Fasciola Species Introgression: Just a Fluke or Something More?

Abstract

Increased demand for animal-derived protein from Fasciola hepatica-endemic countries has led to a growing number of reports of hybridization between F. hepatica and Fasciola gigantica in Southeast Asia.Hybridization and eventual introgression have been reported in a range of protozoan, helminth, and arthropod parasites and act as important drivers of evolutionary change and adaptation.Introgression between Fasciola spp. remains unproven but has potentially serious human and animal health consequences as seen in other parasites.New tools for the characterization of hybridization and introgression events between Fasciola spp. are needed. The threats posed by a range of viral and bacterial zoonotic diseases inevitably receive renewed attention in the wake of global pandemic events due to their overt and devastating impacts on human health and the economy. Parasitic zoonoses, however, many of which affect millions of people each day, are frequently ignored. In the case of fasciolosis, caused by infection with Fasciola hepatica or Fasciola gigantica, this oversight has allowed for the expansion of areas of parasite sympatry and thus increased the incidence of hybridization and possible introgression between the two species. Here we highlight how an increased demand for animal-derived protein, combined with a lack of appropriate tools for detection of these events, is changing the status quo of these zoonotic parasites. The threats posed by a range of viral and bacterial zoonotic diseases inevitably receive renewed attention in the wake of global pandemic events due to their overt and devastating impacts on human health and the economy. Parasitic zoonoses, however, many of which affect millions of people each day, are frequently ignored. In the case of fasciolosis, caused by infection with Fasciola hepatica or Fasciola gigantica, this oversight has allowed for the expansion of areas of parasite sympatry and thus increased the incidence of hybridization and possible introgression between the two species. Here we highlight how an increased demand for animal-derived protein, combined with a lack of appropriate tools for detection of these events, is changing the status quo of these zoonotic parasites. As seen during the current coronavirus disease 2019 pandemic, zoonotic diseases are one of the greatest threats to human health. The high death rates associated with the more overt viral and bacterial diseases demand global attention and a rapid and coordinated response in order to limit human health consequences and impacts to the economy. Chronic and subclinical diseases, however, such as those caused by infection with parasites, are largely overlooked despite affecting millions of people each day. Parasitic diseases of livestock are of particular concern due to the additional threat they pose to animal productivity and food securityi. Despite these concerns, the propensity for these diseases to impact rural communities in developing countries means that they are often neglected by the wider scientific community (Figure 1, Key Figure). One example of a parasitic zoonosis that is largely overlooked in the developing world is fasciolosis, caused by infection with the digenean trematodes F. hepatica and F. gigantica (Box 1). The economic impacts of fasciolosis on livestock production outcomes are underestimated but are expected to exceed US$3 billion/year, with over 180 million people – primarily women and children – considered at risk of infection [1.Keiser J. Utzinger J. Emerging foodborne trematodiasis.Emerg. Infect. Dis. 2005; 11: 1507-1514Crossref PubMed Scopus (503) Google Scholar,2.Sabourin E. et al.Impact of human activities on fasciolosis transmission.Trends Parasitol. 2018; 34: 891-903Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar]. Livestock production impacts due to infection with either Fasciola species range from sudden death, in the case of acute infections, to chronic losses due to decreased milk yield and fertility, reduced body condition scores, liveweight gains, and wool growth [3.Hope Cawdery M.J. et al.Production effects of liver fluke in cattle. I. The effects of infection on liveweight gain, feed intake and food conversion efficiency in beef cattle.Br. Vet. J. 1977; 133: 145-159Crossref PubMed Google Scholar, 4.Howell A. et al.Epidemiology and impact of Fasciola hepatica exposure in high-yielding dairy herds.Prevent. Vet. 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Infection with F. hepatica has been shown to modulate the immune system of infected hosts by causing a shift towards a T helper 2 (Th2) cell response, leaving hosts more susceptible to infection with other bacterial pathogens such as Mycobacterium bovis and Bordetella pertussis [8.Brady M.T. et al.Fasciola hepatica suppresses a protective Th1 response against Bordetella pertussis.Infect. Immun. 1999; 67: 5372Crossref PubMed Google Scholar,9.Naranjo Lucena A. et al.The immunoregulatory effects of co-infection with Fasciola hepatica: From bovine tuberculosis to Johne's disease.Vet. J. 2017; 222: 9-16Crossref PubMed Scopus (18) Google Scholar]. This immunomodulation has also been shown to confound the outcomes of diagnostic tests for diseases, including bovine tuberculosis, due to the suppression of an effective Th1 response, increasing the rate of false-negative results [10.Claridge J. et al.Fasciola hepatica is associated with the failure to detect bovine tuberculosis in dairy cattle.Nat. Commun. 2012; 3: 853Crossref PubMed Scopus (112) Google Scholar].Box 1The Life Cycle of F. hepatica and F. giganticaF. hepatica and F. gigantica have an indirect life cycle, requiring both a mammalian definitive host and a freshwater snail intermediate host. The definitive hosts become infected by ingestion of metacercariae that are either encysted on vegetation or free-floating in water (Figure I). Metacercariae are the most resistant stage of the life cycle and can survive in the environment for over a year when adequate moisture is maintained. Once metacercariae are consumed, excystation occurs in the small an of ingestion and the the the From the towards the the liver The the liver for in the case of F. or for to for F. The reach and in the either for F. or for F. gigantica, which they are the the they the mammalian host the and when are from and to and in the of water to infection of the intermediate snail are but and an intermediate snail host act as intermediate most of which and and are of when these areas of the or which they to the of the snail as from which are This is and with to both and from in water they on and they become metacercariae and are This is on the of the life cycle as by The life of the J. and in Scholar]. F. hepatica and F. gigantica have an indirect life cycle, requiring both a mammalian definitive host and a freshwater snail intermediate host. The definitive hosts become infected by ingestion of metacercariae that are either encysted on vegetation or free-floating in water (Figure I). Metacercariae are the most resistant stage of the life cycle and can survive in the environment for over a year when adequate moisture is maintained. Once metacercariae are consumed, excystation occurs in the small an of ingestion and the the the From the towards the the liver The the liver for in the case of F. or for to for F. The reach and in the either for F. or for F. gigantica, which they are the the they the mammalian host the and when are from and to and in the of water to infection of the intermediate snail are but and an intermediate snail host act as intermediate most of which and and are of when these areas of the or which they to the of the snail as from which are This is and with to both and from in water they on and they become metacercariae and are This is on the of the life cycle as by The life of the J. and in Scholar]. In both human and animal the of fasciolosis on the of infection or and are to the of to the liver S. of in human 2005; PubMed Scopus Google S. et and other J. Parasitol. 2005; PubMed Scopus Google Scholar]. or fasciolosis has been shown to when their to other most in the but also the and the or S. et and in Parasitol. PubMed Scopus Google et in of and of the PubMed Scopus Google Scholar]. of infection with F. hepatica are more in human infection with F. gigantica, to the that F. hepatica has the zoonotic The case however, that human of fasciolosis caused by infection with F. gigantica are due to their in countries to and disease an zoonotic Res. 2015; PubMed Scopus Google Scholar]. In countries livestock production to more such as and the human are S. of in human 2005; PubMed Scopus Google S. et infection their incidence and 2018; PubMed Scopus Google Scholar]. The production however, F. hepatica one of the of parasite in these A. et al.Epidemiology and impact of Fasciola hepatica exposure in high-yielding dairy herds.Prevent. Vet. Med. 2015; 121: 41-48Crossref PubMed Scopus (99) Google J. et in the impact on production and of Fasciola hepatica in PubMed Scopus Google Scholar]. in countries and for the of livestock human and animal Fasciola spp. often and largely (Figure S. of in human 2005; PubMed Scopus Google an zoonotic Res. 2015; PubMed Scopus Google S. et infection their incidence and 2018; PubMed Scopus Google Scholar]. This is despite the of a treatment as a of between and the are primarily associated with the of and fasciolosis is considered to S. of in human 2005; PubMed Scopus Google Scholar]. however, have been a growing number of reports from the and in countries such as and an zoonotic Res. 2015; PubMed Scopus Google Scholar]. fasciolosis is considered a neglected disease in a on production in with an for disease in Southeast in to and a high incidence of to the increased zoonotic disease risk in the S. of in human 2005; PubMed Scopus Google an zoonotic Res. 2015; PubMed Scopus Google S. et and human with a global on disease evolutionary and Parasitol. PubMed Scopus Google Scholar]. on the of Fasciola spp. in Southeast are primarily to one of the countries in the (Figure et fasciolosis in the human fasciolosis in PubMed Scopus Google et status of fasciolosis in an and PubMed Scopus Google Scholar]. of the have of human with more reported between and et status of fasciolosis in an and PubMed Scopus Google Scholar]. on human and animal in the countries is The activities and human in these however, that they are to by fasciolosis, the disease remains of The global of F. hepatica and F. gigantica associated with livestock S. et and human with a global on disease evolutionary and Parasitol. PubMed Scopus Google Scholar]. events are by the indirect life cycle of Fasciola which a of to in order to their expansion a the of hosts snail and and to most of which have been E. et al.Impact of human activities on fasciolosis transmission.Trends Parasitol. 2018; 34: 891-903Abstract Full Text Full Text PDF PubMed Scopus (46) Google et hosts of Fasciola hepatica and Fasciola gigantica 2018; Scopus Google Scholar]. The that the of livestock in the more of these parasites, however, is often overlooked despite growth in global E. et al.Impact of human activities on fasciolosis transmission.Trends Parasitol. 2018; 34: 891-903Abstract Full Text Full Text PDF PubMed Scopus (46) Google This is in Southeast a growing in countries such as and has an in the demand for animal-derived As demand production, and is are from the cattle including and F. hepatica is Livestock and and of In 2019 over a million cattle and from an of on the year of these are livestock the for or The impacts of livestock are in the case of the more overt and devastating viral and bacterial diseases, such as and disease and In an to these disease livestock Southeast have been livestock for of both and the diseases they livestock as they are towards their many other diseases, fasciolosis is often subclinical in infected to these The subclinical of the disease to the of this important parasite in the events to the these parasite events are most in Southeast Fasciola spp. are to such as in the the of and from F. hepatica-endemic countries is the in the of from F. hepatica-endemic to is to changing the status quo of these parasites the world and of parasite sympatry (Figure Livestock and and of Scholar]. that an in the of livestock from F. hepatica-endemic to parasite events, is a lack of to this This is primarily Fasciola spp. to the of from from the of infected during S. et on Fasciola gigantica in PubMed Scopus Google Scholar, S. et of Fasciola spp. in cattle from 2012; PubMed Scopus Google Scholar, I. et characterization of Fasciola species from in Google Scholar]. on to parasites for species in a system that the of the of in that between and of are infected I. et characterization of Fasciola species from in Google and in and Parasitol. 2005; Google Scholar]. In one the and characterization of the of F. hepatica and F. gigantica, but also an Fasciola species in I. et characterization of Fasciola species from in Google Scholar]. the of both this is to the of hybridization between F. hepatica and F. gigantica et of hybridization between Fasciola hepatica and F. 49: PubMed Scopus Google Scholar]. to the these results for the of the livestock to the of these parasites infected and that events in Southeast that Fasciola spp. from have to of parasite events the (Box et species is in the at a time of global livestock for the of Fasciola J. Parasitol. PubMed Scopus Google Scholar]. The detection of F. hepatica in from cattle in a livestock and that are these parasites but that their life are to have become in the et species is in the at a time of global livestock for the of Fasciola J. Parasitol. PubMed Scopus Google Scholar]. The of F. hepatica Southeast is of for concern in due to the human and animal health impacts and for the of anthelmintic in livestock to F. more however, are the possible outcomes of with both of F. hepatica and F. gigantica species to of the is by the of the the liver of infected Once the of infected hosts become an and of considered in the of parasite however, the of for species from is that the of from many an to between and those with Fasciola (Figure I). such as and of these but et species is in the at a time of global livestock for the of Fasciola J. Parasitol. PubMed Scopus Google Scholar]. they the for areas of parasite sympatry with Fasciola and detection these infection with either Fasciola species is and of in of chronic The of production of Fasciola hepatica and the number of in by Vet. J. PubMed Scopus Google Scholar]. this is is and has in the increased the number of on for including and have been for detection of Fasciola spp. infection of the et al.Evaluation of an for detection of to Fasciola hepatica in Parasitol. PubMed Scopus Google et of and production in infected with Fasciola hepatica and F. Parasitol. PubMed Scopus Google Scholar]. more a the of of the of milk et of Fasciola hepatica in dairy in and with an to 2005; Scopus Google Scholar]. This is of infection in as as et of and production in infected with Fasciola hepatica and F. Parasitol. PubMed Scopus Google Scholar]. The of however, the of the to the detection of Fasciola spp. exposure et of on the in naturally infected with Fasciola Res. PubMed Scopus Google et of and and in cattle infected with Fasciola hepatica and treatment with Parasitol. PubMed Scopus Google Scholar]. the of current the detection of F. hepatica and F. gigantica as as and with et for detection of Fasciola hepatica in and cattle a Parasitol. PubMed Scopus Google Scholar]. as with is in to infection in due to in their increased et for detection of Fasciola Dis. PubMed Scopus Google Scholar]. of their to of in infection the the Fasciola species Fasciola species to of the is by the of the the liver of infected Once the of infected hosts become an and of considered in the of parasite however, the of for species from is that the of from many an to between and those with Fasciola (Figure I). such as and of these but et species is in the at a time of global livestock for the of Fasciola J. Parasitol. PubMed Scopus Google Scholar]. they the for areas of parasite sympatry with Fasciola and detection these infection with either Fasciola species is and of in of chronic The of production of Fasciola hepatica and the number of in by Vet. J. PubMed Scopus Google Scholar]. this is is and has in the increased the number of on for including and have been for detection of Fasciola spp. infection of the et al.Evaluation of an for detection of to Fasciola hepatica in Parasitol. PubMed Scopus Google et of and production in infected with Fasciola hepatica and F. Parasitol. PubMed Scopus Google Scholar]. more a the of of the of milk et of Fasciola hepatica in dairy in and with an to 2005; Scopus Google Scholar]. This is of infection in as as et of and production in infected with Fasciola hepatica and F. Parasitol. PubMed Scopus Google Scholar]. The of however, the of the to the detection of Fasciola spp. exposure et of on the in naturally infected with Fasciola Res. PubMed Scopus Google et of and and in cattle infected with Fasciola hepatica and treatment with Parasitol. PubMed Scopus Google Scholar]. the of current the detection of F. hepatica and F. gigantica as as and with et for detection of Fasciola hepatica in and cattle a Parasitol. PubMed Scopus Google Scholar]. as with is in to infection in due to in their increased et for detection of Fasciola Dis. PubMed Scopus Google Scholar]. of their to of in infection the the Fasciola species between F. hepatica and F. gigantica has been reported to in areas of Fasciola spp. sympatry as the of (Box S. et of Fasciola spp. in cattle from 2012; PubMed Scopus Google et of hybridization between Fasciola hepatica and F. 49: PubMed Scopus Google et and the of of Fasciola hepatica and Fasciola gigantica in J. Parasitol. PubMed Scopus Google et and that hybridization between Fasciola hepatica and Fasciola gigantica in 2017; PubMed Scopus Google Scholar]. hybridization between these parasites has been of and and characterization of the and et between Fasciola hepatica and Fasciola PubMed Scopus Google Scholar]. an intermediate to between that of their species and to more F. gigantica on reported rates et between Fasciola hepatica and Fasciola PubMed Scopus Google Scholar]. however, and the intermediate in the Fasciola in the due to the of et between Fasciola hepatica and Fasciola PubMed Scopus Google and the of species PubMed Scopus Google Scholar]. Fasciola a more and thus of these events is the of between and either of the species. the for introgression of from one species the and has been as the of between F. hepatica and F. gigantica, with the an intermediate to between the two species as shown (Figure et between Fasciola hepatica and Fasciola PubMed Scopus Google Scholar]. is the of from one species the of as a of of with either of the species and the of species PubMed Scopus Google J. et are PubMed Scopus Google of introgression between Fasciola spp. remains unproven but is as a of the of Fasciola with F. introgression (Figure is the of a and as a of of many are against and many the is towards other at a rate of the of 2017; PubMed Scopus Google Scholar]. The of is but for increased to definitive or intermediate from intermediate increased of both of the and in the Fasciola can of the in these results the status of the (Figure I). has been as the of between F. hepatica and F. gigantica, with the an intermediate to between the two species as shown (Figure et between Fasciola hepatica and Fasciola PubMed Scopus Google Scholar]. is the of from one species the of as a of of with either of the species and the of species PubMed Scopus Google J. et are PubMed Scopus Google Scholar]. The of introgression between Fasciola spp. remains unproven but is as a of the of Fasciola with F. introgression (Figure is the of a and as a of of many are against and many the is towards other at a rate of the of 2017; PubMed Scopus Google Scholar]. The of is but for increased to definitive or intermediate from intermediate increased of In both of the and in the Fasciola can of the in these results the status of the (Figure I). hybridization between F. hepatica and F. gigantica has been is introgression between these two parasites. the and are frequently the Fasciola spp. and often of the and of either et of hybridization between Fasciola hepatica and F. 49: PubMed Scopus Google et and the of of Fasciola hepatica and Fasciola gigantica in J. Parasitol. PubMed Scopus Google et hybridization and of Fasciola hepatica and Fasciola gigantica in of the Fasciola Parasitol. 2018; PubMed Scopus Google Scholar]. The current lack of between hybridization and introgression in Fasciola spp. is the and outcomes of introgression in other species. introgression has seen the of against and between as as the of in et al.The occurs in the of PubMed Scopus Google Scholar, et of introgression of the and of the in PubMed Scopus Google Scholar, E. et of a susceptible by 2012; PubMed Scopus Google Scholar, et introgression in an with the increased of S. A. 2015; PubMed Scopus Google Scholar]. is that introgression in the of anthelmintic in Fasciola spp. due to the of F. hepatica F. between these two have other important human and animal health including increased and to the infection of intermediate hosts and the of and metacercariae in the The between hybridization and introgression is from in Fasciola their for and the of of these events K. et and on the of in Fasciola Parasitol. Google Scholar, et al.The and of in the liver Fasciola PubMed Scopus Google Scholar, et of and of Fasciola in and their characterization on and PubMed Scopus Google Scholar, J. in and hybridization in animal PubMed Scopus Google Scholar]. the the of hybridization from introgression in Fasciola spp. is due to a to when a or is (Box et hybridization and of Fasciola hepatica and Fasciola gigantica in of the Fasciola Parasitol. 2018; PubMed Scopus Google J. in and hybridization in animal PubMed Scopus Google Scholar, et of Fasciola species from by Parasitol. PubMed Scopus Google Scholar, S. et for the of Fasciola Parasitol. PubMed Scopus Google Scholar, et of Fasciola from cattle in on of Res. PubMed Scopus Google Scholar, the of 2017; PubMed Scopus Google Scholar]. have on to and has a been et for the of Fasciola spp. on the of PubMed Scopus Google K. et of Fasciola is by two and Vet. Med. 2018; PubMed Scopus Google Scholar]. the of as for hybridization in Fasciola due to a lack of in these parasites and the of J. in and hybridization in animal PubMed Scopus Google et and of Fasciola spp. from hosts and by of Parasitol. PubMed Scopus Google Scholar, et of Fasciola hepatica from cattle and in Res. 2012; PubMed Scopus Google Scholar, et of the of Fasciola and Fasciola gigantica, and their with F. 7: PubMed Scopus Google Scholar]. more the of these of naturally hybridization and introgression events The of the F. hepatica and F. gigantica and that rapid and of the of introgression between Fasciola spp. K. et al.The Fasciola hepatica and to the host environment and the for rapid 2015; PubMed Scopus Google et of the liver fluke Fasciola PubMed Scopus Google Scholar]. of these have allowed the of introgression events of and the of et between of the PubMed Google Scholar]. Despite the of of Fasciola with both species to in the of the of introgression between these parasites and to appropriate the characterization of these in the of many from a of to is that a species is et of hybridization between Fasciola hepatica and F. 49: PubMed Scopus Google Scholar]. The of these parasites and their human and animal health impacts in the developing world means that have the of the of livestock in the expansion of The is however, and when considered in to we the impacts of introgression between other parasite the is introgression between F. hepatica and F. gigantica a or and are to Fasciola events the for the increased of and hybridization – the to introgression et species is in the at a time of global livestock for the of Fasciola J. Parasitol. PubMed Scopus Google Scholar]. have been in Fasciola spp. and are to with increased due to the of F. F. gigantica Livestock and and of I. et characterization of Fasciola species from in Google et between Fasciola hepatica and Fasciola PubMed Scopus Google Scholar]. is in of introgression between these two species is a of is time we the and and of these events in order to the impacts on the food and health of Fasciola with both species to or the of introgression between the two is the of during hybridization events between Fasciola are the and of and naturally Fasciola in the immune of definitive hosts to infection with F. F. gigantica, and their and can this to their and is the and of Fasciola spp. and to the of human in hybridization and of are to of definitive have Fasciola been in the and impact this have on areas of parasite of Fasciola with both species to or the of introgression between the two is the of during hybridization events between Fasciola are the and of and naturally Fasciola in the immune of definitive hosts to infection with F. F. gigantica, and their and can this to their and is the and of Fasciola spp. and to the of human in hybridization and of are to of definitive have Fasciola been in the and impact this have on areas of parasite The to and for their and during the of the to those due to the of from one species in the of a stage of Fasciola spp. that from the intermediate snail host to the of between two species in a with from each species. high in a with high of of adequate and a high rate of in the to the of the life the of from one species the of the most resistant encysted stage of Fasciola to mammalian the stage of Fasciola spp. that from the is in the of mammalian hosts and the intermediate snail the for of the from the of and the with more two of in which one of is from each the of time from infection of the mammalian host to the detection of Fasciola spp. in the stage of Fasciola spp. infection of the intermediate snail can by and from infection of by Fasciola spp. that are of or the stage the intermediate snail the of two or more species the at a

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