Synthetic anticoccidials were introduced to the market first. The earliest study on the prophylactic use of anticoccidials was published in 1948 by Leland Grumbles and describes the continuous use of sulfaquinoxaline for the control of coccidiosis in poultry. After their introduction, synthetics were found to be very effacacious and so increased in popularity. Up until 1971 they were the only available option for coccidiosis control as ionophores were not introduced until the 1970's.
Increased interest in synthetic compounds
In recent years, the use of synthetic compounds has increased, especially in the US. This is mainly driven by decreasing use of ionophores that are perceived or classified as antibiotics and can therefore not be used in production systems that promote 'antibiotic-free' or 'no antibiotics ever' (NAE) poultry meat. In these markets, a marked increase in the use of coccidiosis vaccinations for broilers has been seen, often in combination with the use of synthetic anticoccidial products.
Synthetic anticoccidials are very efficacious products, significantly reducing parasite numbers which results in a lower output of oocysts. This in turn reduces infection pressure in a flock which can be very advantageous before rotating to a coccidiosis vaccine. Reducing the parasite population before vaccination will give competitive advantage to the vaccine strains, which is especially beneficial where attenuated vaccines are used. Even when vaccination is not performed, a 'chemical break' from ionophores is needed once per year to reduce the infection pressure that will inevitably come about due to their constant use.
When looking at oocyst output, the number of oocysts in the house will be higher and will increase flock after flock when birds receive only an ionophore (Figure 1). A fully synthetic program will greatly reduce this output (Figure 2). In a reverse shuttle program, an ionophore is applied in the starter and grower phases, followed by a synthetic product in the finisher phase. This will result in another dynamic reduction in the oocyst output at the end of life (Figure 3).
Synthetic compounds have different modes of action, therefore eliminating the risk of cross-resistance between different products.
Synthetic anticoccidials, in contrast to ionophores, have no antimicrobial activity and do not directly inhibit the growth of Gram-positive bacteria such as Clostridium perfringens. They do, however, have a strong effect on subclinical and clinical coccidiosis and therefore have an indirect effect, since they remove one of the most important predisposing factors in the development of necrotic enteritis and dysbacteriosis.
Synthetic compounds are in general quite safe products. This contrasts with ionophores where the safety margin is narrower and issues with toxicity can occur from mixing errors or cross-contamination.
Due to the very strong antiparasitic effect of synthetic compounds, development of reduced sensitivity in the parasite population is a more rapid process compared to that in ionophores. Sensitive parasites are substantially reduced and when resistant parasites are present, it will be easier for them to multiply and move to dominate the parasite population (Figure 4).
For this reason, anticoccidials in general, especially synthetic compounds, need to be used in a judicious way in order to avoid reduced sensitivity (Figure 5).
Alternating the different available options (ionophores, synthetics and vaccines) will ultimately result in optimal coccidiosis control in the long term as it will help safeguard the efficacy of all the control tools available. Considering the advantages and disadvantages of each control tool, as well as practical experience from the field, the following guidelines have been designed.
The general principle is to apply the rotation principle. Overuse of a compound leads to reduced efficacy. Therefore, do not use the same compound for too long, and give the product enough rest before using it again.
Schedule a chemical clean-up once per year
Synthetics are ideally used once each year as a 'clean up' program in a shuttle for one or maximum two grow-outs. The advantage of a shuttle program with an ionophore is the additional beneficial impact that ionophores have on the microbiota during the more challenging grower period. Including the synthetic product at the beginning of the grow out will result in limited contact between parasites and product, and is a safer use of synthetics compared to the 'reverse shuttle' program where synthetics are included in the finisher phase. On the other hand, the reverse shuttle program will decrease the parasite load at the end of the cycle, resulting in lower pressure for the next flock. After using one specific synthetic compound, it should not be used again in the same year. However, other synthetic compounds can be used as there is no cross-resistance (Figure 6).
When a complete break from ionophores is necessary, synthetics can also be used in a full program. Traditionally, a chemical break is performed in the less challenging period of the year, i.e. in Europe this is the summertime. However, this should not be limiting.
Use in combination with probiotics
Since synthetics do not have an effect on Gram-positive bacteria such as Clostridium perfringens, it is advised to add an efficacious probiotic to a synthetic program. When comparing broiler performance in trial conditions using Stenorol® (Halofuginone) and B-Act® (Bacillius licheniformis) separately or combined, a clear trend of improved performance was seen when a synthetic and B-Act® were used together (Figure 7).
It is important to note that for combination products, ionophores and synthetic compounds have different modes of action and therefore development of reduced sensitivity is a slower process. This explains why these products can be used for longer periods compared to purely synthetic products. As such, combination products can be used for up to nine months a year. After use, it is advised to stop using them for at least three months.
In recent years, use of synthetics for coccidiosis control in turkey production has increased. As there are only a limited number of anticoccidials available for use in turkeys, and coccidiosis control is becoming more difficult, producers are using synthetics in a shuttle or a fully synthetic program. In Europe, the toolbox for coccidiosis control in turkeys is more limited as no vaccines are available, so it is even more important to optimize use of all the available options.
Coccidiosis control has always been important for Huvepharma® and will continue to be important in the future. The Huvepharma® coccidiosis control product portfolio is the biggest on the market. In Europe, Coxiril® (diclazuril) and Stenorol® (halofuginone) are registered both for broilers and turkeys, and in the international markets, Coyden® (clopidol) and Amprol® (amprolium) are also available.
In Europe, Coxiril® as a 0-day withdrawal period and is registered for use in broilers, turkeys, guinea fowl and rabbits. The registered dose range is 0.8 - 1.2 ppm. The standard and advised dose for this very safe product is 1ppm. The 0-day withdrawal period of Coxiril® makes it suitable for coccidiosis control up until slaugher age. Therefore, Coxiril® is the product of choice in the flock before the introduction of a coccidiosis vaccine. Using Coxiril® in a reverse shuttle program is advised when the peak of lesions are seen late in the life cycle of the birds (around 35 days).
In Europe, Stenorol® has a 5-day withdrawal period which makes this product more suitable for use in starter and grower feeds. A shuttle program combining Stenorol® with an ionophore is an ideal program to reduce infection pressure when introducing the new flock.
In the US market, Coyden® has been widely used for two decades in broilers, turkeys, and replacement chickens. Coyden® and other synthetic anticoccidials have become an even more valuable tool in coccidiosis control programs since the increased market demand for NAE raised broilers and turkeys. Providing Coyden® as an option has been highly appreciated and proves to be a real benefit.
Amprol® has a 0-day withdrawal period and is registered as a feed additive for broilers, replacement and laying chickens, and turkeys in some markets. In the US, where in 2019, 38% of the total broiler production used coccidiosis vaccines, Amprol® is used together with coccidiosis vaccination in 'bio-shuttle' programs, but also in straight and shuttle programs when no vaccine is used. A bio-shuttle program will reduce the coccidiosis peak, optimizing performance. The wide dose range of Amprol® allows for use a lower levels for immunity development. Introducing Amprol® after coccidiosis vaccination usually occurs when birds are approximately 16 days of age. This bio-shuttle program delivers additional performance benefits compared to vaccination alone.
Synthetic compounds are an important tool in the coccidiosis control toolbox. In recent years, their importance has increased due to the rise of antibiotic free production, and their use in combating the decreasing sensitivity of coccidiosis to other products. As with any other anticoccidials, synthetics should be used responsibly. In traditional production systems where ionophore use is permitted, it is advisable to use a synthetic compound at least once a year in a shuttle program to reduce coccidiosis pressure. In alternative production systems (antibiotic free, NAE, raised without antibiotics), synthetics can be an added value to the coccidiosis vaccines in a bio-shuttle, straight or shuttle synthetic program to improve performance. In this way, clever use of these strong anticoccidial products will be beneficial to effective coccidiosis control.
A version of this article appeared in International Poultry Production, Vol 28 No 3.