AN APPROACH TO ADDRESS NEMATODE/TREMATODE DRUG RESISTANCE IN SA.

Background:                                                                                                                                                                                                                                                Nematode/trematode infection is a serious veterinary health and economic challenge and the existing means are inadequate to address the problem. In general, infestation may result in morbidity, lowered fertility, reduction in milk production and depressed weight gains when feed intake is reduced. In some instances, loss of endogenous protein and anorexia reduces immunity, whereas blood predation may result in anaemia. In worse cases, death may result from critical infections. The level of nematode/trematode infection depends upon the age of the host, the breed, the parasite species involved, and the epidemiological patterns, which include husbandry practices and the physiological status of the animal. An example of a highly pathogenic gastrointestinal nematode of small stock is Haemonchus contortis , which is widely distributed in South Africa and most parts of Africa, whereas the trematode Fasciola hepatica run rife in the UK, Western Europe and the coastal dairy production areas of South Africa.

Control and resistance:                                                                                                                              

The conventional control of nematode/trematode infestations is by synthetic anthelmintic drugs. Since treatment with anthelmintics and the marketing thereof by drug companies worldwide have been successful for several decades, and because of cost, there has been little incentive to do public sector research into chemotherapeutic agents or alternatives.  Lately, several problems associated with the use of anthelmintics have been observed worldwide which makes re-thinking crucial: (i) Development of resistance by the parasites to the available drugs have become widespread. Resistance is now being reported for all major classes of anthelmintics. Even two new compounds launched recently (Derquantal and Monopantel) have started to show resistance by certain strains of helminth parasites. (ii) Consumers of animal products have become cautious of possible contamination of food products as a result of drug-residual effects. For example, a number of the most popular anthelmintic drugs against Fasciolosis in lactating dairy cows have been banned (Nitroxynil, Triclabendazole and Clorsulon), whereas in the case of others such as Albendazole and Oxyclozanide the milk which is intended for human consumption is to be discarded until such time as there are no longer drug residues present. (iii) Some drugs against Fasciolosis show Interference with detection of tuberculosis in cattle due to an immuno-suppressive effect of the parasite on the host. (iv) Small-scale farmers are being pushed out of the livestock industry by the unaffordable cost of drugs.

Alternative approaches:

The problems discussed call for studies seeking alternative methods to control and limit the economic impact of helminth parasite infestation. One strategy should be to preserve drug susceptibility in the parasite population, which could be through refugia: By ensuring that a part of the parasite population remains unexposed to anthelmintic drugs, a pool of susceptible alleles is preserved. Such refugia can be generated by treating only those individuals within a flock or herd which are in need, i.e. whose parasite burden is causing harm. The successful FAMACHA© system for nematode control in sheep in South Africa and which has also shown promise in controlling Fasciolosis in the UK, is an example. What also comes to mind is quick rotational grazing strategies to limit parasite build-up, genomic detection of resistance alleles and selection accordingly, vaccination, supplementing feed with plant extracts such as tannins, phytomedicines containing anthelmintic properties and biological control by natural enemies of nematodes/trematodes such as particular fungi and bacteria.

Research and development:

    *      Surveillance of current trends in anthelminthic resistance in South Africa in various farm animal species should be undertaken

     *      Helminth control and bio-security programmes on farms to establish cause and effect on the development of resistance should be investigated

Non-drug product development:

• Phytomedicinal screening, including more advanced studies on isolated phytomedicinal products, to better understand their mechanisms of action, chemical grouping and pharmacokinetics are required

• Further study of isolated molecules via molecular tweaking, to better optimise their activity should be conducted

• Current vaccine use should be optimized.

• To investigate the feasibility of new vaccine development, including establishment of public-private partnerships.

• To investigate the development of immune modulatory compounds and bio-control agents

Supporting initiatives:

• Genomic isolation of resistance alleles in cattle and sheep and inclusion of disease resistance in selection programmes, e.g. making use of the FAMACHA© results.

• Testing and inclusion of pasture species with anthelmintic properties in established pasture compositions.

• Development of feed supplements containing phytomedicines and toxic substances to helminths.

Education:

• Train farmers and veterinary students in a holistic approach to helminth control utilising all methods and measures discussed above.

• Evaluate the impact of education on the use of anthelminthic drugs and the impact of interventions on farming systems.

• Publication of optimal guidelines based on current trends, results  and understanding

Reference:  

Meissner, H.H. & Naidoo, V., 2016. NEED FOR CAPACITY IN HELMINTHOLOGY AT THE FACULTY OF VETERINARY SCIENCE, UNIVERSITY OF PRETORIA - ONDERSTEPOORT. Proposal to the Dean, December 2016.