Immunology and Microbiology Parasitology

Toxoplasma gondii Research Studies

Description

This cluster of papers focuses on the research related to Toxoplasma gondii and Neospora caninum, including epidemiology, diagnosis, prevention, zoonotic transmission, host-pathogen interactions, virulence factors, genetic diversity, and immune response. The papers cover a wide range of topics from molecular biology to clinical aspects of toxoplasmosis and neosporosis.

Keywords

Toxoplasma gondii; Neosporosis; Epidemiology; Diagnosis; Prevention; Host-Pathogen Interactions; Zoonotic Transmission; Virulence Factors; Genetic Diversity; Immune Response

Neospora caninum infection was diagnosed in 5 young dogs from 2 litters with a common parentage. The pups were born healthy, but developed hind limb paresis 5 to 8 weeks … Neospora caninum infection was diagnosed in 5 young dogs from 2 litters with a common parentage. The pups were born healthy, but developed hind limb paresis 5 to 8 weeks after birth. The predominant lesions were polyradiculoneuritis and granulomatous polymyositis. Neospora caninum was seen microscopically in sections of naturally infected pups, and was isolated in cell cultures, mice, and dogs inoculated with infected canine tissues. Antibodies to N caninum were detected in sera of infected dogs by indirect fluorescent antibody test.
Summary Histologic sections and case histories from 23 dogs with proven fatal toxoplasmosis-like illness at the Angell Memorial Animal Hospital were reviewed. Toxoplasma gondii was identified in 13 dogs. A … Summary Histologic sections and case histories from 23 dogs with proven fatal toxoplasmosis-like illness at the Angell Memorial Animal Hospital were reviewed. Toxoplasma gondii was identified in 13 dogs. A newly identified parasite, Neospora caninum, structurally distinct from T gondii , was found in 10 dogs. The newly discovered organism, belonging to a new genus and new species, formed meronts in many tissues of the dogs, especially the brain and spinal cord. Neospora caninum was located directly in the host cell cytoplasm without a parasitophorous vacuole; it divided by endodyogeny, contained more than 11 rhoptries, and did not react with the anti-T gondii serum in the immunoperoxidase test. Meningoencephalomyelitis and myositis were the main lesions associated with N caninum . Ulcerative and fistulous dermatitis was the major lesion in 1 dog.
To examine the function of IL-10 synthesis during early infection with the intracellular protozoan Toxoplasma gondii, IL-10 knockout (KO) mice were inoculated with an avirulent parasite strain (ME-49). In contrast … To examine the function of IL-10 synthesis during early infection with the intracellular protozoan Toxoplasma gondii, IL-10 knockout (KO) mice were inoculated with an avirulent parasite strain (ME-49). In contrast to control littermates that displayed 100% survival, the IL-10-deficient animals succumbed within the first 2 wk of the infection, with no evidence of enhanced parasite proliferation. The mortality in the IL-10 KO mice was associated with enhanced liver pathology characterized by increased cellular infiltration and intense necrosis. Levels of IL-12 and IFN-gamma in sera of infected IL-10-deficient animals were four- to sixfold higher than those in sera from control mice, as were mRNA levels for IFN-gamma, IL-1 beta, TNF-alpha, and IL-12 in lung tissue. Similarly, macrophages from IL-10 KO mice activated in vitro or in vivo with T. gondii produced higher levels of TNF-alpha and IL-12 than macrophages from control animals. Moreover, spleen cells from IL-10 KO mice infected with T. gondii secreted more IFN-gamma than splenocytes from nondeficient animals. In vitro depletion experiments indicated that CD4+ lymphocytes are the major source of the latter cytokine in the spleen cell populations, and in vivo depletion with anti-CD4 Abs protected the IL-10 KO mice from parasite-induced mortality. Together the data suggest that endogenous IL-10 synthesis plays an important role in vivo in down-regulating monokine and IFN-gamma responses to acute intracellular infection, thereby preventing host immunopathology.
<h3>Abstract</h3> <b>Objective:</b> To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. <b>Design:</b> Case-control study. <b>Setting:</b> Six large European … <h3>Abstract</h3> <b>Objective:</b> To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. <b>Design:</b> Case-control study. <b>Setting:</b> Six large European cities. <b>Participants:</b> Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-<i>Toxoplasma gondii</i> IgM were compared with pregnant women seronegative for toxoplasma (controls). <b>Main outcome measures:</b> Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. <b>Results:</b> Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. <b>Conclusions:</b> Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women.
In vitro and in vivo studies were performed to assess the involvement of IL-12 in resistance to acute and chronic infection with an avirulent strain of Toxoplasma gondii. Our previous … In vitro and in vivo studies were performed to assess the involvement of IL-12 in resistance to acute and chronic infection with an avirulent strain of Toxoplasma gondii. Our previous findings implicated macrophages as a major source of parasite-induced IL-12. This finding was confirmed by showing that peritoneal macrophages exposed to either live parasites or soluble tachyzoite Ags produce IL-12 protein. In mice, increased expression of IL-12 (p40) mRNA in both spleen and peritoneal cells was detected as early as 2 days postinfection. Treatment with neutralizing mAbs against IL-12 increased the susceptibility of C57BL/6, BALB/c, and severe combined immunodeficient (SCID) mice to acute infection, which resulted in 100% mortality within the first 15 days after parasite inoculation. In contrast, neutralization of endogenously produced IL-12 had no effect when given during chronic infection. In agreement with the survival data, treatment with anti-IL-12 resulted in decreased IFN-gamma and enhanced Th2 (IL-4 and IL-10) cytokine synthesis by splenocytes when given during acute, but not chronic, toxoplasmosis. Sorting experiments on spleen cells from acutely infected mice indicated that both CD4+ lymphocytes and NK1.1+/CD3- cells contribute to the early IFN-gamma response. In contrast, CD4+ cells were found to be the major source of the cytokine during chronic disease. Together, these results suggest that the stimulation of macrophage-derived IL-12 plays a major role in both the induction of resistance and Th1 cell subset selection in acute T. gondii infection, but may not be required to maintain established immunity.
Sarcocystis is one of the most prevalent parasites of livestock and also infects many wild mammals, birds, and humans. Written by the authors who pioneered studies of Sarcocystosis of domestic … Sarcocystis is one of the most prevalent parasites of livestock and also infects many wild mammals, birds, and humans. Written by the authors who pioneered studies of Sarcocystosis of domestic animals, Sarcocystosis of Animals and Humans, Second Edition provides a current and comprehensive review of Sarcocystis and the infections it causes in anima
Abstract IL-10, a cytokine produced by CD4+ T lymphocytes belonging to the Th-2 subset, has previously been shown to inhibit the synthesis of IFN-gamma by both T cells and NK … Abstract IL-10, a cytokine produced by CD4+ T lymphocytes belonging to the Th-2 subset, has previously been shown to inhibit the synthesis of IFN-gamma by both T cells and NK cells. We now demonstrate that IL-10 can also down-regulate IFN-gamma-dependent immunity by blocking the ability of that lymphokine to activate macrophages. Thus, IL-10, in a dose-dependent manner, inhibits the microbicidal activity of IFN-gamma-treated inflammatory macrophages against intracellular Toxoplasma gondii as well as the extracellular killing of schistosomula of Schistosoma mansoni. This suppression correlates with the inhibition by IL-10 of IFN-gamma-induced production of toxic nitrogen oxide metabolites, an effector mechanism previously implicated in the killing by macrophages of both parasite targets. IL-10 inhibition of nitric oxide production was shown to occur when the cytokine is given before or together with the IFN-gamma-activating stimulus, but not after its removal from the cultures and to require 12 h of contact for maximal suppressive effect on macrophage function. These results, taken together with previous findings on the down-regulation of Th1 lymphokine production by IL-10, indicate that the induction of IL-10 may be an important strategy by which parasites evade IFN-gamma-dependent, cell-mediated immune destruction.
We applied the polymerase chain reaction to detection of the pathogenic protozoan Toxoplasma gondii based on our identification of a 35-fold-repetitive gene (the B1 gene) as a target. Using this … We applied the polymerase chain reaction to detection of the pathogenic protozoan Toxoplasma gondii based on our identification of a 35-fold-repetitive gene (the B1 gene) as a target. Using this procedure, we were able to amplify and detect the DNA of a single organism directly from a crude cell lysate. This level of sensitivity also allowed us to detect the B1 gene from purified DNA samples containing as few as 10 parasites in the presence of 100,000 human leukocytes. This is representative of the maximal cellular infiltration (10(5)/ml) in 1 ml of cerebrospinal fluid obtained from patients with toxoplasmic encephalitis. The B1 gene is present and conserved in all six T. gondii strains tested to date, including two isolates from patients with acquired immunodeficiency syndrome. No signal was detected by using this assay and DNAs from a variety of other organisms, including several which might be found in the central nervous system of an immunocompromised host. This combination of sensitivity and specificity should make detection of the B1 gene based on polymerase chain reaction amplification a very useful method for diagnosis of toxoplasmosis both in immunocompromised hosts and in congenitally infected fetuses.
Treatment of human fibroblasts with human recombinant gamma interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth of the parasite was measured by a plaque assay … Treatment of human fibroblasts with human recombinant gamma interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth of the parasite was measured by a plaque assay 7 days after infection or by the incorporation of [3H]uracil 1 or 2 days after infection. The antitoxoplasma activity induced in the host cells by gamma interferon was strongly dependent upon the tryptophan concentration of the medium. Progressively higher minimal inhibitory concentrations of gamma interferon were observed as the tryptophan concentration in the culture medium was increased. Treatment with gamma interferon did not make the cells impermeable to tryptophan. The kinetics of [3H]tryptophan uptake into the acid-soluble pools of control and gamma interferon-treated cultures were identical during the first 48 sec. Thereafter uptake of [3H]tryptophan into the acid-soluble pool of control fibroblasts reached the expected plateau after 96 sec. In contrast, uptake of [3H]tryptophan continued for at least 12 min in the gamma interferon-treated cultures. At that time, the acid-soluble pool of the gamma interferon-treated cultures contained 8 times the radioactivity of the control cultures. This continued accumulation was the result of rapid intracellular degradation of [3H]tryptophan into kynurenine and N-formylkynurenine that leaked slowly from the cells. These two metabolites were also recovered from the medium of cultures treated for 1 or 2 days with gamma interferon. Human recombinant alpha and beta interferons, which have no antitoxoplasma activity, did not induce any detectable degradation of tryptophan. Several hypotheses are presented to explain how the intracellular degradation of tryptophan induced by gamma interferon could restrict the growth of an obligate intracellular parasite.
Infection with Toxoplasma gondii can cause severe illness when the organism is contracted congenitally or when it is reactivated in immune-suppressed persons. To determine the prevalence of T. gondii infection … Infection with Toxoplasma gondii can cause severe illness when the organism is contracted congenitally or when it is reactivated in immune-suppressed persons. To determine the prevalence of T. gondii infection in a representative sample of the US population, the authors tested sera from participants in the Third National Health and Nutrition Examination Survey (1988-1994) for immunoglobulin G antibodies to T. gondii. Of 27,145 persons aged > or =12 years, 17,658 (65%) had sera tested. The overall age-adjusted seroprevalence was 22.5% (95% confidence interval (CI): 21.1, 23.9); among women aged 15-44 years, seroprevalence was 15.0% (95% CI: 13.2, 17.0). Age-adjusted seroprevalence was higher in the Northeast (29.2%) than in the South (22.8%), Midwest (20.5%), or West (17.5%) (p < 0.05). In multivariate analysis, risk for T. gondii infection increased with age and was higher among persons who were foreign-born, persons with a lower educational level, those who lived in crowded conditions, and those who worked in soil-related occupations, although in subset analyses risk categories varied by race/ethnicity. Nearly one quarter of adults and adolescents in the United States have been infected with T. gondii. Most women of childbearing age in the United States are susceptible to acute infection and should be educated about ways to minimize exposure to T. gondii.
Neospora caninum is a coccidian parasite of animals. It is a major pathogen for cattle and dogs and it occasionally causes clinical infections in horses, goats, sheep, and deer. Domestic … Neospora caninum is a coccidian parasite of animals. It is a major pathogen for cattle and dogs and it occasionally causes clinical infections in horses, goats, sheep, and deer. Domestic dogs are the only known definitive hosts for N. caninum. It is one of the most efficiently transmitted parasite of cattle and up to 90% of cattle in some herds are infected. Transplacental transmission is considered the major route of transmission of N. caninum in cattle. Neospora caninum is a major cause of abortion in cattle in many countries. To elicit protective immunity against abortion in cows that already harbor a latent infection is a major problem. This paper reviews information on biology, diagnosis, epidemiology and control of neosporosis in animals. Key words: Neospora caninum, neosporosis, animals, cattle, dogs
Mice were injected with a monoclonal antibody to interferon-γ to examine the importance of endogenous production of this lymphokine in resistance against infection with the sporozoan parasite Toxoplasma gondii . … Mice were injected with a monoclonal antibody to interferon-γ to examine the importance of endogenous production of this lymphokine in resistance against infection with the sporozoan parasite Toxoplasma gondii . Mice with intraperitoneal infections of T. gondii that received no antibody survived and developed chronic T. gondii infection, whereas the infected mice that received the monoclonal antibody died of toxoplasmosis. The activation of macrophages, which kill T. gondii in vivo, was inhibited by administration of the monoclonal antibody, but the production of antibodies to T. gondii was not suppressed. The fact that an antibody to interferon-γ can eliminate resistance to acute Toxoplasma infection in mice suggests that this lymphokine is an important mediator of host resistance to this parasite.
An epidemic of cases of toxoplasmic encephalitis is occurring in patients with acquired immune deficiency syndrome (AIDS). Serological or histopathologic studies were performed on 70 cases with AIDS and toxoplasmic … An epidemic of cases of toxoplasmic encephalitis is occurring in patients with acquired immune deficiency syndrome (AIDS). Serological or histopathologic studies were performed on 70 cases with AIDS and toxoplasmic encephalitis. In many cases conventional stains of brain-tissue specimens failed to disclose Toxoplasma organisms; all were positive when stained by the peroxidase-antiperoxidase technique. Except for a single patient, serological titers were not indicative of an acute acquired infection. The ratio of titers in the agglutination test to titers in the Sabin-Feldman dye test seemed to be more predictive of active toxoplasmic encephalitis in patients with AIDS than either test alone. Based on histological and serological data, an approach is presented for diagnosis and treatment of suspected toxoplasmic encephalitis in patients with AIDS.
Immunity against the intracellular protozoan Toxoplasma gondii is highly dependent on interferon gamma (IFN-gamma). We have previously shown that, in addition to T lymphocytes, natural killer (NK) cells can be … Immunity against the intracellular protozoan Toxoplasma gondii is highly dependent on interferon gamma (IFN-gamma). We have previously shown that, in addition to T lymphocytes, natural killer (NK) cells can be stimulated by the parasite to produce this cytokine by a reaction requiring adherent accessory cells and tumor necrosis factor alpha. We now demonstrate that a recently characterized cytokine, interleukin 12 (IL-12), is also necessary for parasite-induced IFN-gamma synthesis by NK cells. Anti-IL-12 antibodies completely inhibited T. gondii or bacterial endotoxin-stimulated IFN-gamma production by NK-enriched spleen cells from severe combined immunodeficient mice. Moreover, potent NK cytokine responses were induced by the combination of IL-12 and tumor necrosis factor alpha. In addition, adherent spleen cells from scid/scid mice or thyoglycollate-elicited macrophages from BALB/c animals produced high levels of both IL-12 (p40) and tumor necrosis factor alpha mRNAs when exposed to either live tachyzoites, parasite extracts, or endotoxin, confirming that these cytokines are produced by accessory cells. Finally, in vivo studies showed that treatment with recombinant IL-12 results in prolonged survival of scid mice after infection with T. gondii by means of a response dependent on both IFN-gamma and NK cells. Together the data argue that IL-12 is required for the T-cell-independent triggering of NK cells by intracellular parasites and that the cytokine may be useful for inducing this protective pathway in immunodeficient hosts.
A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or “apicoplast,” is indispensable, but the complete sequence of both the Plasmodium … A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or “apicoplast,” is indispensable, but the complete sequence of both the Plasmodium falciparum and Toxoplasma gondii apicoplast genomes has offered no clue as to what essential metabolic function(s) this organelle might perform in parasites. To investigate possible functions of the apicoplast, we sought to identify nuclear-encoded genes whose products are targeted to the apicoplast in Plasmodium and Toxoplasma . We describe here nuclear genes encoding ribosomal proteins S9 and L28 and the fatty acid biosynthetic enzymes acyl carrier protein (ACP), β-ketoacyl-ACP synthase III (FabH), and β-hydroxyacyl-ACP dehydratase (FabZ). These genes show high similarity to plastid homologues, and immunolocalization of S9 and ACP verifies that the proteins accumulate in the plastid. All the putatively apicoplast-targeted proteins bear N-terminal presequences consistent with plastid targeting, and the ACP presequence is shown to be sufficient to target a recombinant green fluorescent protein reporter to the apicoplast in transgenic T. gondii . Localization of ACP, and very probably FabH and FabZ, in the apicoplast implicates fatty acid biosynthesis as a likely function of the apicoplast. Moreover, inhibition of P. falciparum growth by thiolactomycin, an inhibitor of FabH, indicates a vital role for apicoplast fatty acid biosynthesis. Because the fatty acid biosynthesis genes identified here are of a plastid/bacterial type, and distinct from those of the equivalent pathway in animals, fatty acid biosynthesis is potentially an excellent target for therapeutics directed against malaria, toxoplasmosis, and other apicomplexan-mediated diseases.
1. Nude is a new recessive gene causing hairlessness in the mouse. It is linked to rex and trembler in linkage group VII. The order of the three loci and … 1. Nude is a new recessive gene causing hairlessness in the mouse. It is linked to rex and trembler in linkage group VII. The order of the three loci and the recombination frequencies are as follows: 2. In addition to hairlessness the new gene causes reduced body growth rate, very low fertility and a liver disease causing death. Nude mice may be classified at birth by the absence of vibrissae. 3. The hairlessness is due to abnormal keratinization of hair in the follicles. The skin histology resembles that of naked mice. The hair follicles were found to be deficient in free sulphydryl groups. 4. The majority of nude mice die of general body weakness within 2 weeks of birth. The survivors grow slowly and may live for a considerable period. But all nude mice eventually die, usually between 3 and 14 weeks of age. 5. The livers of dead or moribund nude mice are covered with lesions and scars. The defect has been traced histologically to its initial stage, namely, necrosis of small areas of tissue. 6. Attempts to relate the deficiency of sulphydryl groups in the hair follicles to abnormal sulphur metabolism in the liver were unsuccessful. 7. Pseudo-cysts of a parasitic protozoan, Toxoplasma gondii , were identified in the liver and brain of nude mice. In one case the free form of the organism was found. 8. The possible relationship between the liver disease and the pathogenic organism is discussed.
Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and … Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.
To estimate the global burden of congenital toxoplasmosis (CT), which results from infection of pregnant women with Toxoplasma gondii.The authors systematically searched 9 major databases for published and unpublished sources … To estimate the global burden of congenital toxoplasmosis (CT), which results from infection of pregnant women with Toxoplasma gondii.The authors systematically searched 9 major databases for published and unpublished sources and established direct contact with the authors of source materials. Searches were country-specific. To be included, studies had to report on the incidence of CT, on positivity to Toxoplasma-specific IgM in infants and pregnant women (including seroconversion results) or on positivity to Toxoplasma-specific IgG in the general population. Various modelling techniques were used, depending on the country-specific data available, to estimate the CT incidence and burden in each country. These data were then synthesized into an estimate of the global incidence of CT and of the global burden of CT in disability-adjusted life years (DALYs).The global annual incidence of congenital toxoplasmosis was estimated to be 190,100 cases (95% credible interval, CI: 179,300-206,300). This was equivalent to a burden of 1.20 million DALYs (95% CI: 0.76-1.90). High burdens were seen in South America and in some Middle Eastern and low-income countries.Congenital toxoplasmosis poses a substantial burden of poor health globally. Toxoplasmosis should be included in future updates of the global burden of disease and the corresponding data should be used to support public health interventions to reduce disease burden.Faire une estimation de la charge mondiale de la toxoplasmose congénitale (TC), qui résulte de l'infection des femmes enceintes par le Toxoplasma gondii.Les auteurs ont recherché des sources publiées et non publiées dans neuf bases de données principales et sont entré en contact direct avec les auteurs des documents source. Les recherches ont été spécifiques par pays. Pour être incluses, les études devaient décrire l'incidence de la TC sur les résultats positifs aux IgM spécifiques de la toxoplasmose chez les nourrissons et les femmes enceintes (y compris les résultats de séroconversion) ou les résultats positifs aux IgG spécifiques de la toxoplasmose dans la population en général. Différentes techniques de modélisation ont été employées, selon les données disponibles spécifiques par pays, pour estimer l'incidence et la charge de la TC dans chaque pays. Ces données ont été synthétisées en une estimation de l'incidence globale de la TC et de la charge globale de la TC en années de vie corrigées du facteur invalidité (AVCI).L'incidence annuelle globale de la toxoplasmose congénitale a été estimée à 190 100 cas (intervalle de crédibilité, IC de 95%: 179 300–206 300), ce qui équivaut à une charge de 1,20 millions d'AVCI (IC de 95%: 0,76–1,90). Des taux élevés ont été observés en Amérique du Sud et dans certains pays du Moyen-Orient et à faibles revenus.La toxoplasmose congénitale représente une charge de morbidité considérable au niveau mondial; elle devrait donc être incluse dans les futures mises à jour de la charge mondiale de morbidité et les données correspondantes devraient être employées pour soutenir les interventions en santé publique visant à réduire la charge de morbidité.Calcular la carga mundial de la toxoplasmosis congénita (TC) derivada de la infección de mujeres embarazadas con el parásito Toxoplasma gondii.Los autores buscaron sistemáticamente en nueve de las principales bases de datos de fuentes publicadas y no publicadas y establecieron contacto directo con los autores del material original. Se realizaron búsquedas específicas para cada país. Para ser incluidos, los estudios debían informar sobre la incidencia de la TC, la positividad de IgM específicos de Toxoplasma en niños y mujeres embarazadas (incluidos los resultados de la seroconversión) o la positividad de IgG específicos de Toxoplasma en la población general. Se utilizaron diferentes técnicas de modelización, dependiendo de los datos específicos disponibles de cada país, con el objetivo de calcular la incidencia y la carga de TC en cada país. A continuación se sintetizarod esos datos en una estimación de la incidencia mundial de la TC y la carga mundial de la TC en los años de vida con discapacidad.Se calculó que la incidencia anual de la toxoplasmosis congénita a nivel mundial es de 190 100 casos (un 95% de intervalo de confianza: 179 300—206 300). Esto equivale a una carga de 1,20 millones de años de vida con discapacidad (un 95% de intervalo de confianza: 0,76 – 1,90). En Sudamérica, algunos países de Oriente Medio y en los países de renta baja se observaron cargas elevadas.La toxoplasmosis congénita plantea una carga importante de salud deficiente a nivel mundial. La toxoplasmosis debería incluirse en las actualizaciones futuras de la carga mundial de morbilidad y deberán utilizarse los correspondientes datos para apoyar las intervenciones en materia de salud pública destinadas a reducir la carga de morbilidad.تقدير العبء العالمي لداء المقوسات الخلقي (CT)، الذي ينجم عن إصابة السيدات الحوامل بعدوى المقوسة الغوندية .قام المؤلفون بالبحث على نحو منهجي في 9 قواعد بيانات رئيسية من أجل الحصول على المصادر المنشورة وغير المنشورة والاتصال المباشر مع مؤلفي مواد المصادر. وكانت الأبحاث خاصة بكل بلد. ولكي يتم إدراج الدراسات، يتعين عليها الإبلاغ عند وجود داء المقوسات الخلقي، بوجود إيجابية للعوز المناعي مفرط الأيج M (IgM) الخاص بالمقوسة لدى الرضع والسيدات الحوامل (بما في ذلك نتائج انقلاب تفاعلية المصل) أو وجود إيجابية لمستضد غلوبين غاما (IgG) الخاص بالمقوسة لدى عامة السكان، وهو ما تقرر إدراجه. وتم استخدام عدة أساليب نمذجة، بناءً على البيانات المتاحة الخاصة بكل بلد، لتقدير معدل الإصابة بداء المقوسات الخلقي والعبء في كل بلد. وتم بعد ذلك استخلاص هذه البيانات في تقدير معدل الإصابة العالمي بداء المقوسات الخلقي والعبء العالمي لداء المقوسات الخلقي بالنسبة لسنوات العمر المصححة باحتساب مدد العجز.بلغ معدل الإصابة العالمي السنوي بداء المقوسات الخلقي وفق التقديرات 190100 حالة (فاصل الثقة 95 %، فاصل الثقة: من 179300 إلى 206300). وكان هذا المعدل معادلاً لعبء 1.20 مليون سنة من سنوات العمر المصححة باحتساب مدد العجز (فاصل الثقة 95 %: من 0.76إلى 1.90). ولوحظت أعباء عالية في أمريكا الجنوبية وفي بعض بلدان الشرق الأوسط والبلدان المنخفضة الدخل.يفرض داء المقوسات الخلقي عبئاً كبيراً على سوء الظروف الصحية على الصعيد العالمي. وينبغي إدراج داء المقوسات في التحديثات المستقبلية للعبء العالمي للمرض وينبغي استخدام البيانات المقابلة لدعم تدخلات الصحة العمومية بُغية تقليل عبء المرض.评估先天性弓形虫病(CT)的全球负担,这种病因孕妇感染刚地弓形虫而导致。作者系统地搜查公布和未公布来源的9 个主要数据库并与来源资料的作者建立直接联系。搜索按国家进行。纳入的研究必须有CT发病率、婴儿和孕妇的弓形虫特定IgM阳性(包含血清转换结果)或者一般人群的弓形虫特定IgG阳性的相关报告。根据各个国家可用的特定数据,使用各种建模技术,估计每个国家的CT发病率和负担。这些数据而后进行合成,以评估CT全球发病率和以伤残调整数字年(DALY)计量的CT全球负担。全球先天性弓形虫病每年发病率估计为190100 例(95%置信区间,CI:179300–206300)。这相当于120 万DALY(95% CI:0.76–1.90)。南美洲和一些中东国家以及低收入国家的负担高。先天性弓形虫病在全球带来不良健康状况的沉重负担。在全球疾病负担的未来更新中应包括弓形体病,并应使用相应的数据以支持公共卫生干预措施,从而减少疾病负担。Оценить глобальное бремя врожденного токсоплазмоза (ВТ), который возникает в результате инфицирования беременных женщин Toxoplasma gondii.Авторы провели систематический поиск опубликованных и неопубликованных источников в 9 основных базах данных и установили прямой контакт с авторами исходных материалов. Поиск проводился с учетом особенностей каждой конкретной страны. Для включения в обзор в исследованиях должно было сообщаться о случаях ВТ, о положительных пробах на присущий Toxoplasma иммуноглобулин М у младенцев и беременных женщин (включая результаты сероконверсии) или положительных пробах на присущий Toxoplasma иммуноглобулин М среди населения в целом. Для оценки уровня заболеваемости и бремени ВТ в каждой стране использовались различные методы моделирования в зависимости от имеющихся данных по конкретной стране. Затем эти данные были обобщены в оценке глобального уровня заболеваемости и глобального бремени ВТ, выраженной в потерянных годах жизни, скорректированных на инвалидность (DALY).Глобальная ежегодная заболеваемость врожденным токсоплазмозом оценивается на уровне 190 100 случаев (95%-ный доверительный интервал, ДИ: 179 300–206 300). Это эквивалентно бремени 1,2 млн потерянных лет жизни, скорректированных на инвалидность (95%-ный ДИ: 0,76-1,90). Высокие уровни бремени были отмечены в Южной Америке, некоторых ближневосточных странах и странах с низким уровнем доходов.Врожденный токсоплазмоз создает значительное бремя плохого здоровья во всем мире. Токсоплазмоз должен быть включен в будущие уточненные варианты глобального бремени болезней, и соответствующие данные должны быть использованы для поддержки мероприятий в области общественного здравоохранения для снижения бремени данной болезни.
SUMMARY Neospora caninum is a protozoan parasite of animals. Until 1988, it was misidentified as Toxoplasma gondii . Since its first recognition in dogs in 1984 and the description of … SUMMARY Neospora caninum is a protozoan parasite of animals. Until 1988, it was misidentified as Toxoplasma gondii . Since its first recognition in dogs in 1984 and the description of the new genus and species Neospora caninum in 1988, neosporosis has emerged as a serious disease of cattle and dogs worldwide. Abortions and neonatal mortality are a major problem in livestock operations, and neosporosis is a major cause of abortion in cattle. Although antibodies to N. caninum have been reported, the parasite has not been detected in human tissues. Thus, the zoonotic potential is uncertain. This review is focused mainly on the epidemiology and control of neosporosis in cattle, but worldwide seroprevalences of N. caninum in animals and humans are tabulated. The role of wildlife in the life cycle of N. caninum and strategies for the control of neosporosis in cattle are discussed.
Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, … Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens.
SUMMARY The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last … SUMMARY The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last 40 years. This obligate intracellular parasite was identified early as a pathogen responsible for congenital infection, but its clinical expression and the importance of reactivations of infections in immunocompromised patients were recognized later, in the era of organ transplantation and HIV infection. Recent knowledge of host cell-parasite interactions and of parasite virulence has brought new insights into the comprehension of the pathophysiology of infection. In this review, we focus on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes. In particular, we provide critical information on diagnostic methods according to the patient's background and discuss the implementation of screening tools for congenital toxoplasmosis according to health policies.
SUMMARY 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 … SUMMARY 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-γ) 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-γ 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-γ, 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.
The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as ‘Fas tumor counterattack,’ has been recently questioned, … The hypothesis that FasL expression by tumor cells may impair the in vivo efficacy of antitumor immune responses, through a mechanism known as ‘Fas tumor counterattack,’ has been recently questioned, becoming the object of an intense debate based on conflicting results. Here we definitely show that FasL is indeed detectable in the cytoplasm of melanoma cells and its expression is confined to multivesicular bodies that contain melanosomes. In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens. Isolated melanosomes express FasL, as detected by Western blot and cytofluorimetry, and they can exert Fas-mediated apoptosis in Jurkat cells. We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells. Hence our data provide evidence for a novel mechanism potentially operating in Fas tumor counterattack through the secretion of subcellular particles expressing functional FasL. Such vesicles may form a sort of front line hindering lymphocytes and other immunocompetent cells from entering neoplastic lesions and exert their antitumor activity.
SUMMARY Infections by the protozoan parasite Toxoplasma gondii are widely prevalent worldwide in animals and humans. This paper reviews the life cycle; the structure of tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites … SUMMARY Infections by the protozoan parasite Toxoplasma gondii are widely prevalent worldwide in animals and humans. This paper reviews the life cycle; the structure of tachyzoites, bradyzoites, oocysts, sporocysts, sporozoites and enteroepithelial stages of T. gondii; and the mode of penetration of T. gondii. The review provides a detailed account of the biology of tissue cysts and bradyzoites including in vivo and in vitro development, methods of separation from host tissue, tissue cyst rupture, and relapse. The mechanism of in vivo and in vitro stage conversion from sporozoites to tachyzoites to bradyzoites and from bradyzoites to tachyzoites to bradyzoites is also discussed.
A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell … A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being
The population genetic structure of Toxoplasma gondii was determined by multilocus restriction fragment length polymorphism analysis at 6 loci in 106 independent isolates from humans and animals. Phylogenetic and statistical … The population genetic structure of Toxoplasma gondii was determined by multilocus restriction fragment length polymorphism analysis at 6 loci in 106 independent isolates from humans and animals. Phylogenetic and statistical analyses indicated a highly unusual population structure consisting of 3 widespread clonal lineages. Extensively mixed genotypes were only apparent in 4 strains, which indicated that, while not separate species, sexual recombination between the 3 lineages is exceedingly rare in natural populations. T. gondii is a major cause of subclinical human infection and an important opportunistic pathogen that causes severe disease in immunocompromised patients. While strains from all 3 lineages were isolated from humans, the majority of human toxoplasmosis cases were associated with strains of a type II genotype. The correlation of specific clonal lineages with human toxoplasmosis has important implications for development of vaccines, drug treatments, and diagnostic protocols.
We tested the hypothesis that the parasite Toxoplasma gondii manipulates the behaviour of its intermediate rat host in order to increase its chance of being predated by cats, its feline … We tested the hypothesis that the parasite Toxoplasma gondii manipulates the behaviour of its intermediate rat host in order to increase its chance of being predated by cats, its feline definitive host, thereby ensuring the completion of its life cycle. Here we report that, although rats have evolved anti-predator avoidance of areas with signs of cat presence, T. gondii's manipulation appears to alter the rat's perception of cat predation risk, in some cases turning their innate aversion into an imprudent attraction. The selectivity of such behavioural changes suggests that this ubiquitous parasite subtly alters the brain of its intermediate host to enhance predation rate whilst leaving other behavioural categories and general health intact. This is in contrast to the gross impediments frequently characteristic of many other host parasite systems. We discuss our results in terms of their potential implications both for the epidemiology of toxoplasmosis and the neurological basis of anxiety and cognitive processes in humans and other mammals.
OBJETIVOS: Analisar o perfil epidemiológico da toxoplasmose gestacional no Estado do Alagoas, entre os anos de 2019 a 2024. MATERIAIS E MÉTODOS: Trata-se de um estudo epidemiológico, retrospectivo, descritivo e … OBJETIVOS: Analisar o perfil epidemiológico da toxoplasmose gestacional no Estado do Alagoas, entre os anos de 2019 a 2024. MATERIAIS E MÉTODOS: Trata-se de um estudo epidemiológico, retrospectivo, descritivo e quantitativo, baseado na análise de dados secundários. As informações foram provenientes do banco de dados do Sistema de Informação de Agravos de Notificação, as variáveis utilizadas incluem: ano de notificação, faixa etária, escolaridade, raça, trimestre de gestação, classificação final e critério de confirmação. RESULTADOS: A prevalência da Toxoplasmose Gestacional é maior nas gestantes de 20 a 30 anos (71,56%), pardas (69,04%), no 2° trimestre de gestação (47,13%). As mulheres analfabetas foram menos suscetíveis a infecção, mostrando discordância com a literatura. O critério laboratorial constitui o principal método de confirmação diagnóstica. CONCLUSÃO: A Toxoplasmose Gestacional em Alagoas sofreu um aumento progressivo nos últimos anos. Levando a necessidade de estratégias que combinem diagnóstico precoce, tratamento adequado e ações preventivas, a fim reduzir a incidência e as consequências da infecção durante a gestação.
The relevance of the problem of congenital toxoplasmosis is due to the prevalence of toxoplasmosis in the world, the severity of congenital toxoplasmosis and the possible development of residual changes … The relevance of the problem of congenital toxoplasmosis is due to the prevalence of toxoplasmosis in the world, the severity of congenital toxoplasmosis and the possible development of residual changes in the central nervous system, sensory organs and other internal organs. The aim of the work is to summarize the data available in the literature on the etiology, epidemiology, clinical picture, diagnostics, treatment and prevention of congenital toxoplasmosis. Materials and methods . A review of domestic and foreign literature over the past 25 years was conducted, including Internet resources, including search engines PubMed, Cochrane Library, Google Scholar. Conclusion. To prevent congenital toxoplasmosis, it is possible to screen both those planning pregnancy and pregnant women. In case of confirmed infection of pregnant women, the attending physician may consider drug prophylaxis, which in the Russian Federation can be carried out using the macrolide drug spiramycin. One of the areas of prevention is the development of vaccines, among which vaccines based on nanoparticles seem to be especially promising.
Toxoplasma gondii ( T. gondii ), an apicomplexan parasite, infects a wide range of warm-blooded animals and poses significant risks to human health. The fatty acid synthesis II (FASII) pathway … Toxoplasma gondii ( T. gondii ), an apicomplexan parasite, infects a wide range of warm-blooded animals and poses significant risks to human health. The fatty acid synthesis II (FASII) pathway in the apicoplast, which is the major source of fatty acids in parasites, is considered a potential drug target. The apicoplast also harbors some enzymes of central carbon metabolism, which are crucial for its survival, but their biological roles remain unclear. In this study, we focused on apicoplast-localized isocitrate dehydrogenase 1 (ICDH1) and deleted it using CRISPR-Cas9 technology. The Δicdh1 mutant tachyzoites displayed markedly impaired growth kinetics, with further suppression under serum-deprived conditions. However, this deletion did not affect the viability or virulence of the Δicdh1 mutant in mice. NADPH, a product of ICDH1-mediated decarboxylation of isocitrate, is an essential cofactor for fatty acid synthesis. Using ¹³C 6 glucose as a metabolic carbon source, we showed that the mutant strains had reduced incorporation of glucose-derived carbons into medium-chain length fatty acids (C14:0 and C16:0). Additionally, the growth of the mutant was partially restored by supplementation with exogenous C14:0 and C16:0 fatty acids. These results indicate that ICDH1 deletion affects the FASII pathway and parasite growth. Consistent with previous studies, this study confirms that T. gondii has metabolic flexibility in the apicoplast that allows it to acquire fatty acids through various pathways.
Toxoplasma gondii, an intracellular parasitic protozoan, which infects almost all warm-blooded animals, including humans, causes toxoplasmosis. However, we lack effective drugs and vaccines to control toxoplasmosis, representing a clinical challenge. … Toxoplasma gondii, an intracellular parasitic protozoan, which infects almost all warm-blooded animals, including humans, causes toxoplasmosis. However, we lack effective drugs and vaccines to control toxoplasmosis, representing a clinical challenge. Therefore, safe and effective vaccines are urgently needed. In this study, a self-replicating mRNA vaccine comprising four T. gondii antigens: ROP18, TGME49_237490, TGME49_268230, and MIC13, named 4x-mRNA-LNP (lipid nanoparticle), was developed, and its protective efficacy was evaluated in mice. The expression of this vaccine in eukaryotic Human embryonic kidney 293 T (HEK-293 T) cells and mouse myoblast (C2C12) cells were analyzed, followed by enzyme-linked immunosorbent assay (ELISA) evaluation of the elicited humoral immune response. Subsequently, the vaccine-triggered immune responses in mice were detected, including antibody titers, T lymphocyte subsets, and cytokine levels. Finally, its immunoprotective effects were evaluated after challenging mice with T. gondii PRU oocysts or tachyzoites of different strains and analyzing the pathological changes, parasite loads, and mouse survival time. Western blotting and ELISA confirmed the successful eukaryotic expression and immunogenicity of 4x-mRNA, respectively. Statistical analyses, including the log-rank (Mantel-Cox) test, Student's t-test, and one-way ANOVA, were performed using GraphPad Prism software. Mice vaccinated with 4x-mRNA-LNP generated higher levels of IgG1 and IgG2a antibodies (P < 0.05) and cytokines (IL-2, IL-4, IL-10, IL-12, IFN-γ) (P < 0.05) compared with the control group. The high specific IgG titer was maintained for at least 10 weeks after the last vaccination. The proportion of CD3+CD4+ T cells and CD3+CD8+ T cells also increased significantly (P < 0.05), along with increased spleen cell proliferation in 4x-mRNA-LNP-vaccinated mice. Notably, limited pathological changes and < 10 fg of parasites/mg were found in the immunized mice tissues post-pathogen challenge. During observation for 30 days, 4x-mRNA-LNP-immunized mice survived significantly longer under challenge with lethal doses of RH, ME49, or WH6 tachyzoites (survival rates = 60%, 80%, and 60%, respectively). Following PRU oocyst challenge, vaccinated mice had notably decreased cyst burdens (72.5%, P < 0.05) compared with control mice. The 4x-mRNA-LNP vaccine triggered effective long-term antibody levels in mice, thus representing a promising candidate to further develop anti-toxoplasmosis vaccines.
Introduction Toxoplasma gondii ( T. gondii ), as a strict intracellular parasite, can infect nearly all mammals, including humans, posing significant threats to public health. Toxoplasmosis in animals also leads … Introduction Toxoplasma gondii ( T. gondii ), as a strict intracellular parasite, can infect nearly all mammals, including humans, posing significant threats to public health. Toxoplasmosis in animals also leads to substantial economic losses in animal husbandry. Currently, no effective treatments are available for toxoplasmosis, creating an urgent need for safe and efficient therapeutics. Methods In this study, we constructed a subunit vaccine using T. gondii glidesome-associated protein 45 (TgGAP45). To enhance immunogenicity, poly (lactic-co-glycolic acid) (PLGA) nanoparticles were employed as delivery carriers to prepare TgGAP45-PLGA nanospheres. For comparison, two oil adjuvants, Montanide™ ISA 660 VG and Montanide™ ISA 206 VG, were used to formulate TgGAP45-206VG and TgGAP45-660VG emulsions. Following safety evaluation, protective immunity was assessed in animals. Antibody levels, cytokine profiles, dendritic cell (DC) maturation and differentiation, and T lymphocyte proliferation and differentiation were analyzed. Results The results demonstrated that TgGAP45-PLGA nanospheres induced a mixed Th1/Th2 immune response against T. gondii . Furthermore, parasite burden analysis in spleen and heart tissues revealed that TgGAP45-PLGA nanospheres provided the strongest immunoprotection among the tested vaccines. Discussion These findings indicate that TgGAP45 delivered via PLGA nanospheres is a promising candidate for preventing acute toxoplasmosis. Further studies and applications are warranted to explore its full therapeutic potential.
Abstract Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii , is one of the most prevalent zoonotic parasitic infections worldwide. When acquired during pregnancy, T. gondii can be transmitted … Abstract Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii , is one of the most prevalent zoonotic parasitic infections worldwide. When acquired during pregnancy, T. gondii can be transmitted to the fetus, with clinical outcomes influenced by gestational age at time of infection and the parasite’s genotype. Prenatal screening enables the detection of maternal seroconversion and offers a critical window for intervention. In Uruguay, despite mandatory serological screening during pregnancy, national data on T. gondii seroprevalence and maternal seroconversion have not been updated in two decades. In addition, the genetic diversity of local strains remains poorly characterized. In this study, we analysed publicly available serological data from pregnant individuals attending Uruguay’s largest public maternity hospital between 2019 and 2023. We found that seroprevalence has modestly declined from 50% (reported in 1998) to 45.5%, with a congenital transmission rate of 0.58%. Clinical analysis of affected newborns revealed chorioretinitis as the predominant manifestation. To investigate parasite diversity, we performed genotyping of T. gondii strains using in silico PCR-RFLP following molecular detection. Our findings revealed substantial genetic diversity, including novel allele combinations not previously described in the region. These results highlight both the continued public health burden and the evolving genetic landscape of T. gondii in Uruguay. Our findings underscore the need to strengthen surveillance and prevention strategies for congenital toxoplasmosis in South America.
Detection of tachyzoites of Toxoplasma gondii in cerebrospinal fluid led to the diagnosis of central nervous system (CNS) toxoplasmosis in a 20 years old male. The cerebrospinal fluid (CSF) was … Detection of tachyzoites of Toxoplasma gondii in cerebrospinal fluid led to the diagnosis of central nervous system (CNS) toxoplasmosis in a 20 years old male. The cerebrospinal fluid (CSF) was obtained by lumbar puncture and two cytology smears were prepared by cytocentrifugation, one of which was stained with the May-Grünwald Giemsa (MGG) stain and the other with Papanicolaou stain. Light microscopic examination revealed pleocytosis along with numerous intracellular phagocytosed as well as extracellular tachyzoites with cytomorphology characteristic of Toxoplasma gondii. The diagnosis was confirmed by the serological elevation of anti-Toxoplasma IgM levels.
ABSTRACT Introduction: Toxoplasmosis is caused by the parasite Toxoplasma gondii, affecting especially children and immunocompromised individuals. Globally widespread, this infection is prevalent in tropical climates, affecting up to 80% of … ABSTRACT Introduction: Toxoplasmosis is caused by the parasite Toxoplasma gondii, affecting especially children and immunocompromised individuals. Globally widespread, this infection is prevalent in tropical climates, affecting up to 80% of the population in South America, including Brazil. Objective: To analyze current literature related to the impacts caused in patients affected by toxoplasmosis with ocular sequelae, in order to contribute to the advancement of the theoretical scope of the area. Materials and Methods: The present study will consist of a systematic literature review on the impacts of toxoplasmosis in patients and its ocular involvement. The research will be based on the methodological guide by Souza, Silva, and Carvalho (2010), which outlines six phases for conducting an integrative review: formulation of the guiding question, literature search, data collection, critical analysis of studies, discussion of results, and presentation of the review. The study will include experimental and non-experimental studies, such as clinical trials, qualitative studies, and theoretical reviews, to provide a holistic understanding of the impacts of toxoplasmosis, with an emphasis on ocular involvement.. Expected Results: The work aims to review the literature on the impacts of toxoplasmosis with ocular sequelae in patients, addressing clinical manifestations such as chorioretinitis and vision loss, as well as psychological and social impacts. It is expected to identify gaps in research, propose improvements in diagnosis and treatment, and develop evidence-based guidelines. Recommendations include new areas of study, collaboration between research centers, and evaluation of new therapies. Public education and awareness are also goals, with the creation of educational materials and campaigns. The study seeks to integrate knowledge from various fields for a holistic understanding of the impacts and advances in the management of ocular toxoplasmosis. Keywords: Toxoplasmosis; Toxoplasma gondii; Parasitic infection; Immune system.
Neosporosis is a major cause of bovine abortion worldwide, leading to substantial economic losses. In western Türkiye, an area characterized by intensive cattle breeding, data on this disease remain limited, … Neosporosis is a major cause of bovine abortion worldwide, leading to substantial economic losses. In western Türkiye, an area characterized by intensive cattle breeding, data on this disease remain limited, and no prior studies have investigated its risk factors. This study aimed to determine the prevalence, associated risk factors, and phylogenetic profile of Neospora caninum in the region. Visceral tissues from 88 aborted cattle fetuses were analyzed through genomic DNA isolation, real-time PCR (qPCR), and sequencing. In parallel, the presence of N. caninum antibodies was assessed in 973 serum samples using ELISA. N. caninum DNA was detected in 8 (9.09%) fetal samples by qPCR, with three of these further confirmed via conventional PCR and sequencing. Sequence analysis validated the presence of N. caninum in these three samples. Serologically, 122 of 973 serum samples (12.53%) tested positive for N. caninum antibodies. Statistical analysis of potential risk factors-including province, gender, age group, origin, and farm type-identified farm type as the most significant determinant of seropositivity. Notably, family-operated farms exhibited a higher prevalence of positive cases. This study represents the first large-scale investigation of N. caninum-associated reproductive losses in western Türkiye. The findings offer valuable insights for the development of targeted control and prevention strategies in affected cattle populations.
Introduction The apicomplexan parasite Toxoplasma gondii establishes chronic infection in the central nervous system, including the retina, causing ocular toxoplasmosis (OT). This persistence relies on a fine balance between inflammatory … Introduction The apicomplexan parasite Toxoplasma gondii establishes chronic infection in the central nervous system, including the retina, causing ocular toxoplasmosis (OT). This persistence relies on a fine balance between inflammatory and immunomodulatory mechanisms, especially in the immune-privileged ocular environment. We previously described the immunologic interactions between retinal cells, and particularly the roles of type I and III interferons. In this study, we investigated the regulatory dynamics of PD-L1, a central immunomodulatory receptor on immune cells. Methods We first investigated the mechanisms of PD-L1 regulation and the roles of type I and III interferons in an in vitro T. gondii infection model using mono- and co-culture systems of human microglia, astrocytes, and Müller cells. We also assessed PD-L1 expression in an outer blood-retina barrier model (oBRB) of differentiated retinal pigmented epithelial (RPE) cells. Additionally, we looked at retinal cell activation, PD-L1 expression and the roles of these interferons in a mouse model of OT. Results Our findings reveal new roles for type I and III interferons in regulating glial cell activation and PD-L1 expression in RPE, Müller, astrocytes and microglial cells. Notably, Müller cells, the most abundant glial cells in the retina, showed the highest baseline PD-L1 expression at both the mRNA and protein levels, and responded robustly to interferon stimulation. This points to a more prominent immunoregulatory role for Müller cells in the retina than previously recognized. Furthermore, we identified a parasite protease-dependent mechanism that reduces PD-L1 expression in our in vitro oBRB model potentially contributing to immune evasion and inflammation during OT. Finally, in a murine model of OT, we demonstrated that PD-L1 expression reached its peak on day 7 post-infection and that interferon neutralization plays a crucial role in regulating both PD-L1 expression and glial activation. Discussion The parasite T. gondii orchestrates the IFN type I and III dependent retinal immune interaction and downregulates PD-L1 in the oBRB by a protease-dependent mechanism, potentially contributing to immune evasion and inflammation in retinal infection. Our results can pave the way to fully elucidate retinal immune networks and PD-L1 regulation mechanisms, offering potential targets for therapeutic interventions in OT and other retinal inflammatory diseases.
Sarcocystis spp. is a prevalent parasite found in livestock raising significant concerns for public health due to the potential risks associated with the consumption of undercooked or raw meat. Sarcocystis … Sarcocystis spp. is a prevalent parasite found in livestock raising significant concerns for public health due to the potential risks associated with the consumption of undercooked or raw meat. Sarcocystis species have been identified in various animals worldwide yet our study marks the first investigation of Sarcocystis infection in slaughtered sheep in and around Hyderabad, Telangana. The prevalence of ovine sarcocystosis was investigated by immuno fluorescent antibody technique standardized in our laboratory. Purified bradyzoites collected from microcysts of Sarcocystis spp. were used to prepare antigenic slides. The sera sample collected from a sheep prior to slaughter whose muscle sample were found positive for the bradyzoites of Sarcocystis spp. by Pepsin HCl acid muscle digestion was used as known positive serum. A blood sample from a newborn lamb was used as a negative reference serum in all the tests. The prepared antigen slides reacted well with positive serum emitting bright yellowish-green fluorescence whereas negative serum with reddish fluorescence or polar fluorescence or no fluorescence. The seroprevalence of ovine sarcocystosis, determined by the laboratory-standardized IFAT, was 58% (145 out of 250) of tested sheep sera. The prevalence varied with age, with a lower infection rate (47%) observed in the 1-2 years age group and an increasing rate (65.3%) in those older than two years. Significant difference (p&lt;0.05) in infection was noticed between sheep older than 2 years and 1-2 year. No significant difference (p&gt;0.05) in infection was noticed between male (56%) and female (59.3%) animals.
Toxoplasmosis is one of the most common and neglected parasitic diseases caused by the intracellular parasite Toxoplasma gondii. The parasitic invasion in humans is associated with certain problems, such as … Toxoplasmosis is one of the most common and neglected parasitic diseases caused by the intracellular parasite Toxoplasma gondii. The parasitic invasion in humans is associated with certain problems, such as the lack of effective immunoprophylaxis or a complex diagnostic algorithm, which require continuous improvement. Both problems can be overcome by the recent development of T. gondii proteomics, which has allowed the design of different recombinant antigens. In this study we evaluated the potential usefulness of nineteen recombinant chimeric T. gondii proteins for serodiagnosis. A chimeric antigen composed of the surface antigens SAG1-SAG2 was developed and used as the basis for the generation of 18 subsequent trivalent chimeric antigens containing different immunodominant fragments of the parasite proteins. The recombinant antigens were used in an indirect enzyme-linked immunosorbent assay (ELISA) test to evaluate their ability to detect specific IgG antibodies in human sera. A total of 338 human sera were analyzed to assess the sensitivity and specificity of the tests. Sixteen of the antigens tested demonstrated 100% sensitivity and specificity in the ELISA for the detection of specific IgG antibodies. These results provide an optimistic outlook for the potential replacement of the currently used native antigen mix with recombinant antigens in human T. gondii serodiagnostics.
A Neosporose é uma doença causada pelo parasita intracelular obrigatório Neospora caninum e está associada à queda dos principais parâmetros reprodutivos e produtivos na bubalinocultura. O objetivo do referido trabalho … A Neosporose é uma doença causada pelo parasita intracelular obrigatório Neospora caninum e está associada à queda dos principais parâmetros reprodutivos e produtivos na bubalinocultura. O objetivo do referido trabalho foi determinar a prevalência de Neospora caninum em bubalinos de corte e leite no estado Paraná. Para a realização do presente estudo, a colheita das amostras foi feita em 349 animais com idade entre 18 e 24 meses de vida, provenientes de 22 rebanhos, e distribuídos em 16 municípios paranaenses pertencentes a seis mesorregiões, a saber: Sudeste, Norte Central, Norte Pioneiro, Centro-Sul, Centro-Oriental e Curitiba. A análise sorológica para a verificação da presença de anticorpos IgG de N. caninum no soro dos bubalinos foi feita utilizando-se o teste Dot-ELISA. Constatou-se uma prevalência global de 60,46% (211/349) para o agente. O teste rápido Dot-ELISA em amostras de soro bubalino mostrou-se uma opção significativa para avaliação de rebanhos, uma vez que é uma alternativa rápida, economicamente viável e de alta sensibilidade, permitindo a adoção de estratégias mitigatórias para o controle e a erradicação do agente.
M. I. Al-Farwachi , Hadeel Asim Mohammad , Israa A. Al-Robaiee | ˜Al-œmağallaẗ al-ʻirāqiyyaẗ li-l-ʻulūm al-bayṭariyyaẗ/Iraqi journal of veterinary sciences
ABSTRACT Carlos J. Ramírez-Flores works in the field of parasitology, focusing on how Toxoplasma gondii crosses host barriers. In this mSphere of Influence article, he reflects on how three papers—by … ABSTRACT Carlos J. Ramírez-Flores works in the field of parasitology, focusing on how Toxoplasma gondii crosses host barriers. In this mSphere of Influence article, he reflects on how three papers—by Shim, Kim, and Gregg—built on Dubey’s foundational mouse work to reshape his view of the parasite’s earliest intestinal events and to inspire his use of gut-on-chip platforms.
Shreetama Bhattacharjee , Aditi Singh | Microbes and Infectious Diseases /Microbes and Infectious Diseases
The in vivo role of RPE cells in ocular toxoplasmosis is poorly understood. Toxoplasma gondii activates Epidermal growth factor receptor (EGFR) to avoid autophagic killing. We examined the in vivo … The in vivo role of RPE cells in ocular toxoplasmosis is poorly understood. Toxoplasma gondii activates Epidermal growth factor receptor (EGFR) to avoid autophagic killing. We examined the in vivo role of RPE using mice with dominant negative (DN) EGFR in RPE. We examined whether EGFR blockade in RPE increased resistance to ocular toxoplasmosis, induced autophagy-dependent killing of T. gondii, and modulated retinal invasion by T. gondii. We bred mice expressing tetracycline-repressible transactivator under the control of MART-1 (RPE promotor) with mice expressing the tetracycline operator upstream of DN EGFR. Mice were infected with T. gondii tissue cysts. Histopathology and T. gondii B1 gene expression (qPCR) were examined. Retinal invasion by T. gondii was examined after intravenous challenge with the parasite. RPE were infected with T. gondii tachyzoites followed by assessment of parasite load and expression of LC3 and LAMP-1 (immunofluorescence). Mice with DN EGFR in RPE exhibited lower parasite load and histopathology that became evident at 4 weeks post infection. No difference in parasite load was noted during hematogenous invasion of the retina by T. gondii. RPE with DN EGFR exhibited spontaneous recruitment of LC3 and LAMP-1 around intracellular parasites and toxoplasmacidal activity that was dependent on the autophagy protein ULK-1 and lysosomal enzymes. DN EGFR in the RPE increases resistance against ocular toxoplasmosis, an effect that would occur after retinal invasion by T. gondii. Protection is accompanied by autophagic killing of T. gondii in RPE. This report provides the first evidence that RPE can protect against ocular toxoplasmosis.