Avian Pathology

ISSN: 0307-9457 (Print) 1465-3338 (Online) Journal homepage: https://www.tandfonline.com/loi/cavp20

Anticoccidial drugs and their effects upon the

development of immunity to Eimeria infections in
poultry

H. D. Chapman

To cite this article: H. D. Chapman (1999) Anticoccidial drugs and their effects upon the
development of immunity to Eimeria infections in poultry, Avian Pathology, 28:6, 521-535, DOI:
10.1080/03079459994317

To link to this article: https://doi.org/10.1080/03079459994317

Published online: 17 Jun 2010.

Submit your article to this journal

Article views: 3761

View related articles

Citing articles: 41 View citing articles

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=cavp20
Avian Pathology (1999) 28, 521±535

REVIEW

Anticoccidial drugs and their effects upon the

development of immunity to Eimeria infections in
poultry

H. D. Chapman*
Department of Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA

The long-held view that anticoccidial drugs, to a greater or lesser extent, interfere with the development
of immunity to Eimeria species may no longer be correct because few drugs, if any, are capable of
preventing some degree of parasite multiplication. Acquisition of immunity is, therefore, a real possibility,
providing suf® cient parasites are present in the environment. Immunity is an important consideration
during the rearing of replacement layers, broiler breeders, turkeys, and gamebirds, but little research has
been carried out on the effects of drugs on immunity development in these categories of stock. In recent
years, there has been a change in the perception of the signi® cance of immunity in broilers, and some
broiler producers have taken this into consideration when designing drug programs for use in the ® eld.
Studies in ¯ oor pens and the ® eld indicate that broilers given various drug programs can develop
immunity when exposed to natural infections but that this process takes time: solid immunity not
developing until birds are 6 to 7 weeks of age. This suggests that drugs should not be withdrawn from the
feed prematurely since birds may not have had time to develop adequate immunity.

Introduction in protecting the fowl from the adverse effects of

Modern intensive poultry production is largely de-
pendent upon chemoprophylaxis for the control of
coccidiosis. Despite the availability of many antic-
occidial drugs, Eimeria parasites are widespread in
poultry ¯ ocks. Outbreaks of coccidiosis, recog-
nized by obvious intestinal lesions and excessive
mortality, occur less frequently than in the past.
Nevertheless, subtle effects of the disease, such as
reduced growth rate and impaired feed conversion,
may contribute to poor performance of commercial
birds. Adoption of sound management practices
and sanitary procedures, and the use of modern
broad-spectrum anticoccidial agents have all
played a part in control of coccidiosis. However, in
view of the many reports of acquired drug resist-
ance, it is perhaps surprising that clinical coccidio-
sis is not encountered more frequently in the
® eld. One possibility is that, despite medication,
the parasite is able to stimulate an immune re-
sponse in the bird, and thus contribute to its own
demise.
Immunity has long been recognized as important
coccidiosis, and there have been several excellent
reviews describing our current knowledge of the
mechanisms of immunity to Eimeria species (for
example, Rose, 1987, 1996; Lillehoj & Trout,
1993). Immunization may be achieved by the in-
tentional infection of the chicken (for example, by
introducing the infective stage, the oocyst, into the
feed or water supply) and live vaccines, compris-
ing oocysts of species that are virulent or have
been attenuated, are available for this purpose
(Shirley & Long, 1990; Shirley & Bedrnik, 1997).
Although vaccines are widely used to immunize
replacement layer and broiler breeder chickens,
they are not widely employed in broilers at the
present time. Coccidiosis vaccines are sometimes
used in turkey production but are not available for
game birds.
Immunity may develop as a result of the use of
vaccines, but can also be acquired incidentally
during the use of anticoccidial drugs. Many com-
pounds have been introduced for the control of
coccidiosis, and these can be classi® ed as either
synthetic drugs that are produced by chemical

* To whom correspondenc e should be addressed. Tel: 1 1 501 575 4870. Fax: 1 1 501 575 4202. E-mail: dchapman@comp.uark.ed u

ISSN 0307-945 7 (print)/ISSN 1465-3338 (online)/99/060521-1 5 Ó 1999 Houghton Trust Ltd

522 H. D. Chapman
synthesis (often referred to as `chemicals’ ) or
ionophorous antibiotics (ionophores) that are pro-
duced by fermentation. Although information is
available concerning the mode of action of some of
these compounds, the biochemical basis for their
selective effects against the parasite are poorly
understood (Chapman, 1997a). None of the cur-
rently available drugs are known to modulate the
immune system of the host. Nevertheless, growth
of the parasite may not be completely suppressed,
and suf® cient development may occur to stimulate
a protective immune response. Immunity may,
therefore, play an important role in the apparent
ef® cacy of different drugs. In this article, our
present knowledge of the effects of anticoccidial
agents upon the acquisition of immunity to Eime-
ria species in poultry is reviewed.
De® nition of Immunity
The term immunity, as used in most of the studies
reviewed here, refers to the acquisition of `resist-
ance’ to a challenge infection with an Eimeria
species. Resistance may be measured by a re-
duction in the pathogenic effects of infection, a
reduction in the extent of macroscopically visible
lesions, or a decrease in the numbers of parasites,
as shown by the production of oocysts in the feces
(Rose, 1987). Various interpretations of the results
of challenge studies have been made by different
workers. Thus, Reid et al. (1968) classi® ed chal-
lenged birds as `susceptible’ if their weight gain
was signi® cantly different at the 5% level from
that of unchallenged birds, and `immune’ if no
signi® cant differences were found. By this very
stringent criterion, several drugs were considered
to `prevent’ or `interfere’ with immunity. In some
cases, immunity was considered to be `delayed’ or
`retarded’ by drugs, even though the actual timing
of the acquisition of immunity was not measured
(Reid et al., 1977). In a subsequent study, an
arbitrary scale (from 0 to 3) was developed to
measure the response of birds to challenge;
0 5 complete suppression of immunity,
1 5 moderate suppression, 2 5 slight suppression,
and 3 5 no suppression (Karlsson & Reid, 1978).
The scale was used to compare results for various
drugs in different experiments. Other workers have
used terms such as `partial’ , `incomplete’ , or `com-
plete’ to describe different degrees of immunity
development (Chapman, 1978).
Both the criteria used to evaluate `resistance’ ,
and the magnitude and timing of the challenge
inoculum will differ from one experiment to an-
other, and, therefore, the extent to which birds are
protected from the consequences of infection are
not directly comparable. The magnitude and fre-
quency of primary exposure will also vary in
different studies, and this will affect the immune
status of the birds. It is desirable to include appro-
priate controls; the most important of which are
challenged birds that have experienced no previous
infection (susceptible controls). Unfortunately, it is
technically dif® cult to keep birds parasite free, and
this may explain why susceptible controls have not
always been included in the design of experiments.
Historical Perspective
Early concepts
When the ® rst true anticoccidials (sulphonamides)
were introduced in the 1940s, one of the ® rst
questions asked was, will they interfere with the
acquisition of immunity? Many studies were con-
ducted to investigate the relationship between the
use of these drugs and immunity development (see
references in Waletzky & Hughes, 1949; Anon,
1953). In the case of sulphaguanidine, Levine
(1941) considered that `Its greatest possible use
may be to aid birds in acquiring an active immu-
nity to coccidiosis’ , and immunity became an es-
sential part of the rationale for sulphonamide
therapy (Kendall & McCullough, 1952). Most
studies were conducted with Eimeria tenella, the
species of principal concern to the poultry industry
at that time, but other species, such as Eimeria
necatrix and Eimeria acervulina in the chicken
(Grumbles & Delaplane, 1947; Dickinson, 1949),
and Eimeria meleagrimitis in the turkey (Peterson,
1949), were also investigated.
Several concepts were introduced, such as the
importance of selecting a concentration of drug
that would control coccidiosis but at the same time
permit the acquisition of immunity (Allen & Farr,
1942), and that protection could be achieved with
a schedule of intermittent medication (Seeger &
Tomhave, 1946; Delaplane et al., 1947) or by the
continuous use of a low level of drug (Allen &
Farr, 1943; Swales, 1946; Brackett & Bliznick,
1949). It was shown that, under conditions of
natural exposure, chicks given sulphaquinoxaline
in the feed did not acquire solid protection until
they were 5 weeks of age (Koutz, 1948).
It was also understood that the number of
oocysts present in the environment might be in-
suf® cient to stimulate resistance against reinfec-
tion. Cuckler et al. (1957) believed that it should
be possible to select a concentration of drug for a
given level of environmental contamination in or-
der to `bring about a balance in which the coccid-
iostat will permit immunity to develop’ . They also
realized, however, that `the chief dif® culty in es-
tablishing an optimum drug level is the extreme
variability in the severity of infection which may
occur ¼ it may be necessary to make adjustments
in medication programs to suit the particular cli-
matic conditions of various areas of the country as
well as the time of the year during which such
replacements are raised.’
Attempts were made to incorporate some of
these early concepts into practical advice for the

management of coccidiosis. A recommendation for
farms where caecal coccidiosis had previously oc-
curred was to institute prompt treatment with a
sulphonamide (via the drinking water or feed) at
the ® rst signs of disease (Swales, 1947). In the case
of farms where birds had previously been raised in
`rapid succession’ and where caecal coccidiosis
had been a `continuous and serious problem’ , it
was suggested that when chicks were 2 to 4 weeks
old, they should be placed in a separate pen con-
taining litter contaminated with oocysts and given
a preventative drug in the feed. After 6 to 10 days
of exposure to infection, they should be transferred
back to clean pens and then reared as broilers or
breeding stock. Goff (1947) was sceptical of the
practicality of such procedures since he believed
that `inclusion of a medicant in the ration over a
prolonged period has proved a safer procedure in
coccidiosis control than has intermittent feeding, or
the suggested practice of delaying treatment until
the symptoms have appeared. Any procedure
should allow for controlled infection so that greater
resistance to coccidiosis might be established.’
Synthetic drugs
The importance of immunity was such that Joyner
et al. (1963) stated that `It is now customary to
include tests for effects upon immunity in the trials
of new prophylactic coccidiostatic drugs’ . Many of
the older synthetic drugs did not completely pre-
vent parasite development and were not fully ef-
fective against all species of Eimeria. Aklomide,
amprolium, arprinocid, dinitolmide, glycarby-
lamide, nicarbazin, nitrofurazone, nitrophenide,
Polystat, robenidine, trithiadol and zoalene were
reported not to prevent immunity developing to
various species (Waletzky et al., 1949; Horton-
Smith & Long, 1952; Gardiner & Farr, 1954; Berg
et al., 1956; Cuckler & Malanga, 1956; Edgar,
1958; McLoughlin & Gardiner, 1962; Karlsson &
Reid, 1978). In the case of amprolium and nicar-
bazin, not all results were in agreement since
several studies suggested that they either delayed
or prevented the development of resistance against
reinfection (Strout et al., 1958; McDougald &
Reid, 1971).
In many of these experiments, birds were given
large doses of oocysts, and this does not simulate
exposure likely to be encountered under ® eld con-
ditions. Therefore, studies were conducted with
birds reared in ¯ oor-pens that were exposed to
infection by contamination from adjacent pens
(Reid, 1960). Immunity to E. acervulina developed
in birds given Bifuran and furazolidone, but with
nicarbazin, birds were partially susceptible to this
species. All three compounds interfered with im-
munity to E. tenella (Reid, 1960).
In the late 1960s and early 1970s, a series of
highly effective, broad-spectrum synthetic drugs
were introduced. Preventative medication, in which
Effect of drugs on immunity to Eimeria 523
these compounds are given from 1 day old almost
to slaughter, was considered to confer life-long
protection against coccidiosis, and, under these
circumstances, evaluation of their effects upon im-
munity was no longer considered important
(Waletzky, 1970). Thus, Ryley & Betts (1973)
stated `¼ since the life of the broiler bird is so
shortÐ it is neither necessary nor expedient to
consider immunity, and the object must be to
achieve total and continued suppression or preven-
tion of coccidiosis’ .
In contrast to older synthetic drugs, the
quinolones (e.g. buquinolate, decoquinate and
methyl benzoquate), clopidol, halofuginone, and
robenidine, can markedly suppress oocyst pro-
duction of drug-sensitive strains and are effective
against all species in the fowl (Ryley, 1967; Ryley
& Wilson, 1975). Interference with immunity
might, therefore, be expected. In the case of
buquinolate and clopidol, results of experiments
are dif® cult to interpret. Thus, with buquinolate,
little or no immunity to a mixture of different
species had developed by 9 weeks (Edgar & Flana-
gan, 1968), but, in another study, birds developed
resistance to E. tenella, E. necatrix and Eimeria
brunetti but not Eimeria maxima, Eimeria mivati
and E. acervulina by 8 weeks of age (Reid et al.,
1968). In the case of clopidol, immunity was
prevented in some experiments (Karlsson & Reid,
1978) but not in others (Reid et al., 1968).
Quinolones (such as methyl benzoquate) and clopi-
dol have a coccidiostatic mode of action and arrest
development of the sporozoite following penetra-
tion of the host cell. The presence of these inhib-
ited parasites does not stimulate a protective
immune response since chickens challenged fol-
lowing withdrawal of medication are fully suscep-
tible to infection (Long & Millard, 1968).
The most recent synthetic drugs to be studied
are diclazuril and the related compound toltrazuril.
According to Suls (1998), diclazuril does not in-
hibit the early schizont generations of E. brunetti,
E. maxima and E. necatrix and therefore does not
interfere with the development of immunity to
these species. Surprisingly, diclazuril does not pre-
vent immunity developing to E. tenella, even
though both schizont and gametocyte stages of the
life cycle are inhibited by the drug (Maes et al.,
1991). Toltrazuril was also claimed not to interfere
with immunity (Johnson et al., 1986), but birds
were not challenged until 1, 2 or 3 weeks after
medication was withdrawn and, therefore, protec-
tion could have resulted from subsequent exposure
to oocysts.
Intermittent medication
The intermittent provision of sulphaquinoxaline to
commercial broilers in various feeding schedules
provided good protection against cecal coccidiosis
and did not prevent the development of immunity
524 H. D. Chapman
(Delaplane et al., 1947; Grumbles et al., 1948).
The concept of intermittent treatment was devel-
oped into the so called `3±2±3 or 3±2±3±2±3’
system, in which sulphadimidine was given in the
drinking water for 3 days, separated by periods of
2 days without medication (Davies & Kendall,
1954; Davies, 1958). It has been suggested that
intermittent medication may be an alternative to
prophylaxis for toltrazuril (Haberkorn, 1984). Evi-
dence to support this was obtained in experiments
in which toltrazuril was found not to prevent the
development of immunity to E. tenella when in-
cluded in the drinking water for periods of 3 days
at weekly intervals (Chapman, 1987). In recent
studies, chickens given intermittent toltrazuril
treatment contained high antibody titers to sporo-
zoite antigens, and this was said to indicate that
birds had developed a humoral immune response
(Greif & Haberkorn, 1997). It was concluded that
therapeutic medication with this drug does not
interfere with development of immunity.
Ionophores
Following the introduction of monensin, many
studies were conducted to investigate whether this
compound would interfere with immunity but, as
in the case of some synthetic drugs, results are
dif® cult to interpret because immunity was sup-
pressed in some experiments (for example, Reid et
al., 1977; Long et al., 1979) but not prevented in
others (for example, Reid et al., 1972; Callender &
Shumard, 1973). Immunity was found to be
strongly suppressed in birds given 121 parts/106
monensin (Karlsson & Reid, 1978), but only mod-
erately suppressed by 100 parts/106 of the drug.
Chapman (1978) investigated the effect of
monensin on the protection arising from repeated
low level infections of three species. Birds were
given either 10, 100, or 1000 oocysts three times a
week for a period of 28 days (Table 1). Resistance
to a challenge inoculum developed in medicated
birds given repeated doses of 100 oocysts of E.
maxima, and partial resistance developed in birds
given 10 oocysts. With E. brunetti, resistance to
challenge developed in birds given 1000 oocysts
and partial resistance in birds given 100 oocysts. E.
tenella was the least immunogenic of the species
studied since resistance to a challenge inoculum
was only partial in birds given 1000 oocysts. The
results showed that a protective immune response
can result if medicated birds are repeatedly ex-
posed to small numbers of oocysts, and that there
is a direct relationship between the level of infec-
tion and the degree of protection.
Surprisingly, there have been few studies with
ionophores other than monensin. According to
Karlsson & Reid (1978), immunity to E. tenella
was strongly suppressed by salinomycin and lasa-
locid. The isolate used was a strain considered to
be drug-sensitive because it had not been exposed
to anticoccidials for at least 25 years. Lasalocid did
not prevent immunity to this species when birds
were given repeated low doses of oocysts (Weber,
1989), and immunity was not prevented when birds
were exposed to a natural infection (Chapman,
1997b).
The relationship between drug concentration and
immunity was illustrated in an experiment in
which birds reared in ¯ oor-pens were given 40, 60,
80, 100 and 120 parts/106 of narasin for 8 weeks
and challenged with a mixture of species 1 week
after withdrawal of medication (Ruff et al., 1980).
Pathogenic effects were more evident with higher
concentrations, indicating progressive interference
with immunity. Birds were initially exposed to
oocysts that were probably fully sensitive to this
drug since they were derived from a coccidiosis
vaccine that contains strains isolated in the 1950s.
Since many ® eld isolates now show reduced sensi-
tivity to ionophores, it would be worthwhile to see
if similar results would be obtained with recent
strains of Eimeria.
Immunity Development in Broilers
Signi® cance of immunity
In recent years, there has been a change in the
perception on the part of some broiler producers of
the signi® cance of immunity. In the US, many still
believe that the most ef® cacious compounds
should be employed and that immunity is of sec-
ondary importance, but a dif® culty is that few
highly effective compounds are currently available.
Drug programs involving one or several com-
pounds have been devised with the objective of
minimizing the level of ¯ ock infection and maxi-
mizing ¯ ock performance, but it is often dif® cult to
know which drug or drugs to use in particular
situations. Other producers have adopted an
alternative philosophy that places reliance upon
immunity. An example of this strategy is to include
an ionophore in the starter feed at less than the
Table 1. Immunity development in chickens medicated with
monensin (125 parts/106) and given 13 doses of three species of
Eimeria
Number
of oocysts Immunity developmenta
oocysts given
Drug ( 3 13) E. maxima E. brunetti E. tenella
Monensin 10 Partial No No
Monensin 100 Yes Partial Partial
Monensin 1000 Yes Yes Partial
None 10 Yes Yes Partial
a
Based upon weight gain after challenge in comparison with that
of challenged and nonchallenged susceptible controls (Chap-
man, 1978).

maximum approved level (in order to permit some
parasite development and, hence, stimulation of an
immune response) and then to use a higher concen-
tration during the grower phase (to prevent clinical
coccidiosis). Interestingly, this is the opposite pro-
cedure to that used with traditional `step-down’
programs employed in replacement breeder stock,
in which the concentration is progressively de-
creased as birds get older to permit the gradual
acquisition of immunity.
The signi® cance of immunity should be reap-
praised because many of the compounds currently
used are no longer as effective as when they were
® rst introduced. This is because of the develop-
ment of drug resistance (Chapman, 1997a). For
example, ionophorous antibiotics are the mainstay
of broiler production, but there have been many
reports of a decrease in the sensitivity of ® eld
isolates to these compounds. It is interesting, there-
fore, that Jeffers (1989) stated that `It is likely that
the development of host immunity is a major factor
accounting for the effectiveness of polyether
ionophores despite the existence of resistant strains
of coccidia in the ® eld’ .
A further consideration is the role that immunity
may play in the selection of drug-resistant strains.
The development of resistance will be slower when
birds are given compounds that do not completely
suppress parasite multiplication since they will
allow the survival of `sensitive’ as well as any
`resistant’ forms. If birds develop immunity, both
the resistant and sensitive parasites will be elimi-
nated, and this will further reduce any `selective
advantage’ of the resistant population.
A measure of the change in perception of the
signi® cance of immunity can be gained from the
commercial advice given to poultry producers re-
garding ionophore usage. In the past, ionophores
were not recommended in situations where immu-
nity is desirable (e.g. during the rearing of replace-
ment layers and broiler breeders). Today,
noninterference with immunity is frequently
claimed as a potential bene® t that may result from
use of these compounds (Bafundo, 1994; Watkins,
1997).
According to Philps (1997), strategies for immu-
nity development are well accepted by the broiler
industry, but production losses and outbreaks of
clinical coccidiosis still occur at too frequent a
level. Drug programs designed to permit immunity
in broilers are less likely to be successful in situa-
tions where challenge is high, and other factors
such as inadequate nutrition, ancillary diseases,
and poor management are present. Under such
circumstances, it is desirable to reduce the level of
challenge, and this can be achieved by increasing
the drug concentration and using a compound
known to be capable of suppressing parasite devel-
opment. Philps believes that alternation of immu-
nity and preventative-based approaches to
coccidiosis control may be advantageous.
Effect of drugs on immunity to Eimeria 525
Current drug programs in broiler production
Commercial broilers are usually provided with sev-
eral rations, and this typically involves a starter
feed (given for the ® rst 2 to 3 weeks of life),
followed by a grower ration (given until 5 or 6
weeks), and a ® nisher or withdrawal feed that may,
or may not, contain an anticoccidial drug. The
same compound may be included in all feeds
(referred to as a single-drug program) or different
compounds may be used (so-called `shuttle’ pro-
grams). Shuttle programs may involve a synthetic
drug and an ionophore, two different ionophores
or, occasionally, two different synthetic drugs. In
the US, approximately one-half of broiler produc-
ers utilize a single drug, the remainder using vari-
ous types of shuttle program.
Salinomycin is the most frequently used drug for
the control of coccidiosis in broilers, and in the
US, a wide variety of programs in which this drug
is used alone or in shuttle programs have been
employed. For example, data submitted by 162
broiler complexes for the month of March 1999
indicate that 67 complexes used salinomycin alone
and a further 31 used salinomycin in a shuttle
program with other drugs (Anon, 1999) (Table 2).
Twenty-two complexes used the same concen-
tration of salinomycin (60, 55, 50 or 30 g/t) in both
starter and grower feeds. Forty-four complexes
used a lower concentration in the starter feed than
in the grower (step-up programs), but only one
complex used a higher concentration in the starter
feed. Grower feeds were followed by a ® nisher and
then a withdrawal feed (also referred to as a ® rst
and ® nal withdrawal feed, respectively). The data
indicate that 34 of the complexes utilized an antic-
occidial (ionophore) during the ® rst `withdrawal’
feed, but none did so for the ® nal withdrawal feed
(data not presented).
Ef® cacy and cost are major considerations in
determining the type of program, concentration,
and time period for which different drugs are
given, but effects upon immunity development are
increasingly being taken into account. A possible
advantage of programs that permit immunity is that
medication can be withdrawn at an early age. This
may result in considerable cost savings but a disad-
vantage is the ever-present risk of clinical coccid-
iosis and poor ¯ ock performance.
Unfortunately, there have been few experimental
studies to help the broiler producer determine the
most appropriate programs for the development of
immunity. In our experience, none of the
ionophores can prevent parasite development even
if used at their maximum concentrations. The value
of using variable concentrations at different times
of the broiler cycle, may, therefore, from the point
of view of immunity, be academic. It is widely
believed that use of synthetic drugs is incompatible
with immunity. This may be the case with `new’
compounds that completely suppress parasite de-
526 H. D. Chapman
Table 2. Use of salinomycin by commercial broiler complexes in the USAa
Program
Concentration (g/t)
Number of
complexes Starter Grower
9 60 60
9 55 55
3 50 50
1 30 30
1 60 54
a
Data for March 1999 (Anon, 1999).
velopment, but most drugs in this category do
allow some parasite multiplication and thus may
not interfere with the acquisition of immunity.
Drug programs and immunity: recent ¯ oor-pen
studies
There have been few recent studies of the effects
of different types of drug programs upon immunity
in broilers. In one experiment, birds reared in
¯ oor-pens were given different synthetic drugs
(nicarbazin, halofuginone, or robenidine) in the
starter feed from 0 to 3 weeks of age, followed by
an ionophore (lasalocid) in the grower ration from
3 to 6 weeks (Chapman & Hacker, 1993). Three
species were introduced (via the feed) at 2 weeks
of age, and birds were challenged with E.
acervulina, E. maxima, or E. tenella at 6 weeks.
None of the programs prevented the development
of immunity (Figure 1).
A second study was conducted in which broilers
were reared on old litter that had been top-dressed
with litter containing oocysts from a previous ¯ ock
in order to simulate `natural’ exposure to infection
(Chapman, 1996). Birds were given halofuginone
in the starter feed followed by salinomycin in the
grower, salinomycin in the starter followed by
halofuginone in the grower, or either drug given in
both feeds. None of the drug programs prevented
parasite multiplication. Signi® cantly reduced
weight gains were seen in medicated birds chal-
lenged with E. acervulina and E. tenella at 5 weeks
of age, suggesting that 5 weeks is insuf® cient time
for immunity to these two species to develop (data
not presented). Immunity had developed to E.
maxima by 5 weeks, with the exception of birds
given salinomycin followed by halofuginone. By 7
weeks, birds had developed immunity to all three
species suggesting that none of the drug programs
had prevented the acquisition of immunity.
A third study was conducted in which broilers
were reared on new litter, or old litter as already
described (Chapman, 1999). Treatments comprised
a synthetic drug or ionophore in the starter and
grower feeds, either drug type given alone, or no
Program
Concentration (g/t)
Number of
complexes Starter Grower
39 40 50±52
2 40 60
2 50 55
1 50 60
± ± ±
medication. At weekly intervals, birds were chal-
lenged with a mixture of three species and their
weight gain compared with that of unchallenged
controls. Unmedicated birds reared on old litter
were susceptible to challenge at 4 weeks, but by 5
weeks, resistance had developed to the challenge
inoculum (Figure 2). In medicated birds, partial
immunity had developed by 5 or 6 weeks, and,
with the exception of birds given an ionophore
followed by a synthetic drug, by 7 weeks they had
developed solid immunity. Partial resistance devel-
oped in birds reared on new litter by 6 weeks of
age, and, with the exception of birds given an
ionophore followed by a synthetic drug, solid pro-
tection did not develop until 7 weeks (data not
presented). Providing an infection is present, drug
programs can, therefore, allow the development of
immunity, but this process takes time. If medi-
cation is withdrawn prematurely, then birds may be
at risk of clinical coccidiosis.
Immunity under ® eld conditions
There have been few surveys to determine the
immune status of broilers raised under ® eld condi-
tions using different drug programs. Kemler &
Reid (1961) found that nine of 16 broiler ¯ ocks
given nitrophenide, seven of 15 ¯ ocks given
Unistat, and ® ve of 9 ¯ ocks given Bifuran had
developed resistance to E. necatrix by 8 to 10
weeks of age, but ¯ ocks given nicarbazin (nine
examined) had not developed resistance to this
species of Eimeria. McDougald & Reid (1971)
found that 28 of 30 broiler ¯ ocks given amprolium
plus ethopabate were susceptible at 7 weeks to
challenge with a mixture of six species. Based
upon lesion scores in different regions of the gut,
most ¯ ocks were considered susceptible to E.
tenella, E. necatrix, and E. maxima but resistant to
E. acervulina and E. mivati.
More recently, two broiler farms in northwest
Arkansas were investigated, where one of the most
widely used shuttle programs (nicarbazin followed
by salinomycin) had been employed (Chapman,
1992). Birds from both farms were resistant to a
 Effect of drugs on immunity to Eimeria 527

Figure 1. Birds reared in ¯ oor-pens had been given different synthetic drugs (nicarbazin, halofuginone, or robenidine) in the starter
feed from 0 to 3 weeks of age, followed by lasalocid in the grower ration from 3 to 6 weeks (N/L, H/L, R/L). Three species of Eimeria
were introduced via the feed at 2 weeks. Three days after removal of medicated feed, they were weighed and challenged with high
doses of either E. acervulina, E. maxima, or E. tenella. Seven days later, they were weighed again and the weight gain calculated.
Weight gain was expressed as a percentage of that of unchallenged controls. Results were compared with those of susceptible (SUS)
birds that had been reared in the absence of infection (Chapman & Hacker, 1993). Means for each species with no common superscript
differ signi® cantly (P , 0.05).

challenge with E. acervulina and E. maxima by 6
weeks of age (Figure 3). Birds from one farm were
resistant to E. tenella, but birds from the other farm
were susceptible to this species. Failure to develop
protection is of some concern since E. tenella is
highly pathogenic and widespread in broiler ¯ ocks.
The timing of the development of immunity in
broilers reared under commercial conditions and
given nicarbazin followed by salinomycin and
monensin was investigated (Chapman & Saleh,
1999a). Birds were challenged with three species
and oocyst production compared with that of sus-
ceptible controls (Figure 4). At 3 weeks, oocyst
numbers were similar to that of the controls. A
progressive decrease in oocyst production oc-
curred, and, by 7 weeks, oocyst production was
substantially reduced (E. acervulina, E. tenella) or
prevented (E. maxima). The results indicate that
protection against challenge is acquired gradually
and is not complete until 7 weeks of age. Immunity
developed more rapidly to E. maxima than the
other species.
Withdrawal of medication
An indication of lack of immunity could be an
increase in the number of oocysts in the litter
following withdrawal of medication. Litter from
birds that had been given nicarbazin or halofugi-
none followed by salinomycin and reared in ¯ oor-
pens was examined, and no increase in oocyst
numbers was evident 7 and 14 days after with-
drawal of salinomycin (Chapman et al., 1993).
Forty-six commercial broiler farms were investi-
gated where halofuginone had been used in the
starter feed and lasalocid or salinomycin in the
grower ration (Chapman & Johnson, 1992). A
signi® cant decrease in the number of small oocysts
(possibly E. acervulina or Eimeria mitis) and a
small but signi® cant increase in large oocysts (E.
528 H. D. Chapman

Figure 2. Birds reared in ¯ oor-pens on old litter containing oocysts from a previous ¯ ock were given a synthetic drug (S) or ionophore
(I) in the starter and grower feeds, a synthetic drug in the starter followed by ionophore in the grower (S/I), and vice versa (I/S) or
no medication (N). Medicated feed was removed at 4, 5, 6 and 7 weeks of age. Three days after removal of medicated feed, they were
weighed and challenged with a mixture of three species of Eimeria. Seven days later, they were weighed again and the weight gain
calculated. Weight gain was expressed as a percentage of that of unchallenged controls (Chapman, 1999). Means for each time period
with no common superscript differ signi® cantly (P , 0.05).

maxima) occurred after medication was withdrawn,
but numbers of medium-sized oocysts (probably E.
tenella) remained the same. Ceca were removed
from a few birds from these farms after slaughter,
but no lesions attributable to E. tenella could be
found. Failure to demonstrate lesions, or an in-
crease in oocyst production following drug with-
drawal, does not necessarily indicate that the birds
have developed protective immunity since a chal-
lenge infection may not have been present. No
evidence was found, however, that coccidiosis was
a problem following withdrawal of medication.
There have been few other studies to investigate
the effects of drug withdrawal upon Eimeria infec-
tions in poultry. Long et al. (1975) considered that
broilers remained susceptible to infection after
withdrawal of monensin and found that when this
drug was replaced by zoalene, a slight but
signi® cant increase in oocyst production occurred.
Vaccination in conjunction with chemotherapy
Acquisition of immunity in medicated birds re-
quires that the drug in question permits some
parasite development in the host and that oocysts
be present in the environment in suf® cient numbers
to stimulate an immune response. The latter
dif® culty could be overcome by combining inten-
tional infection with medication. Seeger (1947)
proposed that chicks should be infected (by includ-
ing oocysts of E. tenella in the feed at 15 days of
age) and then 2 days later given a sulphonamide
(sulfaguanidine) in the feed. The sulphonamide
was thought to inhibit development of the second
and later generations of schizont (responsible for
the pathogenic effects of this species of Eimeria)
but not interfere with the acquisition of immunity.
Dickinson et al. (1959) described a `program of
immunization’ , in which 5 to 10-day-old chicks
 Effect of drugs on immunity to Eimeria 529

Figure 3. Birds reared at two commercial broiler farms (A, B) had been given a shuttle program comprising nicarbazin followed by
salinomycin. They were transferred to the laboratory when 6 weeks old, given an unmedicated feed and, 3 days later, weighed and
challenged with high doses of either E. acervulina, E. maxima, or E. tenella. Seven days later, they were weighed again and the weight
gain calculated. Weight gain was expressed as a percentage of that of unchallenged controls. Results were compared with those of
susceptible (SUS) birds that had been reared in the absence of infection (Chapman, 1992). Means for each species with no common
superscript differ signi® cantly (P , 0.05).

were infected with ® ve species of Eimeria and, 24
to 36 h later, sulphaquinoxaline was included in
the feed for 6 days, after which birds were returned
to a nonmedicated ration. Vaccination combined
with chemotherapy has not been pursued as a
practical method for the control of coccidiosis. It
has been proposed that 1-day-old chicks should be
infected with sensitive strains of E. acervulina, E.
maxima and E. tenella in the hatchery (to induce
immunity) and then be given an ionophore
(monensin) in the feed (Bafundo, 1989). Failure of
monensin to prevent parasite development was
explained by suggesting that sporozoites released
from oocysts in the immunizing dose rapidly pen-
etrate intestinal cells before the ionophore is con-
sumed and that they are, therefore, `protected’
from the `cidal’ effect of the drug that is present in
the intestinal lumen. Danforth (1998) also studied
the effects of vaccination with chemotherapy but,
in this case, birds were infected with a drug-resist-
ant strain of E. maxima. He showed, perhaps not
surprisingly, that the development of immunity
was not prevented if medicated birds were immu-
nized with the drug-resistant strain. The results
were said to indicate that a combination of vacci-
nation and anticoccidial treatment could be effec-
tive in extending the life of anticoccidial
compounds.
Anticoccidial drugs have also been used to ame-
liorate the possible pathogenic effects of nonatten-
uated vaccines (e.g. Coccivac Ò ). Thus, inclusion of
amprolium in the drinking water is recommended
(10 days after vaccination) if excessive build-up of
infection due to recycling of parasites is antici-
pated. Toltrazuril is an alternative drug for use if a
severe post-vaccination reaction occurs (Victoria et
al., 1996).
Immunity Development in Egg-laying Birds
Immunity is an important consideration during the
rearing of egg layers and broiler breeders, particu-
larly if birds are in contact with their feces during
the laying period. Since anticoccidials are not used
once birds come into lay, it is desirable that they
530 H. D. Chapman

Figure 4. Birds reared at a commercial broiler farm had been given nicarbazin followed by salinomycin and monensin. They were
transferred to the laboratory when 3, 4, 5, 6, and 7 weeks of age, given an unmedicated feed and, 3 days later, challenged with a
low dose of either E. acervulina, E. maxima, or E. tenella. Oocyst numbers produced after challenge were expressed as a percentage
of that of susceptible controls that had been reared in the absence of infection (Chapman & Saleh, 1999a). Means for each species
with no common superscript differ signi® cantly (P , 0.05).

have developed a high degree of immunity so that
coccidiosis does not occur following drug with-
drawal (Long & Jeffers, 1986).
An anticoccidial may be unnecessary if birds are
reared on wire ¯ oors since exposure to oocysts is
likely to be minimal. High standards of hygiene
and sanitation are necessary, however, because if
contact with droppings does occur, infection is a
possibility. Birds reared on litter, or litter-and-slats,
and then transferred to cages, may be given a drug
in the feed at a concentration normally used for
prevention of coccidiosis in broilers. Immunity
development is still desirable, however, because
coccidiosis may occur after transfer to cages.
Immunity is very important if birds are reared
on litter and then moved to laying houses with
all-litter or litter-and-slat ¯ oors. Various methods
have been employed to permit the natural develop-
ment of immunity. These include: using a drug that
is no longer very effective, using an effective drug
but at a suboptimal concentration, using a drug in
which the concentration is progressively decreased
(`step-down’ programs), using a drug intermit-
tently, or using no drug at all but relying upon
therapeutic treatment of birds if signs of clinical
coccidiosis occur (Reid et al., 1968). Older syn-
thetic drugs such as amprolium, sulphaquinoxaline,
and zoalene have been employed, but ionophores
such as monensin and salinomycin have also been
used. In recent years, it has been realized that
many compounds once considered `too’ effective
for use during the rearing of egg-laying birds do
not completely prevent parasite multiplication and,
therefore, can be used at concentrations previously
considered likely to interfere with immunity.
In the US, amprolium and zoalene are the only
anticoccidial agents where the development of ac-
tive immunity is a speci® c indication for use (in
replacement stock), and various step-down pro-
grams utilizing different concentrations of drug are
approved for this purpose, depending upon the
anticipated severity and timing of exposure to
infection (Anon, 1997). Monensin and salinomycin
have also been used in a step-down fashion to aid

the development of immunity (Pattison, 1993).
Thus, monensin was given to broiler breeders at 60
parts/10 6 from 0 to 8 weeks and at 40 parts/106
from 8 to 16 weeks (Pattison, 1993). There is little
information on the use of drugs other than ampro-
lium for immunity development in replacement
stock. Long et al. (1982) found that layers reared
under commercial conditions and given decreasing
concentrations of a drug mixture comprising am-
prolium, sulphaquinoxaline, and ethopabate were
resistant to reinfection with E. acervulina, E.
brunetti, and E. maxima but not E. mivati, E.
necatrix, or E. tenella by 7 weeks of age. Di-
clazuril was found not to interfere with the devel-
opment of immunity to E. acervulina when
provided to layer pullets at a concentration of 1
parts/10 6 in the feed until 16 weeks of age (Maes
& Hermans, 1992).
Restricted feeding
Feed restriction is often practiced during the rear-
ing of breeder pullets, and this can result in re-
duced drug intake. Use of a high concentration of
drug may, therefore, be desirable in order to
achieve satisfactory control of coccidiosis (Patti-
son, 1993). Amprolium, clopidol, and monensin
were found to interfere with immunity if breeder
pullets were fed ad libitum but not if their feed
intake was restricted (Ruff & Chute, 1980). Appar-
ently, amprolium, if given in the drinking water on
days when feed is restricted, can provide protection
against coccidiosis, yet still allow the development
of immunity (Ruff et al., 1991). Broiler breeders
subjected to a restricted feeding program were
given monensin at a concentration of 45 parts/106
and exposed to a natural infection via the litter
(Long et al., 1979). Challenge with several species
at 14 weeks indicated that the drug had not pre-
vented the development of resistance to reinfec-
tion.
Immunity Development in Turkeys
For economic reasons, it is not practical to provide
an anticoccidial throughout the life of a turkey
(medication is usually given until poults are 8 to 12
weeks of age) and, therefore, immunity is an im-
portant consideration. It has been suggested that
older birds develop an intrinsic resistance to Eime-
ria, but in no case has proof of the absence of
infection, necessary to demonstrate true age resist-
ance, been provided. Turkeys were found to be
susceptible to infection if challenged at 10 weeks
(McDougald & McQuistion, 1978; Long & Mil-
lard, 1979). There have been few studies of the
effects of anticoccidial drugs on immunity devel-
opment in the turkey. Ionophores (monensin, lasa-
locid and maduramicin) did not prevent the
development of resistance (Reid et al., 1978; Wang
& Ingle, 1992; Mathis, 1993; Mathis et al., 1997),
Effect of drugs on immunity to Eimeria 531
and poults given halofuginone also developed re-
sistance against reinfection (Waibel et al., 1987;
Mathis, 1993), although at the maximum approved
concentration (3 parts/106), some interference with
immunity was found (Mathis, 1993).
An indication of a lack of protection could be
the presence of oocysts in the feces after with-
drawal of medication. Oocyst numbers in the litter
increased following the withdrawal of halofugi-
none (Long & Millard, 1979) but not amprolium
(Mathis et al., 1990). A transient increase in the
number of oocysts in the droppings of turkeys was
observed following removal of monensin and
halofuginone from the feed, but the numbers were
few and no clinical coccidiosis was observed
(Chapman et al., 1998; Chapman & Saleh, 1999b).
If coccidiosis does occur following drug with-
drawal, then consideration should be given to ex-
tending the period of medication.
Immunity Development in Gamebirds
Many synthetic drugs and ionophores have been
shown to be effective in gamebirds but, in the US,
only amprolium (for pheasants), lasalocid (for par-
tridges), and monensin and salinomycin (quail) are
approved for use. An anticoccidial is often in-
cluded in the feed of birds reared in captivity (e.g.
pheasants), and medicated feed may still be avail-
able following release from their pens. Birds will
subsequently ingest increasing amounts of natural
food and may be at risk of coccidiosis. Acquisition
of immunity is, therefore, desirable but, unfortu-
nately, few studies have been conducted to investi-
gate the relationship between drugs and immunity
(Norton, 1989). Lerbek and robenidine were con-
sidered unsuitable for use because they gave no
opportunity for immunity development (Norton,
1986). Whether birds actually acquire immunity is
equivocal since, according to Ruff (1986), game
birds do not readily develop solid resistance to
reinfection even when they have received repeated
inoculations of parasites.
Conclusions
An effective anticoccidial may suppress develop-
ment of the Eimeria parasite suf® ciently to prevent
the acquisition of immunity, and, under such cir-
cumstances, it is advisable to include a drug in the
feed for as long as possible to avoid the risk of
coccidiosis late in the life of the bird. Most new
drugs, particularly if they have a novel mode of
action, may fall into this category and, when ® rst
introduced, should not be withdrawn prematurely.
It may be questioned whether there is a role for
new drugs in husbandry situations where immunity
development is desired. Possibly, such compounds
could be used at less than their optimal concentra-
tions, but this is not recommended because the
deliberate use of suboptimal levels may increase
532 H. D. Chapman
the probability of selecting drug-resistant strains
(Chapman, 1982).
In production systems where few parasites are
present, then immunity may not develop regardless
of whether an anticoccidial is employed. This may
occur at farms where clean-out procedures have
been very effective, where a long break period has
been employed between ¯ ocks, or where manage-
ment procedures have resulted in litter conditions
unsuitable for parasite survival. The number of
parasites present at individual farms can be esti-
mated (by counting oocysts in the litter), but it is
not possible to use such information to predict the
likelihood of immunity developing in the ® eld.
Hampering our efforts to develop improved meth-
ods for the control of coccidiosis is inadequate
knowledge of factors that affect the dynamics of
Eimeria infections in poultry ¯ ocks. It has been
suggested that mathematical models may help im-
prove our understanding of the effects of drugs
upon the immunity process (Henken et al., 1994).
As with all simulation models, their ability to
predict real-life scenarios will depend upon the
accuracy of assumptions regarding biological fac-
tors that in¯ uence the life cycle. The extent to
which immunity is acquired to any species will
depend upon the frequency and magnitude of ex-
posure to infective oocysts, and this will be affec-
ted by many factors, such as type of production
system and environmental conditions within the
poultry house. Initial exposure to infective oocysts
may be less in birds reared on new compared with
used litter, and this may affect the rate at which
birds develop resistance to reinfection. There have
been few studies to determine the effects of en-
vironmental and management factors (such as litter
moisture levels, bird stocking density) on immu-
nity development.
In order for birds to acquire protective immu-
nity, several cycles of parasite development are
necessary: a process that requires time. Challenge
experiments indicate that if birds are reared on
litter and exposed to `natural’ infections, immunity
does not develop by 4 weeks, regardless of
whether birds are given an anticoccidial drug.
Solid immunity does not develop until birds are 6
or 7 weeks of age. These observations have impli-
cations for the choice of an appropriate withdrawal
period, during which drugs are removed from the
feed prior to slaughter. Where birds are reared for
7 or more weeks, then a withdrawal period of 7 to
10 days may be appropriate. In the case of birds
marketed at a younger age (6 weeks or less), then
use of a withdrawal period longer than 7 days may
be inadvisable since the birds may not have ac-
quired adequate immunity. It has been suggested
that `sub-optimal’ concentrations of drug are less
likely to interfere with immunity than the maxi-
mum approved use levels, and various drug pro-
grams, involving increasing or decreasing drug
concentrations in different feeds, have been de-
vised for situations where immunity is desired. For
many currently available drugs, even maximum
use levels are unable to prevent parasite develop-
ment and, therefore, use of lower drug concentra-
tions may be unnecessary.
At one time, ionophorous antibiotics were con-
sidered to be too effective for use in situations
where immunity is desirable (such as during the
rearing phase of egg-laying stock). Today, nonin-
terference with immunity development may con-
tribute to the apparent ef® cacy of these drugs. The
belief that synthetic drugs interfere with immunity
development may also be incorrect. In studies with
various synthetic drugs (nicarbazin, halofuginone
and robenidine), immunity was not prevented
when these drugs were included in the starter feed
followed by an ionophore in the grower. In one
experiment, however, immunity was not complete
when a synthetic drug was included in the grower
ration.
Further studies are necessary to establish the
conditions under which birds develop resistance to
challenge when given various drug programs and
the role that immunity plays in the apparent
ef® cacy of anticoccidial drugs.
References
Allen, R.W. & Farr, M.M. (1942). In¯ uence of sulfaguanidine on
acquired resistance in chickens to cecal coccidiosis. Poultry Sci-
ence, 21, 464±465.
Allen, R.W. & Farr, M.M. (1943). Sulfaguanidine as a prophylacti c
during the period of acquirement of resistance by chickens to cecal
coccidiosis. American Journal of Veterinary Research, 4, 50±53.
Anon (1953). Coccidiosis. Annotated Bibliography. Rahway, NJ:
Merck & Co., Inc.
Anon (1997). Feed Additive Compendium. Minnetonka, MN: The
Miller Publishing Company.
Anon (1999). Live Production Analysis. Fort Wayne, IN: AGRI Stats,
Inc.
Bafundo, K.W. (1989). Protective responses produced by immuniza-
tion of day-old chicks with either Eimeria maxima, E. acervulina or
E. tenella live oocyst vaccines. In P. Yvore (Ed.), Coccidia and
Intestinal Coccidiomorph s, Proceedings of the Vth International
Coccidiosis Conference , Tours, France (pp. 395±400). Paris: INRA
Publications.
Bafundo, K.W. (1994) . Trends in coccidiosis control: present consid-
erations and future concerns. Proceeding s of the 43rd Western
Poultry Disease Conference (pp. 49±52). Sacramento, CA.
Berg, L.R., Hamilton, C.M. & Bearse, G.E. (1956). Nitrofurazone and
nicarbazi n as growth stimulants and coccidiostatic agents for young
chicks. Poultry Science, 35, 1394±1396.
Brackett, S. & Bliznick, A. (1949). The effect of small doses of drugs
on oocyst production of infections with Eimeria tenella. Annals of
the New York Academy of Sciences, 52, 595±610.
Callender, M.E. & Shumard, R.F. (1973) . Effects of monensin on
developmen t of immunity to coccidia. Poultry Science, 52, 2007.
Chapman, H.D. (1978). The effect of monensin on the immunity
arising from repeated low-level infections with Eimeria maxima, E.
brunetti and E. tenella. Avian Pathology, 7, 269±277.
Chapman, H.D. (1982). Anticoccidial drug resistance. In P.L. Long
(Ed.), The Biology of the Coccidia (pp. 429±452). Baltimore, MD:
University Park Press.
Chapman, H.D. (1987). Control of a line of E. tenella partly resistant

to monensin by including toltrazuril discontinuousl y in the drinking
water of chickens . Journal of Comparative Pathology, 97, 21±27.
Chapman, H.D. (1992). Research note: immunity to Eimeria in broilers
reared on nicarbazi n and salinomycin . Poultry Science, 71, 577±580.
Chapman, H.D. (1996). Effects of different types of anticoccidial drug
programs upon the development of immunity to Eimeria species in
the fowl. Proceeding s of the 45th Western Poultry Disease Confer-
ence (pp. 115±117). Cancun, Mexico.
Chapman, H.D. (1997a). Biochemical, genetic and applied aspects of
drug resistance in Eimeria parasites of the fowl. Avian Pathology,
26, 221±244.
Chapman, H.D. (1997b). Immunity development in broilers given
anticoccidial drugs and reared on new or used litter. In M.W.
Shirley, F.M. Tomley & B.M. Freeman (Eds.), Control Of Coccid-
iosis Into The Next Millennium, Proceedings of the VIIth Inter-
national Coccidiosi s Conference (p. 42). Newbury: Institute for
Animal Health.
Chapman, H.D. (1999). The developmen t of immunity to Eimeria
species in broilers given anticoccidial drugs. Avian Pathology, 28,
155±162.
Chapman, H.D. & Hacker, A.B. (1993). The effects of shuttle pro-
grams upon the growth of broilers and the developmen t of immu-
nity to Eimeria species. Poultry Science, 72, 658±663.
Chapman, H.D. & Johnson , Z.B. (1992). Oocysts of Eimeria in the
litter of broilers reared to eight weeks of age before and after
withdrawal of lasalocid or salinomycin . Poultry Science, 71, 1342±
1347.
Chapman, H.D. & Saleh, E. (1999a). Developmen t of immunity to
Eimeria species in broilers reared under commercial conditions.
Proceeding s of the 1999 Australian Poultry Science Symposium 11,
132±134. University of Sydney, Sydney, NSW, Australia.
Chapman, H.D. & Saleh, E. (1999b). Effects of different concentra-
tions of monensin and monensin withdrawal upon the control of
coccidiosis in the turkey. Poultry Science, 78, 50±56.
Chapman, H.D., Hanssens, Q.J. & Kling, H.F. (1993) . Effects of
different withdrawal periods of anticoccidial medication upon broil-
ers. Poultry Science, 72, 19.
Chapman, H.D., Sandstrom, J. & Breeding, S.W. (1998). Effect of the
anticoccidial agents halofuginon e and monensin when given with
growth promoting antibiotics upon the control of coccidiosis in the
turkey. Avian Pathology, 27, 498±504.
Cuckler, A.C. & Malanga, C.M. (1956). The effect of nicarbazi n on
the development of immunity to avian coccidia. Journal of Para-
sitology, 42, 593±605.
Cuckler, A.C., Ott, W.H. & Fogg, D.E. (1957). Factors in the
evaluation of coccidiostats in poultry. The Cornell Veterinarian,
XLVII, 400±412.
Danforth, H.D. (1998). Use of live oocyst vaccines for the control of
avian coccidiosis; experimenta l studies and ® eld trials. International
Journal for Parasitology, 28, 1099±1109.
Davies, S.F.M. (1958) . Value of interrupted treatments and preventive
medication in the control of intestinal coccidiosi s caused by E.
necatrix. Journal of Comparative Pathology & Therapeutics, 68,
363±373.
Davies, S.F.M., & Kendall, S.B. (1954). The effect of sodium sul-
phaquinoxalin e and sodium sulphamezathin e in interrupted sched-
ules of treatment on the development of E. tenella. Journal of
Comparative Pathology & Therapeutics, 64, 87±93.
Delaplane, J.P., Batchelder , R.M. & Higgins, T.C. (1947). Sul-
faquinoxaline in the prevention of Eimeria tenella infection in
chickens. The North American Veterinarian, 28, 19±24.
Dickinson, E.M. (1949). The effect of sulfaquinoxalin e on Eimeria
acervulina infection in pullets in egg production. Poultry Science,
28, 670±674.
Dickinson, E.M., Babcock, W.E. & Kilian J.G. (1959). A program of
immunization against avian coccidia. Proceeding s of the US Live-
stock Sanitary Association 63, 223±225.
Edgar, S.A. (1958). Control of coccidiosis of chickens and turkeys by
immunization. Poultry Science, 37, 1200.
Edgar, S.A. & Flanagan, C. (1968). Coccidiostati c effects of buquino-
late in poultry. Poultry Science, 47, 95±104.
Gardiner, J.L. & Farr, M.M. (1954). Nitrofurazone for the prevention
of experimentally induced Eimeria tenella infections in chickens.
Journal of Parasitology, 40, 42±49.
Effect of drugs on immunity to Eimeria 533
Goff, O.E. (1947) . Concept s of coccidiosi s control. Poultry Science,
26, 541.
Greif, G. & Haberkorn , A. (1997) . Enhancemen t of immunity
and protection against coccidiosis during therapeutic medication
with toltrazuril. In M.W. Shirley & F.M. Tomley (Eds.), Control
of Coccidiosi s into the Next Millennium, Proceedings of the
VIIth International Coccidiosis Conference (pp. 42±43). Newbury:
Institute for Animal Health.
Grumbles, L.C. & Delaplane, J.P. (1947). Sulfaquinoxaline in the
prevention of Eimeria necatrix infection in chickens. Proceedings
of the US Livestock Sanitary Association, 51, 285±289.
Grumbles, L.C., Delaplane, J.P. & Higgins, T.C. (1948). Sulfaquinox-
aline in the control of Eimeria tenella and Eimeria necatrix in
chickens on a commercial broiler farm. Science, 107, 196.
Haberkorn, A. (1984). Bay Vi 9142, a new coccidiocida l drug and a
new concept for prevention of coccidiosis. Proceeding s of the XVII
World’ s Poultry Congress (p. 772). Helsinki, Finland.
Henken, A.M., Ploeger, H.W., Graat, E.A.M. & Carpenter, T.E.
(1994). Description of a simulation model for the population dy-
namics of Eimeria acervulina infection in broilers. Parasitology,
108, 503±512.
Horton-Smith, C. & Long, P.L. (1952). Nitrofurazone in the treatment
of caecal coccidiosis in chickens . The Veterinary Journal, 108,
47±57.
Jeffers, T.K. (1989) . Anticoccidial drug resistance: a review with
emphasis on the polyether ionophores. In P. Yvore (Ed.), Coccidia
and Intestinal Coccidiomorph s, Proceedings of the Vth Inter-
national Coccidiosi s Conference , Tours, France (pp. 295±308).
Paris: INRA Publications.
Johnson , C.A., Kennedy , T.J. & Moeller, M.W. (1986). Immunization
of chickens against coccidiosis by termination of infections with
BAY VI 9142. In L.R. McDougald, L.P. Joyner & P.L. Long
(Eds.), Research in Avian Coccidiosis, Proceedings of the Georgia
Coccidiosis Conference (pp. 253±262). Athens, GA: University of
Georgia Press.
Joyner, L.P., Davies, S.F.M. & Kendall, S.B. (1963). Chemotherapy
of coccidiosis. In R. J. Schnitzer & F. Hawking, (Eds.) Experimen-
tal Chemotherapy, Vol. 1 (pp. 445±486). London: Academic Press.
Karlsson, T. & Reid, W.M. (1978). Developmen t of immunity to
coccidiosis in chickens administered anticoccidials in feed. Avian
Diseases, 22, 487±495.
Kemler, A.G. & Reid, W.M. (1961) . Incidence of the coccidial species
Eimeria necatrix, among Georgia broilers as determined by chal-
lenge techniques. Poultry Science, 40, 60±63.
Kendall, S.B. & McCullough, F.S. (1952). Relationships between
sulphamezathin e therapy and the acquisition of immunity to E.
tenella. Journal of Comparative Pathology, 62, 116±124.
Koutz, F.R. (1948) . Immunity studies in avian cecal coccidiosi s I. The
value of drugs to establish immunity to young chickens. American
Journal of Veterinary Research, 9, 388±395.
Levine, P.P. (1941). Chemotherapy in the control of avian coccidiosis.
Proceeding s of the US Livestock Sanitary Association, 45, 118±120.
Lillehoj, H.S. & Trout, J.M. (1993). Coccidia: a review of recent
advances on immunity and vaccine development . Avian Pathology,
22, 3±31.
Long, P.L. & Jeffers, T.K. (1986). Anticoccidial medication programs
vary for broilers, cage layers and breeders. Feedstuffs, 17 February
1986.
Long, P.L. & Millard, B.J. (1968). Eimeria: effect of meticlorpindol
and methyl benzoquat e on endogenou s stages in the chicken.
Experimental Parasitology, 23, 331±338.
Long, P.L. & Millard, B.J. (1979). Coccidiosis in turkeys: some recent
work in Britain. Turkeys, May/June, 19±21.
Long, P.L., Tompkins, R.V. & Millard, B.J. (1975) . Coccidiosis in
broilers: evaluation of infection by the examination of broiler house
litter for oocysts. Avian Pathology, 4, 287±294.
Long, P.L., Millard, B.J. & Smith, K.M. (1979). The effect of some
anticoccidial drugs on the development of immunity to coccidiosi s
in ® eld and laboratory conditions. Avian Pathology, 8, 453±467.
Long, P.L., Millard, B.J., Batty, A.F. & Davison, C. (1982). Immunis-
ation against coccidiosis in chickens : tests under simulated ® eld
conditions. Avian Pathology, 11, 131±144.
Maes, L. & Hermans, L. (1992). Effects of diclazuril (ClinacoxÒ ) on
the developmen t of protective immunity in pullets. Proceeding s of
534 H. D. Chapman
the 19th World’ s Poultry Congress (pp. 107±111). Amsterdam, The
Netherlands.
Maes, L., Vanparijs, O. & Marsboom, R. (1991). Effect of diclazuril
(ClinacoxÒ ) on the development of protective immunity against
Eimeria tenella: laboratory trial in broiler chickens. Poultry Sci-
ence, 70, 504±508.
Mathis, G.F. (1993). Toxicity and acquisition of immunity to coccidia
in turkeys medicated with anticoccidials. Journal of Applied Poultry
Research, 2, 239±244.
Mathis, G.F., Fuller, A.L. & McDougald, L.R. (1990). Turkey cocci-
diosis: effect of control programs on oocyst shedding patterns and
sensitivity to anticoccidial drugs. Poultry Science, 69, 89.
Mathis, G.F., Castiglia, A. & Cheng, T. (1997) . A comparison of the
turkey anticoccidials: lasalocid, monensin, maduramicin and
halofuginone , using the parameter s of ef® cacy and developmen t of
acquired coccidial immunity. In M.W. Shirley, F.M. Tomley &
B.M. Freeman (Eds.), Control of Coccidiosis into the Next Millen-
nium, Proceedings of the VIIth International Coccidiosis Confer-
ence (p. 44). Oxford, UK.
McDougald, L.R. & McQuistion, T.E. (1978). Innate and acquired
immunity vs. anticoccidial medication in managing coccidiosi s in
turkeys. Avian Diseases, 22, 765±770.
McDougald, L.R. & Reid, W.M. (1971). Susceptibility of broilers to
coccidiosis following early coccidiostat withdrawal. Poultry Sci-
ence, 50, 1164±1170.
McLoughlin, D.K. & Gardiner, J.L. (1962) . The activity of amprolium
in Eimeria tenella infectionsÐ laboratory trials. Avian Diseases, 6,
185±190.
Norton, C.C. (1986) . Coccidiosis in gamebirds: a review. In L.R.
McDougald, L.P. Joyner & P.L. Long (Eds.), Research in Avian
Coccidiosis, Proceedings of the Georgia Coccidiosis Conference
(pp. 85±106). Athens, GA.
Norton, C.C. (1989). Coccidiosis in gamebirds: a review. In P. Yvore
(Ed.), Coccidia and Intestinal Coccidiomorph s, Proceedings of the
Vth International Coccidiosi s Conference, Tours, France (pp. 351±
359). Paris: INRA Publications.
Pattison, M. (1993) . Disease prevention and control in broiler breeder s
and layers In: M. Pattison (Ed.), The Health of Poultry (pp. 176±
204). Harlow, UK: Longman Scienti® c & Technical , Longman
Group UK Ltd.
Peterson, E.H. (1949). Sulfonamides in the control of experi-
mental coccidiosis in the turkey. Veterinary Medicine, 44, 126±
128.
Philps, B.R. (1997). The art and science of productive coccidiosi s
control in broilers. In M.W. Shirley, F.M. Tomley & B.M. Freeman
(Eds.), Control of Coccidiosi s into the Next Millennium, Proceed-
ings of the VIIth International Coccidiosis Conference (pp. 42).
Newbury: Institute for Animal Health.
Reid, W.M., (1960). The relationship between coccidiostat s and poul-
try ¯ ock immunity in coccidiosis control programs. Poultry
Science, 39, 1431±1437.
Reid, W.M., Womack, H.E. & Johnson , J. (1968). Coccidiosi s suscep-
tibility in layer ¯ ock replacemen t programs. Poultry Science, 47,
892±899.
Reid, W.M., Kowalski, L. & Rice, J. (1972). Anticoccidial activity
of monensin in ¯ oor-pen experiments. Poultry Science, 51, 139±
146.
Reid, W.M., Dick, J., Rice, J. & Stino, F. (1977). Effects of monensin-
feeding regimens on ¯ ock immunity to coccidiosis. Poultry Science,
56, 66±71.
Reid, W.M., Anderson, W.I. & McDougald, L.R. (1978). Anticocci-
dial protection and developmen t of immunity to turkey coccidiosi s
while using monensin. Avian Pathology, 7, 569±576.
Rose, M.E. (1987). Eimeria, Isospora, and Cryptosporidium. In E.J.L.
Soulsby (Ed), Immunology, Immunopatholog y and Immunoprophy -
laxis of Parasitic Infections, Vol. 3 (pp. 275±312). Boca Raton, FL:
CRC Press Inc.
Rose, M.E. (1996). Immunity to coccidia. In T.F. Davison, T.R.
Morris & L.N. Payne (Eds.), Poultry Immunology, Poultry Science
Symposium Series, Vol. 24 (pp. 265±299). Abingdon: Carfax Pub-
lishing Company.
Ruff, M.D. (1986). Coccidiosis in gallinaceou s game birds and its
control. In L.R. McDougald, L.P. Joyner & P.L. Long (Eds.),
Research in Avian Coccidiosis, Proceedings of the Georgia Coccid-
iosis Conference (pp. 107±123). Athens, GA.
Ruff, M.D. & Chute, M.B. (1980). Relationship of restricted feeding
and medication to coccidiosis control. Poultry Science, 59, 697±
701.
Ruff, M.D., Reid, W.M., Rahn, A.P. & McDougald, L.R. (1980).
Anticoccidial activity of narasin in broiler chickens reared in ¯ oor
pens. Poultry Science, 59, 2008±2013.
Ruff, M.D., Chute, M.B. & Garcia, R. (1991). Supplemental use of
liquid amprolium in skip-a-day feeding of replacemen t pullets.
Poultry Science, 70, 515±520.
Ryley, J.F. (1967). Methyl benzoquate , a new wide-spectrum coccid-
iostat for chickens. The British Veterinary Journal, 123, 513±520.
Ryley, J.F. & Betts, M.J. (1973). Chemotherap y of chicken coccidio-
sis. Advances in Pharmacolog y & Chemotherapy, 11, 221±293.
Ryley, J.F. & Wilson, R.G. (1975). Laboratory studies with some
recent anticoccidials. Parasitology, 70, 203±222.
Seeger, K.C. (1947) . Flock Eimeria tenella inoculation followed
by sulfaquinoxalin e or sulfamethazin e treatment as a method
of controlling caecal coccidiosis. Poultry Science, 26, 554±
555.
Seeger, K.C. & Tomhave, A.E. (1946). Effect of sulfaguanidin e on
caecal coccidiosis. Delaware Agricultural Experiment Station Bull-
etin No. 260, 1±19.
Shirley, M.W. & Bedrnik, P. (1997). Live attenuated vaccines against
avian coccidiosis. Parasitology Today, 13, 481±484.
Shirley, M.W. & Long, P.L. (1990) . Control of coccidiosis in chick-
ens: immunization with live vaccines. In P.L. Long (Ed.), Coccidio-
sis of Man and Animals (pp. 321±341). Boca Raton, FL: CRC Press
Inc.
Strout, R.C., Dunlop, W.R. & Skoglund, W.C. (1958). Field studies
on coccidiosis immunity. 1. The use of nicarbazi n for replacemen t
¯ ocks. Poultry Science, 37, 1245.
Suls, L. (1998) . Effects of diclazuril on the developmen t of protective
immunity. World Poultry, 14, 53±54.
Swales, W.E. (1946). The chemotherapy of cecal coccidiosi s (Eimeria
tenella) of chickens . IV. Experiment s on the use of chemotherapy
during the immunizing exposure of chicks. Journal of the American
Veterinary Medical Association, 108, 393±400.
Swales, W.E. (1947) . New methods of controlling caecal coccidiosi s
in chicks. Canadian Journal of Comparative Medicine, 11, 5±10.
Victoria, G., Pavon, E., Rebollo, M., Torres, de C.A. & Vazquez, R.
(1996). A comparison of toltrazuril vs. amprolium as coccidial
post-vaccinatio n treatments and their effects on immunity in broil-
ers. Proceedings of the 45th Western Poultry Disease Conference
(pp. 112±115). Cancun, Mexico.
Waibel, P.E., Enueme, J.E., Halvorson, J.C. & Grant, R.J. (1987).
Ef® cacy of halofuginon e as a coccidiostat for turkeys. Poultry
Science, 66, 1629±1634.
Waletzky, E. (1970). Laboratory anticoccidial evaluation trials: review
of designs, variables, criteria, and predictive value for ® eld use.
Experimental Parasitology, 28, 42±62.
Waletzky, E. & Hughes, C.O. (1949). Factors involved in tests
for acquired immunity in Eimeria tenella infections of the
chicken. Annals of the New York Academy of Sciences, 52, 478±
495.
Waletzky, E., Hughes, C.O. & Brandt, M.C. (1949). The anticoccidial
activity of nitrophenide . Annals of the New York Academy of
Sciences, 52, 543±557.
Wang, G.T. & Ingle, D.L. (1992) . Developmen t of immunity to
coccidia in maduramicin- or amprolium-medicate d turkeys. Pro-
ceedings of the World’ s Poultry Congress, Vol. 3 (pp. 563±566).
Amsterdam, The Netherlands.
Watkins, K.L. (1997) . Managing coccidiosi s for long-term stability. In
Managing CoccidiosisÐ Maximizing Your Returns (pp. 13±16). In-
dianapolis, IN: Elanco Animal Health.
Weber, G.M. (1989) . Immunization of chicks by trickle infection with
Eimeria tenella under medication with lasalocid. In P. Yvore (Ed.),
Coccidia and Intestinal Coccidiomorph s, Proceedings of the Vth
International Coccidiosis Conference, Tours, France (pp. 693±696).
Paris: INRA Publications.

REÂ
SUMEÂ
Les anticoccidiens et leurs effets sur le deÂveloppement de
l’immuniteÂvis-aÁ-vis des infections aÁ Eimeria chez les volailles
L’ ideÂe selon laquelle les anticoccidiens , aÁ des degre s diffeÂrents,
interfeÁrent sur le de veloppemen t de l’ immuniteÂdes espeÁces d’ Eimeria,
ne peut plus eà tre conside reÂ
e comme juste parce que quelques produits,
si tant est qu’ il y en ait, sont capables d’ agir aÁ un certain degreÂsur la
multiplication du parasite. L’ acquisition d’ une immuniteÂest par con-
se quent une re elle possibiliteÂ, pourvu que suf® samment de parasites
soient pre sents dans l’ environnement . L’ immuniteÂdoit eà tre prise en
conside ration de facËon importante durant la pe riode d’ eÂlevage des
futures pondeuses, des reproducteur s de type chair des dindes et du
gibier, mais peu de recherches ont e teÂentreprises sur l’ effet des
produits vis-aÁ-vis du de veloppement de l’ immuniteÂchez ces volailles.
Ces dernieÁres anne es, il y a eu un changemen t dans la perception de
la signi® cation de l’ immuniteÂchez les poulets de chair et quelques
producteur s ont pris ceci en conside ration en e tablissant les pro-
grammes anticoccidiens. Les e tudes conduites sur le terrain, dans des
parquets au sol, montrent que les poulets qui ont recËu diffe rents
programmes anticoccidiens peuvent de velopper une immuniteÂquand
ils sont soumis aÁ des infections naturelles mais que ce me canisme
prend du temps et qu’ une bonne immuniteÂne se de veloppe pas avant
l’ aÃ
ge de 6 aÁ 7 semaines. Ceci suggeÁre que les produits ne doivent pas
eÃtre retireÂ
s preÂmature ment, pas avant que les oiseaux aient pu de vel-
opper une immuniteÂade quate.
ZUSAMMENFASSUNG
Antikokzidia und ihre Effekte auf die ImmunitaÈtsbildung gegen
Eimeria-Infektionen beim Ge¯ uÈgel
Die lange vertretene Ansicht, dass Medikamente gegen Kokzidien in
einem mehr oder weniger starken Grad mit der ImmunitaÈtsbildung
gegen Eimeria-Arten interferieren, ist moÈglicherweise nicht mehr
korrekt, weil wenige oder uÈberhaupt keine Medikamente in der Lage
sind, die Parasitenvermehrun g restlos zu verhindern . Das Erwerben
von ImmunitaÈt ist deshal b eine reale MoÈglichkeit, sofern genug
Parasiten in der Umgebung vorhande n sind. Die ImmunitaÈt ist bei der
Aufzucht von neuen Legehennen , Mast-Elterntieren, Puten und Feder-
wild ein wichtiger Gesichtspunkt , aber uÈber die Auswirkungen von
Effect of drugs on immunity to Eimeria 535
Medikamenten auf die ImmunitaÈtsbildung in diesen Nutztierkate-
gorien ist wenig geforscht worden. In den letzten Jahren hat es einen
Wandel in der EinschaÈtzung der Bedeutung der ImmunitaÈt bei Broil-
ern gegeben , und einige Broilerproduzenten haben dies beim Planen
der Arzneimittelprogramm e fuÈr ihre BestaÈ nde beruÈcksichtigt . Studien
in Stallabteilen mit Bodenhaltun g und im Feld zeigen, dass Broiler
unter verschiedene n Arzneimittelprogramme n eine ImmunitaÈt en-
twickeln koÈ nnen, wenn sie natuÈrlichen Infektionen ausgesetz t werden,
aber dieser Prozess braucht seine Zeit, und eine solide ImmunitaÈt
entwickel t sich nicht bevor die Tiere 6 bis 7 Wochen alt sind. Das
laÈsst darauf schlieû en, dass die Medikamente nicht vorzeitig aus dem
Futter weggelassen werden sollten, da die Tiere vielleicht noch keine
Zeit hatten, eine adaÈquate ImmunitaÈt zu entwickeln.
RESUMEN
Coccidiostaticos y sus effectos en el desarrollo de la inmunidad
frente a Eimeria en avicultura
La creencia de que los coccidiost a ticos inter® eren, con una mayor o
menor intensidad, en el desarrollo de la inmunidad frente a los
paraÂsitos del geÂnero Eimeria tendraÂque ser modi® cada, dado que
pocos compuesto s son capaces de preveni r totalmente la multiplica-
cioÂn de los paraÂ
sitos. La adquisici oÂ
n de inmunidad es por lo tanto una
posibilidad real con tal de que exista un nu mero su® ciente de paraÂsitos
en el medio. La inmunidad es un factor importante en la crõ Â a de
ponedoras, reproductores de broilers, pavos y aves de caza, aunque se
han realizado pocos estudios sobre los efectos de diferentes com-
puestos farmacolo gicos en estos tipos de animales. En los u ltimos
anÄos se ha producido un cambio en la valoracio n de la importancia de
la inmunidad en broilers y algunos productores la han tenido en cuenta
a la hora de disenÄ ar los programas de medicacio n en animales de
campo. Los estudios en explotaciones de animales criados en el suelo
y en el campo, indican que broilers sometidos a varios programas de
medicacio n son capaces de desarrollar inmunidad cuando se enfrentan
a infecciones naturales aunque este proceso lleva un tiempoÐ la
inmunidad adecuada no se establece hasta que los animales tienen de
6 a 7 semanas de vida. Este hecho sugiere que la medicaci o n no debe
ser retirada del pienso prematuramente, dado que los animales pueden
no haber tenido tiempo de desarrollar una inmunidad adecuada .