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PubMed1996

Eye manifestations of congenital toxoplasmosis.

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.

Adolescent↗

PubMed1989

Fetal toxoplasmosis: outcome of pregnancy and infant follow-up after in utero treatment.

Eight-nine cases of fetal Toxoplasma infection are reported in women treated with spiramycin during pregnancy. Thirty-four pregnancy terminations were performed (2.7% of the total number of acquired Toxoplasma infections during pregnancy). Fifty-two pregnancies were allowed to proceed (43 being additionally treated with pyrimethamine and sulfonamides), leading to the birth of 54 live infants. After a mean follow-up period of 19 months, 41 infants had evidence of subclinical Toxoplasma infection, 12 had a benign form, and one had severe congenital toxoplasmosis (this infant did not receive the additional treatment during pregnancy). Efficacy of the additional treatment with pyrimethamine and sulfonamides was demonstrated by a significant reduction of severe congenital toxoplasmosis and the relative decrease of the ratio of benign to subclinical forms. We recommended that spiramycin treatment be started as soon as possible once the diagnosis of maternal Toxoplasma infection during pregnancy is proved or strongly suspected, because a prolonged time interval between onset of infection and start of treatment seems to be associated with the presence of severe fetal lesions at the time of prenatal diagnosis.

Female↗

PubMed1985

Prenatal diagnosis of congenital toxoplasmosis.

Prenatal diagnosis of congenital toxoplasmosis was attempted by means of fetal blood sampling at 20-24 weeks' gestation. It was possible to detect in fetal blood samples non-specific laboratory signs of fetal infection, specific antibodies of fetal origin (IgM), and parasitaemia by inoculation of the sample into mice. Amniotic-fluid samples were also inoculated into mice and parasites were often present when the fetus was infected. Ultrasound examination of the fetus was done repeatedly, mainly to detect any enlargement of the cerebral ventricles. Together the results of these examinations allowed a reliable diagnosis, which was confirmed by the presence of necrotic foci of toxoplasmic encephalitis in the fetus in every case. Only 1 case of congenital toxoplasmosis occurred among 209 cases with negative prenatal diagnoses.

Antibodies↗

PubMed1994

Termination of pregnancy for maternal toxoplasmosis.

Termination of pregnancy is usually recommended to pregnant women who have infection with Toxoplasma gondii before 26 weeks of pregnancy if the fetus is infected. No prospective studies are available on the outcome if such pregnancies are allowed to continue with anti-parasitic treatment. We prospectively studied 163 mothers with acute toxoplasma infection before 28 weeks of amenorrhoea. All received anti-parasitic treatment with 9 million IU spiramycin orally. 23 also received pyrimethamine and sulphadiazine. All had cordocentesis and regular obstetric ultrasound examinations. The 162 liveborn infants were followed up for 15 to 71 months. 3 fetuses died in utero. 27 of 162 liveborn infants had proven congenital toxoplasmosis: 10 had one or more clinical signs of congenital toxoplasmosis; 5 had isolated or multiple intracranial calcifications; 7 had peripheral chorioretinitis; and 2 had moderate ventricular dilations. All 27 are free from symptoms and have normal neurological development at 15 to 71 months of age. We conclude that in first and second trimester pregnancies with acute fetal toxoplasma infection, the pregnancy need not be interrupted if repeated fetal ultrasound is normal, and antiparasitic treatment is given.

Abortion, Eugenic↗

PubMed1999

Experimental approaches to understanding virulence in toxoplasmosis.

Toxoplasma gondii is a widespread protozoan parasite that causes severe disease only in immunocompromised individuals. Equipped with excellent animal models and relatively advanced systems for genetics, T. gondii provides an excellent system for understanding pathogenesis. Resistance to toxoplasmosis is governed by rapid innate and adaptive immunity that is characterized by a Th1 type profile of cytokines. Despite this effective response, acute infections can cause considerable damage and the parasite effectively establishes a long-term chronic infection that predisposes the host to reactivation and provides a means of eventual transmission. This complex interaction is brought about by the differentiation of the parasite from a rapidly replicating, lytic form (known as the tachyzoite) to a slow-growing form (known as the bradyzoite) that gives rise to chronic infection. The population structure of T. gondii is remarkably clonal, consisting of just three predominant lineages that are geographically widespread and found in a variety of hosts including humans. Acute virulence is strongly associated with the type I genotype which exhibits an enhanced replication rate in vitro and higher tissue burdens in vivo relative to non-virulent lineages. The pathology associated with acute infection appears to be due to excessive production of acute inflammatory mediators, suggesting that disease is partly due to over-response of the host immune system. A combination of refined animal models and newly developed genetic tools for establishing the relative contribution of genes to pathogenesis will enable a comprehensive analysis of the molecular basis of virulence in toxoplasmosis.

Acute Disease↗

PubMed1997

[Study of developing clinical outbreak and serological rebounds in children with congenital toxoplasmosis and follow-up during the first 2 years of life].

BACKGROUND: The survival of T gondii bradyzoites in cysts explains clinical recurrences and serological rebounds after birth in children with congenital toxoplasmosis. At the present time, management of such manifestations is not well defined. PATIENTS AND METHODS: Sixty-three infants with congenital toxoplasmosis were followed-up at the University Hospital of Lille (France) during the first two years of life. For each child, the treatment before and after birth was well defined. Clinical, ophthalmological, radiological and serological data were collected every third month. Serological assays specially adapted to this age bracket were used for the quantification of specific IgG, or for the detection of T gondii specific IgM and IgA. RESULTS: Seventy-six serological rebounds were reported in 55 of the 63 children (87%). They concerned essentially IgG (96%) and less frequently IgM (47%) or IgA (60%). At the same time, only five clinical recurrences were observed, four of them being preceded by a serological rebound. DISCUSSION: Treatment of fetuses or children with pyrimethamine and sulfonamides versus spiramycin alone was associated with a decrease in the frequency of serological rebounds during the first year of life (P < 0.001). Such a therapeutic regimen during the second year of life decreases the appearance of serological rebounds in children without rebound antecedent (P < 0.001). CONCLUSION: The increase in number of rebounds after the end of a course of pyrimethamine and sulfonamides necessitates the evaluation of such a long term treatment without interruption.

Child, Preschool↗

PubMed1990

Selective antenatal screening for toxoplasmosis and the latex agglutination test.

Recent publicity concerning congenital toxoplasmosis has generated a demand for serological assessment of pregnant women. Many laboratories are requested to undertake primary screening in these cases. We assessed the latex agglutination test (LAT) findings in 158 specimens with detectable toxoplasma specific IgM derived from pregnant women. The LAT titres ranged from 16 to greater than or equal to 4000 reflecting the variable antibody response observed in acute toxoplasmosis. We recommend that non-reference laboratories test specimens from pregnant women using the LAT at a screening dilution of 1:16 and select all reactive samples for detailed investigation.

Agglutination Tests↗

PubMed2000

Inhibition of nitric oxide production exacerbates chronic ocular toxoplasmosis.

There is considerable controversy as to the roles of parasite proliferation and the inflammatory response in destruction of the retina during Toxoplasma gondii infection. A murine model was used to investigate the role of nitric oxide in pathogenesis of chronic ocular toxoplasmosis. Increased quantities of messenger RNA (mRNA) transcripts for iNOS were detected in the eyes of chronically infected C57BL/6 mice compared with noninfected control mice. Inhibition of nitric oxide (NO) by the addition of Lomega-nitro-L-arginine methyl ester (L-NAME) to the drinking water of infected mice between weeks 4-6 of infection, exacerbated ocular inflammation. The amount of inflammation was assessed semiquantitatively in histological sections of the eye. Eyes from L-NAME treated mice showed a significant increase in inflammation of the retina (P = 0.02), choroid (P = 0.03), and vitreous (P = 0.02) compared with control mice. These results demonstrate a protective role for NO in the control of chronic, ocular toxoplasmosis.

Animals↗

PubMed1994

[Intrauterine fetal death in acute toxoplasmosis infection].

This is a report on a rare incident of an intrauterine foetal death with toxoplasmosis in the 25th week of pregnancy. The diagnosis could be made serologically as well as pathologically. The issues connected with serological screening for toxoplasmosis are discussed on the basis of this case.

Adult↗

PubMed1979

Epidemic toxoplasmosis associated with infected cats.

In October, 1977, an outbreak of toxoplasmosis occurred in patrons of a riding stable in Atlanta, Georgia; 37 became ill with toxoplasmosis or had serologic evidence by indirect fluorescent-antibody test of acute infection with Toxoplasma gondii (titer greater than or equal to 1:4096 or a positive fluorescent-antibody test for toxoplasma antibodies). Forty-nine additional patrons did not become ill. Two of the three adult cats from the stable were seropositive for toxoplasma, which was also recovered from the tissues of two kittens and four mice trapped near the stable. Patrons who spent most of their time at the end of the stable where a cat had defecated had the highest incidence of infection. Patrons who attended the stable daily had a higher attack rate than those who attended less frequently. No common meals were consumed, and dietary histroy eliminated meat as the source of infection. The data suggest that toxoplasma oocysts were the source of the infection.

Acute Disease↗

PubMed2006

Mic1-3 knockout of Toxoplasma gondii is a successful vaccine against chronic and congenital toxoplasmosis in mice.

BACKGROUND: We evaluated a new vaccine, Mic1-3KO, against both chronic and congenital toxoplasmosis in mice. Mic1-3KO is a mutant strain of Toxoplasma gondii RH that lacks the mic1 and mic3 genes. METHODS: OF1 mice were vaccinated with Mic1-3KO tachyzoites and challenged orally with T. gondii (strain 76K). Immune responses and protection against chronic infection (cyst load in brain tissue) and congenital infection (maternofetal transmission, survival, body weight, and chronic infection in pups) were evaluated. RESULTS: Mic1-3KO induced a strong humoral and cellular T helper (Th) 1 response and conferred highly significant protection against chronic infection (>96% reduction in cysts in brain tissue). Fewer infected fetuses were observed in vaccinated dams that were infected during pregnancy than in nonvaccinated infected dams (4.6% vs. 33.3%). All pups born to vaccinated infected dams survived and had the same weight as those born to nonvaccinated uninfected dams. Furthermore, they had significantly fewer cysts in brain tissue (>91%) than pups from nonvaccinated infected dams. During pregnancy, protection against congenital disease was associated with a cellular Th1 response regulated by interleukin-10. One month after delivery, vaccinated infected dams had >96% fewer cysts in their brain tissue than nonvaccinated infected dams. CONCLUSION: Mic1-3KO is an effective vaccine against chronic and congenital toxoplasmosis.

Animals↗

PubMed1975

Toxoplasmosis. Historical review, direct diagnostic microscopy, and report of a case.

A case of congenital toxoplasmosis diagnosed by the detection of Toxoplasma gondii organisms in the ventricular fluid of a living patient, confirmed by mouse inoculation, is reported. The subject of toxoplasmosis is reviewed historically, especially in regard to cases diagnosed by direct microscopic examination of cerebrospinal or ventricular fluids. Although several such cases have been reported in the world medical literature, an extensive survey failed to reveal such a case previously reported in the United States.

Brain↗

PubMed1990

The identification of a rabbit-transmitted cervical toxoplasmosis mimicking malignant lymphoma.

A case is presented of acquired cervical toxoplasmosis occurring in a 43-year-old male, which clinically mimicked malignant lymphoma. The histopathology of this case was probable toxoplasmic lymphadenitis. Serologic tests and the use of FITC-labeled antibodies revealed high levels of specific IgG antibodies in the serum and toxoplasmic antigens in paraffin sections of the patient, respectively. During survey of the infection route, it was learned that the patient's pet rabbit and three other rabbits of the same family line had cervicofacial lumps. The pet rabbit had high levels of toxoplasmic antibodies. Immunofluorescence tests on the infraorbital lump also revealed Toxoplasma gondii. Therefore, it was concluded that in this case the rabbit had transmitted Toxoplasma to the patient. The authors know of no other reports of toxoplasmosis transmitted by or through rabbit to human.

Adult↗

PubMed1992

Toxoplasmosis in pediatric recipients of heart transplants.

Toxoplasma gondii has long been recognized as a potential cause of severe disease in the congenitally infected infant and the immunocompromised host. This report describes three children with toxoplasmosis after heart transplantation and reviews the cases of 18 adult recipients of cardiac transplants (reported in the English-language literature) who developed toxoplasmosis postoperatively. Onset of disease was within the first 6 1/2 months following transplantation. Severity ranged from asymptomatic seroconversion to myocardial infiltration or disseminated neurological disease and death. Only one patient was known to be seropositive for antibody to T. gondii prior to transplantation. Transmission was most likely via the donor organ. Seronegative patients who receive organs from seropositive donors are at high risk for serious disease; prophylactic strategies need to be developed.

Adolescent↗

PubMed1992

Toxoplasmosis in bone marrow-transplant recipients: report of seven cases and review.

We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty-four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases.

Adult↗

PubMed1986

A simple model relevant to toxoplasmosis applied to epidemiologic results in France.

A simple mathematical model was applied to the results of a seroepidemiologic study of toxoplasmosis carried out in France in 1982-1983. An adequate fitting to the prevalence data observed on 7,605 women of childbearing age was obtained. Thus, the data were used to estimate the seroconversion rate, allowing the approach to and discussion of insights gained from the model, such as the risk of Toxoplasma infection during pregnancy, the age-related expected risks of maternal seroconversion, as well as an overall prediction of the yearly number of congenitally infected infants in the total population. In addition, the high prevalence of congenital toxoplasmosis in France and the excess risk encountered by young migrant women from lower prevalence areas were confirmed by the model. The model might therefore be useful for public health purposes in other countries.

Adolescent↗

PubMed1983

Immune response to Toxoplasma gondii. I. Toxoplasma-specific proliferation response of peripheral blood lymphocytes from patients with toxoplasmosis.

Peripheral blood leukocytes (PBL) from patients with toxoplasmosis were shown to be highly responsive to in vitro stimulation with Toxoplasma gondii extract as measured by incorporation of [3H]methylated thymidine. Analysis of Toxoplasma-specific proliferative cells in PBL by using monoclonal antibodies specific for human T cell subsets revealed that the Toxoplasma-specific proliferation response of PBL from the patients was mediated by Leu 1, Leu 3a positive cells, that is, helper/inducer T cells. Tests for the Toxoplasma-specific proliferation response may provide a readily available method for the diagnosis of congenital toxoplasmosis, especially during the newborn period.

Antibodies, Monoclonal↗

PubMed1984

Congenital toxoplasmosis: a prospective survey in Brussels.

A prospective survey of antenatal patients was made at a hospital in Brussels over the period 1979-1982 to assess the incidence of congenital toxoplasmosis. Of 2986 patients assessed, 1403 (47%) had no toxoplasma antibodies and were at risk. The susceptible population was assessed every 6 weeks and 20 of these women (1.4%) seroconverted during pregnancy. Ten of the seroconverters had a therapeutic abortion; of the remaining 10 two gave birth to congenitally infected infants. Of the 1583 (53%) patients with a positive serology for toxoplasmosis initially, 17 (1.1%) had high antibody titres indicating that the infection could have taken place early in pregnancy. Nine infants born to these women were followed at our hospital and two of them were affected.

Adult↗