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Association between prenatal treatment and clinical manifestations of congenital toxoplasmosis in infancy: a cohort study in 13 European centres.

AIM: To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis. METHODS: We prospectively identified 255 live-born infants with congenital toxoplasmosis using prenatal or neonatal screening. We determined the effect of prenatal treatment on the risks of intracranial or ocular lesions in infancy, accounting for gestational age at maternal seroconversion. RESULTS: Prenatal treatment within 4 wk of seroconversion reduced the risk of intracranial lesions compared with no treatment (odds ratio, OR 0.28; 95% CI: 0.08-0.75), but there was no significant effect when initiated after 4 wk (OR 0.76; 95% CI: 0.35-1.59; overall p-value 0.19). Compared to spiramycin alone, no treatment doubled the risk of intracranial lesions (OR 2.33; 95% CI: 1.04-5.50), but the risk did not differ with pyrimethamine-sulphonamide treatment (overall p-value 0.52). There was no consistent relationship between the type or timing of treatment and the risk of ocular lesions. Gestational age at maternal seroconversion was inversely associated with the risk of intracranial but not ocular lesions. CONCLUSION: Only early versus no prenatal treatment for intracranial lesions showed a statistically significant benefit. A large randomized controlled trial and/or meta-analysis of individual patient data from cohort studies is required to confirm these findings.

Adult↗

Toxoplasmosis as a cause of perinatal death in goats.

Lesions typical of congenital toxoplasmosis were found in 5 aborted and stillborn kids. Serological findings in 2 of these kids and all their dams supported the diagnosis of congenital toxoplasmosis. In additon. Toxoplasma gondii was isolated from twin kids.

Abortion, Veterinary↗

Demonstration of Toxoplasma antigen containing complexes in active toxoplasmosis.

With an enzyme-linked immunosorbent assay antigen, specific circulating immune complexes (CIC) were demonstrated in experimental and human toxoplasmosis. In experimentally infected mice, CIC became demonstrable as soon as antibodies appeared after fatal infection. When a nonvirulent strain of Toxoplasma was used CIC remained detectable for several weeks. This period was characterized by clinically healthy animals with increasing antibody titers and by cysts growing in the brains of the animals, indicating a subacute stage of the toxoplasma infection. In the human sera, a surprisingly high percentage of CIC was demonstrated. Both immunoglobulin G (IgG) and IgM were found in the CIC; however, IgG was seen in the majority. If the humans were grouped according to other serological results, such as a combination with IgM antibodies, circulating antigens, or both, or a positive complement fixation test, increasingly more CIC were observed. When sera were selected from patients with clinical symptoms generally associated with toxoplasmosis, more CIC were also again demonstrated. On the contrary, in healthy individuals (blood donors), CIC were also regularly observed, suggesting that exacerbations of latent infections or reinfections may regularly occur without leading to clinical signs. In conclusion, we propose that the interpretation of a positive CIC test requires great care but may provide useful information about the activity of a toxoplasma infection.

Animals↗

Detection of anti-toxoplasma immunoglobulin A antibodies by Platelia-Toxo IgA directed against P30 and by IMx Toxo IgA for diagnosis of acquired and congenital toxoplasmosis.

Platelia-Toxo IgA and IMx Toxo IgA assays were used with 260 serum samples, of which 93 were from seroconverted patients, 58 were from 21 congenitally infected children, and 109 were from uninfected patients, to detect anti-P30 immunoglobulin A antibodies. Because of its enhanced sensitivity, Platelia-Toxo IgA is more efficient in diagnosing acute or congenital toxoplasmosis. IMx Toxo IgA must not be used to diagnose congenital toxoplasmosis.

Animals↗

Right active retinitis and left focal retinochoroidal scar in a girl with congenital toxoplasmosis.

In congenital cases, ocular toxoplasmosis often presents as a focal whitish fluffy lesion in the retina adjacent to an inactive chorioretinal scar. We examined a girl who has visible floaters in the right eye. The patient had focal active retinitis in the right fundus, a focal chorioretinal scar in the left fundus, a positive enzyme-linked immunosorbent assay (ELISA) for IgG anti-Toxoplasma antibodies and a negative ELISA for IgM antibodies. We believe that active focal retinitis in one eye and a focal chorioretinal scar in the fellow eye in congenital toxoplasmosis, as demonstrated in our patient, may be rare.

Adolescent↗

Long-term ocular prognosis in 327 children with congenital toxoplasmosis.

OBJECTIVE: Retinochoroiditis is the most frequent consequence of congenital toxoplasmosis. Early diagnosis and treatment are believed to reduce the risk of visual impairment. We report on the clinical evolution of ocular lesions and final visual function in a prospective cohort of congenitally infected children who were identified during monthly maternal prenatal screening. METHODS: The study included 327 congenitally infected children who were monitored for up to 14 years at the Croix Rousse Hospital in Lyon, France. Data on date of maternal infection; time and type of therapy; antenatal, neonatal, and postnatal work-ups; and ocular status were analyzed. RESULTS: All mothers but 52 had been treated. Pyrimethamine and sulfadiazine was given in utero to 38% of children and after birth to 72% of newborns. Fansidar was given for an average duration of 337 days in all but 2 children. After a median follow-up of 6 years, 79 (24%) children had at least 1 retinochoroidal lesion. In 23 (29%) of them, at least 1 new event had been diagnosed up to 10 years after detection of the first lesions: reactivation of an existing lesion (1 case), new lesion in a previously healthy location (19 cases), or both (3 cases). Fifty-five children had lesions in 1 eye; of the 45 children for whom final visual acuity data were available, 31 (69%) had normal vision. Twenty-four children had lesions in both eyes; of the 21 for whom final visual acuity data were available, 11 had normal vision in both eyes. None had bilateral visual impairment. CONCLUSIONS: Clinicians, parents, and elder children with congenital infection should be informed that late-onset retinal lesions and relapse can occur many years after birth but that the overall ocular prognosis of congenital toxoplasmosis is satisfactory when infection is identified early and treated accordingly.

Adolescent↗

PCR for the diagnosis of toxoplasmosis after hematopoietic stem cell transplantation.

Toxoplasma gondii is a ubiquitous pathogen that causes significant morbidity and mortality in immunocompromised patients. Although relatively uncommon, toxoplasmosis is increasingly recognized as a severe complication of hematopoietic stem cell transplantation. Timely and accurate diagnosis of this treatable infection is critical. PCR-based testing has become the preferred method for diagnosis, occasionally replacing tissue biopsy. This article reviews the clinical, diagnostic and therapeutic aspects of toxoplasmosis in the setting of hematopoietic stem cell transplantation and the current and future role of PCR-based testing for early detection and diagnosis.

Animals↗

[Prospective study of pregnants and babies with risk of congenital toxoplasmosis in municipal district of Rio Grande do Sul].

This study followed up 2,126 pregnant women cared for at SUS day-care clinics (Public Health Insurance System) of the northwest of the State of Rio Grande do Sul, Brazil. After serological screening we performed a follow up of all pregnant women and their babies. Serologic tests included: IgG, IgM, IgA and IgG avidity levels, mice inoculation and polymerase chain reaction (PCR) also placentas and umbilical materials were tested using immunoperoxidase as well as clinical evaluation. Of all the pregnant women screened, 74.5% were reactive to toxoplasmosis, and 3.6% presented IgM seropositivity. At ophthalmic evaluation ten women had ocular lesions and one infant presented eye lesions and brain calcification. The presence of anti-T.gondii specific IgM throughout the entire pregnancy did not characterize acute phase infection, for this, complementary tests were necessary. The importance is underscored for attendance of the newborn of mothers presenting serology compatible with this infection even in the absence of signs and symptoms of congenital toxoplasmosis.

Animals↗

Disseminated toxoplasmosis in a Mediterranean pregnant Risso's dolphin (Grampus griseus) with transplacental fetal infection.

Fatal disseminated toxoplasmosis was diagnosed in a Risso's dolphin (Grampus griseus) dam and its fetus on the basis of pathologic findings, immunohistochemistry, and structure of the parasite. The dolphin was stranded alive on the Spanish Mediterranean coast and died a few hours later. At necropsy the dam was in good condition. From the standpoint of pathology, however, it had generalized lymphadenomegaly and splenomegaly, enlargement of and multifocal hemorrhage in the adrenal glands, diffuse mucosal hemorrhage of the glandular and pyloric stomach, ulcerative glossitis and stomatitis, focal erosions and reddening of the laryngeal appendix, and severe paraotic sinusitis with intralesional nematodes Crassicauda grampicola. The dolphin was pregnant, most probably in the first gestational trimester. The most prominent microscopic lesions were multifocal granulomatous encephalomyelitis, diffuse subacute interstitial pneumonia, mild multifocal necrotizing hepatitis and nonsuppurative cholangiohepatitis, gastritis and adrenalitis, mild lymphoid depletion, medullary sinus and follicular histyocitosis, and systemic hemosiderosis. The fetus had foci of coagulative and lytic necrosis in the kidneys, the lung, and the heart. Most lesions were associated with tachyzoites and tissue cysts of Toxoplasma gondii. The diagnosis was confirmed immunohistochemically. This is the first report on toxoplasmosis in a Risso's dolphin (G. griseus) and on transplacental transmission to an early-stage fetus in any cetaceans.

Animals↗

Incidence of congenital toxoplasmosis in the Republic of Slovenia.

Over a 12-month period, 3959 pregnant women were systematically tested with the Sabin-Feldman dye test in order to assess the incidence of congenital toxoplasmosis in Slovenia. The results suggest that this is approximately 3/1000 live births. This relatively high incidence of congenital toxoplasmosis in Slovenia may make the costing of preventive screening programmes justifiable.

Adult↗

Serological screening for toxoplasmosis in pregnancy in Slovenia.

In the period from 1981 to 1994, serological screening for toxoplasmosis was carried out in 20,953 pregnant women in Slovenia. Seropositivity among pregnant women was found to have decreased from 52% in the 1980s to 37% in the recent period, 1991-94, while during the same period the incidence of suspected primary infections acquired in pregnancy rose from 0.33% to 0.75%. These latest figures ought to promote an informed debate on the possible need for obligatory serological screening of pregnant women in Slovenia for toxoplasmosis.

Animals↗

Cost-benefit analysis of screening for toxoplasmosis during pregnancy.

Congenital toxoplasmosis is a risk for fetus both in 'low' and 'high risk' areas. A cost-benefit analysis based on data from a Finnish prospective study (20.3% seropositivity of pregnant mothers and incidence of 2.4/1,000 seronegative pregnancies) and on Finnish cost data was performed to compare the no-screening and screening alternatives for primary toxoplasma infections during pregnancy. A maternal-feto transmission risk of 40%, effectiveness of treatment of 50%, and discount rate of 4% were used as other baseline probabilities. The calculations were carried out by decision analysis combined with sensitivity analysis. The total annual costs of congenital toxoplasmosis without screening amount to US$ 128/pregnancy/year, and with systematic serological screening, US$ 95/pregnancy. Thus screening reduces the costs by 25%. The present value of net savings in Finland would be US$ 2.1 million every year. A one-way sensitivity analysis showed that screening together with health education is preferable to health education without screening if the incidence of maternal primary infections exceeds 1.1/1,000 and effectiveness of treatment is better than 22.1%. Screening for toxoplasma infections during pregnancy is economically worthwhile even in a country with a low incidence. A scheme of systematic screening for maternal primary toxoplasma infections combined with health education should be considered.

Cost-Benefit Analysis↗

A prospective study of seroprevalence of Toxoplasmosis in general population, and in HIV/AIDS patients in Bombay, India.

Two hundred and seventy nine sera (age group 13-50 years) were tested for antitoxoplasma IgG/IgM antibodies by ELISA techniques; the diagnostic titer for positive test is 10 iu/ml or > 1:100. Sera were obtained from (i) 165 (100 men/65 women) healthy adult voluntary blood donors (HIV, HBsAg, VDRL negative); (ii) 89 consecutive HIV/AIDS patients (82 men/7 women); and (iii) 25 patients (HIV negative: 12 men/13 women) treated for cerebral Tuberculoma or Neurocysticercosis during this study from January 1996-June 1997. The overall seroprevalence was 30.9% (51/165) in the immunocompetent adult (group i) 34% (34/100) men and 26.2% (17/65) in women [range: 10-899 iu/ml; (mean: 376.8)]. In HIV infected hosts the seroprevalence [range: 21-340 iu/ml; (mean; 180)] was 67.8% (56/82 men, 04/07 women). The seroprevalence was 20.5% (8/39), 32.8% (22/67), 34.8% (16/46) and 38.4% (5/13) in the 2nd, 3rd, 4th and 5th decades respectively in healthy adults. In HIV/AIDS patients, 69% (29/42) in the 3rd and 70.6% (24/34) in 4th decade were seropositive. The risk of cerebral Toxoplasmosis (encephalitis-02, granuloma-24) was 43.3% (26/60, mean 250 iu/ml). The seroprevalence was 28% in group iii (range 12-80 iu/ml, mean 21 iu/ml). Anti-toxo IgM was negative in all. Primary Toxoplasma infection appears to be subclinical and prevalent throughout life. T. gondii has emerged as an important opportunistic infection in HIV/AIDS patients in Bombay. Recrudescence of cerebral toxoplasmosis (CTOX) is observed with low IgG response during mid-late stage of the disease, as seen in our patients (mean IgG 250 iu/ml, CD4+ = 283/cmm (range 43-504 in 5 patients). Primary prophylaxis for CTOX seems rationale and can be targeted to asymptomatic HIV/AIDS population at risk who are seropositive for T. gondii (mean IgG 111.5 iu/ml in our study). The very high predictive value of a negative test for TOX remains the best serological parameter for excluding acute episode of TOX.

AIDS-Related Opportunistic Infections↗

[Role of chronic toxoplasmosis infection in pathology of the nervous system and eyes in adults].

The authors conducted a statistical correlation of frequencies of neurological and ophthalmological pathology in a group of patients with different disorders of the nervous system, where 556 had positive and 788 negative seroallergical reactions to toxoplasmosis. It was possible to establish that most of the neurological and ophthalmological symptoms of toxoplasmosis were significantly more frequent in individuals of the first group, except patients with disseminated sclerosis, myopathy and myasthenia.

Adolescent↗

[Laboratory diagnosis of toxoplasmosis].

Toxoplasmosis is a world-wide spread parasitosis. The disease potentially highly affects two groups of patients: foetus and immunosuppressed patients. The determination of diagnosis and therapy on the basis of a single serum examination is very important; possible on the basis of a single serum sample. In most cases, it is possible to differentiate between recent and latent infections using a combination of suitable methods, which permit us to confirm particular antibody classes. In the presented paper the authors suggest diagnostic procedures for 4 groups of patients: pregnant, neonates with suspected congenital toxoplasmosis, immunodeficient patients and immunocompetent patients. The diagnostic methods consist of a combination of basic and supplemented diagnostic methods. Each patient's serum should be tested by basic tests which include the detection of total antibodies with CFT or IFT and specific classes of IgM and IgG antibodies by ELISA. The potential activity of toxoplasma infection can be determined by supplementary methods of e.g. IgG avidity antibodies, establishment of IgA antibodies, western blotting method and monitoring of antibodies production. For each situation the authors present interpretations of suspected cases including proposals for clinicians. These procedures are suggested for practical use in laboratories of various diagnostic levels in order to help to the diagnostic procedures in a particular situation as well as for clinical evaluation of established results. (Fig. 4, Ref. 65).

Female↗

Knowledge-based interpretation of toxoplasmosis serology test results including fuzzy temporal concepts--the ToxoNet system.

Transplacental transmission of Toxoplasma gondii from an infected, pregnant woman to the unborn that occurs with a probability of about 60 percent [1] results in fetal damage to a degree depending on the gestational age. The computer system ToxoNet processes the results of serological antibody tests having been performed during pregnancy by means of a knowledge base containing medical knowledge on the interpretation of Toxoplasmosis serology tests. By applying this knowledge ToxoNet generates interpretive reports consisting of a diagnostic interpretation and recommendations for therapy and further testing. For that purpose it matches the results of all serological investigations of maternal blood with the content of the knowledge base returning complete textual interpretations for all given findings. The interpretation algorithm derives the stage of maternal infection from these that is used to infer the degree of fetal threat. To consider varying immune responses of particular patients, certain time intervals have to be kept between two subsequent tests in order to guarantee a correct interpretation of the test results. These time intervals are modelled as fuzzy sets, since they allow the formal description of the temporal uncertainties. ToxoNet comprises the knowledge base, an interpretation system, and a program for the creation and modification of the knowledge base. It is available from the World Wide Web by starting a standard browser like the Internet Explorer or the Netscape Navigator. Thus ToxoNet supports the physician in Toxoplasmosis diagnostics and in addition allows to adopt the way of making decisions to the characteristics of the particular laboratory by modifying the underlying knowledge base.

Algorithms↗

[Toxoplasmosis in the Republic of Mali. An epidemiologic approach].

1664- sera from children and adults were collected in rural and urban areas of Mali and were tested in Toxoplasmosis serology. Immunofluorescent antibody tests and direct agglutination test have been used for this purpose. 65 per cent of adults from urban area and 56 to 58 per cent of adults from rural area gave positive results. Before the age sixteen, only 33 to 40 percent of children are positive in urban area while 51 to 53 per cent are so in rural area. The study of hundreds of sera collected from various animals allows to explain the different ages of the serological changes. In rural area children have been infected very early after catching birds, reptiles and above all, rodents and eating them not cooked enough. In urban area the infection occurs all along the life and, particularly, in adults, after consuming grilled meat. The recent description of three cases of congenital toxoplasmosis demonstrates the interest of such an epidemiological study.

Adolescent↗

[Study on prenatal diagnosis using fluorescence quantitative polymerase chain reaction for congenital toxoplasmosis].

OBJECTIVE: To investigate prenatal diagnosis and treatment of toxoplasmosis in fetuses with fluorescence quantitative polymerase chain reaction (FQ-PCR) technique. METHODS: Of the 70 pregnant women with toxoplasma (TOX) DNA positive, TOX DNA in amniotic fluid and/or fetal umbilical cord blood was detected with FQ-PCR technique to diagnose fetal infection. 48 ones were given routine treatment with spiramycin for 2 therapy periods. Ultrasound examination were undertaken in all of pregnant women to monitor fetal growth. RESULTS: Of the 70 cases with TOX DNA positive, TOX DNA was detected in 21 fetuses. TOX DNA positive rates were similar in amniotic fluid and umbilical cord blood. The higher the TOX DNA, the higher fetal infectious rate. Fetal infectious rate was lower in treatment group (21%) than that in control group (50%), there was a statistically difference between two groups. CONCLUSIONS: Maternal TOX infection may cause fetal damage. Detection of TOX-DNA in amniotic fluid with FQ-PCR technique can diagnose fetal toxoplasmosis exactly. Treatment in pregnant period may decrease intrauterine infection rate.

Adult↗