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Cover Story - Technically Speaking

Dr. Martin Shirley on making your coccidiosis control program state of the art

Martin Shirley, PhD Institute for Animal Health, Compton Laboratory Compton-Newbury, U.K.

For over 50 years, coccidiosis control in intensively reared broiler chickens has depended on a constant stream of new products. In the past, virtually all introductions have been anticoccidial drugs. For the foreseeable future, however, no new drugs can be expected, and it appears that only vaccines will provide the necessary innovation and new options.
Although live vaccines have been available commercially for many years, it is only recently that the momentum for their use has increased due to the availability of a new generation of live vaccines that are based on safer, precocious lines of parasites. In addition, concern among retailers over the use of feed additives and possible implications for human health have favored an increasingly “greener” approach to farming.
Replacing dietary prophylactic drugs with vaccination offers tangible practical advantages. For example, the elimination of 3- to 5-day drug withdrawal periods means that birds of a target weight can be removed from a flock whenever they are needed. In other words, producers now have it within their power to make their coccidiosis control program more flexible, meeting market demands.

Immune Detection

Seven species of Eimeria enter the body of the chicken. They are located within host cells deep inside the gut and are entirely dependent on the host for nutrition as they undergo massive rates of growth and multiplication.

Within just a few hours alter ingesting oocysts, the host chicken begins to respond to the infection; by around 4 days, it will have mounted the start of a specific protective immune response.

The potency of this response varies depending on a variety of factors such as the size of the infective dose, but even a chicken exposed to a single intake of small oocyst numbers will develop substantial immunity to further challenge.

The Anticoccidial Drug Era

The first comprehensive descriptions of most avian coccidia were made in the 1920s and 1930s. Within just a few years, the efficacy of inorganic sulphur for preventing caecal coccidiosis was reported and opened the way for the introduction of new anticoccidial drugs into the marketplace.

The variety of different chemical drugs introduced initially was superseded at the beginning of the 1970s by the most successful of all anticoccidials — the ionophorous antibiotics. Unlike many “totally” effective chemical drugs that readily gave rise to resistant mutants, the ionophores were intrinsically less effective and each newly introduced drug allowed some parasites to develop and complete their life cycle during the course of every infection. This unique mode of action imposed weak selection pressures on coccidia and drug-resistant mutants were not reported for many years.

Ultimately, resistant strains to ionophores appeared, but the drugs have continued to remain the mainstay of coccidiosis control. The use of ionophores, however, is now tempered by the need to manage the high incidence of drug-resistant strains. This is usually achieved through the implementation of drug shuttle programmes.

The huge success of ionophores in conjunction with the more limited use of other drugs has almost certainly been one reason why several animal health companies have reduced their search for, or interest in, the development of new anticoccidial drugs. Other factors that have impacted negatively on research to derive new drugs include the spiralling costs of product development and changing political perceptions about the role of feed additives.

A dramatic decline in the pace of new introductions has thus followed the success of the ionophores; no new anticoccidials were made available during the 1990s. Moreover, reports of potentially active compounds completing the first phase of investigation are now sparse and it appears that no new drugs can be anticipated for the foreseeable future.

Bridging Drugs and Vaccines

Against the backdrop of coccidiosis control by chemotherapy and the need for the poultry industry to adjust the use of individual drugs as their efficacy is compromised by drug resistance, immunity to parasites has played an interesting and increasingly prominent role during the past 10 to 20 years. One investigator theorized that the development of host immunity is a major factor accounting for the effectiveness of polyether ionophores, despite the existence of resistant strains of field coccidia.

It is thus possible to think that some of the drugs, especially the ionophores, have for many years been acting in concert with background coccidial infection to function as “surrogate vaccines” by maintaining low levels (trickle doses) of infection that have immunised the hosts in the absence of disease.

New Control Strategies

Over 20 years ago, it became clear to many scientists that the rich genetic diversity of coccidia would require introduction of new control strategies if the parasites were to be controlled effectively in the long term. In other words, the almost blanket use of chemotherapy would not be adequate. Immunoprophylaxis — the prevention of disease by utilizing natural immunity — largely remained neglected, although progress was made in the mid-1970s and throughout the 1980s on the selection of attenuated parasites that would provide the basis of a new generation of live vaccines.

The use of small numbers of normal, “wild-type” parasites (e.g., those recovered from the field) as vaccine components can be very successful if the delivery system is optimised so that most or all chickens within a flock ingest vaccinal oocysts around the same time. Unfortunately, failure to achieve uniform administration could result in heavy infections in nonvaccinated birds that were exposed to large numbers of oocysts produced by vaccinal oocysts as they recycle through the flock. Thus, the first-generation live vaccines were very effective at generating protective immunity in the host, but they had a comparatively restricted window of safety.

‘Precocious’ Lines

One objective of the search for new vaccine candidates was to derive “modified” parasites that would be protective but offer a greater margin for safety. It was anticipated that such candidates would therefore be eminently suitable for use in broiler production, where a larger margin of safety is required due to high stocking density and the precise economic production targets that are sought. The so-called “precocious” lines of Eimeria spp. fit the bill exactly and provided an ideal combination of:

• Potent immunogenicity (immunising the chicken as effectively as wild-type strains)

• Attenuation of virulence

• Reproduction that enables them to be used as “one-administration” vaccines

Species for a Broiler Vaccine

Of the seven species of avian coccidia, those encountered most frequently in broiler chickens worldwide are the pathogenic species E. acervulina, E. maxima and E. tenella. These three species will therefore form the basis of any live vaccine.

Eimeria brunetti and E. necatrix are highly pathogenic, but they tend to be found in older birds and are uncommon in broilers. Conversely, E. praecox is regarded as relatively benign and not a significant contributor to the general picture of coccidiosis, even though it is common in broilers.

For European flocks, E. mitis must be considered. It is significantly pathogenic but infections with this species are not revealed by the appearance of gross lesions that can be assessed by visual inspection with the naked eye. The contribution of E. mitis to subclinical coccidiosis has almost certainly been underestimated.

Drug-Sensitive Strains

It seems entirely logical that live coccidiosis vaccines will not be used concurrently with anticoccidial drugs and that each approach will be regarded as totally sufficient.

Since live vaccines will be used alone, the choice of drug-sensitive strains of Eimeria as their basis will be advantageous. For example, the use of such a product instead of anticoccidial drugs will introduce drug-sensitive oocysts into the environment and the incidence of drug-resistant strains will be expected to fall as they become diluted out.

Methods of administering coccidiosis vaccines to ensure more uniform application also have been developed.

Necrotic Enteritis

It is clear that both vaccines and anticoccidial drugs can achieve excellent coccidiosis control. Both options also have strengths and weaknesses.

For example, the activity of the antibiotic ionophores includes antibacterial effects; there is a perception by some within the poultry industry that with vaccination, the incidence of necrotic enteritis (NE) will rise, since vaccines will not have similar controlling effects of Clostridium perfringens. Interestingly, some of the first comprehensive data describing the use of live vaccines in broilers revealed more cases of NE in medicated control flocks.

A better understanding of the epidemiology of NE is most definitely required; the multiple factors that underpin cases of NE and any relationship between attenuated and/or wildtype coccidial parasites and Clostridium needs to be determined in the context of modern poultry practices and nutrition. (See article, page 18.)

Conclusion

Safe and effective vaccines based on precocious lines and improved methods of vaccine administration are available. There is also growing concern over the use of feed additives in poultry and increased demand for “greener” poultry production methods. These factors have led to an increasing interest in the worldwide availability of vaccines for use in broiler chickens.

Whatever lies ahead for the control of coccidiosis, it is beyond doubt that coccidia cannot go about their lifestyle of parasitism without the host declaring immunological war. Harnessing that rapid immune response can provide producers with state-of-the-art coccidiosis control and vaccination promises to be a powerful tool for the poultry industry well into the future.



Source: CocciForum Issue No.4, Schering-Plough Animal Health.