Fasciolosis
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ICD9 = | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = ped | eMedicineTopic = 760 | MeshID = D005211 |Fasciolosis is an important helminth disease caused by two trematodes Fasciola hepatica (the common liver fluke) and Fasciola gigantica. This disease belongs to the plant-borne trematode 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.Mas-Coma, S., Bargues, M.D., Valero, M.A., 2005. Fascioliasis and other plant-borne trematode zoonose. Int. J. Parasitol. 35, 1255–1278.The definitive host range is very broad and includes many herbivorous mammals, including humans. The life cycle includes freshwater snails as an intermediate host of the parasite.Torgerson, P., Claxton, J., 1999. Epidemiology and control. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 113–149. Recently, worldwide losses in animal productivity due to fasciolosis were conservatively estimated at over US$3.2 billion per annum.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. 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.Anonymus 1995. Control of Foodborne Trematode Infections. WHO Technical Series No. 849. WHO, Geneva, 157 pp.
Etiology
Fasciolosis is caused by two digenetic trematodes F. hepatica and F. gigantica. Adult flukes of both species are localized in the bile ducts of the liver or gallbladder. F. hepatica measures 2 to 3 cm and has a cosmopolitan distribution. F. gigantica measures 4 to 10 cm in length and the distribution of the species is limited to the tropics and has been recorded in Africa, the Middle East, Eastern Europe and south and eastern Asia. In domestic livestock in Japan, diploid (2n = 20), triploid (3n = 30) and chimeric flukes (2n/3n) have been described, many of which reproduce parthenogenetically. As a result of this unclear classification, flukes in Japan are normally referred to as Fasciola spp.Sakaguchi, Y., 1980. Karyotype and gametogenesis of the common liver fluke, Fasciola sp., in Japan. Jap. J. Parasitol. 29, 507–513. Recent reports based on mitochondrial genes analysis has shown that Japanese Fasciola spp. is more closely related to F. gigantica than to F. hepatica.Itagaki, T., Tsutsumi, K., 1998. Triploid form of Fasciola in Japan: genetic relationships between Fasciola hepatica and Fasciola gigantica determined by ITS-2 sequence of the nuclear rDNA. Int. J. Parasitol. 28, 777–781. In India, a species called F. jacksoni was described in elephants.Singh, K.P., Srivastava, V.K., Prasad, A. and Pandey, A.P., 1994. Pathology due to Fasciola jacksoni in Indian elephants Elephas indicus. Ind. J. Anim. Scien. 64, 802–804.Geographic Distribution
Human and animal fasciolosis occurs worldwide. While animal fasciolosis is distributed in countries with high cattle and sheep production, human fasciolosis occurs, excepting Western Europe, in developing countries. Fasciolosis occurs only in areas where suitable conditions for intermediate hosts exist. Human fasciolosis
Studies carried out in recent years have shown human fasciolosis to be an important public health problem.Chen, M.G., Mott, K.E., 1990. Progress in assessment of morbidity due to Fasciola hepatica infection: a review of recent literature. Trop. Dis. Bull. 87, R1–R38. Human fasciolosis has been reported from countries in Europe, America, Asia, Africa and Oceania. The incidence of human cases has been increasing in 51 countries of the five continents.Mas-Coma, S., Bargues, M.D., Esteban, J.G., 1999. Human fasciolosis. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 411–434.Esteban, J.G., Bargues, M.D., Mas-Coma, S., 1998. Geographical distribution, diagnosis and treatment of human fascioliasis: a review. Res. Rev. Parasitol. 58, 13–42. A global analysis shows that the expected correlation between animal and human fasciolosis only appears at a basic level. High prevalences in humans are not necessarily found in areas where fasciolosis is a great veterinary problem. For instance, in South America, hyperendemics and mesoendemics are found in Bolivia and Peru where the veterinary problem is less important, while in countries such as Uruguay, Argentina, and Chile, human fasciolosis is only sporadic or hypoendemic.Europe
In Europe, human fasciolosis occur mainly in France, Spain, Portugal, and the former USSR. France is considered an important human endemic area. A total of 5863 cases of human fasciolosis were recorded from nine French hospitals from 1970 to 1982.Danis, M., Nozais, J.P., Chandenier, J., 1985. La distomatose à Fasciola hepatica, II: La fasciolose humaine en France. Action Vet. 907. Concerning the former Soviet Union, almost all reported cases were from the Tajik Republic. Several papers referred to human fasciolosis in Turkey.Yilmaz, H., Gödekmerdan, A., 2004. Human fasciolosis in Van province, Turkey. Acta Trop. 92, 161–162. Recently, serological survey of human fasciolosis was performed in some parts of Turkey. The prevalence of the disease was serologically found to be 3.01% in Antalya Province, and between 0.9 and 6.1% in Isparta Province, Mediterranean region of Turkey.Demirci, M., 2003. Insanlarda epidemiyoloji. In: Tinar, R., Korkmaz, M. (Eds.), Fasciolosis. Türkiye Parazitoloji Derněgi, META Basim, Izmir, pp. 343–358 (in Turkish). In other European countries, fasciolosis is sporadic and the occurrence of the disease is usually combined with travelling to endemic areas.Americas
In North America, the disease is very sporadic. In Mexico, 53 cases have been reported. In Central America, fasciolosis is a human health problem in the Caribbean Islands, especially in zones of Puerto Rico and Cuba. Pinar del Rio Province and Villa Clara Province are Cuban regions where fasciolosis was hyperendemic. In South America, human fasciolosis is a serious problem in Bolivia, Peru, and Ecuador. These Andean countries are considered to be the area with the highest prevalence of human fasciolosis in the world. Well-known human hyperendemic areas are localized predominately in the high plain called Altiplano. In the Northern Bolivian Altiplano, prevalences detected in some communities were up to 72% and 100% in coprological and serological surveys, respectively. In Peru, F. hepatica in humans occurs throughout the country. The highest prevalences were reported in Arequipa, Mantaro Valley, Cajamarca Valley, and Puno Region. In other South American countries like Argentina, Uruguay, Brazil, Venezuela and Colombia, human fasciolosis appear to be sporadic, despite the high prevalences of fasciolosis in cattle.Africa
In Africa, human cases of fasciolosis, except in northern parts, have not been frequently reported. The highest prevalence was recorded in Egypt where the disease is distributed in communities living in the Nile Delta.Asia
In Asia, the most human cases were reported in Iran, especially in Gīlān Province, on the Caspian Sea. It was mentioned that more than 10,000 human cases were detected in Iran. In eastern Asia, human fasciolosis appears to be sporadic. Few cases were documented in Japan, Koreas, Vietnam, and Thailand.Australia and the Oceania
In Australia, human fasciolosis is very rare (only 12 cases documented). In New Zealand, F. hepatica has never been detected in humans.Animal fasciolosis
Countries where fasciolosis in livestock was repeatedly reported:Source of infection for humans and transmission
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. Sheep, goats and cattle are considered the predominant animal reservoirs. 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 donkeys and pigs contribute to disease transmission in Bolivia.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. 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.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. In France, nutria (Myocastor coypus) was confirmed as a wild reservoir host of F. hepatica.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. Humans are infected by ingestion of aquatic plants that contain the infected metacercariae.Markell, E.K., Voge, M., 1999. Medical Parasitology, eighth ed.. Saunders Company Publication, pp. 185–188. Several species of aquatic vegetables are known as a vehicle of human infection. In Europe, Nasturtium officinale (common watercress), N. silvestris, Rorippa amphibia (wild watercress), Taraxacum dens leonis (dandelion leaves), Valerianella olitora (lamb’s lettuce), and Mentha viridis (spearmint) were reported as a source of human infections. 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.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. Because F. hepatica cercariae also encyst on water surface, humans can be infected by drinking of fresh untreated water containing metacercariae. In addition, an experimental study suggested that humans consuming raw liver dishes from fresh livers infected with juvenile flukes could become infected.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.Intermediate hosts
Intermediate hosts of F. hepatica are freshwater snails from family Lymnaeidae.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. Snails from family Planorbidae act as an intermediate host of F. hepatica very occasionally.More reading in Fasciola hepaticaPathogenesis
The development of infection in definitive host is divided into two phases: the parenchymal (migratory) phase and the biliary phase.Dubinský, P., 1993. Trematódy a trematodózy. In: Jurášek, V., Dubinský, P. a kolektív, Veterinárna parazitológia. Príroda a.s., Bratislava, 158–187. (in Slovakian) The parenchymal phase begins when excysted juvenile flukes penetrate the intestinal wall. After the penetration of the intestine, flukes migrate within the abdominal cavity and penetrate the liver or other organs. F. hepatica has a strong predilection for the tissues of the liver.Behm, C.A., Sangster, N.C., 1999. Pathology, pathophysiology and clinical aspects. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 185–224. Occasionally, ectopic locations of flukes such as the lungs, diaphragm, intestinal wall, kidneys, and subcutaneous tissue can occur.Boray, J.C., 1969. Experimental fascioliasis in Australia. Adv. Parasitol. 7, 95–209. During the migration of flukes, tissues are mechanically destroyed and inflammation appears around migratory tracks of flukes. The second phase (the biliary phase) begins when parasites enter the biliary ducts of the liver. In biliary ducts, flukes mature, feed on blood, and produce eggs. Hypertrophy of biliar ducts associated with obstruction of the lumen occurs as a result of tissue damage.Clinical Signs
In humans
The course of fasciolosis in humans has 4 main phases:In animals
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:Resistance to infection
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. Resistance to fasciolosis was also documented in rats.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. On the other hand, sheep and goats are not resistant to re-infection with F. hepatica.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.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. However, there is evidence that two sheep breeds, in particular Indonesian thin tail sheep and Red maasai sheep, are resistant to F. gigantica.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.Wamae, L.W., 1996. Comparative pathogenesis and immunochemistry analysis of Fasciola gigantica infection in cattle and sheep. PhD Thesis. University of Edinburgh. No reports concerning the resistance in humans are available.Diagnosis
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.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. Furthermore, eggs of F. hepatica, F. gigantica and Fasciolopsis buski are morphologically indistinguishable. 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 antibodies from sera. The antigenic preparations used have been primarily derived from extracts of excretory/secretory products from adult worms, or with partially purified fractions.Hillyer, G.V., 1999. Immunodiagnosis of human and animal fasciolosis. In: Dalton, J.P. (Ed.), Fasciolosis. CAB International Publishing, Wallingford, pp. 435–447. Recently, purified native and recombinant antigens have been used, e.g. recombinant F. hepatica cathepsin L-like protease.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. 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 several days before a repeat stool examination. 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. 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.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.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. Therefore, these methods provide early detection of the infection.Treatment and prevention
Anthelmintics
In humans
For high efficacy and safety, triclabendazole (Egaten®) in dose 10-12 mg/kg is drug of choice in human fasciolosis.Savioli, L., Chistulo, L., Montresor, A., 1999. New opportunities for the control of fascioliasis. Bull. WHO 77, 300. No drug alternatives are available for humans. On the other hand, nitazoxanide were successfully used in human fasciolosis treatment in Mexico.Rossignol, J.F., Abaza, H., Friedman, H., 1998. Successful treatment of human fascioliasis with nitazoxanide. Trans. Roy. Soc. Trop. Med. Hyg. 92, 103–104. Bithionol is another drug of choice used for treatment of F. hepatica.Ramachandran, A., 2000. Pharmacology Recall.In animals
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:Fairweather, I., Boray, J.C., 1999. Fasciolicides: efficacy, action, resistance and its management. Vet. J. 158, 81–112Next Page
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