| Fasciolosis | |
|---|---|
| Other names | Fascioliasis, fasciolasis, distomatosis, liver rot |
 | |
| Fasciola hepatica | |
| Specialty | Infectious disease,hepatology |
| Symptoms | Abdominal pain, nausea, yellow skin |
| Complications | Pancreatitis,anemia[1] |
| Causes | Fasciola flatworms |
| Risk factors | Eating rawwatercress |
| Diagnostic method | Stool sample[2] |
| Prevention | Proper food preparation |
| Medication | Triclabendazole[1] |
| Frequency | 2 millions[1] |
Fasciolosis is aparasitic worm infection caused by the common liver flukeFasciola hepatica as well as byFasciola gigantica. The disease is a plant-bornetrematodezoonosis,[3] and is classified as aneglected tropical disease (NTD).[4][5] It affects humans, but its main host is ruminants such ascattle andsheep.[4] The disease progresses through four distinct phases; an initial incubation phase of between a few days up to three months with little or no symptoms; an invasive or acute phase which may manifest with: fever, malaise, abdominal pain, gastrointestinal symptoms, urticaria,anemia,jaundice, andrespiratory symptoms.[6] The disease later progresses to a latent phase with fewer symptoms and ultimately into a chronic or obstructive phase months to years later.[7][8] In the chronic state the disease causes inflammation of thebile ducts,gall bladder and may causegall stones as well asfibrosis.[4] While chronic inflammation is connected to increased cancer rates, it is unclear whether fasciolosis is associated with increased cancer risk.[9]
Up to half of those infected display no symptoms,[4] and diagnosis is difficult because the worm eggs are often missed in fecal examination.[4] The methods of detection are through fecal examination, parasite-specific antibody detection, or radiological diagnosis, as well aslaparotomy. In case of a suspected outbreak it may be useful to keep track of dietary history, which is also useful for the exclusion of differential diagnoses.[4] Fecal examination is generally not helpful because the worm eggs can seldom be detected in the chronic phase of the infection. Eggs appear in the feces first between 9–11 weeks post-infection. The cause of this is unknown, and it is also difficult to distinguish between the different species of fasciola as well as distinguishing them fromechinostomes andFasciolopsis.[4] Most immunodiagnostic tests detect infection with very high sensitivity, and as concentration drops after treatment, it is a very good diagnostic method.[4] Clinically it is not possible to differentiate from otherliver and bile diseases. Radiological methods can detect lesions in both acute and chronic infections, while laparotomy will detect lesions and also occasionally eggs and live worms.[4]
Because of the size of the parasite, as adultF. hepatica: 20–30 × 13 mm (0.79–1.18 × 0.51 inches) or adultF. gigantica: 25–75 × 12 mm (0.98–2.95 × 0.47 inches), fasciolosis is a big concern.[4] The amount of symptoms depends on how many worms and what stage the infection is in. The death rate is significant in both cattle (67.55%) and goats (24.61%),[10] but generally low among humans.[citation needed] Treatment withtriclabendazole has been highly effective against the adult worms as well as various developing stages.[4][6]Praziquantel is not effective, and older drugs such asbithionol are moderately effective but also cause more side effects. Secondary bacterial infection causingcholangitis has also been a concern and can be treated with antibiotics, andtoxaemia may be treated withprednisolone.[4]
Humans are infected by eating watergrown plants, primarily wild-grownwatercress in Europe ormorning glory in Asia. Infection may also occur by drinking contaminated water with floatingyoung fasciola or when using utensils washed with contaminated water.[4] Cultivated plants do not spread the disease in the same capacity. Human infection is rare, even if the infection rate is high among animals. Especially high rates of human infection have been found in Bolivia, Peru, and Egypt, and this may be due to consumption of certain foods.[4] No vaccine is available to protect people againstFasciola infection.[11] Preventative measures are primarily treating and immunization of the livestock, which are required to host the live cycle of the worms. Veterinary vaccines are in development, and their use is being considered by several countries on account of the risk to human health and economic losses resulting from livestock infection.[4] Other methods include usingmolluscicides to decrease the number of snails that act as vectors, but it is not practical.[4] Educational methods to decrease consumption of wild watercress and other water plants have been shown to work in areas with a high disease burden.[4]
Fascioliasis occurs in Europe, Africa, the Americas as well as Oceania.[4] Recently, worldwide losses in animal productivity due to fasciolosis were conservatively estimated at over US$3.2 billion per annum.[12] Fasciolosis is now recognized as an emerging human disease: theWorld Health Organization (WHO) has estimated that 2.4 million people are infected withFasciola, and a further 180 million are at risk of infection.[13]
The course of fasciolosis in humans has 4 main phases:[7]
This phase may develop months or years after the 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, biliarycolic,epigastric pain, fatty food intolerance, nausea, jaundice,pruritus, right upper quadrant abdominal tenderness, etc., are clinical manifestations indistinguishable fromcholangitis,cholecystitis andcholelithiasis of other origins. Hepatic enlargement may be associated with an enlargedspleen or ascites. In case of obstruction, the gall bladder is usually enlarged andedematous with thickening of the wall (Ref: Hepatobiliary Fascioliasis:Sonographic and CT Findings in 87 Patients During the InitialPhase and Long-Term Follow-Up. Adnan Kabaalioglu, Kagan Ceken, Emel Alimoglu, Rabin Saba, Metin Cubuk, Gokhan Arslan, Ali Apaydin. AJR 2007; 189:824–828). 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.[7]
Veterinary clinical[15] 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:[16][17]
In blood,anemia,hypoalbuminemia, andeosinophilia may be observed in all types of fasciolosis.[17] Elevation ofliver enzyme activities, such asglutamate dehydrogenase (GLDH),gamma-glutamyl transferase (GGT), andlactate dehydrogenase (LDH), is detected in subacute or chronic fasciolosis from 12 to 15 weeks after ingestion of metacercariae.[18][19] Economical effect of fasciolosis in sheep consists in sudden deaths of animals as well as in the reduction of weight gain and wool production.[20][21] In goats and cattle, the clinical manifestation is similar to sheep. However, acquired resistance toF. hepatica infection is well-known in adult cattle.[22][23] 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.[24] The Importance of cattle fasciolosis consists in economic losses caused by condemnation of livers at slaughter and production losses especially due to reduced weight gain.[25]
In sheep and sometimes cattle, the damaged liver tissue may become infected by theClostridium bacteriaC. novyi type B. The bacteria will release toxins into the bloodstream resulting in what is known asblack disease. There is no cure and death follows quickly. AsC. novyi is common in the environment, black disease is found wherever populations of liver flukes and sheep overlap.[26]
Fasciolosis is caused by twodigenetic trematodesF. hepatica andF. gigantica. Adult flukes of both species are localized in thebile ducts of theliver orgallbladder.F. hepatica measures 2 to 3 cm and has acosmopolitan distribution.F. gigantica measures 4 to 10 cm in length and the distribution of the species is limited to thetropics and has been recorded in Africa, the Middle East, Eastern Europe, and South and Eastern Asia.[28] In domestic livestock in Japan,diploid (2n = 20),triploid (3n = 30) andchimeric flukes (2n/3n) have been described, many of which reproduceparthenogenetically. As a result of this unclear classification, flukes in Japan are normally referred to asFasciola spp.[29] Recent reports based onmitochondrial genes analysis have shown that JapaneseFasciola spp. is more closely related toF. gigantica than toF. hepatica.[30] In India, a species calledF. jacksoni was described inelephants.[31]
HumanF. hepatica infection is determined by the presence of the intermediate snail hosts, domestic herbivorous animals, climatic conditions, and the dietary habits of man.[32] Sheep, goats and cattle are considered the predominant animalreservoirs. While other animals can be infected, they are usually not very important for human disease transmission. On the other hand, some authors have observed thatdonkeys and pigs contribute to disease transmission in Bolivia.[33] Among wild animals, it has been demonstrated that the peridomesticrat (Rattus rattus) may play an important role in the spread as well as in the transmission of the parasite inCorsica.[34] In France,nutria (Myocastor coypus) was confirmed as a wild reservoir host ofF. hepatica.[35] Humans are infected by ingestion of aquatic plants that contain the infectiouscercariae.[36] 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), andMentha viridis (spearmint) were reported as a source of human infections.[7] 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.[37] BecauseF. hepaticacercariae also encyst on water surface, humans can be infected by drinking of fresh untreated water containing cercariae.[32] In addition, an experimental study suggested that humans consuming raw liver dishes from fresh livers infected with juvenile flukes could become infected.[38]
Intermediate hosts ofF. hepatica are freshwater snails from familyLymnaeidae.[28][39] Snails from familyPlanorbidae act as an intermediate host ofF. hepatica very occasionally.[3]
The development of infection in a definitive host is divided into two phases: the parenchymal (migratory) phase and the biliary phase.[16] 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.[17] Occasionally, ectopic locations of flukes such as the lungs,diaphragm, intestinal wall, kidneys, and subcutaneous tissue can occur.[24][32] During the migration of flukes, tissues are mechanically destroyed andinflammation appears around migratory tracks of flukes. The second phase (the biliary phase) begins when parasites enter thebiliary ducts of the liver. In biliary ducts, flukes mature, feed on blood, and produce eggs.Hypertrophy of biliary ducts associated with obstruction of the lumen occurs as a result of tissue damage.[citation needed]
Mechanisms of resistance have been studied by several authors in different animal species. These studies may help to better understand theimmune response toF. hepatica in the host and are necessary for the development of a vaccine against the parasite. It has been established that cattle acquire resistance to challenge infection withF. hepatica andF. gigantica when they have been sensitized with primary patent or drug-abbreviated infection.[22] Resistance to fasciolosis was also documented in rats.[40] On the other hand, sheep and goats are not resistant to re-infection withF. hepatica.[41][42] However, there is evidence that two sheep breeds, in particularIndonesian thin tail sheep andRed maasai sheep, are resistant toF. gigantica.[43][44]
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.[4] In humans, diagnosis of fasciolosis is usually achieved parasitologically by findings the fluke eggs in stool, and immunologically byELISA andWestern 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.[citation needed]
Moreover, in many human infections, the fluke eggs are often not found in the faeces, even after multiple faecal examinations.[32][45] Furthermore, eggs ofF. hepatica,F. gigantica andFasciolopsis buski are morphologically indistinguishable.[45] Therefore, immunological methods such as ELISA and enzyme-linked immunoelectrotransfer blot, also called Western blot, are the most important methods in the diagnosis ofF. hepatica infection. These immunological tests are based on the detection of species-specificantibodies fromsera. Theantigenic preparations used have been primarily derived from extracts of excretory/secretory products from adultworms, or with partially purified fractions.[46] Recently, purified native andrecombinant antigens have been used, e.g. recombinantF. hepaticacathepsin L-likeprotease.[47]
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 andxray 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-freediet several days before a repeat stool examination.[46]
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.[16][28] Similarly to humans, faeces examinations are not reliable. Moreover, the fluke eggs are detectable in faeces 8–12 weeks post-infection. Despite that fact, faecal examination is still the only used diagnostic tool in some countries. While coprological diagnosis of fasciolosis is possible from 8- to 12 weeks post-infection (WPI),F. hepatica specific-antibodies are recognized using ELISA or Western blot after 2-4 weeks post-infection.[48][49] Therefore, these methods provide early detection of the infection.[citation needed]
In some areas, special control programs are in place or have been planned.[11] The types of control measures depend on the setting (such as epidemiologic, ecologic, and cultural factors).[11] 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.[11] Travelers to areas with poor sanitation should avoid food and water that might be contaminated (tainted).[11] Vegetables grown in fields, that might have been irrigated with polluted water, should be thoroughly cooked, as should viscera from potentially infected animals.[11]
Several drugs are effective for fascioliasis, both in humans and in domestic animals. The drug of choice in the treatment of fasciolosis istriclabendazole, a member of thebenzimidazole family ofanthelmintics.[50] The drug works by preventing the polymerization of the moleculetubulin into thecytoskeletal structures,microtubules. Resistance ofF. hepatica to triclabendazole has been recorded in Australia in 1995[51] and Ireland in 1998.[52]
Praziquantel treatment is ineffective.[53][54] There are case reports ofnitazoxanide being successfully used in human fasciolosis treatment in Mexico.[55] There are also reports ofbithionol being used successfully.[56]
Nitazoxanide has been found effective in trials, but is currently not recommended.[4]
Only clorsulon andalbendazole are approved for use in the treatment of domestic animals in the United States, but the available flukicides used worldwide also includetriclabendazole,netobimin, closantel,rafoxanide, nitroxynil, andoxyclozanide; however, this list of available drugs has some drawbacks.[57] Closantel, nitroxynil, and oxyclozanide are not effective against young liver flukes and should only be used to treat subacute and chronic infections. Triclabendazole is effective at killing flukes of any age, but over-use has resulted in increasing resistance to this drug, so it should only be used to treat early infections, with later stages treated with other fasciolicides.[58] The timing of treatment is critical for success, and is determined by environmental factors and analysis of the expected distribution and prevalence of the disease. For example, in European countries that have large numbers of sheep, computerized systems predict when fascioliasis is most likely to make the biggest impact on sheep populations and how many sheep will most likely be affected. The predictions are dependent on guessing when environmental conditions that are most conducive to parasite multiplication will occur, such as the amount of rainfall, evapotranspiration, and the ratio of wet to dry days in a particular month. If heavy infections are expected to occur, treatment for sheep should begin in September/October, then again in January/February, and finally in April/May; the amount of hatching fluke eggs is minimal during these times because they require a warm, wet environment, making treatment more effective.[57]
Human and animal fasciolosis occurs worldwide.[28] 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.[citation needed]
Studies carried out in recent years have shown human fasciolosis to be an importantpublic health problem.[32] 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.[7][8] 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 andmesoendemics 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 orhypoendemic.[8]
In Europe, human fasciolosis occurs mainly in France, Spain, Portugal, and the former USSR.[8] 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.[59] Concerning the former Soviet Union, almost all reported cases were from theTajik Republic.[8] Several papers referred to human fasciolosis in Turkey.[60] Recently,serological survey of human fasciolosis was performed in some parts of Turkey. The prevalence of the disease wasserologically found to be 3.01% inAntalya Province, and between 0.9 and 6.1% inIsparta Province, Mediterranean region of Turkey.[61] In other European countries, fasciolosis is sporadic and the occurrence of the disease is usually combined with travelling to endemic areas.[citation needed]
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 andVilla Clara Province are Cuban regions where fasciolosis was hyperendemic. In South America, human fasciolosis is a serious problem in Bolivia, Peru, and Ecuador. TheseAndean 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 calledaltiplano. In the Northern Bolivian Altiplano, prevalences detected in some communities were up to 72% and 100% incoprological andserological surveys, respectively.[7] In Peru,F. hepatica in humans occurs throughout the country. The highest prevalences were reported inArequipa,Mantaro Valley,Cajamarca Valley, andPuno Region.[3] 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.[citation needed]
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 theNile Delta.[3]
In Asia, the most human cases were reported in Iran, especially inGīlān Province, on theCaspian 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.[7]
In Australia, human fasciolosis is very rare (only 12 cases documented). In New Zealand,F. hepatica has never been detected in humans.[7]
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:[62]
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 inF. hepatica. In animals, triclabendazole resistance was first described in Australia,[63] later in Ireland[64] andScotland[65] and more recently in the Netherlands.[66] 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.[67] Countries where fasciolosis in livestock was repeatedly reported:[citation needed]
On September 8, 2007, Veterinary officials inSouth 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 withsurra andhemorrhagicsepticemia diseases. Surra already affected allbarangays of theSurallah town.[68]
