Fasciolosis

Humans (liver of goat) The course of fasciolosis in humans has 4 main phases: The major symptoms of this phase are: • Fever: usually the first symptom of the disease; • Abdominal pain • Gastrointestinal disturbances: loss of appetite, flatulence, nausea, diarrhea • Hives • Respiratory symptoms (very rare): cough, shortness of breath, chest pain, coughing up blood • Enlargement of the liver and spleen • Fluid in the peritoneal abdominal cavity (ascites) • Low level of red blood cells in the bloodstream • Yellow discoloration of the skin or white parts of the eyes • Latent phase: This phase can last for months or years. The proportion of asymptomatic subjects in this phase is unknown. They are often discovered during family screening after a patient is diagnosed. Fibrous adhesions of the gall bladder to adjacent organs are common. Lithiasis of the bile duct or gall bladder is frequent and the stones are usually small and multiple. signs of fasciolosis are always closely associated with infectious dose (amount of ingested metacercariae). In sheep, as the most common definitive host, the clinical presentation is divided into 4 types: Economical effect of fasciolosis in sheep consists in sudden deaths of animals as well as in the reduction of weight gain and wool production. In goats and cattle, the clinical manifestation is similar to sheep. However, acquired resistance to F. hepatica infection is well-known in adult cattle. Calves are susceptible to disease but more than 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. In sheep and sometimes cattle, the damaged liver tissue may become infected by the Clostridium bacteria C. novyi type B. The bacteria will release toxins into the bloodstream resulting in what is known as black disease. There is no cure and death follows quickly. As C. novyi is common in the environment, black disease is found wherever populations of liver flukes and sheep overlap. ==Cause==

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. Recent reports based on mitochondrial genes analysis have shown that Japanese Fasciola spp. is more closely related to F. gigantica than to F. hepatica. In India, a species called F. jacksoni was described in elephants. 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. 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. In France, nutria (Myocastor coypus) was confirmed as a wild reservoir host of F. hepatica. Humans are infected by ingestion of aquatic plants that contain the infectious cercariae. Several species of aquatic vegetables are known as a vehicle of human infection. In Europe, Nasturtium officinale (common watercress), Nasturtium sylvestre, Rorippa amphibia (wild watercress), Taraxacum dens leonis (dandelion leaves), Valerianella olitoria (lamb's lettuce), and Mentha viridis (spearmint) were reported as a source of human infections. Because F. hepatica cercariae also encyst on water surface, humans can be infected by drinking of fresh untreated water containing cercariae. Intermediate hosts - the most common intermediate host of F. hepatica'' in Europe and South America Intermediate hosts of F. hepatica are freshwater snails from family Lymnaeidae. Snails from family Planorbidae act as an intermediate host of F. hepatica very occasionally. ==Mechanism==

The development of infection in a definitive host is divided into two phases: the parenchymal (migratory) phase and the biliary phase. 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. Occasionally, ectopic locations of flukes such as the lungs, diaphragm, intestinal wall, kidneys, and subcutaneous tissue can occur. On the other hand, sheep and goats are not resistant to re-infection with F. hepatica. However, there is evidence that two sheep breeds, in particular Indonesian thin tail sheep and Red maasai sheep, are resistant to F. gigantica. ==Diagnosis==

Most immunodiagnostic tests will detect infection and have a sensitivity above 90% during all stages of the disease. In addition, antibody concentration quickly drops post-treatment and no antibodies are present one year after treatment, which makes it a very good diagnostic method. Furthermore, eggs of F. hepatica, F. gigantica and Fasciolopsis buski are morphologically indistinguishable. Recently, purified native and recombinant antigens have been used, e.g. recombinant F. hepatica cathepsin L-like protease. Methods based on antigen detection (circulating in serum or faeces) are less frequent. In addition, biochemical and haematological examinations of human sera support the exact diagnosis (eosinophilia, elevation of liver enzymes). Ultrasonography and xray of the abdominal cavity, biopsy of the liver, and gallbladder punctuate can also be used (ref: US-guided gallbladder aspiration: a new diagnostic method for biliary fascioliasis. A. Kabaalioglu, A. Apaydin, T. Sindel, E. Lüleci. Eur. Radiol. 9, 880±882 (1999) . 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. Therefore, these methods provide early detection of the infection. ==Prevention==

In some areas, special control programs are in place or have been planned. The types of control measures depend on the setting (such as epidemiologic, ecologic, and cultural factors). Strict control of the growth and sale of watercress and other edible water plants is important. Individual people can protect themselves by not eating raw watercress and other water plants, especially from endemic grazing areas. Travelers to areas with poor sanitation should avoid food and water that might be contaminated (tainted). Vegetables grown in fields, that might have been irrigated with polluted water, should be thoroughly cooked, as should viscera from potentially infected animals. ==Treatment==

Humans Several drugs are effective for fascioliasis, both in humans and in domestic animals. The drug of choice in the treatment of fasciolosis is triclabendazole, a member of the benzimidazole family of anthelmintics. The drug works by preventing the polymerization of the molecule tubulin into the cytoskeletal structures, microtubules. Resistance of F. hepatica to triclabendazole has been recorded in Australia in 1995 and Ireland in 1998. Praziquantel treatment is ineffective. There are case reports of nitazoxanide being successfully used in human fasciolosis treatment in Mexico. There are also reports of bithionol being used successfully. Nitazoxanide has been found effective in trials, but is currently not recommended. ==Epidemiology==

Human and animal fasciolosis occurs worldwide. Human fasciolosis has been reported by countries in Europe, America, Asia, Africa, and Oceania. The incidence of human cases has been increasing in 51 countries of the five continents. Concerning the former Soviet Union, almost all reported cases were from the Tajik Republic. 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. 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 the zones of Cuba. Pinar del Río 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 areas 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. ==Other animals==

Several drugs have been used to 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: • Halogenated phenols: bithionol (Bitin), hexachlorophene (Bilevon), nitroxynil (Trodax) • Salicylanilides: closantel (Flukiver, Supaverm), rafoxanide (Flukanide, Ranizole) • Benzimidazoles: triclabendazole (Fasinex), albendazole (Vermitan, Valbazen), mebendazol (Telmin), luxabendazole (Fluxacur) • Sulphonamides: clorsulon (Ivomec Plus) • Phenoxyalkanes: diamphenetide (Coriban) Triclabendazole (Fasinex) is considered the most common drug due to its high efficacy against adult as well as juvenile flukes. Triclabendazole is used in the control of fasciolosis of livestock in many countries. Nevertheless, long-term veterinary use of triclabendazole has caused the appearance of resistance in F. hepatica. In animals, triclabendazole resistance was first described in Australia, later in Ireland and Scotland and more recently in the Netherlands. 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 similar to triclabendazole. Countries where fasciolosis in livestock was repeatedly reported: • Europe: UK, Ireland, France, Portugal, Spain, Switzerland, Italy, Netherlands, Germany, Poland • Asia: Turkey, Russia, Thailand, Iraq, Iran, China, Vietnam, India, Nepal, Japan, Korea, Philippines • Africa: Kenya, Zimbabwe, Nigeria, Egypt, Gambia, Morocco • Australia and the Oceania: Australia, New Zealand • Americas: United States, Mexico, Cuba, Peru, Chile, Uruguay, Argentina, Jamaica, Brazil On September 8, 2007, Veterinary officials in South Cotabato, Philippines said that laboratory tests on samples from cows, carabaos, and horses in the province's 10 towns and lone city showed the level of infection at 89.5%, a sudden increase of positive cases among large livestock due to the erratic weather condition in the area. They must be treated forthwith to prevent complications with surra and hemorrhagic septicemia diseases. Surra already affected all barangays of the Surallah town. == See also ==