IgM, IgA and IgE antibodies were tested in 134 patients, namely pregnant women who seroconverted during gestation (n = 20), children with congenital toxoplasmosis (n = 5), patients with toxoplasmic lymphadenitis (n = 56) and immunocompetent individuals with chronic Toxoplasma gondii infection (n = 53). Altogether 172 sera were examined. Specific IgM antibodies were detected in all sera from pregnant women (100%) with recent T. gondii infection (1-8 weeks after seroconversion), in all patients with toxoplasmic lymphadenopathy (1-3 months after onset of symptoms) and in their control examinations after 2 and 5 months (100%) and also in 35 (66%) out of 53 patients with chronic infection. In infants with congenital toxoplasmosis IgM were found only in one new-born; equivocal results were obtained in 3 children during the asymptomatic serological reactivation in the second year of life. Specific IgA antibodies were present in sera from 15 (75%) out of 20 women seroconverted during pregnancy; in 3 cases the results were equivocal. IgA antibodies were detected in sera from 30 (81.1%) out of 37 patients with toxoplasmic lymphadenitis examined once; in 19 patients examined 3 times IgA antibodies were present in all the cases in the first serological examination performed when clinical symptoms were first observed (100%), in 17 patients after 2 months (89.5%) and in 11 patients after 5 months (57.9%). IgA antibodies were also detected in 21 sera (39.6%) from patients with chronic T. gondii infection. In children with congenital toxoplasmosis IgA antibodies were found in 3 cases during serological reactivation after discontinuation of pyrimethamine-sulfadiazine therapy; in these cases equivocal results of IgM antibodies were present, and positive result of IgE antibodies in one case. Specific IgE antibodies were detected in sera from 17 (85%) out of 20 women with seroconversion and in 18 patients with lymphadenopathy (32.1%); in the last group IgE antibodies were not present in the follow-up examination after 5 months. IgE antibodies were detected only in 5 cases (9.4%) with chronic infection. IgA and IgE antibodies in ISAGA begin to appear about a week later than IgM antibodies: in sera collected between the 2nd and 3rd week after invasion the positive results were obtained in all cases (100%). Therefore, ISAGA PLUS IgA/IgM (bioMérieux) is useful for the diagnosis of recent T. gondii infection especially in women with suspected seroconversion during pregnancy. ISAGA PLUS IgA/IgM is more sensitive than any conventional method routinely used and so far is a specially efficient technique for newborns and infants suspected for congenital infection and/OR IN DIAGNOSING CONGENITAL TOXOPLASMOSIS DURING IMMUNOLOGICAL RECRUDESCENCE. tHIS TEST HAS A LIMITED VALUE IN TOXOPLASMOSIS WITH LYMPHADENOPATHY BY REASON OF POSSIBILITY OF A LONG PERSISTENCE OF iGm and IgA antibodies detected by ISAGA. Detection of specific IgE antibodies using ISAGA technique may be useful for differential diagnosis of acute and chronic phase of T. gondii infection and also in some cases of serological reactivation of congenital toxoplasmosis.
INTRODUCTION: Toxoplasma gondii is a ubiquitous parasite of all species of mammals and birds (1). Most often the infection in the immunocompetent persons is asymptomatic. Symptoms (if present) are usually mild and self-limited. Infection in the fetus and immunodeficient patients may lead up to clinically severe and often fatal toxoplasmosis (2). ETIOLOGY: Toxoplasma exists in three forms: oocysts, tissue cysts and tachyzoites. The definitive hosts of Toxoplasma are members of the cat family. They shed unsporulated oocysts in the feces. After sporulation oocysts become infectious. Tachyzoites are crescent-shaped forms responsible for manifestations of acute Toxoplasma infection in the intermediate hosts (6,7). Cysts are formed, particularly in brain, heart muscle and skeletal muscles. The cyst forms of the parasite are seen in the latent stage of the infection. Postnatally acquired toxoplasmosis is a consequence of infection from cysts (by ingestion of undercooked meat of infected animals), oocysts (by ingestion of soil, fruits, vegetables contaminated by cat feces) and tachyzoites (by blood transfusion). Congenital Toxoplasma infection causes congenital toxoplasmosis. PATHOGENESIS: Some authors represented the concept that latent (chronic) infection with Toxoplasma during pregnancy can result in congenital infection in the offspring (8-11). Now it is generally agreed that congenital transmission of Toxoplasma occurs only when the infection is acquired during gestation (6,7, 12-16). More than half of the fetuses escape infection, one-third are definitely infected, and the infection is more often subclinical than clinically obvious (15). The fetus is infected hematogenously from inflammatory foci in the placenta formed during parasitemia in the mother. CLINICAL MANIFESTATIONS: Approximately 75% of congenitally infected newborns are asymptomatic. Wilson's study indicates that nearly all such children will develop adverse sequelae (neurologic, intellectual, audiologic and ophthalmologic) 21). Severe forms of congenital toxoplasmosis occur only in 10% of infected offsprings. Clinical manifestations of congenital toxoplasmosis are different. Clinical findings in patients with congenital toxoplasmosis may include: chorioretinitis and other ocular findings, central nervous system abnormalities (such as microcephaly, hydrocephalus, encephalomyelitis, seizures and mental retardation), icterus, hepatosplenomegaly, rash, anemia, erythroblastosis, thrombopenia. INCIDENCE: Incidence of human congenital toxoplasmosis is different in different countries. The incidence in Britain is 0.6 subclinical infection and 0.09 severe illnesses per 1000 births (22). The incidence in USA is between 1/1000 and 1/8000 live births (23). In France the incidence is 1/2000. In Slovenia the incidence is 2.3 cases per 1000 births (25). DIAGNOSIS: Diagnostic methods are: 1. Isolation of the parasite from the placenta, blood, body fluids (by inoculation of specimens into mice or tissue cultures). 2. Histologically by demonstration of tachyzoites in tissue sections or smears of body fluids. 3. Serologic diagnosis. The most important diagnostic methods are serologic tests. For diagnosis of congenital toxoplasmosis determination of IgM antibody (in the serum of newborn infant) has the greatest importance. The fetus is able to produce IgM specific antibody. The presence of IgM antibodies in serum obtained from the neonate is an evidence of fetus infection in utero. Maternal IgM antibodies do not pass the placenta. IgM antibodies may be demonstrable by indirect fluorescent antibody test (IgM-IFA), enzyme linked immunosorbent assay (IgM-ELISA), double sendwich IgM enzyme-linked immunosorbent assay (DS-IgM-ELISA), IgM immunosorbent agglutination assay (IgM-ISAGA) and reversed enzyme immunoassay (REI). For diagnosis of congenital toxoplasmosis the next tests are also applied: Sabin-Feldman Dye test, indirect fluorescent antibody test for IgG antibodies (IgG-IFA) and enzyme
AIM: Prevention and treatment of congenital toxoplasmosis are still a matter of debate among obstetricians, pediatricians and epidemiologists. There is no consensus about antenatal screening and diagnostic tests, nor there is about treatment for presumed infection in pregnancy. As an example of this type of organisation for health care delivery, a regional model has been promoted as a multidisciplinary approach for prenatal diagnosis of congenital toxoplasmosis. The model had been designed on the national guidelines of the National Health Institute (Istituto Superiore di Sanità, ISS). METHODS: Suspected maternal infections are referred and seen as outpatients at our centre on a specific day of the week; maternal investigation (specific IgG, IgM, IgA and IgG avidity titres) are performed at the Institute of Virology of the University of Bari, and patients are started on spiramycin. All cases of true or presumed seroconversion are counselled for amniotic fluid sampling and the sample is sent to ISS. In cases of late seroconversion and positive amniotic fluid results, patients are prescribed pyrimethamine+sulphonamide+folinic acid and alternate spiramycin until the end of pregnancy. A fetal-neonatal follow-up is performed in all cases. RESULTS: During the period 1999-2001, 180 cases of presumed toxoplasmosis infection have been referred (average 60 cases per year). We have been able to reclute, since the adoption of the national network protocol, 1/3 of presumed regional cases with a positive increasing trend. CONCLUSION: The service for prenatal diagnosis of toxoplasma gondii infection has definitely benefitted from the adoption of this protocol, which combines adherence to a national network and pays respect to regional requirements.
Congenital Toxoplasma infection can only be discovered or prevented by the appropriate serological screening and subsequent treatment of the mother and her offspring. In Colombia, there is no obligatory Toxoplasma screening for pregnant women and both the reporting and follow-up of congenital toxoplasmosis cases is limited, thereby is a public health problem that have no been addressed by health authorities. The aim of this study was to investigate the occurrence of congenital toxoplasmosis in a public hospital from Armenia, Colombia. A total of 200 serum samples of cord blood were collected. We applied a western blot assay (ID Blot DPC Diagnostics, US) for Toxoplasma IgG, IgM and IgA antibodies that was validated in a cohort of children with confirmed presence or absence of congenital infection. The sensitivity of western blot assay was 91 per cent and the specificity was 100 per cent. In the cord blood samples, we found one infected child that died at day 4 of life and his infection was confirmed by PCR of the B1 specific Toxoplasma gene on brain biopsy. This results show a high prevalence (0.5 per cent, IC95 per cent 0.2-0.8) of Toxoplasma infection in Colombian newborns. Thus, we recommend additional studies to determine the cost-effectiveness of a newborn screening program for congenital toxoplasmosis in other settings in Colombia.
When infection with Toxoplasma gondii occurs during pregnancy, there is a risk that the parasite will cause severe congenital toxoplasmosis. We developed a method of diagnosing and treating congenital toxoplasmosis in utero. Diagnosis was based on the identification of maternal acute infection, followed by culture of fetal blood and amniotic fluid, testing of fetal blood for toxoplasma-specific IgM and nonspecific measures of infection, and ultrasound examination of the fetal brain. Treatment included the administration of antibiotics to all mothers with confirmed acute infection during pregnancy, with more intensive antibiotic treatment of those who had infected fetuses and who chose to continue the pregnancy. We report a prospective study of 746 documented cases of maternal toxoplasma infection, in which the infants were followed for at least three months. Infection was diagnosed antenatally in 39 of 42 fetuses. Twenty-four of the 39 pregnancies were terminated, and 15 were continued. All the mothers were treated with spiramycin throughout pregnancy; if fetal infection was demonstrated, pyrimethamine and either sulfadoxine or sulfadiazine were added to the regimen. Of the 15 fetuses with congenital toxoplasmosis who were carried to term, all but 2, who had chorioretinitis, remained clinically well during follow-up. We conclude that prenatal diagnosis of congenital toxoplasmosis is practical and that prenatal therapy in women who wish to continue their pregnancies reduces the severity of the manifestations of the disease.
In France, a national program for the prevention of congenital toxoplasmosis has been set up 25 years ago. This program is here presented and discussed in details. It is based on a decision tree well defined, with pre and/or per gravidic serological screening with several different tests, completed, if necessary, by ultrasounds examinations of the fetus, biomolecular tests (PCR) on amniotic fluid, and by clinical, biological, and radiological surveillance of neo-nates. The purpose of this prevention program is to: 1/identify nonimmune young women and limit their contamination risk during pregnancy by appropriate counseling on hygiene and diet; 2/screen and treat per gravidic toxoplasmosis as early as possible so as to prevent or limit transmission to the fetus and its consequences. 3/in utero diagnose and treat infestation of the fetus; 4/diagnose and treat asymptomatic congenital toxoplasmosis in neonates, to prevent risks of reactivation and late complications, especially ocular. Such a prevention program has a cost validated by the prevalence of acquired toxoplasmosis in adults in France (over 50% of the population) and by the yearly incidence of congenital toxoplasmosis (at least 0.1% of births according to the best hypothesis). These 6 to 700 congenital toxoplasmosis cases per year may be compared to the 6 to 7,000 per gravidic seroconversions which could lead to fetal contamination if no preventive measures are taken. Nevertheless, as it is often the case in the field of prevention, it is very difficult to statistically assess the efficacy of this program even though several arguments show that it allows to eliminate the most serious toxoplasmosis, sources of serious handicaps at birth, and to limit the frequency of late complications (especially retino-choroiditis) of asymptomatic infections in neonates. The position of European countries varies as to prevention of congenital toxoplasmosis. Some countries (Austria, Belgium) have national prevention programs similar to the French one, whereas others have set up only limited programs or set up no systematic prevention. These differences may be accounted for by the different frequencies of toxoplasmic risk. It seems mandatory to forget all dogmatism and not to stick to a strictly statistical approach for a disease with not only medical but also social and human consequences.
The authors have compared the diagnostic value in congenital toxoplasmosis of two recently developed immunological techniques, Enzyme Linked immunofiltration Assay (ELIFA) and IgM-immunocapture (or immunosorbent agglutination assay). The study involved 50 children suffering from congenital toxoplasmosis and 300 unscathed control children, whose mothers suffered from toxoplasmosis during their pregnancies. The ELIFA technique showed a sensitivity of 74 p. cent at the end of the first month after birth (day 30) and 84 p. cent after two months (day 60), whereas the IgM-immunocapture technique gave a sensitivity of 64 p. cent at day 30 and 70 p. cent at day 60. Both methods were at least 95 p. cent specific. The two techniques seem to be complementary to each other, and their association allowed the diagnosis to be confirmed in 80 p. cent of cases at day 30 and in 90 p. cent of cases at day 60. A serum sample taken on the tenth day after birth (day 10) was important both to eliminate the rare cases (5 p. cent) of transplacental transmission of maternal IgM antibodies and to detect transient neonatal synthesis of IgG or IgM toxoplasmic antibodies.
BACKGROUND: Hydrocephalus, intracranial calcification and retinochoroiditis are the most common manifestations of tissue damage due to congenital toxoplasmosis, but the effect of prenatal treatment on these outcomes is unclear. We aimed to determine the effect of prenatal treatment for toxoplasmosis on the risk of intracranial and ocular lesions in congenitally infected children at 3 years of age. METHODS: A cohort of mothers identified during pregnancy with toxoplasma infection and their 181 liveborn children with confirmed congenital toxoplasmosis was retrospectively analysed to determine the presence of intracranial and ocular lesions. As few women are not treated, we compared the effects of the treatment potency (pyrimethamine-sulfadiazine versus spiramycin or no treatment), and the timing of treatment, on the risks of intracranial lesions, time to detection of ocular lesions, and detection of any lesions (intracranial or ocular) by 3 years of age. Analyses took account of the gestation at maternal seroconversion. RESULTS: There was no evidence for an effect of pyrimethamine-sulfadiazine on intracranial, ocular or any lesions by 3 years: odds ratio (OR) for any lesions 0.89 (95% CI : 0.41, 1.88). There was no evidence of an effect of delayed treatment on ocular lesions (hazard ratio = 0.69, 95% CI : 0.28, 1.68) or any lesions by 3 years of age (OR = 0.44, 95% CI : 0.16, 1.19). CONCLUSIONS: Our study failed to detect a beneficial effect of early or more potent anti toxoplasma treatment on the risks of intracranial or ocular lesions in children with congenital toxoplasmosis. However, larger, prospective studies, which determine the effect of prenatal treatment on long-term developmental outcomes are required to justify changes in clinical practice.
BACKGROUND: The purpose of this retrospective clinical study was to demonstrate vascularization of peripheral hyperplastic chorioretinal scars in presumed congenital toxoplasmosis by choroidal vessels and secondly to report vasoproliferative tumors of the sensory retina seen in association with such lesions. METHODS: Retrospective study of a cohort of 13 patients with peripheral hypertrophic chorioretinal scars, including fluorescein angiography (eight eyes) and indocyanine green angiography (seven eyes). Congenital toxoplasmosis was serologically confirmed in seven cases and suspected on clinical grounds in six cases. RESULTS: Sixteen eyes exhibited a peripheral complex scar with a posterior atrophic and an anterior hypertrophic part. These scars were vascularized from the choroid. In eight of these eyes an additional vasoproliferative tumor was seen within or adjacent to the scar and in one fellow eye a vasoproliferative retinal tumor was found as well. These eyes experience visual loss, resulting from vitritis and exudative/traction retinal detachment. Regression of exudation was seen in five of seven cryocoagulated or endophotocoagulated tumors. CONCLUSION: Peripheral hypertrophic scars in presumed congenital toxoplasmosis can be vascularized from the choroid. A vasoproliferative tumor of the sensory retina, secondary to presumed congenital toxoplasmosis scars, can cause vitritis and exudative/traction retinal detachment. Early coagulation of this lesion may prevent a poor outcome.
PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median) and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.