93
ROYAL
SOCIETY
OF TROPICAL
MEDICINE
AND HYGIENE
Ordinary Meeting Symposium on hydatid disease Liverpool School of Tropical Medicine, Thursday, 18th November, 1976 The President: Dr. C. E. Gordon Smith, c.B., F.R.c.P., F.R.C. Path, in the chair
Strain differences in Echinococcus granulosus, with special reference to the status of equine hydatidosis in the United Kingdom J. D. SMYTH Department of Zoology and Applied Entomology, Imperial College, London S W7 2BB Summary The genetics of speciation in the genus Echinococcus are briefly discussed. As the organism is a hermaphrodite and multiplies asexually in the larval stage, the genetic mechanism for the ready production of new strains is inherent in the life-cycle. Some biological, biochemical and nutritional differences between the horse and sheep strains are examined. The sheep strain may be grown to sexu.al maturity, in vitro, in a diphasic system; the horse strain fails to grow in such a system. Differences have also been demonstrated between the soluble proteins of the two strains. The sheep strain is infective to man but, probably, non-infective to horses. The horse strain (which is now the major strain in the U.K. and Ireland) appears to be poorlq infective to sheep and may prove to be non-infective to man. The importance of determining the basic characteristics of other strains of E. granuloslts are also stressed. Introduction and background Hydatid disease (hydatidosis, echinococcosis) is recognized as being one of the world’s major zoonoses. Its distribution is normally associated with underdeveloped countries or those with a large rural population where public health measures are difficult to enforce (e.g. Cyprus, New Zealand, Australia). The general pattern of the life-cycle is well established; the eggs of the causative organism, the dog tapeworm, E. granulosus, when ingested by man or a wide range of ungulates (e.g. sheep, cattle, pigs, goats, horses, camels, buffaloes, etc.) develop into hydatid cysts, the presence of which gives rise to the clinical symptoms of hydatid disease. Dogs become infected by eating hydatid cysts. Human hydatidosis is relatively rare in this country, the Public Health statistics giving an annual overall average of only 0.3 human cases per million (THOMPSON & SMYTH, 1975). Until recently, most of the reported cases have been in Wales (WEST, 1960) but, recently, several cases have been reported from the Isle of Skye (WILLIAMS & ROCHE, 1974). In some sheep-raising countries (e.g. New Zealand), a comparable figure of 43.5 human cases per million was reported IO years after the Second World War. In other countries, where mandog contact is exceptionally close or where other epidemiological conditions are especially favourable, much higher figures occur. Within recent years, however, the epidemiological picture in the United Kingdom has changed dramatically with a remarkable and unexpected rise in the prevalence of hydatidosis in horses (Fig. 1) to a level which now exceeds 60% (THOMPSON& SMYTH, 1975). The implica-
70. 60.
01 /, 1920
1930 1940 1950 1960 1970 Year
Fig. I. Incidence of equine hydatidosis in the U.K. (after THOMPSON& SMYTH,1975; scatter points omitted). tions of this situation, with respect to its potential as a health hazard to man, form the main topic of this paper. Speciation in Echinococcus General account Speciation in the genus Echinococcus has long been a matter of controversy and the question has been the subject of a number of reviews (SMYTH, 1964, 1969; VERSTER,1969; RAUSCH, 1967). It is generally accepted that two main species of Echinococcus are responsible for hydatid disease: (a) E. grunulosus which develops in dogs but generally not in foxes (but see page 95), and which mainly utilizes ungulates as intermediate hosts. It causes unilocular hydatid disease. (b) E. multilocularis which matures in foxes and cats as well as other Canidae and utilizes microtine rodents as its intermediate hosts. It causes alveolar hydatid disease. In Russia, this form is regarded as belonging
94
SYMPOSIUMON HYDATID DISEASE
to a different genus, Alveococcus. The epidemiology has been reviewed by LUKASHENKO(1971). This is probably an oversimplification of a complex speciation problem, and SMYTH & SMYTH (1964) have suggested that a “continuum” of “species” exists between E. granulosus and E. multilocularis. This view is based on the fact that examples of “E. which do not fall easily into either E. granulosus”, granulosus or E. multilocularis, have been found. Thus, a form of E. granulosus which can develop to maturity in foxes has been reported from Bulgaria (MATOFF & YAUCHEV, 1965). Again, in India, GILL & RAO (1967) have reported the occurrence of an “E. granulosus” with a dog/buffalo cycle, which differs from the “classical” descriptions of this species. The matter is further complicated by the discovery of a number of other species in South America, e.g. E. oligarthrus (SOUSA & THATCHER, 1969) and E. vogeli (RAUSCH & BERNSTEIN, 1972), which differ morphologically from E. granulosus and E. multilocularis. These species involve wild tropical felid species (puma, jaguar, jaguarundi, bush dog) and need not concern us here. Genetical basis for strain development in Ehinococcus
As mentioned above, it has been speculated that speciation in Echinococcus is a complex matter with (possibly) well-defined species at each end of a hypothetical scale having morphological, physiological and
ORIGINALWILD TYPE ++
‘;
II +
suppose mutant -genep [recessive] appears :.::: ..:: 233
Echinococcus.
(a) Most adult tapeworms are self-fertilizing hermaphrodites, and self-fertilization has been demonstrated in E. grandosus (SMYTH & SMYTH, 1969). Hence, if a mutation occurs involving the appearance of (say) a recessive gene (c Fig. 2) it can occur in both eggs and sperm, with the result that a double recessive (rr Fig. 2) may be readily formed. (b) The larva (i.e. hydatid) reproduces asexually (by polyembrony?) so that once an oncosphere becomes established in a new host, a large population (or clone) of, perhaps a million, genetically identical individuals bearing the new, double recessive gene rr can be formed. The way in which these characteristics could combine to express a recessive mutation (which would normally be lost) is shown in Fig. 2.
genotypes of oncospheres
++ v
ROYAL
SOCIETY
OF TROPICAL
MEDICINE
AND HYGIENE
Ordinary Meeting Symposium on hydatid disease Liverpool School of Tropical Medicine, Thursday, 18th November, 1976 The President: Dr. C. E. Gordon Smith, c.B., F.R.c.P., F.R.C. Path, in the chair
Strain differences in Echinococcus granulosus, with special reference to the status of equine hydatidosis in the United Kingdom J. D. SMYTH Department of Zoology and Applied Entomology, Imperial College, London S W7 2BB Summary The genetics of speciation in the genus Echinococcus are briefly discussed. As the organism is a hermaphrodite and multiplies asexually in the larval stage, the genetic mechanism for the ready production of new strains is inherent in the life-cycle. Some biological, biochemical and nutritional differences between the horse and sheep strains are examined. The sheep strain may be grown to sexu.al maturity, in vitro, in a diphasic system; the horse strain fails to grow in such a system. Differences have also been demonstrated between the soluble proteins of the two strains. The sheep strain is infective to man but, probably, non-infective to horses. The horse strain (which is now the major strain in the U.K. and Ireland) appears to be poorlq infective to sheep and may prove to be non-infective to man. The importance of determining the basic characteristics of other strains of E. granuloslts are also stressed. Introduction and background Hydatid disease (hydatidosis, echinococcosis) is recognized as being one of the world’s major zoonoses. Its distribution is normally associated with underdeveloped countries or those with a large rural population where public health measures are difficult to enforce (e.g. Cyprus, New Zealand, Australia). The general pattern of the life-cycle is well established; the eggs of the causative organism, the dog tapeworm, E. granulosus, when ingested by man or a wide range of ungulates (e.g. sheep, cattle, pigs, goats, horses, camels, buffaloes, etc.) develop into hydatid cysts, the presence of which gives rise to the clinical symptoms of hydatid disease. Dogs become infected by eating hydatid cysts. Human hydatidosis is relatively rare in this country, the Public Health statistics giving an annual overall average of only 0.3 human cases per million (THOMPSON & SMYTH, 1975). Until recently, most of the reported cases have been in Wales (WEST, 1960) but, recently, several cases have been reported from the Isle of Skye (WILLIAMS & ROCHE, 1974). In some sheep-raising countries (e.g. New Zealand), a comparable figure of 43.5 human cases per million was reported IO years after the Second World War. In other countries, where mandog contact is exceptionally close or where other epidemiological conditions are especially favourable, much higher figures occur. Within recent years, however, the epidemiological picture in the United Kingdom has changed dramatically with a remarkable and unexpected rise in the prevalence of hydatidosis in horses (Fig. 1) to a level which now exceeds 60% (THOMPSON& SMYTH, 1975). The implica-
70. 60.
01 /, 1920
1930 1940 1950 1960 1970 Year
Fig. I. Incidence of equine hydatidosis in the U.K. (after THOMPSON& SMYTH,1975; scatter points omitted). tions of this situation, with respect to its potential as a health hazard to man, form the main topic of this paper. Speciation in Echinococcus General account Speciation in the genus Echinococcus has long been a matter of controversy and the question has been the subject of a number of reviews (SMYTH, 1964, 1969; VERSTER,1969; RAUSCH, 1967). It is generally accepted that two main species of Echinococcus are responsible for hydatid disease: (a) E. grunulosus which develops in dogs but generally not in foxes (but see page 95), and which mainly utilizes ungulates as intermediate hosts. It causes unilocular hydatid disease. (b) E. multilocularis which matures in foxes and cats as well as other Canidae and utilizes microtine rodents as its intermediate hosts. It causes alveolar hydatid disease. In Russia, this form is regarded as belonging
94
SYMPOSIUMON HYDATID DISEASE
to a different genus, Alveococcus. The epidemiology has been reviewed by LUKASHENKO(1971). This is probably an oversimplification of a complex speciation problem, and SMYTH & SMYTH (1964) have suggested that a “continuum” of “species” exists between E. granulosus and E. multilocularis. This view is based on the fact that examples of “E. which do not fall easily into either E. granulosus”, granulosus or E. multilocularis, have been found. Thus, a form of E. granulosus which can develop to maturity in foxes has been reported from Bulgaria (MATOFF & YAUCHEV, 1965). Again, in India, GILL & RAO (1967) have reported the occurrence of an “E. granulosus” with a dog/buffalo cycle, which differs from the “classical” descriptions of this species. The matter is further complicated by the discovery of a number of other species in South America, e.g. E. oligarthrus (SOUSA & THATCHER, 1969) and E. vogeli (RAUSCH & BERNSTEIN, 1972), which differ morphologically from E. granulosus and E. multilocularis. These species involve wild tropical felid species (puma, jaguar, jaguarundi, bush dog) and need not concern us here. Genetical basis for strain development in Ehinococcus
As mentioned above, it has been speculated that speciation in Echinococcus is a complex matter with (possibly) well-defined species at each end of a hypothetical scale having morphological, physiological and
ORIGINALWILD TYPE ++
‘;
II +
suppose mutant -genep [recessive] appears :.::: ..:: 233
Echinococcus.
(a) Most adult tapeworms are self-fertilizing hermaphrodites, and self-fertilization has been demonstrated in E. grandosus (SMYTH & SMYTH, 1969). Hence, if a mutation occurs involving the appearance of (say) a recessive gene (c Fig. 2) it can occur in both eggs and sperm, with the result that a double recessive (rr Fig. 2) may be readily formed. (b) The larva (i.e. hydatid) reproduces asexually (by polyembrony?) so that once an oncosphere becomes established in a new host, a large population (or clone) of, perhaps a million, genetically identical individuals bearing the new, double recessive gene rr can be formed. The way in which these characteristics could combine to express a recessive mutation (which would normally be lost) is shown in Fig. 2.
genotypes of oncospheres
++ v
