When I graduated as a Veterinary Surgeon some 36 years ago, the number of effective anti parasitic components available for clinical use were remarkably few. Many natural products were still in use (extract of male fern, arecoline, oil of chenopodium, kamala, nicotine, derris and the like) many difficult to formulate and to administer, some requiring overnight fasting before use and purgation after use. The compounds of remarkable promise at that time were phenothiazine for nematodes in farm animals, carbon tetrachloride for liver fluke in sheep and cattle, the sulpha durgs for coccidia and two wonder drugs for the arthropods, DDT and BHC.

The major health problems of the world today relate to infections—viral, bacterial or parasitological. Malaria, schistosomiasis and filariasis are a risk to at least 600 million people and the problems of many of these infections are getting worse owing to ecological changes associated with industrial development and burgeoning populations which have increased out of proportion to increases in health resources.

Just as human helminth infections are vitally influenced by the way in which people live, so the helminthiases of domestic animals depend on how these are managed.Veterinary helminthology is a branch of agriculture. The agricultural industry changes quickly, more quickly than the ideas of scientists. Ideas, in their turn change more rapidly than their practical implications are understood. A discussion of anthelmintic use must therefore be partly agricultural, partly historical.

The design of mass and targetted community-based chemotherapy programmes for the control of the major helminth infections of man is discussed in relation to the population and transmission dynamics of the parasites. Rapid reinfection following a single mass or targetted anthelmintic application is shown to be a universal feature of helminth transmission, as a consequence of the regulatory or feed-back mechanisms controlling population abundance within both individuals and the community as a whole. Control of reinfection requires repeated community treatment where the intensity of application and the interval between treatments are dependent on the reproductive life-expectancy of the adult worm, the net force of transmission prior to control (the basic reproductive rate) and the factors which create aggregation in the distribution of parasite loads within the population. Selective or targetted treatment is shown to be most effective for the control of morbidity as opposed to the control of transmission. The impact of targetted treatment depends critically on the factors that generate heterogeneity in parasite burdens and on whether or not selectivity is based on a single or repeated identification of the ‘wormy’ fraction of the community. Monte Carlo simulation studies are employed to assess the likely impacts of different control strategies on average parasite abundance/person and the distributions of parasite loads within populations. Future epidemiological research needs are discussed in relation to theoretical work and recent field studies of predisposition to heavy infection.

There are comparatively few studies concerned specifically with chemotherapy of parasitic infections and its relationship with the immune status of the host being treated. In one sense this is hardly surprising. The disciplines of chemotherapy and immunology have developed independently, and the search for effective drugs has for the most part been an empirical process; when a compound showing some activity has emerged the tendency has been to look for analogues with even greater parasiticidal properties rather than to consider whether effectiveness of the parent compound could be improved if the immune status of the host were different. In many cases, test systems for drug development have actually been selected to reduce as far as possible the complications f an immune response. Thus acute, fatal infections are commonly used for the screens, and questions such as the level of specific resistance at the time of treatment, immunodepression by the parasite, and increased resistance to challenge following chemotherapy are generally irrelevant.

Study of the mode of action of the anti-parasitic ‘hydrogenophore’, closantel, revealed that mitochondria isolated from livers of untreated rats, 13 weeks after infection with Fasciola hepatica metacercariae, were uncoupled. This uncoupling of mitochondria might be induced by a product(s) excreted by the liver fluke. The lipid extractable product(s) binds to albumin and has a molecular weight between 500 and 1000 Daltons. A second unexpected finding indicates that closantel affects the motility of Schistosoma mansoni in vitro by interferin with mitochondrial ATP synthesis. The results obtained are suggestive of a role for aerobic metabolism in the generation of energy required for motility.

In spite of the continuing need for new and improved anti-protozoal drugs for use in man, a considerable contraction of industrially based research on anti-protozoal drugs has occurred in recent years. Newton (1983) reviewed the reasons for this decline and presented a compelling argument that fundamental research on the biology of the parasites is essential for the discovery of leads for the development of a new generation of drugs – a rational chemotherapy. The rapid advance in knowledge of the biochemistry of parasitic protozoa which has occurred in recent years has provided a number of potential leads to new drug development and has permitted a greater understanding of the mode of action of many current drugs. The account of these advances which follows is necessarily selective and relates to protozoan parasites of man.

The resistance in human malaria is mainly of practical importance in relation to Plasmodium falciparum. Strains resistant not only to chloroquine but also to dihydrofolate reductase inhibitors, and even to potentiating combinations of these with sulphonamides or sulphones, are appearing in an ever increasing geographical area which now includes tropical Africa and India. Few new drugs are available or foreseen for the near future, mefloquine and artemisinine being the leading contenders. It is vital that all measures possible should be taken to protect such new compounds, their deployment in the form of judiciously selected combinations with other antimalarials being an essential procedure that should be followed. Drugs in new chemical classes and with different modes of action are still urgently needed. Reliance should not be placed on drugs alone to control malaria on a community basis.

Starting with the work showing activity in the research programme (Table 1), compounds will usually have been entered for various reasons, first into the in vitro testing systems, or more rarely into the in vivo system unless this is the only testing system available for that particular organism.