Management of Congenital Toxoplasmosis

McLeod, Rima; Lykins, Joseph; Noble, A. Gwendolyn; Rabiah, Peter; Swisher, Charles N.; Heydemann, Peter; McLone, David G.; Frim, David M.; Withers, Shawn; Clouser, Fatima; Boyer, Kenneth M.

doi:10.1007/s40124-014-0055-7

Cited by 54 publications

(80 citation statements)

References 174 publications

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“…This is what we are working toward because of the substantial disease burden of toxoplasmosis as a global clinical problem. 38 Data from studies of human cells and mice, in our work, considered together, demonstrate the robust and practical use of this model system. [3][4][5][6]25 Antigen processing and presentation in humans and mice have differences that are well known.…”

Section: Discussionmentioning

confidence: 61%

Protein nanovaccine confers robust immunity against Toxoplasma

Bissati

Zhou

Paulillo³

et al. 2017

npj Vaccines

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We designed and produced a self-assembling protein nanoparticle. This self-assembling protein nanoparticle contains five CD8+ HLA-A03-11 supertypes-restricted epitopes from antigens expressed during Toxoplasma gondii’s lifecycle, the universal CD4+ T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist. These CD8+ T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage. Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice against T. gondii. Immunization, using self-assembling protein nanoparticle-GLA-SE, activated CD8+ T cells to produce IFN-γ. Self-assembling protein nanoparticle-GLA-SE also protected HLA-A*1101 transgenic mice against subsequent challenge with Type II parasites. Hence, combining CD8+ T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex Class I and II molecules. Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.

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Section: Discussionmentioning

confidence: 61%

Protein nanovaccine confers robust immunity against Toxoplasma

Bissati

Zhou

Paulillo³

et al. 2017

npj Vaccines

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“…Disease presentation is highly variable, though severe eye disease resulting in loss of sight is not uncommon, and immunocompromised patients can present with serious infections of the central nervous system (CNS) [2][3][4][5][6][7]. Acquisition of infection during pregnancy can result in vertical transmission, leading to profound disability due to untreated congenital infection; consequences for the infected, untreated infant include cognitive impairment, hydrocephalus, and disability due to loss of sight [8]. Additionally, previous studies posit a role for T. gondii infection in a variety of comorbid conditions, including epilepsy and neurologic diseases [9][10][11][12][13].…”

mentioning

confidence: 99%

“…Active infection with T. gondii is treated successfully with pyrimethamine and sulfadiazine [6][7][8]20]. These are the most effective medicines for treating toxoplasmosis, including ocular and CNS manifestations, and are not indicated in other clinical contexts.…”

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confidence: 99%

Understanding Toxoplasmosis in the United States Through “Large Data” Analyses

Lykins¹,

Wang

Wheeler³

et al. 2016

Clin Infect Dis.

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Background. Toxoplasma gondii infection causes substantial morbidity and mortality in the United States, and infects approximately one-third of persons globally. Clinical manifestations vary. Seropositivity is associated with neurologic diseases and malignancies. There are few objective data concerning US incidence and distribution of toxoplasmosis.Methods. Truven Health MarketScan Database and International Classification of Diseases, Ninth Revision (ICD-9) codes, including treatment specific to toxoplasmosis, identified patients with this disease. Spatiotemporal distribution and patterns of disease manifestation were analyzed. Comorbidities between patients and matched controls were compared.Results. Between 2003 and 2012, 9260 patients had ICD-9 codes for toxoplasmosis. This database of patients with ICD-9 codes includes 15% of those in the United States, excluding patients with no or public insurance. Thus, assuming that demographics do not change incidence, the calculated total is 61 700 or 6856 patients per year. Disease was more prevalent in the South. Mean age at diagnosis was 37.5 ± 15.5 years; 2.4% were children aged 0-2 years, likely congenitally infected. Forty-one percent were male, and 73% of women were of reproductive age. Of identified patients, 38% had eye disease and 12% presented with other serious manifestations, including central nervous system and visceral organ damage. Toxoplasmosis was statistically associated with substantial comorbidities, including human immunodeficiency virus, autoimmune diseases, and neurologic diseases.Conclusions. Toxoplasmosis causes morbidity and mortality in the United States. Our analysis of private insurance records missed certain at-risk populations and revealed fewer cases of retinal disease than previously estimated, suggesting undercoding, underreporting, undertreating, or differing demographics of those with eye disease. Mandatory reporting of infection to health departments and gestational screening could improve care and facilitate detection of epidemics and, thereby, public health interventions.

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“…In our study, it was not possible to follow up the newborns and establish a relationship of maternal infection with the clinical aspects presented by the neonate in the recommended period, which is a limitation of this study (McLeod et al, 2014;Murat et al, 2013b;Robert-Gangneux and Belaz, 2016;Robert-Gangneux and Dardé, 2012).…”

Section: Discussionmentioning

confidence: 89%

Evaluation of serological and molecular tests used to identify Toxoplasma gondii infection in pregnant women attended in a public health service in São Paulo state, Brazil

Murata

Ferreira

Pereira-Chioccola

et al. 2017

Diagnostic Microbiology and Infectious Disease

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Toxoplasmosis during pregnancy can have severe consequences. The use of sensitive and specific serological and molecular methods is extremely important for the correct diagnosis of the disease. We compared the ELISA and ELFA serological methods, conventional PCR (cPCR), Nested PCR and quantitative PCR (qPCR) in the diagnosis of Toxoplasma gondii infection in pregnant women without clinical suspicion of toxoplasmosis (G1=94) and with clinical suspicion of toxoplasmosis (G2=53). The results were compared using the Kappa index, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. The results of the serological methods showed concordance between the ELISA and ELFA methods even though ELFA identified more positive cases than ELISA. Molecular methods were discrepant with cPCR using B22/23 primers having greater sensitivity and lower specificity compared to the other molecular methods.

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Management of Congenital Toxoplasmosis

Cited by 54 publications

References 174 publications

Protein nanovaccine confers robust immunity against Toxoplasma

Protein nanovaccine confers robust immunity against Toxoplasma

Understanding Toxoplasmosis in the United States Through “Large Data” Analyses

Evaluation of serological and molecular tests used to identify Toxoplasma gondii infection in pregnant women attended in a public health service in São Paulo state, Brazil

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