Coccidiosis in Chickens
Infections with a single species of coccidium are rare, and mixed infections are the rule. Eimeria tenella is the most pathogenic and important species. In recent years, however, control of this species with coccidiostats has revealed more and more coccidiosis due to E. necatrix. The other species may contribute to the total picture. E. brunetti is markedly pathogenic but uncommon. E. maxima and E. acervulina are slightly to moderately pathogenic. Both are common. E. mitis and E. praecox are common but non-pathogenic. E. hagani is rare and only slightly if at all pathogenic. Wenyonella gallinae is rare but moderately pathogenic; it has been found so far only in India. Cryptosporidium tyzzeri is rare and non-pathogenic. Isospora gallinae is rare if it is a chicken parasite at all, and is presumably non-pathogenic.
Coccidiosis is primarily a disease of young birds. Older birds are carriers. Birds become infected by ingesting oocysts along with their food or water. Under farm conditions, and even in the laboratory unless extreme precautions are taken, it is practically impossible to avoid exposure to at least a few oocysts.
The disease picture depends upon the number of oocysts of each species which the birds ingest. If they get only a few, there are no signs, and repeated infections produce immunity without disease. If they get more, the disease may be mild and the birds will become immune. Only if they get a large number of oocysts do severe disease and death result.
Crowding and lack of sanitation greatly increase the disease hazard. As the oocysts accumulate, the birds receive heavier and heavier exposures, and the disease becomes increasingly severe in each successive batch of birds placed in contaminated surroundings.
Coccidiosis is a self-limiting disease, and birds which have recovered become immune. The speed with which immunity develops depends upon the species of Eimeria and on the intensity and frequency of infection. Immunity develops rapidly following infections with E. maxima, E. praecox and probably E. hagani, somewhat more slowly following infections with E. tenella and E. brunetti, and is delayed following infections with E. mitis, E. acervulina and E. necatrix.
Immunity is species-specific. Chickens which have become immune to one species are susceptible to all the others. This fact makes it possible to differentiate between species by cross-immunity studies, and indeed it was by means of such studies that Levine (1938), for instance, was able to show that E. hagani was a valid species.
Immunity against coccidia is seldom solid. Birds which have recovered may be reinfected, but such infections are light and do not cause disease. Carriers are extremely common and are a source of infection for other birds. Thus, Levine (1940) found E. mitis, E. acervulina or both in 53%, E. praecox in 33%, E. maxima in 28%, E. necatrix in 38% and E. tenella in 23% of 39 pullets 8 months or more old, but only 8% of them had gross lesions.
Heredity is a factor in resistance to coccidiosis. Herrick (1934) found that chicks from resistant parents were about 100% more resistant to E. tenella than unselected chicks. Champion (1954) and Rosenberg, Alicata and Palafox (1954) established E. tenella-resistant and susceptible lines of chickens by selective breeding. They found that sex linkage, passive transfer of immunity thru the egg and cytoplasmic inheritance did not play a significant part in resistance and susceptibility. Champion considered that they were controlled in large part by non-dominant, multiple genetic factors which presumably act additively. Rosenberg et al. also thought that the factor or factors for resistance or susceptibility did not show marked dominance.
Immunity in older birds is due mostly to previous infection. The birds are exposed repeatedly and almost continuously, and their immunity is continually being reinforced. Coccidiasis is thus extremely common - and indeed normal under natural conditions - while coccidiosis is the result of imbalance between infection rate and resistance. Actually, the best type of environment to control coccidiosis is one in which the chickens become infected lightly enough to develop an immunity without suffering any disease.
Many workers have studied the development of immunity to coccidiosis (Waletzky and Hughes, 1949; Brackett and Bliznick, 1950). Most of this research has been done with E. tenella. Farr (1943) immunized chickens with 1000 oocysts daily for 15 days or with 3 doses of 1000, 5000 and 9000 oocysts given 5 days apart. She also carried out 5 similar experiments with differing numbers of oocysts, all of which showed that repeated small doses of E. tenella oocysts would produce immunity. Horton-Smith (1949), Waletzky and Hughes (1949) and Gordeuk, Bressler and Glantz (1951) found that single doses of oocysts would also produce immunity, and that the degree of protection was proportional to the intensity of the initial infection. Babcock and Dickinson (1954) found that a total of 1600 sporulated oocysts, given either in one or several doses, would produce practical immunity that withstood severe challenge. The number of individual doses required to make the total did not materially affect the immunity produced. It took 4 days longer for immunity to result following exposure to 1050 sporulated oocysts than to 2125. Gordeuk, Bressler and Glantz (1951) found that day-old chicks could develop a certain degree of immunity. They found, too, that feeding the oocysts in the mash resulted in higher mortality than when a similar dose was given by mouth.
Many workers have shown that immunity will develop against coccidiosis in birds on suppressive therapy (Waletzky and Hughes, 1949; Johnson, Mussell and Dietzler, 1949, 1949a; Grumbles et al., 1949; Bankowski, 1950; Kendall and McCullough, 1952). The drugs are ineffective against the sporozoites or first generation schizonts, at least in the concentrations used, but they do kill the merozoites or later stages. The coccidia are thus able to invade the host tissues and stimulate the development of immunity, but are killed before they can multiply enough to harm the host.
A number of workers have attempted to produce immunity by infecting birds with oocysts attenuated in different ways. Jankiewicz and Scofield (1934) heated the oocysts to 46 C for 15 minutes before sporulation, and found that when they were then sporulated and fed to chickens, they stimulated the production of immunity with a minimum of injury. Waxier (1941) produced mild infections with oocysts irradiated with 9000 r of x-rays. Following recovery, the chicks were almost as resistant as those which had had a severe attack after infection with normal oocysts. Uricchio (1953) produced marked immunity by feeding chicks 100,000 oocysts which had been held at -5 C for 5 days, and a lesser degree of immunity with oocysts which had been heated at 45 C for 12 hours.
It is well known that cultures slowly lose their infectivity upon storage. Babcock and Dickinson (1954), for example, observed reduced pathogenicity in a culture of E. tenella after storage for 236 days, and reduced immunogenicity at 344 days. Using a standard immunizing procedure in which 600 oocysts were fed the first day and 1000 the second, they found that it took 3 days to produce immunity with a culture less than 150 days old and 6 days with a culture more than 300 days old.
There is an unanswered question whether such treatments produce true attenuation or whether the observed results are due simply to the death of some of the oocysts. Invasion must take place for immunity to result, and attempts to immunize birds with killed antigens have not succeeded.
Most attempts to find circulating antibodies have failed. However, McDermott and Stauber (1954) found agglutinins against merozoites in the serum of experimentally infected chickens and also produced them in rabbits and roosters by injecting formalinized merozoite suspensions. Becker and Zimmermann (1953) found that infected chicks injected intravenously with an alcoholic horse kidney extract produced fewer oocysts than untreated, infected controls. Burns and Challey (1959) found that when chicks which had been previously infected thru a fistula into a cecal pouch which had been isolated from the intestine were challenged with E. tenella orally, they were somewhat more resistant than the controls, indicating that there is some generalized host response.
Less research has been done on the development of immunity in other species of coccidia. Tyzzer, Theiler and Jones (1932) found that chickens which had recovered from E. necatrix infections were immune, as did Grumbles and Delaplane (1947). Dickinson (1941) and Brackett and Bliznick (1950) showed that immunity developed following infection with E. acervulina. The latter found the same thing with E. maxima. Similar results have been obtained for the other species (Brackett and Bliznick, 1950).
Avian coccidiosis can be diagnosed by finding lesions containing coccidia at necropsy. Diarrhea with or without blood in the droppings, inappetence and emaciation are suggestive, but scrapings of the affected intestinal mucosa must be examined microscopically to determine whether coccidia are present. It is not enough to look for oocysts, but schizonts, merozoites and young gametes should be recognized also.
Coccidiasis is much more common than coccidiosis; hence the mere presence of oocysts in the feces cannot be relied upon for diagnosis. Conversely, the absence of oocysts does not necessarily mean that coccidiosis is not present, since the disease may be in too early a stage to produce oocysts.
Since some species of coccidia are highly pathogenic for the chicken while others are practically non-pathogenic, the species present must be identified to establish a diagnosis. This can often be done in a rough way from the type and location of the lesions.
Many hundreds of papers have been written on the treatment of coccidiosis in chickens, and there is no space here for more than a relatively brief discussion. By far the greatest part of the research has been done on E. tenella.
The first compound found effective against coccidia was sulfur, which Herrick and Holmes (1936) introduced. When 2 to 5% sulfur is mixed with the feed, coccidiosis is largely prevented in young chicks. The use of sulfur had a certain vogue, but it was soon found unsatisfactory because it causes a condition known as sulfur rickets. Even tho the chicks are on an ordinarily adequate diet, the sulfur interferes with calcium utilization and causes rickets.
The use of borax in E. tenella coccidiosis was introduced by Hardcastle and Foster (1944). Several others have done research on it (Wehr, Farr and Gardiner, 1949), and the consensus is that 0.3 to 0.5% borax in the feed prevents death from coccidiosis if administered beginning 1 or 2 days after experimental infection and continued for 3 days or longer. However, it does not prevent cecal hemorrhage or weight losses. It is also toxic, causing loss of weight even when fed alone.
P.P. Levine (1939) was the first to use sulfonamides against coccidiosis. His discovery that sulfanilamide was active opened up the field. Many different - probably several hundred - sulfonamides were tested, and a number of them were found of practical value. Sulfaguanidine was introduced after sulfanilamide. It was followed by sulfamerazine and sulfamethazine (called sulfamezathine in England), and still later by sulfaquinoxaline and N4-acetyl-N1-(4-nitrophenyl) sulfanilamide. All of these compounds are effective against E. tenella, the last 2 are quite effective against E. necatrix, and sulfaquinoxaline and sulfaguanidine are quite effective against E. acervulina. Sodium sulfadimidine is active against E. mitis, but does not completely eliminate it (Joyner, 1958).
Sulfaguanidine is fed at the rate of 0.5% in the mash, sulfamethazine and sulfamerazine at 0.1 to 0.25%, and sulfaquinoxaline at 0.025%. Sodium sulfamethazine and sodium sulfadimidine are given in the drinking water at 0.2%, and sodium sulfaquinoxaline at about 0.04% (see Grumbles, et al., 1949; Farr, 1949; Dickinson, 1949; Kendall and McCullough, 1952; Peterson and Munro, 1949; Peterson and Hymas, 1950; Davies and Kendall, 1954; Bankowski, 1950; Horton-Smith and Long, 1959; and McLoughlin and Chester, 1959 for reviews and further information).
The sulfonamides are in general more effective against the schizonts and merozoites than against the gametes, gametocytes and sporozoites. Bankowski (1950) found that 0.5% sulfaguanidine was coccidiostatic against the first generation schizonts of E. tenella but that 2% sulfaguanidine was required to kill the second generation schizonts in the lamina propria and even this concentration had no effect on the sporozoites. He concluded that this drug must act against the merozoites in the lumen of the ceca, since 0.5% is the usual concentration in the feed. Kendall and McCullough (1952) found that 0.25 to 0.375% sulfamethazine in the feed affected the later stages in the life cycle, but that 0.5 to 1.0% was required to affect the early stages. Farr and Wehr (1947) found that 1% sulfamethazine almost completely destroyed the second generation schizonts and their merozoites, somewhat affected the first generation schizonts but did not completely destroy them, and either damaged or destroyed the young gametes. It did not injure the larger gametes, oocysts or sporozoites. The action of sulfaquinoxaline is similar.
All of the sulfonamides are coccidiostatic rather than truly curative. None will cure coccidiosis once signs of disease have appeared. When fed continuously in the feed, they abort the disease. Sulfaquinoxaline will protect birds when given as late as 4 days after experimental infection. Since the sporozoites are not affected, they invade the intestinal cells and stimulate the development of immunity. However, if too much of a sulfonamide is given, immunity will not develop. Thus, Kendall and McCullough (1952) found that when 0.25 to 0.375% sulfamethazine was given in the feed, immunity developed, but when the concentration was raised to 0.5 to 1.0% it did not.
When given in the recommended amounts, the sulfonamides are not generally harmful. Sulfaquinoxaline does not depress the growth rate of chicks when fed for a long period at rates of 0.01 to 0.02%, but 0.03% gives variable results and higher concentrations are usually toxic. Delaplane and Milliff (1948) found that when 0.05% sulfaquinoxaline was fed continuously to pullets in egg production, signs of poisoning appeared and some birds died. They found greyish-white nodules in the spleens of most birds and in the livers, kidneys, hearts and lungs of some. There were also hemorrhages beneath the skin of the legs and in the combs. Davies and Kendall (1953) found that 0.0645% sodium sulfaquinoxaline in the drinking water was toxic to chickens when fed for as short a period as 5 days. The principal lesions were hemorrhages, especially in the spleen, and accumulation of fluid in the peritoneal cavity. On the other hand, Cuckler and Ott (1955) reported that the continuous administration of 0.05% sulfaquinoxaline in the feed or of 0.025% in the water for as long as 12 weeks had no adverse effects on chickens. The blood clotting time was prolonged and the prothrombin time increased slightly by feeding 0.4% sulfaquinoxaline for 3 to 12 weeks.
Several organic arsenic compounds have been found effective against E. tenella, but not against the other species (Morehouse and Mayfield, 1946; Goble, 1949). All are derivatives of phenylarsonic acid. All are coccidiostatic, and none will cure coccidiosis once signs of disease have appeared. The most widely used of these is perhaps 3-nitro-4-hydroxyphenylarsonic acid, which is generally administered in the feed at a concentration of 0.01%. It apparently acts against the earlier endogenous stages, but not against the sporozoites, and birds which are exposed while under prophylactic treatment become immune. At the recommended dosage it has no harmful effect on the host but is actually a growth stimulant. A mixture of this compound and N4-acetyl-N1-(4-nitrophenyl) sulfanilamide is sold under the name Nitrosal to suppress both cecal and intestinal coccidiosis. Another active organic arsenic compound is arsanilic acid.
A number of alkylidenediphenols, which are diphenylmethane derivatives, are effective against E. tenella, (Johnson, Mussell and Dietzler, 1949, 1949a; Groschke et al., 1949). One of these, Parabis-90, is 2, 2'-methylene-bis-4-chlorophenoh. It is used in the starter feed at a concentration of 0.15%, and later on, when the chicks are 6 to 8 weeks old, in the grower feed at a concentration of 0.12%. These compounds are also coccidiostatic and will not cure coccidiosis once signs of the disease have appeared. They appear to act primarily against the earlier endogenous stages but not against the sporozoites, and birds which are exposed while getting the drug become immune. They do not appear to harm chickens when fed at the recommended levels.
A diphenyl disulfide derivative which has been widely used as a coccidiostat against both E. tenella and E. necatrix is nitrophenide (Megasul). It is 3,3'-dinitrodiphenyldisulfide (Waletzky, Hughes and Brandt, 1949; Peterson and Hymas, 1950; Dickinson, Babcock and Osebold, 1951; Gardiner, Farr and Wehr, 1952; Horton-Smith and Long, 1959). It is mixed with the feed at the rate of 0.025 to 0.05%. It is coccidiostatic and will not cure coccidiosis once signs of the disease have appeared. It acts against both the sporozoites and later stages, but is more effective against the latter and especially against the second generation schizonts. Immunity does not appear to develop if chickens are treated before infection, but it does if treatment begins at the time of infection or later. Nitrophenide is not harmful if fed in therapeutic concentrations. At higher doses Newberne and McDougle (1956) found that it may cause postural and locomotor disturbances, lowered weight gains, liver degeneration and bone marrow changes.
Another coccidiostat is the diphenylsulfide derivative, bithionol, or 2,2'-dihydroxy-3, 3', 5, 5'-tetrachlorodiphenyl sulfide. The commercial coccidiostat, Trithiadol, is a mixture of 5 parts bithionol and 1 part methiotriazamine. The latter is 4, 6-diamino-1-(4-methylmercaptophenyl)-1, 2-dihydro-2, 2-dimethyl-1, 3, 5-triazine. Bithionol is not only coccidiostatic but also antibacterial and antifungal. Methiotriazamine is coccidiostatic at high concentrations and is also an active antimalarial agent. In combination, these drugs are effective against coccidia at lower concentrations than when used alone. A mixture containing 60% active ingredients is fed in the feed at the rate of 2 pounds per ton. The recommended use level is 0.05% bithionol plus 0.01% methiotriazamine. It is effective against E. tenella, E. necatrix, E. maxima and E. acervulina. Chickens fed it develop immunity to these coccidia. McLoughlin and Chester (1959) found that 0.06% Trithiadol gave relatively good protection from mortality due to E. tenella. It was not as good as glycarbylamide and nicarbazin but was about as effective as nitrofurazone and Bifuran and somewhat better than sulfaquinoxaline. Trithiadol is not harmful to growing chickens when fed at the recommended levels (Arnold and Coulston, 1959). It does not appear to affect egg production or egg shell color or quality, but it does affect hatchability to some extent and is not recommended for use in laying mashes.
Two nitrofurans are currently used as coccidiostats. Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) was introduced by Harwood and Stunz (1949, 1949a, 1950) and has been studied further by Peterson and Hymas (1950), Gardiner and Farr (1954), Horton-Smith and Long (1952, 1959) and McLoughlin and Chester (1959), among others. It is mixed with the feed at the rate of 0.011%. It is effective against E. tenella and to a lesser extent against E. necatrix and E. maxima. Higher concentrations give better results against the intestinal species. Nitrofurazone is coccidiostatic and will not cure coccidiosis once signs of the disease have appeared. It acts against the schizonts, and birds infected while receiving the drug develop immunity to reinfection.
Nitrofurazone is not harmful if fed in therapeutic amounts, but 0.04 to 0.05% in the feed is definitely toxic, and an adverse effect on the growth rate has been noted even at 0.022% (Gardiner and Farr, 1954; Peterson and Hymas, 1950). Newberne and McEuen (1957) found that 0.05 to 0.1% of nitrofurazone in the feed produced stunted growth, curledtoe paralysis, clinical polyneuritis, atrophy of the follicles of the bursa of Fabricius, renal tubular degeneration and pulmonary ossification in young chicks. The blood picture remained essentially normal. McLoughlin and Chester (1959) found that 0.0055% nitrofurazone was less effective than glycarbylamide or nicarbazin but more effective than 0.0125% sulfaquinoxaline against E. tenella.
Another nitrofuran coccidiostat, Bifuran, was introduced quite recently. It is a mixture of nitrofurazone and furazolidone (NF 180, or N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidone). The final concentrations in the feed are 0.0055% nitrofurazone and 0.0008% furazolidone. McLoughlin and Chester (1959) found that it was less effective than glycarbylamide and nicarbazin, about as effective as nitrofurazone and more effective than sulfaquinoxaline against E. tenella infections in chicks. Horton-Smith and Long (1959) found that it was effective against E. necatrix when fed at double the above level. Kantor and Levine (unpublished) found that furazolidone by itself was valueless against E. necatrix.
Both nitrofurazone and furazolidone are also antibacterial agents. Furazolidone is used against Salmonella infections in poultry, and also has some effect against Histomonas meleagridis (Harwood and Stunz, 1954) and Trichomonas gallinae (Stabler, 1957).
The anticoccidial properties of substituted carbanilide complexes were discovered by Cuckler et al. (1955). They introduced nicarbazin, which is an equimolar complex between 4, 4'-dinitrocarbanilide and 2-hydroxy-4, 6-dimethylpyrimidine. A simple mixture is no better than the carbanilide alone. Nicarbazin is fed at a concentration of 0.01 to 0.0125% in the feed, or 0.008% in replacement flocks. It is effective against E. tenella, E. acervulina and E. necatrix (Cuckler, Malanga and Ott, 1956; Rubin et al., 1956; Cuckler, Ott and Fogg, 1957; Horton-Smith and Long, 1959). McLoughlin and Chester (1959) found that nicarbazin was about as effective as glycarbylamide against E. tenella, and more effective than nitrofurazone, Bifuran, sulfaquinoxaline or Trithiadol.
Nicarbazin is coccidiostatic, and will not cure coccidiosis once signs of the disease have appeared. It acts against the second generation schizonts and their merozoites (Cuckler and Malanga, 1956), and birds which are infected while receiving the drug develop immunity to reinfection (Cuckler and Malanga, 1956; Marthedal and Veiling, 1957; McLoughlin, Rubin and Cordray, 1957, 1958).
Nicarbazin is not recommended for laying hens. When fed at the recommended level, it makes the egg shells pale (McLoughlin, Wehr and Rubin, 1957). At higher levels the yolks become mottled, blotchy, enlarged and sometimes even brown, the whites may become cloudy, hatchability is affected, and production may be reduced (Snyder, 1956; Sherwood, Milby and Higgins, 1956; Baker et al., 1956; Lucas, 1958).
Other pyrimidine derivatives besides the one in nicarbazine may have a synergistic effect on sulfonamide coccidiostats. Lux (1954) found that pyrimethamine (Daraprim; 2, 4-diamino-5-p-chlorophenyl-6-ethyl pyrimidine), which is a powerful antimalarial drug, acted synergistically with sulfanilamide and other sulfonamides against E. tenella. Joyner and Kendall (1955) found that as little as 0.0025% pyrimethamine allowed the effective concentration of sulfamethazine against E. tenella to be reduced to 1/8 to 1/16 of that normally required for protection. Marthedal and Veiling (1957) found that pyrimethamine acted synergistically with two other sulfonamides, sulfabenzpyrazine and sulfadimidine, against E. tenella.
Most recently, a quaternized derivative of pyrimidine, amprolium, has been introduced. This compound is 1-(2-n-propyl-4-amino-5-pyrimidinylmethyl)-2-methylpyridinium chloride hydrochloride. According to Rogers et al. (1960), 0.0125% amprolium in the feed is effective against E. tenella, E. necatrix and E. acervulina. It is a thiamine antagonist, and 0.003% thiamine in the feed markedly decreased its activity against coccidia. Another name for amprolium is mepyrium, the discovery of which was announced by Aries (1960).
According to Rogers et al. (1960), many other 1-(2-alkyl-4-amino-5-pyrimidinylmethyl)-alkyl pyridinium salts have marked prophylactic activity in coccidiosis of poultry. Analogous 3-thiazolium compounds are also effective.
The imidazole derivative, glycarbylamide (4, 5-imidazoledicarboxamide) was introduced as a coccidiostat by Cuckler et al. (1958). It is fed in a concentration of 0.003% in the feed. It is effective against E. tenella, E. necatrix and E. acervulina, but Horton-Smith and Long (1959a) found that it is inferior to sulfaquinoxaline against the last. McLoughlin and Chester (1959) found that it is about as effective as nicarbazin against E. tenella, and more effective than nitrofurazone, Bifuran, sulfaquinoxaline or Trithiadol.
Glycarbylamide is coccidiostatic, and will not cure coccidiosis once signs of the disease have appeared. It acts against the stages prior to the second generation schizonts, and birds which are infected while receiving the drug develop immunity to reinfection. It is apparently non-toxic when fed at the recommended level.
Several benzamide derivatives are effective coccidiostats. Morehouse and McGuire (1957, 1959) found that 3, 5-dinitrobenzamide and several aliphatic N-substituted derivatives are effective against E. tenella and somewhat less effective against E. necatrix. They found that Unistat, a "coccidiostatic growth stimulant" mixture containing 30% N4-acetyl-N1-(4-nitrophenyl) sulfanilamide, 25% 3, 5-dinitrobenzamide and 5% 3-nitro-4-hydroxyphenylarsonic acid in an inert carrier, when fed at a concentration of 0.1% in the feed, prevented death and permitted normal or near normal weight gains in chicks infected with potentially lethal doses of E. tenella, E. necatrix and E. acervulina.
Another benzamide derivative is zoalene (3, 5-dinitro-o-toluamide). Hymas, Stevenson and Shaver (1960) reported that it prevents mortality and weight losses from infections with E. tenella, E. necatrix, E. acervulina, E. maxima and E. brunetti when fed continuously in the ration of chicks at levels ranging from 0.0025 to 0.015%. They recommended a level of 0.0125% for broilers and lower levels for replacement pullets. This compound is most effective against E. necatrix.
The benzamide derivatives are coccidiostatic and will not cure the disease once signs have appeared. Birds which are infected while receiving them develop immunity to reinfection.
Hemorrhage is an important cause of death from cecal coccidiosis, and its control will ameliorate the disease. Harms and Tugwell (1956) and Tugwell, Stephens and Harms (1957) found that the vitamin K activity of alfalfa meal or menadione sodium bisulfite complex (Klotogen F) prevented deaths from cecal coccidiosis in birds on a basic vitamin K-deficient diet. Otto et al. (1958) confirmed their work, finding that 1.0 g of the water soluble menadione sodium bisulfite complex per ton of feed was just as effective as 3 g per ton of menadione.
Sulfonamides and other coccidiostats have been mixed in poultry feed for so many years that it was inevitable that drug resistant strains of coccidia would develop. The first report of this was by Waletzky, Neal and Hable (1954), who found that a field strain of E. tenella from a Delaware broiler fiock was more than 40 times as resistant to sulfaquinoxaline and 5 times as resistant to sulfamethazine as ordinary strains. It was unaffected by 1.0% sulfaquinoxaline in the feed. Cuckler and Malanga (1955) studied 40 field strains of allegedly drug-resistant cecal or mixed intestinal and cecal coccidia from chickens. They found that 43% were resistant to nitrophenide, 45% to sulfaquinoxaline and 57% to nitrofurazone. Twenty-two percent were resistant to all 3 drugs, 18% to 2 and 18% to 1. None were resistant to nicarbazin, which had only recently been placed on the market. They produced resistance against sulfaquinoxaline in 1 strain of E. acervulina and 2 strains of E. tenella by exposure to suboptimal dosages of the drug during 15 serial passages, but 1 strain of E. tenella was not rendered resistant to nitrophenide, nitrofurazone or nicarbazin by the same method for 15 serial passages.
Drug resistance is becoming increasingly common. It seems to develop with especial ease against glycarbylamide. As a consequence, we are in a race between the discovery of new coccidiostats and the development by the parasites of resistance against the older ones. In the long run, prevention of coccidiosis without reliance on drugs appears to hold more promise.
Prevention and Control
Coccidian oocysts are extremely resistant to environmental conditions. They may remain alive in the soil for a year or more (Warner, 1933; Farr and Wehr, 1949; Koutz, 1950). They will not sporulate in the absence of oxygen, and they are killed in time by subfreezing temperatures. Thus, Edgar (1954) found that the oocysts of E. tenella were dead after 7 days at -12° C.
Ordinary antiseptics and disinfectants are ineffective against them. Perard (1924), for instance, found that the oocysts of rabbit coccidia would sporulate unharmed in 5% formalin, 5% phenol, 5% copper sulfate, or 10% sulfuric acid. Horton-Smith, Taylor and Turtle (1940) confirmed this with E. tenella and added 5% potassium hydroxide and 5% potassium iodide to the list. Indeed, the standard storage solutions for coccidian oocysts are 2.5% potassium bichromate or 1% chromic acid solution.
The oocysts may be destroyed by ultra-violet light, heat, desiccation or bacterial action in the absence of oxygen. Long (1959) found that exposure to a temperature of 52° C for 15 minutes killed the oocysts of E. tenella and E. maxima. However, Horton-Smith and Taylor (1939) found that even a blowtorch did not kill all the oocysts on the floors of poultry houses unless it was applied long enough to make the wood start to char. The problem is to reach and maintain a lethal temperature at the spot where the oocysts are.
While formaldehyde fumigation is ineffective against coccidia, Horton-Smith, Taylor and Turtle (1940) showed that ammonia fumigation is of practical value. E. tenella oocysts were killed by an 0.0088% solution of ammonia in 24 hours, by an 0.044% solution in 2 hours and by an 0.088% solution in 45 minutes. They fumigated poultry houses successfully with 3 oz. ammonia gas per 10 cu. ft. For satisfactory results, the houses should be sealed so that the gas does not leak out.
Boney (1948) found that methyl bromide is also an effective fumigant. It inactivated sporulated oocysts of E. tenella in the litter or soil when applied at the rate of approximately 1 lb. per 1000 square feet (0.3 ml per sq. ft.). It prevented infection in brooder houses using artificially contaminated cane pulp litter on wooden floors when used as a space fumigant at the rate of 2 lb. per 1000 cu. ft.
Since it is practically impossible under farm conditions to prevent chickens from picking up at least a few oocysts, prevention of coccidiosis depends upon preventing a heavy enough infection to produce disease while at the same time permitting a symptomless infection (coccidiasis) to develop and to produce immunity. This can be accomplished by proper sanitation and management. Strict sanitation is effective alone, but it is usually supplemented by the use of a coccidiostatic drug.
Young chickens should be raised apart from older birds, since the latter are a source of infection. If birds are raised on the floor, each new brood of chicks should be placed in a clean house containing clean, new litter. The litter should be kept dry, stirred frequently and removed when wet. The feeders and waterers should be washed in boiling water before use, and should be cleaned at least weekly with hot water and detergent. The waterers should be placed on wire platforms over floor drains, and the feeders should be raised high enough to prevent their being fouled. Enough feeders should be provided so that all the birds can feed at once without crowding.
Chicks raised on wire have much less chance of contamination than those raised on the floor. However, the wire should be cleaned regularly.
Flies, rats and mice around the poultry houses and yards should be eliminated, since they may carry coccidia mechanically. Damp areas around the poultry house should be filled in or drained.
Feeding a coccidiostat during times when the birds are especially susceptible may also be helpful. The drug may be fed until the birds are 8 or 9 weeks old, after which they have ordinarily become immune. In addition, it is often recommended that a coccidiostat be fed to pullets for the first 2 or 3 weeks after they have been moved into laying houses.
If an outbreak of coccidiosis occurs, all sick birds should be removed from the flock and placed in a separate pen. They should be given ample food and water, but it is useless to attempt to treat them. The remaining, apparently healthy birds should be treated with a coccidiostat in the dosage recommended by the manufacturer. Birds which become ill should be removed. The litter should be kept dry and stirred frequently.
All dead birds should be burned. The litter should also be burned or put someplace where chickens will never have access to it.
Care should be taken not to track coccidia from sick birds to healthy ones. Special rubbers or overshoes should be put on before entering pens containing sick birds, and should be cleaned thoroughly after each use. Veterinarians going from one farm to another should disinfect their boots before leaving each premises.
The use of old, built-up, deep floor litter has been recommended by Kennard and Chamberlin (1949) and others to reduce losses from coccidiosis. By this method, the litter is not changed when new batches of birds are placed in a house, but some fresh litter may be added from time to time as needed to keep it in good condition. The litter is stirred every 2 or 3 days for the first 8 weeks and every day thereafter. Every 2 to 4 weeks, hydrated lime may be mixed in with the litter at the rate of 10 to 15 lb. per 100 square feet of litter, but this is not necessary. The litter will keep dry for 8 to 16 weeks. Using this method, Kennard and Chamberlin (1949) observed a mortality of 7% as compared to a mortality of 19% in chickens kept on fresh litter removed and changed every 2 weeks.
On the other hand, Koutz (1952, 1952a) found that many coccidian oocysts and nematode eggs remain alive in deep litter. Horton-Smith (1954), too, pointed out the dangers inherent in its use. He noted, however, that the ammonia produced would kill many oocysts. Long and Bingstead (1959) found that chicks on old, built-up litter did not gain as well as chicks on wire or new wood shavings, and that coccidia appeared in them earlier. Because of the dust, ammonia fumes, and danger of other diseases, the use of built-up litter in raising chickens is not recommended.
Edgar (1955a) developed a coccidiosis "vaccine" which is said to be highly successful in immunizing chicks. It is a mixture of sporulated oocysts of E. tenella, E. necatrix, E. maxima, E. acervulina and E. hagani (Libby, Bickford and Glista, 1959). It is recommended for use when the chicks are 3 to 5 days old. They are starved for about 3 hours and then given feed freshly mixed with the commercially prepared oocyst culture. The chicks are supposed to develop light infections and seed the litter with the oocysts which they produce. These oocysts produce reinfections in turn. It is recommended that a coccidiostat be fed at a low level until 5 weeks after vaccination, i.e., until the birds are 5,5 to 6 weeks old. Under these conditions, the birds are said to become immune without suffering disease. While this system often works well, failures have been encountered too often to justify recommending its general use at present.