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| {{Infobox_Disease |
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| Name = {{PAGENAME}} |
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| Image = |
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| Caption = |
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| DiseasesDB = 4757 |
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| ICD10 = {{ICD10|B|66|3|b|65}} |
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| ICD9 = {{ICD9|121.3}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = |
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| eMedicineSubj = ped |
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| eMedicineTopic = 760 |
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| MeshID = D005211 |
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| {{Fasciolosis}} | | {{Fasciolosis}} |
| | '''This page is about clinical aspects of the disease. For microbiologic aspects of specific causative organisms:''' |
| | {{Seealso|Fasciola hepatica}} |
| | {{Seealso|Fasciola gigantica}} |
| | {{CMG}} |
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| ==[[Fasciolosis overview|Overview]]== | | ==[[Fasciolosis overview|Overview]]== |
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| ==Related Chapters== | | ==Related Chapters== |
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| '''Fasciolosis''' is an important [[helminth]] disease caused by two [[trematode]]s ''[[Fasciola hepatica]]'' (the common [[Liver Fluke|liver fluke]]) and ''[[Fasciola gigantica]]''. This disease belongs to the plant-borne trematode [[zoonosis|zoonoses]]. In [[Europe]], the [[Americas]] and [[Oceania]] only ''F. hepatica'' is a concern, but the distributions of both species overlap in many areas of [[Africa]] and [[Asia]].<ref name=Mas-Coma05>Mas-Coma, S., Bargues, M.D., Valero, M.A., 2005. Fascioliasis and other plant-borne trematode zoonose. Int. J. Parasitol. 35, 1255–1278.</ref>
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| The definitive host range is very broad and includes many [[Herbivory|herbivorous]] [[mammal]]s, including humans. The [[Biological life cycle|life cycle]] includes freshwater [[snail]]s as an [[intermediate host]] of the parasite.<ref name=Torges99>Torgerson, P., Claxton, J., 1999. Epidemiology and control. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 113–149.</ref> Recently, worldwide losses in animal productivity due to fasciolosis were conservatively estimated at over US$3.2 billion per annum.<ref name=spithill99>Spithill, T.W., Smooker, P.M., Copeman, D.B. 1999. ''Fasciola gigantica'': epidemiology, control, immunology and molecular biology. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 465–525.</ref> In addition, fasciolosis is now recognized as an emerging human disease: the [[World Health Organization]] (WHO) has estimated that 2.4 million people are infected with ''Fasciola'', and a further 180 million are at risk of infection.<ref>Anonymus 1995. Control of Foodborne Trematode Infections. WHO Technical Series No. 849. WHO, Geneva, 157 pp.</ref>[[Image:Fasciola hepatica.JPG|right|thumb|300px|''Fasciola hepatica'']]
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| ==Source of infection for humans and transmission==
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| Human ''F. hepatica'' infection is determined by the presence of the intermediate snail hosts, domestic herbivorous animals, climatic conditions and the dietary habits of man.<ref name=Chen/> Sheep, goats and cattle are considered the predominant animal [[Natural reservoir|reservoir]]s. While other animals can be infected, they are usually not very important for human disease transmission. On the other hand, some authors have observed that [[donkey]]s and [[pig]]s contribute to disease transmission in Bolivia.<ref>Mas-Coma, S., Rodriguez, A., Bargues, M.D., Valero, M.A., Coello, J., Angles, R., 1998. Secondary reservoir role of domestic animals other than sheep and cattle in fascioliasis transmission on the northern Bolivian Altiplano. Res. Rev. Parasitol. 57, 39–46.</ref> Among wild animals, it has been demonstrated that the peridomestic [[rat]] (''Rattus rattus'') may play an important role in the spread as well as in the transmission of the parasite in [[Corsica]].<ref>Mas-Coma, S., Fons, R., Feliu, C., Bargues, M.D., Valero, M.A., Galán-Puchades, M.T., 1988. Small mammals as natural definitive hosts of the liver fluke, ''Fasciola hepatica'' Linnaeus, 1758 (Trematoda: Fasciolidae): a review and two new records of epidemiologic interest on the island of Corsica. Rivista di Parassitologia 5, 73–78.</ref> In France, [[nutria]] (''Myocastor coypus'') was confirmed as a wild reservoir host of ''F. hepatica''.<ref>Menard, A., Agoulon, A., L’Hostis, M., Rondelaud, D., Collard, S., Chauvin, A., 2001. ''Myocastor coypus'' as a reservoir host of ''Fasciola hepatica'' in France. Vet. Res. 32, 499–508.</ref> Humans are infected by ingestion of aquatic plants that contain the infected [[metacercariae]].<ref>Markell, E.K., Voge, M., 1999. Medical Parasitology, eighth ed.. Saunders Company Publication, pp. 185–188.</ref> Several species of aquatic vegetables are known as a vehicle of human infection. In Europe, ''[[Nasturtium (genus)|Nasturtium]] officinale'' (common [[watercress]]), ''N. silvestris'', ''[[Rorippa]] amphibia'' (wild watercress), ''Taraxacum dens leonis'' ([[dandelion]] leaves), ''Valerianella olitora'' ([[Corn salad|lamb’s lettuce]]), and ''Mentha viridis'' ([[spearmint]]) were reported as a source of human infections.<ref name=Mas-Coma99/> In the Northern Bolivian Altiplano, some authors suggested that several aquatic plants such as bero-bero (watercress), algas ([[algae]]), kjosco and tortora could act as a source of infection for humans.<ref>Bjorland, J., Bryan, R.T., Strauss, W., Hillyer, G.V., McAuley, J.B., 1995. An outbreak of acute fascioliasis among Aymara Indians in the Bolivian Altiplano. Clin. Infect. Dis. 21, 1228–1233.</ref> Because ''F. hepatica'' [[cercaria]]e also encyst on water surface, humans can be infected by drinking of fresh untreated water containing metacercariae.<ref name=Chen/> In addition, an experimental study suggested that humans consuming raw liver dishes from fresh livers infected with juvenile flukes could become infected.<ref>Taira, N., Yoshifuji, H., Boray, J.C., 1997. Zoonotic potential of infection with ''Fasciola'' spp. by consumption of freshly prepared raw liver containing immature flukes. Int. J. Parasitol. 27, 775–779.</ref>
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| ==Intermediate hosts==
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| [[Image:Galba truncatula.jpg|280px|thumb|''Galba truncatula'' - the most common intermediate host of ''F. hepatica'' in Europe and South America]]
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| Intermediate hosts of ''F. hepatica'' are freshwater snails from family [[Lymnaeidae]].<ref name=Torges99/><ref>Graczyk, T.K., Fried, B., 1999. Development of ''Fasciola hepatica'' in the intermediate host. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 31–46.</ref> Snails from family [[Planorbidae]] act as an intermediate host of ''F. hepatica'' very occasionally.<ref name=Mas-Coma05/>
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| More reading in ''[[Fasciola hepatica]]''
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| ==Pathogenesis==
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| ==Clinical Signs==
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| ===In humans===
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| ===In animals===
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| Clinical signs of fasciolosis are always closely associated with infectious dose (amount of ingested metacercariae). In sheep, as the most common definitive host, clinical presentation is divided into 4 types:<ref name=Dubinsky/><ref name=Behm99/>
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| *'''Acute Type I Fasciolosis''': infectious dose is more than 5000 ingested metacercariae. Sheep suddenly die without any previous clinical signs. [[Ascites]], [[abdomen|abdominal]] [[haemorrhage]], [[icterus]], [[pallor]] of membranes, weakness may be observed in sheep.
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| *'''Acute Type II Fasciolosis''': infectious dose is 1000-5000 ingested metacercariae. As above, sheep die but briefly show pallor, loss of condition and ascites.
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| *'''Subacute Fasciolosis''': infectious dose is 800-1000 ingested metacercariae. Sheep are [[lethargic]], anemic and may die. Weight loss is dominant feature.
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| *'''Chronic Fasciolosis''': infectious dose is 200-800 ingested metacercariae. Asymptomatic or gradual development of bottle jaw and ascites (ventral [[edema]]), emaciation, weight loss.
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| In blood, [[anemia]], [[hypoalbuminemia]], and [[eosinophilia]] may be observed in all types of fasciolosis.<ref name=Behm99/> Elevation of [[liver enzyme]] activities, such a [[glutamate dehydrogenase]] (GLDH), [[gamma-glutamyl transferase]] (GGT), and [[lactate dehydrogenase]] (LDH), is detected in subacute or chronic fasciolosis from 12-15 week after ingestion of metacercariae.<ref>Anderson, P.H., Matthews, J.G., Berrett, S., Brush, P.J., Patterson, D.S., 1981. Changes in plasma enzyme activities and other blood components in response to acute and chronic liver damage in cattle. Res Vet Sci. 31, 1-4.</ref><ref>Sykes, A.R., Coop, A.R., Robinson, M.G., 1980. Chronic subclinical ovine fascioliasis: plasma glutamate dehydrogenase, gamma glutamyl transpeptidase and aspartate aminotransferase activities and their significance as diagnostic aids. Res. Vet. Sci. 28, 71–78.</ref> Economical effect of fasciolosis in sheep consists in sudden deaths of animals as well as in reduction of weight gain and wool production.<ref>Sinclair, K.B., 1962. Observations on the clinical pathology of ovine fascioliasis. Brit. Vet. J. 118, 37–53.</ref><ref>Roseby, F.B. 1970. The effect of fasciolosis on the wool production of merino sheep. Aust. Vet. J. 46, 361–365.</ref> In goats and cattle, the clinical manifestation is similar to sheep. However, acquired [[resistance]] to ''F. hepatica'' infection is well-known in adult cattle.<ref name=Haroun86>Haroun, E.M., Hillyer, G.V., 1986. Resistance to fascioliasis – a review. Vet. Parasitol. 20, 63–93.</ref><ref>Doyle, J.J., 1973. The relationship between the duration of a primary infection and the subsequent development of an acquired resistance to experimental infections with ''Fasciola hepatica'' in calves. Res. Vet. Sci., 14, 97-103.</ref> Calves are susceptible to disease but in excess of 1000 metacercariae are usually required to cause clinical fasciolosis. In this case the disease is similar to sheep and is characterized by weight loss, anemia, hypoalbuminemia and (after infection with 10,000 metacercariae) death.<ref name=Boray69/> Importance of cattle fasciolosis consist in economic losses caused by condemnation of livers at slaughter and production losses especially due to reduced weight gain.<ref>Phiri, I.K., Phiri, A.M., Harrison, L.J.S., 2006. Serum antibody isotype responses of Fasciola-infected sheep and cattle to excretory and secretory products of ''Fasciola'' species. Vet. Parasitol. 141, 234–242.</ref>
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| ==Resistance to infection==
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| Mechanisms of resistance have been studied by several authors in different animal species. These studies may help to better understand the [[immune response]] to ''F. hepatica'' in host and are necessary in development of vaccine against the parasite. It has been established that cattle acquire resistance to challenge infection with ''F. hepatica'' and ''F. gigantica'' when they have been sensitized with primary patent or drug-abbreviated infection.<ref name=Haroun86/> Resistance to fasciolosis was also documented in rats.<ref>Van Milligen, F.J., Cornelissen, J.B.W.J., Bokhout, B.A., 1998. Location of induction and expression of protective immunity against ''Fasciola hepatica'' at the gut level: a study using an ex vivo infection model with ligated gut segments. J. Parasitol. 84, 771–777.</ref> On the other hand, sheep and goats are not resistant to re-infection with ''F. hepatica''.<ref>Chauvin, A., Bouvet, G., Boulard, C., 1995. Humoral and cellular immune responses to Fasciola hepatica experimental primary and secondary infection in sheep. Int. J. Parasitol. 25, 1227-41.</ref><ref>Martinez-Moreno, A., Martínez-Moreno, F.J., Acosta, I., Gutiérrez, P.N., Becerra, C., Hernández, S. 1997. Humoral and cellular immune responses to experimental Fasciola hepatica infections in goats. Parasitol. Res. 83, 680–686.</ref> However, there is evidence that two sheep breeds, in particular [[Indonesian thin tail sheep]] and [[Red maasai sheep]], are resistant to ''F. gigantica''.<ref>Roberts, J.A., Estuningsih, E., Wiedosari, E., Spithill, T.W., 1997. Acquisition of resistance against ''Fasciola gigantica'' by Indonesian thin tail sheep. Vet. Parasitol. 73, 215–224.</ref><ref>Wamae, L.W., 1996. Comparative pathogenesis and immunochemistry analysis of Fasciola gigantica infection in cattle and sheep. PhD Thesis. University of Edinburgh.</ref> No reports concerning the resistance in humans are available.
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| ==Diagnosis==
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| In humans, diagnosis of fasciolosis is usually achieved by parasitologically by findings the fluke eggs in stool, and immunologically by [[ELISA]] and [[Western blot]]. Coprological examinations of stool alone are generally not adequate because infected humans have important clinical presentations long before eggs are found in the stools. Moreover, in many human infections, the fluke eggs are often not found in the faeces, even after multiple faecal examinations.<ref name=Hillyer88>Hillyer, G.V., 1988. Fascioliasis and fasciolopsiasis. In: Balows, A., Hausler, W.J., Ohashi, M. and Turano, A. (eds) Laboratory Diagnosis of Infectious Diseases. Principles and Practice. I. Bacterial, Mycotic, and Parasitic Diseases, Vol. 90. Springer-Verlag, Berlin, pp. 856–862.</ref><ref name=Chen/> Furthermore, eggs of ''F. hepatica'', ''F. gigantica'' and ''Fasciolopsis buski'' are morphologically indistinguishable.<ref name=Hillyer88/> Therefore, immunonological methods such ELISA and enzyme-linked immunoelectrotransfer blot, also called Western blot, are the most important methods in diagnosis of ''F. hepatica'' infection. These immunological tests are based on detection of species-specific [[antibody|antibodies]] from [[Blood plasma|sera]]. The [[antigen]]ic preparations used have been primarily derived from extracts of excretory/secretory products from adult [[worm]]s, or with partially purified fractions.<ref name=Hillyer99>Hillyer, G.V., 1999. Immunodiagnosis of human and animal fasciolosis. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 435–447.</ref> Recently, purified native and [[Recombinant DNA|recombinant]] antigens have been used, e.g. recombinant ''F. hepatica'' [[cathepsin L]]-like [[protease]].<ref>O’Neill, S.M., Parkinson, M., Strauss, W., Angles, R., Dalton, J.P., 1998. Immunodiagnosis of ''Fasciola hepatica'' infection (fasciolosis) in a human population in the Bolivian Altiplano using purified cathepsin L cysteine proteinase. Am. J. Trop. Med. Hyg. 58, 417–423.</ref> Methods based on antigen detection (circulating in serum or in faeces) are less frequent. In addition, biochemical and haematological examinations of human sera support the exact diagnosis (eosinophilia, elevation of liver enzymes). [[Ultrasonography]] and [[RTG]] of the abdominal cavity, [[biopsy]] of liver, and gallbladder punctuate can also be used. False fasciolosis ([[pseudofasciolosis]]) refers to the presence of eggs in the stool resulting not from an actual infection but from recent ingestion of infected livers containing eggs. This situation (with its potential for misdiagnosis) can be avoided by having the patient follow a liver-free [[diet (nutrition)|diet]] several days before a repeat stool examination.<ref name=Hillyer99/> In animals, intravital diagnosis is based predominantly on faeces examinations and immunological methods. However, clinical signs, biochemical and haematological profile, season, climate conditions, [[epidemiology]] situation, and examinations of snails must be considered.<ref name=Torges99/><ref name=Dubinsky/> Similarly to humans, faeces examinations are not reliable. Moreover, the fluke eggs are detectable in faeces 8-12 weeks post-infection. In spite of that fact, faecal examination is still the only used diagnostic tool in some countries. While coprological diagnosis of fasciolosis is possible from 8-12 week post-infection (WPI) ''F. hepatica'' specific-antibodies are recognized using ELISA or Western blot since 2-4 week post-infection.<ref>Zimmerman, G.L., Jen, L.W., Cerro, J.E., Farnsworth, K.L., Wescott, R.B., 1982. Diagnosis of ''Fasciola hepatica'' infections in sheep by an enzyme-linked immunosorbent assay. Am. J. Vet. Res. 43, 2097–2100.</ref><ref>Duménigo, B.E., Espino, A.M., Finlay, C.M., Mezo, M., 2000. Kinetics of antibody-based antigen detection in serum and faeces of sheep experimentally infected with ''Fasciola hepatica''. Vet. Parasitol. 89, 153-161.</ref> Therefore, these methods provide early detection of the infection.
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| ==Treatment and prevention==
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| ===[[Anthelmintic]]s===
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| ====In humans====
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| For high efficacy and safety, [[triclabendazole]] (Egaten®) in dose 10-12 mg/kg is drug of choice in human fasciolosis.<ref>Savioli, L., Chistulo, L., Montresor, A., 1999. New opportunities for the control of fascioliasis. Bull. WHO 77, 300.</ref> No drug alternatives are available for humans. On the other hand, [[nitazoxanide]] were successfully used in human fasciolosis treatment in Mexico.<ref>Rossignol, J.F., Abaza, H., Friedman, H., 1998. Successful treatment of human fascioliasis with nitazoxanide. Trans. Roy. Soc. Trop. Med. Hyg. 92, 103–104.</ref>
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| Bithionol is another drug of choice used for treatment of [[fasciola hepatica]].<ref>Ramachandran, A., 2000. Pharmacology Recall.</ref>
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| ====In animals====
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| [[Image:Triclabendazole.png|230px|thumb|Formula of triclabendazole]]A number of drugs have been used in control fasciolosis in animals. Drugs differ in their efficacy, mode of action, price, and viability. Fasciolicides (drugs against Fasciola spp.) fall into five main chemical groups:<ref>Fairweather, I., Boray, J.C., 1999. Fasciolicides: efficacy, action, resistance and its management. Vet. J. 158, 81–112</ref>
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| *'''[[Halogenate]]d [[phenol]]s''': bithionol (Bitin), hexachlorophene (Bilevon), nitroxynil (Trodax)
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| *'''[[Salicylanilides]]''': closantel (Flukiver, Supaverm), rafoxanide (Flukanide, Ranizole)
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| *'''[[Benzimidazoles]]''': triclabendazole (Fasinex), albendazol (Vermitan, Valbazen), mebendazol (Telmin), luxabendazole (Fluxacur)
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| *'''[[Sulphonamides]]''': clorsulon (Ivomec Plus)
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| *'''[[Phenoxyalkane]]s''': diamphenetide (Coriban)
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| Triclabendazole (Fasinex) is considered as the most common drug due to its high efficacy against adult as well as juvenile flukes. Triclabendazole is used in control of fasciolosis of livestock in many countries. Nevertheless, long-term veterinary use of triclabendazole has caused appearance of resistance to ''F. hepatica''. In animals, triclabendazole resistance was first described in Australia,<ref>Overend, D.J., Bowen, F.L., 1995. Resistance of ''Fasciola hepatica'' to triclabendazole. Aust. Vet. J. 72, 275–6.</ref> later in Ireland<ref>O’Brien, D.J., 1998. Fasciolosis: a threat to livestock. Irish Vet. J. 51, 539–541.</ref> and [[Scotland]]<ref>Mitchell, G.B., Maris, L., Bonniwell, M.A., 1998. Triclabendazole-resistant liver fluke in Scottish sheep. Vet. Rec. 143, 399.</ref> and more recently in the Netherlands.<ref>Moll, L., Gaasenbeek, C.P.H., Vellema, P., Borgsteede, F.H.M., 2000. Resistance of ''Fasciola hepatica'' against triclabendazole in cattle and sheep in the Netherlands. Vet. Rec. 91, 153–158.</ref> Considering this fact, scientists have started to work on the development of new drug. Recently, a new fasciolicide was successfully tested in naturally and experimentally infected cattle in Mexico. This new drug is called compound Alpha and is chemically very much closed to triclabendazole.<ref>Ibarra, F., Vera, Y., Quiroz, H., Canto, J., Castillo, R., Hernandez, A., Ochoa, P. 2004. Determination of the effective dose of an experimental fasciolicide in naturally and experimentally infected cattle. Vet. Parasitol. 120, 65–74.
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| </ref>
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| ==References==
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| {{Reflist}}
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| ==See also==
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| *''[[Fasciola hepatica]]'' | | *''[[Fasciola hepatica]]'' |
| *''[[Fascioloides magna]]'' | | *''[[Fascioloides magna]]'' |
| *[[Fasciolopsiasis]] | | *[[Fasciolopsiasis]] |
| *[[Clonorchiasis]] | | *[[Clonorchiasis]] |
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| ==External links==
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| *[http://www.dpd.cdc.gov/dpdx/HTML/Fascioliasis.htm Fasciolosis Overview] at [[Centers for Disease Control and Prevention|CDC]]
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| *[http://www.ajtmh.org/cgi/content/abstract/58/4/417?ck=nck Immunodiagnosis of fasciolosis in Bolivian Altiplano]
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| *[http://www.stanford.edu/class/humbio103/ParaSites2001/fascioliasis/Fasciola.htm#transmission Fasciolosis]
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| *[http://www.k-state.edu/parasitology/625tutorials/Hepatica.html Pictures of adult flukes]
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| *[http://www.k-state.edu/parasitology/625tutorials/Fasciola02.html Pictures of ''F. hepatica eggs'']
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| {{Helminthiases}}
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| [[Category:Parasitic diseases]]
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| [[Category:Veterinary helminthology]]
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| [[Category:Animal diseases]]
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| [[cs:Fasciolóza]]
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| [[de:Fasziolose]]
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| [[pt:Fasciolíase]]
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