Treatment option against Fascioliasis

Fascioliasis is a disease of herbivores animals and humans. It is a neglected foodborne disease of zoonotic significance and caused by many species of trematodes of the genus Fasciola.

By Shahid Ahmad, Manahil Waheed, Muhammad Kasib Khan, Muhammad Adnan Sabir Mughal

Its distribution is worldwide and depends upon the lymnaeid snails as an intermediate host. These snails lived mostly in slightly cool and humid areas where eggs and juveniles can survive. Liver flukes are the cause of disease in most grazing sheep and cattle. It has been noted that Fasciola hepatica affects about 300 million cattle and 250 million sheep while Fasciola gigantica causes a loss of about 3oo missions US dollars annually worldwide. The disease due to F.gigantica has been mostly reported in tropical and sub-tropical parts of the world because the snail which is the intermediate host is naturally present in these areas.

Life cycle:

  • Adult liver fluke lives in the bile ducts and feeds on the epithelial cells and blood
  • The adults are hermaphrodite and so undergo sexual reproduction and lay down the eggs which are passed in the small intestine and then into the feces
  • if the eggs fall in water hatch to produce miracidia
  • miracidia swim in the water and enter the snail’s body
  • The asexual reproduction occurs in snails and thousands of cercariae are formed and come out of the snail
  • This metacercaria encyst on the vegetation and when mammals eat that vegetation on the edges of any waterbody they got infected with fascioliasis
  • These metacercaria enters the small intestine and develops into the juvenile liver flukes
  • These flukes move from the intestine to the peritoneal cavity and ultimately to the liver

 

Life cycle of Liver Fluke

Diagnosis:

The infection of fascioliasis can be detected at different stages by different tests on different samples in different states according to the facilities available or according to a situation like:

  • A flute egg count test (FEC) and the fecal sample are required for this test
  • Coproantigen ELISA test and the fecal sample are required
  • Gamma-glutamyl transferase (GGT) and the clotted blood sample are required
  • Albumen test and the clotted blood sample are required
  • Glutamate dehydrogenase (GLDH) and clotted blood are required
  • Aspartate aminotransferase (AST) and clotted blood are required
  • Differential WBC (eosinophil) count and EDTA blood required
  • PCV and EDTA blood required
  • Antibody ELISA and clotted blood or bulk tank milk is required

Signs and symptoms:

Acute infections cause weight loss, malaise, urticaria, fever, nausea, vomiting, hepatomegaly, and abdominal pain. Chronic infections may be asymptomatic or cause obstructive jaundice, cholangitis, cholelithiasis, etc. Heavy infections can cause biliary cirrhosis, sclerosing cholangitis, and ectopic lesions in the intestinal walls, lungs, and other organs.

Treatment:

There are a lot of various treatments against fascioliasis but here we are going to discuss some conventional and modern treatments for this disease.

 

Conventional treatment:

 The treatments that were used by people of ancient times are less known but some of the treatments used by them are as follows:

  1. Commiphora molmol plant has myrrh in it and it is proved to be a very good antibacterial, antiviral and antiparasitic drug. It has been proved that if it was used daily before breakfast for 6 days it proved an effective treatment against hepatica.
  2. Valeriana officinalis has valeric acid, volatile acid, alkaloids, and GABA and it is proved to be an effective treatment against nervous and intestinal disorders.
  3. Cirsium tuberosum has volatile alkaloids and cnicin. IT has been used as emetic and emmenagogue.
  4. Smilax aspera also called Rough bindweed contains flavonoids, smilagenin, volatile oil, tannins, and smilacin. It has been used against psoriasis and is similar to the radia of the Etruscan age

Plants.

  1. Thymus vulgaris contains oils mostly thymol, bitters, tannins, rosmarinic acid, and flavones that are used as an expectorant, anesthetic agents, and cough. Thyme was common by the name of mutuka in Etruscans.
  2. Anagallis arvensis commonly called Pimpernel contains saponins, tannins, flavonoids, and cucurbitacins. It is used in the treatment of liver and gallbladder disturbances as well as treating skin rashes. The Etruscan were familiar with such species.
  3. Punica granatum contains tannins and alkaloids that were used as vermifuge and anthelmintic. It is used in the treatment of tapeworms and roundworms and for treating bowl and dysentery. In the 2nd BC Catto in its writing prescribe pomegranate seed in wine to eradicate GIT problems. IN recent days, interviewing about 300 farmers, villagers and shepherds told that they are still using pomegranate seed for the treatment of children against worm infections. Punica granatum roots and bark are used as anthelmintic and molluskicides without knowing the exact way that how it works.
  4. Rubia Sativa also known as Madder and is used as a cholagogue, an emmenagogue, but due to its carcinogenic nature, it was no longer used.
  5. Helichrysum arenarium also known as Immortelle. It is used in the treatment of anti-inflammatory, analgesics, and anti-viral. Etruscan garuleum, The existence of this word indicates its presence in early Italy.
  6. Centaurium erythraea is commonly known as Centaury. Its constituents are flavonoids, alkaloids, acids, triterpenoids, etc. It is used as a sedative, antipyretic, and tonic-hepatic. Its antipyretic effect has been proved experimentally and is also documented. Herbal medicines have also written their effect against liver fluke, but it has not been proved experimentally. Centaury is extensively used as an anthelmintic in many areas. Herbalists reported that one oz of Centaury mixed with fat and flour and one oz daily dose had been given to the patient.
  7. Hyoscyamus niger is commonly known as henbane. It contains atropine, alkaloids, hyoscyamine, and scopolamine. It is commonly used in asthma, cough, as a sedative, anesthetic, and many other uses.
  8. Gentiana lutea is commonly known as Gentian. It contains amarogentin, gentianine, and glycosides. It has been used to solve GIT problems.
  9. Artemisia absinthium is commonly known as Wormwood. Its constituents are phenolic acids, volatile oil, and sesquiterpene lactones. Wormwood is used as anti-inflammatory, anthelmintic, antiparasitic, carminative, choleretic, and enhances the immune system. A tincture of Wormwood was used by west Indians as a preventive in horses, cattle, and sheep and some older farmers in Italy added it to the drinking water of animals as an anthelmintic. Three cups of Wormwood dilution were used to treat jaundice and lack of appetite.
  10. Chamomilla/Matricaria recutita is commonly known as Wild chamomile. It is used internally to treat peptic ulcers, jaundice, pinworm, and threadworm infections as well as GIT and respiratory spasms. Plants like Wild chamomile containing high content of tannin were extensively used as dewormed in ruminants in Italy and are documented as an effective treatment against parasitic infections.

Modern Treatment:

Trematode infections can be controlled by using Trematocides. Flukicides commonly used for the treatment of F.hepatica infection are Albendazole, Triclabendazole, Nitroxynil, Closantel, Oxyclozanide, Rafoxanide, and Clorsulon. They have a different spectrum of activity against different aged flukes.

Salicylanilides are effective against Fasciola species. Historically, the first line of defense for F.hepatica was Chloroquine. Emetine is an amebicidal alkaloid that is derived from ipecac. It was recommended as a drug of choice for F.hepatica. This drug was given intramuscularly in repeated doses which causes substantial gastric irritation.

Praziquantel is a broad-spectrum drug. It possessed an excellent therapeutic ratio and good efficacy against several trematodes. In contrast to praziquantel, the drug which is more effective against F.hepatica is Benzimidazole triclabendazole. It inhibits motility and diminishes the tegumentary potential of flukes in vitro.

Treatment of human fascioliasis is the use of anthelmintics to kill the flukes along with antispasmodics to treat biliary colic etc.

Albendazole is another option for the treatment of fascioliasis but it has limited anthelmintic activity against flukes older than 12 weeks. Albendazole resistance in F.hepatica has been described in Peru, Turkey, Egypt, and Tanzania.

Triclabendazole

It is a Benzimidazole derivative of ampholytic character. It was developed by Ciba to treat fascioliasis and has been in veterinary use since 1983-22. Its development for human use was started in the 1990s by a collaboration between Ciba (the manufacturer of Fasinex) and WHO.

Triclabendazole is a narrow-spectrum anthelmintic that has activity against F.hepatica. It is effective at all stages of infection. The mechanism of action is not fully clear but has multiple targets like tegumental disruption by inhibition of microtubule-based processes.

In healthy volunteers and fascioliasis patients, all the pharmacokinetic parameters were similar. Two studies were performed in Peru and Europe. One was under fasting conditions and the other was fed. Overall, food increased 2.2 fold increase in the AUC of sulphoxide metabolite. The enhanced exposure to the drug under fed conditions led to the fact that triclabendazole should always be taken with food.

It is still the first choice to treat fascioliasis because of its efficacy against both mature and immature flukes.

 

Resistance

The first case of anthelmintic resistance in liver flukes against triclabendazole was described by Overend and Bowen in sheep Numerous cases of its resistance are reported on small ruminants and cattle farms worldwide.

Triclabendazole resistance is seen in much of Europe. Closantel resistance is also seen in some reports.

Nitazoxanide proves to be a good alternative to triclabendazole in chronic cases. It is recommended as 500 mg B.D for 7 days in adults.

Recommended doses

  1. Albendazole is administered orally. It comes with the trade names Albex 10% or Albendazole. Albendazole should be given as 30ml/100kg body weight. It is available in USA and Canada. It should be given in fluke life from 10 weeks onwards.
  2. Rafoxanide is also an orally administered drug. It comes with the trade name Rafoxanide. Its recommended dose is 2.5ml/10kg body weight. It should be given a fluke life of 4 weeks onwards.
  3. Oxyclozanide is an oral drug that comes with the trade name Zanil. Recommended dose is 30ml/100kg body weight. It should be given 10 weeks onwards of fluke life.
  4. Oxyclozanide 15mg/kg is also administered orally and comes with the name Zande. Its concentration is Oxyclozanide 15mg/kg and levamisole 7.5mg/kg. Its recommended dose is 50ml/100kg body weight.
  5. Closantel comes with the trade name Flukiver 5%. It is an orally administered drug. Recommended dose is 10mg/kg.
  6. Triclabendazole is also an orally administered drug. Its trade names are fluke scan or fascines 240 24%. Its concentration is 10%. The recommended dose is 6ml/50 kg. It is administered 2 weeks onwards of fluke life.
  7. Clorsulon is given 10 weeks onwards of fluke life. It can be effective from 8 weeks but higher doses are required for better results.