Foodborne trematodes (FBTs) have a worldwide distribution (with particular prevalence in south-east Asia) and are believed to infect almost 75 million people, with millions more living at risk of infection. Although mortality due to trematodiasis is low, these infections cause considerable morbidity and some species are associated with the development of cancer in hyperendemic regions. Despite this, FBTs are often side-lined in terms of research funding and have been dubbed neglected tropical diseases by the World Health Organisation. Thus, the aim of this special issue was to provide an update of our understanding of FBT infections, to shine a light on current work in the field and to highlight some research priorities for the future. With contributions from leading researchers, many from endemic regions, we review the major FBT species. In doing so we revisit some old foes, uncover emerging infections and discover how outbreaks are being dealt with as a result of new approaches to parasite control. We also report advances in our understanding of the interactions of FBTs with their mammalian hosts and uncover new interplay between trematodes and host microbiome components. We hope that this article collection will stimulate discussion and further research on the FBTs and help raise them from their neglected status.

Foodborne trematodes (FBT) of public health significance include liver flukes (Clonorchis sinensis, Opisthorchis viverrini, O. felineus, Fasciola hepatica and F. gigantica), lung flukes (Paragonimus westermani and several other Paragonimus spp.) and intestinal flukes, which include heterophyids (Metagonimus yokogawai, Heterophyes nocens and Haplorchis taichui), echinostomes (Echinostoma revolutum, Isthmiophora hortensis, Echinochasmus japonicus and Artyfechinostomum malayanum) and miscellaneous species, including Fasciolopsis buski and Gymnophalloides seoi. These trematode infections are distributed worldwide but occur most commonly in Asia. The global burden of FBT diseases has been estimated at about 80 million, however, this seems to be a considerable underestimate. Their life cycle involves a molluscan first intermediate host, and a second intermediate host, including freshwater fish, crustaceans, aquatic vegetables and freshwater or brackish water gastropods and bivalves. The mode of human infection is the consumption of the second intermediate host under raw or improperly cooked conditions. The major pathogenesis of C. sinensis and Opisthorchis spp. infection includes inflammation of the bile duct which leads to cholangitis and cholecystitis, and in a substantial number of patients, serious complications, such as liver cirrhosis and cholangiocarcinoma, may develop. In lung fluke infections, cough, bloody sputum and bronchiectasis are the most common clinical manifestations. However, lung flukes often migrate to extrapulmonary sites, including the brain, spinal cord, skin, subcutaneous tissues and abdominal organs. Intestinal flukes can induce inflammation in the intestinal mucosa, and they may at times undergo extraintestinal migration, in particular, in immunocompromised patients. In order to control FBT infections, eating foods after proper cooking is strongly recommended.

The title of this article refers to Table 1 in Zhou (2022, Infectious diseases of poverty: progress achieved during the decade gone and perspectives for the future. Infectious Diseases of Poverty 11, 1), in which it is indicated that Paragonimus species, like many other foodborne trematodes, are ancient pathogens that are also re-emerging to cause disease in modern times. This article provides a general overview of Paragonimus species and the disease they cause. This is followed by comments on several specific topics of current interest: taxonomy and distribution of members of the genus; details of the life cycle; global and regional prevalence of paragonimiasis; genomics of lung flukes and possible effects of global environmental change. Unresolved questions relating to these topics are discussed and gaps in knowledge identified.

Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis in humans. Clonorchiasis is prevalent in East Asian countries, and approximately 15–20 million individuals are estimated to be infected with this fluke globally. This review highlights the current status of C. sinensis and clonorchiasis in Korea from the epidemiological perspective involving the analysis of humans and intermediate hosts. Despite the recent decline in C. sinensis infection rate in Korea, C. sinensis infections remain endemic in 5 major river basins (Han-gang, Geum-gang, Seomjin-gang, Yeongsan-gang and Nakdong-gang; gang means river) with a high incidence of cholangiocarcinoma. A noticeable pattern involves increasing mild infections among patients diagnosed positive for C. sinensis eggs. The infection rate of C. sinensis metacercariae in the second intermediate host, freshwater fish, is also maintained at a substantial level. Thus, the One Health approach integrating different sectors and disciplines is recommended to accelerate and sustain control of C. sinensis, thereby leading to successful eradication. Health promotion via information dissemination and health education should be extended to prevent the consumption of raw freshwater fish by residents living in high-risk areas.

The foodborne liver trematode Opisthorchis felineus (Rivolta, 1884) is a member of the triad of phylogenetically related epidemiologically important Opisthorchiidae trematodes, which also includes O. viverrini (Poirier, 1886) and Clonorchis sinensis (Loos, 1907). Despite similarity in the life cycle, Opisthorchiidae liver flukes also have marked differences. Two species (O. viverrini and C. sinensis) are recognized as Group 1A biological carcinogens, whereas O. felineus belongs to Group 3A. In this review, we focus on these questions: Are there actual differences in carcinogenicity among these 3 liver fluke species? Is there an explanation for these differences? We provide a recent update of our knowledge on the liver fluke O. felineus and highlight its differences from O. viverrini and C. sinensis. In particular, we concentrate on differences in the climate of endemic areas, characteristics of the life cycle, the range of intermediate hosts, genomic and transcriptomic features of the pathogens, and clinical symptoms and morbidity of the infections in humans. The discussion of these questions can stimulate new developments in comparative studies on the pathogenicity of liver flukes and should help to identify species-specific features of opisthorchiasis and clonorchiasis pathogenesis.

In the present paper, we review two of the most neglected intestinal food-borne trematodiases: echinostomiasis, caused by members of the family Echinostomatidae, and gastrodiscoidiasis produced by the amphistome Gastrodiscoides hominis. Both parasitic infections are important intestinal food-borne diseases. Humans become infected after ingestion of raw or insufficiently cooked molluscs, fish, crustaceans, amphibians or aquatic vegetables. Thus, eating habits are essential to determine the distribution of these parasitic diseases and, traditionally, they have been considered as minor diseases confined to low-income areas, mainly in Asia. However, this scenario is changing and the population at risk are currently expanding in relation to factors such as new eating habits in developed countries, growing international markets, improved transportation systems and demographic changes. These aspects determine the necessity of a better understanding of these parasitic diseases. Herein, we review the main features of human echinostomiasis and gastrodiscoidiasis in relation to their biology, epidemiology, immunology, clinical aspects, diagnosis and treatment.

Human autochthonous infections with the trematode Paragonimus kellicotti are increasingly being reported in North America, but the true prevalence and geographic distribution are unknown. Ingestion of raw crayfish is reported in most human cases, typically in the context of alcohol intoxication. Risk of infection varies depending on what part of the crayfish is ingested as metacercariae of P. kellicotti (>50% mature to adults) localize to the heart and pericardium of the crayfish. Reported human cases have manifested primarily in otherwise healthy young adults presenting with severe eosinophilic pneumonia, pleuritis, systemic symptoms, dermatologic lesions and cerebral involvement. However, it is likely that many infections go unreported due to lack of awareness, mild illness or the absence of rapid commercially available diagnostic tests. Promising advances have been made related to novel diagnostic targets. Conservation of these antigen targets among at least four Paragonimus species could make these antigens viable for diagnostic testing of P. kellicotti specifically as well as other Paragonimus species, but additional studies and funding investments are required. Public and physician awareness may have improved due to targeted education campaigns, but ongoing activities to raise awareness are needed, particularly in areas where cases have not been frequently reported to date.

The liver fluke Opisthorchis viverrini is a foodborne trematode that, in chronic infection, is a leading cause of bile-duct cancer – cholangiocarcinoma. Cats and dogs are acknowledged as reservoir hosts of this parasite. However, this assumption is based on morphological similarity of flukes recovered from these hosts, without any molecular genetic evidence. The aim of this study was to obtain molecular data from O. viverrini eggs present in feces of humans and cats in the same locality in Thanya sub-district, Kalasin, Thailand. The mitochondrial cytochrome c oxidase subunit 1 (cox1) gene was used as the marker for a population-genetic study. A DNA fragment of the cox1 gene was amplified from stool samples and subjected to nucleotide sequencing. Phylogenetic and haplotype network analyses were performed. The cox1 sequences of O. viverrini eggs from humans and cats largely formed separate clades on the phylogenetic trees, with an Fst value of 0.64 (P < 0.05), indicating largely distinct populations in the 2 species. However, 5 samples from cats were placed in the human cluster and 1 sample from a human was placed in the cat cluster. This suggests that host specificity of ‘human’ and ‘cat’ clades is not absolute. These results indicate that there are 2 populations of O. viverrini, one circulates primarily in humans and the other in cats. However, cross-transmission can occur between these 2 hosts. Taken altogether, the population-genetic evidence from this study partially supports the assumption that the cat can act as a reservoir host of O. viverrini.

Fasciola gigantica, the causative agent of tropical fasciolosis, is a food-borne zoonotic trematode that affects around 80% livestock of Bangladesh. Triclabendazole (TCBZ), nitroxynil (NTON) and oxyclozanide (OCZN) are frequently used against fascioliasis; however, the current status of potency of these flukicides was unknown. In this study, in vitro efficacy of TCBZ, NTON and OCZN at various concentrations on F. gigantica has been evaluated by relative motility (RM), morphological distortions of apical cone through an inverted microscope, architectural and ultra-structural changes through histopathological and scanning electron microscopy (SEM). It is observed that TCBZ, NTON and OCZN at higher concentrations significantly (P < 0.05) reduced RM of the flukes compared to untreated control. NTON at 150 μg mL−1 was the most potent to reduce the motility within 4 h whereas TCBZ and OCZN were much delayed. Histopathological changes showed swollen, extensive cracking, numerous vacuoles and splitting of the tegument surrounding the spines; spine dislodged from its socket in treated flukes compared to untreated worms. Histopathological changes were more conspicuous at higher doses of TCBZ, NTON and OCZN. SEM has shown the disruption of the apical cone, apart from swelling of the tegument on the ventral surface corrugation and disruption of the ventral apical cone. All these changes indicate that NTON is the most potent in killing flukes in vitro among the tested flukicides and suggest the presence of TCBZ-resistant fluke populations in Bangladesh. It is imperative to explore the in vivo effects of these flukicides and subsequently their molecular mechanisms.

The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.

Host mucins have crucial physical roles in preventing the parasitic establishment and maturation, and also in expelling the invading parasites. However, some parasites utilize mucinase enzymes to facilitate the infection. Recently, we have identified a mucinase enzyme of the liver fluke Opisthorchis viverrini, Ov-M60-like-1, which exhibits metallopeptidase activity against bovine submaxillary mucin substrate. Here, we aimed to study the localization of this enzyme in O. viverrini and the bile duct of hamsters using immunohistochemistry and functional analysis by mucin digestion in hamsters and mice tissues. The results showed that Ov-M60-like-1 was detected strongly in the tegument, tegumental cells, vitelline glands and mature eggs with miracidium. Expression in the gut, ovary and testis of the parasite was moderate while parenchyma showed slight colour intensity. In addition, the mucinase was also detected in the host biliary epithelial cells and goblet cells surrounding the worm. The mucinase assay revealed that the Ov-M60-like-1 could digest neutral mucin in the parenchyma, testis and seminal receptacle, but not the mucin in the tegument, tegumental cells and vitelline glands of the worm. The enzyme can also digest mucin in the cholangiocytes and modified the mixture type in the bile duct goblet cells of the infected hamsters, a susceptible host. In contrast, the enzyme was unable to digest neutral, acid and mixture mucin in the bile duct of the mice, a non-susceptible host. These findings indicate that Ov-M60-like-1 may have functions in both housekeeping tasks and host–parasite interactions, especially in modification of host susceptibility.

The food-borne trematodes, Opisthorchis viverrini and Clonorchis sinensis, are classified as group 1 biological carcinogens: definitive causes of cancer. By contrast, infections with Fasciola hepatica, also a food-borne trematode of the phylum Platyhelminthes, are not carcinogenic. This review explores the premise that the differential activation of macrophages during infection with these food-borne trematodes is a major determinant of the pathological outcome of infection. Like most helminths, the latter stages of infection with all 3 flukes induce M2 macrophages, a phenotype that mediates the functional repair of tissue damaged by the feeding and migratory activities of the parasites. However, there is a critical difference in how the development of pro-inflammatory M1 macrophages is regulated during infection with these parasites. While the activation of the M1 macrophage phenotype is largely suppressed during the early stages of infection with F. hepatica, M1 macrophages predominate in the bile ducts following infection with O. viverrini and C. sinensis. The anti-microbial factors released by M1 macrophages create an environment conducive to mutagenesis, and hence the initiation of tumour formation. Subsequently, the tissue remodelling processes induced by the M2 macrophages promote the proliferation of mutated cells, and the expansion of cancerous tissue. This review will also explore the interactions between macrophages and parasite-derived signals, and their contributions to the stark differences in the innate immune responses to infection with these parasites.

Recent reports implicate both the liver fluke Opisthorchis viverrini as a reservoir of Helicobacter pylori within the human gastrointestinal tract and H. pylori in the pathogenesis of opisthorchiasis-associated cholangiocarcinoma. We postulated that adherence of bacterial ligands to host receptors initiates colonization of the live fluke by H. pylori and here we aimed to assess the molecular interaction between O. viverrini and H. pylori by investigating host receptors for H. pylori in the fluke. Several known receptors of H. pylori including Lewis B, sialyl-Lewis X, Toll-like receptor 4 and L-fucose were detected immunohistochemically and histochemically by focusing analysis on the gut epithelium and tegument of the adult stage of the fluke. The frequency of detection of Lewis B, sialyl-Lewis X, TLR4 and L-fucose in 100 individual worms was 3, 3, 19 and 70%, respectively. Detection of H. pylori by a diagnostic ureA gene-based PCR assay revealed the presence of H. pylori in individual O. viverrini worms in 41 of 49 (79%) worms examined. In addition, numbers of bacteria decreased in a dose- and time-dependent fashion following exposure to fucosidase. These findings suggested that L-fucose represents a tractable receptor for H. pylori that can mediate bacterial colonization of the gut of O. viverrini.