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Screening for toxoplasmosis in pregnancy.

Randomly collected sera from 386 pregnant women attending obstetric and gynecology clinics at Kind Khalid University Hospital, Riyadh, Saudi Arabia, were examined for toxoplasma antibodies by five serological methods, i.e. latex agglutination test (LAT), two indirect hemagglutination tests (IHAT) (Carter-Wallace, USA and Ismunit, Italy), enzyme immunoassay (EIA) and indirect fluorescent antibody test (IFAT). The percentage of sensitivity, specificity and coincidence value of these tests were compared with IFAT which was used as a reference test. For routine screening of toxoplasmosis, LAT has proved in this study to be the most suitable test. The LAT is cost effective and easy to perform. In this study of the three tests (IFAT, EIA, immunosorbent agglutination assay) to demonstrate specific IgM for toxoplasmosis, the EIA test proved to be the most satisfactory because of its 99% specificity. If EIA equipment is available, it can be used for routine screening (IgG) as well as IgM determination. The incidence of toxoplasmosis in pregnant women varied between 25.4% and 36.3% depending on the method used.

Female↗

Efficacy of atovaquone in treatment of toxoplasmosis in patients with AIDS. The NIAID-Clinical Center Intramural AIDS Program.

Atovaquone (formerly 566C80) is a hydroxynaphthoquinone with potent activity against Toxoplasma in vitro and in laboratory animals. Eight patients with AIDS and presumed or biopsy confirmed toxoplasmosis who were intolerant of or had not responded to standard therapies were treated with oral atovaquone 750 mg four times a day. Seven patients showed radiographic improvement; the other remained radiographically stable. Six patients died 6-60 weeks after enrollment with no clinical (six) or necropsy (three) evidence of recurrent toxoplasmosis; two patients relapsed at 10 and 32 weeks. Toxicity was mild: only one patient required temporary discontinuation of drug due to a rash. Atovaquone is a well-tolerated drug that appears to be an effective alternative for patients with toxoplasmosis who are intolerant of standard therapies.

Acquired Immunodeficiency Syndrome↗

Prevalence of sensorineural hearing loss due to toxoplasmosis in Saudi children: a hospital based study.

A survey to identify the aetiology of hearing impairment among Saudi children was carried out. Children were divided into 2 groups according to presence or absence of laboratory evidence of toxoplasmosis "at risk' and "not at risk.' Serological tests for toxoplasmosis were done to 1054 children. We found positive IgM antibody against Toxoplasma gondii in the blood of 70 of the 1054 children (6.6%) (age ranged between 12 months and 14 years). Forty nine of the seventy infected children (70%) were found to have bilateral sensorineural hearing loss (11 of 19 children of the at risk group and 38 of 51 from the "not at risk' group). Hearing impairment was bilateral in all cases profound in 9, moderate to severe in 29 and mild in 11. Known causes of hearing impairment were excluded. The high prevalence of hearing impairment among children due to toxoplasmosis is presented.

Adolescent↗

Congenital toxoplasmosis complicated by central diabetes insipidus in an infant with Down syndrome.

We describe an infant with the unusual combination of Down syndrome, congenital toxoplasmosis, and central diabetes insipidus. Hydrocephalus was documented by fetal ultrasonography at 36 weeks' gestation. He developed central diabetes insipidus as a neonate, followed by interstitial pneumonia, anemia, and hepatosplenomegaly. The patient's serum titer for Toxoplasma-specific IgM (ELISA) at 37 days after delivery was negative, but the Toxoplasma SAG1 gene was detected from the cells of the cerebrospinal fluid on the same day using the polymerase chain reaction (PCR) method. Congenital toxoplasmosis can contribute to the development of central diabetes insipidus in infants. PCR was useful in diagnosing congenital toxoplasmosis rapidly and accurately.

Animals↗

Computed tomographic findings in cerebral toxoplasmosis in adults.

The clinical and computerized tomographic (CT) findings in 10 patients with cerebral toxoplasmosis are reviewed. All patients with cerebral toxoplasmosis were homosexuals and/or intravenous drug users, and all patients had other manifestations of AIDS. Two presented with focal seizures, 4 presented with focal neurological deficit which progressively worsened, and 4 had evidence of diffuse neurological dysfunction (altered consciousness, generalized seizures). CT showed a single lesion in 3 patients and multiple lesions in 7 patients. Two patients had hypodense nonenhancing lesions(s). Eight patients had hypodense lesions with peripheral or nodular enhancement. The lesions were more commonly located in the cerebral hemispheres and subcortical gray matter nuclear masses (thalamus, basal ganglia). The finding of a hypodense lesion with a central slightly hyperdense noncalcified region that showed dense nodular homogeneous enhancement was quite characteristic of cerebral toxoplasmosis, but this pattern may also be seen in other neurological conditions including brain lymphomas.

Acquired Immunodeficiency Syndrome↗

[Congenital toxoplasmosis: a new case of infection during pregnancy in an previously immunized and immunocompetent woman].

UNLABELLED: Congenital toxoplasmosis is a potentially serious infection which usually affects infants born to non immune women. CASE REPORT: Our case report focuses on a baby born to a normally immunocompetent woman previously immunized against toxoplasmosis. To our knowledge only three similar cases have been published until now. CONCLUSION: We conclude that in front of a patient neonatal congenital infection picture, toxoplasmosis cannot be excluded on the ground of maternal immunity status and must be quickly investigated, given the emergency of appropriate treatment.

Angola↗

Refinement of the mouse model of congenital toxoplasmosis.

The goals of the present investigation, focusing on the BALB/c mouse model of congenital toxoplasmosis, were: (1) to find a method to determine pregnancy in the mouse. The method has 100% sensitivity and 72% specificity; (2) to test congenital transmission during the chronic stage of toxoplasmosis. This occurred in 2 of 10 mice tested; (3) to investigate the relationship between the infective dose and the rate of congenital transmission. This was not demonstrated for doses of 10(2) to 10(3) bradyzoites and oocysts of Prugniaud, M3 and M7741 strains, with transmission rates of 3 of 8 to 6 of 10 mice inoculated; (4) to determine homologous and heterologous protection. Homologous protection was demonstrated with Prugniaud cysts, and heterologous protection was found between ME-49 and M3 cysts. This finding is consistent with the uniform natural protection against congenital toxoplasmosis seen in immune women and ewes.

Animals↗

Is toxoplasmosis prophylaxis necessary in cardiac transplantation? Long-term follow-up at two transplant centers.

Cardiac transplant recipients are often given prophylactic treatments to prevent opportunistic infections such as Pneumocystis carinii. Toxoplasmosis prophylaxis is commonly prescribed for transplant recipients who have not been exposed to this disease but receive a heart from an exposed donor. We reviewed the collective 28-year experience at two urban transplant programs with 596 patients, and found no cases of toxoplasmosis, but all patients received trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia. We conclude that specific anti-toxoplasmosis prophylaxis is unnecessary in heart transplant recipients.

Adult↗

Specific antibody levels in the aqueous humor and serum of two distinct populations of patients with ocular toxoplasmosis.

The population of Erechim, Southern Brazil, is characterized by a high incidence of ocular toxoplasmosis, which is presumed to be of acquired origin. We wished to compare the local specific humoral immune response of individuals from this region with that of Swiss patients suffering from the same disease. Paired samples of aqueous humor and serum were withdrawn from 27 Brazilian and 50 Swiss patients presenting consecutively with active ocular toxoplasmosis. The total and specific levels of IgG in each of these were determined. The populations did not differ with respect either to age or sex. The serum levels of total IgG in Brazilian (10.8 g/l) and Swiss patients (11.1 g/l) were similar (p = 0.499), but the aqueous humor ones were higher in the former group (95 vs. 20 mg/l; p = 0.0001). The systemic and local levels of specific IgG were likewise higher in Brazilian patients [206 i.u. vs. 72 i.u. (p = 0.001) and 14 i.u. vs. 4 i.u. (p = 0.005), respectively] and the number of individuals without detectable levels of local specific IgG was correspondingly lower (11% vs. 54%; p = 0.0005). The Goldmann-Witmer coefficient (an index of local specific antibody production) did not differ between Brazilian and Swiss patients (2.1 vs. 0.08, respectively; p = 0.107). Our findings are indicative of a more pronounced uveovascular barrier breakdown in Brazilians than in Swiss patients with active ocular toxoplasmosis. That the systemic and local specific immune response is weaker in Swiss than in Brazilian patients has not been hitherto documented. This finding may reflect differences in the immunological handling of the infection.

Adult↗

Fitness of Toxoplasma gondii is not related to DHFR single-nucleotide polymorphism during congenital toxoplasmosis.

Factors that regulate the pathogenesis of Toxoplasma gondii in humans are poorly understood. When acquired during pregnancy, toxoplasmosis can be disastrous, leading to fetal loss or conversely to subclinical disease. In congenitally infected infants, evolution is highly unpredictable. Genotype based virulence patterns have been described in mice, but in humans this classification does not correlate with the gravity of the disease. Mutations on DHFR-TS loci have recently been reported to confer T. gondii fitness cost. In this study, we investigated the relationship between the virulence of the parasite, as measured by clinical outcome in the fetus or newborn, fitness, as measured by parasitic load in amniotic fluid, and allelic polymorphism in DHFR. Six cases of severe congenital toxoplasmosis and 23 cases of mild congenital infections were included in the study. Quantitative PCR was performed to evaluate total T. gondii DNA load in amniotic fluid and detection of mutations was carried out with a LightCycler using hybridisation probes. Parasitic load was significantly higher in severe infections than in mild diseases. Among isolates from severe or non-severe cases of congenital toxoplasmosis, no polymorphism could be detected at loci 36, 83 or 245 of the DHFR gene. The virulent RH strain presented the same melting temperature as the non-virulent PRU strain for codons 36, 83 and 245. Only mutated clones, M2M3 and M2M4 with allelic replacement at these positions, displayed different profiles allowing a clear distinction between wild and mutant types. We concluded that the DHFR gene mutations we investigated do not regulate T. gondii fitness in humans.

Animals↗

T cell mediated immune responses to Toxoplasma gondii in pregnant women with primary toxoplasmosis.

The aim of this study was to investigate T cell immunity to Toxoplasma gondii (Tg) in pregnant women with primary toxoplasmosis. This issue has never been addressed before in humans and available information derives from murine models. Peripheral blood mononuclear cells (PBMC) from pregnant women with primary Tg infection were stimulated with Tg tachyzoites, excretory-secretory antigens (ESA) or recombinant surface antigen-1 (rSAG-1), and tested for proliferation, immunophenotype, cytokine production and antigen specific cytotoxic activity. Pregnant women with primary toxoplasmosis displayed a significant decrease of the CD4/CD8 T cell ratio and a significant increase of circulating T cell receptor (TCR) gammadelta+ cells as compared to their uninfected counterparts. T cells from Tg infected pregnant women proliferated to Tg tachyzoites, ESA or rSAG-1. Most tachyzoite and ESA specific T cell blasts were CD4+, whereas SAG-1 specific blasts were CD4+ and CD8+. ESA and tachyzoite specific T cell blasts displayed a Th1 or Th0 cytokine profile with overexpression of IFN-gamma. This pattern was unchanged upon in vitro exposure of T cells to progesterone, tested at a concentration close to that reached in vivo at the maternal-fetal interface. Finally, tachyzoite or ESA specific T cell blasts lysed, through a granule exocytosis dependent mechanism, autologous lymphoblastoid cell lines presenting Tg antigens. In conclusion, pregnant women with primary toxoplasmosis mounted in vitro Tg-specific Th1/Th0 responses whose impact on neonatal infection warrants further investigation.

Animals↗

Diagnostic approaches to severe, atypical toxoplasmosis mimicking acute retinal necrosis.

PURPOSE: To describe the means of diagnosis and clinical features of atypical toxoplasmic chorioretinitis mimicking acute retinal necrosis. DESIGN: Observational case series. PARTICIPANTS: Twenty-two patients (25 eyes) with widespread chorioretinitis resulting from toxoplasmosis examined between 1990 and 2001. TESTING: Patients were diagnosed by various techniques, including polymerase chain reaction (PCR) of aqueous and vitreous, serum and intraocular antibody determination, culture of intraocular fluid, retinal biopsy, histopathologic examination, therapeutic trial of antibiotics active against toxoplasmosis, or a combination thereof. MAIN OUTCOME MEASURES: The primary outcome measure was diagnosis of disseminated toxoplasmic chorioretinitis by any combination of tests or by empiric use of specific antibiotics. The secondary outcome measure was visual and anatomic outcome of treatment. RESULTS: Mean age was 53.5 years (range, 19-77 years), with a median of 59.5 years. There were 9 women and 13 men. Six patients were infected with HIV, and 3 patients, 1 with HIV, had bilateral disease. Mean initial vision was 20/110 (median, 20/400; range, 20/20 to no light perception [NLP]). Sixteen patients (73%) had received oral or injectable corticosteroids and 11 (50%) had received antiviral therapy before the diagnosis of toxoplasmosis. Diagnosis was made solely by clinical response to antitoxoplasmosis medications in 4 patients. Sixteen patients were diagnosed based on evaluation of intraocular fluids and tissue by antibody determinations, culture, PCR, histopathologic examination, or a combination thereof. Visual acuity improved after treatment in 7 of 25 eyes (28%). Mean final visual acuity was 20/156 (median, 20/2500; range, 20/30 to NLP). Anatomically, 18 of 23 eyes with follow-up had healed or improved chorioretinitis. Retinitis was progressive in 1 eye, 2 eyes were enucleated, and 2 were phthisical. CONCLUSIONS: Diagnosis of atypical toxoplasmic chorioretinitis that mimics viral retinitis can be accomplished by several means. Prompt diagnosis may help avoid poor visual and anatomic outcomes after prolonged initial treatment with oral prednisone or antiviral medications.

Adult↗

Granulomatous villitis formed by inflammatory cells with maternal origin: a rare manifestation type of placental toxoplasmosis.

We present a case of placental toxoplasmosis with granulomatous villitis. The patient was a 26-year-old gravida 1 female with the findings of intrauterine death at 16th week of gestation. The pregnancy was terminated. Pathological examination revealed an autolysed fetus and a placenta with necrotizing granulomas within the villous stroma. Encysted Toxoplasma gondii was rarely observed within the granulomas and serologic examination of the mother confirmed acute toxoplasmosis. A fluorocein in situ hybridization examination, using sex chromosome probes, revealed that the villous granulomas were formed by inflammatory cells, originated from the maternal immune system. In conclusion, T. gondii should be taken into consideration as a rare cause of placental granulomatous inflammation. To the best of our knowledge, this is the first case of granulomatous villitis due to toxoplasmosis, in which formation by maternal inflammatory cells has been demonstrated.

Abortion, Induced↗

Seroepidemiological study of toxoplasmosis in intellectual disability children in rehabilitation centers of northern Iran.

Serological studies revealed that toxoplasmosis has world wide distribution. Although the infection by Toxoplasma gondii is widely prevalent in humans and animals, the disease is uncommon and most of the acquired infections are asymptomatic. The important aspect of this parasitic infection is the probable danger of congenital transmission and its severe effects on the fetus. There have been many reports about the prevalence of anti-T. gondii antibody among different groups of people in Iran; however the epidemiological data in intellectual disability (ID) persons are rare. This study was performed to evaluate the seroprevalence of toxoplasmosis among the inhabitants of rehabilitation centers of northern Iran. A total of 336 serum samples (161 males, 175 females) were examined for the IgG antibodies by indirect immunofluorescense technique. First of all, 1:50 titer dilution was tested, in the cases of positive result, further dilutions (1:100, 1:200, 1:400, 1:800, 1:1600, and 1:3200) were prepared and the last dilution was recorded. Among 336 sera, 77.4% showed seropositivity by IFAT. The positive rates of males and females were 77.6% (125/161) and 80% (140/175), respectively. However, there were no significant differences between sexes. Comparing the age groups, the highest seropositive rate showed in 19 or higher, and their rates had a tendency to increase with age. Prevalence of the infection in 10 rehabilitation centers was not significant either. Nevertheless, our data (77.4%) in rehabilitation centers in northern Iran suggest that infection is the same as in many other reports in normal population in this area, therefore toxoplasmosis is not a major problem in rehabilitation centers of this geographical area.

Adolescent↗

Efficacy of azithromycin in a murine toxoplasmosis model, employing a Toxoplasma gondii strain from Turkey.

A murine toxoplasmosis model with Balb/C mice was used to investigate the therapeutic and prophylactic efficacy of azithromycin in a native strain of Toxoplasma gondii. Initially, seven groups--four studies and three controls--were established and 10(3) tachyzoites of this native strain of T. gondii were injected intraperitoneally to the mice in groups 1, 2, 3, 4 and 7. Azithromycin was given to groups 1-4 at different times of infection orally between 100 and 300 mg/kg/day for 10 days. Azithromycin was found to be effective at 200 mg/kg/day and above in the prophylaxis, at 250 mg/kg/day and above in the treatment of toxoplasmosis. These results suggest that azithromycin is effective in the prophylaxis and early infection of a highly virulent strain of T. gondii, and it doubled the survival time in the late infection. Azithromycin could be an alternative treatment regimen for human toxoplasmosis, if supported by further clinical investigations.

Animals↗

Atypical anterior optic neuropathy caused by toxoplasmosis.

PURPOSE: To report atypical anterior optic neuropathy due to toxoplasmosis. METHODS: Interventional case report. A 33-year-old male presented with sudden painless loss of vision and floaters in the right eye. Examination demonstrated a best-corrected visual acuity of 20/200, optic nerve head edema, retinal hemorrhages, and vitreous opacities. RESULTS: Nine days later, a granuloma at the optic nerve head was apparent, and the patient was treated with pyrimethamine, sulfadiazine, folinic acid, and prednisone. Six weeks after initiating therapy, best-corrected visual acuity had improved to 20/25. CONCLUSION: Optic nerve involvement in toxoplasmosis is uncommon and, when it occurs, usually presents with a white inflammatory mass on the optic disk. The current case demonstrates the importance of including toxoplasmosis in the differential diagnosis of unilateral anterior optic neuropathy, even if a focal inflammatory mass is not apparent.

Adult↗

An update on current practices in the management of ocular toxoplasmosis.

PURPOSE: To update information that was published by the AMERICAN JOURNAL OF OPHTHALMOLOGY in 1991 about treatment practices for ocular toxoplasmosis by uveitis specialists. DESIGN: Physician survey. METHODS: A written questionnaire was distributed to all physician-members (n = 147) of the American Uveitis Society. The questionnaire was modeled after a similar device used to survey uveitis specialists in 1991. Information contained on 96 returned questionnaires was tabulated. RESULTS: Among 79 respondents who evaluate and manage patients with ocular toxoplasmosis, 15% treat all cases regardless of clinical findings (in contrast to 6% in 1991). The major indications for treatment among other respondents were severe inflammatory responses and proximity of retinal lesions to the fovea and optic disk. The majority of clinical factors considered in five categories (vision, lesion location, lesion size, lesion characteristics, and vitreous inflammatory reaction) were identified to be relative or absolute indications for treatment by a greater proportion of respondents in the current survey than in the 1991 survey. A total of nine drugs (or commercially available combinations) were used in 24 different regimens as treatments of choice for typical cases of recurrent toxoplasmic retinochoroiditis, with the combination of pyrimethamine, sulfadiazine, and prednisone being the most commonly used regimen (29% of respondents). CONCLUSIONS: Uveitis specialists appear to be more likely to treat patients with ocular toxoplasmosis in 2001 than in 1991. Although the majority of survey respondents adhere to a traditional approach to the management of toxoplasmic retinochoroiditis (a discrete course of systemic drug treatment during active disease using multiple antiparasitic drugs with or without corticosteroids), there is still no consensus regarding the choice of antiparasitic agents for treatment regimens. Survey results provide useful information for treating physicians and for clinical investigators interested in therapy.

Adult↗

A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis.

OBJECTIVE: To compare the effects of two treatment regimens, one of which included azithromycin, for the treatment of sight-threatening (near optic disk or fovea) ocular toxoplasmosis. DESIGN: Prospective, randomized open-labeled multicenter study, masked in part with regard to evaluation. METHODS: PARTICIPANTS TOTAL ENROLLMENT: 46 patients with sight-threatening ocular toxoplasmosis; pyrimethamine and azithromycin group: 24 patients; pyrimethamine and sulfadiazine group: 22 patients. INTERVENTION: Patients were randomized into two treatment regimens. Group 1 was treated with pyrimethamine and azithromycin complemented with folinic acid and the addition of prednisone from day 3. Group 2 was treated with pyrimethamine and sulfadiazine complemented with folinic acid and the addition of prednisone from day 3. Patients used study medications daily for 4 weeks. Ocular and laboratory examinations were performed at least weekly during the observation period. The study was masked in part with regard to evaluation. MAIN OUTCOME MEASURES: An assessment was made of the time to resolution of the intraocular inflammatory activity, the size of the retinochoroidal lesion, and visual acuity before and after the treatment as well as all adverse effects of treatments. RESULTS: Adverse effects were more frequent in the pyrimethamine/sulfadiazine group (P <.04), and three patients in this group had to discontinue treatment. The time to resolution of inflammatory activity, decrease in size of retinochoroidal lesions, and optimal visual acuity did not differ between the two treatment groups. The number of patients who developed recurrences during the first year after treatment was similar for both groups. CONCLUSIONS: The efficacy of the multidrug regimen with pyrimethamine and azithromycin was similar to the standard treatment with pyrimethamine and sulfadiazine. However, the frequency and severity of adverse effects was significantly lower with a regimen containing pyrimethamine and azithromycin. Multidrug therapy with the combination of pyrimethamine and azithromycin appears to be an acceptable alternative for treatment of sight-threatening ocular toxoplasmosis.

Adolescent↗