The molecular biology and immune control of chronic Toxoplasma gondii infection.

Toxoplasma gondii is an incredibly successful parasite owing in part to its ability to persist within cells for the life of the host. Remarkably, at least 350 host species of T. gondii have been described to date, and it is estimated that 30% of the global human population is chronically infected. The importance of T. gondii in human health was made clear with the first reports of congenital toxoplasmosis in the 1940s. However, the AIDS crisis in the 1980s revealed the prevalence of chronic infection, as patients presented with reactivated chronic toxoplasmosis, underscoring the importance of an intact immune system for parasite control. In the last 40 years, there has been tremendous progress toward understanding the biology of T. gondii infection using rodent models, human cell experimental systems, and clinical data. However, there are still major holes in our understanding of T. gondii biology, including the genes controlling parasite development, the mechanisms of cell-intrinsic immunity to T. gondii in the brain and muscle, and the long-term effects of infection on host homeostasis. The need to better understand the biology of chronic infection is underscored by the recent rise in ocular disease associated with emerging haplotypes of T. gondii and our lack of effective treatments to sterilize chronic infection. This Review discusses the cell types and molecular mediators, both host and parasite, that facilitate persistent T. gondii infection. We highlight the consequences of chronic infection for tissue-specific pathology and identify open questions in this area of host-Toxoplasma interactions.

Protistology Conferences: The Beginnings. The First International Protozoology Conference (Prague 1961) and the Tribute to Otto Jírovec, its Spiritual Father.

Two events have helped to shape protozoology/protistology as a specific scientific discipline. The first such event was the creation of the Society of Protozoologists in the U.S. in 1947 (and of its Journal of Protozoology, first published in 1954), the second event was the First International Conference on Protozoology, held in 1961 in Prague. The history of the Society of Protozoologists was comprehensively treated by Corliss (1998); the history of the Prague Conference is presented here as reminiscences and personal interpretation of events of the author, who was one of the conference organizers and a member of the organization committee. Special attention is given to the personality and scientific accomplishments of Otto Jírovec, the 1961 conference spiritual father and president. It is concluded that the Prague Conference, while establishing the tradition of protistology meetings, helped protistology to attain its present status as a fundamental science discipline, which discovers and interprets the web of life at one of its, basic, "microbial" levels. Protists literally permeate the earth biosphere and in a way represent the "dark matter" of the living world, still awaiting many discoveries.

Recovery of Toxoplasma gondii DNA in experimentally mummified skin and bones: Prospects for paleoparasitological studies to unveil the origin of toxoplasmosis.

Paleoparasitology studies parasite infections by finding the parasites' remains in preserved organic remains such as natural or artificial mummy tissues, skeletons, teeth, and coprolites, among others. However, some currently important infections like toxoplasmosis have not been studied by paleoparasitology. The reasons include this parasite's complex life cycle, the resulting difficulties in locating this protozoan in the intermediate host tissues, and the limitation of coprolite studies to felines, the protozoan's definitive host. The current study thus aimed to produce an experimental model for molecular diagnosis of toxoplasmosis, prioritizing its study in bones and skin, the most abundant materials in archeological collections and sites. The study demonstrated the feasibility of recovering Toxoplasma gondii DNA from desiccated material, including bones and skin, in experimental models both with circulating tachyzoites (RH strain), characteristic of acute infection, and with cysts (ME49 cystogenic strain), characteristic of chronic infection. At present, most individuals with T. gondii infection are in the chronic phase, and the same was probably true in the past. The current study thus expands the odds of finding the parasite in archeological material, enhanced by the nature of the material in which the diagnosis was made. Finding the parasite may help answer questions that are widely debated in the literature on this protozoan's origin (Old World versus New World). In addition, when conditions do not allow ideal storage of samples for molecular tests, the methodology creates the possibility of testing oven-dried samples transported at room temperature.

An overview of seventy years of research (1944-2014) on toxoplasmosis in Colombia, South America.

This paper summarizes prevalence of Toxoplasma gondii in humans and animals and associated correlates of infection, clinical spectrum of disease in humans, and genetic diversity of T. gondii isolates from Colombia. Recent studies, especially in the states of Antioquia, Quindío and Cundinamarca, indicate that toxoplasmosis is a major public health problem. Approximately half of the women of child bearing age have T. gondii antibodies, and the clinical disease in congenitally infected children is more severe than in Europe. Limited studies indicate that the strains of T. gondii from Colombia are genetically and phenotypically different than in Europe and North America. However, epidemiological factors, such as the involvement of domestic and/or wild animals in transmission, the distribution of strain diversity by natural geographic regions, and the variation in risk factors between regions that are associated with human infection in Colombia, remain unknown. Areas of research for the future are outlined. This review should be of interest to biologists, veterinarians, physicians, and parasitologists.

Alfonso Splendore: facetas da vida do descobridor do toxoplasma / Alfonso Splendore: facets of life of the toxoplasma discoverer

O autor aborda aspectos da vida profissional e familiar de seu avô.

The author presents aspects of the professional and familiar life of his grandfather.

A brief history and overview of Toxoplasma gondii.

Toxoplasma gondii was discovered by scientists working in North Africa and Brazil around 100 years ago. The parasite has since been found to be capable of infecting all warm-blooded animals including humans making it one of the most successful parasitic organisms worldwide. The pathogenic potential of T. gondii was recognized in the 1920s and 1930s, in congenitally infected children presenting with the classic triad of symptoms, namely hydrocephalus, retinochoroiditis and encephalitis. In addition, around the same time T. gondii parasites were found to be associated with severe intraocular inflammation. In the 1980s, T. gondii emerged as a major cause of death in patients with acquired immunodeficiency syndrome, illustrating the importance of the immune system in controlling T. gondii infection. T. gondii was reported as a major cause of abortion in sheep in New Zealand in the 1950s, which raised questions about potential new transmission routes for the parasite. The discovery of the cat as the definitive host in the 1960s was a very important finding as it helped to complete our understanding of the parasite's life cycle, and the oocyst stage of T. gondii shed in the faeces of infected cats was found to be an important source of infection for many intermediate hosts and helped to explain infection in herbivorous animals and people with a vegetarian diet. In addition, this stage of the parasite was very robust and could survive in the environment, depending on the climatic conditions, for up to 12-18 months. Knowledge of the parasite's life cycle, transmission routes, risk groups and host immune responses has helped in the development of strategies to control the disease, reduce transmission of the parasite and limit environmental contamination.

History of the discovery of the life cycle of Toxoplasma gondii.

It has been 100 years since the discovery of Toxoplasma gondii in 1908. Its full life cycle was not discovered until 1970 when it was found that it is a coccidian parasite of cats with all non-feline warm blooded animals (including humans) as intermediate hosts. The discovery of the environmentally resistant stage of the parasite, the oocyst, made it possible to explain its worldwide prevalence. In the present paper, events associated with the discovery of its life cycle are recalled.

A history of studies that examine the interactions of Toxoplasma with its host cell: Emphasis on in vitro models.

This review is a historical look at work carried out over the past 50 years examining interactions of Toxoplasma with the host cell and attempts to focus on some of the seminal experiments in the field. This early work formed the foundation for more recent studies aimed at identifying the host and parasite factors mediating key Toxoplasma-host cell interactions. We focus especially on those studies that were performed in vitro and provide discussions of the following general areas: (i) establishment of the parasitophorous vacuole, (ii) the requirement of specific host cell molecules for parasite replication, (iii) the scenarios under which the host cell can resist parasite replication and/or persistence, (iv) host species-specific and host strain-specific responses to Toxoplasma infection, and (v) Toxoplasma-induced immune modulation.

Identification of faecal transmission of Toxoplasma gondii: Small science, large characters.

The first clue to the elucidation of the complete life cycle of Toxoplasma gondii was the identification of an infectious form in cat faeces that could be transmitted orally and could survive in the external environment for extended periods. This personal review describes the scientist (W.M. Hutchison) and the background to the initial discovery and covers the period to the complete elucidation of the life cycle of T. gondii.

Toxoplasma gondii: 1908-2008, homage to Nicolle, Manceaux and Splendore.

The discovery of Toxoplasma gondii independently by Nicolle and Manceaux (1908) and Splendore (1908) was to open a 'Pandora's Box' that has led research on this parasite into a number of scientific disciplines. In the 100 years since its discovery, the mystery surrounding T. gondii and its inter-relationship with humans has continued to provide a stimulating source of material in many areas of research, resulting in the publication of almost 20,000 papers and a number of books. This flood of diverse information shows no sign of abating, with an average of 10 papers per week appearing in PubMed. Herein, it is impossible to do more than provide a very superficial comment on what has become a massive body of scientific information. T. gondii has many unique features and seems to be the 'exception to almost every rule' thus acting as a focus for research in disciplines from epidemiology to immunology to human behaviour to cell biology to human disease. In this review a number of the historical advances will be mentioned and combined with a description of the basic biology of the parasite.

Development of forward genetics in Toxoplasma gondii.

The development of forward genetics as a functional system in Toxoplasma gondii spanned more than three decades from the mid-1970s until now. The initial demonstration of experimental genetics relied on chemically induced drug-resistant mutants that were crossed by co-infecting cats, collecting oocysts, sporulating and hatching progeny in vitro. To capitalise on this, genetic markers were employed to develop linkage maps by tracking inheritance through experimental crosses. In all, three generations of genetic maps were developed to define the chromosomes, estimate recombination rates and provide a system for linkage analysis. Ultimately this genetic map would become the foundation for the assembly of the T. gondii genome, which was derived from whole genome shotgun sequencing, into a chromosome-centric view. Finally, application of forward genetics to multigenic biological traits showed the potential to map and identify specific genes that control complex phenotypes including virulence.

The early years of Toxoplasma research: What's past is prologue.

In the century since the first description of Toxoplasma gondii history and circumstance have led scientists to define this organism in diverse contexts. From its discovery by researchers shaped by early 20th century versions of the germ theory to its more recent roles as an important globally distributed pathogen and a model apicomplexan, our definitions of Toxoplasma are as much a reflection of our frame of reference as they are an absolute definition of this organism. Although these transformations act as portals for new avenues of investigation, the essential questions that inform current research are founded in the work of early investigators who studied Toxoplasma.

Toxoplasma gondii: 1908-2008, homage to Nicolle, Manceaux and Splendore

The discovery of Toxoplasma gondii independently by Nicolle and Manceaux (1908) and Splendore (1908) was to open a "Pandora's Box" that has led research on this parasite into a number of scientific disciplines. In the 100 years since its discovery, the mystery surrounding T. gondii and its inter-relationship with humans has continued to provide a stimulating source of material in many areas of research, resulting in the publication of almost 20,000 papers and a number of books. This flood of diverse information shows no sign of abating, with an average of 10 papers per week appearing in PubMed. Herein, it is impossible to do more than provide a very superficial comment on what has become a massive body of scientific information. T. gondii has many unique features and seems to be the "exception to almost every rule" thus acting as a focus for research in disciplines from epidemiology to immunology to human behaviour to cell biology to human disease. In this review a number of the historical advances will be mentioned and combined with a description of the basic biology of the parasite.

Toxoplasmosis: A history of clinical observations.

It has been 100 years since Toxoplasma gondii was initially described in Tunis by Nicolle and Manceaux (1908) in the tissues of the gundi (Ctenodoactylus gundi) and in Brazil by Splendore (1908) in the tissues of a rabbit. Toxoplasma gondii is a ubiquitous, Apicomplexan parasite of warm-blooded animals that can cause several clinical syndromes including encephalitis, chorioretinitis, congenital infection and neonatal mortality. Fifteen years after the description of T. gondii by Nicolle and Manceaux a fatal case of toxoplasmosis in a child was reported by Janku. In 1939 Wolf, Cowen and Paige were the first to conclusively identify T. gondii as a cause of human disease. This review examines the clinical manifestations of infection with T. gondii and the history of the discovery of these manifestations.

The history of Toxoplasma gondii--the first 100 years.

In this paper the history of Toxoplasma gondii and toxoplasmosis is reviewed. This protozoan parasite was first discovered in 1908 and named a year later. Its medical importance remained unknown until 1939 when T. gondii was identified in tissues of a congenitally infected infant, and veterinary importance became known when it was found to cause abortion storms in sheep in 1957. The discovery of a T. gondii specific antibody test, Sabin-Feldman dye test in 1948 led to the recognition that T. gondii is a common parasite of warm-blooded hosts with a worldwide distribution. Its life cycle was not discovered until 1970 when it was found that felids are its definitive host and an environmentally resistant stage (oocyst) is excreted in feces of infected cats. The recent discovery of its common infection in certain marine wildlife (sea otters) indicates contamination of our seas with T. gondii oocysts washed from land. Hygiene remains the best preventive measure because currently there is no vaccine to prevent toxoplasmosis in humans.

[Historical review about the research on toxoplasmosis]. / Reseña histórica acerca de las investigaciones relacionadas con la toxoplasmosis.

Toxoplasmposis is one of the zoonotic diseases which is widely spread all over the world. It is caused by Toxoplasma gondii. In this paper we made a chronological synthesis of some of the numerous investigations that have been made in the world and in Cuba.

Toxoplasmose na gestação e suas repercussões no feto / Toxoplasmosis in pregnancy and its effects on the fetus

O presente trabalho tem como prioridade considerar a toxoplasmose na gestante, uma vez que a infecção aguda na gravidez pode ocasionar graves repercussões no feto. Com o intuito de estudar o perfil sorológico das gestantes atendidas no Hospital Universitário Antonio Pedro (HUAP), foi realizada a análise de 1330 sorologias para toxoplasmose de gestantes atendidas no HUAP, durante o ano de 1996, pela técnica ELFA. Observou-se uma alta prevalência da infecção (80%), o que correlacionou-se com outros trabalhos nacionais e regionais. Das 1330 gestantes, 1033 (77,7%) apresentavam infecção crônica, 266 (20%) estavam desprovidas de imunidade e 31 (2,3%) eram suspeitas de apresentarem infecção aguda. Foi possível obter informações clínicas e laboratoriais de 14 gestantes que apresentavam IgM no soro e de seus respectivos filhos. Ao finalizar o trabalho foi possível concluir que o número de reações sorológicas positivas para toxoplasmose aumenta de acordo com a idade das gestantes; a toxoplasmose foi uma infecção de alta prevalência na população estudada (80%)...Foi sugerido que para maior precisão no diagnóstico da toxoplasmose, outras provas sorológicas devam ser realizadas com a avidez de IgG, a dosagem de IgA e IgE ou o teste de aglutinação diferencial. Os testes sorológicos clássicos como a hemaglutinação, a fixação de complemento e a imunofluorescência também são alternativas que auxiliam o diagnóstico da toxoplasmose quando realizados de forma complementar à investigação.