Special Report

International conference maps future direction for control

The tropical far north of Queensland, Australia, seems a world removed from broiler houses or research labs, but in July 2001 it was the gathering place for some of the best scientific minds in the business.

The 8th International Coccidiosis Conference, sponsored by the Australian Society for Parasitology, was attended by some of the world’s foremost parasitologists. It was a truly international gathering. As well as the strong contingents from the United States and host Australia, there were visitors from the U.K. and Europe, Brazil, South Africa, Japan, China, New Zealand and many others.

And despite such a diverse grouping, some strong themes emerged. It revealed that efforts to meet the challenge of one of poultry’s major health problems are — like many things — becoming globalized. Issues that affect the large-scale broiler producer in Georgia or North Carolina can be just as pertinent for a low-tech operation in the south of China.

For people in the poultry industry, the scientists offered a fascinating window into the future management of coccidiosis. In this overview of the conference presentations and discussions, CocciForum takes a look at some of these themes and trends from the Cairns gathering.

COCCIDIOSIS: TRULY A GLOBAL ISSUE

Compared with some other internal parasites, the Eimeria species in poultry are remarkably stable. Although there may be variability in the pathogenicity of the different species, the sudden appearance of ‘hot’ new strains seen with avian viruses is not usually an issue for the industry.
This could lead to the mistaken conclusion that with such a stable target like coccidiosis, control is simply a matter of finding a management system that works and sticking with it.
Nothing could be further from the truth. There are many “drivers” of change in the industry and a range of these fall outside the direct control of producers and animal health specialists. For example:

Gene technology promises benefits, but … Unravelling the genetic codes of parasites such as the Eimeria species in the poultry industry will help researchers understand how the organisms seem to stay one step ahead of chemical controls by evolving resistance. But don’t hold your breath for a quick answer. Contributors to a roundtable discussion on the subject (see article, page 12) said researchers are only just beginning to explore the very complex ways that microorganisms learn to live with chemicals such as antibiotics. For example, one parasite is thought to have evolved a protein that literally “pumps” the drug away. Developing ways to understand, let alone counteract, biological tricks like this is expected to take many years. The message: Biotechnology offers some exciting long-term prospects, but don’t expect it to deliver any quick fixes to the problems of resistance to chemical treatments.

• Consumer perceptions Consumers are increasingly turning away from products they perceive as being “unnatural,” or those containing residues from drugs or antibiotics. This is happening in markets throughout the developed world. Consumers are demanding more product information and are concerned about animal welfare, as well as the possibility of chemical residues or pathogens in the food they buy.
Fear about the transfer of antibiotic resistance to the arena of human health is emerging as another major issue for consumers. Vaccination provides the industry with a sustainable, consumerfriendly strategy.

• Economics The economics of production have a profound impact on animal health management, especially in such an intensive environment as broiler production. This involves not only in-house factors — feed or animal health costs, for instance — but also external forces such as market conditions. While niche markets are developing for premium “drug-free” poultry products, there are also strong pressures to minimize production costs to keep them priced competitively.

• Technology Rapid advances in biotechnology are providing new insights into Eimeria species — what’s out in the field, how they respond to different control measures, and how they interact with their host. New diagnostic techniques featuring DNA analysis are giving scientists an unprecedented close-up picture of these surprisingly complex organisms. This will help researchers develop more subtle, better targeted control measures, while continuing to improve the effectiveness of existing strategies such as vaccination and, to a lesser extent, new-generation feed additives.

• Parasite and host Although they are relatively stable organisms, Eimeria species are still traveling down the evolutionary road. As well as evolving to build up resistance to chemical and ionophore treatments, the composition of field populations is also constantly shifting. This happens partly in response to the way they are managed by growers, but there are also very complex relationships that scientists are now just beginning to understand.
The relationship with the host is a very close one. As the genetic codes for the parasite and host are revealed, researchers hope to learn more about genetic factors that control the impact of coccidia on its host (i.e., virulence) or how well the host can resist or tolerate the parasite.
It’s also becoming apparent that the interaction between different Eimeria species ingested by one bird can have an impact, as does the presence of other microflora in the gut.
This news probably won’t change management practices right now, but it does point the way to the future. By learning more about Eimeria at this molecular level, products such as vaccines can be refined to keep ahead of the evolutionary game.

Chemical Tools

Drug resistance unpredictable Resistance to drugs among Eimeria species can develop in as little as 6 months. Experience in countries such as China, where use of chemicals or ionophores to control coccidiosis is relatively recent, has shown neither rhyme nor reason to the way resistance develops. Scientists at the coccidiosis conference in Cairns were told that development of resistance to drugs can be gradual or sudden. Dr. Martin Shirley from the U.K. Institute of Animal Health said some drug combinations are difficult to license. And for every combination that is developed, a resistant strain will develop to match it. Dr. Greg Mathis from Southern Poultry Research Inc., Athens, Ga., said vaccination plays an important role in combating or delaying drug resistance by replacing resistant strains with drug-sensitive lines.

The range of chemical and ionophore treatments for coccidiosis is unlikely to be extended. The era of development that started with the anticoccidial “wonder drugs” in the 1960s and 70s and progressed to the more recent ionophores is virtually complete.
The result? The poultry industry must learn to extend the lives of these products as much as possible within the constraints caused by the increasing resistance of both coccidia and consumers.
While integrating chemicals and ionophores with vaccination programs can extend product life, growers are also turning their attention back to the basics of good husbandry.
The cure-all originally offered by chemical tools cannot be totally relied upon for control of coccidiosis and other problems such as necrotic enteritis. (More than once, poultry scientists at Cairns commented that today’s broiler stock seem “softer” than their predecessors. If the shield thrown up by chemical or ionophore treatments loses effectiveness, birds seem less able to deal with challenge from coccidia.)
This is leading growers to refocus on managing such areas as bird density, ventilation, moisture and litter — all factors in the uptake of oocysts by poultry.

The Search for Alternatives

As cracks start to appear in the longterm sustainability of traditional coccidiosis treatments, interest is growing in some quarters in “organic” treatments based on plant products. While the jury is still out on the effectiveness of these products, they present real difficulties for regulatory authorities when it comes to registration and quality assurance.
This is because they are based on complex organic compounds and it is not always clear what components, if any, have a therapeutic effect.

Vaccination: The Growth Area

In the meantime, vaccination is emerging as the strong growth area in coccidiosis management for poultry producers. This theme resounded continually throughout the week-long conference in Cairns.
Dr. Harry Danforth, technology transfer coordinator with the USDA, said new vaccines are likely to emerge, featuring different mixes of Eimeria species/strains. They will also be developed to match conditions in different regions or countries.
“Coccidial vaccines are now well established in Europe, Canada and the United States, and new products are being developed in Europe and the United States as well as Australia,” he said.
“Use of vaccines based on live oocysts such as Coccivac-B still has considerable potential for growth.”
Danforth’s comments were echoed by Dr. David Chapman of the University of Arkansas. He said the development of Paracox-5 in Europe was just one example of the way vaccines can be formulated to suit the needs of a geographic region.

The Next Generation?

There was general agreement at Cairns that the current generation of coccidiosis vaccines, which are based on live oocysts, are highly effective but still on the lower slopes of a steep growth curve in poultry industries worldwide. But scientists are still excited about the potential for the next generation of vaccines.
The “Next Big Thing” will be subunit, or recombinant vaccines. Rather than using live oocysts, they’ll be focused on antigens specific to the parasite and expressed through a bacterial vector — E. coli, for example.
Using biotechnology tools, some of which are still very much in their infancy, this next generation of vaccines will be highly targeted and sustainable. They might be injectable or administered via a spray cabinet as some products are now.
However, the next wave of products is still very much on the research bench. Danforth said that while there’s no doubt these products will eventually emerge, there is still much basic research to be done, including the mapping of the genome for Eimeria species.
Once that’s done, specific genes can be targeted for vaccines or drug therapy.
“It’ll be a tough nut to crack,” he said. “Some of the genetic research being done on other coccidia such as Toxoplasma and Cryptosporidium will have spinoffs for work on Eimeria in poultry.”

What Lies Ahead?

If there was a common thread running through the discussions at Cairns it was: “It’s time to think outside the box.” These are just some of the things that could be just over the horizon:

• Changing the basic approach to Eimeria species by redefining the host/parasite relationship. Using genetic modification technology, it may be possible to create dominant strains that are easy to manage and have minimal impact on their host. The logic? Get the parasite to respond to the poultry industry’s requirements rather than the reverse situation.
• Easy-to-use diagnostic kits that can be used in commercial situations to “map” the breakdown of Eimeria species present. Management programs could then be tailored to suit the specific populations.
• Using partially drug-resistant lines of Eimeria in live vaccines. This concept appears to fly against conventional wisdom that a key benefit of vaccines is that they “reseed” poultry houses with drug-sensitive strains. Trials have shown that the drug-sensitive strains do indeed re-establish on pen floors after a flock is vaccinated, although drug resistance seems to subsequently re-emerge after several growouts using a drug regime.
The logic behind using drug-resistant strains in a live vaccine is that it could allow drug therapies for the control of drug-sensitive coccidial species and other organisms (e.g., clostridia) in tandem with vaccination. (At present this can’t be done with most live oocyst vaccines, because anticoccidial drugs would compromise the coccidial strains used in these vaccines.) It’s a radical concept but there is already one such vaccine being developed in Europe.
• Creating a universal strain of the species used in vaccines to deal effectively with all field strains of Eimeria species. This development, which would also grow out of genetic modification technology, would address the challenges posed by regional variations in Eimeria populations.

Talking Coccidiosis

Notes from the Australia Roundtable

Roundtable Participants

Dr. David Chapman, Department of Poultry Science, University of Arkansas (Chair)

Dr. Tim Cherry, Stephen F. Austin University, Texas

Dr. Harry Danforth, Technology Transfer Coordinator, USDA

Dr. Grant Richards, Eimeria Pty Ltd, Victoria, Australia

Dr. Martin Shirley, Institute for Animal Health, Compton, U.K.

Dr. Ray Williams, Schering-Plough Animal Health, Harefield, U.K.

It was billed as a “controversial roundtable” and was strategically slotted on the last day of the 8th International Coccidiosis Conference in Queensland, Australia. The focus: The role of live vaccines in the sustainable control of coccidiosis in poultry production.

Led by some of the heaviest hitters in this branch of poultry science, the roundtable discussion lived up to its billing and attracted a standing-room-only crowd. Following are CocciForum’s notes from this lively session

Take an Integrated Approach

Danforth: Proven treatments are emerging.

A decision to use vaccination against coccidiosis isn’t a question of ‘all-or-nothing’.
While vaccination isn’t currently used in the same flock with chemical or ionophore treatments, vaccination can become part of an effective rotational program, alternating with existing medication- based regimes. Harry Danforth gave a graphic example of how this works in practice. He has done trials that confirmed how Coccivac-B repopulated farms with coccidia that were sensitive to salinomycin. This helps enhance the usefulness of the drug if it is used in a later growout.

Watch the Arsenic

Some populations of Eimeria tenella — one of the most significant coccidia species — are becoming very resistant to salinomycin.
One way of dealing with this has been to use roxarsone (3-Nitro), an arsenical treatment that’s been used since the 1970s and is currently used by around 60% of the U.S. poultry industry.
Danforth said that with increasing concerns about arsenic in the environment, growers’ access to this tool may be limited in the future. Proven treatments such as vaccination are emerging as viable alternatives.

New drug compounds still face long road to approval Two new feed additives recently registered in the United States have taken 8 years to make it from initial submission to final registration. Dr. Thomas Letonja from the FDA’s Center for Veterinary Medicine said the timeline is a fairly typical one for new veterinary compounds to make it through the regulatory system. And that’s despite a move in 1996 to streamline the process by removing the need for the FDA to replicate the trials done by the sponsors of a new compound. He said the caution required for human food safety assurance causes the biggest delays in the regulation process. Letonja said the industry may already have all the veterinary drugs it needs. He noted that in Europe there was a trend to remove, rather than add, new drugs to the list of those available. At the same time, growers were starting to make more judicious use of existing compounds. Vaccines do not require the same lengthy approval process.

Keep Tabs on Coccidia

Two presenters at the roundtable explained why it is important to understand what’s happening in a flock as the coccidia respond to treatment. Looking at the numbers of coccidia, as well as what species they are, shows how the treatments are working.
Eimeria populations can be tracked by measuring how many oocysts are excreted by the birds. Dr. Ray Williams said that in medicated flocks, the oocysts per gram (OPG) counts can vary a lot, but usually peak at around week 4 or 5.
Williams also noted that, in these flocks, the coccidia can peak again toward the end of the growout after the medication is withdrawn. This can indicate that the birds are still susceptible to the disease, and the prophylaxis has only suppressed the coccidia rather than giving immunity.
In vaccinated flocks, there are typically two peaks in the output of oocysts, the first occurring usually between weeks 2 and 4. This happens as immunity is being established. The second peak represents a wild-type challenge around week 4 or 5.
Once the second peak has passed, the OPG counts drop rapidly — a good indicator that immunity has kicked in successfully.
Danforth explained that a new diagnostic tool developed in Europe and based on molecular biology (polymerase chain reaction, or PCR) shows researchers very accurately which of the seven Eimeria species are involved in a flock. This is important to help design good, targeted treatments. It also helps monitor exactly how well different programs are working.

Team Up with Vaccines

Williams said that because vaccination is a biological process using live organisms, growers need to learn to work as a team with the vaccine to make sure it delivers maximum effectiveness. The treatment depends on the birds successfully excreting a generation of vaccinal coccidia and then “recycling” them by picking them up from the litter. The uptake of coccidia is part of the build-up of immunity. To successfully “sporulate” in the environment, coccidia need the right balance of oxygen, warmth and moisture. If the litter is too dry, there may not be enough oocysts shed to challenge the birds sufficiently for immunization; if it is too wet, the numbers of coccidia could overwhelm the birds and cause a disease outbreak.
Williams said stocking density and access to feed are two other important factors in the birds’ uptake of coccidia from litter. Good husbandry is essential.

Williams: Work as a team with the vaccine.

‘Compensatory Gain’

Dr. Tim Cherry said immunity in vaccinated birds is developed by 4 weeks of age. Weight gain and feed efficiency are initially affected as immunity develops, but birds subsequently catch up — a scenario known as “compensatory gain.”
It used to be thought that vaccinated birds compensated for the initial weight gain suppression as immunity was established, usually by 4.8 lbs. But Schering- Plough Animal Health data have shown that weight gain and feed conversion in vaccinated birds are comparable to birds in coccidiostat programs after 35 days.

The Clostridial Question

Some in the industry are concerned that vaccinated birds may not receive the protection they need from clostridial bacteria. This is because the ionophores normally used to prevent coccidiosis also provide some protection against clostridial diseases like necrotic enteritis. Ionophores cannot be used with live coccidiosis vaccines, as they would compromise their performance.

Drug resistance a problem in China They don’t do things by halves in China. Professor Mingquan Xie of the Guangdong Academy of Agricultural Sciences gave conference-goers an outline of his country’s massive poultry industry. There are three native types of chicken grown — black, yellow and white — accounting for 80% of poultry output. The remaining 20% is shared between ducks and geese. Production techniques vary from very small-scale and primitive to highly modernized units that would be more familiar to U.S. growers. Xie says anticoccidial drugs have been abused in China, where coccidiosis tends to be worse in the hotter southern and eastern regions, including Taiwan. As a result, vaccination is playing an increasingly important role in management of coccidiosis in that country. An evaluation of anticoccidial drugs showed that about two-thirds of the Eimeria tenella strains were resistant to five or more different products — a worrying sign. In the trials, diclazuril performed very well, Xie said.

Nevertheless, Williams said that in trials he’s observed, necrotic enteritis affected both vaccinated birds and control groups of birds treated with a growth promoter and ionophore.
He said there’s a perception in the industry that coccidiosis makes birds more susceptible to clostridial diseases like necrotic enteritis, but more research is urgently required to confirm this idea. (For more insights on managing necrotic enteritis in vaccinated birds, see page 18.)

What About Diet?

Factors such as diet could play a part in both coccidiosis and clostridial diseases. Williams said it’s been shown that coccidiosis and clostridial diseases are affected by dietary changes (e.g., more or less wheat or maize content).
How this works isn’t known yet, but it could be a function of vitamins or the “viscosity” of feces. The less viscous, the more easily bacteria are “flushed out” of the bird’s system. More research could show how diet could play a part in coccidiosis management.

Looking Ahead

At the roundtable discussion, Dr. Martin Shirley was very enthusiastic about the future of coccidiosis control through vaccination. He expects to see the growing use of “big” vaccines (i.e., those available currently), complemented by the development of new, specialized vaccines for different markets.He also expects to see vaccines developed to manage necrotic enteritis.
In line with the growth in vaccine use, Shirley said that concerns over the use of in-feed medication were likely to increase, especially within Europe, and the possible wider banning of some or all coccidiostat in-feed medication could now be seen on the horizon.
Shirley also predicted that biotechnology will lead the way to development of more sophisticated and targeted vaccines. This will come about as the parasite genes responsible for inducing immunity are identified, and scientists learn how to manipulate and deliver antigens. He also said biotechnology would help scientists keep up with dealing with any immunologically different (vaccine-resistant) strains should they appear in the field.

Vaccination has role in organic production Consumers in Europe are turning away from animal products that have been treated with antibiotics or synthetic chemicals and producers should take notice, according to Dr. Jean-Michel Répérant of the French Agency for Food Safety. He told CocciForum that some drugs are being banned in Europe. (See article, page 30.) In France, some producers are turning to unproven and unregulated plantbased treatments, which is a concern for regulatory authorities. However he says the trend away from the use of drugs to treat coccidiosis underlines the key role played by vaccination. He says some organic producers in France choose anti-coccidial vaccination, as this still meets the requirements of organic standards.

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