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Progress of Who-essential Flukicide Triclabendazole and Its Remarkable Impact in Combating Fascioliasis in Human and Animal Herbivores

Rahman, M. M.
Department of Veterinary & Animal Sciences, University of Rajshahi, Rajshahi-6205, Bangladesh

Kabir, A., Ahmed
Department of Veterinary & Animal Sciences, University of Rajshahi, Rajshahi-6205, Bangladesh

S., Islam, M. K
Department of Veterinary & Animal Sciences, University of Rajshahi, Rajshahi-6205, Bangladesh

M. Alam
Department of Veterinary & Animal Sciences, University of Rajshahi, Rajshahi-6205, Bangladesh

Abstract/ Executive Summary:

Fascioliasis is a food-borne important disease in ruminants caused by Fasciola hepatica and Fasciola gigantico. WHO classifies the disease as a neglected tropical zoonosis with estimated millions of people infected and at risk of infection. Triclabendazole has become a medicine of choice both for animal and human fascioliasis. Owing to its high flukicidal efficacy, especially, against immature flukes, it has become established as the principal anti-fluke drug on the market. Consequently, triclabendazole resistance in livestock and humans continues to be reported necessitating a better insight of the crucial aspects of this drug, including pharmacokinetics, pharmacodynamics, and understanding of the mechanism of resistance and reversal of the drug. Despite years of research, the full mystery of triclabendazole use in medicine has not been yet fully deciphered and thus the issue well deserves to be dealt with. Keeping that in mind we have endeavored to elucidate the potential progress as well as aforementioned crucial aspects of the drug.

Keywords: Triclabendazole, Genesis, Fascioliasis, Pharmacokinetics, Interactions, New targets, Eficacy

Location: Department of Veterinary & Animal Sciences, University of Rajshahi, Rajshahi, Bangladesh

Start Date:

End Date:

Program Area: Resource Development and Management

Commodity: Diseases

Objectives:

To address the latest progress of triclabendazole by revisiting its efficacy, pharma- cokinetics, mechanism of actions, drug resistance and global implications.

Methodology:

Morphology, Transmission and Pathogenesis of Liver Fluke: The liver fluke Fasciola spp are leaf-shaped worms, large enough to be visible to the naked eye, adult Fasciola hepatica measures 20-30 mm x 13 mm and adult Fasciola gigantica 25-75 mm x 12 mm. The worms reside in the large biliary ducts of the mammalian host (CDC, 2015). The life-‹v cIe of Fasciola is complex. It involves a final host where the adult worm lives, an intermediate host where the larval stages of the worm develop and a carrier entailing suitable aquatic plants. The process starts when infected animals defecate in fresh-water sources. Since the worm lives in the bile ducts of such animals, its eggs are evacuated in feces and hatch into larvae that lodge in a particular type of water snail the intermediate host. Once in the snail, the larvae reproduce and eventually release more larvae into the water. These larvae swim to nearby aquatic or semi-aquatic plants, where they attach to the leaves and stems and form small cysts called metacercariae. When the plants with the small cysts attached are ingested, they act as carriers of the infection. Grass in the marshy land, watercress and water-mint are good plants for transmitting fascioliasis, but encysted larvae may also be found on many other salad vegetables. Ingestion of free metacercariae floating on water possibly detached from carrier plants may also be a possible mode of transmission (WHO, 2017b; Phil Scott, 2016; CDC, 2015). Orally administered triclabendazole (TCBZ) is well absorbed into the bloodstream. Then in the liver the drug is metabolized into a number of compounds and 9UICkIy oxidized to its effective flukicidal sulfoxide (TCBZ.SO) and sulphone (TCBZ.SO,) derivatives. Triclabendazole is highly effective against adults of the common liver flukes F. hepatica, F. gigantica and Fascioloides magna as well as all immature stages of the parasites, including early immature larvae of 1 to 9 weeks old. Triclabendazole is on the WHO's list of essential medicines and is the only flukicide effective against all early immature liver fluke larvae. Efficacy against these early immature larvae is important because these larvae significantly damage the liver tissue when migrating towards the bile ducts. In contrast with most of the other benzimidazoles and their derivatives, triclabendazole has no efficacy against nematodes or cestodes. This flukicide has only a limited residual effect. This means that a single administration will kill the parasites present in the host at the time of treatment and protect against re-infestations for a few days, but not for weeks. However, since triclabendazole kills not only the adult flukes but also the immature stages, the treated animals recover more completely and for a longer period of time. It is used abundantly in small and large ruminants mainly as a drench, or in the form of boluses, tablets often mixed with other broad-spectrum nematicides such as ivermectin, levamisole, tetramisole, albendazole, fenbendazole and abamectin. It is not used on pig, poultry, dogs or cats. For administration of triclabendazole, it is advisable to access to feed especially to fresh pasture, not to water 24 hours before administration. For increase the bioavailability of the drug, it is better to keep the animals away from food for about 6 hours after drenching. However sick, weak, or pregnant animals should not be kept away from food and fasting animals should have access to water. The drug is sold under the brand name Egaten* for the medication of human fascioliasis and Fasinex ^® is a widely used brand name for veterinary use. The drug is safe during pregnancy at certain dose, however biliary colic may occur due to dying worm (Trifina et al., 2011; Stitt et al., 1993; Wessely et al., 1988).

Source of Information: Bangladesh Journal of Veterinary and Animal Sciences, Vol.S, July 201; BJVAS, Vol. S, No. 2, July 2017; ISSN 2227-6416

Article Link (Online Journal): www.cvasu.ac.bd/journal/userlist

Funding Source:

Budget:

Total Budget (Tk.) :

Achievement/Findings:

It is obvious that various aspects of triclabendazole, for example, mechanisms of action, true extent of resistance and the pharmacodynamic interactions between the fluke and its metabolites remain to be elucidated. Reliable information on the current scenario of this drug is missing owing to a lack of dependable tests, a lack of standardized protocols and a dearth of precision in how data is assessed and reported. Given the dominant position of triclabendazole in the marketplace, the spread of resistance to It is a matter of great concern. The problem needs to be addressed by updating the current knowledge before the situation becomes as serious. Human therapy should be accompanied by advocacy and educational messages to avoid uncooked vegetables. Drug's efficacy should be maintained by enlightening the farmer to implement improved flock or herd health management program. Affinity purification of target proteins using triclabendazole as ligand, or metabolomic studies of the parasitic response to triclabendazole could be a good prospect for detection of the protein target(s) or sensitive molecular marker(s), which in turn helps for the eventual control of fascioliasis in humans and animals.

Knowledge Management: Journal