Invited Review
Echinococcus granulosus sensu lato genotypes infecting humans – review of current knowledge

https://doi.org/10.1016/j.ijpara.2013.08.008Get rights and content

Highlights

Abstract

Genetic variability in the species group Echinococcus granulosus sensu lato is well recognised as affecting intermediate host susceptibility and other biological features of the parasites. Molecular methods have allowed discrimination of different genotypes (G1–10 and the ‘lion strain’), some of which are now considered separate species. An accumulation of genotypic analyses undertaken on parasite isolates from human cases of cystic echinococcosis provides the basis upon which an assessment is made here of the relative contribution of the different genotypes to human disease. The allocation of samples to G-numbers becomes increasingly difficult, because much more variability than previously recognised exists in the genotypic clusters G1–3 (=E. granulosus sensu stricto) and G6–10 (Echinococcus canadensis). To accommodate the heterogeneous criteria used for genotyping in the literature, we restrict ourselves to differentiate between E. granulosus sensu stricto (G1–3), Echinococcus equinus (G4), Echinococcus ortleppi (G5) and E. canadensis (G6–7, G8, G10). The genotype G1 is responsible for the great majority of human cystic echinococcosis worldwide (88.44%), has the most cosmopolitan distribution and is often associated with transmission via sheep as intermediate hosts. The closely related genotypes G6 and G7 cause a significant number of human infections (11.07%). The genotype G6 was found to be responsible for 7.34% of infections worldwide. This strain is known from Africa and Asia, where it is transmitted mainly by camels (and goats), and South America, where it appears to be mainly transmitted by goats. The G7 genotype has been responsible for 3.73% of human cases of cystic echinococcosis in eastern European countries, where the parasite is transmitted by pigs. Some of the samples (11) could not be identified with a single specific genotype belonging to E. canadensis (G6/10). Rare cases of human cystic echinococcosis have been identified as having been caused by the G5, G8 and G10 genotypes. No cases of human infection with G4 have been described. Biological differences between the species and genotypes have potential to affect the transmission dynamics of the parasite, requiring modification of methods used in disease control initiatives. Recent investigations have revealed that the protective vaccine antigen (EG95), developed for the G1 genotype, is immunologically different in the G6 genotype. Further research will be required to determine whether the current EG95 vaccine would be effective against the G6 or G7 genotypes, or whether it will be necessary, and possible, to develop genotype-specific vaccines.

Introduction

Echinococcus granulosus sensu lato (s. l.) is the etiological agent causing cystic echinococcosis (CE) in animals and humans. This cestode parasite has a worldwide distribution, particularly affecting pastoral and poor rural communities where people raise livestock in close contact with dogs.

Variability of the agents of CE has been recognised for a long period of time and has been described as affecting such things as host specificity as well as morphological, biochemical and other biological differences. With the advent of modern DNA-based methods, this genetic variability was confirmed and a number of genotypes were recognised (G1–10). Further revisions have proposed a new taxonomy for the genus, retaining the name E. granulosus sensu stricto (s. s.) for G1–3, giving species status to G4 (Echinococcus equinus), G5 (Echinococcus ortleppi), the genotypic cluster G6–10 (Echinococcus canadensis) and the ‘lion strain’ (Echinococcus felidis). This genetic characterisation has been remarkably important in understanding the transmission pattern of the parasite between definitive and intermediate hosts, and humans. While it is well known that the G1 genotype is responsible for most of the cases of human CE, other genotypes are also known to be infective to humans. This review provides an assessment of the evidence for infection of humans with the different species and genotypes, and provides a quantitative assessment of their relative contribution to CE in humans according to data published to date.

Section snippets

Molecular identification and distribution of genotypes

A variety of different molecular methods have been used to study genetic variability of Echinococcus spp. Investigations using nuclear DNA have involved regions encoding rRNA, such as the internal transcribed spacer 1 (ITS1) (Bowles and McManus, 1993b), Antigen B/1 (AgB/1), BG1 DNA probe, Actin III (ActIII), MS microsatellite U1 snRNA region (MS) (Bart et al., 2004), elongation factor 1 alpha (ef1a) (Moro et al., 2009), Eg9 and Eg16 PCR (Gonzalez et al., 2002) as well as Random Amplification of

Genotypes and human infection

Descriptions of human CE cases where the parasite genotype has been characterised are summarised in Table 1. No case has been reported of an infection in an individual patient with parasites belonging to more than one genotype.

Contribution of different species and genotypes to the global burden of cystic echinococcosis and relative infectivity for humans

It is not possible to be precise about differences in infectivity of the different genotypes of E. granulosus s. l. for humans. The observed prevalence of particular genotypes is likely to be influenced by, among other things, the relative abundance of different genotypes in animal intermediate hosts, the potential for humans to have contact with infected definitive hosts, differences in social behaviour concerning the slaughter of different livestock host species influencing exposure to dogs

Differences in CE pathology between species and genotypes

Relatively little information is available concerning possible differences in the clinical sequelae of human CE caused by different agents. Analyses of CE cases from Canada (Meltzer et al., 1956) and Alaska (Wilson et al., 1968), which were considered to be due to sylvatically-transmitted strain(s), were interpreted as suggesting that the pathological consequences were less severe than were CE infections involving other genetic strains of E. granulosus s. l. For this reason, it was recommended

Implications of genotype variation on CE control measures

Genetic variation in factors affecting biological attributes of E. granulosus s. l., such as its rate of attaining fertility in both the definitive and intermediate hosts, could affect the biological potential of the different genotypes and aspects of the management of a CE control programs. Echinococcus canadensis G6 and G7, now known to cause significant numbers of infections in humans, have been described as exhibiting precocious development in dogs (Eckert et al., 1989, Eckert et al., 1993)

Acknowledgements

Financial support is acknowledged from National Health and Medical Research Council, Australia, Grants GNT1003546 and GNT1043327.

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