Addis Ababa University

College of Veterinary Medicine and Agriculture

Anthelmintic and their mode of action

By: Professor Yacob Hailu

• Anthelmintic is the term used to describe a
drug used to treat infections of animals with
parasitic worms. This includes both flat
worms, e.g., flukes (trematodes) and
tapeworms (cestodes) as well as round worms
(nematodes). The parasites are of huge
importance for human tropical medicine and
for veterinary medicine.
• Anthelmintic is the term used to describe a
drug used to treat infections of animals with
parasitic worms. This includes both flat
worms, e.g., flukes (trematodes) and
tapeworms (cestodes) as well as round worms
(nematodes). The parasites are of huge
importance for human tropical medicine and
for veterinary medicine.
 For treatment of cestodes many good anthelmintics available:
The most common treatment for tapeworm infection
involves oral medications that are toxic to the adult
tapeworm, including: Praziquantel
(Biltricide) Albendazole (Albenza) Nitazoxanide
(Alinia)
 Mechanism of action: Ex: Praziquantel works by causing
severe spasms and paralysis of the worms' muscles.
 For treatment of trematodes many good anthelmintics available: The most
common treatment for trematodes infection involves oral medications that are
toxic to the adult flukes, including: Praziquantel (Biltricide) Albendazole
(Albenza) Nitazoxanide (Alinia), Triclabendazole (TCZ) has selective
activity against immature and mature trematodes and is used for treatment of
fascioliasis

• Mechanism of action: Ex:Praziquantel has a selective effect on the tegument

of trematodes and increases permeability of calcium.
• Praziquantel works by causing severe spasms and paralysis of the
worms' muscles. Some kinds of worms are then passed in the stool

 Other anthelmintics have a biochemical mode of action. The benzimidazole

drugs bind selectively to beta-tubulin of nematodes, cestodes and fluke
interrupt parasite energy metabolism by binding to tubulin, thereby disrupting
microtubular cell structure and preventing nutrient uptake and other functions.

 Similarly, triclabendazole results from inhibition of microtubule formation.

 For treatment of nematodes many good anthelmintics
available:
 Levamisole
 Pyrantel
 Benzimidazoles(BZ)
 Macrocyclic lactones (ML’s): Ivermectin
 ML’s: High efficacy, often 100% against immature stages
 Low toxicity, some anthelmintics are cheap
Mechanism of action: Some anthelmintic drugs act rapidly
and selectively on neuromuscular transmission of
nematodes
 Efficacy of anthelmintics (I)

 Be sure that you have anthelmintics of good quality: Try to evaluate the efficacy of
your anthelmintics! Buy from companies you trust
 In tropical countries many anthelmintics are false or of limited efficacy
 In a confidential report it was seen in Brazil that out of 11 formulations of
ivermectin:
 2 of them had 100% of the stated efficacy
 2 of them had no active drug present (No risk or resistance!)
 7 of them had amounts of active drug between 11 & 85%
 In Ethiopia, there is no any report of ivermectin resistance [Yacob et la., 2009
reported that because of the fact that this drug is not used for startegic deworming
like I Europe and some African countries where resistance is already reported]
H.T. Yacob, Ch. Mistre, A.H. Adem 1, A.K. Basu (2009): Parasitological and
clinical responses of lambs experimentally infected with Haemonchus contortus
(L3) with and without ivermectin treatment. Veterinary Parasitology 166
(2009) 119–123.
 Levamisole - Pyrantel

 Both are good nematocides

 Efficacy against adults: > 90%
 Efficacy against immatures > 80%
 Efficacy against inhibited stage: Nill
 Administration: oral, levamisole also injectable
 Safe
 Pyrantel is drug of choice to treat toxocara in calves( at the age
of 10-16 days): 97% efficacy against immatures, 100% against
adults
 Benzimidazoles

 Several molecules available:

 Albendazole
 Fenbendazole
 Mebendazole
 Febantel
 Netobimine
 They are very good nematocides:
• Efficacy against adults > 95%
• Efficacy against immatures > 90%
• Efficacy against inhibited stages: variable
• Administration : Oral (suspension/bolus)
 Macrocyclic lactones
 Several drugs are available:
 Ivermectin
 Doramectin
 Moxidectin
 Eprinomectin
 Abamectin
 Best nematocides!
• Efficacy against adults > 99%
• Efficacy against immatures > 99%
• Efficacy against inhibited stages > 99%
• The macrocyclic lactones act by binding to glutamate-gated chloride
channel receptors in nematode and arthropod nerve cells. This causes
the channel to open, allowing an influx of chloride ions.
 Ivermectin

 Revolutionized antiparasite because:

 High efficacy against both endoparasites and ectoparasites
o Efficacy against more than 300 species of parasites
 High efficacy ( often > 99%) against all developmental stages
of nematodes: inhibited, adults, immature
 Persistent efficacy of several weeks
 Can be used in wide range of hosts: production animals,
companion animals and man
 Why chemical control of nematodes is
important?
 Good anthelmintics available
 Reductions of pasture contamination will be achieved
 Any control program is not aimed to eradicate nematode
infections (Impossible!) but to reduce parasite population at
the level :
 production losses are minimized
 Animals are still able to develop immunity
 Any long term worm control program should aim at reducing
the contamination of the environment (Prophylaxis)
 Anthelmintic resistance

 AH resistance is a situation when normal dosage of a drug

does not promote a consistent reduction of worms or excreted
eggs
 Resistant genes exist as rare alleles in natural populations
 It develops when selection pressure is high
 Family resistance, multiple resistance
 Is it possible to reverse resistance? No hope!
 Antihelminitic resistance

 In small ruminants: H. contortus, T. circumcinata, T.

colubriformis (+++)
 Cattle: Cooperia spp, H. placei, T. axei, O. ostertagi (+/_ )
 Equines: Cyathostomes (++)
 Prevalence of antihelmintic resistance

Parasite Country BZ Levamisole LM

H. contortus Australia + + +
Europe + + +
USA + + +
Asia + + _
T. cirumcinata Australia + + +
Europe + + _
USA + + _
T. coubriformis Australia + + _
Europe + _ _
USA + _ -
Africa /Ethiopia
?
 Mechanisms of AH resistance

 Their long-term utilization, inappropriate handling and under

dosage may be some of the reasons for their reduced efficacy
and for the increasing development of drug resistance.
 Anthelmintic Resistance mechanisms includes:
 mutation or deletion of one or more amino acids in the
target genes
 reduction in the number of receptors,
decreased affinity of receptors for drugs,
absence of bio-activating enzymes.
 Spreading of resistant alleles

 Factors related to human activities:

• Animal Breeding
• Frequent use of antihelmintics
 Factors related to ecology and biology of parasites:
 Factors related to the genetics of resistance:
• Dominant/recessive character
 Contributing factors to AH resistance

 Under dosing
 Treatment frequency (use of the same AH family)
 Population size in refugia at the time of treatment
 Purchase of infected hosts
 The use of common pastures
NB: an area in which a population of organisms can survive
through a period of unfavourable conditions
 Recommended dose of AH in sheep and goats

• Double doses of AH in goats are required compared to sheep

because plasma concentration of Ah in goats will be less as a
result of increased metabolic rate resulting in faster &
immediate excretion of anthelmintics
Recommended doses of the main molecules in
sheep & goats (BZ, LEV,ML, Closantel)

Anthelmentic Molecule Ovine dose Caprine dose

BZ Albendazole 3.8 7.6
Febantel 5 10
Thiabendazole 50 100
Mebendazole 15 30
Netobimin 7.5 15
Oxfendazole 5 20
Lev/Pyr Levamisole 7.5 15
Pyrantel 20 40
ML Ivermectine 0.2 0.4
Eprinomectin 0.5 1
Salicylanides Closantel 10 20
 Evaluation of AH resistance

• Is there resistance or not?

• Determination of resistance on eggs by:
 Fecal egg count reduction test (FECRT)
 Egg hatch assay (EHA)
• Determination of resistance on larvae or adult by
 Larval development assay (LDA)
 Adult reduction test (ART)
 Genotyping (BZ resistance only)
 The fecal egg count reduction test

 Determines the efficacy of a treatment in invivo

 < 90% reduction 10-14 days after treatment indicates
resistance
 Determined using eggs excreted by controls and eggs excreted
by treated group
 Reduction rate = controls – treated
controls
 Limitation: Not sensitive enough when the frequency of
resistant alleles is low in a population
 Egg hatch assay (EHA)

• Test in vitro
• Determination of a 50% lethal dose (LD 50)
• Resistance when LD 50 > 0.1 µg de TBZ/ml
• When you increase AH concentration egg hatchability
decreases
 Control of AH resistance

 Change AH family each year

 Use correct doses
 Be careful when purchasing animals (Before introducing new animals to a
flock treat them with 2 or 3 different anthelmintics and keep them for 48
hours before mixing to the flock)
 Avoid mixing of sheep and goats on the same pasture to avoid circulation
of parasites
 Selective treatments How?
 FAMACHA system
 Treat the host category at risk: May be calves/ young animals/ high
producing animals