Anthelmintic resistance

doi:10.1016/j.rvsc.2004.09.001

Research in Veterinary Science

Volume 78, Issue 2, April 2005, Pages 99-108

https://doi.org/10.1016/j.rvsc.2004.09.001 Get rights and content

Abstract

The full extent of anthelmintic resistance in nematodes of farm animals is not known. Resistance can be detected with a faecal egg count reduction test and two in vitro tests, the egg hatch and larval development tests. The sensitivity of these two in vitro tests can be increased by using discriminating doses rather than calculating LD₅₀ values. Only benzimidazole resistance can be detected with PCR based tests because the molecular mechanisms of resistance to levamisole and the macrocyclic lactones remain unknown. Resistance detection is important because it enables the appropriate management strategies to be put in place. The development of resistance is delayed by keeping sufficient parasites in refugia (not exposed to anthelmintic), but the necessary management details have not yet been validated in the field. It is probably too late to use combination products to delay the development of resistance, except in cattle but quarantining animals to prevent introduction of resistant helminths onto a farm is important. Dilution of resistant worms with susceptible ones is only at the preliminary research stage and the application of non-chemical methods of control to delay resistance is not yet a practical option. Extensive research is required to manage resistance, especially in the control of resistance in Fasciola hepatica.

Introduction

Antibiotic resistance has quite correctly become a major political issue because human lives are being placed at risk due to the development of bacteria that are not controlled by existing antibiotics. There has also been a large international commitment to improve the control of malaria which is a major killer of young children, particularly in Africa. As with bacterial infections, the failure of existing antimalarials combined with insecticide resistance is the major issue in malarial control. The almost inevitable failure of vital drugs in humans is raising the realisation in funding agencies on an international level that the development of resistance to chemicals has to be addressed seriously in all cases of human and animal infections and infestations with parasites. As revealed by sales figures in many countries, parasites are the major health issue in most farm animals. Despite this, veterinary parasitology has been in decline for a relatively long period (Coles, 2001) due largely to the availability of excellent drugs, especially the macrocyclic lactones, for killing ecto- and endo-parasites. It is to be hoped that this trend in veterinary parasitology will be reversed in order that trained personnel are available to address the large practical problems that are developing. It is, therefore, timely to ask what can be done to slow or reverse the seemingly relentless rise of anthelmintic resistance in both nematodes and liver fluke.

Section snippets

Current information

There have been a number of reviews on anthelmintic resistance that have documented the available information on the species of nematodes to which resistance has been detected, to which drugs it had developed and in what countries it has been found (e.g. Prichard, 1994, Condor and Campbell, 1995, Jackson, 1993, Jackson and Coop, 2000, Kaplan, 2002, Sangster, 1999, Waller, 1997). Determining the extent of resistance depends on the existence of tests to detect resistance and standardised tests

Factors affecting the development of resistance

There are four features determining how fast resistance develops in the field, (1) the numbers of worms in refugia, (2) the gene frequency for resistance in untreated populations, (3) whether resistance is dominant or recessive and (4) the biological fitness of resistant worms compared with susceptible ones.

The detection of resistance

In order to be able to detect resistance and thus confirm how management actually affects the development of resistance, sensitive tests are required.

Resistance surveillance

The true extent of anthelmintic resistance is not known in almost any part of the world. Even where surveys have been undertaken, as in South America (Waller et al., 1996), they are likely to become rapidly out of date. Data from surveys have two potential uses. It may be possible to relate the extent of anthelmintic resistance to management practices and thus adjust the way anthelmintics are used. In addition, data can give a warning that if different approaches for worm control are not

The role of refugia

Although the importance of keeping some nematodes in refugia (unexposed to anthelmintic) was recognised a long time ago (e.g. Michel, 1985), it was not until the recent paper by Van Wyk (2001) that its importance was given the full recognition it deserves. There was also general agreement on the importance of refugia in an internet conference hosted from South Africa. (Van Wyk et al., 2002). The principle in insect resistance management is that some areas are left untreated so that these

Alternative methods of control

By reducing reliance on the use of anthelmintics alternative methods of nematode control should delay the development of anthelmintic resistance. In practice, apart from success in selecting for resistance to nematodes, particularly in New Zealand, most non-chemical methods of control have yet to be applied in the field. A large effort has gone into the development of vaccines. Although the first report was made more than 17 years ago of protection against H. contortus using an extract of the

Resistance in liver fluke

The extent of the development of resistance to the most widely used product, triclabendazole is not known in the UK but may be widespread in the western part of Ireland. There are no standardised faecal egg count reduction tests because it is not known how long it takes for fluke in bile ducts to disintegrate and release all their eggs. There are currently no in vitro tests for resistance and as the molecular mechanisms of action and resistance to fasciolicides are not known there are no

Research requirements

The basis of any control programme must be the ability to rapidly detect resistance. Whilst the FECRT is a robust farm based test for anthelmintic resistance, novel sensitive tests are required, particularly if the relationship between management and the development of resistance is to be examined. Therefore, it is to be hoped that the major molecular mechanisms of resistance to both levamisole and the macrocyclic lactones will be established and that it will prove possible to develop tests

Conclusions

The development of anthelmintic resistance poses very large threats to the future welfare and production of grazed animals. In cattle correct management can probably prevent resistance becoming a serious issue where Haemonchus sp. are not a problem, providing only first year animals are treated and they are grazed on a different pasture the following year, although this requires confirmation. Current trends suggest that farmers are increasing the use of anthelmintics, particularly MLs, to try

References (82)

O.S. Anziani et al.
Resistance to benzimidazole and macrocyclic lactone anthelmintics in cattle nematodes in Argentina
Veterinary Parasitology
(2004)
E.H. Barnes et al.
Worm control and anthelmintic resistance: adventures with a model
Parasitology Today
(1995)
D.J. Bartley et al.
A survey of anthelmintic resistant nematode parasites in Scottish sheep flocks
Veterinary Parasitology
(2003)
F.H.M. Borgsteede et al.
Lack of reversion of a benzimidazole resistant strain of Haemonchus contortus after six years of levamisole use
Research in Veterinary Science
(1989)
D. Cioli et al.
Drug resistance in schistosomes
Parasitology Today
(1993)
G.C. Coles
The future of veterinary parasitology
Veterinary Parasitology
(2001)
G.C. Coles et al.
Tolerance of Kenyan Schistosoma mansoni to oxamniquine
Transactions of the Royal Society of Tropical Medicine and Hygiene
(1987)
G.C. Coles et al.
Larval development test for detection of anthelmintic resistant nematodes
Research in Veterinary Science
(1988)
G.C. Coles et al.
World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance
Veterinary Parasitology
(1992)
R.L. Coop et al.
Nutrition–parasite interaction
Veterinary Parasitology
(1999)

I. Fairweather et al.

Fasciolicides: efficacy, action, resistance and its management

Veterinary Journal

(1999)

J.H. Gill et al.

Avermectin inhibition of larval development in Haemonchus contortus – effects of ivermectin resistance

International Journal for Parasitology

(1995)

J.H. Gill et al.

Evidence of multiple mechanisms of avermectin resistance in Haemonchus contortus

International Journal for Parasitology

(1998)

W.N. Grant

Genetic variation in parasitic nematodes and its implications

International Journal for Parasitology

(1994)

H. Hoste et al.

Comparison of selective and sytematic treatments to control nematode infection of the digestive tract in dairy goats

Veterinary Parasitology

(2002)

J.F. Humbert et al.

Molecular approaches to studying benzimidazole resistance in trichstrongylid nematode parasites of small ruminants

Veterinary Parasitology

(2001)

F. Jackson