Trematodes of the family Opisthorchiidae: a minireview

Article information

Abstract

INTRODUCTION

The liver flukes (Digenea) of the genera Clonorchis Looss, 1907 and Opisthorchis Blanchard, 1895 are notorious as causative agents of human infections transmitted by fish. The disease clonorchiasis, and the closely related opisthorchiasis, annually infect millions of people in regions where raw or undercooked fish harbouring opisthorchiid metacercariae are consumed, particularly in Southeast Asia and circumpolar parts of Eurasia and North America. However, the family Opisthorchiidae also includes numerous genera whose members rarely infect humans (Yamaguti, 1971).

The family Opisthorchiidae has been studied fairly exhaustively in a number of monographs or comprehensive volumes: Skrjabin and Petrov (1950), Yamaguti (1958, 1971, and 1975). In these works, the family was thought to include approximately 50 genera, encompassing several hundred species; however, the lack of more recent research has brought the taxonomic status and validity of these genera into question. Also, as no new data have been compiled recently as a specific condensed volume, very little is known about the family as a whole. The species composition, geographical distribution, life cycles and phylogenetic relationships within the family have all been insufficiently examined.

It is the purpose of this review, therefore, to give a brief summary of the family as a whole and to provide information concerning the taxonomy of the family in an attempt to eliminate invalidities and synonyms amongst genera. Information will also be provided on the host spectrum, life cycles, geographic distribution, and socioeconomic factors of the family.

CLASSIFICATION AND TAXONOMY

The main problem with classifying any group of digenetic trematodes is the fact that they have complex life cycles involving 2-4 hosts and many different larval stages. Thus, there are many morphologically different forms on which taxonomy can be based.

Yamaguti (1971) refers to his previous classifications and, indeed, those of others, when he maintains that the adult morphology of digeneans is the best method of classification. However, he also states: "We must be content for the present with an artificial classification based chiefly on adult morphology." It is with this statement in mind that another school of thought has arisen, which many believe is a much more accurate means of classification. It involves the examination of cercariae, as these are believed to be recapitulations of ancestral forms, and thus enable the production of a more phylogenetically accurate classification. It is considered that the use of cercarial forms also eliminates the possibility of misidentification through convergent evolution (Brooks et al. 1985).

Brooks et al. (1985) went some way towards addressing the issues concerned with the classification of digeneans and have carried out an extensive study on the phylogenetic relationships of the entire Digenea. Using both adult morphology and larval forms, they have attempted to provide a starting point for future phylogenetic studies on this diverse group, which, they hope, will grow into a comprehensive and increasingly accurate method of classification. However, the use of evidence from both adult and cercarial forms seems to further outline the prevalence of conflicting theories concerning the classification of this group. Until such inconsistencies can be overcome to a greater extent, the Digenea and methods used to classify them seem destined to remain under scrutiny. Indeed, Pearson (1992) argues that the methods of classification used by Brooks et al. (1985) are not reliable enough to base the phylogenetics of the digeaneans on. After his analysis of the characters used by Brooks et al. (1985), he states that 97 of the 212 characters used in the cladistic classification of the Digenea were invalidly used, resulting in the homoplasy increasing by 18% to 37%, with an accompanying decrease in resolution from 82% to 32%.

Cribb et al. (2001) have attempted to further unravel some of the mysteries surrounding digenean evolution and expand on such studies of Brooks et al. (1985) and Pearson (1992), among others, in order to resolve some of the many inconsistencies that can be found in this area of study. They have attempted to do this by combining many data sets, including those containing morphological and molecular characters, to provide a truer representation of the relationships between digenean families. The use of combined data sets can be controversial in itself, as outlined by de Queiroz et al. (1995) who have reviewed the arguments both for and against the use of combined data sets in phylogenetic analyses.

Although the studies mentioned above have used extensive phylogenetic analysis in order to try and resolve the relationships between all the families within the Digenea, such work is important when individual families are re-examined in order to validate subfamilies and genera. In essence, when classifying trematodes within a particular family, in this case the Opisthorchiidae, it is the species that are closely related enough to be included within the same family, subfamily, and genus that are being identified. The taxonomic state of the entire class or subclass being studied plays an important role in such a re-examination as closely related families can provide information on the composition of the family of interest.

Perhaps still considered as the most extensive attempt to form a complete classification of digenetic trematodes was that of Yamaguti (1971) (with the life cycles treated separately in 1975). Although three decades old, the material in these volumes is still referred to as one of the most comprehensive studies of digeneans, and for this review, these volumes were a starting point from which to source the original descriptions of members of the Opisthorchiidae. Subsequently, it was these original descriptions which formed the basis of the reclassification reported in this study.

Firstly, by referring to papers containing the original descriptions of each genus, 11 genera can be omitted from the family on the basis of being invalid or not belonging to the Opisthorchiidae at all:

The two genera found not to belong to the Opisthorchiidae are thought to be synonymous with one another, and, as indicated by their morphology, belong to the family Acanthostomidae (subfamily Acanthostominae of the Cryptogominidae according to some authors) as originally reported. Thus, with all of the above genera omitted from the family, it is proposed that the family Opisthorchiidae contain only 33 genera, as listed below:

Secondly, on the basis that characteristics of a less refined nature can be common to one or more genera, each genus can be allocated to a specific subfamily. Under Yamaguti's (1971) classification, the above genera would be accommodated by no less than 13 subfamilies, many of which are represented by only one or two genera (number of genera in parentheses):

The number of subfamilies supposedly housed within the Opisthorchiidae is inconsistent with the number of genera they contain, especially when over half of the above mentioned subfamilies contain only one genus. Although not having been re-examined for this study, we suggest that future revisions of the family will result in the subfamilies being reduced considerably in number to leave a truer representation.

Thirdly, the overall classification of the Opisthorchiidae family, as well as being covered in Yamaguti's volumes, was extensively covered by Brooks et al. (1985), with specific regard to the phylogeny and adaptive radiation of phylum Platyhelminthes as a whole.

Clearly, Brooks et al. (1985) have primarily based their classification on the examination of cercarial stages, whereas Yamaguti (1971) relied chiefly on adult morphology. As mentioned in the previous section on classification and taxonomy, much controversy still surrounds which of these methods is more reliable, and whether or not the use of combined data sets would provide a truer representation. Indeed, Wykoff et al. (1965) reported that they were unable to distinguish between Opisthorchis viverrini and O. felineus using adult or egg morphology alone, and that the only means of separating the two species was to use the flame cell patterns of cercaria or metacercaria.

SURVEY OF GENERA

On the basis of the revision of the pertinent literature of family Opisthorchiidae, we propose that the following genera (housed in the subfamilies suggested by Yamaguti (1971)) constitute a true representation of the family with all invalidities and synonyms removed. Clearly, the family has been greatly reduced in size, now compromising of only 33 genera; however, it is still a cosmopolitan family with the species inhabiting various geographical areas and having many different hosts. It should also be noted that this reduction represents the first step in a critical re-examination of the validity of opisthorchiid genera, which should be expanded upon to include the examination of specimens.

DEFINITIVE HOSTS

It is the definitive host of members of this family that provides the site for development of opisthorchiid metacercariae into the adult forms, and thus the means to reproduce. Adult opisthorchiid worms exploit all major vertebrate groups as definitive hosts, with birds being the most common exclusive host for adult flukes. However, like humans and other mammals, this is probably due to the fact that fish are a major dietary component (genera in bold are specific to the vertebrate class):

LIFE CYCLES

The life cycles of Opisthorchiidae flukes are complex in that they have various larval stages, three different hosts (two intermediate and one definitive), and both asexual and sexual stages of reproduction. Although opisthorchiid flukes can have several generations within different larval stages, there are five main larval stages before the sixth and final adult form emerges. Each stage of the fluke's life cycle is morphologically distinct from the others, making each stage uniquely suited to its environment and role in the development of the adult form.

IMPORTANCE TO HUMAN HEALTH

Far and away the most important members of family Opisthorchiidae, with regards to human health, are Clonorchis sinensis, Opisthorchis viverrini and O. felineus. These species are responsible for the diseases of clonorchiasis and opisthorchiosis, respectively, and collectively it is thought that these species are responsible for infecting over 30 million people worldwide (Roberts and Janovy, 1996) with a further 290 million people at risk (Rim et al., 1994). It should be noted, however, that different levels of infection are consistently quoted in literature, so these figures can be in no way absolute. In addition to the health problems (outlined further, below) associated with theses helminth species, comes a huge economic burden for countries where infection with these species is endemic; for example, infections with O. viverrini alone, can cost Northeast Thailand $120 million per year (Murrell et al., 1991).

Clinically, clonorchiasis and opisthorchiasis are indistinguishable from one another as they both produce symptoms of chills, diarrhoea, fever, lower abdominal pain, jaundice, swelling of the liver, and malnutrition. Morphologically the species are very similar, evident by the fact that some authors refer to the first species as Opisthorchis sinensis (see Kassai, 1999), and are only distinguishable by the branched (dendritic) testes of Clonorchis in comparison to the lobed testes of Opisthorchis. For the purpose of convenience and ease of explanation, therefore, all human infections caused by any of these species shall be referred to as clonorchiasis, unless otherwise stated.

The flukes causing clonorchiasis inhabit the liver of their host, which may make them somewhat less immediately life threatening than the flukes that cause schistosomiasis, for example. Nevertheless, this disease can have devastating effects on entire communities in addition to the aforementioned symptoms, in cases of prolonged and heavy infections where the worm load is in excess of 200, cirrhosis, pancreatitis, and cholangiocarcinoma can also occur. Indeed, cholangiocarcinoma, rare in other areas of the world, has a high prevalence in countries where clonorchiasis is endemic (Haswell-Elkins et al., 1992; Lee et al., 1994).

Clonorchiasis caused by Clonorchis sinensis and Opisthorchis viverrini is endemic throughout Southeast Asia in countries such as China, Korea, Japan, Taiwan, Vietnam, Laos, Thailand, and Cambodia (Tinga et al., 1999). Infection with Opisthorchis felineus is prevalent in Russia, particularly Siberia, and also in Kazakhstan and the Ukraine (Mas-Coma and Bargues, 1997). The disease can also be found in Europe and North America, although to a much lesser extent, and probably only due to the increasing import of fish from countries where the disease is widespread. Perhaps the most prominent reason for such a distribution of the disease lies in the traditional eating habits of the inhabitants of the aforesaid Asian and Russian countries. Many traditional Asian dishes such as yue-shan chuk (a Cantonese delicacy) consist of raw fish with rice, vegetables, and soup. Since the fish in these dishes is eaten raw or only slightly cooked, the metacercarial cysts can survive to excyst on consumption and mature to adults in their definitive host, in this case humans. Species of cyprinid fish are cultivated for human consumption and the increased breeding of the grass carp Ctenopharyngodon idellus for this purpose creates a wealth of second intermediate hosts for opisthorchiid cercariae, which can increase the prevalence rates of clonorchiasis (Bisseru and Chong, 1969). In Russia, frozen, raw, pickled or smoked fish are eaten and a study by Fan (1998) showed that metacercariae from Clonorchis sinensis can actually remain viable, even after the fish has been frozen or salted for several days. Other piscivorous mammals such as cats, dogs, and farm livestock can also act as definitive hosts such a wide range of definitive hosts ensures that large numbers of eggs are washed into water reservoirs with faecal matter and so the life cycle can begin again.

The living conditions to which people are exposed also contribute to a high incidence of this disease in Asian countries. As the main occupation in many areas is fishing or agriculture, many villages are built on the edges of lakes or reservoirs. Such villages rarely have adequate plumbing and consistently lack sanitation facilities, thus people usually defecate either close to or actually in the water, which allows the opisthorchid eggs to begin the aquatic stages of their life cycle (Ditrich et al., 1990).

Due to the medical significance of this disease, many studies have been carried out to investigate the impact that it has on human populations. Such studies provide information on, among other things, the prevalence and spread of the disease in endemic regions, which drugs are best at combating infection, and how public health programmes can help to curb the spread of the disease (see Rim et al., 1994 for review; Yu, 1996). One such study by Sornami et al. (1973) highlighted the problems caused by the construction of the Ubolratana dam in Northeast Thailand, with regards to the health status of individuals living in the newly built villages around the banks of the man-made lake. The villagers were traditionally farmers living in the area flooded by the building of the dam; it was a natural progression, therefore, that they moved to the banks of the lake and replaced farming with fishing. The study was carried out over a period of several months during the early rainy season of the area, and was primarily concerned with the gathering of information to investigate the general health status of the villagers. The results clearly showed that the living conditions of the villagers greatly increased their chances of being the definitive host for the opisthorchiid worms as well as other helminth parasites. The traditional dishes of raw or undercooked fish, coupled with the poor sanitation facilities (only one house from the three villages had a latrine) provided a near perfect environment for the spread of infections (Sornmani et al., 1973).

Another study, carried out by Joo et al. (1997), reported on the changing patterns of clonorchiasis in Korea over a period of two years. This study also provides information on the prevalence of metacercariae in species of fresh-water fishes common to the area, and highlights the need for a continued and amplified treatment programme.

Just as there is a wealth of information on the rates of infection of clonorchiasis, there is also a multitude of studies as to what is the best form of treatment for this disease. Many studies (e.g., see Rim et al., 1981; Chen et al., 1983; Radomyos et al., 1998) have concentrated on the use of praziquantel as the most effective drug with which to treat cases of clonorchiasis, and outline extensively the best dosage and frequency of administration. However, other studies have questioned the effectiveness of this drug in the treatment of clonorchiasis; namely, Hong et al. (1998) and Tinga et al. (1999) who showed that certain dosages of praziquantel were ineffective as a means of treating clonorchiasis. However, due to the fact that praziquantel targets more than one helminth species means that it will probably remain the drug of choice for diseases such as clonorchiasis.

VETERINARY IMPORTANCE

Although Kassai (1999) states that opisthorchiid trematodes are of low veterinary significance, these helminths can still have adverse affects on domestic and wild animals. Since humans and other animals are inextricably linked in many Asian communities, where farming and fishing are the main sources of employment, such diseases as clonorchiasis can be so prevalent that they become established within entire communities. Obviously, the health risks to farm animals can be debilitating for the community as the disease weakens the animals, thus lowering the quality of the produce derived from them, or renders them too weak to be used for manual work. The situation is worsened by the fact that such animals act as reservoir hosts for the opisthorchiid worms and so their close contact with humans can exacerbate the problems of infection and control within human populations.

Similarly, wild animals can act as reservoir hosts for many helminths, and this allows the parasites to have a continual presence in the environment. As discussed by Shimalov et al. (2000), otters (Lutra lutra Linnaeus, 1758) in Russia are a host to many species of helminths, including three species from the family Opisthorchiidae; namely, Opisthorchis felineus, Pseudamphistomum truncatum, and Metorchis bilis. Introduced animal species in Russia are also hosts to a wide range of helminths. Ivanov and Semenova (2000) studied introduced animal species, including American muskrats (Ondatra zibethicus), American mink (Mustela vison), and Siberian raccoon dogs (Nyctereutes procyonoides), and found that they had acquired parasitic fauna of the area, which includes M. bilis and P. truncatum.

CONCLUSIONS

It is clear that even with invalid genera removed from the family, the Opisthorchiidae are still an interesting and cosmopolitan group of digeneans, and although much work has been done on the medically important species of family, relatively little is known about the other genera. This review is intended to be the first step in a critical re-examination of the Opisthorchiidae, the subsequent steps of which should be based on the examination of specimens. It is hoped that this review has gone some way to providing a truer classification of the family as a whole, at genera-level at least, and that this information may be expanded upon in future studies to further resolve inconsistencies and invalidities within the family, particularly with regards to subfamily classification.

Article information Continued