Perspectives for the control of coccidiosis in poultry by chemotherapy and vaccination

H. D. Chapman, Department of Poultry Science, University of Arkansas, Fayetteville, AR, 72701, USA. dchapman@uark.edu

Introduction
Despite the introduction of live vaccines, in most countries prophylactic chemotherapy is still the preferred method for the control of coccidiosis (Chapman, 2000). Significant improvements in the performance of commercially reared poultry have been made during the last half of the twentieth century and a recent study has shown that in the USA these improvements have continued, and are measurable even for the relatively short time period of 1995-2001 (Chapman et al., 2003). It has often been assumed that these improvements would not have been possible without the introduction of a succession of ever more effective anticoccidial agents to control coccidiosis. In recent years, however, few new drugs have been introduced. The most widely used compounds, ionophorous antibiotics, have been utilized with apparent success for more than thirty years; these drugs have been used extensively in commercial broilers and are also employed to some degree during the rearing of broiler breeder and replacement layer stock (Chapman, 1993; 2001). Synthetic drugs (chemicals) have been used to a lesser extent; in the USA nicarbazin was introduced in 1955 and is still used in broiler production (Chapman, 1994a)! In the 1970s many other highly efficacious synthetic drugs were introduced only to be withdrawn because of the development of drug resistance.
At first it was thought that resistance would not develop to the ionophores but many recent studies have shown this not to be the case. For example, Mathis (1999) examined the sensitivity of recent isolates of E. acervulina, E. maxima, and E. tenella to monensin, salinomycin, narasin and lasalocid and found that these drugs were only marginally or poorly effective; similar conclusions have been made by others (e.g. Chapman and Hacker, 1994). Anecdotal information provided to the author by those involved in rearing poultry indicates that coccidiosis is not generally considered to be a major problem. How can this be true if the principal drugs used are no longer as effective as in the past? Possible reasons are discussed in this article.

Acquired drug resistance
Conventional methods for evaluating drug efficacy involve challenging birds with isolates of Eimeria obtained from the field using a sufficiently large dose of oocysts to induce a depression of weight gain and/or lesions in susceptible birds (Chapman, 1998; Holdsworth et al., 2004). Such studies can indicate whether a drug is able to control an infection capable of causing clinical disease and if not the isolates may be classified as showing various degrees of “resistance” to the drug. Some authors have questioned whether current experimental methods for determining resistance are appropriate (Watkins, 1997). Experiments with isolates considered “resistant” to ionophores showed lack of control by these drugs whether a large or small dose of oocysts was administered, and weight gain or oocyst production in the feces respectively used to assess efficacy (Chapman and Shirley, 1989). An explanation for the efficacy of ionophores under commercial conditions where ionophore resistant strains are present must be sought elsewhere. A possibility is that these drugs do not prevent the acquisition of immunity and that this may develop before birds are exposed to potentially pathogenic numbers of oocysts (Chapman, 1999a). Indeed, reliance upon immunity development in flocks medicated with ionophores is a major strategy used to control coccidiosis by poultry producers in the USA (see below). Whether resistance will translate into drug failure in the field will depend upon the extent of exposure to infective oocysts in the commercial poultry house. Such exposure will in turn depend upon many environmental and management factors.
Our knowledge of the extent to which resistance is present in the field would be increased if methods were available for identifying resistant strains; such information may be forthcoming in the future (Sangster et al., 2002).

Management and Environment
The pioneering studies of Johnson and Tyzzer in the 1920s laid the groundwork for our understanding of coccidiosis and the important management and environmental factors that affect the incidence and epizootiology of this disease (Chapman, 2003). Of the many improvements in husbandry and housing that have occurred over the years, one of the most significant may have been the comparatively recent introduction of nipple type drinking systems. These systems require careful management but have the potential to reduce litter wetness that is known to be a major factor in the occurrence of clinical coccidiosis. The introduction of efficient ventilation systems and enclosed housing has facilitated better environmental control and may also have helped reduce the likelihood of coccidiosis. An example of the effect of management upon the effectiveness of coccidiosis control programs was given by Williams; higher parasite numbers were produced by vaccinated birds where “clean-out” between flocks was demonstrably inadequate (Chapman et al., 2002).

Other diseases and pathogens
There is some published evidence that coccidiosis is more prevalent in flocks where other diseases, bacterial and viral, are present. The introduction of modern vaccination programs for a variety of such diseases may therefore have contributed to the decreased occurrence of clinical coccidiosis. Many antibiotics have been introduced to improve the performance of commercial poultry and are generally thought to work by suppressing the growth of pathogenic bacteria; these are often used along with anticoccidial drugs. A recent study has clearly demonstrated improved performance of flocks where growth promoters are included in the feed in combination with anticoccidial drugs (Chapman and Johnson, 2002).

Host genetics
It is known that different breeds of chicken may vary in their susceptibility to infection with Eimeria species. Although breeding programs to select for resistance to coccidiosis have not been undertaken by the commercial poultry industry, selection for “fitness” will include resistance to common environmental pathogens of which Eimeria is one component. It would be of interest to establish whether the modern broiler is less susceptible to coccidiosis than its antecedents.

Ionophores and immunity
Recent studies have shown that a factor in the efficacy of ionophores has been their lack of interference with the development of immunity (Chapman, 1999b). The poultry industry has taken advantage of this by increasing the withdrawal period of medication prior to slaughter with considerable savings in the costs of medication. This can, however, result in poorer performance, particularly in situations where birds may be exposed to heavy infections late in life (Chapman et al., 2004).

Vaccines
It seems logical that if immunity is desired then this should be achieved by use of live vaccines. Guidelines to assist those interested in designing studies to evaluate the efficacy of new vaccines have recently been published (Chapman, et al., 2005b). Vaccination has become more practical with the development of new methods for vaccinating birds in the hatchery. It has recently been shown however that even with highly immunogenic species of Eimeria, such as E. maxima, reinfection is necessary for the establishment of solid immunity at 4 weeks of age when birds are given a small dose of oocysts following hatch (Chapman et al., 2005a). Exposure to large numbers of oocysts prior to 4 weeks could result in clinical coccidiosis before birds acquire protective immunity. Thus with vaccines as well as drugs success of vaccination is likely to depend upon environmental and management factors that affect numbers of infective oocysts in commercial poultry houses.
In recent years several new methods of vaccinating chickens have been introduced but in few cases has the route of infection been clearly demonstrated and the proportion of birds infected established; the latter is relatively easily determined (Chapman and Cherry, 1997).

Restoration of drug sensitivity
Use of live vaccines comprising drug sensitive strains results in the restoration of sensitivity to ionophores such as monensin (Chapman, 1994b); similar conclusions were reached for salinomycin and diclazuril (e.g. Mathis, 2003). It is difficult to demonstrate that restoration of sensitivity has resulted in long term improvements in flock performance, nevertheless programs involving the rotation of vaccines with traditional chemotherapy have been advocated (Chapman et al., 2002) and are used by the poultry industry.

Current coccidiosis control in the USA
In the USA accurate information on the use of feed additives, including anticoccidial drugs, in the feed of poultry is available from a commercial database that covers almost the entire broiler industry (Agri. Stats Inc.). Data from 1995-1999 indicate drug usage had a characteristic cyclical annual pattern (Chapman, 2001). Programs comprising a single or two different ionophores were used extensively (80-90% of broiler complexes) in the summer and fall (June-November) followed by a decrease (70-50% of complexes) in winter and spring (December-May). During the latter period there was an increase in the use of shuttle programs (20-50% of complexes) in which a synthetic drug and ionophore were employed. Overall, more than 95% of broilers were given an anticoccidial drug in the feed for some part of their life.
Data from 2004/2005 indicate a different pattern of drug usage. Shuttle programs in which a synthetic drug was employed during winter and spring were still widespread (20-60% of complexes). However, during the summer and fall the use of a single or two ionophores had declined to approximately 50-60%. The remaining complexes (10-30%) used no anticoccidial medication during this period and it is speculated that the reason was the adoption of coccidiosis vaccines. In the USA, vaccines are primarily used in the summer months; it will be interesting to see if this pattern persists in the future.

The Future
Crystal ball gazing is not without risk as the premature anticipation of recombinant DNA vaccines illustrates. The dearth of new drugs to control coccidiosis makes it tempting to speculate that the “age of chemotherapy”, having been extremely successful and lasting almost sixty years, (since the demonstration in 1947 that sulphonamides can be used prophylactically) may be nearing its end. As already indicated, in the USA where accurate data are available, the use of drugs is still extensive; in Brazil, a country with a broiler industry similar in size to that of the USA, approximately 92-95 % of broilers receive an anticoccidial drug in the feed (Viana, personal communication). Although coccidiosis vaccines have been available since the 1950s their use in the USA is limited although as indicated above this situation may be changing (attenuated vaccines that are apparently widely used in Europe and elsewhere are not presently available). It may be premature therefore to consider that the ‘age of vaccination” is upon us. An unknown factor is the extent to which national authorities, in response to perceived consumer pressure, may impose restrictions on the use of anticoccidial drugs in poultry feeds. Vaccination is now considered a more realistic proposition than in the past but this does not mean that it is without problems and many questions remain to be answered. In the case of attenuated vaccines, not the least will be the logistics of providing sufficient oocysts to vaccinate billions of broilers worldwide. A likely scenario in the coming decades is a combination of approaches in which chemotherapy and vaccination are integrated in programs designed to achieve sustainable coccidiosis control for the foreseeable future.

References
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