Changing product mixes at U.S. broiler companies and concern on the part of consumers and regulators over the emergence of antibiotic resistant strains of human bacterial pathogens are stimulating an evaluation of current and future methods of suppressing coccidiosis.
The USA's broiler integrators spend upwards of $110 million dollars annually to suppress coccidiosis, the most significant erosive infection impacting the industry. It is estimated that approximately 92 percent of all U.S. broilers are reared using dietary incorporation of anticoccidials in shuttle programs. Meanwhile, anticoccidial oocyst vaccines satisfy defined segments of the broiler industry estimated to represent between 7 percent and 9 percent of current production.
Recent epidemiological studies relating to the emergence of antibiotic resistant strains of human bacterial pathogens have stimulated a series of risk analyses by regulators and public health advocates to evaluate the impact of growth-promoting additives in livestock feeds. Concern, whether justified or not, among consumers has resulted in the demand for a range of "drug-free" labeled broilers and derived products which command a premium in specific market segments.
Since ionophores have antibiotic properties, the status of this significant class of anticoccidials remains the subject of scrutiny. Last year, a major U.S. integrator was not allowed to label products as being "raised without antibiotics" despite deletion of antibiotic growth promoters from diets. After initial label approval, the USDA ruled that the inclusion of ionophores, in consistency with use as approved by the FDA, represented deceptive labeling. This issue was resolved by a compromise in which the label claim was changed to "Chicken raised without antibiotics that impact antibiotic resistance in humans."
During fall, winter and early spring, a high proportion of broiler complexes use nicarbazin in the starter diet followed by an ionophore in the grower and, depending on circumstances, in the finisher diet. Some companies use specific ionophores including monensin and salinomycin through the terminal growing period, based on an FDA zero-withdrawal clearance before slaughter. Many companies are apparently able to withdraw all anticoccidial medication after 25 days, especially during summer.
It is common practice in the USA to incorporate 3-Nitro together with nicarbizin to potentiate activity against E. tenella and to serve as a non-antibiotic growth promoter. Recently, there has been considerable opposition to the use of 3-Nitro based on ill-founded and unjustified concerns over environmental contamination. Arsenic in 3-Nitro is in the non-toxic pentavalant form, is sequestered in soil and does not leach into ground water, notwithstanding the claims made in recent environmental lawsuits.
Anticoccidial oocyst vaccines comprise a balanced mixture of three Eimeria spp. of clinical and commercial significance. The major applications for anticoccidial vaccines include heavy broilers grown to a live weight over seven pounds in addition to the relatively limited "Certified USDA Organic" and "drug free" market segments.
Flocks receiving anticoccidial vaccines, even with optimal administration and adequate litter moisture content, show evidence of mild exposure. This usually results in the loss of one to two days growth. Over a 60-70 day grow-out cycle, this is relatively insignificant compared to birds grown to conventional weight. The loss associated with transient coccidiosis challenge in heavy broilers attributed to vaccines is offset by reduced expenditure on conventional feed medication.
A second problem associated with anticoccidial vaccines relates to the temporal association of mild coccidiosis, which may be followed by subclinical or overt clostridial enterotoxemia. Toxigenic strains of clostridial organisms can precipitate necrotic enteritis, cholangiohepatitis and are associated with gangrenous dermatitis. Generally mild coccidiosis will not result in clostridial enterotoxemia if effective growth-promoting antibiotics are added to the diet. Virginiamicin, bacitracin and lincomycin, all approved antibiotic growth promoters, will suppress Clostridium spp., reducing the impact of low-grade or subclinical coccidiosis associated with oocyst vaccination.
Special measures are required to suppress necrotic enteritis in "drug free" flocks. These may include addition of mannanoligosaccharides (Bio-Mos) alone or in combination with botanicals such as oregano (Natustat). Administration of probiotics including Lactobacillus spp. may also be considered to suppress clostridial enterotoxemia, if anticoccidial vaccines are used as the principal method of control.
Table 1: U.S. Approved Anticoccidial Feed Additives, Broilers
Concern among consumers has resulted in the demand for a range of 'drug-free' labeled broilers. During the past year, Schering-Plough Animal Health, the manufacturer of the leading anticoccidial vaccine, introduced a Cl. perfringens TypeA toxoid positioned as a vaccine against necrotic enteritis. The product is administered to replacement pullets which are immunized and transfer protective maternal antibody to broiler progeny. Bottom-line contribution may be enhanced by using necrotic enteritis toxoid in complexes with an ongoing problem of necrotic enteritis or gangrenous dermatitis, especially when rearing drug-free flocks.
The Embrex subsidiary of Pfizer Animal Health has worked to develop Inovocox for a number of years. This oocyst vaccine intended for in ovo administration is based on Eimeria isolates originally developed by Pfizer scientists. Despite extensive research, and demonstration of efficacy at the laboratory level and presumably during pre-registration trials, the product has not yet been launched commercially.
Merial-Select intends to market a vaccine based on precocious strains of the significant Eimeria spp. isolated by the late Dr. Peter Long. Precocious strains only undergo one stage of schizogony and are inherently less pathogenic than the strains incorporated in conventional oocyst vaccines. The Merial-Select product is undergoing pre-registration evaluation and availability is anticipated during the summer of 2008. If effective, this product could be positioned for the 4- to 6-pound broiler market, based on the expectation of effective control of coccidiosis without the undesirable low-grade infection characterized by growth suppression of one to two days in duration.
Schering-Plough has not introduced its UK-origin precocious vaccine, Paracox into the U.S. market, but it is anticipated that should the Merial product prove both effective and commercially acceptable, the company would be obliged to launch Paracox or an equivalent product to defend its considerable market share for anticoccidial vaccines.
During the late 1990s, ABIC of Israel introduced CoxAbic positioned as a maternal immunization. The vaccine is administered twice to pullets during rearing. CoxAbic is derived from proteins extracted from gametocytes of Eimeria maxima. Maternal antibody transfer apparently protects chicks from lesions during early exposure, which results in premunity. The vaccine, which has met with mixed results in a number of markets, including Europe, Southern Africa and Latin America, is not registered in the USA.
Scientists at the USDA-ARS Parasitology, Biology and Epidemiology Laboratory in Beltsville, Md., have worked for over two decades on vaccines based on the molecular biology and immunology of Eimeria. A DNA vaccine is under development involving administration of genes encoding for the antigenic proteins of the parasite. Although there is extensive literature on the principle of administering genes as vaccines, limited studies have shown that special promoters are required for expression and subsequent elaboration of antibodies. The current stage of development suggests that not only would the Eimeria gene complex have to be administered individually to recipients but synergistic cytokines and other promoters will be required. It is generally considered that the industry will not benefit directly from the USDA-ARS-PBE Beltsville research for at least a decade, if at all.
Recent studies conducted in the UK and the USA focus on isolating a specific Eimeria protein which is broadly antigenic. This line of research runs parallel to the project on describing the Eimeria genome. If the specific genes coding for a universally immunogenic protein could be identified, it would be possible to develop a non-pathogenic vector species such as Eimeria mitis which could effectively serve as a vaccine. This would represent a practical approach but only if the vector is compatible with in ovo or coarse spray mass administration.
Balancing the high cost of developing anticoccidial drugs against the uncertainties of the regulatory environment and commercial acceptance will inhibit development of novel anticoccidial feed additives. There is no indication from any of the animal health companies, all of which are subsidiaries of pharmaceutical multinationals, that anticocidials are a component of either long- or short-term development programs.
If current anticoccidial chemical and ionophore compounds are retained, the industry will be dependent on medication for at least the next two decades. Accordingly, every attempt should be made to preserve the efficacy of the limited range of available products. Reducing dosage will only increase the rate at which strains of the significant Eimeria spp. develop resistance. Cutting dosages from the recommended levels represents false economy and will create future problems on individual complexes and ultimately for the entire industry.
It will be necessary to extend the life of available ionophores by widening the range of this class of compounds currently used by applying more frequent rotation irrespective of minor cost differences. Decisions relating to selection of drugs should be based on ongoing routine surveillance of flocks by assessing lesion scores and correlating performance with the use of alternative medication programs.
Clinical coccidiosis does not occur as an isolated host-pathogen interaction. Establishing and maintaining the active immune status of flocks by appropriate suppression of Marek's disease, infectious bursal disease and chicken anemia is necessary to facilitate and potentiate the immune response to coccidiosis. Although premunity against protozoal pathogens occurs at the cellular level, it is known that immunosuppression, especially as it appeared on the Delmarva Peninsula during the 1980s as a result of variant IBD exposure, is frequently manifested as unexplained outbreaks of coccidiosis and gangrenous dermatitis.
Oocysts require adequate litter moisture to sporulate and become infectious. Strides have been made in the past 10 years to reduce the moisture content of litter by improved ventilation and insulation of houses and introduction of nipple drinkers. Dry litter is generally beneficial to the health of flocks but may represent a problem in that there is inadequate early exposure to sporulated oocysts when using recycled litter. Depriving chicks of naturally encountered "trickle vaccination" may complicate suppression of coccidiosis in some areas or production systems.
A number of prebiotics and probiotics are now available and have achieved acceptance in the "drug free" segment of the market. Extending the use of oligosaccharides, defined bacterial cultures and some botanicals, which have been shown to be effective, may be required to potentiate the action of existing chemical and ionophore compounds.
The principal objective of any comprehensive program to suppress coccidiosis is to optimize financial return in terms of saleable product over expenditure on control and not merely to minimize cost.
