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Evaluation of the possibilities for preventing congenital toxoplasmosis.

Little is known about the best way to prevent congenital toxoplasmosis. Until recently, the major effort was directed at preventing the disease during pregnancy by the application of hygienic measures (primary prevention). With the advent of detecting congenital toxoplasmosis antenatally, another method for reducing the incidence of congenital toxoplasmosis becomes possible (secondary prevention). In this study, we evaluate these two methods for the prevention of congenital toxoplasmosis. For 12 consecutive years, we studied the incidence of congenital toxoplasmosis in 11,286 consecutive pregnant women. The impact of primary prevention was studied by measuring the reduction in seroconversion when hygienic measures were systematically applied. Primary prevention reduces the seroconversion rate during pregnancy by 63% (P = 0.013). The effect of secondary prevention was studied in 76 pregnant women at risk of delivering a child with congenital toxoplasmosis. Secondary prevention by means of serological screening combined with prenatal diagnosis detected congenital toxoplasmosis correctly in eight infected fetuses. Secondary prevention reduced the incidence of congenital toxoplasmosis an additional 40%. This reduction would predominantly be seen in the group of mildly to severely affected fetuses. From this study, the effectiveness of primary prevention is obvious. Health education on how to avoid toxoplasmosis during pregnancy should become standard obstetric care. Adequate serological screening and prenatal diagnosis can be helpful in reducing further the incidence of congenital toxoplasmosis. Whether or not screening for toxoplasmosis during pregnancy should be combined with primary prevention depends on the importance of congenital toxoplasmosis as a health problem in a given geographic area.

Belgium↗

Reactivations of ocular toxoplasmosis after cataract extraction.

PURPOSE: To determine the risk of reactivation of ocular toxoplasmosis following cataract extraction. DESIGN: Retrospective case-control study. PARTICIPANTS: Out of 154 patients with ocular toxoplasmosis, 14 patients (15 eyes) who had undergone a cataract extraction and 45 age- and sex- matched controls without cataract were selected. INTERVENTION: A review of the medical records of 14 patients with ocular toxoplasmosis and cataract and 45 control patients with ocular toxoplasmosis but without cataract. The clinical records of the controls and patients were assessed for an identical 4-month period following the date of the cataract extraction in the index patients. MAIN OUTCOME MEASURES: Development of a new active retinal lesion within 4 months after cataract surgery in patients and age -and sex matched-controls. The presence of risk factors such as sex, congenital or postnatal acquisition of ocular toxoplasmosis, age at first clinical manifestation of ocular toxoplasmosis, total number of attacks per affected eye, type of cataract, age at the time of cataract surgery and the intervals between surgery and first clinical manifestation of ocular toxoplasmosis and between surgery and the last recurrence of ocular toxoplasmosis, as well as the use of antiparasitic medication during surgery, type and complications of surgery and optimal visual acuity before and after cataract surgery. RESULTS: Reactivations of ocular toxoplasmosis following cataract extraction occurred in 5/14 patients (5/15 eyes), which was higher than the incidence of recurrences in age -and sex-matched controls (p < 0.001). No additional risk factors for the development of recurrences of ocular toxoplasmosis after cataract surgery were found. Incidence of recurrences preceding surgery did not differ between patients and controls. CONCLUSION: We identified an increased risk of reactivation of ocular toxoplasmosis following cataract extraction which implies that prophylactic treatment with antiparasitic drugs during and after the cataract surgery might be worthwhile for patients at risk of visual loss.

Adolescent↗

Serologic evaluation of patients with primary and recurrent ocular toxoplasmosis for evidence of recent infection.

PURPOSE: To identify the frequency of recently acquired vs chronic systemic Toxoplasma gondii infections in patients with ocular toxoplasmosis. METHODS: Serum samples from 22 patients with primary ocular toxoplasmosis (not from scars) and 42 patients with recurrent ocular toxoplasmosis were tested for the presence of anti-T. gondii IgM, IgG, and IgA antibodies and compared with samples from 24 patients with other causes of uveitis. Intraocular production of anti-T. gondii IgG and IgA, and the presence of T. gondii DNA was determined in patient s and control subjects from whom ocular fluid was available. RESULTS: Serologic evidence of recently acquired infection was found for 11 (50%) of 22 patients with primary ocular toxoplasmosis and for one (2%) of 42 with recurrent ocular toxoplasmosis. In the uveitis control group, anti-T. gondii IgM antibodies could be detected in two (8%) of 24 patients, but anti-T. gondii IgA antibodies were not detectable. Patients with primary ocular toxoplasmosis and serologic markers of recently acquired systemic infection were significantly older than those with chronic infection (P = .008). Intraocular production of anti-T. gondii IgG was more frequently noted in patients with recurrent than primary ocular toxoplasmosis (81% vs 41%; P < .001), but intraocular T. gondii DNA was more frequently found in patients with primary ocular toxoplasmosis than in those with recurrent ocular toxoplasmosis (37% vs 4%; P < .01). CONCLUSIONS: Primary ocular toxoplasmosis can be seen in either recently acquired or chronic T. gondii infection. Patients with ocular disease and recently acquired infection were older and more likely to have T. gondii DNA in intraocular fluids.

Adolescent↗

[Congential toxoplasmosis and ocular involvement. A review with 6 case reports].

A review is presented of the ocular affections in congenital toxoplasmosis. The epidemiological, pathogenetic and pathological conditions are reviewed together with the clinical manifestations and the diagnostic and therapeutic possibilities. On the basis of incidence investigations and knowledge from the literature, it must be assumed that approximately 190 infants with congenital toxoplasmosis are born annually in Denmark. Only approximately 15% of the infections will be symptom-producing and will be diagnosed neonatally, but more than 85% of the children with congenital toxoplasmosis will develop chorioretinitis on delivery or later in life and this will frequently cause reduction in vision or blindness. Congenital toxoplasmosis must be regarded as the commonest cause of chorioretinitis and it is probable that congenital toxoplasmosis and chorioretinitis due to toxoplasmosis are considerably underdiagnosed in Denmark. Treatment of congenital toxoplasmosis from birth improve the prognosis. Toxoplasmosis should be suspected in all cases of chorioretinitis. When antibodies to Toxoplasma gondii are demonstrated and the clinical picture is compatible with toxoplasmosis and when there is no other diagnosis, anti-Toxoplasma treatment should be considered. It is important to inform pregnant women about prophylactic measures. If investigations for toxoplasmosis were introduced in the prenatal or perinatal examinations, treatment could be initiated from birth and the diagnosis could be confirmed by possible activation of the chorioretinitis at a later date. Six case reports are presented.

Adult↗

Screening for toxoplasmosis in pregnancy: what is the evidence of reducing a health problem?

OBJECTIVES: Toxoplasma gondii is a parasite which may give rise to congenital infection. Screening pregnant women for antibodies against toxoplasmosis is being debated in many countries. The preventive impact of toxoplasmosis screening of pregnant women depends on the magnitude of disease caused by congenital toxoplasmosis (incidence x transmission rate to fetus x diseased proportion of infected children), on the one hand, and the preventable proportion of disease (sensitivity of the screening test x efficacy of the treatment x compliance), on the other. In this study the preventive impact of screening pregnant women for toxoplasmosis antibodies is assessed by letting the value for these variables change within reasonable limits. METHODS: To obtain information on these variables, relevant publications were reviewed in the Medline database from 1983 to February 1996 and the Cochrane Pregnancy and Childbirth Database. References in review articles on congenital toxoplasmosis were also studied. RESULTS: The literature review showed that no population based prospective studies of the natural history of toxoplasmosis infection during pregnancy, nor any randomised controlled trials of the efficacy of antiparasitic treatment, had been carried out. In the empirical studies which have been performed the values of most variables show considerable differences. According to these values, the estimates in this study of the impact of toxoplasmosis screening in pregnancy may range from 0 to 40 children in whom disease is preventable per 100,000 pregnant women susceptible to toxoplasmosis infection. CONCLUSION: Sufficient scientific evidence is not yet available to propose screening for toxoplasmosis in pregnant women, and efforts should be made to provide such knowledge. Also, the magnitude of the negative impact of screening, such as induced abortion of healthy fetuses, anxiety in women with false positive screening tests, and side effects of treatment, has not been sufficiently examined.

Antiprotozoal Agents↗

[Toxoplasmosis in French Guiana. Atypical (neo-)tropical features of a cosmopolitan parasitosis].

Toxoplasmosis, a typical cosmopolitan parasitosis, is a major health problem in French Guiana. Three factors account for this situation, i.e., (1) severity of toxoplasmosis in patients with HIV infection that is particularly prevalent in the area, (2) high risk of congenital transmission as shown by the steadily increasing prevalence of seropositivity in function of age in most of the Guianese population and (3) recent identification of severe primary toxoplasmosis infection in immunocompetent patients. In AIDS patients, the epidemiologic aspects of toxoplasmosis are correlated to the special features of the HIV-positive population in French Guiana and its clinical expression, mainly in the form of cerebral toxoplasmosis, does not suggest involvement of a particularly virulent strain of Toxoplasma. Similarly congenital toxoplasmosis does not present special tropical features other than problems associated with prevention, diagnosis and follow-up in poor and/or remote settings. These features are fully compatible with the classic domestic cat cycle of Toxoplasma gondii. However severe forms of primary infection, particularly in immunocompetent adults, appear to be associated with atypical features. These forms appear to be correlated with a forest-based cycle involving wild cats, which are still numerous in French Guiana, and their prey. Ingestion of undercooked wildcat prey, which is also a delicacy for man, can also be a source of contamination as can be consumption of untreated river water infected with oocysts excreted by felines. Observation of higher toxoplasmosis seroprevalence in wild noncarnivorous mammals that live by foraging on the ground in uninhabited forest zones suggests that infection can also be due to ingestion of oocysts eliminated into the soil. Since there are no domestic cats in the area, it must be assumed that these oocysts are shed by wild felines. More convincing proof can be seen in the fact that T. gondi strains presenting polymorphism, similarities and atypical genetic features can be found both in this animal reservoir, particularly in jaguars, and in patients presenting the more severe form of toxoplasmosis. In addition to the purely scientific interest of confirming the existence of the forest-based cycle, knowledge of this atypical form of toxoplasmosis that is probably not confined to French Guiana or to the Amazon region has obvious practical medical implications not only for diagnosis but also for therapy and prevention.

Animals↗

[Acquired toxoplasmosis of ocular or neurologic site: 49 cases].

OBJECTIVES: Over a period of 13 years (1982-1995), 49 cases of acquired toxoplasmosis complicated with ocular and/or neurologic or meningeal involvement were observed in our toxoplasmosis laboratory. This series includes 43 cases of isolated ocular lesions, 3 cases of meningoencephalitis (associated with retinochoroiditis in 1 case), 1 case of meningitis with uveitis, 1 case of polyradiculoneuritis and 1 case of facial nerve palsy. METHODS: The patients were aged 1 to 62 years. None had either spontaneous or iatrogenic immunodeficiency. There were two steps in the diagnosis. First congenital infection was eliminated on one or several of the following criteria: any possibility of maternal infection during pregnancy ruled out in 26 cases, evidence of recent acquired infection (i.e. clinical and/or serological evidence of recent acquired toxoplasmosis in 17 cases, retinochoroiditis in non-twin siblings in 3 cases). The second step was to confirm the diagnosis of toxoplasma infection. Apart from serological evidence of recent infection, confirmation included specific local antibody synthesis in the aqueous humor of the eye and/or in cerebro-spinal fluid or ocular lesions characteristic of toxoplasmosis and absence of other etiology. RESULTS: Ocular lesions were unilateral in 43 cases among 45. A mean follow-up of 37.9 months revealed relapses in 14 among 36 patients (39%). As routine serological examination for toxoplasmosis is compulsory in France since 1978, it was possible to document retrospectively the immune status of the mothers of many of the patients of the present series during pregnancy and to rule out congenital toxoplasmosis in a number of cases. This might explain the discrepancy between the relatively large number of cases in the present series and the fact that complicated acquired toxoplasmosis has been considered hitherto as relatively rare in immunocompetent patients. CONCLUSION: Based on the epidemiology of ocular toxoplasmosis and the data obtained here, it is suggested that the acquired pattern of ocular toxoplasmosis might be more frequent than estimated up to now.

Adolescent↗

Cerebral toxoplasmosis in HIV-positive patients in Brazil: clinical features and predictors of treatment response in the HAART era.

A prospective study of 55 confirmed or presumptive cases of cerebral toxoplasmosis in HIV positive patients in Brazil was performed to describe clinical characteristics and to identify predictive factors for clinical response to the anti-Toxoplasma treatment. Cerebral toxoplasmosis led to the diagnosis of HIV infection in 19 (35%) patients, whereas it was the AIDS defining disease in 41 (75%) patients. Of these, 22 (54%) patients were previously know to be HIV-positive. At diagnosis of cerebral toxoplasmosis, only 4 (7%) patients were on highly active antiretroviral therapy (HAART), and 6 (11%) were receiving primary cerebral toxoplasmosis prophylaxis. The mean CD4+ cell count was 64.2 (+/- 69.1) cells per microliter. Forty-nine patients (78%) showed alterations consistent with toxoplasmosis on brain computed tomography. At 6 weeks of treatment, 23 (42%) patients had complete clinical response, 25 (46%) partial response, and 7 (13%) died. Alteration of consciousness, Karnofsky score less than 70, psychomotor slowing, hemoglobin less than 12 mg/dL, mental confusion, Glasgow Coma Scale less than 12 were the main predictors of partial clinical response. All patients were placed on HAART within the first 4 weeks of diagnosis of cerebral toxoplasmosis. One year after the diagnosis, all available patients were on HAART and toxoplasmosis prophylaxis, and only 2 patients had relapse of cerebral toxoplasmosis. In Brazilian patients with AIDS, cerebral toxoplasmosis mainly occurs as an AIDS-defining disease, and causes significant morbidity and mortality. Signs of neurologic deterioration predict an unfavorable response to the treatment. Early start of HAART seems to be related to better survival and less relapses.

AIDS-Related Opportunistic Infections↗

Evaluation of serological markers for the immunodiagnosis of acute acquired toxoplasmosis.

The detection of specific IgM antibodies has been the most frequently used serological marker for diagnosing recent toxoplasmosis. However, the persistence of specific IgM antibodies in some patients and the use of tests with a low specificity have complicated the interpretation of serological results when toxoplasmosis is suspected. The purpose of the present study was to determine the value of newer serological techniques in the diagnosis of acute acquired toxoplasmosis. Sixty-four sera, 31 from patients with Toxoplasma gondii infection and 33 from patients with latent infection, were tested. Anti-T. gondii IgA was measured by two antibody capture ELISA tests (Platelia Toxo IgA and ETI-TOXOK A) and an automated direct ELISA (IMx Toxo IgA); all three assays detected antibody levels compatible with a recent infection in sera from all 31 patients with acute toxoplasmosis. However, significant levels of IgA were also detected with high frequency by all three assays in sera from patients with latent infection. IgE antibodies detected by IgE immunosorbent agglutination assay (ISAGA) were present in 26 (84%) of 31 patients with acute toxoplasmosis and in sera from two subjects with latent infection taken >1 year after the beginning of the clinical symptoms of infection. Thirty (97%) of 31 patients with a recent T. gondii infection and 15 (45%) of 33 subjects with latent infection had an AC/HS pattern compatible with acute toxoplasmosis. The avidity of T. gondii IgG was evaluated by two methods. One method was based on the titration of each serum sample and calculation of the titres, in the absence and presence of urea, in relation to a defined cut-off value. In the other method, a single serum dilution was used and the absorbances of the reactions in the presence and absence of urea were compared. The titration method was more sensitive for diagnosing recent primary infection; all 31 sera from patients with acute toxoplasmosis had avidity indices compatible with acute toxoplasmosis by the titration method, whereas with the single dilution method, sera from four patients had equivocal results. In the 33 individuals with latent infection, similar results were obtained with the two avidity methods; only one serum sample had a non-compatible avidity value with the titration method. The results obtained in the present study show that the current serological markers used for diagnosing acute acquired toxoplasmosis have significant limitations. The data suggest that determination of the avidity of T. gondii-specific IgG by the titration method in patients with detectable IgM antibodies defines most accurately the stage of infection by T. gondii.

Acute Disease↗

Prevention of toxoplasmosis during pregnancy--an epidemiologic survey over 22 consecutive years.

BACKGROUND: Prevention of congenital toxoplasmosis is most often based on the results of a serological screening program in pregnant women followed by prenatal and postnatal treatment of women and their newborns when infection is already established during pregnancy or on cord blood (secondary prevention). Little effort has been made to study primary prevention of toxoplasmosis during pregnancy. OBJECTIVE: To assess the possibilities of two different programs aimed at preventing the acquisition of toxoplasmosis during pregnancy. METHODS: During the first study period (1979-1982) the natural incidence of toxoplasmosis in pregnancy was studied in 2986 pregnant women. In the second study period (1983-1990) the incidence of toxoplasmosis was studied in 8300 women. During this period, seronegative women received a written list of recommendations on how to avoid a toxoplasma infection during pregnancy. In the third study period (1991-2001) the incidence of toxoplasmosis was studied in 16,541 women. During this period, the prevention campaign consisted of a leaflet explaining a) toxoplasmosis as a disease and b) what measures should be taken to avoid toxoplasmosis during pregnancy. The third part of the campaign involved a reiteration of these recommendations during antenatal classes held around mid-gestation. The impact of the two prevention programs was studied by measuring the seroconversion rate in seronegative women. RESULTS: Twenty of 1403 seronegative women in the first period (1.43%), 19 of 3605 women in the second period (0.53%) and 8 of 8492 in the third period (0.09%) seroconverted during pregnancy. The first prevention campaign reduced the seroconversion rate by 63% (p<0.05 OR 2.729 95% CI 1.452-5.084). The second prevention program resulted in a reduction rate of 92% compared to the seroconversion rate in the first period (p<0.0001 OR 15.34 95% CI 6.741-34.89). CONCLUSION: Promotion of simple measures is very effective in the prevention of toxoplasmosis during pregnancy. Primary prevention should not only be based on education about preventive measures given by physicians, but these guidelines should be reiterated during antenatal classes and leaflets distributed containing written recommendations on the nature of the disease and its avoidance.

Belgium↗

[Ocular toxoplasmosis: our experience].

Ocular toxoplasmosis can be a progressive and recurring disease that can threaten visual function. Retinochoroiditis develops gradually weeks to years after subclinical congenital toxoplasmosis; this is the preponderant form, which is frequently bilateral; with healing, white or dark-pigmented scars may result. Toxoplasmosis acquired in older children and adults rarely progresses to retinochoroiditis; it is generally unilateral. We report the results of a clinical study concerning 16 patients with ocular toxoplasmosis observed for the first time in the period from 1992 to 2004 and followed up until today. The patients came to the Department of Infectious Diseases of the Second University of Naples. We studied 16 patients, 10 of whom were females; 11 cases presented ocular signs of congenital toxoplasmosis, while in 5 cases ocular impairment was related to an acquired toxoplasmosis. Only one case of congenital toxoplasma chorioretinitis was symptomatic at birth: it was complicated by microphthalmia and strabismus, calcifications in the brain and epilepsy; 10 congenital cases were asymptomatic at birth and were recognized after several years because of a reactivation of infection. In 5 patients congenital chorioretinitis was bilateral, with presence of scars in the contralateral eye. The 5 cases of acquired toxoplasma retinitis were ascertained by anamnestic, serologic and ophthalmologic examinations; in 4 of them the lesion was typical and unilateral; the 5th case was a 6-year-old boy with acquired toxoplasma bilateral neuroretinitis. 13/16 cases of ocular toxoplasmosis were treated with the combination of pyrimethamine, sulfadiazine; they were followed up and re-treated if necessary. The therapy was curative in each case. Our experience confirms that late-onset retinal lesions and relapse can occur many years after birth but that the overall ocular prognosis is satisfactory when congenital damage is recognized early and treated appropriately. Prevention of congenital and acquired toxoplasmosis is very important in controlling ocular toxoplasmosis.

Adolescent↗

[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

Female↗