Asked about the threat to the use of in-feed anticoccidials in the modern world threatened and whether vaccination will regain added importance for managing coccidiosis, Dr Larry R. McDougald, Professor Emeritus at the Department of Poultry Science of the University of Georgia told Poultry Health Today that several decades ago, there were several new in-feed anticoccidials in the pipeline. They eventually were approved and marketed.

At the time, however, he predicted that the increasing cost of drug development and risky returns on investment would make it difficult or impossible for traditional pharmaceutical companies to discover, develop and market new anticoccidials for managing coccidiosis.

His concerns of long ago are unfortunately being realised. Dr McDougald said that, in today’s regulatory environment, where it now takes seven to 10 years to develop a major new animal drug and can cost up to $100 million, there is little incentive for animal health companies to develop new drugs for common diseases such as coccidiosis. Not surprisingly, there are no new anticoccidials coming to market anytime soon.

By the 1980s, he suggested that if animal health companies devoted more research to the development of new coccidiosis vaccines, we would have suitable products for use in broilers. Even though much of the research was done with limited resources, the companies’ efforts paid off. In fact, we have seen several coccidiosis vaccines vie for position in the broiler market over the years.

Anticoccidials

Even though in-feed anticoccidials have been used somewhat universally for managing coccidiosis, new pressures, especially consumer concerns about adding any antimicrobials to the feed of food animals, could eventually reduce their use in some markets, said Dr McDougald.

Apart from public pressure, the other complication that occurs with the long-term use of anticoccidials is a technical problem, and that is the eventual development of drug resistance if the products are not used correctly. In fact, drug resistance resulting from overuse has resulted in the demise of several fine products.

Many poultry producers have learned to manage the problem of resistance by using “hybrid” programmes. The so-called shuttle programmes, where one product is used in the starter ration and another in the grower, have been invaluable over the years and still remain important.

A good example of this is using nicarbazin in the starter, followed by an ionophore in the grower, according to Dr McDougald. In the US, this is principally used in the cooler winter months, when coccidiosis management is most difficult. Producers normally rotate to another programme in the spring, as warmer temperatures make the use of nicarbazin hazardous. Often a synthetic (or chemical) anticoccidial is used to complement ionophores. Vaccination is used on many farms as well.

Aside from these seasonal “tweaks” to coccidiosis-management programmes, ionophores remain the most commonly used products. In some areas of the world, however, their future is uncertain.

He explained that, in the EU, several anticoccidials are forbidden from use. In the US, there has been argument in some circles about whether certain anticoccidials, particularly ionophores, should be restricted for use in food animals since they are technically antibiotics; this is due to the perceived risk of contributing to antibiotic-resistant infections in people.

For now, the US Food and Drug Administration (FDA) has stated that anticoccidials are not medically important to human medicine, and there are no restrictions on the use of ionophores in poultry – except for use in programmes following “no antibiotics ever” guidelines.

Anticoccidial/vaccination Rotation

Another way the industry has dealt with the coccidial-resistance problem is by rotating vaccination into the coccidiosis-management programme, according to Dr McDougald. As far back as the 1970s, Jeffers proposed the seasonal rotation of drugs and live vaccines. At the time, the efficacy of straight drug programmes was being compromised by the emergence of Eimeria strains resistant to ionophores.

Integrating vaccination into coccidiosis-management programmes replaces drug-resistant field strains of coccidia with drug-sensitive vaccine strains. The ionophores then show improved efficacy, at least for a time. The success of this method depended on the development of live vaccines specific for use in broilers.

Broiler vaccines can be used reliably and cost-effectively, and this approach saw more common usage with good results but still accounted for a minority of the anticoccidial market. In recent years, growth in the use of vaccines stalled somewhat since roxarsone, which was used to enhance feed conversion in vaccinated flocks, was pulled from the market.

Vaccination with Live Vaccines

The dream of many investigators as early as the 1930s was to make live vaccines that would provide “stand-alone” management of coccidiosis. Dr McDougald explained that, in the early days, this seemed like a simple task, since chickens readily become resistant to coccidia after exposure to a light infection, and the self-limiting nature of the coccidial life cycle would keep the birds from breaking with coccidiosis while the birds’ immune response developed.

Dr. S.A. Edgar of Auburn University was the first to champion this cause, with the commercialisation in the 1950s of a vaccine product that contained all of the known, pathogenic species of coccidia.

The vaccine worked well at protecting birds against coccidiosis but it had the disadvantage of adversely affecting feed conversion. Sometimes more than 10 points were lost – an intolerable figure for broiler production. The vaccine found a niche in layer pullets and broiler breeder replacements, where feed conversion was not affected. Still, the product enjoyed only limited commercial success, probably because other, more familiar programmes were preferred by producers.

Big strides forward with vaccination came about in the 1980s and 1990s, said Dr McDougald, when research focused on improved administration techniques. Vaccination via the drinking water, long known to be inaccurate and highly variable, was abandoned in favour of more effective methods including individual bird inoculation, eye-spray, spray cabinet, edible gels and in-ovo vaccination. These approaches all improve the uniformity of vaccination.

Meanwhile, other research began to produce results on the attenuation of coccidia. Jeffers was one of the first to produce attenuated coccidia by genetic selection for a shortened life cycle. This work was repeated in the UK and resulted in a live vaccine marketed mostly in Europe.

Today, at least eight live vaccines are available in some countries for use in poultry, and there are several for broilers. Most are not attenuated and owe their success to the improvements in administration techniques. They are producing uniform exposure to improve protection against coccidiosis and reduce vaccine reactions, and can be cost-effective in broilers by streamlining the number of coccidia species that are included in the vaccines.

On the downside, coccidia are known to interact with clostridia to precipitate outbreaks of necrotic enteritis (NE). If NE is to be treated or prevented, it will require the use of antibiotics, which is counterproductive for producers who want to produce antibiotic-free meat. There has been some anecdotal evidence that attenuated vaccine strains might have less propensity to add to the NE problem but this needs to be studied and will no doubt be considered as further improvements are made to live vaccines.

Future Challenges

There is no fun in seeing one’s predictions come true, especially when they foresee the demise of major disease-control programmes that we have depended upon, Dr McDougald told Poultry Health Today. Live coccidiosis vaccines have played a major role in the management of coccidiosis, particularly in the US, and in some seasons, have accounted for 40 per cent of coccidiosis programmes.

What remains to be seen is whether special-interest and consumer groups will challenge the use of anticoccidials in food animals as they have with antibiotics, despite the FDA’s position on anticoccidials. If they do, we could face further restrictions on the use of drugs and chemicals in poultry for managing coccidiosis, and if this is the case, vaccination will become more important. With more than nine billion broilers produced in the US per year, the magnitude of vaccine production required would be astounding.

Dr McDougald is one of the leading experts on coccidiosis in poultry in the United States. He has extensively researched and published on the subject and, as a poultry science professor, has made major contributions to the training of poultry veterinarians.

This interview was first published in 'Poultry Health Today', which is sponsored by Zoetis Animal Health.

February 2014