Toxoplasma gondii presentations at the 10th International Workshops on Opportunistic Protists: 100 years and counting.

Toxoplasma gondii, an apicomplexan parasite of mammals, was first identified over 100 years ago (in 1908) by Nicolle and Manceaux, who isolated tachyzoites from the gundi, a North African rodent (34). Splendore also identified this parasite in the tissue of a rabbit in 1908 (46). The genus Toxoplasma was named for its bow-like shape (from the Greek “toxo,” for bow or arc, and “plasma,” for creature). The presence of a tissue cyst (bradyzoite) life stage was rapidly recognized, but it was not until almost 60 years later that this organism was recognized to be a coccidian and that felines were identified as being the definitive hosts by several groups working independently, including Dubey and Frenkel in 1970 (16). The association of T. gondii with food-borne and waterborne transmission has resulted in its classification as a National Institute of Allergy and Infectious Diseases (NIAID) category B priority agent. Due to the extensive repertoire of applicable experimental techniques available for this pathogen, it has become a model organism for the study of intracellular pathogens. Research on T. gondii continues to move rapidly, and this review will address information related to recent advances in our understanding of the biology of T. gondii presented at the IWOP-10 held in Boston, MA, 28 to 31 May 2008, and the symposium entitled “Centenary Celebration of Toxoplasma Discovery” held at that meeting. History, epidemiology, and life cycle. The details of the history of the discovery of T. gondii were reviewed at IWOP-10 by Dubey (15) and were also described in recent reviews (1, 14). T. gondii is estimated to infect about one-third of the world’s human population and is a significant zoonotic and veterinary pathogen. In humans and veterinary hosts, T. gondii is frequently associated with congenital infection and abortion. This parasite can be transmitted by the vertical transmission of the rapidly growing tachyzoite form if an immunologically naïve mother acquires a new infection during pregnancy. In addition, T. gondii is an opportunistic pathogen associated with encephalitis or systemic infections in immunocompromised hosts such as individuals with advanced human immunodeficiency virus infection (i.e., AIDS). Tachyzoites divide rapidly within host cells and are thought to be responsible for the clinical manifestations of infection. In humans, T. gondii is most commonly acquired by the oral ingestion of tissue cysts containing bradyzoites in meat. In Portugal, the location of the 2006 IWOP meeting, it was reported that 9.1% of pigs were found to be seropositive for T. gondii, which suggests that they are a significant source of infected meat products (37). Improved animal husbandry practices and increased awareness of the risk of eating undercooked meat have resulted in a decreased prevalence of toxoplasmosis (50). T. gondii infection can also be acquired by the ingestion of oocysts containing sporozoites that are the product of the sexual cycle in cat intestines. In Lisbon, Portugal, a recent survey demonstrated that 26.2% of cats were seropositive, which is a decrease from previous surveys in 1984 and 1992 (13). Once tissue cysts or the environmental oocysts are ingested, their contents, the bradyzoites and sporozoites, respectively, invade host cells and differentiate into tachyzoites. Oocysts are very resistant to harsh environmental conditions and are highly infectious. As illustrated by studies in Canada (7) and South America (3, 5), oocysts transmitted via water or other environmental sources are a significant source of T. gondii infection. A method has been developed to extract highquality RNA from T. gondii oocysts that can be used to study the biology of this least-well-understood life stage using microarray or similar studies (42). T. gondii is unusual in that its propagation does not require passage through the definitive host (felids in whose intestinal tissues the sexual cycle occurs). It is an obligate intracellular parasite and cannot be propagated axenically. Tachyzoites differentiate into latent bradyzoite forms, which are surrounded by a carbohydrate-rich cyst wall within the parasitophorous vacuole. These forms were first recognized in 1928 by Levaditi, and the term tissue cyst was defined by Dubey and Beattie in 1988 (14, 15, 50). This differentiation can be increased by the exposure of the organism to stress conditions in culture and the developing immune response to the tachyzoites in vivo. These tissue cysts can persist indefinitely for the life of the host, perhaps due to a cycle of reactivation and reinfection. Analysis using enzyme zymodemes and single-nucleotide polymorphisms suggests that most T. gondii isolates from North America and Europe can be grouped into one of three genotypes, e.g., types I, II, and III (22, 44). Most likely, these lineages are related to the domestication of animals by humans about 10,000 years ago (48). Type I strains grow rapidly in vitro, are hypervirulent in mice, and are frequently associated with ocular toxoplasmosis and acute outbreaks (19). Type II and type III isolates are less virulent in mice and readily form cysts in vitro, and type II strains are commonly isolated from clinical cases of toxoplasmosis, particularly in immunodeficient hosts. Data indicate that other genotypes are predominant in other parts of the world (29), which may represent zoonotic * Corresponding author. Mailing address: Department of Pathology, Division of Parasitology and Tropical Medicine, Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Room 504, Forchheimer Building, Bronx, NY 10461. Phone: (718) 430-2142. Fax: (718) 430-8543. E-mail: [email protected]. Published ahead of print on 23 January 2009.