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      Serological diagnosis of Toxoplasma gondii: analysis of false-positive IgG results and implications Translated title: Diagnostic sérologique de Toxoplasma gondii : analyse des IgG faux positifs et implications

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      1 , 2 , * , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 1 , 2 , 1 , 2
      (Collab)
      Parasite
      EDP Sciences
      Toxoplasma gondii, IgG, False-positive, Serology, Architect, Toxoplasmosis

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          Abstract

          Background: Primary infection by Toxoplasma gondii in pregnant women can result in serious outcomes for the foetus. A false-positive IgG result during pregnancy can lead to a misdiagnosis of past infection and to stopping preventive measures. We collected 189 sera with positive Architect ® Toxo IgG assay (Abbott Laboratories) and negative IgG results with at least two other serological tests, in order to find an explanation for the suspected false-positive IgG results. We used the recomLine Toxoplasma IgG ® immunoblot (Mikrogen Diagnostik) to search for specific antigenic reactivities of the sera, and the LDBio Toxo II IgG ® immunoblot (LDBio Diagnostics) as a confirmatory test. Results: The bands GRA8 and/or GRA7 were positive for 148 samples (78.3%). GRA8 was the most frequent band, appearing in 133 patterns (70.4%), whereas GRA7 was present for 49 samples (25.9%). Of the 81 samples tested with LDBio ®, 23 (28.4%) turned out to be positive. Of the 58 negative LDBio ® tests (71.6%) (real false-positive Architect ® IgG), 23 samples (39.6%) did not show either a GRA8 or p30 band by recomLine ®. Their false positivity with Architect ® remains unexplained since Abbott uses these two recombinant antigens for their assay. Conclusions: The Architect ® IgG false positivity for T. gondii seems to be due to reactivity against GRA8 for the majority of the sera and GRA7 to a lesser extent. The hypothesis of past contact with parasites genetically close to T. gondii such as Hammondia hammondi or Neospora caninum seems promising and should be assessed further.

          Translated abstract

          Contexte : La primo-infection à Toxoplasma gondii chez la femme enceinte peut avoir de graves conséquences pour le fœtus. Un résultat IgG faussement positif pendant la grossesse peut mener à un diagnostic erroné d’infection ancienne et à stopper les mesures préventives. Nous avons collecté 189 sérums présentant un résultat Architect ® Toxo IgG (Abbott Laboratories) positif ainsi qu’un résultat IgG négatif par au moins deux autres tests sérologiques, dans le but de trouver une explication aux résultats IgG suspectés faux positifs. Nous avons utilisé l’immunoblot recomLine Toxoplasma IgG ® (Mikrogen Diagnostik) pour chercher certaines réactivités antigéniques spécifiques des sérums et l’immunoblot LDBio Toxo II IgG ® (LDBio Diagnostics) comme test de confirmation. Résultats : Les bandes GRA8 et/ou GRA7 étaient positives pour 148 (78,3 %) échantillons. GRA8 était la bande la plus fréquente, apparaissant dans 133 (70,4 %) profils alors que GRA7 était présente pour 49 (25,9 %) échantillons. Sur les 81 échantillons testés en LDBio ®, 23 (28,4 %) se sont révélés positifs. Sur les 58 (71,6 %) tests LDBio ® négatifs (réels faux positifs IgG Architect ®), 23 (39,6 %) échantillons n’ont montré ni bande GRA8 ni bande p30 en recomLine ® et leur fausse positivité reste donc inexpliquée puisque Abbott utilise ces deux antigènes recombinants dans son test. Conclusions : La fausse positivité IgG Architect ® pour T. gondii semble être due à une réactivité envers la protéine GRA8 pour la majorité des sérums et envers GRA7 dans une moindre mesure. L’hypothèse d’un contact passé avec des parasites génétiquement proches de T. gondii comme Hammondia hammondi ou Neospora caninum semble prometteuse et devrait être approfondie.

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          Foodborne toxoplasmosis.

          Toxoplasmosis can be due to congenital infection or acquired infection after birth and is one of the leading illnesses associated with foodborne hospitalizations and deaths. Undercooked meat, especially pork, lamb, and wild game meat, and soil contaminated with cat feces on raw fruits and vegetables are the major sources of foodborne transmission for humans. The new trend in the production of free-range organically raised meat could increase the risk of Toxoplasma gondii contamination of meat. Foodborne transmission can be prevented by production practices that reduce T. gondii in meat, adequate cooking of meat, washing of raw fruits and vegetables, prevention of cross contamination in the kitchen, and measures that decrease spread of viable oocysts into the environment.
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            Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection.

            The intracellular protozoan Toxoplasma gondii is a widespread opportunistic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining strong T-cell-mediated immunity is crucial in preventing the emergence of T. gondii as a serious pathogen. The parasite induces high levels of gamma interferon (IFN-gamma) during initial infection as a result of early T-cell as well as natural killer (NK) cell activation. Induction of interleukin-12 by macrophages is a major mechanism driving early IFN-gamma synthesis. The latter cytokine, in addition to promoting the differentiation of Th1 effectors, is important in macrophage activation and acquisition of microbicidal functions, such as nitric oxide release. During chronic infection, parasite-specific T lymphocytes release high levels of IFN-gamma, which is required to prevent cyst reactivation. T-cell-mediated cytolytic activity against infected cells, while easily demonstrable, plays a secondary role to inflammatory cytokine production. While part of the clinical manifestations of toxoplasmosis results from direct tissue destruction by the parasite, inflammatory cytokine-mediated immunopathologic changes may also contribute to disease progression.
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              Congenital toxoplasma infection: monthly prenatal screening decreases transmission rate and improves clinical outcome at age 3 years.

              Toxoplasma infection during pregnancy exposes the fetus to risks of congenital infection and sequelae that depend heavily on gestational age (GA) at time of infection. Accurate risk estimates by GA are necessary to counsel parents and improve clinical decisions. We analyzed data from pregnant women diagnosed with acute Toxoplasma infection in Lyon (France) from 1987 to 2008 and assessed how the risks of congenital toxoplasmosis and of clinical signs at age 3 years vary depending on GA at the time of maternal infection. Among 2048 mother-infant pairs, 93.2% of mothers received prenatal treatment and 513 (24.7%) fetuses were infected. Because of a significant reduction in risk since 1992 when monthly screening was introduced (59.4% vs 46.6% at 26 GA weeks; P = .038), probabilities of infection were estimated on the basis of maternal infections diagnosed after mid-1992 (n = 1624). Probabilities of congenital infection were <10% for maternal infections before 12 weeks of gestation, rose to 20.0% at 19 weeks, and then continued increasing to 52.3% and almost 70% at 28 and 39 GA weeks, respectively. Because of a significant reduction in risk of clinical signs of congenital toxoplasmosis in infected children born from mothers diagnosed after 1995 when polymerase chain reaction testing on amniotic fluid was initiated (87/794 vs 46/1150; P = .012), probabilities of clinical signs at 3 years were estimated based on 1015 maternal infections diagnosed after 1995 including 207 infected children, with symptoms in 46 (22.2%). These analyses demonstrated that introduction of monthly prenatal screening and improvement in antenatal diagnosis were associated with a significant reduction in the rate of congenital infection and a better outcome at 3 years of age in infected children. Our updated estimates will improve individual management and counseling in areas where genotype II Toxoplasma is predominant.
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                Author and article information

                Journal
                Parasite
                Parasite
                parasite
                Parasite
                EDP Sciences
                1252-607X
                1776-1042
                2020
                07 February 2020
                : 27
                : ( publisher-idID: parasite/2020/01 )
                : 7
                Affiliations
                [1 ] Service de Parasitologie-Mycologie, CHU de Nice, Université Côte d’Azur 06202 Nice France
                [2 ] Inserm U1065, C3M 06204 Nice France
                [3 ] Service de Parasitologie-Mycologie, CHU de Toulouse 31300 Toulouse France
                [4 ] PharmaDev, IRD UMR 152, Université de Toulouse 31062 Toulouse France
                [5 ] Service de Microbiologie, Hôpital La Source, CHR d’Orléans 45100 Orléans France
                [6 ] Parasitologie-Mycologie, CHU de Nantes 44093 Nantes France
                [7 ] Université de Nantes, Nantes Atlantique Universités, EA1155-IICiMed, Institut de Recherche en Santé 2 44200 Nantes France
                [8 ] Institut de Parasitologie et de Pathologie Tropicale, EA 7292, Fédération de Médecine Translationnelle, Université de Strasbourg 67000 Strasbourg France
                [9 ] EA7510, ESCAPE, Laboratoire de Parasitologie-Mycologie, Université de Reims Champagne-Ardenne, SFR Cap Santé FED 4231 51096 Reims France
                Author notes
                [a]

                Toxoplasma p35 Study Group: Jean-François Carod, Bernard Cimon, Rita Donsimoni, Valérie Ernault, Hélène Fricker-Hidalgo, Juliette Gillon, Nadine Godineau, Géraldine Gonfrier, Marie Hautecoeur, Stéphane Liguori, Marie-Noëlle Noulard, Hervé Pelloux, Cécile Poggi.

                [* ]Corresponding author: simon.l@ 123456chu-nice.fr
                Author information
                http://orcid.org/0000-0001-5583-1272
                http://orcid.org/0000-0002-5277-189X
                http://orcid.org/0000-0002-7415-4198
                http://orcid.org/0000-0002-6192-3293
                Article
                parasite190154 10.1051/parasite/2020006
                10.1051/parasite/2020006
                7006501
                32031519
                40867634-8e2b-4c7c-86f0-c7a2c8231f01
                © L. Simon et al., published by EDP Sciences, 2020

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 December 2019
                : 29 January 2020
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 48, Pages: 9
                Categories
                Research Article

                toxoplasma gondii,igg,false-positive,serology,architect,toxoplasmosis

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