The Control of Parasites: the Role of Drugs1
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OF WASHINGTON, VOLUME 44, NUMBER 1, JANUARY 1977 17 Steinert, M., and A. B. Novikoff. 1960. The associated structures of Fasciola hepatica. existence of a cytostome and the occurrence Quart. J. Microsc. Sci. 104: 505-512. of pinocytosis in the trypanosome, Trypano- Thorsell, W., and N. Bjorkman. 1966. In soma mega. }. Biophys. Biochem. Cytol. 8: vitro studies on the effect of hexachlorophene 563-569. and its dimethylether on the liver fluke Fas- Sterling, C. R., and M. Aikawa. 1973. A ciola hepatica L. Z. Parasitenk. 28: 116- comparative study of gametocyte ultrastruc- 124. ture in avian Haemosporidia. J. Protozool. Van den Bossche, H., and P. A. J. Janssen. 20: 81-92. 1967. The biochemical mechanism of action Sterling, C. R., and D. L. DeGiusti. 1972. of the anthelmintic drug tetramisole. Life Ultrastructural aspects of schizogony, mature Sci. 6: 1781-1792. schizonts, and merozoites of Haemoproteus , and . 1969. Biochemical mech- metchnikovi. J. 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Life Sci. 10: 701-711. sites. 2nd ed. Academic Press, New York. •, and . 1971b. Ultrastructural lo- Yamao, Y. 1954. Histochemical studies on en- calization of NADH- and NADPH-dehydro- doparasites. V. distributions of the glycero- genases in the erythrocytic stages of the ro- monophosphates in the tissues of flukes, dent malaria parasite, Plasmodium berghei. Eurytrema coelomaticum, E. pancreaticum, Life Sci. 9: 421-428. Dicrocoeliiim lanceatum and Clonorchis sinen- Threadgold, L. T. 1963. The tegument and sis. J. Coll. Arts. Sci. Chiba Univ. 1: 9-13. The Control of Parasites: The Role of Drugs1 W. C. CAMPBELL Merck Institute for Therapeutic Research, Rahway, New Jersey 07065 ". the play is the tragedy 'Man', are the prevailing social and political forces in and its hero, the Conqueror Worm" the case of man, and the husbandry practices Edgar Allan Poe in the case of domestic animals. Of the mech- anisms invoked intentionally to reduce para- Poe's words were allegorical rather than sitism, biological control and vaccination have parasitological; but parasite control might be played roles that have been overshadowed by regarded, in large measure, as an attempt to the role of chemotherapy. It seems likely that strip the worm of its role as conqueror. antiparasitic drugs will continue to be of im- Undoubtedly the major extrinsic factors in portance for some time. determining the extent and degree of parasitism Antiparasitic drugs actually play many roles —not just because there are many drugs, but because one drug in its time plays many parts. Some are general roles—the parts played by Copyright © 2011, The Helminthological Society of Washington 18 PROCEEDINGS OF THE HELMINTHOLOGICAL SOCIETY Table 1. Productivity of Merino sheep from age Despite the very evident immunogenicity of 6 months to age 18 months (50 sheep per group, the infection, vaccination has not become a all groups grazed together). Anthelmintic B has significant means of control; and it has been broader spectrum than A, and greater activity the role of the antiparasitic drugs to make against immature worms. Both drugs were ad- ministered monthly. From Gordon, 1963. feasible the modern intensive production of an important food animal. % sheep of In helminthiasis we have to a lesser, but 70 Ih or % fleeces over at 18 Wool showing still significant extent, moved from the use of months per head defective drugs for the salvage of sick animals to the Treatment old Ib. wool prevention of disease. This is accomplished Controls — n o not by continuous chemoprophylaxis but by anthelmintic treatment 16 6.7 32 tactical treatment (administration of drugs Anthelmintic A 35 7.4 14 whenever local conditions make a buildup of Anthelmintic B 62 7.9 4 parasitism seem likely) or strategic treatment (administration of drugs according to a sched- ule based on the epidemiological conditions drugs in the overall scheme of parasite control prevailing in a given region). Quite suddenly, —and I shall say a little bit about those. There as these things go, we no longer hear of dev- are innumerable specific roles: this drug kills astating outbreaks of acute fascioliasis in the Haemonchus in sheep, that drug kills Ancylo- United Kingdom, or of haemonchosis in Aus- fitoma in man, and so on. I am not going to tralia. More important, perhaps, than the pre- say anything about those roles. They have been vention of overt disaster is the prevention of recounted many times in recent years. There the more subtle deleterious effects of parasitism are specific roles of another kind—the biochem- on the quantity and quality of livestock prod- ical roles. I do want to say something about ucts. In either case, anthelmintics, too, are those, partly because they are not often pulled currently playing the role of enhancer of agri- together in one place, but mostly because I cultural production. Obviously the increase in want to end by discussing how they might productivity is easy to demonstrate under con- relate to the discovery of tomorrow's anti- ditions favorable to clinical parasitism, and parasitic drugs. becomes more difficult and more controversial under conditions where parasitism is very much subclinical. An example of enhanced produc- The Role of Drugs in tivity may be found in the work of Gordon Livestock Parasitism (1963); some of his data are given in Table 1. Although I will be focusing attention on I want, however, to go beyond such well- helminth infections, the general role of drugs documented effects and to consider a more in controlling parasitic diseases in domestic recent and more comprehensive examination of animals is perhaps best illustrated by the the subject. situation in coccidiosis. Since the introduction Only in recent years have attempts been of medicated diets for the control of coccidiosis made to determine whether the increased pro- in 1948, it has been virtually axiomatic that an ductivity associated with drugs necessarily re- effective coccidiostat is indispensable for suc- sults in economic benefit. Just last month a cessful intensive production of chickens—this, paper appeared that is, I think, a striking ex- mind you, in a parasitic situation in which im- ample of how parasitological and economic munity to reinfection is easily demonstrated studies can be combined and focused on this under both experimental and field conditions. point (Anderson et al, 1976). These workers Indeed the natural immunological protection determined the economic returns from 2 is exploited in conjunction with chemo- strategic schemes of helminth control in therapy, and the poultryman, in this day of weaned lambs in Western Victoria, Australia; sophisticated agriculture, takes a great interest and they compared these with returns from in the degree to which a given coccidiostat flocks without a treatment scheme and, in part, will permit the development of natural im- with flocks subjected to unusually intensive munity, especially in replacement chickens. treatment. The economic analysis included Copyright © 2011, The Helminthological Society of Washington OF WASHINGTON, VOLUME 44, NUMBER 1, JANUARY 1977 19 Table 2. Maximum financial return (given favorable economic conditions) from flocks of lambs with no treatment schedule, a "traditional" strategic schedule, a "critical" strategic schedule, or an intense (biweekly) schedule. From Anderson, et al. 1976. Maximum return ( Australian dollars ) None Traditional Critical Intensive Gross return per 100 sheep 1029 1115 1205 1441 Net return per 100 sheep* 1023f 1097 1186 1271 Percent return on cost of treatment:!: — 617 1254 151 * Gross return minus cost of treatment. t Lambs received one treatment to control clinical parasitism. :j: Cost in addition to cost of single treatment in flocks with no treatment schedule. extrapolation of data to years in which eco- The Role of Drugs in nomic conditions were more favorable or less Parasitism of Man favorable than the year in which the data were collected. The figures in Tables 2 and 3 have First we must remember that antiparasitic been extracted from the wealth of information drugs have played, and continue to play, a life- in this paper to illustrate the following points. saving role. I seem to recall from some intro- (1) All schemes of anthelmintic treatment gave ductory textbook that visceral leishmaniasis better livestock production than no treatment was about 95% fatal before the introduction scheme, and thus a higher gross financial re- of antimonial drugs, and about 95% nonfatal turn. (2) Under favorable economic condi- afterwards. The lifesaving role of the anti- tions, all treatment schemes also gave a higher malarial drugs needs no elaboration. Control net return. Thus treatment always made eco- of morbidity on a population basis has also nomic sense, although the intensive (biweekly) been of importance in protozoal and helminthic treatment was not nearly so profitable as the infections, but it must be admitted that the more judicious schemes. (3) Under unfavor- overall success rate has been disappointingly able economic conditions, both strategic treat- low, and the need for effective strategic control ment schedules were economically advantage- remains distressingly great.