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Coccidiosis in poultry: anticoccidial products,

vaccines and other prevention strategies

H.W. Peek & W.J.M. Landman

To cite this article: H.W. Peek & W.J.M. Landman (2011) Coccidiosis in poultry: anticoccidial
products, vaccines and other prevention strategies, Veterinary Quarterly, 31:3, 143-161, DOI:
10.1080/01652176.2011.605247

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Veterinary Quarterly
Vol. 31, No. 3, September 2011, 143–161

REVIEW ARTICLE
Coccidiosis in poultry: anticoccidial products, vaccines and other prevention strategies
H.W. Peeka* and W.J.M. Landmanab
a
Animal Health Service – GD, Deventer, The Netherlands; bDepartment of Farm Animal Health,
Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
(Received 27 June 2011; final version received 4 July 2011)

Coccidiosis in chickens is a parasitic disease with great economic significance, which has been controlled
successfully for decades using mainly anticoccidial products. However, large-scale and long-term use of
anticoccidial drugs has led to the worldwide development of resistance against all these drugs. In order to
minimize the occurrence of resistance, the rotation of various anticoccidial drugs in single and/or shuttle
programmes is used. Unfortunately, this has not solved the anticoccidial resistance problem. Recently, live
anticoccidial vaccines have been incorporated into rotation programmes, resulting in an increasing incidence of
anticoccidial drug-sensitive Eimeria spp. field isolates, which may ameliorate the efficacy of anticoccidial drugs.
Nevertheless, possible upcoming bans restricting the use of anticoccidials as feed additives, consumer concerns on
residues and increasing regulations have prompted the quest for alternative coccidiosis control strategies.
Although management and biosecurity measures could halt the introduction of Eimeria spp. to a farm, in practice
they do not suffice to prevent coccidiosis outbreaks. Phytotherapy, aromatherapy and pre- and probiotics either
show conflicting, non-consistent or non-convincing results, and have therefore not been applied at a large scale in
the field. So far, live attenuated and non-attenuated anticoccidial vaccines have proved to be the most solid and
successful coccidiosis prevention and control strategy. Despite the drawbacks associated with their production
and use, their popularity is increasing. If with time, the immunogenicity of subunit vaccines can be improved,
they could represent the next generation of highly efficient and low-cost anticoccidial strategies.
Keywords: poultry; chickens; coccidiosis; Eimeria; Isospora; anticoccidial drugs; anticoccidial sensitivity test;
vaccines

1. Introduction Administration (Chapman 1997; McDougald 2003;

Coccidiosis is a disease caused by parasites of the genus
Eimeria and Isospora belonging to the phylum
Apicomplexa with a complex life cycle, affecting
mainly the intestinal tract of many species of mammals
and birds. It is of great economic significance in farm
animals, especially chickens. Most knowledge on
coccidiosis has been obtained from chickens, where
the disease has been studied most intensively as it is in
commercial poultry that this parasite causes the most
damage due to the fact that birds are reared together in
large numbers and high densities. The economic
significance of coccidiosis is attributed to decreased
animal production (higher feed conversion, growth
depression and increased mortality) and the costs
involved in treatment and prevention. Worldwide, the
annual costs inflicted by coccidiosis to commercial
poultry have been estimated at 2 billion E, stressing the
urgent need for more efficient strategies to control this
parasite.
2. Anticoccidial products
Numerous anticoccidial drugs have been introduced
since 1948, when sulphaquinoxaline and nitrofurazone
were first approved by the American Food and Drug
Conway and McKenzie 2007). Most of the antic-
occidial products currently approved in different
regions of the world for the prevention of coccidiosis
in chickens are listed in Table 1. Moreover, national
regulatory limitations may apply to some products.
A number of anticoccidials have been withdrawn
overtime because of safety or efficacy issues; neverthe-
less, many of these drugs are still available and used.
2.1. Categories
The anticoccidial products can be classified in three
categories according to their origin (Chapman 1999a,
1999b; Allen and Fetterer 2002).
(1) Synthetic compounds. These compounds are
produced by chemical synthesis and often
referred to as ‘chemicals’. Synthetic drugs
have a specific mode of action against the
parasite metabolism. For example, amprolium
competes for the absorption of thiamine (vita-
min B1) by the parasite.
(2) Polyether antibiotics or ionophores. These prod-
ucts are produced by the fermentation of
Streptomyces spp. or Actinomadura spp. and
destroy coccidia by interfering with the balance

*Corresponding author. Email: h.peek@gddeventer.com

ISSN 0165–2176 print/ISSN 1875–5941 online

ß 2011 Taylor & Francis
DOI: 10.1080/01652176.2011.605247
http://www.informaworld.com
144 H.W. Peek and W.J.M. Landman

Table 1. Contemporary anticoccidial products and recom- Ethopabate, which is often used in combination
mended doses for prophylactic treatment of coccidiosis in with amprolium to improve the spectrum of efficacy, is
chickens (modified from Conway and McKenzie 2007).
a folate antagonist and blocks a step in the synthesis of
Poultry Concentration para-aminobenzoic acid (PABA) and prevents the
Chemical name category in feed (ppm) formation of nucleic acids of vitamins (Rogers et al.
1964). It is most active against Eimeria maxima and
Chemicals Eimeria brunetti.
Amprolium Broiler, rearing 125–250
Similar to ethopabate, sulphonamides prevent the
Amprolium þ Broiler, rearing 125–250 þ 4
ethopabate synthesis of dihydrofolate by interfering with the
Aprinocid Broiler 60 dihydropteroate synthetase reaction, blocking the con-
Clopidol Broiler, rearing 125 jugation of pteridine and PABA. Dihydropteroate
Decoquinate Broiler 30 synthetase is only present in the parasite. They are
Diclazuril Broiler, rearing 1
very effective against E. brunetti, E. maxima and
Dinitolmide (zoalene) Broiler, rearing 125
Halofuginone Broiler, rearing 3 Eimeria acervulina and to a much lower degree against
Nequinate Broiler, rearing 20 Eimeria tenella and Eimeria necatrix (Ryley and Betts
(methyl benzoquate) 1973). A major drawback of sulphonamides is their
Nicarbazin Broiler 125 small safety margin, which easily leads to intoxications
Robenidine Broiler 33
especially if they are used as treatment for coccidiosis
Polyether ionophores outbreaks.
Lasalocid Broiler 75–125 A third product affecting the folate pathway of
Maduramicin Broiler 5–6
Monensin Broiler, rearing 100–120
coccidia is pyrimethamine. It prevents the reduction of
Narasin Broiler 60–80 dihydrofolate to tetrahydrofolate by inhibiting the
Narasin þ nicarbazin Broiler 54–90 enzyme dihydrofolate reductase. Pyrimethamine has a
(of both drugs) clear synergistic effect with sulphonamides (Kendall
Salinomycin Broiler, rearing 44–66 and Joyner 1956). Ethopabate, sulphonamides and
Semduramycin Broiler 25
pyrimethamine affect the second generation of schiz-
Notes: Products listed are known to be used more or less onts (Reid 1973, 1975).
frequently in Europe, Latin America, Asia/Pacific region Thiamine analogues, like amprolium, block the
and/or North America. absorption of thiamine completely and have probably
an antagonistic effect on the vitamin B1 supply.
of important ions like sodium and potassium. Amprolium seems especially efficacious during
The following groups of ionophores exist: schizogony as then the demand of thiamine is at its
highest (James 1980). There is a difference in sensitivity
. Monovalent ionophores (monensin,
of the thiamine transport system of host and parasite
narasin and salinomycin).
(more sensitive) to amprolium. It affects the first
. Monovalent glycosidic ionophores
generation of schizonts and to a lesser extent the
(maduramicin and semduramycin).
gametogony (Reid 1973) allowing immune response to
. Divalent ionophores (lasalocid).
develop.
(3) Mixed products. A few drug mixtures, consist-
ing of either a synthetic compound and 2.2.2. Products affecting mitochondrial function
ionophore (nicarbazin/narasin (MaxibanÕ )) or
Quinolone drugs, amongst which buquinolate, deco-
two synthetic compounds (meticlorpindol/
quinate and nequinate (methyl benzoquate) are listed,
methylbenzoquate (LerbekÕ )), are also used
show anticoccidial activity at very low concentrations.
against coccidiosis.
These products inhibit the respiration of coccidia by
blocking the electron transport in their mitochondria
(Wang 1975). Quinolones arrest the development of
2.2. Mode of action sporozoites (Yvoré 1968; Reid 1973).
Although detailed knowledge on the selective action of Meticlorpindol is the most important compound of
anticoccidial compounds against specific stages of the the pyridone group. Similar to the quinolones, it
parasite is often lacking (Wang 1982), a broad inhibits electron transport in mitochondria, but
categorization of the mode of action of anticoccidials possibly at another level as cross-resistance with
on the parasite metabolism has been undertaken quinolones does not occur. A synergistic effect between
(Chapman 1997). meticlorpindol and 4-hydroxiquinolones has been
described (Challey and Jeffers 1973). A widely used
pyridone–quinolone combination drug is LerbekÕ ,
2.2.1. Products affecting cofactor synthesis consisting of meticlorpindol and methyl benzoquate.
Several anticoccidial products influence essential The true mode of action of nicarbazin (4,40 -
biochemical pathways of the parasitic cell by affecting dinitrocarbanilide) is unknown. The product has been
an important cofactor (Greif et al. 2001). shown to inhibit both the succinate-linked NAD
 Veterinary Quarterly
reduction in mitochondria of beef hearts and the
energy dependent transhydrogenase and accumulation
of Ca2þ ions by rat liver mitochondria (Dougherty
1974). It is not suitable for layers as it negatively affects
the egg production and quality.
The exact anticoccidial mechanism of robenidine (a
guanidine derivative) is still unknown. However, from
studies in mammals, it is assumed that it inhibits the
oxidative phosphorylation of mitochondria (Wong
et al. 1972).
Another anticoccidial drug possibly affecting mito-
chondrial function is the triazinetrione compound
toltrazuril, which is applied in drinking water for
preventive and therapeutic treatment. Harder and
Haberkorn (1989) showed that activities of some
enzymes of the respiratory chain, such as succinate-
cytochrome C reductase, nicotinamide adenine
dinucleotide (NADH) oxidase and succinate oxidase
from mouse liver, were reduced in the presence of
toltrazuril. They also showed an inhibitory effect on
the dihydroorotate-cytochrome C reductase from
mouse liver. More recently, it has been suggested that
toltrazuril might affect plastid-like organelles
(Hackstein et al. 1995). Toltrazuril is efficacious
against all intracellular stages (schizogony and game-
togony) of all important Eimeria spp. in the chicken
(Mehlhorn et al. 1984, 1988). It induces cidal changes
in the organelles of the parasite at multiple levels and
does not seem to impair the development of natural
immunity (Greif and Haberkorn 1997; Greif 2000).
2.2.3. Products affecting cell membrane function
Polyether antibiotics influence the transport of mono-
or divalent cations (Naþ, Kþ and Caþþ) across cell
membranes inducing osmotic damage (Berger 1951;
Shumard and Callender 1967). These drugs are accu-
mulated by extracellular stages (like sporozoites and
merozoites) of the parasite in the lumen of the intestine
(Long and Jeffers 1982).
Depending on the dose given, ionophore antic-
occidials allow the development of immunity against
coccidia (Jeffers 1989; Chapman and Hacker 1993;
Chapman 1999b).
2.2.4. Products with unknown mode of action
Diclazuril is a nucleoside analogue thought to be
involved in nucleic acid synthesis, possibly affecting
later phases of coccidia differentiation (Verheyen et al.
1988). It has been shown to affect parasite wall
synthesis resulting in the formation of an abnormally
thickened, incomplete oocyst wall and zygote necrosis
in both E. brunetti and E. maxima (Verheyen et al.
1989).
Halofuginone is a quinazolinone derivative with an
unknown mode of action, which particularly affects
the first generation of the schizogony.
145
2.3. Antimicrobial and growth-promoting properties
Ionophores have been found to inhibit Gram-positive
organisms and mycoplasmas (Shumard and Callender
1967; Dutta and Devriese 1984; Stipkovits et al. 1987).
Monensin and narasin were shown to inhibit
Clostridium perfringens (types A and C) in chickens
and turkeys (Elwinger et al. 1992; Vissiennon et al.
2000). Ionophores may therefore have contributed in
some cases to the control of necrotizing enteritis
(Martel et al. 2004).
Salinomycin has been shown to reduce the number
of resistant coliforms (sulphadiazine) and Streptococci
(erythromycin and lincomycin; George et al. 1982). It
also seemed to reduce the number of resistant
Salmonella typhimurium bacteria (Ford et al. 1981).
2.4. Incompatibilities
Ionophores are incompatible with some therapeutic
antibiotics like tiamulin, chlorampheniol, erythromy-
cin, oleandromycin and certain sulphonamides.
Ionophores are also incompatible with some antioxi-
dants (XAX-M, Duokvin, TD; Umemura et al. 1984;
Prohaszka et al. 1987; Dowling 1992; Von Wendt et al.
1997).
2.5. European Union regulations
The future status of anticoccidial drugs is uncertain at
this moment: their current status as feed additives may
be maintained or new legislation and phasing-out of
these drugs as feed additives could be proposed. Article
11 of Regulation 1831/2003 called for a report of the
European Commission on this subject. In April 2008,
the commission submitted a report (COM 2008) in
which it clearly recommends the maintenance of the
use of anticoccidial products, including ionophores as
feed additives, due to a lack of alternatives and to
safeguard the economical feasibility of the poultry
industry. It is not clear whether the European Council
will follow this recommendation or not.
Actual and forthcoming information of the
obtained regulations can be found on the website of
the European Commission animal nutrition feed addi-
tives (http://ec.europa.eu/food/food/animalnutrition/
feedadditives/legisl_en.htm).
2.6. Resistance
The World Health Organization (WHO) defines drug
resistance in antimalarial chemotherapy, which can
also be applied to coccidiology, as ‘the ability of a
parasite strain to survive and/or multiply despite the
administration and absorption of a drug in doses equal
to or higher than those usually recommended but
within the limits of tolerance of the subject’
(WHO 1965).
Generally, drug resistance in coccidia can be
complete, in which case increasing doses up the
146 H.W. Peek and W.J.M. Landman
maximum tolerated by the host is ineffective
(i.e. diclazuril and nicarbazin). In contrast, relative
resistance to anticoccidial drugs is characterized by the
fact that increasing doses tolerated by the host still will
show efficacy (i.e. ionophores).
The worldwide intensive use of anticoccidial drugs
to prevent coccidiosis has inevitably led to the devel-
opment of resistance to all anticoccidial drugs as long-
term exposure to any drug will result in loss of
sensitivity. The widespread occurrence of resistance
has been described in the United States of America,
South America, Europe and China (Jeffers 1974a,
1974b, 1989; Chapman 1978, 1982, 1984, 1997; Ryley
1980; Hamet 1986; Litjens 1986; McDougald et al.
1986, 1987; Zeng and Hu 1996; Zhou et al. 2000; Peek
and Landman 2003; Peek and Landman 2004). In
some cases resistance is induced very quickly, as in the
case of quinolones and pyridinols, which led to a
decline in their use, while in other instances it may take
several years as in the case of the ionophores.
Despite the widespread occurrence of resistance, at
least in Europe, coccidiosis outbreaks seem to have had
limited impact so far. This is explained by the fact that
resistance in many cases will have allowed the occur-
rence of trickle infections, which are essential in the
building up of immunity (Jeffers 1989; Chapman 1998;
Peek and Landman 2003; McDougald and Shirley
2009).
2.6.1. Management of resistance
To minimize the occurrence of resistance, rotation (a
given anticoccidial product is used during a maximum
of 2 months or two fattening periods) of various
anticoccidial drugs or shuttle programmes (two or
more anticoccidial drugs are used within a fattening
period) is used. The rationale behind this is the fact
that, as said previously, the loss of sensitivity is
correlated to the length of drug exposure, which
should be kept short if possible. Due to the occurrence
of cross-resistance between anticoccidial drugs, antic-
occidial drugs with distinct mode of action should be
used within rotation and shuttle programmes.
In order to optimize the use of prophylactic
medication in the field, scientific information on the
drug-sensitivity profiles of Eimeria spp. concerning
field isolates is vital. This information can only be
obtained by performing an in vivo Anticoccidial
Sensitivity Test (AST) in battery cages. Despite the
fact that the AST is the only accurate tool to detect
anticoccidial drug resistance, the procedure is slow and
expensive; isolates frequently originate from disease
outbreaks (and may not always be representative for
the field) and need to be propagated first in specified
pathogen-free chickens for multiplication (which may
result in the selection of non-relevant coccidia).
Nevertheless, it is generally accepted by the scientific
community that ASTs provide valuable information
and should be given more attention in coccidiosis
prevention programmes.
A more recent development in managing antic-
occidial drug resistance is the rotation of anticoccidial
drugs with live Eimeria spp. vaccines. Several studies
have documented a higher incidence of sensitive
Eimeria spp. field isolates when live anticoccidial
vaccines and anticoccidial products are rotated. The
exact mechanism resulting in an increase of sensitivity
of Eimeria spp. field isolates is currently unknown, but
it is explained by the fact that chicken houses are
seeded with drug-sensitive vaccine oocysts (Jeffers
1976; Mathis and McDougald 1989; Chapman 1994,
1996; Newman and Danforth 2000; Mathis and
Broussard 2006; Peek and Landman 2006). This may
lead to the outgrowth of resistant strains by reproduc-
tively more advantageous drug-sensitive coccidia,
interbreeding between field and vaccine parasites
resulting in (more) sensitive interbreeds or a combina-
tion of both. Moreover, in case live attenuated
coccidiosis vaccines are used, less virulent interbreed
field isolates may be produced (Shimura and Isobe
1994; Williams 2002a).
3. Vaccines
Immunity to coccidiosis, which can be induced by
passive or active immune responses, is generally
defined as the occurrence of ‘resistance’ to a challenge
infection with an Eimeria spp. and can be determined
by a reduction of the pathogenic effects of coccidiosis:
less macroscopically visible lesions and/or a decrease in
oocyst production, and increased performance of
birds.
The first study showing that chickens infected with
E. tenella were resistant to homologous challenge was
reported by Beach and Corl (1925) and formed the
basis of modern coccidiosis vaccinology. However, it
took another 27 years before the first commercial live
coccidiosis vaccine CocciVacÕ was registered in the
USA (Edgar and King 1952).
During the past 20 years, various reports describing
coccidiosis vaccines and their use in poultry have been
published (Shirley 1988; Williams 1992, 1996, 1998,
1999, 2000; 2002a, 2002b; Dalloul and Lillehoj 2006;
Shirley et al. 2007). In Table 2, an overview showing
most available coccidiosis vaccines and their usage is
given (Williams 2002a; Shirley et al. 2005).
Vaccination can be alternated with anticoccidial
drugs in feed within rotation programmes and in
combination with biosecurity.
3.1. Subunit vaccines
Subunit vaccines are composed of a purified antigenic
determinant that is separated from the virulent organ-
ism. Such vaccines can be obtained by different
technologies and may consist of native antigens or of
recombinant proteins expressed from DNA of various
developmental stages (sporozoites, merozoites and
gametes) of the Eimeria parasite.
Table 2. Overview of anticoccidial vaccines that are being used or being registered for use in chickens (modified from Williams 2002a; Shirley et al. 2005; manufacturer’s technical
information bulletins and websites).

Vaccine (manufacturer) Eimeria speciesa Attenuation Bird type Administration route First registration
Õb
ADVENT (Novus Eac, Emax, Eten Non-attenuated Broilers Hatchery spray, water or 2002 (USA)
International) feed spray
CocciVacÕ -B (Schering Eac, Emax, Emiv, Eten Non-attenuated Broilers Ocular, hatchery spray, 1952 (USA)
Plough Animal Health) water or feed spray
CocciVacÕ -D (Schering Eac, Ebr, Eha, Emax, Emiv, Non-attenuated Breeders/layers Ocular, hatchery spray, 1951 (USA)
Plough Animal Health) Enec, Epra, Eten water or feed spray
CoxAbicÕ (Abic Biological Killed antigen of Emax Breeders (to protect Killed antigen, one species, 2002 (Israel)
Laboratories) gametocytes hatchlings) intramuscular
EimerivacÕ Plus Eac, Emax, Eten Attenuated Breeders/layers/broilers Oral Expected (China)
(Guangdong Academy of
Agricultural Sciences)
EimeriavaxÕ 4 m Eac, Emax, Enec, Eten Attenuated (precocious) Breeders/layers/broilers Eye-drop application 2003 (Australia)
(Bioproperties Pty)
HipracoxÕ Broilers Eac, Emax, Emit, Epra, Attenuated Broilers Drinking water 2007 (Spain)
(Laboratorios Hipra, Eten
SA)
ImmucoxÕ C1 (Vetech Eac, Emax, Enec, Eten Non-attenuated Broilers Water or gel 1985 (Canada)
Laboratories)
ImmucoxÕ C2 (Vetech Eac, Ebr, Emax, Enec, Eten Non-attenuated Breeders/layers Water or gel 1985 (Canada)
Laboratories)
InmunerÕ Gel-Coc Eac, Ebr, Emax, Eten Attenuated Breeders/layers/broilers Oral 2005 (Argentina)
Veterinary Quarterly

(Vacunas Inmuner)
InovocoxÕ (Embrex Inc.
and Pfizer)
LivacoxÕ Q (BioPharm)
LivacoxÕ T (BioPharm)
ParacoxÕ -8 (Schering
Plough Animal Health)
ParacoxÕ -5 (Schering
Plough Animal Health)
SupercoxÕ (Qilu Animal
Pharmaceutical
Company)
Eac, Emax 2, Eten Non-attenuated Broilers In ovo injection with the 2006 (USA)
InovojectÕ system
Eac, Emax, Enec, Eten Attenuated (precocious, Breeders/layers Hatchery spray, water or 1992 (Czech Republic)
except Eten (embryo- feed spray
adapted))
Eac, Emax, Eten Attenuated (precocious, Broilers Hatchery spray, water or 1992 (Czech Republic)
except Eten (embryo- feed spray
adapted))
Eac, Ebr, Emax 2, Emit, Attenuated (precocious) Breeders/layers Water or feed spray 1989 (UK)
Enec, Epra, Eten
Eac, Emax 2, Emit, Eten Attenuated (precocious) Broilers Hatchery spray, water or 1989 (UK)
feed spray
Eac, Emax, Eten Attenuated (precocious: Broilers Oral 2005 (China)
Eten) non-attenuated (Eac
and Emax)

Notes: aEac, E. acervulina; Ebr, E. brunetti; Eha, E. hagani; Emax, E. maxima; Emit, E. mitis; Emiv, E. mivati; Enec, E. necatrix; Epra, E. praecox; Eten, E. tenella; and Emax 2, two
antigenically different lines of E. maxima.
b
ADVENTÕ enables in vitro assessment of parasite viability using ViacystSM (non-viable sporocysts stain with ethidium bromide).
147
148 H.W. Peek and W.J.M. Landman
Despite an increasing number of manuscripts on
exploring the feasibility of subunit vaccines against
coccidiosis, no commercial products, except
CoxAbicÕ , have been marketed to date (Brother
et al. 1988; Jenkins et al. 1989; Miller et al. 1989;
Jenkins et al. 1990; Crane et al. 1991; Bhogal et al.
1992; Jenkins 1998; Vermeulen 1998; Jenkins 2001;
Vermeulen et al. 2001; Dalloul and Lillehoj 2006). A
major limiting factor has been that until now no
antigens able to induce potent protective immune
response against Eimeria have been isolated.
Systematic and detailed analysis of host–parasite
interactions at the molecular and cellular levels includ-
ing studies of basic immunology need to be completed
before successful subunit vaccine products will be
made available. In this regard, the E. tenella genome
project may help to further understand how protective
immune responses against Eimeria spp. are developed
and help to identify antigens of vital importance in
coccidial immunology (Shirley et al. 2007).
3.1.1. Maternal immunization, transmission blocking
immunity
CoxAbicÕ is a vaccine against coccidiosis, which
induces maternally derived antibodies to protect
broiler chickens (Michael 2003, 2007; Finger and
Michael 2005; Ziomko et al. 2005). It is an inactivated,
subunit vaccine (oil emulsion) containing affinity-
purified proteins (56, 82 and 230 kDa) from the
oocyst wall-forming bodies of E. maxima gametocytes.
Cross-protection resulting in lower oocyst shedding of
E. maxima, E. acervulina and E. tenella has been
described after the administration of low-dose
challenge inocula using the aforementioned Eimeria
spp. (Wallach et al. 1995; Wallach 1997). This is
remarkable because after natural Eimeria infections,
cross-immunity has not been described (Rose and
Long 1962). However, Crane and co-workers (1991)
found cross-protection against four Eimeria spp.
(E. acervulina, E. maxima, E. necatrix and E. tenella)
after administration of a single recombinant antigen.
Offspring originating from vaccinated parent birds
are fed an anticoccidial drug-free diet in order to
ensure natural exposure to the parasites and subse-
quent development of active immunity after maternal
antibodies have disappeared.
3.2. Live vaccines
Live Eimeria vaccines consist of sporulated oocysts
and are either non-attenuated (wild-type strains of
Eimeria spp.) or attenuated. Further differentiation is
based on the Eimeria spp. included, their anticoccidial
drug sensitivity profile and application. Protective
immunity can be achieved if chickens are infected
with either a single high dose or multiple low doses
(trickle infections) of Eimeria (vaccine) parasites
(Joyner and Norton 1973, 1976; Long et al. 1986). It
is crucial that anticoccidial drugs are withdrawn from
feed in case chicken flocks are vaccinated with drug-
sensitive live vaccine parasites in order to avoid
vaccination failures.
3.2.1. Non-attenuated (or wild-type strains of
Eimeria spp.) vaccines
Non-attenuated vaccines consist of Eimeria parasites,
which have not been modified in any way to change
their pathogenicity and originate from laboratory or
field strains. Examples of such vaccines are:
CocciVacÕ , ImmucoxÕ , InovocoxÕ and ADVENTÕ .
Some of these vaccines (CocciVacÕ and
ImmucoxÕ ) are available as two different products
and the choice of products depends on the poultry to
be vaccinated, e.g. broilers versus breeders and layers.
During the usage of non-attenuated coccidiosis
vaccines, it is crucial that all birds are given the
required dose and the occurrence of clinical coccidiosis
is avoided. Therefore, application protocols should be
followed strictly (Chapman et al. 2002). In order to
diminish the risk of coccidiosis outbreaks following
vaccination, attenuated vaccines have been developed.
3.2.2. Attenuated vaccines
Attenuated vaccines consist of Eimeria spp. strains,
which have been manipulated in the laboratory in
order to decrease their virulence. Reduced virulence
has been performed by serial passages of the parasite in
chicken embryos; e.g. E. tenella in LivacoxÕ vaccines.
Selection for precocity is the second described method
for attenuation; e.g. remaining Eimeria spp. in
LivacoxÕ and all lines in ParacoxÕ vaccines
(McDonald and Shirley 1984; Shirley and Millard
1986; Shirley et al. 1995; Shirley and Bedrnik 1997).
Precocity is characterized by a shortened endogenous
life-cycle due to the fact that the number of generations
of schizogony is decreased because last generations of
schizogony disappear by selecting early oocysts. As a
consequence, the number of oocysts produced during
infection is reduced. However, the immunizing poten-
tial is maintained (Jeffers 1975, 1986; McDonald et al.
1986; Shirley and Millard 1986).
A major drawback of live coccidiosis vaccines is
their loss of infectivity with time affecting their expiry
(Jeston et al. 2002). Other concerns are their high
production costs and management shortcomings
during their application such as dosage errors that
may result in insufficient immune response or clinical
coccidiosis in case non-attenuated vaccines are used,
the erroneous addition of anticoccidial drugs to the
feed frustrating effective vaccination of drug-sensitive
strains and vaccination of sick birds. Furthermore,
reversal of virulence of live vaccines may be another
point of concern. Subunit vaccines offer possibilities to
circumvent mentioned drawbacks and could provide a
sustainable solution for the coccidiosis problem in
commercial poultry if with the help of new technolo-
gies their immunogenicity can be increased.
 Veterinary Quarterly
A full list of anticoccidial vaccines, including,
amongst others, their composition and route of
administration, has been given in Table 2.
4. Other preventive strategies against coccidiosis
The prevention and control of coccidiosis in commer-
cial poultry and mainly broilers is largely based on the
administration of anticoccidial drugs in feed, although
in some cases an anticoccidial drug administered
shortly via drinking water is applied (Mathis et al.
2004). Moreover, biosecurity measures aiming at
preventing the introduction of the parasite to the
farm can be of additional strategic value against
clinical coccidiosis. During the past decade, live
coccidiosis vaccination has become increasingly
popular as an alternative strategy to control Eimeria
spp. In feed, products with supposed anticoccidial
activity like herbs, essential oils, probiotics and
prebiotics have been added more recently.
The development of resistance against all antic-
occidial drugs used in feed to date and a loud call for
residue-free poultry products, which in Europe has
been translated first into a re-evaluation of all existing
anticoccidial products and regulations safeguarding
lower residues, have prompted the search for
alternative control and prevention strategies.
4.1. Management and biosecurity
Good health and hence optimal immune response are
essential in order to minimize the impact of infectious
diseases. General management measures safeguarding
the basic requirements of poultry should therefore
always be implemented: birds should be provided with
proper feed and drinking water intake, adequate
bedding, temperature, humidity, lighting and
ventilation.
Management and biosecurity measures for the
control of coccidiosis should focus on the prevention
of the introduction of the parasite into the premises,
and control of its multiplication and spread in case
flocks have been infected. However, strict biosecurity
leading to coccidiosis-free flocks is almost impossible
to attain in practice. Therefore, already in the early
days of coccidiosis research gradual building up of
immunity through repeated light (trickle) infections
was advocated as a mean to control this disease
(Chapman 2003).
4.1.1. Avoiding the introduction of the parasite
Eimeria parasites are ubiquitous and have enormous
reproduction capabilities leading to high contamina-
tion levels of infected poultry houses and their
surroundings. Moreover, the oocyst wall protects the
parasite from desiccation and chemical disinfectants,
ensuring long-term survival in the environment, from
which it may be introduced to a farm through a variety
149
of ways. On the other hand, oocysts may already be
present in the farm house if cleaning and disinfection
was not adequate.
Biosecurity measures aiming to prevent the intro-
duction of Eimeria parasites to the farm are similar to
those applied for the prevention of other infectious
poultry diseases and should focus on:
(1) Isolation. Birds should be separated from the
environment by fencing and other animals
including rodents and insects should be kept
out.
(2) Traffic control should not only be performed at
the farm, but also the traffic between farms
should be restricted.
(3) Sanitation includes disinfection of materials,
people and equipment entering the farm and
poultry house.
4.1.2. Environmental factors
In case coccidiosis infections occur, their multiplication
cannot be restricted by influencing the climate envi-
ronment of the chicken house as Eimeria spp. thrives in
atmospheric conditions that are beneficial to the birds
also.
In order for Eimeria spp. to become infective, it
must sporulate after excretion in the faeces. The degree
and rate of sporulation of excreted oocysts determine
the infection pressure in a chicken flock. Sporulation of
the oocyst depends mainly on the following basic
factors: temperature, humidity and aeration (access to
oxygen) (Kheysin 1972).
The best sporulation temperature is approximately
24–28 C (Edgar 1955), while a temperature above 35 C
is lethal for oocysts (Schneider et al. 1979). Due to the
fact that the ideal sporulation temperature is within
the range of temperatures frequently encountered in
the poultry environment and that high temperatures
are detrimental to the birds, temperature is not a factor
that can be used to control parasite multiplication.
A general misconception, regarding humidity is the
belief that the drier the climate, the less coccidiosis
occurs. Research data have shown that in the field
sporulation in wet litter is suboptimal possibly due to
the occurrence of ammonia and bacteria (Williams
1995); in fact, dry litter showed better sporulation rates
(Graat et al. 1994; Waldenstedt et al. 2001). However,
increasing the litter humidity as a control measure to
reduce sporulation does not seem feasible as it might
cause footpad lesions and skin burns in the birds.
Adequate ventilation of the poultry house is
essential for good performance and health of the
birds although proper aeration will also favour
sporulation.
Theoretically, a higher bird density will result in
greater oocyst accumulation in the litter and increase
the chances of clinical coccidiosis (Williams et al.
2000). Thus, reducing bird density could help to
control Eimeria infections.
150 H.W. Peek and W.J.M. Landman
4.1.3. Cleaning and disinfection
Cleaning and disinfection between flocks and maxi-
mizing the downtime period is important in order to
significantly reduce the number of parasites in
contaminated chicken houses. However, there are
mixed points of view regarding the use of cleaning
and disinfection for the control of coccidiosis. Some
consider that the presence of oocysts in the poultry
environment enabling early establishment of immunity
in order to avoid outbreaks at later age is beneficial. In
case coccidiosis vaccines are used to repopulate the
houses with drug-sensitive strains, survival of vaccine
parasites between vaccinated and non-vaccinated
flocks is desired and therefore cleaning and disinfection
should be skipped. Nevertheless, in case of severe
clinical coccidiosis outbreaks especially due to
anticoccidial drug-resistant strains, it is customary in
Europe, where birds are not housed on deep litter,
to clean and disinfect the chicken houses in order to
reduce infection pressure.
Ammonium hydroxide has been reported as a
highly effective disinfectant against sporulated and
non-sporulated oocysts. It has been shown to be
effective at a concentration of 5% in both fluid and
vapour forms (Chroustova and Pinka 1987). Also,
products that generate ammonia after mixing two
components (ammonium salt and sodium hydroxide)
have shown to be oocidal (OocideÕ , Antec
International Ltd, UK). More recently, a cresol-
based product (NeopredisanÕ 135-1, Menno Chemie,
Norderstedt, Germany) has been marketed in
Germany for the control of coccidiosis by chemical
disinfection. It has been shown to be efficient against
various Eimeria spp. (Daugschies et al. 2002; Houdek
et al. 2002). In a recent study, the efficacy of eight
disinfectants against E. tenella unsporulated oocysts
isolated from broilers was studied in vitro. The best
disinfection efficacy was observed for the combination
formol 37% and sodium dodecylbenzene sulphonate
12% (Gumarães et al. 2007).
In practice, poultry houses in the Netherlands are
often disinfected using calcium hydroxide in
combination with ammonium sulphate (per 500 m2
40 kg calcium hydroxide is spread and subsequently
moisturized with approximately 500 L water, after
which 80 kg ammonium sulphate is added).
4.2. Alternative coccidiosis control
Various alternative methods like homeopathy, phy-
totherapy and aromatherapy have been used during
the past decennia for the treatment of various poultry
diseases. Homeopathy is a system for treating disease
based on the administration of minute doses of a drug
that in massive amounts produces clinical signs in
healthy individuals similar to those of the disease itself.
The treatment is thus based on law of similars, i.e.
similia similibus curentur ¼ the most similar remedy
will cure (Saine 2000). It is thought to enhance the
body’s natural defenses. Homeopathy is often confused
with herbalism also known as botanical medicine,
medicinal botany, medical herbalism, herbal medicine,
herbology and phytotherapy. It is based on the use of
plant and plant extracts for the treatment and preven-
tion of disease. Its scope is sometimes extended to
include fungi, bee products, minerals, shells and certain
animal parts. Aromatherapy, which is closely related to
phytotherapy, is the treatment or prevention of disease
by means of essential oils, and other scented
compounds from plants. It involves the use of distilled
plant volatiles, a twentieth century innovation.
Essential oils differ in chemical composition from
other herbal products because the distillation process
only recovers lighter phytomolecules.
Although many papers have been published on the
efficacy of homeopathic treatment in humans, its
effectiveness has remained a matter of debate to the
scientific community. Studies assessing the methodo-
logical quality of a large number of human homeo-
pathic experiments report a lack of evidence for
efficacy of homeopathic treatments because of frequent
low methodological quality and publication bias
(Kleynen et al. 1991; Linde et al. 2001). According to
Velkers et al. (2005), ‘Efficacy of medicines should be
beyond placebo effect and observation and interpreta-
tion should be without subjective elements. Therefore,
all medicines, including homeopathic remedies, should
be tested in a double blind randomized clinical trial’.
Published studies on homeopathy in poultry are rare
and similar to human studies, are frequently affected
by low methodological quality (Velkers et al. 2005).
There are no scientific reports on the homeopathic
treatment of coccidiosis.
Some plant products or derived pharmaceutical
drugs have been incorporated into mainstream medi-
cine; nevertheless, most herbal treatments have been
developed without modern scientific assessment.
Although later on many herbs have been found
efficacious in in vitro animal models and/or clinical
studies (Srinivasan 2005), there are also many studies
showing negative results (Pittler et al. 2000). However,
evaluation of the literature on complementary/alterna-
tive therapies is difficult due to the occurrence of
location bias in the corresponding controlled clinical
trials. More positive than negative trials are published,
except in high-impact mainstream medical journals.
Furthermore, in complementary/alternative medicine
journals, positive studies are of poorer quality than
corresponding negative studies. The latter was not the
case in mainstream medical journals publishing on a
wider range of therapies.
Pre- and probiotics have also been included within
alternative coccidiosis control strategies although they
are quite distinct from phytotherapy and aromather-
apy. Probiotics consist of live bacteria or yeasts
administered in feed, which are supposed to be
beneficial for the individual’s health. In contrast,
prebiotics are non-digestible food ingredients, which
also have a beneficial effect on the host’s health.
 Veterinary Quarterly
4.2.1. Plant (herb) extracts
Many different herbal compounds have been
investigated for their potential use as a dietary supple-
ment to control coccidiosis and are reported next in
alphabetical order. The main conclusions obtained in
the research of alternative coccidiosis control have
been summarized in Table 3 and Figure 1.
4.2.1.1. Artemisinin. Artemisinin is an herbal extract,
which can be obtained from Artemisia annua (annual
wormwood) and Artemisia sieberi. Positive effects were
found for E. tenella (Oh et al. 1995; Allen et al. 1997b),
mixed results for E. acervulina (Allen et al. 1997b; Arab
et al. 2006) and negative results for E. maxima (Allen
et al. 1997b; Arab et al. 2006).
4.2.1.2. Betaine. Betaine is a sweet crystalline alkaloid
(trimethylglycine C5H11NO2), choline analogue and
methyl donor occurring in sugar beets and other
plants, which is used in the treatment of certain
metabolic disorders (muscular weakness and degener-
ation). It has been shown to protect cells against
osmotic stress by stabilizing cell membranes enabling
the maintenance of osmotic pressure in the cells and
ensuring normal metabolic activity (Rudolph et al.
1986). The osmoprotective effect of betaine is not
restricted to the intestinal cells, but also affects the
developing stages of the coccidia. It protects different
cell types against chemical and environmental stresses
(Kunin and Rudy 1991), including the asexual stages
(sporozoites) of E. acervulina against the destructive
action of salinomycin (Augustine and Danforth 1999).
Nevertheless, feed efficacy and weight gain were
significantly improved in birds infected with a mixture
of E. acervulina, E. maxima and E. tenella if betaine
(0.15%) and salinomycin (44 or 66 ppm) were supple-
mented separately, but much more if both components
were given together suggesting a palliative effect of
betaine on the coccidiosis infection. Betaine alone did
not influence the severity of lesion scores and mortality
(Augustine et al. 1997). Both products alone or in
combination inhibited the invasion of E. acervulina and
E. tenella (sporozoites) and the development of
E. acervulina (second generation schizonts).
The ionophore-amplifying effect of betaine was
only observed once and could not be found with other
anticoccidial ionophore drugs like monensin and
narasin (Matthews et al. 1997; Waldenstedt et al.
1999), while other scientists found contradictory results
(Fetterer et al. 2003).
The weight gain and feed conversion-promoting
capabilities found in some studies may be explained by
betaine’s osmoprotectant properties ensuring normal
metabolism of intestinal cells. This may warrant
normal development of the chicks despite the fact
that the coccidiosis infection is not fully halted.
Another contributing factor to the positive effect of
betaine on coccidiosis infection may be the fact that it
151
increases intraepithelial lymphocytes in the duodenum
and the functional properties of phagocytes of
Eimeria-infected chickens (Klasing et al. 2002).
4.2.1.3. Citric extracts. A product based on citric
extracts and organic acids amongst others supple-
mented to broilers showed a moderate efficacy against
a challenge with various Eimeria spp. considering
coccidiosis lesion scores and oocyst production
(Tamasaukas et al. 1996, 1997).
4.2.1.4. Echinacea purpurea. The anticoccidial effect
of E. purpurea has been attributed to its immunomo-
dulating properties, which have been widely docu-
mented (Stimple et al. 1984; Burger et al. 1997; See
et al. 1997; Sun et al. 1999; Currier and Miller 2001;
Goel et al. 2002). Ground root preparations of
E. purpurea (0.1–0.5%) supplemented to broilers
during 2 weeks reduced weight gain retardation and
coccidial lesions after a mixed infection at the age of 28
days with E. acervulina, E. maxima, E. tenella and
E. necatrix (Allen 2003).
4.2.1.5. Gentian violet. Gentian violet, also named
crystal violet, methyl violet and hexamethyl pararos-
aniline chloride, is derived from coal tar and known for
its antifungal and antibacterial properties. It has been
shown to reduce coccidiosis lesion scores in the
duodenum and improve weight gain in Eimeria spp.
challenged birds. In combination with anticoccidial
drugs, it improved feed conversion (Sharkey 1978).
4.2.1.6. Mushrooms and their extracts. Mushrooms
and their extracts have gained interest in medicine
and as dietary supplement due to their immune
enhancing and antitumour properties. However, they
should be used cautiously as mushrooms may harbour
toxic levels of metals (arsenic, lead, cadmium and
mercury) and radioactive contamination with 137Cs
(Borchers et al. 2004).
Polysaccharide extracts originating from Lentinus
edodes and Tremella fuciformes as well as the herb
Astragalus membranaceus showed a positive effect on
the cellular and humoural immunity of E. tenella
infected female broilers (Guo et al. 2004). In another
study, the birds treated with the same extracts had
better growth during immunization in comparison with
the non-treated vaccinated birds and had lower
E. tenella oocyst countings after challenge (Guo et al.
2005).
Extracted lectin from the mushroom Fomitella
fraxinea injected in 18-day-old embryos, protected
broilers inoculated with E. acervulina at 1 week post-
hatch against weight loss and was associated with a
significant reduction in oocyst shedding compared to
untreated embryos (Dalloul et al. 2006).
Table 3. Overview of the influence of alternative feed additives, including the active compound, dose per kg feed and mode of action, on a coccidiosis infection in poultry.
152

Coccidiosis model
Alternative Active compound Mode of Infection dose (no. Effect on clinical
feed additive and dose action Eimeria spp. of oocysts) parameters Global effecta References

Artemisia Artemisinin extracts Induction oxidative Eimeria tenella Unknown BWGb " – Oh et al. (1995)
annua stress (free radicals) FCEb "
LSb #
Artemisia Dried leaves at 5, 10 Induction oxidative Eimeria acervulina 105 OPGb # Eimeria tenella  Allen et al. (1997)
annua and 50 g/kg 3 weeks stress (free radicals) Eimeria tenella 5  104 LS # Eimeria acervulina 
Pure artemisinin Eimeria maxima 5  103 No effect Eimeria maxima ¼
0.002, 0.0085 and
0.017 g/kg 4 weeks
Mushrooms Polysaccharide Immune stimulation Eimeria tenella 6  104 BWG " – Guo et al. (2004,
extracts extracts (1 g/kg) 9  104 2005)
Mushrooms Lectin (FFrL) Immune stimulation Eimeria acervulina 104 BWG " – Dalloul et al.
extracts injected into amniotic OPG # (2006)
cavity (100 mg in
100 mL/egg)
Oregano Essential oil, Stimulation mucosal Eimeria tenella 5  104 BWG " – Giannenas et al.
carvacrol and thymol immunity (antimicro- (2003)
(0.3 g/kg) bial effect)
Oregano Essential oil, thymol, Stimulation mucosal ADVENTÕ No beneficial effect ¼ Oviedo-Rondón
eugenol, curcumin immunity (antimicro- (day 1) on vaccination et al. (2006)
and piperin (0.1 g/kg) bial effect) Challenged
(day 19)
Eimeria acervulina 2  102
Eimeria maxima 102
Eimeria tenella 5  103
H.W. Peek and W.J.M. Landman

Herb(s) Various Indian herb Unknown Eimeria necatrix Unknown LS # – Mandal et al.
extracts extracts (6 g/kg) (1994)
Herb(s) Preparation of Unknown Mixed infection 5  104 BWG " – Hayat et al. (1996)
extracts Persian lilac (Melia Eimeria spp. OPG #
azedarach) 0.3 g/kg
and bitter melon
(Momordica
charantia) 30 g/kg
Herb(s) Fifteen Asian herb(s) Unknown Eimeria tenella 105 Variable results dif- þ/ Youn and Noh
extracts extracts (6–30 g/L ferent herbs (2001)
drinking water)
Herb extract Neem fruit Unknown Eimeria tenella 3  104 (3 g/kg) – Tipu et al. (2002)
(Azadirachta indica) Mort #
(1, 2 and 3 g/kg) OPG #
Herb(s) Complex of eight Unknown Eimeria tenella 105 LS # – Du and Hu (2004)
extracts herbs (2 g/mL and BWG "
10 g/kg)
Herb(s) Complex of four Unknown Eimeria tenella 6  104 BWG " – Christaki et al.
extracts herbs (Apacox) (0.5 FCE " (2004)
and 1.0 g/kg) OPG #
Herb extract Green tea (5 and Unknown Eimeria maxima 104 BWG ¼ – Jang et al. (2007)
20 g/kg) OPG #
Betaine (sugar Trymethylglycine Stabilization cell Mixed infection Various BWG " – Augustine et al.
beet solids) (0.5, 0.75, 1, 1.5 and membranes and Eimeria acervulina OPG ¼ (1997)
5 g/kg) immune stimulation Eimeria tenella LS ¼ Mathews et al.
(osmoprotectant) Eimeria maxima (1997)
Waldenstedt et al.
(1999)
Klasing et al.
(2002)
Citric fruits Extracts and organic ? Mixed infection 4.5  104 LS # Mixed infection  Tamasaukas et al.
acids (2, 3 and 4 mL/ Eimeria acervulina OPG # (1996, 1997)
10 L drinking water) Eimeria maxima
Eimeria tenella (E. tenella 5  103) Except for E. tenella Eimeria tenella ¼
Eimeria brunetti
Eimeria mivati
Echinacea Dried ground root Immune stimulation, ImmucoxÕ C1 115 (0.5  dose) BWG " – Allen (2003)
purpurea preparation including enhancement macro- (day 1) LS #
glycoproteins, chiro- phage activity Challenged 2.3  105
ric acid and alka- (day 28) (1000  vaccine
mides (1–5 g/kg first 2 dose)
weeks)
Turmeric Diferuleolymethane Immune stimulation Eimeria maxima Unknown BWG " – Allen et al. (1998)
(Curcuma (phenolic compound, by inactivation of LS #
longa) curcumin 10 g/kg) reactive nitrogen rad- OPG #
icals ( -tocopherol Eimeria tenella Unknown No effect ¼
like)
Prebiotics MOS 1, 0.5 and Immune stimulation Eimeria acervulina Various Variable results þ/ Elmusharaf et al.
10 g/kg (Bio-MosÕ ) and blocking binding Eimeria tenella (2006, 2007)
Veterinary Quarterly

to mucosal surface Eimeria maxima McCann et al.

(2006)
Probiotics Lactobacillus Stimulation local cell Eimeria acervulina 104 OPG # – Dalloul et al.
(PrimalacÕ , 1 g/kg) immunity (2003a, 2003b,
2005)
Probiotics Pediococcus Immune stimulation Eimeria acervulina 5  103 or 104 BWG # – Lee et al. (2007a)
(Mito-GrowÕ , 1 and (enhanced humoural OPG #
2 g/kg) response) Eimeria tenella 5  103 BWG ¼ ¼
OPG ¼
Probiotics Pediococcus and Immune stimulation Eimeria acervulina 5  103 BWG ¼ – Lee et al. (2007b)
Sacchromyces (enhanced humoural Eimeria tenella 5  103 OPG #
(MitoMaxÕ 0.1, 1 response)
and 10 g/kg)

Notes: a‘’ indicates that the substrate has an inhibiting effect on coccidiosis, ‘þ’ indicates that the substrate promotes coccidiosis and ‘¼’ indicates no effect on coccidiosis.
b
BWG, body weight gain; FCE, feed conversion efficiency (g weight gain/g food intake); LS, lesion scores; Mort, mortality; OPG, oocysts per gram faeces.
153
154 H.W. Peek and W.J.M. Landman

Figure 1. Artemisinin extracts, citric fruits and different herb extracts seem to have an inhibitory effect on the development of
Eimeria spp. Prebiotics and oregano have an indirect inhibitory effect on the development of Eimeria parasite. Betaine has an
indirect effect on the development of the parasite through its osmoprotective properties on the intestinal mucosa and stimulation
of the intraepithelial lymphocytes. Echinacea purpurea, mushrooms extracts, turmeric and probiotics have an indirect inhibitory
effect on the development of Eimeria spp. through stimulation of the immune system.

4.2.1.7. Oregano. The essential oils of Origanum
vulgare are known for their antibacterial activity
(Hammer et al. 1999) and effect against some parasites
(Milhau et al. 1997). Furthermore, some essential oils
-tocopherol. The antioxidative prop-
of oregano, mainly carvacrol and thymol, have an
anticoccidial effect against E. tenella although lower
than lasalocid (Giannenas et al. 2003). However, in
has been shown previously (Brouet and
subsequently performed studies with diets supple-
mented with a mixture of the essential oils, oregano,
thymol, eugenol, curcumin and piperin, a beneficial
effect of these oils on a coccidiosis vaccination was not
found (Oviedo-Rondón et al. 2006).
found for both Eimeria spp. (Allen et al. 1998). A
similar effect on lesion scores, oocyst shedding,
growth, and plasma NO 
2 and NO3 concentrations
was found for
erties of curcumin by inhibiting NOS induction by
macrophages stimulated with lipopolysaccharide and
interferon-
Ohshima 1995). Although NO is an important defence
mechanism against the invasion of different
Apicomplexa parasites (Adams et al. 1990; Mellouk
et al. 1991), it was suggested more recently that NO
might itself promote the development of coccidial
lesions (Allen 1997a, 1997b).

4.2.1.8. Turmeric (Curcuma longa). Turmeric is a

spice and colourant made from the rhizomes of the
plant C. longa, a leafy plant belonging to the ginger
family. Its phenolic compound curcumin has been
shown to have antioxidative, anti-inflammatory and
antitumour properties (Mukhopadhyay et al. 1982;
Conney et al. 1991; Ammon et al. 1993; Brouet and
Ohshima 1995).
Eimeria maxima-infected chicks fed with diets
supplemented with 1% curcumin showed an improved
weight gain and a reduction in the lesion scores and
oocyst excretion. Nevertheless, the activity was only
shown against E. maxima and not against E. tenella. A
significant reduction of plasma NO 2 and NO
concentrations was only found in E. maxima-infected
and curcumin-treated birds and provide a possible
explanation for the difference in anticoccidial activity
4.2.1.9. Incidental reports on the anticoccidial activity
of other herb(s) extracts. The anticoccidial effect of a
number of herbs and extracts has been documented in
single manuscripts and summarized in Table 3 for
convenience. Although anticoccidial activity was
reported, to our knowledge, none of these studies
was repeated and has not led to the large-scale
application of any of these compounds in practice.
4.2.2. Pre- and probiotics
The term prebiotic was introduced by Gibson and
3 Roberfroid (1995), who defined it as ‘a non-digestible
food ingredient that beneficially affects the host by
selectively stimulating the growth and/or activity of
one or a limited number of bacteria in the colon, and
 Veterinary Quarterly
thus improves the host’s health. The positive influence
of prebiotics on the intestinal flora has been confirmed
by a number of studies (Van Loo et al. 1999). Recently,
the definition of the prebiotics was narrowed with the
introduction of a prebiotic index by Roberfroid (2005),
who stated that a preparation might be called prebiotic
if it is capable to produce at least 4  108 colony-
forming units of Bifidobacteria/gram faeces per daily
dose (gram) ingested. Only three large groups meet this
criterion: inulin and oliogofructose, galactose
oligosaccharides and xylooligosaccharides.
Probiotics consist of beneficial live bacteria or
yeasts supplemented to the diet. According to the Food
and Agriculture Organization (FAO) and WHO pro-
biotics are ‘live microorganisms, which when adminis-
trated in adequate amounts confer a health benefit on
the host’ (FAO/WHO 2002). The most frequently used
probiotics in humans are species of the genera
Lactobacillus and Bifidobacteria, whereas species of
Bacillus, Enterococcus and Saccharomyces yeasts have
been the most commonly used organisms in livestock.
In poultry production, probiotics are known for their
capacity to restore the intestinal microflora after being
disrupted by antibiotic treatment or enteric infections
(Rada and Rychly 1995; Line et al. 1998; Pascual et al.
1999). They are also known for their ability to boost
the immune system and used against allergies and
other immune diseases (Zulkifli et al. 2000; Dalloul
et al. 2003b; Kabir et al. 2004; Koenen et al. 2004).
A treatment with prebiotics can be easily combined
with a probiotic in a so-called ‘synbiotic’ approach
(Gibson and Roberfroid 1995). An advantage of this
combination is the improved survival of probiotics
when given in a medium of prebiotics. The use of pre-
and probiotics in poultry has been reviewed by
Patterson and Burkholder (2003).
4.2.2.1. Prebiotics. Mannan oligosaccharides (MOS)
are derived from the cell wall of the yeast
Saccharomyces cerevisiae and are widely used in
animal feed to promote gastrointestinal health and
performance. MOS have been described as a prebiotic,
but are thought to block the binding of pathogens to
mannan receptors on the mucosal surface and stimu-
late the immune response (Spring et al. 2000).
In an experiment performed with coccidia, dietary
MOS (1 g/kg feed) were able to reduce the severity of a
single E. tenella infection with 3500 or 5000 sporulated
oocysts (Elmusharaf et al. 2006). In another
experiment, a dietary supplementation of MOS at a
concentration of 10 g/kg feed reduced the oocyst
excretion and diminished the severity of E. acervulina
lesions in birds infected orally with a mixture of
E. acervulina, E. maxima and E. tenella at subclinical
doses of 900, 570 and 170 sporulated oocysts,
respectively (Elmusharaf et al. 2007).
In contrast, in a study performed by McCann et al.
(2006) supplementation of MOS (0.5 g/kg feed) or
tannin (0.5 g/kg feed) either individually or in
155
combination did not reduce the severity of a mixed
coccidiosis infection of E. acervulina, E. maxima and
E. tenella given orally at clinical doses of 50,000, 15,000
and 15,000 sporulated oocysts, respectively. These
contradictory results are possibly explained by the
differences in MOS concentrations in feed and the
magnitude of Eimeria spp. inoculation doses.
4.2.2.2. Probiotics. Lower intestinal invasion, devel-
opment of coccidia and oocyst production, explained
by enhanced local cell-mediated immunity, were
observed with a Lactobacillus-based probiotic supple-
mented diet in E. acervulina-infected broilers (Dalloul
et al. 2003a, 2003b, 2005).
More recently, in a study performed with a
Pediococcus-based commercial probiotic
(MitoGrowÕ ) given to birds infected with either
E. acervulina or E. tenella, increased resistance of
birds against coccidiosis and a partial protection
against growth retardation were demonstrated (Lee
et al. 2007a). In another study, performed with a
Pediococcus- and Saccharomyces-based probiotic
(MitoMaxÕ ), less E. acervulina and E. tenella oocyst
shedding and a better antibody response were found
(Lee et al. 2007b).
5. Conclusions and perspectives
To date, coccidiosis control has relied mainly on
chemoprophylaxis. However, the occurrence of resis-
tance, consumer concerns and the increasing regula-
tions as well as possible upcoming bans on the use of
anticoccidial drugs as feed additives, have prompted
the quest for alternative control strategies, amongst
which vaccines, phytotherapy, aromatherapy, pre- and
probiotics have been quite extensively studied. So far,
live vaccines have proved to be the most solid and
successful anticoccidiosis alternative approach.
Although a number of drawbacks are associated with
the production and use of live coccidiosis vaccines,
their efficacy and ability to increase the sensitivity of
Eimeria spp. isolates to anticoccidial drugs, have
further stimulated their use. If the immunogenicity of
subunit vaccines can be improved, they could represent
the next generation of highly efficient and low-cost
anticoccidial strategies.
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