Thursday, January 27, 2011

What The Heck Is Liver Rot? Its A Fluke

Off The Cuff

After watching the video and reading this entry you may be up all night.............

By Dr. Hans Orlent, Dr. Dominik Selleslaq,and Dr. Stefaan Vandecasteele.

Published previously in Gastroenterology2007;132:15-6.

A 62-year-old woman presented with a 2-week history of intermittent right upper quadrant biliary pain. No abnormalities were noted on clinical examination.

Laboratory examinations showed a white cellcount of 13,100 (neutrophils 17%,eosinophils 48%, lymphocytes 19%),AST of 36 U/L, ALT of 49 U/L, alkaline phosphatase of 216 U/L, gamma-glutamyl transferase of 101U/L, and a normal serum bilirubin.

Abdominal ultrasound showed an irregularly demarcated zone with a diameter of 4 cm in the right liver lobe. T2-weighted turbospin-echo image MRI showed an in homogeneous hyperintense a realocated subcapsular in segmentVI/VII containing multiple hypointense areas. T1-weighted 3-Dgradient-echo image displayed inhomogeneous contrast-enhancement

What is the most likely diagnosis in this patient?
Which diagnostic procedure would you perform?

Answer to ‘What’s Your Diagnosis?’

Fasciola hepatica Infection

In view of the clinical presentation, a Fasciola hepatica infection was suspected. No ova were detected in a first fresh stool sample. Serology for Fasciola hepatica was requested. Repeat stool examination confirmed the presence of a Fasciola egg (see image at right) by the time the serology result was known to be strongly positive. Fascioliasis is a zoonosis that is prevalent in domestic livestock worldwide, where the disease is known as liver rot.

The liver fluke Fasciola hepatica has a digenetic lifecycle, requiring water snails as intermediate host. Man becomes an accidental final host after the ingestion of loof – typically watercress – that is contaminated with infectious metacercariae.

The metacercariae exist in the human upper gastrointestinal tract, penetrate the intestinal wall, and migrate through the visceral peritoneum, finally boring their way through the liver capsule. The young flukes migrate from the subcapsular parenchyma to the biliary tree were the hermaphrodite adult flatworms can reside for years, giving rise to obstructive jaundice, cholangitis, or cholangiocarcinoma.

This migratory cycle explains the symptoms in the right upper quadrant that is invariably accompanied by a marked eosinophilia in the acute phase (1). cross-sectional imaging reflect the parenchymal migration of the young flukes in the early phase of infection from the liver capsule to the biliary tree(2).

Diagnosis can be easily confirmed with serology and stool examination.The current treatment of choice consistsof oral triclabendazole

(3).References1. Arjona R, et al. Medicine (Baltimore).1995;74:13-23.2. Han JK, et al. Trop. Med. Int. Health1996;1:367-72.3. Graham CS, et al. Clin. Infect. Dis. 2001

The Adult Worm - Averaging 30mm in length and 13 mm in width, Fasciola hepatica is one of the largest flukes in the world. The adult worm has a very characteristic leaf shape with the anterior end being broader than the posterior end and an anterior cone-shaped projection.

Agent: Fasciola Hepatica (Sheep Liver Fluke)

The fluke possesses a powerful oral sucker at the end the anterior cone and a ventral sucker at the base of the cone which allow it to attach to the lining of the biliary ducts. Each worm possesses ovaries and testes which are highly branched and allow for individual flukes to produce eggs independently.
The Egg - The eggs of Fasciola hepatica are operculated and average 140 μm in length and 75 μm in width.

Eggs of Fasciola hepatica have been found in mummies, showing that human infection was occuring at least as early as Pharaonic times. Indeed, F. hepatica was the first fluke or trematode to be reported. It was first discovered, however, not in humans, but in sheep where it causes a more obvious burden.
Great Video !

A French man, Jehan de Brie, made the earliest references to F. hepatica and accurately recognized the source of infection in his 1379 publication, Le Bon Berger (The Good Shepherd). It is from this early text that F. hepatica required its common name, sheep liver fluke. References to the sheep liver fluke appear in animal husbandry texts throughout the next several centuries until it was given its Latin name by Linnaeus in 1758 and it was not until the late 19th century that F. hepatica's life cycle was elucidated and its role in humans was commonly recognized. Since then, fascioliasis has become one of the most studied hemintic infections and holds a high-raking position in the minds of public health policy makers.

Fasciola hepatica is found on every continent with nearly 180 million people at risk and an estimated 2.4 million people already infected worldwide. Prevalence is highest in areas where extensive sheep and cattle raising occurs and where dietary practices include the consumption of raw aquatic vegetables. In many locations such as Portugal, the Nile delta, northern Iran, parts of China, and the Andean highlands of Ecuador, Bolivia, and Peru, infections rates are high enough to make fascioliasis a serious public health concern.

The need for temperate, slow-moving or standing water in F. hepatica's life cycle and transmission had previously kept infection limited to populations within well-defined watershed boundaries. Recently however, urbanization, migration, and development practices such as dam building and irrigation have increased the populations at risk and the incidence of human infection has increased significantly over the past 20 years.

There is no vector in Fasciola hepatica transmission.
Transmission occurs through the ingestion of raw, fresh-water vegetation on which the flukes in their metacercariae form are encysted. The plants become exposed to the metacariae when the body of water that the vegetation is growing in becomes contaminated by eggs in the fecal matter of an infected host. Nearly all cases are a result of watercress consumption, although alfalfa and water lettuce play a large role is some areas. A form of infection known as halzoun that is specific to the Middle East is contracted by eating the raw liver of an infected animal.

Despite high infection rates, humans are only accidental hosts of of the Fasciola hepatica parasite. The primary definitive hosts of F. hepatica are domestic and wild ruminants although infections have been found in any number of mammalian herbivores. Fascioliasis in sheep and cattle is a serious problem both in terms of economic loss and transmission to humans. Because so many animals can ac as hosts, the reservoir for F. hepatica is large and represents a serious challenge to control efforts.

Clinical Presentation:
Up to 50% of Fasciola hepatica infections are asymptomatic and disease may appear anywhere from a few days to several years after infection.

Eosinophilia is present with all infections at all stages and can be used as a diagnostic factor in ectopic and early stage infections when eggs are not be present in the stool.

When symptoms do appear, they occur in the following patterns:
Acute Phase – The acute phase of infection is rarely seen in humans and occurs only when a large number of metacercariae are ingested at once. Fever, tender hepatomegaly, and abdominal pain are the most frequent symptoms of this stage of infection although vomiting, diarrhea, urticaria (hives), anemia, and may all be present.

The above characteristics of the acute phase are caused by the migration of the F. hepatica larvae throughout the liver parenchyma. The larvae penetrate the liver capsule and begin to produce the above symptoms 4-7 days after ingestion. Migration and thus the acute phase continues for 6-8 weeks until the larvae mature and settle in the bile ducts.

Chronic Phase – The symptoms of chronic infection are much more common in human populations and include biliary cholic, abdominal pain, tender hepatomegaly, and jaundice. In children, severe anemia is a common result of infection and is the greatest source of disability from infection in this age group. These symptoms reflect the biliary obstruction and inflammation caused by the presence of the large adult worms and their metabolic waste in the bile ducts.

Inflammation of the bile ducts eventually leads to fibrosis and a condition called "pipestem liver", a term describing the white appearance of the bilary ducts after fibrosis. The final outcome of severe infections is portal cirrhosis and even death.

Halzoun – The condition commonly known as halzoun is a type of Fasciola hepatica infection in which the worm settles in the pharynx. This occurs when an individual consumes infected raw liver. The young adult worms then attach themselves to the pharangeal mucosa which causes considerable pain, edema, and bleeding that can interfere with respiration. The adults can live in the biliary ducts, causing symptoms for up to 10 years.
Ectopic Infection – Ectopic infections through normal transmission are infrequent but can occur in the peritoneal cavity, intestinal wall, lungs, subcutaneous tissue, and very rarely in other locations.

Diagnostic Tests:
The definitve and most widely used form of diagnosis is the directly observed presence of Fasciola hepatica eggs either in a stool sample, duodenal aspirate or biliary aspirate.
However, the flukes do not begin to produce eggs until roughly 4 months after infection. Until this time and in the case of ectopic infections where eggs are not present in the stool, serological tests can be used, the FAST-ELISA being the most popular. It has a sensitivity of 95% and can detect specific F. hepatic antibodies as early as 2 weeks after infection. False positives are not common although there is some possibility of cross-reactivity with the schistosomiasis antibodies. The FAST-ELISA can also be used to confirm effective cure as antibody levels return to normal in 6-12 months after the cessation of infection.
Ultrasound can be used to visualize the adult flukes in the bile ducts and a CT scan may reveal the burrow tracts made by the worms and dialation of the bile ducts.

Management and Therapy:
Treatment for fascioliasis has a 80-100% success rate.
In many countries, a 5-10 day course of oral bithionol at 30 mg/kg body weight is not only the preferred treatment but the only one available. It is highly effective when administered as above, but the high dose, cost and length of treatment have made it problematic for large-scale control efforts.

Triclabendazole, an antihelmintic agent long used in veterinary medicine, has recently been proven to provide substantial human benefit at much lower doses than bithionol. In 1990, the WHO and pharmaceutical company, Ciba-Geigy, partnered to conduct clinical trials of triclbendazole and found that 1-2 oral doses at 10 mg/kg body weight administered in a single 24 hour period results in virtually no side effects and has a success rate approaching 100%. Following this research, the Ministry of Health of the Arab Republic of Egypt registered triclabendazole for human use and the WHO Expert Committee on the Use of Essential Drugs has recommended that it be added to the WHO's list of essential drugs. Triclabendazole remains unavailable in most countries but its future both in terms of individual treatment and broad-scale public health measures appears very promising.
Along with pharmaceutical therapy, surgery may be necessary in very extreme cases to clear the biliary tract.

Public Health and Prevention Strategies:
The presence of infection in a population is dependent upon and exacerbated by four factors:
the presence of a substantial reservoir
the presence of the intermediate host, the Lymanaea snails
the opportunity for water source contamination by human and non-human hosts
dietary practices that include the consumption of raw, untreated aquatic vegetation
Therefore, the most effective public health measures need to address several, if not all, of these factors.
Education – Behaviour changes have the potential to be the most effective and cost efficient approaches to disease control and thus, education is an essential aspect of any public health effort. The primary message of Fasciola hepatica campaigns is to keep domestic animal herds separate from the growing sites of aquatic. This limits the risk of contaminating the vegetation and thus decreases bith human infection and the animal reservoir.
Teaching the washing of vegetables in either 6% vinegar or potassium permanganate for 5 to 10 minutes, which destroys the encysted metacercariae, is another useful educational effort. This approach has proven more acceptable to communities than past attempts to entirely halt the consumption of raw vegetables.

Despite the prevalence of fascioliasis in many regions, physicians and health workers often do not consider the possibility of Fasciola hepatica infection when treating patients and thus, would benefit from awareness training. This would increase timely identification and treatment, decreasing both the individual disease burden and transmission by way of the human reservoir.
Molluscicides – The most frequently used public health intervention is the application of molluscicides to decrease the population of Lymnaea snails, the intermediate hosts of Fasciola hepatica. Molluscicides have been particularly popular because they also decrease transmission of many other trematodes of importance, such as the various Schistosoma species.
Chemotherapy – Chemotherapy has been used for years in animal populations to decrease the animal reservoir and reduce agricultural losses. Until recently, however, bithionol was the only treatment available for fascioliasis and its cost, high doses, and the extended length of treatment effectively prohibited its use for large-scale campaigns. The antihelmintic Tribendazole is not yet approved in most countries, but shows great promise for its utility in single-dose chemotherapy efforts to control morbidity and transmission in endemic areas.

No comments:

Post a Comment