murdoch research repository · 2014-11-24 · incidence of cystic hydatid disease in australia, and...
TRANSCRIPT
MURDOCH RESEARCH REPOSITORY
This is the author’s final version of the work, as accepted for publication following peer review but without the publisher’s layout or pagination.
The definitive version is available at http://dx.doi.org/10.1016/j.ijpara.2014.07.005
Thompson, R.C.A. and Jenkins, D.J. (2014) Echinococcus as a model system: biology and epidemiology. International Journal
for Parasitology, 44 (12). pp. 865-877.
http://researchrepository.murdoch.edu.au/23613/
Copyright: © 2014 Elsevier B.V.
It is posted here for your personal use. No further distribution is permitted.
1
2
45
6
7 Q1
89
101112
1 4
1516171819
20212223242526272829
3 0
44
45
46
47 Q2
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
Contents lists available at ScienceDirect
International Journal for Parasitology
journal homepage: www.elsevier .com/locate / i jpara
Invited Review
Echinococcus as a model system: biology and epidemiology
http://dx.doi.org/10.1016/j.ijpara.2014.07.0050020-7519/� 2014 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.
⇑ Tel.: +61 8 9360 2466; fax: +61 8 9310 4144 (R.C.A. Thompson). Tel./fax: +61 026933 4179 (D.J. Jenkins).
E-mail addresses: [email protected] (R.C.A. Thompson), [email protected] (D.J. Jenkins).
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus as a model system: biology and epidemiology. Int. J. Parasitol. (2014)dx.doi.org/10.1016/j.ijpara.2014.07.005
R.C.A. Thompson a,⇑, D.J. Jenkins b,⇑a School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA 6150, Australiab Animal and Veterinary Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia
313233343536373839404142
a r t i c l e i n f o
Article history:Received 11 June 2014Received in revised form 19 July 2014Accepted 21 July 2014Available online xxxx
Keywords:EchinococcusDevelopmentCytodifferentiationHost–parasite interfaceTaxonomyEpidemiologyWildlifeDomestic hosts
a b s t r a c t
The introduction of Echinococcus to Australia over 200 years ago and its establishment in sheep rearingareas of the country inflicted a serious medical and economic burden on the country. This resulted inan investment in both basic and applied research aimed at learning more about the biology and life cycleof Echinococcus. This research served to illustrate the uniqueness of the parasite in terms of developmen-tal biology and ecology, and the value of Echinococcus as a model system in a broad range of research,from fundamental biology to theoretical control systems. These studies formed the foundation for aninternational, diverse and ongoing research effort on the hydatid organisms encompassing stem cellbiology, gene regulation, strain variation, wildlife diseases and models of transmission dynamics. Wedescribe the development, nature and diversity of this research, and how it was initiated in Australiabut subsequently has stimulated much international and collaborative research on Echinococcus.
� 2014 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.
43
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
1. Introduction
Echinococcus remains a major cause of zoonotic diseases of pub-lic health and economic significance (Jenkins et al., 2005a; Budkeet al., 2006; Davidson et al., 2012; Hegglin and Deplazes, 2013).Despite advances in control strategies, clinical management andvaccine development, the parasite continues to thrive in countriesthroughout the world.
Hydatid disease, cystic and alveolar, is a typical cyclozoonosisthat can be perpetuated in nature in wild animal cycles withoutimpacting on public health but with human interference(Thompson, 2013), directly or accidentally, with spillover todomestic cycles can lead to severe clinical disease and death. It isalso an important cause of economic losses to livestock industries,particularly Echinococcus granulosus in sheep and cattle (Table 1).
It is now well known that Echinococcus has a two-host life cyclewith a sexual stage in the intestine of a carnivore definitive hostand a unique, cystic larval stage in the tissues of non-carnivorousmammals and omnivores (Thompson, 1995). It is interesting thatmuch of the research that revealed the unique features of the par-asite’s way of life were undertaken in Australia. This is not a coin-cidence and relates to the impact Echinococcus had on a developing
88
89
90
91
agricultural society following early European settlement of a con-tinent with huge temperate areas perfect to exploit for raisinglivestock.
It was the upsurge in sheep farming at the end of the 19th cen-tury, with expanding exports to Europe, that contributed to theserious and largely undocumented human health problem thatexisted during the late 19th and early 20th centuries (Gemmell,1990). During the first half of the 20th century, there was a highincidence of cystic hydatid disease in Australia, and to a lesserextent alveolar hydatid disease, either contracted in Australia(E. granulosus) or in migrants from endemic areas overseas(E. granulosus and Echinococcus multilocularis) (Dew, 1935). Therewas thus a need for regular surgical intervention. It was surgeonssuch as Harold Dew who had an interest in the basic biology ofthe parasite and who published in international journals such asthe ‘‘British Journal of Surgery’’ and ‘‘British Medical Journal’’ thatled to widespread recognition of the research being undertakenon hydatid disease in Australia. This was enhanced by Dew’s con-tributions in the literature (Dew, 1953) and at conferences to thedebate raging at the time on whether cystic and alveolar hydatiddisease were caused by the same or different species of Echinococ-cus (‘dualists’ versus ‘monists’) as well as his collaboration withresearchers in Europe such as Félix Dévé.
Dew recognised the developmental differences of the twostages in the life cycle and studied the metacestode stage of thecystic and alveolar forms (Fig. 1) in depth, both in human cases
, http://
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
Table 1Current taxonomy of Echinococcus spp.
Species Strain/genotype Known intermediate hosts Known definitive hosts Infectivity tohumans
Echinococcus granulosus Sheep/G1 Sheep (cattle, pigs, camels, goats, macropods) Dog, fox, dingo, jackal and hyena YesTasmanian sheep/G2 Sheep Dog, fox YesBuffalo/G3 Buffalo Dog Yes
Echinococcus equinus Horse/G4 Horses and other equines Dog Probably notEchinococcus ortleppi Cattle/G5 Cattle Dog YesEchinococcus canadensis Cervids/G8,G10 Cervids Wolves, dog YesEchinococcus intermedius Camel/Pig/G6/G7 Camels, pigs, sheep Dog YesEchinococcus felidis Lion/– Warthog (possibly zebra, wildebeest,
bushpig, buffalo, various antelope, giraffe,hippopotamus)
Lion Uncertain
Echinococcusmultilocularis
Some isolatevariation
Rodents, domestic and wild pig, dog, monkey Fox, dog, cat, wolf, racoon-dog,coyote
Yes
Echinococcus shiquicus –/– Pika Tibetan fox UncertainEchinococcus vogeli None reported Rodents Bush dog YesEchinococcus oligarthrus None reported Rodents Wild felids Yes
Data from: Thompson et al. (1995), Thompson and McManus (2002), Jenkins et al. (2005a), Thompson (2008), and Carmena and Cardona (2014).
host tissue
adventitial layer
laminated layer
germinal layer
a
b
c
d
d
e
distantmetastaticfoci
circulation
vesicles
protrusions of germinal layer
E. granulosus
E. multilocularis
A
B
Fig. 1. Diagrams illustrating the structural differences between the metacestodes of(A) Echinococcus granulosus (a–d, stages in development of protoscoleces and broodcapsule; e, daughter cyst) and (B) Echinococcus multilocularis (redrawn fromThompson, 1995).
2 R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
and animals (Dew, 1922, 1925, 1928, 1935). He thus comple-mented much of Dévé’s research undertaken in rodents (Dévé,1919, 1946) and built on this. Dew demonstrated that an intactlaminated layer was a fundamental and unique component of the‘healthy’ hydatid cyst and considered this layer to be of host origin,and demonstrated that elements of the cyst wall (germinal layer)could regenerate (Dew, 1935). He realised that the cyst encloseda sterile environment and was under intracystic pressure, andspeculated on the reasons for this being indicative of viabilityand a function of the germinal layer. In observations of what wenow know to be the metacestode of E. multilocularis, Dewdescribed naked prolongations of the nucleated germinalmembrane (layer) in direct contact with host tissues (Dew,1935), a fundamental feature of the infiltrating metastatic meta-cestode of E. multilocularis (Fig. 1) subsequently described usingelectron microscopy 60 years later (Mehlhorn et al., 1983; andsee Section 2.4). Thus it was Harold Dew that led to Australia beingreferred to as the ‘home of hydatids’ in terms of research. He pavedthe way for other researchers and did much to establish Echinococ-cus as a model organism. ‘‘In this country of Australia we all haveunrivalled opportunities to investigate this disease, both in manand in animals, and it is our duty to contribute our share to futureadvances in its study’’ (Dew, 1935).
The economic impact and public health significance of cystichydatid disease in Australia worsened over the next 30 years,which provided an opportunity for obtaining research funds fromorganisations supporting health and livestock research. J.D. Smythobtained funds from these sources and took a physiologicalapproach in his research aimed at increasing understanding ofthe developmental biology of Echinococcus. Having forged an inter-est in developing in vitro cultivation procedures for Schistocephaluswith success in establishing much of the life cycle of this cestode inculture (Smyth, 1946, 1950), he turned his attention to Echinococ-cus (see Smyth, 1990) for which the ability to study and maintainthe parasite in vitro would provide a great research tool for inves-tigating methods of control.
The practical and ethical difficulties of undertaking in vivo stud-ies in the canid or felid definitive hosts of Echinococcus further rein-forced the need to develop in vitro systems. It was these pioneeringstudies of Smyth (Smyth et al., 1966 and reviewed in Smyth andDavies, 1974a; Howell and Smyth, 1995) that demonstrated thepotential of Echinococcus as a model for studying principles ofdevelopmental biology, differentiation, host–parasite relationshipsand evolutionary biology (Smyth, 1969; Smyth et al., 1966), andwhich have influenced research and theoretical understanding farbeyond parasitology (Thompson and Lymbery, 2013). Smyth saw
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
the potential of exploiting Echinococcus as a novel model systemfor studying parasitism as distinct from a model for studies onevaluating anthelmintic or other anti-parasitic drugs (Smyth,1969). He thus expanded the definition of a ‘model’ to embrace
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx 3
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
studies on all the biological activities that supported the parasitelife style of Echinococcus, as well as the potential of this model sys-tem for broader studies of a more fundamental nature in biology,for example stem cells (Smyth, 1969, 1987). As such the promotionof such a eukaryotic, metazoan model was at the time somewhat ofa ‘first’.
Smyth worked closely with his Australasian colleague MichaelGemmell, who also had an interest in Echinococcus but who waskeen to understand the epidemiology of hydatid disease, its eco-nomic impacts and impediments to control (Gemmell, 1990). Assuch, he was the first to apply mathematical models to Echinococ-cus and the concept of the basic reproductive rate (R0) in order todefine the conditions under which transmission of Echinococcusand other taeniids occur, and the regulatory role of immunity(Gemmell, 1990; Gemmell and Roberts, 1995).
In this review, we describe the research, particularly thatundertaken in Australia, which has demonstrated the value of Echi-nococcus as a model system influencing advances in biology andepidemiology of parasites and parasitic infections.
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
2. Developmental biology
2.1. Growth and maturation
Echinococcus has two developmental stages in its life cycle; theadult tapeworm, which is the sexual stage, and the cystic or infil-trative larval metacestode that reproduces asexually (Fig. 1). Themetacestode of E. granulosus, which was easily accessible frominfected livestock in the abattoir or from human surgical cases,was the logical starting point for experimental manipulations. Ini-tially, these were undertaken in rodents where the asexual prolif-erative nature of the parasite was first observed, a phenomenonthat was subsequently exploited with the development of rodentmodels of secondary hydatidosis (Dévé, 1919). These provided ameans to maintain the parasite virtually indefinitely in vivo byserial passage (e.g., Thompson, 1976; Whitfield and Evans, 1983;Kamiya et al., 1985).
Although a number of workers had reported vesicular/cysticdevelopment and proliferation of protoscoleces in vitro, a majorgoal was to provide appropriate conditions to stimulate and sup-port development in an adult (strobilate) direction. It was not untilSmyth and his colleagues refined procedures with the aim toreproduce the conditions that protoscoleces would be exposed toin the gut of the definitive host that strobilate development wasobtained (Smyth et al., 1966). Smyth took a physiological approachto this research, with the cyst as a starting point. Its sterile environ-ment provided the perfect ‘entry point’ if accessed aseptically tocarefully remove essentially ‘dormant’ invaginated protoscolecesand then expose them to appropriate physiochemical conditions(Smyth and Davies, 1974a). Of particular significance was the pro-vision, in addition to the liquid medium, of a solid proteinaceousbase in the culture flask (diphasic medium) which was found tobe important in stimulating proglottisation and segmentation inE. granulosus with maturation to the pre-fertilisation stage(reviewed in Smyth and Davies, 1974a; Howell and Smyth,1995). Similar results were obtained with E. multilocularis butproglottisation without segmentation will take place without asolid proteinaceous base (Smyth and Davies, 1975; Smyth, 1979;Thompson et al., 1990). This and other developmental abnormali-ties observed in E. multilocularis were considered to reflect a differ-ence in gene expression between the two species (Howell andSmyth, 1995 and see Section 2.3). Although the conditions devel-oped supported reproducible strobilate development, fertilisationand egg production eluded Smyth and other workers. However,they served to emphasise the complexity of the process and to
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
support observations made from in vivo and population geneticstudies of the importance of the host intestinal ecosystem inproviding the correct physical and physiochemical conditionsnecessary to support fertilisation (Smyth, 1982; Smyth andDavies, 1974a; Lymbery and Thompson, 1988, 2012; Lymberyet al., 1989; Howell and Smyth, 1995).
The success with cultivating Echinococcus and the elucidation ofconditions that would support maturation stimulated studies onother taeniids including Taenia pisiformis and Taenia crassiceps(Esch and Smyth, 1976; Osuna-Carrillo and Mascaró-Lazcano,1982), as well as Mesocestoides corti (Barrett et al., 1982;Thompson et al., 1982). These largely supported the observationsmade with Echinococcus but also served to illustrate the unique-ness of the Echinococcus model system.
During the 25 years Smyth and his colleagues spent studyingand optimising strobilate development and maturation of Echino-coccus in vitro, many valuable observations were made that haveserved to establish Echinococcus as a model system not only interms of developmental biology, but also for cytodifferentiationand the host–parasite interface.
2.2. Developmental plasticity
Studies on the in vitro cultivation of Echinococcus from thelarval protoscolex to the adult worm demonstrated the inherentplasticity of the parasite – a phenomenon eloquently describedas ‘heterogeneous morphogenesis’ (Smyth et al., 1967; Smyth,1987), unique in most metazoan organisms apart from coelenter-ates such as Hydra, and making Echinococcus an unusual modelfor differentiation studies. Depending upon the culture conditions,protoscoleces can either develop in a cystic or adult direction. Cys-tic development itself may take a variety of paths, again influencedby environmental conditions. These alternative developmentalpathways have been described in detail by Howell and Smyth(1995). Protoscoleces can also develop into an adult tapewormunder different conditions to those supporting cystic development,most importantly the need for a diphasic medium incorporating asolid supporting substrate thought to provide nutrients and/or acontact stimulus (see Section 2.1). However, observations on thedevelopment of adult E. granulosus and E. multilocularis demon-strated that in addition to ‘normal’ worms, cultures often con-tained worms that had matured but not segmented (monozoic)and worms with more than one scolex and other malformations(reviewed in Howell and Smyth, 1995). Interestingly, adult wormsthat have developed from protoscoleces can ‘de-differentiate’ in acystic direction under adverse conditions (see Sections 2.3 and2.4; Smyth, 1969; Thompson and Lymbery, 1990; Thompsonet al., 1990). These observations raised two important and funda-mental questions: how is this complex and plastic developmentcontrolled and what cells have the potential to develop in such amyriad of different routes?
2.3. Developmental control
Smyth developed a hypothetical yet logical model to explainhow genes regulate differentiation and developmental shifts inEchinococcus (Smyth, 1969). This was based on the Jacob–Monodmodel of genetic expression and showed the complex interactionsand regulatory switches that may be involved in controlling devel-opment and differentiation in Echinococcus. Since then a number ofstudies have isolated and characterised regulatory genes from Echi-nococcus (reviewed in Thompson, 1995 and Parkinson et al., 2012)but how they fit together in a control network has yet to be deter-mined. Recently, Parkinson et al. (2012) identified long non-coding(nc)RNAs that may be involved in the regulation of gene expressionin response to environmental cues in the host. They also identified
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294 Q3
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
4 R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
a number of genes reflecting specificities of particular stages,including those whose expression is up-regulated by pepsin-acidactivation. It is to be hoped that Smyth’s models will help to pro-vide functionality to the genomic data that is now available forboth E. granulosus and E. multilocularis (Tsai et al., 2013; Zhenget al., 2013). However, differences in development between E.granulosus and E. multilocularis highlighted by studies in vitro areconsidered to reflect differences in the control of gene expression(Howell and Smyth, 1995).
2.4. Cytodifferentiation
Slais (1973) demonstrated that the post-oncospheral develop-ment of Echinococcus was initiated by the growth and division ofprimary germinal cells, and Swiderski (1983) described five pairsof these cells in the posterior pole of the oncosphere. Observationson the development of Echinococcus in vitro demonstrated that thefundamental processes of germinal and somatic differentiation,comprising cystic development, proglottisation, maturation,growth and segmentation (strobilisation), can take place indepen-dently. This not only illustrated the complexity of cytodifferentia-tion but also the possible existence of several primitive cell lines.However, to date all the evidence suggests that only one primitivemorphological cell type exists as a pool of uncommitted, undiffer-entiated multipotent germinal, or stem, cells in both the adult andmetacestode (Smyth, 1969; Gustafsson, 1976; Thompson et al.,1990; Thompson, 1995; Koziol et al., 2014). The undifferentiatedgerminal cells are a component of the syncytial germinal layer ofthe metacestode and neck region of the adult cestode. Ultrastruc-tural studies reveal unremarkable rounded cells of variable sizeof approximately ? lm diameter (Gustafsson, 1976; Mehlhornet al., 1983; Albani et al., 2010). Cell proliferation derives fromthe continuous replicative activity of these dividing stem cellslocated in the germinal layer or neck region of the adult tapeworm(Gustafsson, 1976; Galindo et al., 2003). They have considerableproliferative potential (Eckert et al., 1983; Mehlhorn et al., 1983;Galindo et al., 2003; Martínez et al., 2005), and are the only prolif-erating cells in Echinococcus (Koziol et al., 2014). This is particularlywell illustrated by the capacity of the parasite for indefinite perpet-uation in the larval stage by passage of protoscoleces or germinallayer material in rodents (secondary hydatidosis; Howell andSmyth, 1995). In alveolar hydatid disease caused by the metaces-tode of E. multilocularis, the proliferating larval parasite has aninfiltrative capacity to establish distant foci of infection due tothe distribution via blood or lymph of detached germinal cells(Ali-Khan et al., 1983; Eckert et al., 1983; Mehlhorn et al., 1983;Fig. 1).
Problems with host cell contamination dogged early attemptsto establish germinal cell lines of E. granulosus and E. multilocularis(reviewed in Howell and Smyth, 1995). In addition, their isolationfrom the germinal layer, and their in vitro propagation, could havebeen hampered by the fact that the germinal layer is a syncytium.However, the establishment and long-term perpetuation of Echino-coccus germinal cells has now been achieved for both species(Yamashita et al., 1997; Spiliotis and Brehm, 2009; Spiliotis et al.,2008; Albani et al., 2010). The germinal cells behave similarly toclassical stem cells with the formation of cell aggregates and clus-ters with cavity formation, and there is cytological evidence oftransformation (Spiliotis et al., 2008; Albani et al., 2013).
Galindo et al. (2003) found evidence of the regionalisation ofDNA and protein synthesis in developing stages of Echinococcus,although no morphological evidence has been found of differentprimitive or germinal cell lines to explain the concept of heteroge-neous morphogenesis (Smyth, 1969). However, such heterogeneityhas now been confirmed at the molecular level. Germinal cells arein fact heterogeneous, with the existence of subpopulations with
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
different gene expression patterns (Koziol et al., 2014), thus con-firming Smyth’s predictions.
2.5. Host–parasite interface
2.5.1. Definitive hostObservations that contact of the scolex with a proteinaceous
base stimulated strobilate development in E. granulosus led tostudies on the nature of the interface both in vitro and in vivo,and the discovery of the rostellar gland which comprises a modi-fied group of tegumental cells situated in the apical rostellum(Smyth, 1964; Smyth et al., 1969; Thompson et al., 1979;Thompson and Eckert, 1983; Fig. 2). The rostellar gland releasessecretory material by a holocrine process into the interfacebetween parasite and host (Thompson et al., 1979). The originand site of synthesis of the secretion has still to be determined,although large amounts occur in both the perinuclear and distalcytoplasm of the tegument as well as in the tegumental nuclei(Thompson et al., 1979; Herbaut et al., 1988). The secretion is pro-teinaceous, containing cystine and lipid. It is not known if there areone or more proteins secreted but Siles-Lucas et al. (2000) demon-strated that the secretion contains a regulatory protein (14-3-3)that is released into the host–parasite interface.
The rostellar gland of Echinococcus is seemingly unique to Echi-nococcus. Although rostellar secretions have been described in lar-val T. crassiceps (Krasnoshchekov and Pluzhnnikov, 1981), no glandhas been described. Rostellar glands have been described in otheradult cestodes, particularly proteocephalids, but their function isalso unclear and structurally they are different to the rostellargland in Echinococcus (McCullough and Fairweather, 1989;Zd’árská and Nebesárová, 2003). There is clearly a need for morestudies on the interface of attached adult cyclophyllidean cestodes(Pospekhova and Bondarenko, 2014).
This intimate association of the rostellar gland and its secre-tions suggests a role(s) that enhances the host–parasite relation-ship in favour of the parasite, which may be regulatory,nutritional and/or protective. The relationship between rostellargland activity and localised humoral and cellular reactions(Deplazes et al., 1993) is not known but such localised reactionsdemonstrate stimulation of host immune effector mechanisms.The secretory molecules would seem to be obvious candidatesfor exploitation in vaccine studies since a focus on prophylaxis ofthe definitive host may be more attractive than the intermediatehost, particularly for the control of E. multilocularis, from both com-mercial and practical perspectives. As pointed out by Heath (1995)the scolex is in intimate contact with the systemic circulation evenin the Peyers patches and would appear to maintain its privilegedintegrity by suppression of cytotoxic and effector cell activity inthe region of the scolex.
The few studies on definitive host vaccines do not seem to havetargeted rostellar gland secretions and have produced resultswhich are controversial and open to contrasting interpretation(Zhang et al., 2006; Petavy et al., 2008; Torgerson, 2009;Kouguchi et al., 2013). The studies by Petavy et al. (2008) demon-strated a strong inflammatory response in the intestine of vacci-nated compared with infected controls but did not show if thiswas localised to where worms were situated. More recently,Kouguchi et al. (2013) used a surface glycoprotein from E. multiloc-ularis as a vaccine in dogs which induced significant protectionwhen administered via a mucosal route and demonstrated anti-bodies raised by their vaccine on the surface of the suckers, rostellaand hooks. These results emphasise the importance of characteris-ing the secretions produced by the rostellar gland of Echinococcuswhich will contribute to the further development of vaccinesagainst the adult parasite. Unfortunately in vivo studies requireresearch on the definitive host, usually dogs, which is ethically
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
A B
Fig. 2. Diagram illustrating adult Echinococcus in situ in the intestine, with suckers on the scolex grasping the epithelium at the base of the villi. Rostellum is deeply insertedinto a crypt of Lieberkühn (A, B) and extensibility of the apical rostellar region is shown in B. Rostellar gland with secretory material is anterior to the rostellar pad (r).
R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx 5
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
challenging and hazardous if patent infections are maintained.Thus reports of successful patent infections in experimentallyinfected immunosuppressed rodents (Kamiya and Sato, 1990a,b)were regarded as an important breakthrough (Howell and Smyth,1995; Thompson, 1995). Unfortunately, these results have notbeen further exploited and should perhaps form the basis forfuture research.
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
2.5.2. Intermediate hostA unique interface is also found in the intermediate host where
the laminated layer presents a physiochemical barrier with appar-ent multifunctionality and a structure whose biosynthesis hasbecome a model system for carbohydrate chemistry (Diaz et al.,2011a,b; Parkinson et al., 2012). The laminated layer is a specia-lised extracellular matrix unique to Echinococcus (Fig. 1), whosesynthesis is a major metabolic activity of the much thinner germi-nal layer (Diaz et al., 2011a; Lin et al., 2012; Parkinson et al., 2012).The origin of the laminated layer was controversial for some time,i.e. whether it is entirely of parasite origin or if there is a host con-tribution. Holcman and Heath (1997) demonstrated that it isentirely of parasite (germinal layer) origin by studying the earlystages of cyst development from oncospheres in vitro.
Considerable metabolic activity in the germinal layer isrequired to synthesise and maintain the interfacial barrier of thelaminated layer (Parkinson et al., 2012). The role of the laminatedlayer would appear to be one of protection since cyst survival isdependent upon its integrity (Gottstein et al., 2002). Whether thisis purely physical or if there is selective permeability is not known.Monteiro et al. (2010) identified several molecules in hydatid cystfluid that could play a role in host evasion. Smyth commented onthe significance of the presence of a human blood group P-like sub-stance in the laminated layer of Echinococcus and its significance asa model system in better understanding the immunological basisof the host-parasite relationship. This P1 blood-antigen motif hassince attracted much attention and has been further characterisedas a protein-carbohydrate, trisaccharide/mucin complex contain-ing galactosamine, yet no biological function has been described
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
to date (Lin et al., 2012). There is also increasing evidence of theimmune-regulatory role of the laminated layer, probably in associ-ation with the immuno-modulatory activities of the glycoproteinsknown as Antigen 5 and Antigen B (Diaz et al., 2011b).
2.6. Taxonomy and speciation
One of the most important observations made as a result ofstudies on the in vitro cultivation of Echinococcus was the failureof protoscoleces collected from hydatid cysts in horses to developin the same way as those of sheep origin. Protoscoleces from horsesevaginated and increased in length but failed to undergo proglotti-sation or segmentation, even though they were grown in exactlythe same diphasic medium (Smyth and Davies, 1974b). This fairlysimple observation resulted in radical shifts in our understandingof the epidemiology of hydatid disease and transmission of theaetiological agents as well as their taxonomy and phylogeneticrelationships. The results demonstrated that there were funda-mental physiological differences between E. granulosus of sheepand horse origin and the coining of the term ‘physiological straindifferences’ (Smyth and Davies, 1974b; Smyth, 1982). This had abroad influence beyond Echinococcus, and in particular the impor-tance of combining phenotypic and genetic differences in the char-acterisation and description of parasites at the intraspecific level(Thompson and Lymbery, 1990, 1996; Lymbery and Thompson,2012).
In terms of Echinococcus, the observation of physiological differ-ences between the two parasites of sheep and horse origin comple-mented earlier epidemiological and taxonomic studies onEchinococcus of horse origin (Williams and Sweatman, 1963). Thesedemonstrated morphological differences between the two formswhich were considered to be taxonomically significant, and toreflect differences in host specificity and the life cycles whichmaintained the two parasites. This was subsequently shown tobe correct with the sympatric occurrence of distinct sheep- andhorse-dog cycles in several European countries (Thompson andSmyth, 1975; Thompson, 2001; Gonzalez et al., 2002). In addition,
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
6 R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
epidemiological evidence has not only demonstrated distinct dif-ferences in intermediate host specificity but also that, unlike thesheep strain (E. granulosus), the horse strain (Echinococcus equinus)(Table 1) does not appear to be infective to humans (Thompsonand Lymbery, 1988, 1991).
The concept of host-adapted strains of E. granulosus led to stud-ies on other forms of the parasite in other species of intermediatehosts such as cattle, pigs, camels and cervids. These studies notonly confirmed the existence of a number of host-adapted lifecycles in different parts of the world but also provided additionaldata on developmental differences between strains which mayimpact on control (reviewed in Thompson and Lymbery, 1988;Thompson et al., 1995; Thompson, 2008).
Subsequent molecular characterisation of host-adapted strainsof Echinococcus, coupled with molecular epidemiological studiesin endemic areas, has confirmed their genetic and morphologicaldistinctness and revealed phylogenetic relationships which sup-port a robust, meaningful taxonomy based on a previously sug-gested nomenclature (Table 1; Bowles et al., 1994; Thompsonet al., 1995, 2006; Cruz-Reyes et al., 2007; Harandi et al., 2002;Thompson and McManus, 2002; Lavikainen et al., 2003; Jenkinset al., 2005a; Romig et al., 2006; Moks et al., 2008; Thompson,2008; Huttner et al., 2009; Saarma et al., 2009; Nakao et al.,2013). Interestingly, the nomenclature used for these ‘species’ con-forms to that proposed by observational parasitologists in the1920s–1960s, before molecular tools were available to confirmtheir morphological descriptions and epidemiological observations(Thompson et al., 1995; Thompson and McManus, 2002;Thompson, 2008).
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
3. Epidemiology of E. granulosus in Australia
3.1. Introduction
Much of the basic knowledge regarding the epidemiology andcontrol of E. granulosus in Australia was generated by MichaelGemmell. His contribution to the field has been immense; thebreadth of his studies were wide, covering the impact of climateon egg longevity, immune responses against the parasite in defin-itive and intermediate hosts, prevalence in domestic dogs and live-stock, studies on infection in wildlife and mathematical modellingof transmission as an aid to more effective control (Gemmell andLawson, 1986). Gemmell’s work has provided a solid platform formany of the current studies reviewed below. However, probablyhis greatest legacy was his contribution to the development ofstrategies for the control of E. granulosus transmission. Neverthe-less, in the Australian situation, although control of E. granulosus,domestically, has largely been achieved (Jenkins et al., 2014), thepresence of an extensive wildlife reservoir on mainland Australiaensures the compete eradication of E. granulosus is unlikely to everbecome a reality. Further, unlike the situation with E. multilocularisand Echinococcus canadensis which are maintained in natural wild-life cycles, the wildlife cycle in Australia is an artificial one estab-lished as a result of anthropogenic activities and spillover fromdomestic cycles (Thompson, 2013).
The work of Gemmell had broad ramifications internationally interms of the epidemiological principles of hydatid control. Manysubsequent hydatid control programmes world-wide looked atGemmell’s critical analysis of the epidemiology in Australia andNew Zealand and based their programmes on his data. Theseserved as a foundation for the development of control programmesin many countries, and the epidemiological principles he devel-oped similarly have been used as a model (Eckert et al., 2001).
Echinococcus granulosus is the only member of the genus tooccur in Australia, having been introduced with domestic dogs
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
and livestock, mainly sheep, during European settlement(Gemmell, 1990). Domestically, the parasite spread rapidlythrough sheep and dog populations (Gemmell, 1990), due mainlyto a complete lack of understanding of the association betweentaeniid tapeworms in dogs and cysts in sheep. It was not until1851, (63 years after the first European settlers and their animalsarrived in Australia) that infection experiments were undertaken,demonstrating the relationship between cysts and tapeworms.Küchenmeister, working in Germany, fed metacestodes of T. pisi-formis to foxes and obtained tapeworms (Küchenmeister, 1851)and in 1853 fed tapeworm eggs to sheep and obtained metaces-todes. In the next few years von Siebold and Küchenmeister, work-ing independently, fed protoscoleces of Echinococcus to dogs andobtained tapeworms (von Siebold, 1853; Küchenmeister, 1855).An additional important infection experiment, also undertaken inGermany, was that of Naunyn in 1863 who fed protoscoleces froma human cyst to dogs and obtained adult E. granulosus, reportinghis results the same year. This experiment demonstrated for thefirst time the association between hydatid cysts of sheep andhumans and the role of dogs in the life cycle of human hydatidosis.However it was not until 1876 that Leuckart demonstrated eggs ofEchinococcus when fed to intermediate hosts (pigs) led to thedevelopment of hydatid cysts (Leuckart, 1876). A detailed reviewof the elucidation of the Taenia and Echinococcus life cycles canbe found in Grove (1990). Word of these discoveries took time toreach Australia but it was not long before experimental studieswere undertaken in Australia that confirmed Naunyn’s data(Thomas, 1884).
Hydatid disease soon became a major public health problem inthe growing population of new Australians (Gemmell, 1990) caus-ing serious illness and leading to the deaths of many colonists.
3.2. Wildlife hosts of E. granulosus in Australia
Data generated in studies on wildlife in Australia have world-wide relevance, an example being the work of Barnes (Barneset al., 2007a,b, 2008, 2011) investigating the health impacts andgrowth rate of hydatid cysts in macropodids. Barnes showed thathydatid cysts have a major impact on respiration capacity in mac-ropods, indicating infected animals to be more susceptible to pre-dation by wild dogs. This work complements and validates thestudies of Mech (1966) and Jolly and Messier (2004) in the USAwith respect to the impact of hydatid disease on moose (Alcesalces), rendering infected animals more susceptible to predationby wolves (Canis lupus). Another good example is the study onthe encroachment of E. granulosus-infected foxes (Vulpes vulpes)and wild dogs into urban areas in Australia and associated publichealth implications (Jenkins and Craig, 1992; Jenkins et al.,2008). These studies complement and support work undertakenin Europe with the encroachment into urban centres of foxesinfected with E. multilocularis (Deplazes et al., 2004) and studiesin Alberta, Canada on E. multilocularis in urban coyotes (Canislatrans) (Catalano et al., 2012).
Australian native wildlife species evolved in isolation from E.granulosus; consequently, they were highly susceptible to infectionwith this new parasite and wildlife species were soon acting as amajor sylvatic reservoir for the perpetuation of E. granulosus inAustralia (Durie and Riek, 1952), a situation that prevails today(Jenkins and Morris, 2003).
Initially, transmission of E. granulosus to macropodids occurredthrough accidental consumption of eggs spread in the environmentby the dogs of colonists. Infection in dingoes eventuated throughpredation of sheep on the recently established sheep farms. How-ever, it would not have been long before the dingoes themselvesbegan to spread eggs throughout their territories, exposing an everincreasing population of macropodids to infection with hydatid
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx 7
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
disease. Transmission of E. granulosus to wildlife from domesticanimals in the more remote areas of Australia was likely to havebeen enhanced through transhumance grazing (King, 1959). Trans-humance grazing was undertaken for over 100 years in the statesof New South Wales and Victoria, with the last ‘‘Snow Lease’’ inNew South Wales being revoked in 1972. In this process hundredsof thousands of sheep (and tens of thousands of cattle), accompa-nied by drovers and their dogs, were moved to the higher altitudesof the Great Dividing Range each summer to graze the alpine pas-tures. This was a highly organised process where families leaseddefined areas of pasture for their animals to graze for 3 - 4 monthseach year. Therefore, annually these pastures would have becomecontaminated with eggs from infected sheep dogs acting as asource of infection of both sheep and macropodids. Dingoes wouldhave been infected through predating on sheep and opportunistscavenging of dead sheep and offal discarded by the drovers whenthey killed a sheep to eat whilst staying on the lease.
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
Q4 692
693
694
695
696
697
698
699
700
701
702
703
704
705
3.2.1. DingoesThe Australian wildlife top-order predator coincidentally was a
placental canid, the dingo (Canis lupus dingo), introduced fromsouth-eastern Asia by visiting seafarers (Corbett, 1995). Dingoeswere medium sized wild dogs (11–17 kg) capable of killing sheep.
Settlers moving to Australia also brought their domestic dogsand it soon became evident that dingoes were able to breed withdomestic dogs and produce fertile hybrid offspring. The resulthas been that currently in most areas of remaining suitable habitatin south-eastern and eastern Australia the resident top order pred-ator populations no longer consist of pure-bred dingoes but mainlydingo/domestic dog hybrids with occasional pure-bred dingoes(Claridge et al., in press). Animals in these populations are referredto as wild dogs. Pure-bred dingoes are mostly restricted to remoteareas, especially in northern parts of Western Australia. Neverthe-less, there is no indication that hybrid dingoes are any more or lesssusceptible to infection with E. granulosus than pure-bred animalssince no difference in the range of worm burdens has been notedbetween hybrid and pure-bred dingoes (Jenkins and Morris,2003; Jenkins et al., 2008). The hunting and pack behaviours ofdingo hybrids compared with dingoes also appear to be similar(Claridge et al., in press). The one important physiological differ-ence between dogs and dingoes is breeding capacity; femaledomestic dogs come into oestrus twice each year whilst for din-goes it is only once. Data collected on the breeding behaviour ofdingo hybrids does not indicate they are having more litters peryear than pure-bred dingoes, but there have been reports that littersizes in hybrids are larger than those of pure-bred dingoes and thesize of wild dogs has increased approximately 20% during the last40 years (Claridge et al., in press).
Anecdotally, in many areas wild dog population numbersappear to be increasing, a likely combination of increased litter sizeand increased food resources due to environment modification.Provision of more pasture and watering points for livestock hasled to major increases in macropodid populations in many areas,providing increased food supply for wild dogs. With increased wilddog populations it is reasonable to assume that the biomass andrate of transmission of E. granulosus in wildlife is also increasing.
706
707
708
709
710
711
712
713
714
3.3. Echinococcus granulosus-infected wild dog encroachment intourban areas
With increasing wild dog numbers and the spread of urbanisa-tion into areas of hitherto wild dog habitat has displaced youngand old animals seeking new uncontested habitat. These animalsare encroaching into outer urban areas and bringing E. granulosuswith them (Brown and Copeman, 2003; Jenkins et al., 2008).
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
Reports of E. granulosus-infected wild dog encroachment intoouter suburban areas have begun to appear; Townsville (Brownand Copeman, 2003), Maroochy Shire (Jenkins et al., 2008), thenorth-western suburbs of Brisbane in the Pine River Shire, Queens-land and the outer suburbs of Katoomba in New South Wales (D.J.Jenkins, unpublished data). In a number of urban areas, wild dogshave become numerous and a public nuisance raiding garbagebins, killing domestic pets and menacing residents. They havebecome such a problem in a number of places that local authoritieshave employed professional wild dog controllers to remove themusing lethal methods. Examination of the intestines of some ofthese euthanised wild dogs from several locations has revealedhigh prevalences and heavy worm burdens of E. granulosus(Brown and Copeman, 2003; Jenkins et al., 2008). The establish-ment of peri-urban transmission cycles are unlikely, but regularencroachment of E. granulosus-infected wildlife definitive hostsinto outer suburbs of urban centres has been demonstrated(Brown and Copeman, 2003; Jenkins et al., 2008), which is difficultto control and likely to be an ongoing issue for local councils tomanage.
Hitherto, it was supposed urban human populations in Australiawere insulated from exposure to E. granulosus, and clearly, with theencroachment of E. granulosus-infected wild dogs (and foxes, seeSection 3.7.1) into urban areas this is no longer the case.
3.4. Australian native carnivores as definitive hosts for E. granulosus
Infection with adult E. granulosus has never been reported fromAustralian native marsupial carnivores. In 2005, Jenkins et al.undertook a small study investigating the faeces from wild-caughtspotted-tailed quolls (Dasyurus maculatus) for coproantigens of E.granulosus and reviewed the literature regarding experimentalinfection of dasyurids with E. granulosus. None of the quoll faecestested were found to be positive for coproantigens of E. granulosus(Jenkins et al., 2005b) and in none of the attempted experimentalinfections of several species of dasyurid have E. granulosus beenrecovered. From these data, Jenkins et al. (2005b) concluded thatdasyurids are refractory to infection with E. granulosus.
3.5. Wildlife intermediate hosts
Macropodid marsupials are highly susceptible to infection withthe intermediate stage of E. granulosus (Jenkins and Morris, 2003;Banks, 2006), often carrying multiple large metacestodes (hydatidcysts). This is especially the case in a number of wallaby species,namely swamp wallabies (Wallabia bicolor) in south-eastern Aus-tralia (Jenkins and Morris, 2003). Swamp wallabies are commonlyinfected with E. granulosus (Jenkins and Morris, 2003) and are alsoa favourite dietary item for wild dogs (Claridge et al., in press),making them pivotal in the transmission of E. granulosus in wildlifein south-eastern Australia. Other wallaby species appear to be ofsimilar importance in other parts of Australia (Banks et al., 2006a).
Curiously, on the island state of Tasmania macropodid marsupi-als never become infected with E. granulosus (Howkins, 1966),despite there having been high levels of transmission in domesticanimals. This may have been associated with the absence of din-goes and the presence of a dasyurid top order predator, the thyla-cine (Thylacine cynocephalus), refractory to infection with E.granulosus (see Section 3.4). Nevertheless, human hydatidosisbecame such a major public health problem in Tasmania that aprogram of intense control was introduced that continued for30 years (Beard et al., 2001).
Other species of native wildlife susceptible to infection with E.granulosus are wombats (Wombatus ursinus). However, hydatidinfection in wombats has only been reported once (Grainger andJenkins, 1996). Wombats are consumed periodically by wild dogs
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
8 R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
but appear to only be an occasional host for E. granulosus, thereforethey cannot be regarded as an important component of the E. gran-ulosus life cycle in Australia.
3.6. Factors contributing to the transmission success of E. granulosus inAustralian wildlife
Hydatid disease of macropodids is almost exclusively confinedto the lungs, causing major respiratory impairment (Jenkins andMorris, 2003; Barnes et al., 2007a,b, 2008, 2011) that may lead tothe death of the host (Johnson et al., 1998; Barnes et al., 2008).Why hydatid infection in macropods should be mainly confinedto the lungs is unclear, however, this is also seen with hydatidinfection in cervids (Schantz et al., 1995). Hydatid-infected macro-podids are rendered highly susceptible to predation by dingoes, asimilar situation to that with the interaction of wolves and hyda-tid-infected moose (A. alces) in the USA (Mech, 1966; Jolly andMessier, 2004). In addition, cysts in macropodids develop quickly,becoming fertile (containing protoscoleces) in 8–9 months (Barneset al., 2007a), compared with sheep where the earliest time to fer-tility is approximately 2 years (Slias, 1980). The increased suscep-tibility of hydatid-infected macropodids to predation by wild dogsmeans that wild dogs are catching and consuming a disproportion-ately large number of infected animals which is likely to be a majorcontribution to the high worm burdens seen in many wild dogs.Within all wild dog populations surveyed, a proportion of the sam-ple has been wild dogs with worm burdens in excess of 100,000 E.granulosus (Jenkins and Morris, 1991, 2003; Jenkins et al., 2008).These animals are the ‘‘super spreaders’’ of the population(Gemmell and Lawson, 1986), ensuring large numbers of eggsbeing released into the environment. The home range of wild dogsvaries depending on the sex of the animal and availability of foodand water; in eastern Australia home ranges average approxi-mately 100 km2 (Claridge et al., in press). Therefore large areascan become contaminated with eggs from a single animal, butsince packs of wild dogs consisting of several animals usuallyoccupy these spaces (Claridge et al., in press), contamination ofthe environment with faeces can become heavy in areas used com-monly by a resident pack.
The longevity of eggs of E. granulosus in the environment isthought to be several months to perhaps approximately 1 year,so long as the environment is not too hot and dry (Eckert andDeplazes, 2004). However, in a study in Argentina (Thevenetet al., 2005), E. granulosus egg-laden dog faeces were left in theenvironment for 41 months. After this time eggs were separatedfrom the faeces and fed to each of four sheep. Hydatid cysts devel-oped in each of the sheep, suggesting that the longevity of eggs ofE. granulosus in Australia under optimal conditions may be longerthan 12 months. Studies reported in Gemmell (1958) revealedthe most important environmental conditions required for trans-mission for E. granulosus in Australia to be at least 25 mm of rainfor 6 months of the year with temperatures up to 30 �C. Conse-quently, E. granulosus has become more prevalent in eastern Aus-tralia, in areas associated with the Great Dividing Range, and inan elevated area of Western Australia (Thompson et al., 1988;Jenkins and Macpherson, 2003) (Fig. 3).
3.7. Echinococcus granulosus in introduced wildlife species
3.7.1. FoxesThe first creditable report of E. granulosus infection in foxes in
Australia was by Gemmell (1959a) where a single terminalsegment was recovered from the intestine of one of 41 animalscollected in New South Wales. Nevertheless, based on the availableexperimental infection and survey data, Gemmell (1959a) felt thatAustralian foxes were not acting as a definitive host for
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
E. granulosus. More recently, E. granulosus have been recoveredfrom a number of naturally infected foxes in various studies(Thompson et al., 1985; Obendorf et al., 1989; Jenkins and Craig,1992; Reichel et al., 1994; Jenkins and Morris, 2003). Almostexclusively, worm burdens have been small, usually less than 50tapeworms/fox. However, in one study (Reichel et al., 1994) severalthousand E. granulosus in each of two foxes from Victoria werereported. These data are so at odds with all other existing fox E.granulosus worm burden data that they should be regardedcautiously. However, if corroborated then the role of foxes in thetransmission of E. granulosus may have to be re-evaluated. The cur-rent consensus is that foxes act as definitive hosts for E. granulosusbut are of minor importance in the transmission of the parasite inrural areas of Australia. However, foxes infected with E. granulosusare of potential public health importance when infected animalsencroach into urban areas (Jenkins and Craig, 1992).
3.7.2. Feral catsInfection of Australian feral cats with adult E. granulosus has
never been reported. Jenkins and Morris (2003) examined theintestines of 23 feral cats collected in an area of high E. granulosustransmission in the local wildlife and none was found infected.Jenkins also fed protoscoleces recovered from a wallaby to two catsand two fox cubs, and small numbers of E. granulosus wererecovered from both foxes but nothing was found in the cats(D.J. Jenkins, unpublished data). It is generally considered that feralcats in Australia are not definitive hosts for E. granulosus.
3.7.3. Feral pigs, goats, deer, horses and rabbitsHydatid disease occurs in Australian feral pigs (Jenkins and
Morris, 2003; Lidetu and Hutchinson, 2007). The study of Jenkinsand Morris (2003) was conducted in south-eastern New SouthWales; 204 pigs were examined, 22.5% contained hydatid cystsand depending on the survey area between 15 and 22% of the cystswere fertile. In contrast, the study of Lidetu and Hutchinson (2007)was conducted in tropical northern Queensland; 74 pigs wereexamined and 31.1% contained hydatid cysts, but the rate of fertil-ity was almost three times that of the pigs collected in New SouthWales. The reason for this difference in cyst fertility is unclear.There is no doubt feral pigs could contribute to transmission of E.granulosus in wildlife but the degree to which they contribute isdebatable. Adult feral pigs (the animals most likely to harbour fer-tile cysts) are big and strong and difficult for wild dogs to catch andkill; consequently, wild dogs mainly predate on piglets, animalsleast likely to contain fertile cysts. Inevitably, adult pigs eventuallydie and their carcasses become available for scavenging by wilddogs and foxes. However, particularly in summer, scavengerswould need to find the carcass soon after death before fertile cystsbecame non-infective due to putrefaction. Therefore, the role ofpigs in the transmission of E. granulosus in Australian is likely tobe minor.
Hydatid infection in goats has never been reported except for ananecdotal report from Western Australia (R.C.A. Thompson, unpub-lished data). Periodically, one of the current authors (D.J. Jenkins)has examined small numbers of feral goats, collected from variousareas of south-eastern New South Wales, and has never found anyinfected with hydatid cysts (D.J. Jenkins, unpublished data). Theabsence of hydatid infection in Australian feral goats is curiousbecause in many countries goats are important intermediate hosts(Schantz et al., 1993).
Hydatid cysts have never been reported from feral horses ordeer in Australia. Therefore, until data to the contrary are available,feral goats, deer and horses appear not to be part of the lifecycle ofE. granulosus in Australia.
Rabbits naturally infected with hydatid disease have rarelybeen reported. The two reports, (cited in Gemmell, 1959b) are
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897Q5
898
899
900
Fig. 3. Map depicting areas of high, low, rare and no transmission of Echinococcus granulosus in Australia (red, high transmission; orange, low transmission; beige, raretransmission; grey, no transmission). (Modified version of the map published by Jenkins and Macpherson (2003)).
R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx 9
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
thought to be a mis-identification of metacestodes of Taenia serial-is. Wild Australian rabbits have been shown to be susceptible toexperimental infection with hydatid disease (Jenkins andThompson, 1995). The cysts established in the lungs and appearedto be developing normally. However, the rabbits were given a largedose of eggs, far higher than anything they would normally beexposed to in the wild, which may have been the reason theybecame infected.
3.8. Current prevalence of E. granulosus in Australian domestic dogs,sheep and cattle on mainland Australia and the island state ofTasmania
3.8.1. DogsThe most recently published study on intestinal helminths in
Australian mainland dogs is that of Palmer et al. (2008) where1400 faecal samples collected in vet clinics were sent to theauthors for testing. These samples were from urban dog ownerswith a close interest in the health of their pets; unsurprisingly,no taeniid cestodes were identified in any of the samples collected.The most recent study of intestinal helminths in rural dogs (Jenkinset al., 2014) screened faeces from 1425 rural dogs living in easternAustralia (1119 mainland; 306 Tasmania) with faecal flotation,molecular methods and the E. granulosus coproantigen test(Jenkins et al., 2000). Surprisingly, taeniid eggs in faeces were alsouncommon, being recovered from the faeces of only 11 dogs. Thisis likely to be because more than 98% of owners reported feedingdry commercial dog food exclusively or as a major component oftheir dog’s diet and approximately 50% of owners either de-wormed their dog(s) 2 monthly or 4 monthly with a de-wormercontaining praziquantel. Nevertheless, an additional 45 dogs werepositive in the E. granulosus coproantigen test (1.9% of mainland
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
samples and 7.8% of Tasmanian samples). Some coproantigen-posi-tive faecal samples were also positive in an E. granulosus coproPCR(Jenkins et al., 2014).
3.8.2. SheepHydatid disease prevalence data are not collected in Australian
abattoirs, but in Tasmania occurrence of infection in livestock ismonitored and traced back to the property of origin. Hydatid dis-ease still occurs periodically in Australian sheep, however theprevalence has declined steadily during the last 30 years (D.J. Jen-kins, personal observations), no doubt a reflection of the decline ofE. granulosus infection in rural domestic dogs (Jenkins et al., 2014).Sheep populations now most at risk of contracting hydatid diseaseare those grazed on pasture abutting national and state parks andforests containing populations of wild dogs (Grainger and Jenkins,1996). These wild dogs periodically enter pastures to predate onthe sheep but whilst there also defecate, contaminating the pasturewith eggs of E. granulosus. Nothing recent has been publishedregarding the prevalence of hydatid disease in mainland sheep.The most up-to-date data have been collected by the NationalSheep Health Monitoring Program (Animal Health Australia,2011, http://www.animalhealthaustralia.com.au/programs/dis-ease-surveillance/the-national-sheep-health-monitoring-project/).
Routine monitoring of slaughtered sheep for hydatid infection isstill undertaken in Tasmania. Since the declaration of provisionaleradication in 1996, there have been two reports of infection insheep; one in 2011 in sheep sent to a mainland abattoir forslaughter (Jenkins et al., in press) the other, more recently in2013 (D.J. Jenkins, unpublished data) in a single animal, residenton a property in the midlands area of Tasmania. Currently, the ori-gins of this animal are still being investigated.
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974Q6
975
976
977
978
979
980
981982983984985986987988989990991992993994
10 R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
3.8.3. Cattle‘‘High levels’’ of hydatid disease in slaughtered cattle have been
reported, anecdotally, from abattoirs in south-eastern Queensland,north-eastern New South Wales and eastern Victoria. No recentdata have been published regarding hydatid disease prevalence inAustralian cattle, but according to abattoir management prevalenceis high enough to be causing substantial financial losses to theabattoirs through condemnation of offal. An estimated loss to thenorthern Queensland beef industry of $6 million per year due tohydatid-infected offal was reported for 2004, with prevalence levelsranging between 20–51% in cattle from coastal areas and 3% inthose from inland areas (Banks et al., 2006b). The source of infectionin these cattle is likely from wildlife since cattle are commonlygrazed in areas inhabited by wild dogs because predation impactsare less severe than if sheep were grazed in the same areas.
As with sheep, hydatid disease is monitored in slaughtered cat-tle in Tasmania. Since declaration of provisional eradication in1996, over 200 hydatid-infected cattle have been identified. Mostof these animals proved to be imports from the mainland, mainlyGippsland in Victoria, an area where hydatid infection in cattle iscommon. However, 31 were animals less than 3 years old andhad never left Tasmania (Jenkins et al., 2014). DNA was extractedand sequenced from cysts removed from four of the infected cattle;their infections proved to be the G1 sheep strain of E. granulosus(Jenkins et al., unpublished data). The G1 sheep strain not onlyinfects sheep but can also infect cattle, pigs, goats and macropodidmarsupials. Less than 5% of G1 hydatid cysts in Australian cattleare fertile (Kumaratilake and Thompson, 1982), therefore cystsfrom infected cattle, if consumed by dogs, dingoes or their hybrids,commonly do not contribute to transmission of E. granulosus.
The 24 Tasmanian domestic dogs that tested positive in the E.granulosus coproantigen ELISA and the hydatid-infection data fromsheep and cattle found since declaration of provisional freedom in1996 indicate that hydatid disease has not been completely eradi-cated from the island as was previously thought but continues tobe transmitted at low levels (Jenkins et al., 2014).
995996997998999100010011002100310041005100610071008100910101011101210131014101510161017101810191020102110221023
3.9. Human prevalence
The prevalence of human hydatidosis on mainland Australia isunknown, because in most jurisdictions human hydatid diseasehas ceased to be notifiable. The last published data on humanhydatid disease on mainland Australia was that of Jenkins andPower (1996) but these data were only collected in New SouthWales and the Australian Capital Territory and are now out of date.Nevertheless, new cases continue to be identified annually onmainland Australia. A proportion of these new cases are in recentlyarrived immigrants from a range of countries who were infected intheir country of origin. In the study of Jenkins and Power (1996),60% of cases diagnosed in residents living in major urban centreswere recent immigrants. There has been a recent publication onhuman hydatid disease in Tasmania (O’Hern and Cooley, 2013).The authors described human hydatid disease in Tasmania sincethe declaration of provisional freedom in 1996. Transmission ofhydatid disease to humans in Tasmania has now ceased, althoughone or two new cases are diagnosed annually. However, all of thesenew cases are in elderly people who were thought to have beeninfected pre-1996.
10241025Q710261027102810291030103110321033
4. Conclusions
Australia has a long history of research on hydatid disease andthe causative agent Echinococcus. Much of this was borne fromnecessity, given the impact the parasite had on public health andthe agricultural economy in the late 19th and early 20th centuries
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
in Australia. However, the research that has been conducted inAustralia has contributed much to the international research efforton Echinococcus and hydatid disease, in particular the value of theorganism as a model in studies on developmental biology andepidemiology, not just concerned with Echinococcus but morebroad-ranging in terms of basic biology and theoretical models oftransmission dynamics. We hope that Australia will continue tocontribute to research on Echinococcus and that this will have animpact internationally and sustain the collaborations that havedeveloped with research groups and centres world-wide.
5. Uncited references
(Gemmell et al., 1986; Harris and Revfeim, 1980; Lavikainenet al., 2006).
Acknowledgements
We are very grateful to Mark Preston (Graphic Designer,Murdoch University, Australia) for producing the graphical imagesand to Craig Poynter (Spacial Analysis Unit, Charles SturtUniversity, Australia) for preparing the map.
References
Albani, C.M., Elissondo, M.C., Cumino, A.C., Chisari, A., Denegri, G.M., 2010. Primarycell culture of Echinococcus granulosus developed from the cystic germinal layer:biological and functional characterization. Int. J. Parasitol 40, 1269–1275.
Albani, C.M., Cumino, A.C., Elissondo, M.C., Denegri, G.M., 2013. Development of acell line from Echinococcus granulosus germinal layer. Acta Trop. 128, 124–129.
Ali-Khan, Z., Siboo, R., Gomersall, M., Faucher, M., 1983. Cystolytic events and thepossible role of germinal cells in metastasis in chronic alveolar hydatidosis.Ann. Trop. Med. Parasitol. 77, 497–512.
Banks, D.J., Copeman, D.D., Skerratt, L.F., 2006a. Echinococcus granulosus in northernQueensland. 2. Ecological determinants of infection in beef cattle. Aust. Vet. J.84, 308–311.
Banks, D.J., Copeman, D.D., Skerratt, L.F., Molina, E.C., 2006b. Echinococcus granulosusin northern Queensland. 2. Prevalence in cattle. Aust. Vet. J. 84, 303–307.
Barnes, T.S., Hinds, L.A., Jenkins, D.J., Coleman, G.T., 2007a. Precious development ofhydatid cysts in a macropod host. Int. J. Parasitol. 37, 1379–1389.
Barnes, T.S., Morton, J.M., Coleman, G.T., 2007b. Clustering of hydatid infection inmacropods. Int. J. Parasitol. 37, 943–952.
Barnes, T.S., Goldizen, A.W., Morton, J.M., Coleman, G.T., 2008. Cystic Echinococcus ina wild population of the brush-tailed rock-wallaby (Petrogale penicillata) athreatened macropodid. Parasitology 135, 715–723.
Barnes, T.S., Hinds, L.D., Jenkins, D.J., Bielefeldt-Ohmann, H., Lightowlers, M.W.,Coleman, G.T., 2011. Comparative pathology of pulmonary hydatid cysts inmacropods and sheep. J. Comp. Pathol. 144, 113–122.
Barrett, N.J., Smyth, J.D., Ong, S.J., 1982. Spontaneous sexual differentiation ofMesocestoides corti tetrathyridia in vitro. Int. J. Parasitol. 12, 315–322.
Beard, T., Bramble, A.J., Middleton, M.J., 2001. Eradication in Our Time: a Log Book ofthe Hydatid Control Program 1962–1996. Department of Primary Industry,Water and Environment, Hobart.
Bowles, J., Blair, D., McManus, D.P., 1994. Molecular genetic characterisation of thecervid strain (‘‘northern form’’) of Echinococcus granulosus. Parasitology 109,215–221.
Brown, B., Copeman, D.B., 2003. Zoonotic importance of parasites in wild dogscaught in the vicinity of Townsville. Aust. Vet. J. 81, 700–702.
Budke, C.M., Deplazes, P., Torgerson, P.R., 2006. Global socioeconomic impact ofcystic echinococcosis. Emerg. Infect. Dis. 12, 296–303.
Carmena, D., Cardona, G.A., 2014. Echinococcosis in wild carnivorous species:epidemiology, genotypic diversity, and implications for veterinary publichealth. Vet. Parasitol. 202, 69–94.
Catalano, S., Lejeune, M., Liccioli, S., Verocai, G.G., Gesy, K.M., Jenkins, E.J., Kutz, S.J.,Fuentealba, C., Duignan, P.J., Mossolo, A., 2012. Echinococcus multilocularis inurban coyotes, Alberta, Canada. Emerg. Infec. Dis. 18, 1625–1628.
Claridge, A.W., Spencer, R.J., Wilton, A.N., Jenkins, D.J., Dall, D., Lapidge, S.J., in press.When is a dingo not a dingo? Hybridisation with domestic dogs. In: Glen, A.S.,Dickman, C.R. (Eds), Carnivores of Australia. CSIRO Publishing, Collingwood,Australia.
Corbett, L., 1995. The Dingo in Australia and Asia. University of New South WalesPress, Sydney, Australia.
Cruz-Reyes, A., Constantine, C.C., Boxell, A.C., Hobbs, R.P., Thompson, R.C.A., 2007.Echinococcus granulosus from Mexican pigs is the same strain as that in Polishpigs. J. Helminthol. 81, 287–292.
Davidson, R.K., Romig, T., Jenkins, E., Tryland, M., Robertson, L.J., 2012. The impact ofglobalisation on the distribution of Echinococcus multilocularis. Trends Parasitol.28, 239–247.
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
10341035103610371038103910401041104210431044104510461047104810491050105110521053105410551056105710581059106010611062106310641065106610671068106910701071107210731074107510761077107810791080108110821083108410851086108710881089109010911092109310941095109610971098109911001101110211031104110511061107110811091110111111121113111411151116111711181119
112011211122112311241125112611271128112911301131113211331134113511361137113811391140114111421143114411451146114711481149115011511152115311541155115611571158115911601161116211631164116511661167116811691170117111721173117411751176117711781179118011811182118311841185118611871188118911901191119211931194119511961197Q811981199120012011202120312041205
R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx 11
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
Deplazes, P., Thompson, R.C.A., Constantine, C.C., Penhale, W.J., 1993. Primaryinfection of dogs with Echinococcus granulosus: systemic and local (Peyer’spatches) immune responses. Vet. Immunol. Immunopathol. 40, 171–184.
Deplazes, P., Hegglin, D., Gloor, S., Romig, T., 2004. Wilderness in the city: theurbanisation of Echinococcus multilocularis. Trends Parasitol. 20, 77–84.
Dévé, F., 1919. Secondary echinococcosis. Lancet ii, 835–838.Dévé, F., 1946. L’Echinococcose Secondaire. Masson et Cie, Paris.Dew, H.R., 1922. Observations on the mode of development of brood capsules and
scolices in the encysted stage of Taenia Echinococcus. Med. J. Aust. 2, 381–384.Dew, H.R., 1925. The histogenesis of the hydatid parasite (Taenia echinococcus) in
the pig. Med. J. Aust. I, 101–110.Dew, H.R., 1928. Hydatid Disease, Its Pathology, Diagnosis and Treatment.
Australian Medical Publishing Company, Sydney.Dew, H.R., 1935. Advances in our knowledge of hydatid disease during the
twentieth century. Br. Med. J. 2, 620–622.Dew, H.R., 1953. Hydatid disease in Australia. Arch. Int. Hidatidosis 13, 1319–1332.Diaz, A., Casaravilla, C., Irigoin, F., Lin, G., Previato, J.O., Ferreira, F., 2011a.
Understanding the laminated layer of larval Echinococcus I: structure. TrendsParasitol. 27, 204–213.
Diaz, A., Casaravilla, C., Allen, J.E., Sim, R.B., Ferreira, F., 2011b. Understanding thelaminated layer of larval Echinococcus II: immunology. Trends Parasitol. 27,263–272.
Durie, P.H., Riek, R.F., 1952. The role of the dingo and wallaby in the infestation ofcattle with hydatids (Echinococcus granulosus Batch 1786) (Rudolphi 1805) inQueensland. Aust. Vet. J. 28, 249–254.
Eckert, J., Deplazes, P., 2004. Biological, epidemiological and clinical aspects ofEchinococcus, a zoonosis of increasing concern. Clin. Microbiol. Rev. 17, 107–135.
Eckert, J., Thompson, R.C.A., Mehlhorn, H., 1983. Proliferation and metastasesformation of larval Echinococcus multilocularis. I. Animal model, macroscopicaland histological findings. Z. Parasitol. 69, 737–748.
Eckert, J., Meslin, F.-X., Pawlowski, Z.S. (Eds.), 2001. WHO/OIE Manual onEchinococcosis in Humans and Animals: a Public Health Problem of GlobalConcern. World Organisation for Animal Health and World Health Organisation,Geneva.
Esch, G.W., Smyth, J.D., 1976. Studies on the in vitro culture of Taenia crassiceps. Int.J. Parasitol. 6, 143–149.
Galindo, M., Paredes, R., Marchant, C., Miño, V., Galanti, N., 2003. Regionalization ofDNA and protein synthesis in developing stages of the parasitic platyhelminthEchinococcus granulosus. J. Cell. Biochem. 90, 294–303.
Gemmell, M.A., 1958. Hydatid disease in Australia III. Observations on the incidenceand geographical distribution of hydatid disease in sheep in New South Wales.Aust. Vet. J. 34, 269–280.
Gemmell, M.A., 1959a. Hydatid disease in Australia. VI. Observations on thecarnivore of New South Wales as definitive hosts for Echinococcus granulosus(Batch 1786), (Rudolphi 1801) and their role of the spread of hydatidosis indomestic animals. Aust. Vet. J. 35, 450–455.
Gemmell, M.A., 1959b. Hydatid disease in Australia VII. An appraisal of the presentposition and some problems in control. Aust. Vet. J. 35, 505–514.
Gemmell, M.A., 1990. Australasian contributions to an understanding of theepidemiology and control of hydatid disease caused by Echinococcusgranulosus-past, present and future. Int. J. Parasitol. 20, 431–456.
Gemmell, M.A., Lawson, R.J., 1986. Epidemiology and control of hydatid disease. In:Thompson, R.C.A. (Ed.), The Biology of Echinococcus and Hydatid Disease. GeorgeAllen and Unwin, London, UK, pp. 179–216.
Gemmell, M.A., Roberts, M.G., 1995. Modelling Echinococcus life cycles. In:Thompson, R.C.A., Lymbery, A.J. (Eds.), Echinococcus and Hydatid Disease. CABInternational, Wallingford, UK, pp. 333–354.
Gemmell, M.A., Lawson, J.R., Roberts, M.G., 1986. Population dynamics inechinococcosis and cysticercosis: biological parameters of Echinococcusgranulosus in dogs and sheep. Parasitology 92, 599–620.
Gonzalez, L.M., Daniel-Mwambete, K., Montero, E., Rosenzvit, M.C., McManus, D.P.,Garate, T., Cuesta-Bandera, C., 2002. Further molecular discrimination ofSpanish strains of Echinococcus granulosus. Exp. Parasitol. 102, 46–56.
Gottstein, B., Dai, W.J., Walker, M., Stettler, M., Müller, N., Hemphill, A., 2002. Anintact laminated layer is important for the establishment of secondaryEchinococcus multilocularis infection. Parasitol. Res. 88, 822–828.
Grainger, H.J., Jenkins, D.J., 1996. Transmission of hydatid disease to sheep fromwild dogs in Victoria, Australia. Aust. Vet. J. 26, 1263–1270.
Grove, D.I., 1990. A History of Human Helminthology. CAB International,Wallingford, Oxon, UK.
Gustafsson, M.K.S., 1976. Basic cell types in Echinococcus granulosus (Cestoda,Cyclophyllidea). Acta Zool. Fenn. 146, 1–16.
Harandi, F.M., Hobbs, R.P., Adams, P.J., Mobedi, I., Morgan-Ryan, U.M., Thompson,R.C.A., 2002. Molecular and morphological characterisation of Echinococcusgranulosus of human and animal origin in Iran. Parasitology 125, 367–373.
Harris, R.E., Revfeim, K.J.A., 1980. Simulating strategies for control of Echinococcusgranulosus, Taenia hydatigena and T. ovis. J. Hyg. 84, 389–404.
Heath, D.D., 1995. Immunology of Echinococcus infections. In: Thompson, R.C.A.,Lymbery, A.J. (Eds.), Echinococcus and Hydatid Disease. CAB International,Wallingford, UK, pp. 183–199.
Hegglin, D., Deplazes, P., 2013. Control of Echinococcus multilocularis: strategies,feasibility and cost benefit analyses. Int. J. Parasitol. 43, 327–337.
Herbaut, C., Petavy, A.-F., Deblock, S., Gabrion, C., 1988. Nuclear inclusions ofrostellar cells of Echinococcus multilocularis (Cestoda). Parasitol. Res. 74, 399–402.
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
Holcman, B., Heath, D.D., 1997. The early stages of Echinococcus granulosusdevelopment. Acta Trop. 64, 5–17.
Howell, M.J., Smyth, J.D., 1995. Cultivation. In: Thompson, R.C.A., Lymbery, A.J.(Eds.), Echinococcus and Hydatid Disease. CAB International, Wallingford, Oxon,UK, pp. 200–232.
Howkins, A.B., 1966. The role of macropodidae in Tasmania as intermediate hosts inhydatid disease. Aust. Vet J. 42, 240–241.
Huttner, M., Siefert, L., Mackenstedt, U., Romig, T., 2009. A survey of Echinococcusspecies in wild carnivores and livestock in East Africa. Int. J. Parasitol. 39, 1269–1276.
Jenkins, D.J., Craig, N.A., 1992. Role of foxes (Vulpes vulpes) in the epidemiologyof Echinococcus granulosus in urban environments. Med. J Aust. 157, 754–756.
Jenkins, D.J., Macpherson, C.N.L., 2003. Transmission ecology of Echinococcusgranulosus in wildlife in Australia and Africa. Parasitology 127, S63–S72.
Jenkins, D.J., Morris, B., 1991. Unusually heavy infections of Echinococcus granulosusin wild dogs in south-eastern Australia. Aust. Vet. J. 68, 36–37.
Jenkins, D.J., Morris, B., 2003. Echinococcus granulosus in wildlife in and around theKosciuszko National Park, southeastern New South Wales. Aust. Vet. J. 86, 81–85.
Jenkins, D.J., Power, K., 1996. Human hydatidosis in New South Wales and theAustralian Capital Territory, 1987–1992. Med. J. Aust. 164, 18–21.
Jenkins, D.J., Thompson, R.C.A., 1995. Hydatid cysts in an experimentally infectedrabbit. Vet. Rec. 137, 148–149.
Jenkins, D.J., Fraser, A., Bradshaw, H., Craig, P.S., 2000. Detection of Echinococcusgranulosus coproantigens in Australian canids with natural or experimentalinfection. J. Parasitol. 86, 140–145.
Jenkins, D.J., Murray, A.J., Claridge, A.W., Story, G.L., Bradshaw, H., Craig, P.S., 2005a.The contribution of spotted-tailed quolls in the transmission of Echinococcusgranulosus in the Byadbo Wilderness Area of the Kosciuszko National Park,Australia. Wild. Res. 32, 37–41.
Jenkins, D.J., Romig, T., Thompson, R.C.A., 2005b. Emergence/re-emergence ofEchinococcus spp. – a global update. Int. J. Parasitol. 35, 1205–1219.
Jenkins, D.J., Allen, L., Goullet, M., 2008. Encroachment of Echinococcus granulosusinto urban areas of eastern Queensland, Australia. Aust. Vet. J. 86, 294–300.
Jenkins, D.J., Lievaart, J.J., Boufana, B., Lett, W., Bradshaw, H., Armua-Fernandes, M.T.,2014. Echinococcus granulosus and other intestinal helminths in rural dogs fromeastern Australia, the current situation. Aust. Vet. J. 92, 292–298.
Johnson, P.M., Speare, R., Beveridge, I., 1998. Mortality in wild and captive rockwallabies and nailtail wallabies due to hydatid disease caused by Echinococcusgranulosus. Aust. Mammal. 20, 419–423.
Jolly, D.O., Messier, F., 2004. The distribution of echinococcosis in moose: evidencefor parasite-induced vulnerability to predation to wolves? Cecolodia 140, 586–590.
Kamiya, M., Sato, H., 1990a. Survival, strobilation and sexual maturation ofEchinococcus multilocularis in the small intestine of golden hamsters.Parasitology 100, 125–130.
Kamiya, M., Sato, H., 1990b. Complete life cycle of the canid tapeworm, Echinococcusmultilocularis, in laboratory rodents. FASEB J. 4, 3334–3339.
Kamiya, M., Ooi, H.-K., Oku, Y., Yagi, K., Ohbayashi, M., 1985. Growth anddevelopment of Echinococcus multilocularis in experimentally infected cats.Jpn. J. Vet. Res. 33, 135–140.
King, H.W.H., 1959. Transhumance grazing in the snow belt of New South Wales.Aust. Geogr. 7, 129–140.
Kouguchi, H., Matsumoto, J., Nakao, R., Yamano, K., Oku, Y., Yagi, K., 2013.Characterization of a surface glycoprotein from Echinococcus multilocularis andits mucosal vaccine potential in dogs. PLoS ONE 8, e69821.
Koziol, U., Rauschendorfer, T., Rodríguez, L.Z., Krohne, G., Brehm, K., 2014. Theunique stem cell system of the immortal larva of the human parasiteEchinococcus multilocularis. EvoDevo 5, 10.
Krasnoshchekov, G.P., Pluzhnnikov, L.T., 1981. Rostellar organ of Taenia crassiceps(Cestoda: Taeniidae) larvae. Parazitologia 15, 519–524 (in Russian).
Küchenmeister, F., 1851. Vorläufige Mittheilung (Über Cysticercus pisiformis derKaninchen). Z. Klin. Med. 2, 240.
Küchenmeister, F., 1855. Echinococcen. In: Küchenmeister, F. (Ed.), Die in und andem Körper des lebenden Menschen vorkommenden Parasiten. Teubner,Leipzig, Germany, pp. 139–153.
Kumaratilake, L.M., Thompson, R.C.A., 1982. Hydatidosis/echinococcosis inAustralia. Helminthol. Abst. Ser. A Anim. Hum. Helminthol. 51, 233–252.
Lavikainen, A., Lehtinen, M.J., Meri, T., Hirvelä-Koski, V., Meri, S., 2003. Moleculargenetic characterization of the Fennoscandian cervid strain, a new genotypicgroup (G10) of Echinococcus granulosus. Parasitology 127, 207–215.
Lavikainen, A., Lehtinen, M.J., Laaksonen, S., Agren, E., Oksanen, A., Meri, S., 2006.Molecular genetic characterization of Echinococcus isolates of cervid origin fromFinland and Sweden. Parasitology 133, 565–570.
Leuckart, R., 1876. Die menschlichen Parasiten und die von ihnen herrührendenKrankheiten. Ein hand- und Lehrbuch für Naturforscher und Aertze. C.F.Winter’sche Verlagshandlung, Leipzig, Germany.
Lidetu, D., Hutchinson, G.W., 2007. The prevalence, organ distribution and fertilityof cystic echinococcosis in feral pigs in tropical North Queensland, Australia.Onderst. J. Vet. Res. 74, 73–79.
Lin, G., Todeschini, A.R., Koizumi, A., Neves, J.L., González, H., Dematteis, S., Hada, N.,Previato, J.O., Ferreira, F., Mendonça-Previato, L., Díaz, A., 2012. Furtherstructural characterization of the Echinococcus granulosus laminated layercarbohydrates: the blood-antigen P1-motif gives rise to branches at differentpoints of the O-glycan chains. Glycobiology 23, 438–452.
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
12061207120812091210121112121213121412151216121712181219122012211222122312241225122612271228122912301231123212331234123512361237123812391240124112421243124412451246124712481249125012511252125312541255125612571258125912601261126212631264126512661267 Q9126812691270127112721273127412751276127712781279128012811282128312841285128612871288128912901291
12921293129412951296129712981299130013011302130313041305130613071308130913101311131213131314131513161317131813191320132113221323132413251326132713281329133013311332133313341335133613371338133913401341134213431344134513461347134813491350135113521353135413551356135713581359136013611362136313641365136613671368136913701371137213731374137513761377
12 R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
Lymbery, A.J., Thompson, R.C.A., 1988. Electrophoretic analysis of genetic variationin Echinococcus granulosus from domestic hosts in Australia. Int. J. Parasitol. 18,803–811.
Lymbery, A.J., Thompson, R.C.A., 2012. The molecular epidemiology of parasiteinfections: tools and applications. Mol. Biochem. Parasitol. 181, 102–116.
Lymbery, A.J., Hobbs, R.P., Thompson, R.C.A., 1989. The dispersion of Echinococcusgranulosus in the intestine of dogs. J. Parasitol. 75, 562–570.
Martínez, C., Paredes, R., Stock, R.P., Saralegui, A., Andreu, M., Cabezón, C., Ehrlich, R.,Galanti, N., 2005. Cellular organization and appearance of differentiatedstructures in developing stages of the parasitic platyhelminth Echinococcusgranulosus. J. Cell. Biochem. 94, 327–335.
McCullough, J.S., Fairweather, I., 1989. The fine structure and possible functions ofscolex gland cells in Trilocularia acanthiaevulgaris (Cestoda, Tetraphyllidea).Parasitol. Res. 75, 575–582.
Mech, L.D., 1966. The Wolves of Isle Royale: Fauna of the National Parks of the USA,Fauna Series 7. US Government Printing Office, Washington, DC, USA.
Mehlhorn, H., Eckert, J., Thompson, R.C.A., 1983. Proliferation and metastasesformation of larval Echinococcus multilocularis II. Ultrastructural investigations.Z. Parasitol. 69, 749–763.
Moks, E., Jogisalu, I., Valdmann, H., Saarma, U., 2008. First report of Echinococcusgranulosus genotype G8 in Eurasia and a reappraisal of the phylogeneticrelationships of ‘genotypes’ G5–G10. Parasitology 135, 647–654.
Monteiro, K.M., de Carvalho, M.O., Zaha, A., Ferreira, H.B., 2010. Proteomic analysisof the Echinococcus granulosus metacestode during infection of its intermediatehost. Proteomics 10, 1985–1999.
Nakao, M., Lavikainen, A., Yanagida, T., Ito, A., 2013. Phylogenetic systematics of thegenus Echinococcus (Cestoda: Taeniidae). Int. J. Parasitol. 43, 1017–1029.
Naunyn, B., 1863. Ueber die zu Echinococcus hominis gehörige tänie. Arch. Anat.Physiol. Wiss. Med. 4, 412–416.
Obendorf, D.L., Matheson, M.J., Thompson, R.C.A., 1989. Echinococcus granulosusinfection in foxes in south-eastern New South Wales. Aust. Vet J. 66, 123.
O’Hern, J.A., Cooley, L., 2013. A description of human hydatid disease in Tasmania inthe post-eradication era. Med. J. Aust. 199, 117–120.
Osuna-Carrillo, A., Mascaró-Lazcano, M.C., 1982. The in vitro cultivation of Taeniapisiformis to sexually mature adults. Z. Parasitenkd. 67, 67–71.
Palmer, C.S., Thompson, R.C.A., Traub, R.J., Rees, R., Robertson, I.D., 2008. Nationalstudy of the gastrointestinal parasites of dogs and cats in Australia. Vet.Parasitol. 151, 181–190.
Parkinson, J., Wasmuth, J.D., Salinas, G., Bizarro, C.V., Sanford, C., Berriman, M.,Ferreira, H.B., Zaha, A., Blaxter, M.L., Maizels, R.M., Fernandez, C., 2012. Atranscriptomic analysis of Echinococcus granulosus larval stages: implicationsfor parasite biology and host adaptation. PLoS Negl. Trop. Dis. 6, e1897.
Petavy, A.-F., Hormaeche, C., Lahmar, S., Ouhelli, H., Chabalgoity, A., Marchal, T.,Azzouz, S., Schreiber, F., Alvite, G., Sarciron, M.-E., Maskell, D., Esteves, A.,Bosquet, G., 2008. An oral recombinant vaccine in dogs against Echinococcusgranulosus, the causative agent of human hydatid disease: a pilot study. PLoSNegl. Trop. Dis. 2, e125.
Pospekhova, N.A., Bondarenko, S.K., 2014. Morpho-functional characteristics of thescolex of Wardium chaunense (Cestoda: Aploparaksidae) penetrated into hostintestine. Parasitol. Res. 113, 131–137.
Reichel, M.P., Lyford, R.A., Gasser, R.B., 1994. Hyperendemic focus of echinococcosisin north-eastern Victoria. Med. J. Aust. 60, 499–501.
Romig, T., Dinkel, A., Mackenstedt, U., 2006. The present situation of echinococcosisin Europe. Parasitol. Int. 55, S187–S191.
Saarma, U., Jogisalu, I., Moks, E., Varcasia, A., Lavikainen, A., Oksanen, A., Simsek, S.,Andresiuk, V., Denegri, G., Gonzalez, L.M., Ferrer, E., Garate, T., Rinaldi, L.,Maravilla, P., 2009. A novel phylogeny for the genus Echinococcus, based onnuclear data, challenges relationships based on mitochondrial evidence.Parasitology 136, 317–328.
Schantz, P.M., Chai, J., Craig, P.S., Eckert, J., Jenkins, D.J., Macpherson, C.N.L., Thakur,A., 1995. Epidemiology and control of hydatid disease. In: Thompson, R.C.A.,Lymbery, A.J. (Eds.), ????. CAB International, Wallingford, USA, pp. 233–331.
Siles-Lucas, M., Nunes, C.P., Zaha, A., Breijo, M., 2000. The 14-3-3 protein is secretedby the adult worm of Echinococcus granulosus. Parasite Immunol. 22, 521–528.
Slais, J., 1973. Functional morphology of cestode larvae. Adv. Parasitol. 11, 395–480.Slias, J., 1980. Experimental infection of sheep and pigs with Echinococcus granulosus
(Batch 1786) and the origin of pouching in hydatid cysts. Acta Vet. Acad. Sci.Hung. 28, 375–387.
Smyth, J.D., 1946. Studies on tapeworm physiology, the cultivation ofSchistocephalus solidus in vitro. J. Exp. Biol. 23, 47–70.
Smyth, J.D., 1950. Studies on tapeworm physiology. V. Further observations on thematuration of Schistocephalus solidus (Diphyllobothriidae) under sterileconditions in vitro. J. Parasitol. 36, 371–383.
Smyth, J.D., 1964. Observations on the scolex of Echinococcus granulosus, withspecial reference to the occurrence and cytochemistry of secretory cells in therostellum. Parasitology 54, 515–526.
Smyth, J.D., 1969. Parasites as biological models. Parasitology 59, 73–91.Smyth, J.D., 1979. Echinococcus granulosus and E. multilocularis: in vitro culture of the
strobilar stages from protoscoleces. Angew. Parasitol. 20, 137–147.Smyth, J.D., 1982. Speciation in Echinococcus: biological and biochemical criteria.
Rev. Iber. Parasitol. Special Volume Extra, 25–34.Smyth, J.D., 1987. Changing concepts in the microecology, macroecology and
epidemiology of hydatid disease. In: Geerts, S., Kumar, V., Brandt, J. (Eds.),Helminth Zoonoses. Martinus Nijhoff, Dordrecht, Netherlands, pp. 1–11.
Smyth, J.D., 1990. Parasitological serendipity: from Schistocephalus to Echinococcus.Int. J. Parasitol. 20, 411–423.
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
Smyth, J.D., Davies, Z., 1974a. In vitro culture of the strobilar stage of Echinococcusgranulosus (sheep strain): a review of basic problems and results. Int. J.Parasitol. 4, 631–644.
Smyth, J.D., Davies, Z., 1974b. Occurrence of physiological strains of Echinococcusgranulosus demonstrated by the in vitro culture of protoscoleces from sheep andhorse hydatid cysts. Int. J. Parasitol. 4, 443–445.
Smyth, J.D., Davies, Z., 1975. In vitro suppression of segmentation in Echinococcusmultilocularis with morphological transformation of protoscoleces intomonozoic adults. Parasitology 71, 125–135.
Smyth, J.D., Howkins, A.B., Barton, M., 1966. Factors controlling the differentiationof the hydatid organism, Echinococcus granulosus, into cystic or strobilar stagesin vitro. Nature 211, 1374–1377.
Smyth, J.D., Miller, H.J., Howkins, A.B., 1967. Further analysis of the factorscontrolling strobilization, differentiation and maturation of Echinococcusgranulosus in vitro. Exp. Parasitol. 21, 31–41.
Smyth, J.D., Morseth, D.J., Smyth, M.M., 1969. Observations on nuclear secretions inthe rostellar gland cells of Echinococcus granulosus (Cestoda). Nucleus 12, 47–56.
Spiliotis, M., Brehm, K., 2009. Axenic in vitro cultivation of Echinococcusmultilocularis metacestode vesicles and the generation of primary cellcultures. Mol. Biol. 470, 245–262.
Spiliotis, M., Lechner, S., Tappe, D., Scheller, C., Krohne, G., Brehm, K., 2008.Transient transfection of Echinococcus multilocularis primary cells and completein vitro regeneration of metacestode vesicles. Int. J. Parasitol. 38, 1025–1039.
Swiderski, Z., 1983. Echinococcus granulosus: hook-muscle systems and cellularorganisation of infective oncospheres. Int. J. Parasitol. 13, 289–299.
von Siebold, C.T., 1853. Ueberdie VerwandlungderEchinococcus-Brutin Taenien. Z.Wiss. Zool. 4, 409–425.
Thevenet, P.S., Jensen, O., Drut, R., Cerrone, G.E., Grenóvero, M.S., Alvarez, H.M.,Targovnik, H.M., Basualdo, J.A., 2005. Viability and infectiousness of eggs ofEchinococcus granulosus aged under natural conditions of inferior arid climate.Vet. Parasitol. 133, 71–77.
Thomas, J.D., 1884. Hydatid Disease with Special Reference to its Prevalence inAustralia. E. Spiller, Government Printer, North Terrace, Adelaide, Australia.
Thompson, R.C.A., 1976. The Mongolian gerbil (Meriones unguiculatus) as alaboratory host for the cystic stage of Echinococcus granulosus of British horseorigin. Int. J. Parasitol. 6, 505–511.
Thompson, R.C.A., 1995. Biology and systematics of Echinococcus. In: Thompson,R.C.A., Lymbery, A.J. (Eds.), Echinococcus and Hydatid Disease. CAB International,Wallingford, Oxon, UK, pp. 1–50.
Thompson, R.C.A., 2001. Echinococcosis. In: Gillespie, S.H., Pearson, R.D. (Eds.),Principles and Practice of Clinical Parasitology. Wiley, Sussex, UK, pp. 595–612.
Thompson, R.C.A., 2008. The taxonomy, phylogeny and transmission ofEchinococcus. Exp. Parasitol. 119, 439–446.
Thompson, R.C.A., 2013. Parasite zoonoses and wildlife: one health, spillover andhuman activity. Int. J. Parasitol. 43, 1079–1088.
Thompson, R.C.A., Eckert, J., 1983. Observations on Echinococcus multilocularis in thedefinitive host. Z. Parasitol. 69, 335–345.
Thompson, R.C.A., Lymbery, A.J., 1988. The nature, extent and significance ofvariation within the genus Echinococcus. Adv. Parasitol. 27, 210–263.
Thompson, R.C.A., Lymbery, A.J., 1990. Echinococcus: biology and strain variation.Int. J. Parasitol. 20, 457–470.
Thompson, R.C.A., Lymbery, A.J., 1991. The epidemiological significance of biologicalvariation in Echinococcus. Arch. Hidatidosis 30, 195–200.
Thompson, R.C.A., Lymbery, A.J., 1996. Genetic variability in parasites and host-parasite interactions. Parasitology 112, S7–S22.
Thompson, R.C.A., Lymbery, A.J., 2013. Lets not forget the thinkers. Trends Parasitol.29, 581–584.
Thompson, R.C.A., McManus, D.P., 2002. Towards a taxonomic revision of the genusEchinococcus. Trends Parasitol. 18, 452–457.
Thompson, R.C.A., Smyth, J.D., 1975. Equine hydatidosis: a review of the currentstatus in Great Britain and the results of an epidemiological survey. Vet.Parasitol. 1, 107–127.
Thompson, R.C.A., Dunsmore, J.D., Hayton, A.R., 1979. Echinococcus granulosus:secretory activity of the rostellum of the adult cestode in situ in the dog. Exp.Parasitol. 48, 144–163.
Thompson, R.C.A., Jue Sue, L.P., Buckley, S.J., 1982. In vitro development of thestrobilar stage of Mesocestoides corti. Int. J. Parasitol. 12, 303–314.
Thompson, R.C.A., Deplazes, P., Eckert, J., 1990. Uniform strobilar development ofEchinococcus multilocularis in vitro from protoscolex to immature stages. J.Parasitol. 76, 240–247.
Thompson, R.C.A., Lymbery, A.J., Hobbs, R.B., Elliot, A.D., 1988. Hydatid disease inurban areas of Western Australia: an unusual cycle involving western greykangaroos (Macropus fuliginosus), feral pigs and domestic dogs. Aust. Vet. J. 65,188–190.
Thompson, R.C.A., Lymbery, A.J., Constantine, C.C., 1995. Variation in Echinococcus:towards a taxonomic revision of the genus. Adv. Parasitol. 35, 145–176.
Thompson, R.C.A., Nicholas, W.L., Howell, M.J., Kumartilake, L.M., 1985. Echinococcusgranulosus in a fox. Aust. Vet. J. 62, 200–201.
Thompson, R.C.A., Boxell, A.C., Ralston, B.J., Constantine, C.C., Hobbs, R.P., Shury, T.,Olson, M.E., 2006. Molecular and morphological characterization ofEchinococcus in cervids from North America. Parasitology 132, 439–447.
Torgerson, P.R., 2009. Dogs, vaccines and Echinococcus. Trends Parasitol. 25, 57–58.Tsai, I.J., Magdalena Zarowiecki, M.N.H., Garciarrubio, A., Sanchez-Flores, A., Brooks,
K.L., Tracey, A., Bobes, R.J., Fragoso, G., Sciutto, E., Aslett, M., Beasley, H., Bennett,H.M., Cai, J., Camicia, F., Clark, R., Cucher, M., De Silva, N., Day, T.A., Deplazes, P.,
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://
137813791380138113821383138413851386138713881389139013911392
139313941395139613971398139914001401140214031404
1405
R.C.A. Thompson, D.J. Jenkins / International Journal for Parasitology xxx (2014) xxx–xxx 13
PARA 3681 No. of Pages 13, Model 5G
13 August 2014
Estrada, Fernández, C., Holland, P.W.H., Hou, J., Hu, S., Huckvale, T., Hung, S.S.,Kamenetzky, L., Keane, J.A., Kiss, F., Koziol, U., Lambert, O., Liu, K., Luo, X., Luo, Y.,Macchiaroli, N., Nichol, S., Paps, J., Parkinson, J., Pouchkina-Stantcheva, N.,Riddiford, N., Rosenzvit, M., Salinas, G., Wasmuth, J.D., Zamanian, M., Zheng, Y.,Cai, X.The Taenia solium Genome Consortium, Soberón, X., Olson, P.D., Laclette,J.P., Brehm, K., Berriman, M., 2013. The genomes of four tapeworm speciesreveal adaptations to parasitism. Nature 496, 57–63.
Whitfield, P.J., Evans, N.A., 1983. Pathogenesis and asexual multiplication amongparasitic platyhelminths. Parasitology 86, 121–160.
Williams, R.J., Sweatman, G.K., 1963. On the transmission, biology and morphologyof Echinococcus granulosus equinus, a new subspecies of hydatid tapeworm inhorses in Great Britain. Parasitology 53, 391–407.
Yamashita, K., Uchino, J., Sato, N., Furuya, K., Namieno, T., 1997. Establishment of aprimary culture of Echinococcus multilocularis cells. J. Gastroenterol. 32, 344–350.
Please cite this article in press as: Thompson, R.C.A., Jenkins, D.J. Echinococcus asdx.doi.org/10.1016/j.ijpara.2014.07.005
Zd’árská, Z., Nebesárová, J., 2003. Ultrastructure of the early rostellum ofSilurotaenia siluri (Batsch, 1786) (Cestoda: Proteocephalidae). Parasitol. Res.89, 495–500.
Zhang, W., Zhang, Z., Shi, B., Li, J., You, H., Tulson, G., Dang, X., Song, Y., Yimiti, T.,Wang, J., Jones, M.K., McManus, D.P., 2006. Vaccination of dogs againstEchinococcus granulosus, the cause of cystic hydatid disease in humans. J.Infect. Dis. 194, 966–974.
Zheng, H., Zhang, W., Zhang, L., Zhang, Z., Li, J., Lu, G., Zhu, Y., Wang, Y., Huang, Y.,Liu, J., Kang, H., Chen, J., Wang, L., Chen, A., Yu, S., Gao, Z., Jin, L., Gu, W., Wang, Z.,Zhao, L., Shi, B., Wen, H., Lin, R., Jones, M.K., Brejova, B., Vinar, T., Zhao, G.,McManus, D.P., Chen, Z., Zhou, Y., Wang, S., 2013. The genome of the hydatidtapeworm Echinococcus granulosus. Nat. Genet. 45, 1168–1175.
a model system: biology and epidemiology. Int. J. Parasitol. (2014), http://