Congenital Toxoplasmosis in Chronically Infected and Subsequently Challenged Ewes.
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ABSTRACT:
SUBMITTER: Dos Santos TR
PROVIDER: S-EPMC5082944 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PURPOSE:To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis. METHODS:Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed. RESULTS:In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions. CONCLUSIONS:In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.
| S-EPMC2194289 | biostudies-literature
Project description:NALP1 is a member of the NOD-like receptor (NLR) family of proteins that form inflammasomes. Upon cellular infection or stress, inflammasomes are activated, triggering maturation of proinflammatory cytokines and downstream cellular signaling mediated through the MyD88 adaptor. Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines that are important in innate immunity. In this study, susceptibility alleles for human congenital toxoplasmosis were identified in the NALP1 gene. To investigate the role of the NALP1 inflammasome during infection with T. gondii, we genetically engineered a human monocytic cell line for NALP1 gene knockdown by RNA interference. NALP1 silencing attenuated progression of T. gondii infection, with accelerated host cell death and eventual cell disintegration. In line with this observation, upregulation of the proinflammatory cytokines interleukin-1? (IL-1?), IL-18, and IL-12 upon T. gondii infection was not observed in monocytic cells with NALP1 knockdown. These findings suggest that the NALP1 inflammasome is critical for mediating innate immune responses to T. gondii infection and pathogenesis. Although there have been recent advances in understanding the potent activity of inflammasomes in directing innate immune responses to disease, this is the first report, to our knowledge, on the crucial role of the NALP1 inflammasome in the pathogenesis of T. gondii infections in humans.
| S-EPMC3028851 | biostudies-literature
Project description:1. Five well-nourished Scottish Blackface ewes carrying twin lambs were used. An umbilical artery and vein of each foetus in two sheep and one foetus in three sheep were catheterized at 109-112 days of gestation and both maternal jugular veins were catheterized 2 days before experiment. Two-day experiments were conducted between days 124 and 141 of gestation when [2-3H,U-14C]glucose was infused intravenously over 9 h into either the mother or one foetus, separate days being used for each infusion. 2. Plasma glucose specific radioactivities of the mother and infused foetus at plateau were used to determine the glucose flux rates within and between mother and foetus. The corresponding values for the uninfused foetus were calculated by using the relative weights of each twin foetus and were used to correct the maternal flux rates for the presence of the second foetus. 3. The net rate of glucose utilization by the foetus was 11.2 +/- 1.3 mg/min per kg of foetus (mean +/- S.E.M; n = 11). The corresponding rate in the mother was 1.1 +/- 0.1 mg/min per kg of live weight (n = 11). 4. The net rate of foetal uptake of glucose from the mother accounted for only 56 +/- 4% of the glucose used by the foetus. The remainder was provided by an input of 4.9 +/- 0.7 mg/min per kg of foetus to the foetal glucose pool via foetal gluconeogenesis. 5. The rate of glucose futile cycling in the foetus was high, equal to 95 +/- 19% of the net foetal glucose-utilization rate. 6. The rate of glucose utilization (mg/min per kg of foetus) decreased progressively over the observational period of 124-141 days of gestation. There was no increase in the rates of net foetal glucose uptake or of foetal gluconeogenesis to counter this decline.
| S-EPMC1162980 | biostudies-other
Project description:AimsTo determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern).Materials and methodsWe collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life.Results61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city.ConclusionsIncidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis.
| S-EPMC3104965 | biostudies-literature
Project description:Toxoplasma gondii is a cause of congenital diseases, miscarriages and stillbirths in production animals. In Brazil, non-archetypal genotypes of the parasite may be related to severe disease. Experimental infection with T. gondii was studied in sheep to analyse congenital transmission-related parameters in reinfections with different Brazilian parasite strains. Thirteen T. gondii-seronegative sheep were orally infected with 2 × 103oocysts for the primary infection: G1 (4 animals) were inoculated with TgCatBr71 strain (Type BrI genotype) and G2 andG3 (5 and 4 animals, respectively) withTgCatBr60 strain (Type BrIII genotype). After chronification of infection, the animals were impregnated. A second infection was performed after 60 days of gestation. TheG1 andG3 animals were inoculated withTgCatBr60BrIII and the G2 animals withTgCatBr71 BrI oocysts. The effects of reinfection were compared with a control group (5 animals) through physical examination, ultrasound imaging and serology. Ovine experimental infections were evaluated using mouse bioassays, molecular analysis, serological tests, histopathology, and immunohistochemistry. No abortions occurred; a seropositive lamb and a mummified fetus from G2-BrIIIxBrI were produced. The vertical transmission rate detected in lambs from chronically infected sheep was 31.6% (6/19). It is demonstrated that reinfection and subsequent congenital transmission occured in one sheep with a primary Brl infection challenged with BrIII genotype of T. gondii. In a twin pregnancy from G2-BrIIIxBrI, congenital transmission from a latent infection was detected in both lambs. Congenital transmission could not be tracked in three lambs. Overall, previous T. gondii infection may fail to protect against congenital transmission from a reinfection and primary infection induced insufficient protection against vertical transmission which must be taken into account in decision-making for the use of seropositive animals as breeders. Similar trials with larger groups and contemplating host cellular immune response studies should be conducted to evaluate the actual impact of T. gondii reinfection involving different strains in sheep.
| S-EPMC6454189 | biostudies-literature
Project description:BackgroundCongenital toxoplasmosis (CT) causes a substantial disease burden worldwide. The aim of this study was to estimate the disease burden of CT in Denmark, a developed country with free public healthcare and nationwide data available.MethodsUsing data primarily from two public health surveillance programmes conducted between 1992 and 2007, we estimated the incidence, occurrence of sequelae, mortality and the burden of disease in terms of disability-adjusted life years (DALYs) of CT in Denmark in 2014.FindingsWe estimated that 14 children were born with CT in 2014, of which six will have developed sequelae by the age of 12. CT resulted in a total disease burden of 123 DALYs (95% uncertainty interval [UI], 100-148), of which 78 (95% UI, 64-94) were due to foetal loss and 2 (95% UI, 1-3) were due to neonatal death; the remaining burden was due to moderate to severe life-long sequelae. A comparison of the estimated incidence of CT with the number of reported CT cases in 2008-2014 indicated that for each reported CT case, at least five other CT cases could be expected to have occurred and gone unreported.InterpretationEarly onset, severity, and life-long duration of sequelae have a major effect on the disease burden of CT. Our data suggest that CT is under-diagnosed or under-reported in Denmark. The estimated disease burden and public health impact in Denmark is lower than in other European countries, highlighting the need for country-specific studies.
| S-EPMC5448755 | biostudies-literature
Project description:In Panama, epidemiological data on congenital toxoplasmosis are limited, making it difficult to understand the scope of clinical manifestations in the population and factors that may increase the risk of infection. This study provides insight into the epidemiological situation of maternal and congenital toxoplasmosis in Panama and contributing information on the burden of this disease in Central America. Blood samples were collected from 2326 pregnant women and used for the detection of anti-T. gondii antibodies. A high seroprevalence (44.41%) was observed for T. gondii infection in pregnant women from different regions of Panama, with an estimated incidence rate of congenital toxoplasmosis of 3.8 cases per 1000 live births. The main risk factors associated with T. gondii infection using bivariate statistical analysis were an elementary level education and maternal age range of 34-45 years. Multivariate statistical analyses revealed that in some regions (San Miguelito, North and West regions), the number of positive cases correlated with the presence of pets, stray dogs and the consumption of poultry. In other regions (East and Metropolitan regions), the absence of pets was considered a protective factor associated with negative cases, while the presence of stray cats and the age range of 25-34 years did not represent any risk in these regions.
| S-EPMC8234371 | biostudies-literature
Project description:The Disorders of Sex Development (DSDs) are congenital conditions characterized by inconsistency among chromosomal, gonadal, and anatomical sex development. The aim of this research is to report the clinical and cytogenetic findings of four DSD cases and 13 couples of heterosexual twins in sheep. To this purpose, C- and R-banding techniques were used, and the analyses of the SRY (Sex Determining Region Y) and AMEL (Amelogenin) genes were carried out. Moreover, morphopathological analyses were performed in one case. The four DSD sheep cases were registered as females at birth, and for none of them it was possible to establish whether the subjects were born from heterosexual multiple births. Three of the four cases were diagnosed as XX/XY blood lymphocyte chimaeras, while the fourth case was diagnosed as a 54, XY SRY-positive DSD sheep. None of the heterosexual twins showed XX/XY blood chimaerism. This finding suggests that the blood chimaeric cases detected could also be due to a zygote/embryo fusion. Moreover, no gene variants involved in sheep DSD are known, the identification of which would be very useful for the sheep industry.
| S-EPMC6826438 | biostudies-literature
Project description: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. METHODS:We compared prospective cohorts of children with congenital toxoplasmosis identified by universal neonatal screening in Brazil and neonatal or prenatal screening in Europe between 1992 and 2003, using the same protocol in both continents. RESULTS:Three hundred and eleven (311) children had congenital toxoplasmosis: 30 in Brazil and 281 in Europe, where 71 were identified by neonatal screening. Median follow up was 4.1 years in Europe and 3.7 years in Brazil. Relatively more children had retinochoroiditis during the first year in Brazil than in Europe (15/30; 50% versus 29/281; 10%) and the risk of lesions by 4 years of age was much higher: the hazard ratio for Brazil versus Europe was 5.36 (95%CI: 3.17, 9.08). Children in Brazil had larger lesions, which were more likely to be multiple and to affect the posterior pole (p<0.0001). In Brazil, visual impairment (<6/12 Snellen) was predicted for most affected eyes (87%, 27/31), but not in Europe (29%; 20/69, p<0.0001). The size of newly detected lesions decreased with age (p = 0.0007). CONCLUSIONS:T. gondii causes more severe ocular disease in congenitally infected children in Brazil compared with Europe. The marked differences in the frequency, size and multiplicity of retinochoroidal lesions may be due to infection with more virulent genotypes of the parasite that predominate in Brazil but are rarely found in Europe.
| S-EPMC2493041 | biostudies-literature
Project description:Typically, human noroviruses cause symptoms of acute gastroenteritis for 2 to 4 days. Often, the virions are shed in stool for several days after the symptoms recede, which in turn can lead to further contamination and transmission. Moreover, a number of reports have considered that chronic norovirus infections, i.e., lasting months and years, might even function as reservoirs for the generation of novel strains that can escape the herd immunity or have modified binding interactions with histo-blood group antigens (HBGAs). In this study, we analyzed noroviruses isolated from a patient who has presented a chronic infection for more than 6 years. We found that the isolated capsid sequences clustered into two main genetic types (termed A and B), despite a plethora of capsid quasi-sequences. Furthermore, the two genetic types corresponded well with distinct antigenicities. On the other hand, we showed that numerous amino acid substitutions on the capsid surface of genetic types A and B did not alter the HBGA binding profiles. However, divergent binding profiles for types A and B were observed with human milk oligosaccharides (HMOs), which structurally mimic HBGAs and may act as natural antivirals. Importantly, the isolated capsid sequences only had approximately 90% amino acid identity with other known sequences, which suggested that transmission of these chronic noroviruses could be limited. IMPORTANCE The norovirus genogroup II genotype 4 (GII.4) variants have approximately 5% divergence in capsid amino acid identity and have dominated over the past decade. The precise reason(s) for the GII.4 emergence and persistence in the human population is still unknown, but some studies have suggested that chronically infected patients might generate novel variants that can cause new epidemics. We examined GII.4 noroviruses isolated from an immunocompromised patient with a long-term infection. Numerous norovirus capsid quasi-species were isolated during the 13-month study. The capsid quasi-species clustered into two genetic and antigenic types. However, the HBGA binding profiles were similar between the two antigenic clusters, indicating that the amino acid substitutions did not alter the HBGA binding interactions. The isolated sequences represented two new GII.4 variants, but similar sequences were not found in the database. These results indicated that chronically infected patients might not generate novel noroviruses that cause outbreaks.
| S-EPMC5371696 | biostudies-literature