80 Yearbook of Agriculture 1956 tion of the magnitude of preventable search Service, He was trained as a para- loss from parasites is the chief stimulus sitologist in the Johns Hopkins University to an awakened interest. School oj Hygiene and Public Health. He received the degree of doctor oj science from AuREL O. FOSTER is head of the Para- that institution in igjj- He taught in Balti- site Treatment Section^ Animal Disease aiid more and conducted research in Panama be- Parasite Research Branchy Agricultural Re- fore entering the Department in ig^g. Chemotherapeutic Agents for Internal Parasites AUREL O. FOSTER CHEMICALS are our oldest weapons significant as new drugs. Today, in for combating the parasitic infections. consequence of a better understanding They arc also the most practicable and of the nature and gravity of para- powerful weapons in modern use. sitism, the strictly curative use of anti- The Ebers Papyrus—the oldest parasitic chemicals is becoming rare. medical document, dating from about Emphasis is on prevention rather than 1550 B. C.—mentions the use of cure, and the concept of parasite pomegranate against intestinal worms. control embraces all feasible steps that Pomegranate is listed for the same minimize economic losses from para- purpose in a late edition of the United sites. States Dispensatory, an official docu- A corollary viewpoint is that anti- ment, which gives ''original informa- parasitic chemicals may attack any tion about new drugs and current vulnerable stage of a parasite and are data about drugs already in use." best and most efficiently employed as Both volumes also mention castor oil adjuncts to other control measures as a purgative. rather than as substitutes for them: Pomegranate is listed because of However necessary and useful these longevity, not because of newness or agents are for treating heavily infested because of uses that we can recom- animals, they are used most profitably mend. Castor oil is still without a peer in proved programs of systematic, in its line. preventive medication. We see this at But specific treatments ordinarily its highest development in the exten- arc products of the times and for the sive use of free-choice and low-level times. None of the treatments current- systeiTis of medication to control ly in wide use against internal para- the gastrointestinal parasites of cattle, sites was known two decades ago. sheep, and horses, and in programs of There is the probability and the hope, continuous and intermittent medica- therefore, that we shall have many tion for controlling coccidiosis and new and better ones a decade or two blackhead of chickens and turkeys. hence. Chemotherapeutic agents, or chemi- Methods of using drugs against para- cals used in treatment or control of sites also change. The effects of new parasitic infestations and infectious approaches and viewpoints are fully as diseases, ordinarily come into use only Chemotherapeutic Agents for Internal Parasites 81 after critical evaluation from stand- ship of particle size to therapeutic points of safety and efficiency. Never- efficiency of the chemical and to low- theless, the most widely used drugs are level and free-choice use of it; those about which we are constantly The versatility and mode of action learning most. Phenothiazine, for ex- of programs of systematic, preventive ample, has been in wide and increas- medication; ing use throughout the w^orld for The applicability of these programs more than 15 years, yet the scientific to parasite control in dairy cattle and literature now contains more accounts goats; of research and experience with it The economic benefits of periodic than with all other anthelmintics medication and of low-level and free- combined. In the last analysis, then, choice methods of administration for treatments, like the language, are the control of subclinical parasitism; made by use. The significance of catalytic iodine in commercial products; PHENOTHIAZINE is a synthetic organic The net longtime efifects of low-level compound prepared by the union of and free-choice medication; and diphenylamine and sulfur in the pres- The evolution and occurrence of ence of iodine as a catalyst. It has well phenothiazine-resistant strains of para- established applications in horses, cat- sites. tle, sheep, goats, swine, and poultry. New problems arise, but sound usage Against many of the damaging gastro- of the chemical depends largely on intestinal roundworms, it is the most solving the old problems. effective treatment—and for some spe- Of the remarkable anthelmintics that cies the only known treatment. have been developed—carbon tetra- Phenothiazine evolved in three pe- chloride in 1921, tetrachloroethylene riods: The discovery of its application in 1925, and hexachloroethane, sodium as a standard anthelmintic (1938- fluoride, lead arsenate, toluene, and 1940); standardization and develop- many others in later years—phenothia- ment of methods of using the drug to zine must be ranked as outstanding. achieve efifective control of parasites It combines a unique range of applica- (1941-1948); and its greatly increased tion, a high degree of efficiency, an use (from 1948 on) in cattle, particu- unusual margin of safety, an ease and larly free-choice and low-level systems versatility of administration, and a of preventive medication of beef ani- variation and range of antiparasitic mals and dairy calves. The third stage actions not found in any other anthel- marks an awakening to the importance mintic. of parasitism in cattle and a recogni- But phenothiazine has some disad- tion of the benefit that may be derived vantages. It is comparatively expen- from controlling subclinical parasitism sive. Therapeutic doses are very bulky. in cattle and other livestock. A few animals, especially horses and Despite the extensive use and study swine, are rather susceptible to in- of phenothiazine and despite the well- toxication by it. Treated animals elim- marked stages in its evolution, many inate breakdown products as a red problems remain unsolved. They have dye, in the urine and feces, which is grown in importance. Among them sometimes alarming, although harm- are: less. The dye temporarily stains the The mechanism of action of pheno- wool of treated sheep, which are ani- thiazine against parasites; mals in which the drug has great over- Subjective factors that influence its all usefulness. The dye also discolors therapeutic efficiency, such as diet and the milk of dairy animals. Finally, the condition of animals requiring treat- drug is deficient in desired efficacy ment; against some important parasites, such Physical factors, such as the relation- as the trichostrongylcs of sheep and 300304"--56 7 82 Yearbook of Agriculture 1956 several gastrointestinal ncmatodes of Because of disadvantages of the cattle. These considerations make it treatment, researchers have looked to clear that there is a place for an even other chemicals, including cadmium better drug. salts and piperazine derivatives, as possible substitutes. SODIUM FLUORIDE is a very efficient chemotherapeutic agent for removing CADMIUM SALTS, the oxide and the large roundworms from swine. As de- anthranilate, showed promise of su- veloped in 1945 and later, the admin- perseding sodium fluoride as treat- istration of the chemical (technical ments to remove large roundworms grade, tinted) in dry, ground feed at from swine. Cadmium oxide was first a concentration of i percent for i day marketed in 1953. Cadmium anthrani- is a safe treatment for growing pigs. late was marketed in 1954. Both salts The treatment removes immature are administered in feed for 3 con- and mature parasites and is more ef- secutive days, the former at a con- fective than ascaricides that formerly centration of 0.015 percent and the were available. Because the round- latter at 0.044 percent. worms take about 10 weeks to mature These compounds are as effective in pigs, effective chemotherapeutic and simple as the sodium fluoride attack on it requires strategic dosing treatment; and they are also safer and at intervals just short of 10 weeks. more palatable, although they pre- For systematic control, therefore, pigs sent the similar problem of poten- should be treated when they are about tial residues in tissues. Our limited .8 weeks old, or at weaning time, and data, however, suggest that the residues again at about 16 weeks. are not dangerous to consumers. Never- The treatment is not safe unless theless, it is recommended that treated properly administered—sodium fluo- animals not be slaughtered within 30 ride is poisonous. Some pigs have been days. Retreatment is not recommended killed by incorrect dosage and by add- for hogs intended for food for people. ing the chemical to slops, garbage, Cadmium treatments are more ex- milk, water, and wet feed. Properly pensive than the sodium fluoride treat- administered, the treatment has nat- ment, but, despite their excellence and ural safeguards. Its taste is unpleasant, popularity, seem destined to be sur- and it irritates the stomach—factors passed by chemicals, such as the piper- that prevent excess consumption of azines, which have become prominent medicated feed and cause reflex vom- in the experimental field. iting if too much is taken in. Sodium fluoride has other disad- PIPERAZINE COMPOUNDS were first in- vantages. It presents the hazard of vestigated for antiparasitic action by a poisoning not only to pigs but to users, commercial company in the United children, and pets. Transient diarrhea States. A useful