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      El nexo entre biología, respuesta inmune y clínica en la infección por Toxoplasma gondii Translated title: Relationship between biology, immune response and clinical characteristics in Toxoplasma gondii infection

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          Abstract

          RESUMEN La toxoplasmosis ha sido considerada la parasitosis del siglo XX, con una seroprevalencia entre 25-30 % de la población humana general; en Cuba puede oscilar entre 50 %-75 %. A pesar de la casuística, Toxoplasma gondii no es bien conocido por la población general, inclusive por el personal médico; Cuba no escapa de esta realidad. Los objetivos del trabajo son caracterizar biológicamente a Toxoplasma gondii y la respuesta inmune desplegada, e identificar los elementos que facilitan el diagnóstico clínico de la toxoplasmosis. La Toxoplasma gondii puede infectar probablemente a todos los animales de sangre caliente incluyendo los humanos. Se han descrito cuatro linajes clonales diferentes y posee tres estadios principales de transmisión a los hospederos definitivos e intermediarios, siendo el gato el agente principal agente transmisor de la infección. Las transmisiones oral y placentaria son las principales vías de transmisión de Toxoplasma gondii. La respuesta celular Th1 origina un factor de resistencia en el hospedador, al decaer el parásito recupera su patogenicidad y puede ocasionar enfermedad diseminada. Los principales grupos en riesgo a padecer la enfermedad son los individuos inmunodeprimidos en quienes es capaz de causar enfermedad oportunista; en individuos inmunocompetentes la infección primaria es generalmente auto-limitada. Los factores de riesgo más evocados son el estrecho contacto con animales y hábitos higiénicos inadecuados. A pesar de que existe un tratamiento satisfactorio, las medidas de profilaxis constituyen el principal pilar de tratamiento para la toxoplasmosis. Aunque la biología del parásito le confiera patogenicidad, un sistema inmune competente y adecuadas medidas de control pueden limitar la infección.

          Translated abstract

          ABSTRACT Toxoplasmosis has been considered the 20th century parasitic disease, with a seroprevalence of 25-30% of the world human population, and 50%-75% in Cuba. Despite the large number of cases, Toxoplasma gondii is not well known by the general population or even the medical personnel, a fact of which Cuba is not an exception. The objectives of the study were to biologically characterize Toxoplasma gondii and the immune response displayed, and identify the elements facilitating the clinical diagnosis of toxoplasmosis. Toxoplasma gondii may probably infect all warm-blooded animals, including humans. Four different clonal lineages have been described, as well as three main stages in the transmission to definitive and intermediate hosts, cats being the main transmission agents of the infection. Oral and placental transmission are the main routes of transmission of Toxoplasma gondii. Th1 cell response creates a resistance factor in the host. When reduced, the parasite recovers its pathogenicity and may cause disseminated disease. The main groups at risk of contracting the disease are immunocompromised individuals, due to their vulnerability to opportunistic infections. In immunocompetent individuals the primary infection is generally self-limited. The risk factors most commonly cited are close contact with animals and poor hygiene. Despite the availability of satisfactory therapies, prophylactic measures continue to be the main pillar of the treatment of toxoplasmosis. Although the biology of the parasite grants it pathogenicity, a competent immune system and adequate control measures may limit the infection.

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          Novel Approaches Reveal that Toxoplasma gondii Bradyzoites within Tissue Cysts Are Dynamic and Replicating Entities In Vivo

          ABSTRACT Despite their critical role in chronic toxoplasmosis, the biology of Toxoplasma gondii bradyzoites is poorly understood. In an attempt to address this gap, we optimized approaches to purify tissue cysts and analyzed the replicative potential of bradyzoites within these cysts. In order to quantify individual bradyzoites within tissue cysts, we have developed imaging software, BradyCount 1.0, that allows the rapid establishment of bradyzoite burdens within imaged optical sections of purified tissue cysts. While in general larger tissue cysts contain more bradyzoites, their relative “occupancy” was typically lower than that of smaller cysts, resulting in a lower packing density. The packing density permits a direct measure of how bradyzoites develop within cysts, allowing for comparisons across progression of the chronic phase. In order to capture bradyzoite endodyogeny, we exploited the differential intensity of TgIMC3, an inner membrane complex protein that intensely labels newly formed/forming daughters within bradyzoites and decays over time in the absence of further division. To our surprise, we were able to capture not only sporadic and asynchronous division but also synchronous replication of all bradyzoites within mature tissue cysts. Furthermore, the time-dependent decay of TgIMC3 intensity was exploited to gain insights into the temporal patterns of bradyzoite replication in vivo. Despite the fact that bradyzoites are considered replicatively dormant, we find evidence for cyclical, episodic bradyzoite growth within tissue cysts in vivo. These findings directly challenge the prevailing notion of bradyzoites as dormant nonreplicative entities in chronic toxoplasmosis and have implications on our understanding of this enigmatic and clinically important life cycle stage.
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            Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions

            Background The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Methodology/Principal Findings Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. Conclusion/Significance This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations.
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              TOXOPLASMOSIS IN MEXICO: EPIDEMIOLOGICAL SITUATION IN HUMANS AND ANIMALS

              Toxoplasmosis is a parasitic disease widely distributed throughout the world, infecting a wide variety of animal species including humans. In Mexico, this parasite has been detected in different parts of the country, particularly in the tropical areas where the parasite can remain infective for long periods of time due to the environmental conditions (i.e. high temperature and humidity over the whole year). Several epidemiological studies have been conducted in both human and animal populations, but despite the wide distribution of the agent in the country, there is a significant lack of knowledge on the parasite transmission, treatment alternatives and control measures. The lack of feral cat populations and control measures in sites of meat production for human consumption are playing a role that has led to the wide spread of the disease in the country, particularly in tropical areas of Southeastern Mexico. For these reasons, this manuscript aims to review the published information on relevant epidemiological aspects of infection with T. gondii in humans and animals from Mexico.
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                Author and article information

                Journal
                ibi
                Revista Cubana de Investigaciones Biomédicas
                Rev Cubana Invest Bioméd
                ECIMED (Ciudad de la Habana, , Cuba )
                0864-0300
                1561-3011
                December 2019
                : 38
                : 4
                : e256
                Affiliations
                [2] Cuenca orgnameHospital Psiquiátrico “Humberto Ugalde Camacho” Ecuador
                [3] La Habana La Habana orgnameUniversidad de Ciencias Médicas de La Habana orgdiv1Facultad de Ciencias Médicas “Miguel Enríquez” orgdiv2Laboratorio Central de Líquido Cefalorraquídeo (LABCEL) Cuba
                [1] La Habana orgnameInstituto de Ciencias Básicas y Preclínicas “Victorias de Girón” Cuba
                Article
                S0864-03002019000400014 S0864-0300(19)03800400014
                c0e4afd1-911b-4ef7-ba29-f2d2b4b27af5

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 06 September 2019
                : 09 July 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 51, Pages: 0
                Product

                SciELO Cuba

                Categories
                ARTÍCULOS DE REVISIÓN

                inmunodeprimidos,respuesta inmune,immune response,ciclo de vida,Toxoplasma gondii,life cycle,immunocompromised

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