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Risk of Visual Impairment in Children with Congenital Toxoplasmic Retinochoroiditis
Abstract
Reliable information is needed to counsel parents of children with congenital toxoplasmosis regarding the long-term risk of visual impairment resulting from ocular toxoplasmosis.
Prospective cohort study of children with congenital toxoplasmosis identified by prenatal or neonatal screening.
After three years of age, ophthalmologists reported the site of retinochoroidal lesions and visual acuity and parents reported visual impairment. An ophthalmologist predicted the child's vision based on the last retinal diagram. Selection biases were minimized by prospective enrollment and data collection, high rates of follow-up, and exclusion of referred cases.
Two hundred and eighty-one of 284 infected children who underwent ophthalmic examinations were followed up to a median age of 4.8 years. One in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole. In children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23). Analyses based on affected eyes showed that 42% (29/69) had a posterior pole lesion, of which just more than half (15/29, 52%) had normal vision, as did 84% (16/19) of eyes with a peripheral lesion alone. Vision predicted by the ophthalmologist was moderately sensitive (59%) but overestimated impairment associated with posterior pole lesions. Of 44 children with information on acuity, four (9%) had bilateral visual impairment worse than 6/12 Snellen.
Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye.
... Congenital Toxoplasmosis increased the risk of visual impairment (RR: 5.07; 95% CI 2.62-9.81) [7,57,66]; however, in these patients visual impairment is also determined by macular localization (RR: 3.06; 95% CI 1. 16-9.28) [66]. ...
... Congenital Toxoplasmosis increased the risk of visual impairment (RR: 5.07; 95% CI 2.62-9.81) [7,57,66]; however, in these patients visual impairment is also determined by macular localization (RR: 3.06; 95% CI 1. 16-9.28) [66]. ...
... In addition to the previously mentioned factors (macular location of the lesions and recurrences) [7,27,32,35,37,64,65], other factors that increased the risk of blindness are extensive or atypical lesions in patients aged more than 45 years [7,27,32,64,79], and congenital toxoplasmosis [7,57,66]. Therefore, a closer follow-up and optimized treatment should be considered in these patients. Moreover, we evidence that few articles detail the immunological status of patients, which should be added in future studies in order to quantify the impact of this variable. ...
Background: Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide.
Methods and findings: We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836).
Results: Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%–58%), being more frequent in the South American population tan in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%–48%) and blindness in
20% (95% CI 13%–30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72–8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59–6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment.
Conclusion: Our Systematic Review showed that clinical factors such as being older
than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy.
... Nevertheless, first lesions may arise more than 12 years after birth [17,93]. In European patients, lesions are present in 17% of children after 3 years [21] and in 24% of children after a follow-up of 6 years [9]. Expanding the follow-up to more than 10 years, ocular lesions were found in 29.8% of treated children, which were unilateral in 69.0% and did not cause vision loss in 80.6%. ...
... Expanding the follow-up to more than 10 years, ocular lesions were found in 29.8% of treated children, which were unilateral in 69.0% and did not cause vision loss in 80.6%. Bilateral visual impairment thus seems rare in European cohorts, and two-thirds present with normal vision in either eye [9,15,21]. ...
... Beyond secondary pathologies, squinting (strabismus) was the most prevalent (16%). The overall functional prognosis of CT in Europe is better than would be expected on the basis of literature findings, between less than 2% and 9% suffering bilateral visual impairment [4,21]. The consequences of CT are rarely severe in European children treated in utero and until the end of their first year of life. ...
Even in the absence of manifestations at birth, children with congenital toxoplasmosis (CT) may develop serious long-term sequelae later in life. This systematic review aims to present the current state of knowledge to base an informed decision on how to optimally manage these pregnancies and children. For this, a systematic literature search was performed on 28th July 2022 in PubMed, CENTRAL, ClinicalTrials.gov, Google Scholar and Scopus to identify all prospective and retrospective studies on congenital toxoplasmosis and its long-term outcomes that were evaluated by the authors. We included 31 research papers from several countries. Virulent parasite strains, low socioeconomic status and any delay of treatment seem to contribute to a worse outcome, whereas an early diagnosis of CT as a consequence of prenatal screening may be beneficial. The rate of ocular lesions in treated children increases over time to 30% in European and over 70% in South American children and can be considerably reduced by early treatment in the first year of life. After treatment, new neurological manifestations are not reported, while ocular recurrences are observed in more than 50% of patients, with a mild to moderate impact on quality of life in European cohorts when compared to a significantly reduced quality of life in the more severely affected South American children. Though CT is rare and less severe in Europe when compared with South America, antenatal screening is the only effective way to diagnose and treat affected individuals at the earliest possible time in order to reduce the burden of disease and achieve satisfying outcomes.
... 5 Cohort studies of children with congenital toxoplasmosis showed that ocular disease, usually chorioretinitis, develops in 17%-80% of them. [6][7][8][9][10][11][12] Earlier studies performed more than 30 years ago reported higher risk of ocular lesions -approximately 80%. 6,7 Some of them had a small sample size. ...
... More recent prospective studies report lower risk of chorioretinitis, ranging from 17% to 30%. [8][9][10][11][12] Chorioretinitis mainly occurs before the age of 5 years, 2,8 but first ocular lesion has been reported as late as 12 years after birth. 9 These studies confirm an overall good prognosis of congenital toxoplasmosis in Europe and North America. ...
... More than 90% of children with chorioretinitis have normal vision in their best eye, and severe bilateral impairment is rare. [10][11][12] In contrast, cohort studies in South America reported more frequent and more severe ocular disease. In the study of Gilbert et al, two-thirds of children with congenital toxoplasmosis in Brazil had eye lesion by 4 years of age, compared with one in six in Europe. ...
We report a case of a newborn male child with congenital toxoplasmosis. During pregnancy seroconversion occurred and positive titers of antitoxoplasmic antibodies (immunoglobulin M and G) were found in the mother, in the third trimester. She received treatment with spiramycin. After birth, the neonate presented with chorioretinitis and intracranial calcifications. The neonate received treatment with pyrimethamine, sulfadiazine, and leucovorin for 1 year. In addition to using a previously described method, we report for the first time in Greece an estimation regarding the percentage of ocular toxoplasmosis caused by congenital or acquired infection. We estimate that ocular toxoplasmosis in Greece is caused in 7% of the cases by congenital infection, and in 93% of the cases by acquired infection.
... There are also atypical strains present in the Americas thought to have a higher level of virulence resulting in worse clinical manifestations, even in immunocompetent infected hosts. 1,3,4 ...
... Significant visual loss, especially bilateral vision loss, has been rare in these cohorts. [3][4][5][6][7][8]10,15,16 Prenatal and antenatal treatment with various antibacterial agents have not shown any effect on the development of retinal lesions, though it has shown to reduce risk of intracranial lesions. 5,7,16 Incidence and severity of retinal scarring, intracranial calcifications, and developmental delay have been shown to be significantly higher in one US study. ...
Background
Toxoplasmosis gondii is ubiquitously present on earth and infection, including congenital infection, is common. Neurological, developmental, and ocular effects can be devastating in the congenital toxoplasmosis population. At present, there is no standard, nation-wide neonatal screening for this disease in the United States.
Case Presentation
A 17-month-old Caucasian female presented to our institution by way of referral for macular scarring. She was diagnosed with intrauterine growth retardation and born with low birth weight and microcephaly at an outside institution, but no systemic workup was conducted at that time. On ocular examination, she was found to have nystagmus and extensive multifocal chorioretinal pigmented scars involving the macula and peripheral retina in both eyes with fibrous vitreous strands extending between scars in the right eye. Toxoplasmosis immunoglobulin G was found to be highly positive. Magnetic resonance imaging of the brain showed supratentorial intracranial calcifications.
Conclusions
Our patient presented with severe chorioretinal lesions, microcephaly, and nystagmus with a positive immunoglobulin G toxoplasmosis titer. She did not receive any evaluation, including TORCH infectious panel workup, on being born with low birth weight and microcephaly. There are currently no national programs in place for toxoplasmosis to be included in routine neonatal screening, despite the grave sequelae of congenital infection or that studies in other countries have shown cost-effectiveness in early screening and treatment.
... T. gondii retinal lesion location has been shown to have an effect on visual acuity in patients [5,8,17]. Recently, in a prospective study of 281 children with congenital toxoplasmosis, Tan et al., observed that nearly half the children with a posterior pole lesion developed a visual impairment in the affected eye, compared to less than 20% of those with more peripheral lesions [17]. ...
... T. gondii retinal lesion location has been shown to have an effect on visual acuity in patients [5,8,17]. Recently, in a prospective study of 281 children with congenital toxoplasmosis, Tan et al., observed that nearly half the children with a posterior pole lesion developed a visual impairment in the affected eye, compared to less than 20% of those with more peripheral lesions [17]. Additionally, Bosch-Driessen et al., attributed legal blindness in nearly one quarter of 154 patients to the macular location of retinal lesions and retinal detachments [5]. ...
p> Purpose: To characterize the clinical features of ocular toxoplasmosis (OT) in Central Cuba.
Methods: A database at a large regional referral center was searched for patients who, from April 1, 2011 to May 31, 2013, had the potential diagnosis of OT. Inclusion criteria were the clinical diagnosis of OT, characterized by focal retinochoroidal inflammation. Medical records were reviewed to confirm inclusion criteria (visual acuity recorded in decimal form).
Results: 279 patients (329 total eyes) were affected with OT. Overall, 66.7% were diagnosed with acquired OT with a mean age of 35.4 years and 1.8% with congenital OT with a mean age of 3.4 years. The time of onset of OT could not be determined in 28.3% (n=79) of patients. Patient clinical presentations were posterior uveitis (72.8 %), quiescent retinochoroiditis (16.1 %), and panuveitis (11.1%). Fourteen percent of patients had a slight decrease (0.9-0.6) in visual acuity, 44.4% a moderate decrease (0.5-0.2), and 41.6% a marked decrease (< 0.1).
Conclusion: There exist large numbers of patients with active toxoplasmic uveitis in the Central Cuban region. To our knowledge, this is the first report in the English medical literature describing OT in the Cuban population.</p
... A large retrospective study in the US estimated the number at approximately one in 10,000 live births (Guerina et al., 1994), whereas three in 10,000 live births were observed in France (Villena et al., 2010). A prospective cohort study on European children with confirmed congenital toxoplasmosis found retinal lesions in one of six of these children, who received treatment for at least 1 year, after the first 4 years of life (Tan et al., 2007). Curiously, some North American studies found retinal lesions in more than 70% of congenitally infected and untreated, and 58% of treated children (Mets et al., 1996;Phan et al., 2008). ...
... Manifestations at birth are less severe and recurrences are fewer in those who were treated promptly, early in the course of their disease in utero and in the first year of life. European studies suggested that up to 9% of children with retinal lesions due to congenital toxoplasmosis have significant bilateral vision impairment (Tan et al., 2007). ...
Retinal lesions or other ocular manifestations are serious consequences of infection with the protozoan parasite Toxoplasma gondii. Whilst classically considered a consequence of congenital transmission, recent screening studies estimated that 2% of T. gondii seropositive persons in Europe and North America have retinal lesions, most of them persisting unnoticed. The situation is more dramatic in South America, probably due to the predominance of virulent strains. Some of these strains seem to exhibit ocular or neuronal tropism and are responsible for severe ocular lesions. Despite the medical importance, the physiopathological mechanisms have only recently begun to be elucidated. The particular immune-privileged situation in the eye has to be considered. Studies on French patients showed low or undetectable ocular parasite loads, but a clear Th1/Th17 type immune reaction. Suitable mouse models have appeared in the last few years. Using such a model, IL-17A proved to impair parasite control and induce pathology. In contrast, in South American patients, the parasite seems to be much less efficiently controlled through a Th2 type or suppressive immune response that favors parasite replication. Finally, several host genetic markers controlling immune response factors have been associated with ocular involvement of T. gondii infection, mainly in South America.
... Previous European cohorts provided similar results: 7e33% of children presented with ocular lesion, lower numbers being associated with shorter followups. 3,4,7,9,25 Congenital toxoplasmosis most often involved peripheral retinal area in previous works as in our study 9,11 and therefore had little impact on quality of life and visual performance. 18 We showed additionally for the first time that late lesions were more likely to be peripheral and therefore not associated with impairment of visual acuity, in line with the good long-term functional prognosis. ...
... These outcomes were similar to previous European reports using various treatment regimens. 3,4,7,9,25 Notably, 26% of children treated for 24 months developed chorioretinitis in a previous cohort. 7 Even shorter postnatal treatments (3 months) are currently evaluated by the TOSCANE (NCT01202500) clinical trial. ...
Congenital toxoplasmosis remains a public health problem throughout the world. Long-term longitudinal studies are still needed to argument controversial screening and treatment strategies and to enable to accurately counsel parents.
We conducted a prospective cohort study over 16 years in Marseilles, France. Seronegative pregnant women underwent monthly serological testing. Children were treated antenatally with rovamycine as soon as maternal infection was detected and with pyrimethamine and sulfadoxine in case of positive Toxoplasma PCR on amniotic fluid. Postnatal treatment with pyrimethamine and sulfadoxine was systematically prescribed for one year and possibly continued at the physician discretion.
127 children were included. 24 children (18.9%) presented ocular lesions causing visual impairment in eight cases. Eleven children (8.7%) presented with ocular lesions at birth, mostly macular. Sixteen children (12.6%) developed ocular lesions during follow-up, mostly peripheral. The first ocular lesion could occur as late as 12 years after birth. No significant risk factor of chorioretinitis was identified including gestational age at infection, type of antenatal treatment and shorter postnatal treatment.
These results confirm the overall good prognosis of congenital toxoplasmosis in Europe but highlight though a low risk of late ocular manifestation. Chorioretinitis affected 18.9% of children suffering from congenital toxoplasmosis despite antenatal and neonatal screening associated with early treatment. Long-standing follow-up is needed because first lesion can occur as late as 12 years after birth. Late lesions were less often macular but nevertheless caused sometimes visual impairment.
... 102 New active satellite lesions appear adjacent to an atrophic scar with hyperpigmented borders 98 either in congenital or in acquired infections ( Figure 5). Bilateral retinochoroidal lesions and macular involvement are more common in congenital case 84,89,90,98,102,104,[106][107][108][109][110][111][112] (Figure 6). Severe inflammation can affect the anterior chamber, leading to granulomatous anterior uveitis and high intraocular pressure. ...
Purpose: To describe the most important cause of infectious posterior uveitis in pediatric patients.
Methods: Review of the literatura.
Results: The most important causes of infectious uveitis in pediatric patients are: cat-scratch disease, toxocariasis, tuberculosis, viral diseases and toxoplasmosis. Ocular manifestations include retinitis, neuroretinitis, choroidal granulomas, peripheral granulomas and posterior pole granulomas.
Conclusion: Infectious posterior uveitis is a challenging subject and should be considered in the differential diagnosis of any posterior uveitis in children. Infectious uveitis must be excluded before initiating immunosuppressive therapy.
... Visual impairment of the more strongly affected eye occurs in 29 % of children with toxoplasma retinochoroiditis [19]. Severe bilateral visual impairment is rare (9 %) [20,21]. Ocular lesions may first appear several years after birth (39 % at birth, 85 % before 5 years of age, 96 % before 10 years of age) [16]. ...
Aim The AGG (Working Group for Obstetrics and Prenatal Diagnostics, Section Maternal Diseases) has issued these recommendations to improve the detection and management of Toxoplasma gondii infection in pregnancy.
Methods Members of the Task Force developed the recommendations and statements presented here using recently published literature. The recommendations were adopted after a consensus process by members of the working group.
Recommendations This article focuses on the epidemiology and pathophysiology of Toxoplasma gondii infection in pregnancy and includes recommendations for maternal and fetal diagnosis, transmission prophylaxis, therapy, prevention, screening, and peripartum management.
... A delay between maternal seroconversion and the beginning of treatment, and especially the presence of cerebral calcifications, are risk factors of retinochoroiditis during the first 2 years of life (77). In a prospective cohort study on 3 years old children with congenital toxoplasmosis, more than 90% of children with chorioretinitis had normal vision in the best eye, and only 9% had severe bilateral impairment (78). ...
Infection with the protozoan parasite Toxoplasma gondii occurs worldwide and usually causes no symptoms. However, a primary infection of pregnant women, may infect the fetus by transplacental transmission. The risk of mother-to-child transmission depends on week of pregnancy at the time of maternal infection: it is low in the first trimester, may reach 90% in the last days of pregnancy. Inversely, however, fetal disease is more severe when infection occurs early in pregnancy than later. Systematic serologic testing in pregnant women who have no antibodies at the beginning of pregnancy, can accurately reveal active maternal infection. Therefore, the risk of fetal infection should be assessed and preventive treatment with spiramycin must be introduced as soon as possible to reduce the risk of mother-to-child transmission, and the severity of fetal infection. When maternal infection is confirmed, prenatal diagnosis with Polymerase Chain Reaction (PCR) on amniotic fluid is recommended. If fetal infection is certain, the maternal treatment is changed to a combination of pyrimethamine-sulfonamide and folinic acid. Congenitally infected newborns are usually asymptomatic at birth, but at risk for tardive sequelae, such as blindness. When congenital infection is evident, disease include retinochoroiditis, cerebral calcifications, hydrocephalus, neurocognitive impairment. The diagnosis of congenital infection must be confirmed at birth and management, specific therapy, and follow-up with multidisciplinary counseling, must be guaranteed.
... A study including 281 of 284 infected children who underwent ophthalmic examinations and followed up to a median age of 4.8 years found that one in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole and 41% (20/49) had bilateral lesions whether clinical manifestations were present or not at birth. A study of children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23) (Tan et al., 2007). ...
Prenatal systematic screening for congenital toxoplasmosis has been performed in Austria and France since 1975 and neonatal screening for congenital toxoplasmosis has been part of the New England Newborn screening program since 1986.
In this narrative review we review the data leading up to the systematic screening programs in Austria and France, highlighting the main finding of the European Union funded research in the 1990s and early 2000s. Different descriptive studies of the effect of pre- or postnatal treatment are discussed. Toxoplasma gondii has different genetic lineages with different pathogenicity in humans. This means that results in areas with a low pathogenic lineage cannot be extrapolated to an area with highly pathogenic lineages. The importance of meat as a source of infection is discussed in the light of an increased prevalence of T.gondii in organic livestock production .
... However, higher doses of pyrimethamine were not found to be accompanied by better outcomes [53] while the optimal duration of postnatal treatment is still disputed [54]. Follow up results of Faucher et al. [52] compared with that of previous European reports irrespective of the treatment duration [26,32,45,55,56]. In the United States, the TOXOGEST (NCT01189448) trial was carried out to determine whether antenatal treatment with pyrimethamine and sulfadiazine is associated with better results than spiramycin. ...
Toxoplasma gondii is an obligate intracellular parasite which is known to infect one-third of the total world population chronically though it is asymptomatic in immunocompetent patients. However, in an immunocompromised patient or an infected fetus, it may cause devastating effects. The parasite may cross the placenta of an infected pregnant woman and probably infect the fetus congenitally. The severity of the infection depends on the gestational age at which the infection has occurred i.e., if it has occurred in the early phase, the rate of transmission is low but the severity is high if the fetus is infected and if it has occurred in the later phase then transmission rate is higher while the severity would be low. Congenital toxoplasmosis may result in non-specific consequences like abortion, intra-uterine growth restriction, jaundice, hepatosplenomegaly or even intra-uterine death. It may also result in neurological or ocular manifestations like intracranial calcifications, hydrocephalus or retinochoroiditis. The diagnosis may be done by serological screening of anti-Toxoplasma antibodies (IgM and IgG) while PCR of the amniotic fluid or the placenta is the confirmatory test. Acute or chronic infections may be differentiated by IgG avidity tests. The treatment regimens include spiramycin to prevent congenital transmission from an infected mother, pyrimethamine, sulfadoxine and folinic acid to treat the infected fetus, CSF shunting for the treatment of hydrocephalus and a combination of pyrimethamine, azithromycin, and corticosteroids for treating ocular toxoplasmosis.
... The classic presentation of congenital toxoplasmosis includes bilateral RC in approximately 85 % of affected individuals, with a predilection for the posterior pole and macula [11][12][13] and older patients may present with atypical findings, including large, multiple, and/or bilateral lesions, with or without associated chorioretinal scars. ...
Parasitic and fungal infections of the eye are major, worldwide distributed causes of infectious posterior uveitis that may lead to blindness. The causative agents include several species of Protozoa and Helminths that have a natural predilection for the eye. These parasitic infections may be transmitted by vectors, food consumption, or acquired indirectly from the environment. Ocular involvement can be due to damage directly caused by the infectious pathogen, indirect pathology caused by toxic products, or the immune response incited by infections or ectopic parasitism. Epidemiologic data, clinical features, diagnostic tools, and management of the clinically important species of parasites involved in posterior uveitis including toxoplasmosis and toxocariasis are reviewed in this chapter. Presumed ocular histoplasmosis syndrome, which is considered to be of fungal origin, also will be discussed.
... A British survey of visual impairment in congenitally infected children reported that 17% presented at least one retinal lesion and 9% suffered from severe bilateral impairment. 39 There is a need for public health strategies in terms of early detection and treatment as well as routine serological screening of all pregnant women as practiced elsewhere. 40 In conclusion, we found ocular toxoplasmosis was associated with older age. ...
Purpose:
To conduct the first ever population-based survey on ocular toxoplasmosis in the Central Region of Ghana.
Methods:
A cross-sectional population-based study was conducted in three randomly selected communities in the Central Region, Ghana. Visual acuity (VA) measurement, dilated fundus examination by indirect ophthalmoscopy and serology testing were performed on all participants. Ocular toxoplasmosis was diagnosed based on characteristic retinal lesions and supported by positive serologic testing using commercial enzyme-linked immunosorbent assay (ELISA) kits.
Results:
A total of 390 subjects aged 10-100 years (mean age 47 years) were examined; 118 (30.3%) were male and 272 (69.7%) female. Ten subjects (6 females and 4 males) had toxoplasmic ocular lesions (prevalence 2.6%). Of these, two had bilateral lesions and eight had unilateral lesions. Subjects with toxoplasmic ocular lesions were older than those without lesions (p = 0.028). The development of ocular toxoplasmosis was not associated with rural dwelling, sex, keeping cats, or consumption of meat.
Conclusion:
The prevalence of ocular toxoplasmosis in our Ghanaian study population was lower than findings from Southern Brazil, where there is a similar prevalence of infection in the general population.
... A large retro- 122 spective study in the US estimated the number at approximately 123 one in 10,000 live births (Guerina et al., 1994), whereas three in 124 10,000 live births were observed in France (Villena et al., 2010). 125 A prospective cohort study on European children with confirmed 126 congenital toxoplasmosis found retinal lesions in one of six of 127 these children, who received treatment for at least 1 year, after 128 the first 4 years of life (Tan et al., 2007). Curiously, some North 129 American studies found retinal lesions in more than 70% of congen- 130 itally infected and untreated, and 58% of treated children (Mets 131 et al., . ...
Ocular involvement, mainly retinochoroiditis, is one of the most severe sequelae of Toxoplasma gondii infection. However, the pathophysiological mechanisms of retinal destruction are poorly understood. Several studies suggested a more frequent and more severe ocular involvement in South American infections compared with European infections, probably due to different T. gondii strains (Type I/III, and atypical vs. Type II). To compare the clinical characteristics and biological and immunological responses in a single study and using the same parameters, in Colombian and French patients with active ocular toxoplasmosis (OT), as well as to study the local cytokinome in aqueous humor of these patients and correlate it with the clinical features. We prospectively collected and compared the clinical features of patients with active OT, evaluated at the Department of Ophthalmology of Strasbourg University Hospital and of Quindio University Health-Center. Results of biological tests in the collected aqueous humor samples were compared between Colombian and French patients: the pattern of protein recognition by immunoblotting (IB); the relative diagnostic sensitivities of IB and Polymerase Chain Reaction (PCR); and the cytokine and chemokine profiles. We found that Colombian and French OT patients presented not only different clinical characteristics but also biological characteristics, and that more virulent South American strains might be responsible for these differences, due to a disruption of the protective effects of interferon gamma (IFN-γ). Retinal lesions were 50% greater in Colombian patients. Macular localization leading to visual impairment was observed in 56% of Colombian cases, compared with 13% of French patients. Moreover, more vitreous inflammation and vasculitis were observed in Colombian patients. However, cytokine assays of the aqueous humor showed upregulation of inflammatory responses in European patients, notably IL-17, which we did not observe in Colombian patients. In a mouse model, intraocular tachyzoite injection of type II and atypical T. gondii strains resulted in differences in parasite multiplication and pathology similar to those observed in human infections. Production of IL-17 and other inflammatory markers, like IL-6, MCP-1, and the Th17 transcription factor ROR-γt was observed upon infection with the type II PRU strain, but was much less with the atypical LEF strain. In a previous work, the cytokine and mRNA patterns showed an upregulation of Th1 responses, notably IFN-γ production, in French patients, and anti-IL-17A antibody markedly diminished clinical damage and retinal inflammation, and also diminished parasite proliferation. In contrast to these previous findings in French patients, the cytokinome of aqueous humor of OT Colombian patients showed a downregulation of Th1 and Th17 responses and an upregulation of the Th2 response. Correlation between the clinical characteristics of Colombian patients with active OT and the levels of cytokines in aqueous humor (AH) showed that local production of cytokines differed between patients with OT, and particular cytokine levels were related to more severe clinical characteristics. Some cytokines were related to a higher number of recurrences.There are clinical and biological differences between Colombian and French patients with OT. There seem to be strain-specific differences in IL-17 and IFN-γ induction, which play an important role in the pathogenesis of this disease. These differences should be considered when thinking in perspectives of any possible immune-modulatory treatment in OT.
... Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half of the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye (Tan et al. 2007). Numerous children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. ...
... Several The Official Periodical of the Libyan National Center for Infectious Diseases Prevention and Control studies have shown that the risk and severity of congenital toxoplasmosis are greatest when acquired during the first three months of pregnancy (4)(5)(6). The consequences of congenital toxoplasmosis range from spontaneous abortion and prematurity to generalized and neurological symptoms which often involve ocular complications (7,8). ...
Background and Objective: Maternal viral and protozoan infections contribute to many complications in early pregnancies leading to spontaneous abortion. The present study was aimed to determine the prevalence of toxoplasmosis and rubella infections in women experienced spontaneous abortion. Materials and Methods: 692 serum samples were tested for the presence of antibodies for toxoplasmosis and rubella using ELISA techniques. The investigations were carried out in the laboratory of Tripoli Central Hospital from January 2002 to December 2007. Results: Testing results showed serological evidence of previous infection in 17.6% of tested women for toxoplasmosis and only 4.3% for rubella with co-existence of both infections in only 1.8% of women. Conclusion: It seems that testing is more useful in excluding rather than establishing etiology. Considering the study outcome, it appears that toxoplasmosis and rubella represent only about one fifth of the total number of spontaneous abortion, this means that there are some other factors involved that have to be identified and deeply studied in order to establish prevention and therapeutic strategies.
... These were used as a surrogate measure as children in Brazil did not have visual acuity measures. However, limited accuracy in ophthalmologist prediction (85% specific and 59% sensitive for visual impairment of ,6/18 Snellen), [45] is unlikely to explain the very large differences in predicted visual impairment observed between Brazil and Europe. ...
Background: Toxoplasmic retinochoroiditis appears to be more severe in Brazil, where it is a leading cause of blindness, than in Europe, but direct comparisons are lacking. Evidence is accumulating that more virulent genotypes of Toxoplasma gondii predominate in South America.
... In the United States, approximately 9% of children with congenital toxoplasmosis have significant visual impairment, [46] whereas rates are much higher in other regions. Within Europe, 29% of such children have visual impairment, compared with 87% from the Brazilian cohorts, in the three to four years following birth. ...
Toxoplasmosis, a disease described worldwide, which is caused by the protozoan Toxoplasma gondii, commonly involves the retina. The disease has a higher impact in immunocompromised individuals and in congenital infection because of the severity of central nervous system involvement. Although simple prophylactic measures could reduce transmission, T. gondii seroprevalence is still high, especially in South America. Educational campaigns and the development of new drugs to prevent primary infection could potentially reduce the burden of the disease.
... The authors concluded that in their cohort bilateral impaired vision of worse than 6/12 is rare, and that half of eyes with a posterior pole lesion will have normal or near normal vision. 60 OT can also impact the cognitive functions in children with congenital toxoplasmosis and bilateral macular disease. Roizen and colleagues, 61 reported that in patients with OT, scaled scores were lowest on timed tests that require discrimination of fine intersecting lines. ...
... The primary outcome was serious neurological sequelae or death (SNSD), a composite outcome, comprising a pediatric report at any age of microcephaly, insertion of intraventricular shunt, an abnormal or suspicious neurodevelopmental examination that resulted in referral to a specialist, seizures during infancy or at an older age that required anticonvulsant treatment, severe bilateral visual impairment (visual acuity of Snellen 6/60 or less in both eyes assessed after 3 y), cerebral palsy, or death from any cause before 2 y of age including termination of pregnancy [9]. The consistency of SNSD findings was checked through multiple assessments. ...
The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known.
Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15) after maternal seroconversion at 10 weeks, and 18 (9-75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%).
The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection. Please see later in the article for the Editors' Summary.
... 7,32 We also reported involvement of the foveal center, which is more apt to be associated with significant visual impairment, especially if the involvement is bilateral. 33 Unilateral and bilateral foveal involvement were seen in 33.7% (120) and 18.0% (32) of newborns, respectively, in our study, but further follow-up should provide more information as to its true functional impact, because relatively large central lesions in CT may be associated with reasonably good visual acuity. 9 The high prevalence of retinochoroidal lesions that we found, many of which were active, may have been influenced by the neonatal screening strategy, as well as by the lack of prenatal treatment. ...
To report results of early ophthalmologic examinations in a large cohort of newborns with congenital toxoplasmosis (CT) after neonatal screening.
Cross-sectional analysis of a cohort.
A total of 178 newborns with confirmed CT from 146,307 screened babies (95% of live births) from Minas Gerais state, southeastern Brazil.
From November 2006 to May 2007, newborns underwent neonatal screening by immunoglobulin (Ig)M capture of dried blood samples. On all positive or suspected cases, confirmative serology was performed on babies and their mothers. Congenital toxoplasmosis was confirmed in newborns who had IgM and/or IgA and IgG, or IgG associated with suggestive ocular lesions (with IgM and IgG in the mother). Ophthalmologic evaluation consisted of indirect ophthalmoscopy with a lid speculum. Pediatric examination and radiologic studies of the central nervous system were also performed. In selected cases, biomicroscopy of the anterior segment, fundus photographs, or ultrasonography (B-scan) was performed.
Prevalence of retinochoroidal lesions, either cicatricial or active, and their location and associated findings, such as vascular sheathing, hemorrhage, vitreous opacities, and retinal detachment, were evaluated. The occurrence of cataract, microphthalmia, microcephaly, intracranial calcification, and hydrocephalus was also recorded.
Of 146,307 neonates screened, 190 had CT, yielding a prevalence of 1 in 770 live births, of whom 178 (93.7%) underwent standardized ophthalmologic examination at an average age of 55.6+/-16.6 days. Of these 178 infants, 142 (79.8%) had retinochoroidal lesions consistent with CT in at least 1 eye. Bilateral involvement was noted in 113 patients (63.5%). Macular involvement was seen in 165 eyes (46.3%) of 111 patients (62.4%). Active lesions were observed in 142 eyes (39.9%) of 85 patients (47.8%). These lesions were located in the macula of 75 eyes (21.1%) and were associated with retinal vascular sheathing in 44 eyes (12.4%).
A high prevalence of CT was encountered (1/770) with high rates of early retinochoroidal involvement ( approximately 80%) and many active lesions (in approximately 50%), indicating a possibly more severe ocular involvement by CT in Brazil than in other parts of the world. The hypotheses of higher parasite virulence and increased individual susceptibility are being currently investigated.
... genital toxoplasmosis caused ocular disease in 12%-30% of children prospectively followed up by serial ophthalmologic evaluations [9][10][11][12], with new ocular lesions occurring in up to 31% of referred children who were treated and followed up to a mean age of 10.8 years [13]. In addition, postnatal infection is now thought to cause more cases of ocular toxoplasmosis than congenital infection [4]. ...
Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States.
We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires.
We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women.
In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.
Zusammenfassung
Etwa 5–10 % aller Uveitisfälle treten bei Kindern auf. Die Erkrankung verläuft oft ohne Symptome, was zu einer verzögerten Diagnose und möglichen Schäden an den Augen führen kann. Infektiöse und nichtinfektiöse Ursachen können zur Uveitis führen, wobei die juvenile idiopathische Arthritis die häufigste Ursache bei Kindern und Jugendlichen ist. Die Behandlung hängt von der Ursache ab und kann eine Immunsuppression beinhalten. Katarakt, Glaukom und Amblyopie sind die häufigsten Komplikationen, die das Sehvermögen beeinträchtigen können. Regelmäßige Kontrollen sind auch nach Inaktivität der Uveitis wichtig, um erneute Entzündungsschübe frühzeitig zu erkennen und die Therapie anzupassen. Das Ziel dieser Arbeit ist es, einen Überblick über das klinische Erscheinungsbild, potenzielle Ursachen, Therapiemöglichkeiten und Komplikationen der Uveitis bei Kindern zu geben.
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii. Despite infecting a major fraction of the global population, T. gondii rarely results in clinically significant disease. Cats are the only known definitive host for this parasite, which sheds millions of oocysts in its feces every day, which then sporulate and become infective in the environment.
This comprehensive review article aims to explain the etiology, pathogenesis, epidemiology, transmission, clinical symptoms, diagnosis, risk factors, public health importance, economic effect, treatment, and prevention of toxoplasmosis. A search for various publications in English with the criteria of reviewing articles explaining toxoplasmosis was carried out.
T. gondii reproduces through two life cycles, namely the sexual cycle and the asexual cycle. In general, consuming parasite cysts in tainted food or water is how humans and other warm-blooded animals become infected with T. gondii. Nearly every region of the world has reported incidences of toxoplasmosis in humans, and around one-third of people are susceptible to latent infection. According to the reports, the main ways through which diseases spread are by water, tainted food, eating tissue cysts or oocysts, and congenital transmission. Infected individuals may experience asymptomatic cervical lymphadenopathy during an acute systemic infection. Diagnostic evaluation is very important for early detection, prevention of transmission, and as a reference for treatment options for infected pregnant women. Consuming undercooked meat is traditionally seen as a significant risk factor for developing toxoplasmosis. The impact of toxoplasmosis is very significant in humans because it causes abortion and disease in newborns, resulting in serious economic losses. To treat toxoplasmosis, dihydropteroate synthetase and dihydrofolate reductase inhibitors are advised. Toxoplasma transmission to humans can be avoided by thoroughly washing your hands with soap after handling meat, poultry, or shellfish.
Background
The management of uveitis in children can be extremely challenging as they constitute a unique population of patients. The aim of this review is to summarize current knowledge encompassing the clinical findings, diagnostic work-up, and therapeutic approach of uveitis in children.
Material and methods
A thorough literature search was performed of PubMed. An additional search was made in Google Scholar to complete the collected items.
Results
Uveitis is less common in children than in adults, but it may be more complicated due to its often asymptomatic nature or due to the inability of children to express complaints. Uveitis in children can be chronic, persistent, recurrent, and resistant to conventional treatment. The most common type of uveitis in pediatric patients is anterior uveitis, whereas the prevalence of intermediate, posterior, and panuveitis depends on the ethnic group and geographical distribution. Although many cases of pediatric uveitis are idiopathic, the differential diagnosis requires awareness of etiologies, as uveitis in children may be associated with various systemic inflammatory disorders, infections, or masquerade syndromes. Ocular complications of uveitis include cataracts, synechiae formation, glaucoma or hypotony, band keratopathy, macular edema, epiretinal membrane, choroidal neovascular membranes, and retinal detachment. These complications are associated with not only the nature of the disease but also with the use of topical and systemic corticosteroids, leading to irreversible structural damage and visual loss.
Conclusion
The therapeutic approach depends on the etiologic factor and the individual characteristics of each patient. Regular monitoring is crucial for early detection of any complications of uveitis or even adverse effects from treatments. Multidisciplinary management is also vital for providing more holistic care to young patients and their families ensuring a better quality of life. This study aims to review the current literature on the management of uveitis in pediatric patients.
Optical coherence tomography (OCT) is widely applied in diagnosis and management of retina diseases particularly macular diseases in adult retina practices. However, it has been under-utilized in pediatric retinal diseases especially in neonates and infants. Utilization of OCT in primary macular diseases in this age group is also uncommon and is less reported. Challenges involved in image acquisition and limitations with available devices technique can explain the limited research and accurate data availability in the literature in this field. Purpose of this review article is to summarize the use of OCT and its importance in various infantile retinal pathologies such as vascular diseases, tumors, retinal dystrophies, and optic nerve pathologies with primary focus on neonates and infants, along with infant choroid. In addition, we also discuss about future directions including OCT angiography for infants.
Pediatric uveitis accounts for 5-10% of all uveitis. Uveitis in children differs from adult uveitis in that it is commonly asymptomatic and can become chronic and cause chronic damage to ocular structures. The diagnosis might be delayed for multiple reasons, including the preverbal age and difficulties in examining young children. Pediatric uveitis may be infectious or non-infectious in etiology. The etiology of non-infectious uveitis is presumed to be autoimmune or autoinflammatory. The most common causes of uveitis in this age group are idiopathic and juvenile idiopathic arthritis-associated uveitis. The stepladder approach for the treatment of pediatric uveitis is based on expert opinion and algorithms proposed by multidisciplinary panels. Uveitis morbidities in pediatric patients include cataract, glaucoma, and amblyopia. Pediatric patients with uveitis should be frequently examined until remission is achieved. Once in remission, the interval between follow-up visits can be extended; however, it is recommended that even after remission the child should be seen every 8-12 weeks depending on the history of uveitis and the medications used. Close follow up is also necessary as uveitis can flare up during immunomodulatory therapy. It is crucial to measure the impact of uveitis, it's treatment, and it's complications on the child and the child's family. Visual acuity can be considered as an acceptable criterion for assessing visual function. Additionally, the number of cells in the anterior chamber can be a measure of disease activity. We review different aspects of pediatric uveitis. We discuss the mechanisms of noninfectious uveitis, including autoimmune and autoinflammatory etiologies, and the risks of developing uveitis in children with systemic rheumatologic diseases. We address the risk factors for developing morbidities, the Standardization of Uveitis Nomenclature (SUN) criteria for timing and anatomical classifications and describe a stepladder approach in the treatment of pediatric uveitis based on expert opinion and algorithms proposed by multi-disciplinary panels. We describe the most common entities for each type of anatomical classification and complications of uveitis for the pediatric population. Additionally, we address monitoring of children with uveitis and evaluation of Quality of Life.
Background:
Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis. We aimed to describe the ocular outcome and factors that may influence the visual prognosis of these patients.
Methods:
Cohort of patients with confirmed congenital toxoplasmosis seen between 1996 and 2017 in Porto Alegre, southern Brazil.
Results:
Seventy-seven patients were included, of which 65 (85.5%) were identified by routine screening. Median age at the end of the follow-up was 10 years (minimum 2, maximum 25). Retinochoroiditis was present in 55 patients (71.4%). New retinochoroidal lesions developed after the first year of life in 77.8% of the patients who began treatment after the fourth month of life, compared with 35.2% among those treated before 4 months of life (relative risk = 0.45, 95% confidence intervals: 0.27-0.75, P = 0.02) and 33.3% among those treated before 2 months of life (relative risk = 0.42, 95% confidence intervals: 0.25-0.72, P = 0.01). There was a peak incidence of new retinochoroidal lesions between 4 and 5 years and another peak between 9 and 14 years, the latter only among girls. Thirty-four patients with retinochoroiditis were followed up for 10 years or more, and the school performance was appropriate in 28 (82.4%).
Conclusions:
The high incidence of new retinochoroidal lesions during the follow-up period indicates the importance of long-term follow-up of patients with congenital toxoplasmosis. Initiating treatment within the first 4 months of life, especially within the first 2 months, was a protective factor against the later development of retinochoroiditis. Despite the usual favorable prognosis, the high morbidity of congenital toxoplasmosis in Brazil was confirmed.
Ocular toxoplasmosis is a retinitis –almost always accompanied by vitritis and choroiditis– caused by intraocular infection with Toxoplasma gondii. Depending on retinal location, this condition may cause substantial vision impairment. T. gondii is an obligate intracellular protozoan parasite, with both sexual and asexual life cycles, and infection is typically contracted orally by consuming encysted bradyzoites in undercooked meat, or oocysts on unwashed garden produce or in contaminated water. Presently available anti-parasitic drugs cannot eliminate T. gondii from the body. In vitro studies using T. gondii tachyzoites, and human retinal cells and tissue have provided important insights into the pathogenesis of ocular toxoplasmosis. T. gondii may cross the vascular endothelium to access human retina by at least three routes: in leukocyte taxis; as a transmigrating tachyzoite; and after infecting endothelial cells. The parasite is capable of navigating the human neuroretina, gaining access to a range of cell populations. Retinal Müller glial cells may be preferred initial host cells. T. gondii infection of the retinal pigment epithelial cells alters the secretion of growth factors and induces proliferation of adjacent uninfected epithelial cells. This increases susceptibility of the cells to parasite infection, and may be the basis of the characteristic hyperpigmented toxoplasmic retinal lesion. Infected epithelial cells also generate a vigorous immunologic response, and influence the activity of leukocytes that infiltrate the retina. A range of T. gondii genotypes are associated with human ocular toxoplasmosis, and individual immunogenetics –including polymorphisms in genes encoding innate immune receptors, human leukocyte antigens and cytokines– impacts the clinical manifestations. Research into basic pathogenic mechanisms of ocular toxoplasmosis highlights the importance of prevention and suggests new biological drug targets for established disease.
Pediatric uveitis differs from adult-onset uveitis and is a topic of special interest because of its diagnostic and therapeutic challenges. Children with uveitis are often asymptomatic and the uveitis is often chronic, persistent, recurrent, and resistant to conventional treatment. Anterior uveitis is the most common type of uveitis in children; the prevalence of intermediate, posterior, and panuveitis varies geographically and among ethnic groups. Regarding etiology, most cases of pediatric uveitis are idiopathic but can be due to systemic inflammatory disorders, infections, or a manifestation of masquerade syndrome. Ocular complications include cataracts, hypotony or glaucoma, band keratopathy, synechiae formation, macular edema, optic disc edema, choroidal neovascular membranes, and retinal detachment. These complications are often severe, leading to irreversible structural damage and significant visual disability due to delayed presentation and diagnosis, persistent chronic inflammation from suboptimal treatment, topical and systemic corticosteroid dependence, and delayed initiation of systemic disease‒modifying agents. Treatment for noninfectious uveitis is a stepwise approach starting with corticosteroids. Immunomodulatory therapy should be initiated in cases where quiescence cannot be achieved without steroid dependence. Patients should be monitored regularly for complications of uveitis along with systemic and ocular adverse effects from treatments. The goals are to achieve steroid-free durable remission, to reduce the risk of sight-threatening complications from the uncontrolled ocular inflammation, and to avoid the impact of lifelong burden of visual loss on the child and their family. Multidisciplinary management will ensure holistic care of affected children and improve the support for their families.
Congenital toxoplasmosis (CT) is a parasitic disease that can cause significant fetal and neonatal harm. Coordinated efforts by pregnant women, researchers, physicians, and health policy makers regarding potential primary and secondary preventive measures for CT and their implementation may lead to a lower incidence of CT as well as lower morbidity and mortality rates associated with CT. In the United States, the age-adjusted seroprevalence of Toxoplasma gondii among women of childbearing age (15-44 years) has declined over time (15%, 11%, and 9% in 1988-1994, 1999-2004, and 2009-2010, respectively; among US-born women only, the seroprevalence rates during these time periods were 13%, 8%, and 6%, respectively). Thus, approximately 91% of women of childbearing age in the United States are susceptible to Toxoplasma infection. Should these women become infected during pregnancy and remain undiagnosed and untreated, they could deliver an infant with CT. However, the incidence of acute primary infection is likely very low in the current era and is probably much lower than the 1.1 in 1000 pregnant women originally reported in 1960s.
Uveitis occurring before the age of 16 is defined as childhood uveitis. The majority of ophthalmologists are anxious to treat children with uveitis. This is not only due to the rareness of disease but also a result of the limited number of publications on this topic. In addition, associated entities, frequency and range of complications, treatment regimens, and risk of visual loss are different for children than for adults. Patient care, e.g., medical history, examination, and treatment compliance, is more difficult in children than in adults. Furthermore, the parents’ fear has a marked influence on patients and ophthalmologists.
Results: Twenty-nine children were evaluated. In 26 cases polymerase chain reaction to T. gondii in amniotic fluid (PCR-AF) was performed. The test was positive in 2 cases, and treatment was started. Of the 24 cases with negative PCR-AF, 3 were diagnosed with infection with positive serology during postnatal follow-up. In 1 of the 3 cases that did not have PCR-AF done, a very late seroconversion was seen. Serologies in the other 2 cases were negative at 6 months. In total, 6 children (20.7%) had a congenital infection confirmed.
• A causative diagnosis is essential to proper treatment.
• There may be more than one etiology.
• There is often corollary pathology: glaucoma, synechiae, cataract, and macular edema.
• Elimination of all inflammation is the cornerstone of therapy.
• Infection should be treated prior to or simultaneous to antiinflammatory treatment.
• Maintenance therapy, when indicated, should be minimally sufficient.
• Eyes must be completely quiet for 6 months prior to elective surgery.
Ocular toxoplasmosis is the most prevalent form of infectious posterior uveitis worldwide. Although congenital infections have long been considered to account for most ocular disease, there is now clear evidence that the majority of ocular toxoplasmosis infections are acquired after birth. Following either congenitally or postnatally acquired infection, Toxoplasma gondiimay induce a latent disease wherein T. gondiitissue cysts establish residence in various organs, including the eye. These cysts may subsequently rupture, resulting in clinical recurrence. Active ocular toxoplasmosis may occur at any age but is most common during the second through fourth decades of life.
Purpose. Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction, the immune imbalance implies especially Th17 and T regulatory (Treg) cells.Methods. In a prospective clinical study of acute intraocular inflammation including ocular toxoplasmosis, viral uveitis, systemic inflammatory disease related uveitis and bacterial endophthalmitis we evaluated the cytokine pattern in aqueous humors of affected patients. To further study the immunological mechanisms involved during ocular toxoplasmosis, weevaluated the intraocular inflammation, the parasite load and the immunological response characterized on mRNA and protein level in a mouse model. To evaluate the role of IL-17A, anti IL-17A monoclonal antibodies (mAbs) were administered concomitantly with the parasite.Results. Cytokines networks are different, depending on the cause of intraocular inflammation. In OT, we observed severe ocular inflammation and cytokine patterns comparable to human cases, including IL-17A production. Neutralizing IL-17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed upregulation of Treg and Th1 pathways. When IFN-γ was neutralized concomitantly, the initial parasite multiplication rate was partially restored.Conclusions. Local IL-17A production plays a central role in pathology of OT. The balance of Th17 and Th1 responses (especially IFN-γ) is crucial for the outcome of infection. These data open new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL-17A mAbs.
Congenital toxoplasmosis (CT) can elicit severe damage to several organs, especially the eye, and may be manifested at birth or later. We assessed the long-term ocular prognosis in a cohort of congenitally infected children treated according to a standardized protocol and monitored for up to 22 years.
This prospective study included confirmed cases of CT, which were identified by obligatory antenatal screening at the Lyon (France) reference center between 1987 and 2008. Data obtained through ocular examinations were recorded on a standardized form and confirmed by an independent external committee. Risk factors for retinochoroiditis were identified by using a multivariable Cox model and a flexible model that accounted for changes in the factor effects during follow-up.
A total of 477 of 485 infected live-born children were followed for a median of 10.5 years (75th percentile: 15.0 years). During the follow-up, 142 patients (29.8%) manifested at least 1 ocular lesion. Lesions were unilateral in 98 individuals (69.0%) and caused no vision loss in 80.6%. Lesions were first manifested at a median age of 3.1 (0.0-20.7) years. In 48 (33.8%) of the children, recurrences or new ocular lesions occurred up to 12 years after the appearance of the first lesion. Early maternal infection and confirmation of CT in children, prematurity, and nonocular CT lesions at baseline were associated with a higher risk of retinochoroiditis.
Although the consequences of CT are rarely severe in treated children, regular postnatal monitoring is nevertheless justified because of the lifelong persisting risk of new ocular manifestations.
Congenital toxoplasmosis is caused by transplacental contamination of the fetus withToxoplasma gondiifollowing maternal primary infection.
The risk of mother-to-child transmission depends on the term of pregnancy at the time of maternal infection. The risk is lower than 5% in the first trimester but can reach 90% in the last days of pregnancy. Inversely, however, fetal disease is more severe when contamination occurs early in pregnancy.
The French prevention program officially recommends monthly serological screening of susceptible women during pregnancy and information about hygiene and dietary rules.
Prenatal diagnosis of congenital toxoplasmosis is based on a combination of examinations: PCR testing for the parasite in amniotic fluid, mouse inoculation, fetal ultrasonography, and magnetic resonance imaging. Neonatal screening consists of PCR of the placenta, mouse inoculation, detection of specific IgM and IgA in the newborn, ocular fundus examinations by indirect ophthalmoscopy, and transfontanellar ultrasonography.
As soon as maternal infection is suspected, preventive treatment with spiramycin begins; the treatment is changed to a combination of pyrimethamine-sulfonamide if fetal infection is proved. Some teams are using this combination as first-line treatment after 30 weeks of gestation, without performing amniocentesis. Recent European multicenter studies raise questions about the effectiveness of prenatal treatment on mother-to-child transmission and on the reduction in the number and severity of fetal sequelae. A randomized controlled trial is required to prove the efficacy of prenatal treatment in general and of specific drugs, in particular.
As soon as infection is confirmed, infected children are treated with the pyrimethamine-sulfonamide combination for 12 to 24 months. Recent multicenter studies show that postnatal treatment does not prevent ocular lesions: 5% of treated children had choroiditis lesions at birth, 20% at 5 years, and 30% at 8 years of age. Furthermore no consensus exists about the duration of postnatal treatment (3 months in Denmark versus 12 months in France). A multicenter randomized controlled trial is necessary to assess the efficacy of postnatal treatment and determine its duration.
A surveillance system was set up in 2007 by the National Reference Center for Toxoplasmosis to determine the perinatal burden of this infection and to assess the national policy.
IgM may persist for months, presenting a risk of an erroneous diagnosis where serology is the only available tool. Indeed, IgM may be detected in secondary infection as a result of crossreactivity and/or nonspecific stimulation of the immune system. One test that can aid the serologist is IgG avidity testing, in that the avidity of IgG is low early in infection with the avidity of IgG antibodies increasing over time. Congenital toxoplasmosis can induce serious sequelae. Detectable IgM usually persists long after the acute infection. IgG avidity can be an important aid in diagnosis and assessing the risk to the fetus. Another infection that is of concern in pregnancy is cytomegalovirus (CMV). In pregnant women it is very important to differentiate primary from secondary infection, as primary infection presents the highest risk to the fetus. Serologic detection of IgM alone is not a specific marker of primary CMV infection. IgG avidity can have utility in identifying or excluding primary CMV infections during pregnancy. Outside of pregnancy, IgG avidity testing is increasingly recognized as a valuable tool. During the recent West Nile virus (WNV) epidemic in the US, it was recognized that WNV-specific IgM may persist for 6 - 12 months following exposure. Thus, a person presenting to their clinician with nonspecific symptoms may be tested and return a positive WNV IgM that may be the product of exposure during the previous period. In this environment, WNV IgG avidity testing is able to provide some assistance. IgG avidity testing should not be used alone and without an understanding of the limitations of the technique. Serology remains an important tool for the diagnosis and management of infectious disease. Classically, IgM is defined as a marker of acute infection and IgG, in the absence of clinical disease, is often considered a marker of past infection. However, the clinical reality can be quite different.
Toxoplasma gondii, rubella, cytomegalovirus and herpes simplex virus have in common that they can cause congenital (TORCH) infection, leading to fetal and neonatal morbidity and mortality. During the last decades, TORCH screening, which is generally considered to be single serum testing, has been increasingly used inappropriately and questions have been raised concerning the indications and cost-effectiveness of TORCH testing. The problems of TORCH screening lie in requesting the screening for the wrong indications, wrong interpretation of the single serum results and in case there is a good indication for diagnosis of congenital infection, sending in the wrong materials. This review provides an overview of the pathogenesis, epidemiology and clinical consequences of congenital TORCH infections and discusses the indications for, and interpretation of, TORCH screens.
To describe the clinical features of Ocular Toxoplasmosis in pediatric patients.
A retrospective, non-comparative series of cases was studied. We reviewed the clinical records of patients 16 year old or younger diagnosed with Ocular Toxoplasmosis.
Forty patients (56 eyes) were included. The mean age was 9.5 yrs old. Twenty were female. Unilateral involvement was noticed in 60% of patients. The most common symptoms were strabismus (32.1%) and reduced VA in (23.2%). An inactive retinal scar was observed in most cases (71.4%). Panuveitis was found in 8 eyes (14.2%), and posterior uveitis in 7 eyes of 7 patients (12.5%); one eye presented neuroretinitis. The most frequent location of retinochoroidal lesions was the posterior pole (72.7%).
In children, ocular toxoplasmosis is most commonly diagnosed during the inactive stage. When inflammation is present, it can be severe and frequently associated with other complications such vasculitis and papillitis.
Infectious aetiologies represent the largest entity in patients affected by posterior uveitis. As a single diagnosis, ocular toxoplasmosis ist the most frequently diagnosed infectious entity, wheres Behçet's uveitis represents the most frequently encountered immunologic aetiology. In acute posterior uveitis, an exact clinical diagnosis is sometimes prohibited by a dense vitreal infiltration. In this situation, the clinical course and progression of the disease may help in the differential diagnosis. Rapidly progressive instances such as viral retinal necrosis may be differentiated from cases of ocular toxoplasmosis and Behçet's disease, which tend to present in the office within one to two weeks of symptoms, and from other more slowly progressive diseases such as mycotic or nematode infections. The clinical picture at presentation is influenced by the duration of disease, underlying systemic conditions, and by the natural course of disease including the healing process and scare formation. Generally, visual function has to be assumed at risk, if a lesion is located close to the macula, if frequent recurrences increase the likelihood of macular involvement and, furthermore, if secondary complications affect the macula, e. g., macular oedema. In paediatric cases, the risk of amblyopia is frequently under-estimated, namely in the context of persistent dense vitreal infiltration. Therefore, a rapid interdisciplinary clinically tailored diagnostic access has to be reinforced in order to establish an early, targeted and etiologically based therapeutic strategy including steroid-sparing immunomodulating agents and possibly surgical alternatives.
© Georg Thieme Verlag KG Stuttgart · New York.
Long-term evolution of congenital toxoplasmosis is not documented. We assessed the outcome of treated congenital toxoplasmosis in a cohort of adult individuals who had undergone ante- and postnatal treatment to provide information for pediatricians and parents on the evolution of the disease.
We conducted a questionnaire study on 126 adults with congenital toxoplasmosis (mean age: 22.2 years; age range: 18-31 years) monitored regularly until the time of inclusion. The main outcome measures were quality of life (Psychological General Well-Being Index) and visual function (VF14 questionnaire), and the outcomes were correlated with disease-specific factors.
Of the 102 patients (80.9%) who were finally included in the study, 12 (11.8%) presented neurologic effects and 60 (58.8%) manifested ocular lesions; in the latter category, 13 individuals (12.7%) had reduced visual function. The overall global quality-of-life score (74.7 ± 14.2) was close to the expected normal range for the general population (73.7 ± 15.3). Overall, visual function was only slightly impaired (M = 97.3; 95% confidence interval, 95.8-98.8). Although disease-independent critical life circumstances were associated with a reduced Psychological General Well-Being Index, this index was not influenced by any of the clinical characteristics of congenital toxoplasmosis. Neurologic pathologies, reduced visual acuity, foveal location of the retinal lesion, and squinting contributed to decreased visual function at follow-up.
Our data reveal that treated congenital toxoplasmosis has little effect on the quality of life and visual function of the affected individuals. These encouraging findings may help to alleviate the anxiety of affected individuals and their parents.
Much of the brain is devoted to vision. Damage causes visual problems ranging from profound impairment, to cognitive visual problems only. A child with cerebral blindness may have intact perception of movement. The principal cognitive visual pathways comprise the dorsal and the ventral streams. The dorsal stream runs between the occipital lobes (which process incoming visual data), the posterior parietal lobes (which process the whole visual scene and give attention to component parts), the motor cortex (which facilitates movement through the visual scene) and the frontal cortex (which directs attention to chosen parts of the visual scene). The ventral stream runs between the occipital lobes and the temporal lobes (which enable recognition of people and objects, facilitate route finding and serve visual memory). Damage to these pathways disrupts these functions in a variety of combinations. This paper reviews cerebral visual impairment in children, the differential diagnosis and the management.
Summary:
Background: Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment.
Methods: We did a systematic review of cohort studies based on universal screening for congenital toxoplasmosis. We did a meta-analysis using individual patients' data to assess the effect of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Analyses were adjusted for gestational age at maternal seroconversion and other covariates.
Findings: We included 26 cohorts in the review. In 1438 treated mothers identified by prenatal screening, we found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 or more weeks (adjusted odds ratio [OR] 0·48, 95% CI 0·28–0·80; p=0·05). In 550 infected liveborn infants identified by prenatal or neonatal screening, we found no evidence that prenatal treatment significantly reduced the risk of clinical manifestations (adjusted OR for treated vs not treated 1·11, 95% CI 0·61–2·02). Increasing gestational age at seroconversion was strongly associated with increased risk of mother-to-child transmission (OR 1·15, 95% CI 1·12–1·17) and decreased risk of intracranial lesions (0·91, 0·87–0·95), but not with eye lesions (0·97, 0·93–1·00).
Interpretation: We found weak evidence for an association between early treatment and reduced risk of congenital toxoplasmosis. Further evidence from observational studies is unlikely to change these results and would not distinguish whether the association is due to treatment or to biases caused by confounding. Only a large randomised controlled clinical trial would provide clinicians and patients with valid evidence of the potential benefit of prenatal treatment.
Hydrocephalus, intracranial calcification and retinochoroiditis are the most common manifestations of tissue damage due to congenital toxoplasmosis, but the effect of prenatal treatment on these outcomes is unclear. We aimed to determine the effect of prenatal treatment for toxoplasmosis on the risk of intracranial and ocular lesions in congenitally infected children at 3 years of age.
A cohort of mothers identified during pregnancy with toxoplasma infection and their 181 liveborn children with confirmed congenital toxoplasmosis was retrospectively analysed to determine the presence of intracranial and ocular lesions. As few women are not treated, we compared the effects of the treatment potency (pyrimethamine-sulfadiazine versus spiramycin or no treatment), and the timing of treatment, on the risks of intracranial lesions, time to detection of ocular lesions, and detection of any lesions (intracranial or ocular) by 3 years of age. Analyses took account of the gestation at maternal seroconversion.
There was no evidence for an effect of pyrimethamine-sulfadiazine on intracranial, ocular or any lesions by 3 years: odds ratio (OR) for any lesions 0.89 (95% CI : 0.41, 1.88). There was no evidence of an effect of delayed treatment on ocular lesions (hazard ratio = 0.69, 95% CI : 0.28, 1.68) or any lesions by 3 years of age (OR = 0.44, 95% CI : 0.16, 1.19).
Our study failed to detect a beneficial effect of early or more potent anti toxoplasma treatment on the risks of intracranial or ocular lesions in children with congenital toxoplasmosis. However, larger, prospective studies, which determine the effect of prenatal treatment on long-term developmental outcomes are required to justify changes in clinical practice.
The aim of this study was to identify the high-risk factors associated with the development of ocular lesions in a large cohort of children with congenital toxoplasmosis (CT), irrespective of their gestational age at the time of maternal infection. Children were managed according to a standardized protocol and monitored for up to 14 years at the Croix-Rousse Hospital, Lyon, France. Cox model and a flexible regression, spline-based method were used for the analysis. During a median follow-up time of 6 years, 79 of the 327 children (24%) had at least one retinochoroidal lesion. No bilateral impairment of visual acuity was observed. The risk of a child developing ocular disease was higher not only when mothers were infected early during pregnancy, which was expected, but also when CT was diagnosed prior to or at the time of birth, when non-ocular manifestations were present at baseline and when birth was premature.
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.
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.
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.
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.
Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. The aim of this study was to determine the nature of the latter in treated cases of the disease and to assess their impact on visual function.
Four hundred and thirty consecutive children with serologically confirmed congenital toxoplasmosis were included in this study. Data were prospectively collected using standardized ophthalmological assessment forms. The presence of retinochoroiditis and of associated pathologies was ascertained, and their impact on visual function was assessed.
After a median follow-up of 12 years [range 0.6-26 years], 130 children manifested retinochoroiditis. We detected 22 foci of retinochoroiditis at birth and 264 additional ones during the follow-up period. Of these, 48 (17%) were active when first diagnosed. Twenty-five of the 130 children (19%) had other associated ocular pathologies. Of these, 21 (16%) had a strabismus, which was due to macular lesions in 86% of the cases; 7 (5.4%) presented with unilateral microphthalmia, and 4 (3%) with cataracts. Most of these events were detected after the onset of retinochoroiditis. None of the children presented with ocular involvement in the absence of chorioretinal lesions. Macular lesions occurred more frequently in children with associated pathologies (p<0.0001), and associated pathologies were likewise more common in individuals with macular lesions (p=0.0003). Visual impairment occurred in 31/130 cases, and in all but 3 of these eyes it was due not to an associated pathology but to macular retinochoroiditis.
At the end of the follow-up period, ocular involvement existed in 30% of the treated children with congenital toxoplasmosis. Associated eye pathologies were manifested less frequently than anticipated. They may occur later in life and are an indirect marker of the severity of congenital toxoplasmosis, but they do not have a direct impact on visual acuity. The overall functional prognosis of congenital toxoplasmosis is better than would be expected on the basis of literature findings, with only 2 of the 130 children suffering bilateral visual impairment.
To document loss of central field in patients with scars from toxoplasmic retinochoroiditis close to the disc after resolution of disease.
Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled from four centres. Automated central visual field testing was performed when their disease had settled and retinal photographs of the lesions were taken. The type of central field defect (whether absolute or relative) and whether it broke out to the periphery were correlated with the size of the retinochoroidal scar and its proximity to the optic nerve head.
69 eyes were enrolled; 16 (26%) were discarded because of poor field performance. Of the 53 remaining eyes, 31 showed absolute defects and 20 relative defects. Scars within one disc diameter of the disc were more likely to be associated with absolute defects breaking out to the periphery.
The scarring induced by toxoplasmic retinochoroiditis is associated with considerable field loss when it occurs close to the optic nerve head. Current treatment is unlikely to ameliorate this situation. The degree of visual field loss should be an outcome measure for future trials of the efficacy of treatment trials for the disease.
Information is lacking on the effects of congenital toxoplasmosis on development, behavior, and impairment in later childhood, as well as on parental concerns and anxiety. This information is important for counselling parents about the prognosis for an infected child and for policy decisions on screening.
We prospectively studied a cohort of children identified by screening for toxoplasmosis in pregnant women or neonates between 1996 and 2000 in ten European centers. At 3 years of age, parents of children with and without congenital toxoplasmosis were surveyed about their child's development, behavior, and impairment, and about parental concerns and anxiety, using a postal questionnaire.
Parents of 178/223 (80%) infected, and 527/821 (64%) uninfected children responded. We found no evidence that impaired development or behavior were more common in infected children, or that any potential effect of congenital toxoplasmosis was masked by prenatal treatment. Parents of infected children were significantly more anxious and reported more visual problems in their children.
On average, children aged three to four years with congenital toxoplasmosis identified by screening and treated during infancy in this European setting had risks of abnormal development and behavior similar to uninfected children. Parental anxiety about infected children needs to be addressed by clinicians. Future studies with longer follow up and clinician-administered assessments may be better able to detect any subtle differences in child outcomes.
Perspective on the paper by Schmidt et al (see page661)
The report on the Danish newborn screening programme for congenital toxoplasmosis in this month’s issue adds to evidence from similar programmes across the globe that newborn screening is feasible.1–5 Screening for toxoplasma specific IgM antibodies in newborn dried blood spots was first offered in 1988 by the New England Neonatal Screening Program. Since then, newborn screening programmes for congenital toxoplasmosis have been established in Denmark (in 1992),1 Poznan, Poland (in 1994),4 Porto Alegre, Brazil (in 1995),6 and Campos dos Goytazaces, Brazil (in 1999).7 In addition, screening studies have been conducted for a limited period in southern Sweden (1997–98)8 and Ireland (2005–07).9 The estimated birth prevalence of congenital toxoplasmosis per 10 000 live births reported by these programmes ranges from 0.7 in Sweden8 and 0.8 in Massachusetts,3 to 7.1 in Poland,4,10 and in Brazil, 5.4 in the private sector2 and 20 in the public sector.7 In European cohorts, approximately 10% of infected children have retinochoroiditis during infancy, rising to 16–18% by 4 years old.11,12 Bilateral visual impairment is rare, affecting up to 4% of children with retinochoroiditis.13 Screening detects between 43% and 85% of infected neonates.4,8,14–17 The very low false positive rate means that the probability of congenital toxoplasmosis in screen positive infants is usually over 25%.1,2,4,8
Newborn screening offers an apparently attractive option for preventing sequelae from congenital toxoplasmosis. It costs about one tenth as much as antenatal screening and avoids the inconvenience of repeated testing during pregnancy, the risk associated with amniocentesis for prenatal diagnosis, prolonged antibiotic administration during pregnancy, and termination of fetuses at very low risk of disability.18–20 …
To assess functional impairment in terms of visual acuity reduction and visual field defects in inactive ocular toxoplasmosis.
61 patients with known ocular toxoplasmosis in a quiescent state were included in this prospective, cross-sectional study. A complete ophthalmic examination, retinal photodocumentation and standard automated perimetry (Octopus perimeter, program G2) were performed. Visual acuity was classified on the basis of the World Health Organization definition of visual impairment and blindness: normal (> or =20/25), mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (<20/400). Visual field damage was correspondingly graded as mild (mean defect <4 dB), moderate (mean defect 4-12 dB) or severe (mean defect >12 dB).
8 (13%) patients presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28 (41%) eyes had reduced visual acuity, showing perimetric findings to be more sensitive in detecting chorioretinal damage (p<0.001). Correlation with the clinical localisation of chorioretinal scars was better for visual field (in 70% of the instances) than for visual acuity (33%). Moderate to severe functional impairment was registered in 65.2% for visual field, and in 27.5% for visual acuity.
In its quiescent stage, ocular toxoplasmosis was associated with permanent visual field defects in >94% of the eyes studied. Hence, standard automated perimetry may better reflect the functional damage encountered by ocular toxoplasmosis than visual acuity.
We read the editorial of Gilbert and Desateux.1 In their analysis, they take into account some newborn screening programmes for congenital toxoplasmosis in developing countries such as Brazil and Mexico, with reported rates of up to a maximum of 20 cases/10 000 live births; however, they did not mention our recent report that found a prevalence of 0.5% in a reference hospital in Colombia.2 This study found one child who died 1 week after birth. As we had information only on the frequency of deaths in a reference hospital, we carried out a study in a representative sample of all newborns from Quindio and found nearly the same prevalence: 0.6% (see letter in Archives of Disease in Children in response to the paper …
INTRODUCTION The rationale for preschool vision screening programmes has recently been questioned. Evidence about the effects of early treatment is needed, but it is not known how early the target conditions can reliably be detected. In this study, an intensive programme comprising several different screening methods, used at different ages up to 37 months, was compared with the usual practice of visual surveillance and ad hoc referrals.METHODS Two groups were randomly selected from children in a population birth cohort study. The control group (n = 1461) received visual surveillance only. The intervention group (n = 2029) was offered in addition a programme of regular visual assessments by orthoptists testing visual acuity, ocular alignment, stereopsis and non-cycloplegic photorefraction.RESULTS The intervention group programme yielded more children with amblyopia (1.6% vs. 0.5%, p < 0.01), and was more specific (95% vs. 92%, p < 0.01), than the control programme. The individual components of the intervention programme were compared. The cover test and visual acuity tests were poorly sensitive until the children were 37 months, but were always >99% specific. Photorefraction was more sensitive than acuity testing at all ages below 37 months, with specificity >95% at 31 and 37 months.CONCLUSIONS Photorefraction would have detected more children less than 37 months of age with straight-eyed amblyopia than did visual acuity testing, but with more false positives. At 37 months, photore-fraction plus a cover test would have been comparable in effectiveness to visual acuity testing plus a cover test.
Objective: To determine the effects on mother to child transmission of the timing and type of prenatal treatment, taking into account gestational age at maternal seroconversion. Design: Prospective cohort study. Setting: European centres offering prenatal screening for toxoplasmosis. Population: Children born to a cohort of pregnant women with toxoplasma infection. Methods: We determined the effects on mother to child transmission of the interval between seroconversion and start of treatment (treatment delay), and the type of treatment, taking into account gestational age at maternal seroconversion. Main outcome measure: Congenital infection status confirmed by toxoplasma IgG results at one year postnatal age. Results: Of 1208 women analysed, 72% were first prescribed spiramycin, 19% pyrimethamine-sulphonamide and 9% (mostly infected during the last trimester) were untreated. The odds ratios for mother to child transmission for all women treated after a delay of four to seven weeks was 0.77 (95% CI 0.34-1.69), and after eight weeks or more was 1.33 (0.56-2.89) compared with less than four weeks. The odds ratio per week of treatment delay was 1.01 (0.93-1.08). There was no evidence that transmission risk differed in women first treated with pyrimethamine-sulphonamide versus spiramycin: odds ratio 1.10 (0.63-1.91) or in untreated versus treated women: odds ratio 0.57 (0.27-1.17). Conclusion: We were unable to demonstrate a beneficial effect of the timing or type of prenatal treatment on the risk of mother to child transmission but we could not exclude a clinically important effect. Randomised controlled trials are required to determine the effect of prenatal treatment on mother to child transmission.
The best method for prevention and control of congenital toxoplasma infection is uncertain. Prenatal screening is done in Austria and France, but the effect of treatment during pregnancy is not well documented. The aim of our study was to find out the maternofetal transmission rate and outcome in infants born to mothers who were not treated during pregnancy.
We analysed 89873 eluates from phenylketonuria (PKU) cards from neonates and paired first-trimester serum samples from the mothers for specific IgG antibodies to Toxoplasma gondii. Children born to mothers who seroconverted during pregnancy were followed-up clinically and serologically to 12 months of age. In addition, 21144 PKU cards were analysed for toxoplasma-specific IgM antibodies during the last 12 months of the study.
In 24989 (27.8%) cases both the PKU eluate and the first-trimester samples were IgG positive, which indicates previous maternal infection. 139 of the 64884 seronegative women acquired toxoplasma infection during pregnancy and gave birth to 141 infants (two sets of twins). 27 of these children were diagnosed with congenital toxoplasma infection. The transmission rate was 19.4% (95% CI 13.2-27.0). Clinical signs and symptoms were found in four (15%) of the 27 children. The additional analysis for toxoplasma-specific IgM antibodies from the PKU card identified seven of nine children with congenital toxoplasma infection. The false-positive rate for the IgM test was 0.19 per 1000, and no false-negatives were found.
The risks of transmission of infection and of disease in the infant are low in an area with a low risk of toxoplasma infection. A neonatal screening programme based on detection of toxoplasma-specific IgM antibodies alone will identify between 70% and 80% of cases of congenital toxoplasmosis.
To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision.
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).
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.
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.
Methods for detecting subnormal vision early in life are needed to adequately diagnose the condition and begin treatment and rehabilitation.
Forty-six children ages 1 month to 1 1/2 years with either assumed normal vision, visual impairment due to eye disease, or strabismus were examined with the following tests: Stycar rolling balls; preferential looking (Teller acuity cards); and the ability to detect raisins, puffed rice, and sugar strands on two different backgrounds, one white and one black.
Children with visual impairment and strabismus often showed normal values for their age, and children with assumed normal vision sometimes had values below those established for normal development of vision with the Stycar rolling balls and the Teller acuity cards.
It is not possible to use these tests to reliably differentiate among normal vision, visual impairment, or strabismus in children younger than 1 1/2. Not until recognition acuity, symbols, or letters can be tested can reliable results be obtained. However, the tests are useful to estimate the general visual function of children in this age group.
The rationale for preschool vision screening programmes has recently been questioned. Evidence about the effects of early treatment is needed, but it is not known how early the target conditions can reliably be detected. In this study, an intensive programme comprising several different screening methods, used at different ages up to 37 months, was compared with the usual practice of visual surveillance and ad hoc referrals.
Two groups were randomly selected from children in a population birth cohort study. The control group (n = 1461) received visual surveillance only. The intervention group (n = 2029) was offered in addition a programme of regular visual assessments by orthoptists testing visual acuity, ocular alignment, stereopsis and non-cycloplegic photorefraction.
The intervention group programme yielded more children with amblyopia (1.6% vs. 0.5%, p < 0.01), and was more specific (95% vs. 92%, p < 0.01), than the control programme. The individual components of the intervention programme were compared. The cover test and visual acuity tests were poorly sensitive until the children were 37 months, but were always >99% specific. Photorefraction was more sensitive than acuity testing at all ages below 37 months, with specificity >95% at 31 and 37 months.
Photorefraction would have detected more children less than 37 months of age with straight-eyed amblyopia than did visual acuity testing, but with more false positives. At 37 months, photorefraction plus a cover test would have been comparable in effectiveness to visual acuity testing plus a cover test.
Screening for amblyopia in early childhood is done in many countries to ensure that affected children are detected and treated within the critical period, and achieve a level of vision in their amblyopic eye that would be useful should they lose vision in their non-amblyopic eye later in life. We aimed to investigate the risk, causes, and outcomes of visual impairment attributable to loss of vision in the non-amblyopic eye.
For 24 months from July, 1997, national surveillance was done to identify all individuals in the UK with unilateral amblyopia (acuity worse than 6/12) who had newly acquired vision loss in the non-amblyopic eye, resulting in acuity of worse than 6/12 or visual-field restriction precluding driving. Information about participants was obtained at presentation and 1 year later. Participants were categorised as having socially significant visual impairment, or visual impairment, severe visual impairment, or blindness, in accordance with WHO taxonomy.
Of 370 eligible individuals, at presentation 104 (28%) had socially significant visual impairment, 180 (49%) visual impairment, and 86 (23%) severe visual impairment or blindness. The minimum risk of permanent visual impairment by age 95 years was 32.9 (95% CI 29.1-36.9) per 100,000 total population. The projected lifetime risk of vision loss for an individual with amblyopia was at least 1.2% (95% CI 1.1-1.4). Only 36 (35%) of 102 people previously in paid employment were able to continue.
In the UK, where screening for amblyopia is under review, risk of serious vision loss affecting the non-amblyopic eye and its results are greater than that previously assumed. Thus, in addition to the benefits of improved vision in the amblyopic eye, treatment of amblyopia during childhood is a potentially valuable strategy to prevent incapacitating vision loss later in life.
To determine the effects on mother to child transmission of the timing and type of prenatal treatment, taking into account gestational age at maternal seroconversion.
Prospective cohort study.
European centres offering prenatal screening for toxoplasmosis.
Children born to a cohort of pregnant women with toxoplasma infection.
We determined the effects on mother to child transmission of the interval between seroconversion and start of treatment (treatment delay), and the type of treatment, taking into account gestational age at maternal seroconversion.
Congenital infection status confirmed by toxoplasma IgG results at one year postnatal age.
Of 1208 women analysed, 72% were first prescribed spiramycin, 19% pyrimethamine-sulphonamide and 9% (mostly infected during the last trimester) were untreated. The odds ratios for mother to child transmission for all women treated after a delay of four to seven weeks was 0.77 (95% CI 0.34-1.69), and after eight weeks or more was 1.33 (0.56-2.89) compared with less than four weeks. The odds ratio per week of treatment delay was 1.01 (0.93-1.08). There was no evidence that transmission risk differed in women first treated with pyrimethamine-sulphonamide versus spiramycin: odds ratio 1.10 (0.63-1.91) or in untreated versus treated women: odds ratio 0.57 (0.27-1.17).
We were unable to demonstrate a beneficial effect of the timing or type of prenatal treatment on the risk of mother to child transmission but we could not exclude a clinically important effect. Randomised controlled trials are required to determine the effect of prenatal treatment on mother to child transmission.
To describe the ophthalmologic outcomes of cases of congenital toxoplasmosis treated prenatally and postnatally.
Observational case series.
Follow-up ophthalmologic examinations of 18 children born to mothers who were infected before 25 weeks gestation were performed concurrently by two ophthalmologists. The infection in these children was first suspected when their mothers seroconverted during gestation. Toxoplasmic infection of the fetus was diagnosed by fetal blood or amniotic fluid analysis. Mothers were treated by a regimen of alternating pyrimethamine-sulfonamides and spiramycin during gestation. Pyrimethamine-sulfonamides treatment was continued from birth to 1 year of age.
The median age of the children was 4.5 years (range 1-11), when the follow-up ophthalmologic examinations were performed. Visual acuity was decreased in only one child, who had extensive bilateral macular and peripheral lesions. A posterior pole scar was noted in four eyes (four children) for whom visual acuity remained normal. Peripheral lesions were observed in nine eyes (five children). Both eyes were normal in 11 of 18 (61%) of the children.
In these children at a high risk for congenital toxoplasmic retinochoroiditis, a favorable visual outcome was observed in all but one case.
To update clinical information about ocular toxoplasmosis. Part II reviews the spectrum of disease manifestations and factors that influence severity of disease. Implications for disease management are discussed.
Literature review.
Selected articles from the medical literature, information from several recent scientific meetings, and the author's personal experiences were reviewed critically in preparation for the LX Edward Jackson Memorial Lecture.
The appearance of toxoplasmic retinochoroiditis lesions varies with duration of active retinal infection and intensity of inflammation. Severe ocular disease occurs in immunocompromised hosts. Older patients who are recently infected with Toxoplasma gondii may have a higher prevalence of ocular involvement and more severe ocular disease because of altered host defenses. Most disease-producing isolates of T. gondii belong to one of three clonal lineages (types I, II, III); type I has been associated with severe disease in both animals and human beings. Many observational studies suggest a benefit of short-term antimicrobial therapy for toxoplasmic retinochoroiditis in immunocompetent patients, although the efficacy of these treatments has not been proven in randomized clinical trials. Intermittent trimethoprim/sulfamethoxazole treatment was associated with fewer recurrences than placebo during a 20-month randomized clinical trial.
Variations in disease characteristics may be related to host, parasite, or environmental factors. The genotype of the infecting parasite appears to be an important determinant of disease severity in immunocompetent patients. Secondary prophylaxis may reduce the rate of recurrences in high-risk patients. A better clinical understanding of ocular toxoplasmosis can lead to more effective prevention and treatment strategies.
To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis.
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.
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.
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.
Despite three decades of prenatal screening for congenital toxoplasmosis in some European countries, uncertainty remains about the effectiveness of prenatal treatment.
We did a systematic review of cohort studies based on universal screening for congenital toxoplasmosis. We did a meta-analysis using individual patients' data to assess the effect of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Analyses were adjusted for gestational age at maternal seroconversion and other covariates.
We included 26 cohorts in the review. In 1438 treated mothers identified by prenatal screening, we found weak evidence that treatment started within 3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after 8 or more weeks (adjusted odds ratio [OR] 0.48, 95% CI 0.28-0.80; p=0.05). In 550 infected liveborn infants identified by prenatal or neonatal screening, we found no evidence that prenatal treatment significantly reduced the risk of clinical manifestations (adjusted OR for treated vs not treated 1.11, 95% CI 0.61-2.02). Increasing gestational age at seroconversion was strongly associated with increased risk of mother-to-child transmission (OR 1.15, 95% CI 1.12-1.17) and decreased risk of intracranial lesions (0.91, 0.87-0.95), but not with eye lesions (0.97, 0.93-1.00).
We found weak evidence for an association between early treatment and reduced risk of congenital toxoplasmosis. Further evidence from observational studies is unlikely to change these results and would not distinguish whether the association is due to treatment or to biases caused by confounding. Only a large randomised controlled clinical trial would provide clinicians and patients with valid evidence of the potential benefit of prenatal treatment.
United Kingdom; e-mail: r.gilbert@ich.ucl.ac.uk ©
- Ruth Gilbert Inquiries
Inquiries to Ruth Gilbert, Centre for Pediatric Epidemiology and Biostatistics, UCL Institute of Child Health, 30, Guilford Street, London WC1N 1EH, United Kingdom; e-mail: r.gilbert@ich.ucl.ac.uk © 2007 BY ELSEVIER INC. ALL RIGHTS RESERVED. 2003;131:1157–1168.
Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment
- M Lebech
- O Andersen
- Christensen
- Nc
Lebech M, Andersen O, Christensen NC, et al. Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Lancet 1999;353:1834 –1837.
European Multicentre Study on Congenital Toxoplasmosis
- Gilbert
Ocular toxoplasmosis: a global reassessment
- Holland