Review of Toxoplasma gondii genotypes and potential intermediate hosts of virulent strains

Abstract

Toxoplasma gondii is a protozoan parasite that causes the zoonotic disease toxoplasmosis. Cats are the definitive hosts, and all mammals and birds can act as intermediate hosts (1). Even without felines, T. gondii can be transmitted by predation between intermediate hosts. The genetic diversity of T. gondii contains three major clonal lineages (types I, II, and III) (2).

Full Text

Toxoplasma gondii is a protozoan parasite that causes the zoonotic disease toxoplasmosis. Felines are the definitive hosts, and all mammals and birds can be intermediate hosts (1). Even without felines, T. gondii can be transmitted by predation between intermediate hosts. Cats (F. catus) become infected with this parasite through ingestion of oocysts excreted in the feces of infected cats or through tissue cysts from latently infected intermediate hosts (2). However, less than half of cats excrete oocysts after ingesting oocysts. In contrast, most cats excrete oocysts after ingesting tissue cysts obtained from intermediate hosts (3). Thus, the intermediate host route of transmission of T. gondii is thought to be the more important source of infection for cats. Rodents are the primary prey of cats. Although cats can become infected through predation on infected intermediate hosts, including rodents, cats rarely become ill with toxoplasmosis but excrete large numbers of oocysts in their feces. This makes cats an effective source of infection for other animals, including livestock and humans. Rodents are therefore a risk to animal husbandry and public health.

The genetic diversity of T. gondii contains three major clonal lineages (types I, II, and III) (2). Most type I strains are highly virulent and lethal to most strains of laboratory mice, while most type II and III strains are not. In addition to typical type I strains, a number of strains have been reported that are believed to be chimeras of type I and other types. In such strains, some genomic loci have sequences belonging to type I, while other loci have sequences belonging to other types. Although the loci used for genotyping are not necessarily all directly involved in pathogenicity, such strains may have virulence factors similar to those of highly virulent type I strains. Many strains with many loci similar to type I are highly virulent in laboratory mice.

If type I or type I-like T. gondii kills all intermediate hosts in the field, as it does in laboratory mice, then such parasites will not be able to spread in the environment. It is therefore believed that some animals are asymptomatically infected with type I and type I-like parasites and transmit them. Recently, CIM, CAST/EiJ, and CTP (Mus musculus castaneus) mice collected in Thailand and India, respectively, were found to be asymptomatic and resistant after infection with T. gondii type I. Host resistance to infection is usually understood as a dichotomy between "susceptibility," in which pathogens replicate in the body and cause disease or death, and "resistance," in which infection does not occur. However, the situation in which infection is established but the pathogen persists in the body for an extended period without causing disease is distinct from either of these two categories and should be termed "tolerance." Animals in a tolerant state may act as reservoirs for type I parasites in cats and may be a source of infection for humans and livestock. However, it is unclear which animal species may be the primary intermediate hosts transmitting highly virulent T. gondii strains such as type I in the field. It is also unknown how often and in what areas intermediate hosts capable of asymptomatic latent infection with highly virulent strains are present. T. gondii type I strains are considered highly virulent based on their lethality in most strains in laboratory mice. Although the virulence of T. gondii type I in humans and livestock has not yet been clearly demonstrated, several studies suggest that type I strains are also more pathogenic in humans and livestock than type II and III. Khan et al. (2005) found predominantly type I strains but no non-type I strains in the cerebrospinal fluid of 11 patients with toxoplasmic encephalitis. In a study in the United States, serotyping among three major lineages showed that the type I strain was more common in patients with psychiatric disorders. Another study found no significant association between non-type I T. gondii serotypes and the risk of psychosis in adolescents, but children of mothers with type I T. gondii infection had a significantly increased risk of psychosis compared with control mothers. Howe and Sibley's (1995) study of 106 human isolates of diverse origin from North America and Europe found that type I isolates were significantly more often associated with cerebral toxoplasmosis (58). Another study found an association between severe Toxoplasma retinochoroiditis and T. gondii type I. In livestock, type I (GT1 strain) infection in pregnant sows resulted in transplacental infection, anorexia, and respiratory distress. It was also reported that young chickens (1 month old) infected with T. gondii type I (GT1 strain) oocysts developed clinical toxoplasmosis, whereas those infected with T. gondii type II (ME49) oocysts did not develop any clinical signs. These results from different studies suggest high virulence of T. gondii type I not only in mice but also in humans and livestock. Given the risk of T. gondii type I in humans and livestock, type I-tolerant wild rodents may pose a risk to public health and livestock as an asymptomatic reservoir of type I and/or type I-like parasites.

The first type I strain to be isolated was the BK strain, isolated in the Netherlands in 1948. However, there have been few reports of type I or type I-like parasites isolated in Europe over the past 20 years. In contrast, type I and type I-like T. gondii strains are common in Asia (Fig. 1).

Fig. 1 Overview of T. gondii genotypes isolated in Europe and Asia. Note: Type I, type I-like, and non-type I genotypes were distributed on a timeline over the past 20 years based on the reported year of sample collection. The website https://scholar.google.com/ was used to search for T. gondii strain isolates and information on strains with genotyping at 5 or more genomic loci was listed. Criteria for distinguishing genotypes were: Type I: all loci tested were type I genotype, Type I-like: half or more of the loci tested were type I genotype, non-type I: less than half of the reported loci were type I genotype or non-type I loci were present. The large right arrow with years labeled is the history timeline. It represents the genotype reported in Europe (grey) and Asia (blue). The timeline lines (red, green, blue) represent each of the reported type I (red), type I-like (green), and non-type I (blue) strains. Small black arrows indicate extended intervals of the timeline for years in which large numbers of T. gondii genotypes were published. The template for creating a map of Eurasia has been taken under educational use from yourfreetemplates.com.

Over the past 20 years, Asia, but not Europe, may have become a hotspot for highly virulent type I and type I-like T. gondii strains. Given the situation, tolerant rodents may also spread across Asian countries. So far, type I-tolerant M. musculus have only been reported from India and Thailand. However, such mice may be widespread in Asia, where type I and type I-like strains have been consistently reported, and they may serve as reservoirs for highly virulent strains.