Fascioliasis
Encyclopedia
Fasciolosis also known as Fascioliasis, Fasciolasis, distomatosis and liver rot, is an important helminth disease caused by two trematodes Fasciola hepatica
Fasciola hepatica
Fasciola hepatica, also known as the common liver fluke or sheep liver fluke, is a parasitic flatworm of the class Trematoda, phylum Platyhelminthes that infects the livers of various mammals, including humans. The disease caused by the fluke is called fascioliasis . F...

(the common liver fluke
Liver fluke
Liver flukes are a polyphyletic group of trematodes .Adults of liver flukes are localized in the liver of various mammals, including humans. These flatworms can occur in bile ducts, gallbladder, and liver parenchyma. They feed on blood...

) and Fasciola gigantica
Fasciola gigantica
Fasciola gigantica is a parasitic flatworm of the class Trematoda, which causes tropical fascioliasis. It is regarded as one of the most important single platyhelminth infections of ruminants in Asia and Africa...

. This disease belongs to the plant-borne trematode zoonoses
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...

. 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.

The definitive host range is very broad and includes many herbivorous mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s, including humans. The life cycle
Biological life cycle
A life cycle is a period involving all different generations of a species succeeding each other through means of reproduction, whether through asexual reproduction or sexual reproduction...

 includes freshwater snail
Freshwater snail
A freshwater snail is one kind of freshwater mollusc, the other kind being freshwater clams and mussels, i.e. freshwater bivalves. Specifically a freshwater snail is a gastropod that lives in a watery non-marine habitat. The majority of freshwater gastropods have a shell, with very few exceptions....

s as an intermediate host
Intermediate host
A secondary host or intermediate host is a host that harbors the parasite only for a short transition period, during which some developmental stage is completed. For trypanosomes, the cause of sleeping sickness, humans are the primary host, while the tsetse fly is the secondary host...

 of the parasite. Recently, worldwide losses in animal productivity due to fasciolosis were conservatively estimated at over US$3.2 billion per annum. In addition, fasciolosis is now recognized as an emerging human disease: the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) has estimated that 2.4 million people are infected with Fasciola, and a further 180 million are at risk of infection.

Etiology

Fasciolosis is caused by two digenetic
Digenea
Digenea is a subclass within the Platyhelminthes consisting of parasitic flatworms with a syncytial tegument and, usually, two suckers, one ventral and one oral. Adults are particularly common in the digestive tract, but occur throughout the organ systems of all classes of vertebrates...

 trematodes F. hepatica and F. gigantica. Adult flukes of both species are localized in the bile duct
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...

s of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 or gallbladder
Gallbladder
In vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated....

. F. hepatica measures 2 to 3 cm and has a cosmopolitan distribution
Cosmopolitan distribution
In biogeography, a taxon is said to have a cosmopolitan distribution if its range extends across all or most of the world in appropriate habitats. For instance, the killer whale has a cosmopolitan distribution, extending over most of the world's oceans. Other examples include humans, the lichen...

. F. gigantica measures 4 to 10 cm in length and the distribution of the species is limited to the tropics
Tropics
The tropics is a region of the Earth surrounding the Equator. It is limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately  N and the Tropic of Capricorn in the southern hemisphere at  S; these latitudes correspond to the axial tilt of the Earth...

 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
Chimera (genetics)
A chimera or chimaera is a single organism that is composed of two or more different populations of genetically distinct cells that originated from different zygotes involved in sexual reproduction. If the different cells have emerged from the same zygote, the organism is called a mosaic...

 flukes (2n/3n) have been described, many of which reproduce parthenogenetically
Parthenogenesis
Parthenogenesis is a form of asexual reproduction found in females, where growth and development of embryos occur without fertilization by a male...

. As a result of this unclear classification, flukes in Japan are normally referred to as Fasciola spp. Recent reports based on mitochondrial genes
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...

 analysis has 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 elephant
Elephant
Elephants are large land mammals in two extant genera of the family Elephantidae: Elephas and Loxodonta, with the third genus Mammuthus extinct...

s.

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
Public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...

 problem. 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. 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. Concerning the former Soviet Union, almost all reported cases were from the Tajik Republic
Tajikistan
Tajikistan , officially the Republic of Tajikistan , is a mountainous landlocked country in Central Asia. Afghanistan borders it to the south, Uzbekistan to the west, Kyrgyzstan to the north, and China to the east....

. Several papers referred to human fasciolosis in Turkey. Recently, serological survey of human fasciolosis was performed in some parts of Turkey. The prevalence of the disease was serologically
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

 found to be 3.01% in Antalya Province
Antalya Province
Antalya Province is located on the Mediterranean coast of south-west Turkey, between the Taurus Mountains and the Mediterranean sea.Antalya Province is the centre of Turkey's tourism industry, attracting 30% of foreign tourists visiting Turkey. The province of Antalya corresponds to the lands of...

, and between 0.9 and 6.1% in Isparta Province
Isparta Province
Isparta Province is a province in southwestern Turkey. Its adjacent provinces are Afyon to the northwest, Burdur to the southwest, Antalya to the south, and Konya to the east. It has an area of 8,993 km² and a population of 448,298 up from 434,771...

, 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 zones of Puerto Rico and Cuba. Pinar del Rio Province
Pinar del Río Province
Pinar del Río is one of the provinces of Cuba. It is at the western end of the island of Cuba.-Geography:The Pinar del Río province is Cuba's westernmost province and contains one of Cuba's three main mountain ranges, the Cordillera de Guaniguanico, divided into the easterly Sierra del Rosario and...

 and Villa Clara Province
Villa Clara Province
Villa Clara is one of the provinces of Cuba. It is located in the central region of the island bordering with the Atlantic at north, Matanzas Province by west, Sancti Spiritus by east, and Cienfuegos on the South. Villa Clara shares with Cienfuegos and Sancti Spiritus on the south the Escambray...

 are Cuban regions where fasciolosis was hyperendemic. In South America, human fasciolosis is a serious problem in Bolivia, Peru, and Ecuador. These Andean
Andes
The Andes is the world's longest continental mountain range. It is a continual range of highlands along the western coast of South America. This range is about long, about to wide , and of an average height of about .Along its length, the Andes is split into several ranges, which are separated...

 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
Altiplano
The Altiplano , in west-central South America, where the Andes are at their widest, is the most extensive area of high plateau on Earth outside of Tibet...

. In the Northern Bolivian Altiplano, prevalences detected in some communities were up to 72% and 100% in coprological and serological
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

 surveys, respectively. In Peru, F. hepatica in humans occurs throughout the country. The highest prevalences were reported in Arequipa
Arequipa
Arequipa is the capital city of the Arequipa Region in southern Peru. With a population of 836,859 it is the second most populous city of the country...

, Mantaro Valley
Mantaro Valley
The Mantaro Valley, with its main city of Huancayo, lies east of the capital of Peru, Lima. It is a fertile valley containing fields of corn, artichokes, carrots and potatoes, alongside which flows the Mantaro River. The Mantaro Valley is also renowned as an area containing many sites of...

, Cajamarca
Cajamarca
Cajamarca may refer to:Colombia*Cajamarca, Tolima a town and municipality in Tolima DepartmentPeru* Cajamarca, city in Peru.* Cajamarca District, district in the Cajamarca province.* Cajamarca Province, province in the Cajamarca region....

 Valley, and Puno Region
Puno Region
Puno is a region in southeastern Peru. It is bordered by Bolivia on the east, the Madre de Dios Region on the north, the Cusco and Arequipa regions on the west, the Moquegua Region on the southwest, and the Tacna Region on the south...

. 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
Nile Delta
The Nile Delta is the delta formed in Northern Egypt where the Nile River spreads out and drains into the Mediterranean Sea. It is one of the world's largest river deltas—from Alexandria in the west to Port Said in the east, it covers some 240 km of Mediterranean coastline—and is a rich...

.

Asia

In Asia, the most human cases were reported in Iran, especially in Gīlān Province
Gilan Province
Gilan Province is one of the 31 provinces of Iran. It lies along the Caspian Sea, just west of the province of Mazandaran, east of the province of Ardabil, north of the provinces of Zanjan and Qazvin....

, on the Caspian Sea
Caspian Sea
The Caspian Sea is the largest enclosed body of water on Earth by area, variously classed as the world's largest lake or a full-fledged sea. The sea has a surface area of and a volume of...

. 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:
  • Europe: UK, Ireland, France, Portugal, Spain, Switzerland, Italy, Netherlands, Turkey, Germany, Poland
  • Asia: 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
South Cotabato
South Cotabato is a province of the Philippines located in the SOCCSKSARGEN region in Mindanao. Its capital is Koronadal City, and it borders Sultan Kudarat to the north and west, Sarangani to the south and east, and Davao del Sur to the east...

, Philippines said that laboratory tests on samples from cows, carabao
Carabao
The carabao or Bubalus bubalis carabanesis is a subspecies of the domesticated water buffalo found in the Philippines, Guam, Indonesia, Malaysia, and various parts of Southeast Asia...

s, 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 errati] weather condition in the area. They mus be treated forthwih to prevent complications with surra
Surra
Surra is a disease of vertebrate animals. The disease is caused by protozoan trypanosomes, specifically Trypanosoma evansi, of several species which infect the blood of the vertebrate host, causing fever, weakness, and lethargy which lead to weight loss and anemia...

 and hemorrhagic septicemia diseases. Surra already affected all barangays of the Surallah town.

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 reservoir
Natural reservoir
Natural reservoir or nidus, refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic and non-lethal...

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
Donkey
The donkey or ass, Equus africanus asinus, is a domesticated member of the Equidae or horse family. The wild ancestor of the donkey is the African Wild Ass, E...

s and pigs contribute to disease transmission in Bolivia. Among wild animals, it has been demonstrated that the peridomestic rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...

 (Rattus rattus) may play an important role in the spread as well as in the transmission of the parasite in Corsica
Corsica
Corsica is an island in the Mediterranean Sea. It is located west of Italy, southeast of the French mainland, and north of the island of Sardinia....

. 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 infected metacercariae. Several species of aquatic vegetables are known as a vehicle of human infection. In Europe, Nasturtium
Nasturtium (genus)
Nasturtium is a genus of five plant species in the family Brassicaceae , best known for the edible watercresses Nasturtium microphyllum and Nasturtium officinale...

 officinale
(common watercress
Watercress
Watercresses are fast-growing, aquatic or semi-aquatic, perennial plants native from Europe to central Asia, and one of the oldest known leaf vegetables consumed by human beings...

), N. silvestris, Rorippa
Rorippa
Rorippa is a flowering plant genus in the cabbage family , containing approximately 80 species native to Europe through central Asia, Africa, and North America. Rorippa species are annual to perennial herbs, usually with yellow flowers and a peppery flavour.Rorippa formerly included several species...

 amphibia
(wild watercress), Taraxacum dens leonis (dandelion leaves), Valerianella olitora (lamb's lettuce
Corn salad
Corn salad is a small dicot annual plant of the family Valerianaceae...

), and Mentha viridis (spearmint
Spearmint
Mentha spicata syn. M. cordifolia is a species of mint native to much of Europe and southwest Asia, though its exact natural range is uncertain due to extensive early cultivation. It grows in wet soils...

) 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
Algae
Algae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...

), kjosco and tortora could act as a source of infection for humans. 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.

Intermediate hosts


Intermediate hosts of F. hepatica are freshwater snails from family Lymnaeidae
Lymnaeidae
Lymnaeidae is a taxonomic family of small to large air-breathing freshwater snails, aquatic pulmonate gastropod mollusks, that belong to the clade Hygrophila....

. Snails from family Planorbidae
Planorbidae
Planorbidae, common name the ramshorn snails or ram's horn snails, is a family of air-breathing freshwater snails, aquatic pulmonate gastropod mollusks....

 act as an intermediate host of F. hepatica very occasionally.

Pathogenesis

The development of infection in 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
Thoracic diaphragm
In the anatomy of mammals, the thoracic diaphragm, or simply the diaphragm , is a sheet of internal skeletal muscle that extends across the bottom of the rib cage. The diaphragm separates the thoracic cavity from the abdominal cavity and performs an important function in respiration...

, intestinal wall, kidneys, and subcutaneous tissue can occur. During the migration of flukes, tissues are mechanically destroyed and inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 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
Hypertrophy
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It should be distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number...

 of biliar ducts associated with obstruction of the lumen occurs as a result of tissue damage.

In humans

The course of fasciolosis in humans has 4 main phases:
  • Incubation
    Incubation period
    Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

     phase
    : from the ingestion of metacercariae to the appearance of the first symptoms; time period: few days to 3 months; depends on number of ingested metacercariae and immune status of host
  • Invasive or acute phase: fluke migration up to the bile ducts. This phase is a result of mechanical destruction of the hepatic tissue and the peritoneum
    Peritoneum
    The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...

     by migrating juvenile flukes causing localized and or generalized toxic and allergic reactions. The major symptoms of this phase are:
    • Fever: usually the first symptom of the disease; 40-42°C
    • Abdominal pain
    • Gastrointestinal disturbances: loss of appetite, flatulence
      Flatulence
      Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...

      , nausea
      Nausea
      Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

      , diarrhoea
    • Urticaria
      Urticaria
      Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...

    • Respiratory symptoms (very rare): cough
      Cough
      A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...

      , dyspnoea, chest pain, hemoptysis
      Hemoptysis
      Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...

    • Hepatomegaly
      Hepatomegaly
      Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

       and splenomegaly
      Splenomegaly
      Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...

    • Ascites
      Ascites
      Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

    • Anaemia
    • Jaundice
      Jaundice
      Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

  • 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.
  • Chronic or obstructive phase:

This phase may develop months or years after initial infection. Adult flukes in the bile ducts cause inflammation and hyperplasia of the epithelium. The resulting cholangitis and cholecystitis, combined with the large body of the flukes, are sufficient to cause mechanical obstruction of the biliary duct. In this phase, biliary colic
Colic
Colic is a form of pain which starts and stops abruptly. Types include:*Baby colic, a condition, usually in infants, characterized by incessant crying*Renal colic, a pain in the flank, characteristic of kidney stones...

, epigastric pain, fatty food intolerance, nausea, jaundice, pruritus, right upper-quadrant abdominal tenderness, etc., are clinical manifestations indistinguishable from cholangitis, cholecystitis
Cholecystitis
-Signs and symptoms:Cholecystitis usually presents as a pain in the right upper quadrant. This is known as biliary colic. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site...

 and cholelithiasis of other origins. Hepatic enlargement may be associated with an enlarged spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

 or ascites. In case of obstruction, the gall bladder is usually enlarged and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

tous with thickening of the wall. 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.

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:
  • Acute Type I Fasciolosis: infectious dose is more than 5000 ingested metacercariae. Sheep suddenly die without any previous clinical signs. Ascites
    Ascites
    Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

    , abdominal
    Abdomen
    In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...

     haemorrhage, icterus, pallor
    Pallor
    Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

     of membranes, weakness may be observed in sheep.
  • Acute Type II Fasciolosis: infectious dose is 1000-5000 ingested metacercariae. As above, sheep die but briefly show pallor, loss of condition and ascites.
  • Subacute Fasciolosis: infectious dose is 800-1000 ingested metacercariae. Sheep are lethargic, anemic and may die. Weight loss is dominant feature.
  • Chronic Fasciolosis: infectious dose is 200-800 ingested metacercariae. Asymptomatic or gradual development of bottle jaw and ascites (ventral edema
    Edema
    Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

    ), emaciation, weight loss.


In blood, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

, hypoalbuminemia
Hypoalbuminemia
Hypoalbuminemia is a medical condition where levels of albumin in blood serum are abnormally low. It is a specific form of hypoproteinemia.Albumin is a major protein in the human body, making up about 60% of total human plasma protein by mass...

, and eosinophilia
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...

 may be observed in all types of fasciolosis. Elevation of liver enzyme activities, such a glutamate dehydrogenase
Glutamate dehydrogenase
Glutamate dehydrogenase is an enzyme, present in most microbes and the mitochondria of eukaryotes, as are some of the other enzymes required for urea synthesis, that converts glutamate to α-Ketoglutarate, and vice versa. In animals, the produced ammonia is, however, usually bled off to the urea...

 (GLDH), gamma-glutamyl transferase (GGT), and lactate dehydrogenase
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...

 (LDH), is detected in subacute or chronic fasciolosis from 12-15 week after ingestion of metacercariae. Economical effect of fasciolosis in sheep consists in sudden deaths of animals as well as in 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 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. Importance of cattle fasciolosis consist in economic losses caused by condemnation of livers at slaughter and production losses especially due to reduced weight gain.

In sheep and sometimes cattle, the damaged liver tissue may become infected by the Clostridium
Clostridium
Clostridium is a genus of Gram-positive bacteria, belonging to the Firmicutes. They are obligate anaerobes capable of producing endospores. Individual cells are rod-shaped, which gives them their name, from the Greek kloster or spindle...

 bacteria C. novyi
Clostridium novyi
Clostridium novyi a Gram-positive, endospore- forming, obligate anaerobic bacteria of the class clostridia. It is ubiquitous, being found in the soil and faeces. It is pathogenic, causing a wide variety of diseases in man and animals. It comes in three types, labelled A, B, and a non-pathogenic...

 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.

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. 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. No reports concerning the resistance in humans are available.

Diagnosis

In humans, diagnosis of fasciolosis is usually achieved parasitologically by findings the fluke eggs in stool, and immunologically by ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

 and Western blot
Western blot
The western blot is a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native proteins by 3-D structure or denatured proteins by the length of the polypeptide...

. 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. 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
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 from sera
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

. The antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

ic preparations used have been primarily derived from extracts of excretory/secretory products from adult worm
Worm
The term worm refers to an obsolete taxon used by Carolus Linnaeus and Jean-Baptiste Lamarck for all non-arthropod invertebrate animals, and stems from the Old English word wyrm. Currently it is used to describe many different distantly-related animals that typically have a long cylindrical...

s, or with partially purified fractions. Recently, purified native and recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...

 antigens have been used, e.g. recombinant F. hepatica cathepsin L
Cathepsin L
Cathepsin L can refer to:* Cathepsin L1, previously called cathepsin L* Cathepsin L2 or cathepsin V...

-like protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

. 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
RTG
RTG may refer to:* Radio Télévision Guinéenne, national broadcasting company of Guinea* Radioisotope thermoelectric generator, a nuclear electrical generator* Regular tree grammar, a formal grammar that describes a set of directed trees...

 of the abdominal cavity, biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 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
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...

 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
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

 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. Therefore, these methods provide early detection of the infection.

In humans

For high efficacy and safety, triclabendazole (Egaten) in dose 10–12 mg/kg is drug of choice in human fasciolosis. No drug alternatives are available for humans. On the other hand, nitazoxanide
Nitazoxanide
Nitazoxanide, also known by the brand names Alinia and Annita is a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent.Nitazoxanide is a light yellow...

 were successfully used in human fasciolosis treatment in Mexico.
Bithionol is another drug of choice used for treatment of F. hepatica.
More recently, Mirazid, an Egyptian drug made from myrrh
Myrrh
Myrrh is the aromatic oleoresin of a number of small, thorny tree species of the genus Commiphora, which grow in dry, stony soil. An oleoresin is a natural blend of an essential oil and a resin. Myrrh resin is a natural gum....

, has been investigated as an oral treatment of trematode-caused ailments including fascioliasis.

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:
  • Halogenated phenol
    Phenol
    Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...

    s
    : bithionol (Bitin), hexachlorophene (Bilevon), nitroxynil (Trodax)
  • Salicylanilides: closantel (Flukiver, Supaverm), rafoxanide (Flukanide, Ranizole)
  • Benzimidazoles: triclabendazole (Fasinex), albendazole
    Albendazole
    Albendazole, marketed as Albenza, Eskazole, Zentel and Andazol, is a member of the benzimidazole compounds used as a drug indicated for the treatment of a variety of worm infestations. Although this use is widespread in the United States, the U.S. Food and Drug Administration has not approved...

     (Vermitan, Valbazen), mebendazol (Telmin), luxabendazole (Fluxacur)
  • Sulphonamides
    Sulfonamide (medicine)
    Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...

    : clorsulon (Ivomec Plus)
  • Phenoxyalkanes: diamphenetide (Coriban)


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, later in Ireland and Scotland
Scotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...

 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.

See also

  • Fasciola hepatica
    Fasciola hepatica
    Fasciola hepatica, also known as the common liver fluke or sheep liver fluke, is a parasitic flatworm of the class Trematoda, phylum Platyhelminthes that infects the livers of various mammals, including humans. The disease caused by the fluke is called fascioliasis . F...

  • Fascioloides magna
    Fascioloides magna
    Fascioloides magna, also known as giant liver fluke, large American liver fluke or deer fluke, is an important parasite of a variety of wild and domestic ruminants in North America and Europe. Adult flukes occur in the liver of the definitive host and feed on blood...

  • Fasciolopsiasis
    Fasciolopsiasis
    Fasciolopsiasis results from an infection by the trematode Fasciolopsis buski, the largest intestinal fluke of humans .-Infection cycle:...

  • Clonorchiasis
    Clonorchiasis
    Clonorchiasis is an infectious disease caused by the Chinese liver fluke, Clonorchis sinensis.Clonorchiasis is a known risk factor for the development of cholangiocarcinoma, a neoplasm of the biliary system....


External links

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