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      Global initiative for congenital toxoplasmosis: an observational and international comparative clinical analysis

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          Abstract

          Globally, congenital toxoplasmosis remains a significant cause of morbidity and mortality, and outbreaks of infection with T. gondii represent a significant, emerging public health burden, especially in the developing world. This parasite is a threat to public health. Disease often is not recognized and is inadequately managed. Herein, we analyze the status of congenital toxoplasmosis in Morocco, Colombia, the United States, and France. We identify the unique challenges faced by each nation in the implementation of optimal approaches to congenital toxoplasmosis as a public health problem. We suggest that developed and developing countries use a multipronged approach, modeling their public health management protocols after those in France. We conclude that education, screening, appropriate treatment, and the development of novel modalities will be required to intervene successfully in caring for individuals with this infection. Gestational screening has been demonstrated to be cost-effective, morbidity-sparing, and life-saving. Recognition of the value and promise of public health interventions to prevent human suffering from this emerging infection will facilitate better patient and societal outcomes.

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          Most cited references62

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          Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases.

          The population structure of Toxoplasma gondii includes three highly prevalent clonal lineages referred to as types I, II, and III, which differ greatly in virulence in the mouse model. Previous studies have implicated a family of serine/threonine protein kinases found in rhoptries (ROPs) as important in mediating virulence differences between strain types. Here, we explored the genetic basis of differences in virulence between the highly virulent type I lineage and moderately virulent type II based on successful genetic cross between these lineages. Genome-wide association revealed that a single quantitative trait locus controls the dramatic difference in lethality between these strain types. Neither ROP16 nor ROP18, previously implicated in virulence of T. gondii, was found to contribute to differences between types I and II. Instead, the major virulence locus contained a tandem cluster of polymorphic alleles of ROP5, which showed similar protein expression between strains. ROP5 contains a conserved serine/threonine protein kinase domain that includes only part of the catalytic triad, and hence, all members are considered to be pseudokinases. Genetic disruption of the entire ROP5 locus in the type I lineage led to complete attenuation of acute virulence, and complementation with ROP5 restored lethality to WT levels. These findings reveal that a locus of polymorphic pseudokinases plays an important role in pathogenesis of toxoplasmosis in the mouse model.
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            Fatal outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects.

            Well-documented outbreaks of human toxoplasmosis infection are infrequently reported. Here, we describe a community outbreak of multivisceral toxoplasmosis that occurred in Patam, a Surinamese village near the French Guianan border. From the end of December 2003 through the middle of January 2004, 5 adult patients in Patam, including 2 pregnant women, were initially hospitalized for multivisceral toxoplasmosis. A French-Surinamese epidemiological investigation was conducted in the village; inquiries and clinical examinations were performed, and blood and environmental samples were obtained. For all serologically confirmed cases of toxoplasmosis, molecular analysis and mouse inoculations were performed for diagnosis and genetic characterization of Toxoplasma gondii. The hospitalized patients, who did not have any immunodeficiencies, presented with an infectious disease with multivisceral involvement. Serological examination confirmed acute toxoplasmosis. One adult died, and a neonate and a fetus with congenital toxoplasmosis also died. During the investigation, 4 additional acute cases of toxoplasmosis were diagnosed among the 33 villagers. Only 3 inhabitants had serological evidence of previous T. gondii infection. In total, we reported 11 cases of toxoplasmosis: 8 multivisceral cases in immunocompetent adults, resulting in 1 death; 2 cases of lethal congenital toxoplasmosis in a neonate and a fetus; and 1 symptomatic case in a child. Molecular analysis demonstrated that identical isolates of only 1 atypical strain were responsible for at least 5 of the 11 cases of toxoplasmosis in the outbreak. No epidemiological sources could be linked to this severe community-wide outbreak of toxoplasmosis. This report is in agreement with the particular features of toxoplasmosis involving atypical strains that were recently described in French Guiana.
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              Toxoplasma gondii oocyst survival under defined temperatures.

              The survival of sporulated Toxoplasma gondii oocysts in water at -10 C to 70 C for various periods was investigated. Infectivity of T. gondii was tested by bioassay in mice. There was no marked loss of infectivity of oocysts stored at 10 C, 15 C, 20 C, and 25 C for 200 days, whereas there was a 100-fold loss of infectivity of oocysts stored at 30 C for 107 days. Oocysts stored at 35 C were infective for 32 days but not 62 days, at 40 C oocysts were infective for 9 days but not 28 days, at 45 C, oocysts were infective for 1 day but not 2 days, at 50 C oocysts were infective for 1 hr but not 2 hr. At 55 C and 60 C oocysts were rendered noninfective in 2 and 1 min, respectively. Oocysts remained infective up to 54 mo at 4 C and there was no loss of infectivity in oocysts stored for 106 days at -5 C and at -10 C and for 13 mo at 0 C.
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                Author and article information

                Contributors
                kelbissati@uchicago.edu
                Journal
                Emerg Microbes Infect
                Emerg Microbes Infect
                Emerging Microbes & Infections
                Nature Publishing Group UK (London )
                2222-1751
                27 September 2018
                27 September 2018
                2018
                : 7
                : 165
                Affiliations
                [1 ]ISNI 0000 0004 1936 7822, GRID grid.170205.1, Department of Ophthalmology and Visual Sciences, , University of Chicago, ; Chicago, IL 60637 USA
                [2 ]Institut de Parasitologie et de Mycologie Médicale Hôpital de la Croix Rousse, 103 grande rue de la Croix Rousse, 69317 Lyon, France
                [3 ]ISNI 0000 0004 0458 8737, GRID grid.224260.0, Department of Emergency Medicine, Department of Internal Medicine, , Virginia Commonwealth University Health System, ; Richmond, VA 23219 USA
                [4 ]GRID grid.418480.1, Institut National d’ Hygiène, ; Rabat, Morocco
                [5 ]ISNI 0000 0001 2168 4024, GRID grid.31143.34, Research Team on Mother-Child Health and Nutrition, Faculté de Médecine et de Pharmacie de Rabat, , Université Mohammed V, ; Rabat, Morocco
                [6 ]GRID grid.411835.a, Department d’Ophtalmologie, , Hôpital des Spécialités, CHU, ; P6220 Rabat, Morocco
                [7 ]ISNI 0000 0001 2168 4024, GRID grid.31143.34, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V, ; Rabat, Morocco
                [8 ]ISNI 0000 0004 1936 738X, GRID grid.213876.9, Department of Infectious Diseases, College of Veterinary Medicine, , University of Georgia, ; Athens, GA 30602 USA
                [9 ]Analytics, Graham School, University of Chicago, Chicago, IL 60637 USA
                [10 ]GRID grid.441861.e, Grupo de Estudio en Parasitología Molecular (GEPAMOL), Centro de Investigaciones Biomédicas, , Universidad del Quindio, Av. Bolivar 12N, ; Armenia, Quindio Colombia
                [11 ]ISNI 0000 0004 1936 7822, GRID grid.170205.1, Department of Ophthalmology and Visual Sciences, Department of Pediatrics (Infectious Diseases), Institute of Genomics, Genetics, and Systems Biology, Global Health Center, Toxoplasmosis Center, CHeSS, The College, , University of Chicago, ; Chicago, IL 60637 USA
                Author information
                http://orcid.org/0000-0002-3424-0104
                http://orcid.org/0000-0001-8246-6848
                http://orcid.org/0000-0001-6472-3329
                Article
                164
                10.1038/s41426-018-0164-4
                6160433
                30262847
                ae3bc5f1-7450-4b18-a770-92be1d58c3f0
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 May 2018
                : 30 July 2018
                : 6 August 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: DMID-NIAID U01 AI77887, R01 27530
                Award Recipient :
                Categories
                Review Article
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                © The Author(s) 2018

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