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Coccidiosis in poultry: anticoccidial products,

vaccines and other prevention strategies
a a b
H.W. Peek & W.J.M. Landman
a
Animal Health Service – GD, Deventer, The Netherlands
b
Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University,
Utrecht, The Netherlands

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other prevention strategies, Veterinary Quarterly, 31:3, 143-161

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 Most knowledge on A number of anticoccidials have been withdrawn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

*Corresponding author. Email: [email protected]

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
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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 145

reduction in mitochondria of beef hearts and the 2.3. Antimicrobial and growth-promoting properties
energy dependent transhydrogenase and accumulation Ionophores have been found to inhibit Gram-positive
of Ca2þ ions by rat liver mitochondria (Dougherty organisms and mycoplasmas (Shumard and Callender
1974). It is not suitable for layers as it negatively affects 1967; Dutta and Devriese 1984; Stipkovits et al. 1987).
the egg production and quality. Monensin and narasin were shown to inhibit
The exact anticoccidial mechanism of robenidine (a Clostridium perfringens (types A and C) in chickens
guanidine derivative) is still unknown. However, from and turkeys (Elwinger et al. 1992; Vissiennon et al.
studies in mammals, it is assumed that it inhibits the 2000). Ionophores may therefore have contributed in
oxidative phosphorylation of mitochondria (Wong some cases to the control of necrotizing enteritis
et al. 1972). (Martel et al. 2004).
Another anticoccidial drug possibly affecting mito- Salinomycin has been shown to reduce the number
chondrial function is the triazinetrione compound of resistant coliforms (sulphadiazine) and Streptococci
toltrazuril, which is applied in drinking water for (erythromycin and lincomycin; George et al. 1982). It
preventive and therapeutic treatment. Harder and also seemed to reduce the number of resistant
Haberkorn (1989) showed that activities of some Salmonella typhimurium bacteria (Ford et al. 1981).
enzymes of the respiratory chain, such as succinate-
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cytochrome C reductase, nicotinamide adenine

dinucleotide (NADH) oxidase and succinate oxidase 2.4. Incompatibilities
from mouse liver, were reduced in the presence of Ionophores are incompatible with some therapeutic
toltrazuril. They also showed an inhibitory effect on antibiotics like tiamulin, chlorampheniol, erythromy-
the dihydroorotate-cytochrome C reductase from cin, oleandromycin and certain sulphonamides.
mouse liver. More recently, it has been suggested that Ionophores are also incompatible with some antioxi-
toltrazuril might affect plastid-like organelles dants (XAX-M, Duokvin, TD; Umemura et al. 1984;
(Hackstein et al. 1995). Toltrazuril is efficacious Prohaszka et al. 1987; Dowling 1992; Von Wendt et al.
against all intracellular stages (schizogony and game- 1997).
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 2.5. European Union regulations
does not seem to impair the development of natural The future status of anticoccidial drugs is uncertain at
immunity (Greif and Haberkorn 1997; Greif 2000). 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
2.2.3. Products affecting cell membrane function 11 of Regulation 1831/2003 called for a report of the
Polyether antibiotics influence the transport of mono- European Commission on this subject. In April 2008,
or divalent cations (Naþ, Kþ and Caþþ) across cell the commission submitted a report (COM 2008) in
membranes inducing osmotic damage (Berger 1951; which it clearly recommends the maintenance of the
Shumard and Callender 1967). These drugs are accu- use of anticoccidial products, including ionophores as
mulated by extracellular stages (like sporozoites and feed additives, due to a lack of alternatives and to
safeguard the economical feasibility of the poultry
merozoites) of the parasite in the lumen of the intestine
industry. It is not clear whether the European Council
(Long and Jeffers 1982).
will follow this recommendation or not.
Depending on the dose given, ionophore antic-
Actual and forthcoming information of the
occidials allow the development of immunity against
obtained regulations can be found on the website of
coccidia (Jeffers 1989; Chapman and Hacker 1993;
the European Commission animal nutrition feed addi-
Chapman 1999b).
tives (http://ec.europa.eu/food/food/animalnutrition/
feedadditives/legisl_en.htm).

2.2.4. Products with unknown mode of action

Diclazuril is a nucleoside analogue thought to be 2.6. Resistance
involved in nucleic acid synthesis, possibly affecting The World Health Organization (WHO) defines drug
later phases of coccidia differentiation (Verheyen et al. resistance in antimalarial chemotherapy, which can
1988). It has been shown to affect parasite wall also be applied to coccidiology, as ‘the ability of a
synthesis resulting in the formation of an abnormally parasite strain to survive and/or multiply despite the
thickened, incomplete oocyst wall and zygote necrosis administration and absorption of a drug in doses equal
in both E. brunetti and E. maxima (Verheyen et al. to or higher than those usually recommended but
1989). within the limits of tolerance of the subject’
Halofuginone is a quinazolinone derivative with an (WHO 1965).
unknown mode of action, which particularly affects Generally, drug resistance in coccidia can be
the first generation of the schizogony. complete, in which case increasing doses up the
 146 H.W. Peek and W.J.M. Landman

maximum tolerated by the host is ineffective A more recent development in managing antic-
(i.e. diclazuril and nicarbazin). In contrast, relative occidial drug resistance is the rotation of anticoccidial
resistance to anticoccidial drugs is characterized by the drugs with live Eimeria spp. vaccines. Several studies
fact that increasing doses tolerated by the host still will have documented a higher incidence of sensitive
show efficacy (i.e. ionophores). Eimeria spp. field isolates when live anticoccidial
The worldwide intensive use of anticoccidial drugs vaccines and anticoccidial products are rotated. The
to prevent coccidiosis has inevitably led to the devel- exact mechanism resulting in an increase of sensitivity
opment of resistance to all anticoccidial drugs as long- of Eimeria spp. field isolates is currently unknown, but
term exposure to any drug will result in loss of it is explained by the fact that chicken houses are
sensitivity. The widespread occurrence of resistance seeded with drug-sensitive vaccine oocysts (Jeffers
has been described in the United States of America, 1976; Mathis and McDougald 1989; Chapman 1994,
South America, Europe and China (Jeffers 1974a, 1996; Newman and Danforth 2000; Mathis and
1974b, 1989; Chapman 1978, 1982, 1984, 1997; Ryley Broussard 2006; Peek and Landman 2006). This may
1980; Hamet 1986; Litjens 1986; McDougald et al. lead to the outgrowth of resistant strains by reproduc-
1986, 1987; Zeng and Hu 1996; Zhou et al. 2000; Peek tively more advantageous drug-sensitive coccidia,
and Landman 2003; Peek and Landman 2004). In interbreeding between field and vaccine parasites
some cases resistance is induced very quickly, as in the resulting in (more) sensitive interbreeds or a combina-
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case of quinolones and pyridinols, which led to a tion of both. Moreover, in case live attenuated
decline in their use, while in other instances it may take coccidiosis vaccines are used, less virulent interbreed
several years as in the case of the ionophores. field isolates may be produced (Shimura and Isobe
Despite the widespread occurrence of resistance, at 1994; Williams 2002a).
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- 3. Vaccines
rence of trickle infections, which are essential in the
Immunity to coccidiosis, which can be induced by
building up of immunity (Jeffers 1989; Chapman 1998;
passive or active immune responses, is generally
Peek and Landman 2003; McDougald and Shirley
defined as the occurrence of ‘resistance’ to a challenge
2009).
infection with an Eimeria spp. and can be determined
by a reduction of the pathogenic effects of coccidiosis:
2.6.1. Management of resistance less macroscopically visible lesions and/or a decrease in
oocyst production, and increased performance of
To minimize the occurrence of resistance, rotation (a
birds.
given anticoccidial product is used during a maximum
The first study showing that chickens infected with
of 2 months or two fattening periods) of various
E. tenella were resistant to homologous challenge was
anticoccidial drugs or shuttle programmes (two or
reported by Beach and Corl (1925) and formed the
more anticoccidial drugs are used within a fattening
basis of modern coccidiosis vaccinology. However, it
period) is used. The rationale behind this is the fact
took another 27 years before the first commercial live
that, as said previously, the loss of sensitivity is
coccidiosis vaccine CocciVacÕ was registered in the
correlated to the length of drug exposure, which
USA (Edgar and King 1952).
should be kept short if possible. Due to the occurrence
During the past 20 years, various reports describing
of cross-resistance between anticoccidial drugs, antic-
coccidiosis vaccines and their use in poultry have been
occidial drugs with distinct mode of action should be
published (Shirley 1988; Williams 1992, 1996, 1998,
used within rotation and shuttle programmes.
1999, 2000; 2002a, 2002b; Dalloul and Lillehoj 2006;
In order to optimize the use of prophylactic
Shirley et al. 2007). In Table 2, an overview showing
medication in the field, scientific information on the
drug-sensitivity profiles of Eimeria spp. concerning most available coccidiosis vaccines and their usage is
field isolates is vital. This information can only be given (Williams 2002a; Shirley et al. 2005).
obtained by performing an in vivo Anticoccidial Vaccination can be alternated with anticoccidial
drugs in feed within rotation programmes and in
Sensitivity Test (AST) in battery cages. Despite the
fact that the AST is the only accurate tool to detect combination with biosecurity.
anticoccidial drug resistance, the procedure is slow and
expensive; isolates frequently originate from disease
outbreaks (and may not always be representative for 3.1. Subunit vaccines
the field) and need to be propagated first in specified Subunit vaccines are composed of a purified antigenic
pathogen-free chickens for multiplication (which may determinant that is separated from the virulent organ-
result in the selection of non-relevant coccidia). ism. Such vaccines can be obtained by different
Nevertheless, it is generally accepted by the scientific technologies and may consist of native antigens or of
community that ASTs provide valuable information recombinant proteins expressed from DNA of various
and should be given more attention in coccidiosis developmental stages (sporozoites, merozoites and
prevention programmes. gametes) of the Eimeria parasite.
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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. Eac, Emax 2, Eten Non-attenuated Broilers In ovo injection with the 2006 (USA)
and Pfizer) InovojectÕ system
LivacoxÕ Q (BioPharm) Eac, Emax, Enec, Eten Attenuated (precocious, Breeders/layers Hatchery spray, water or 1992 (Czech Republic)
except Eten (embryo- feed spray
adapted))
LivacoxÕ T (BioPharm) Eac, Emax, Eten Attenuated (precocious, Broilers Hatchery spray, water or 1992 (Czech Republic)
except Eten (embryo- feed spray
adapted))
ParacoxÕ -8 (Schering Eac, Ebr, Emax 2, Emit, Attenuated (precocious) Breeders/layers Water or feed spray 1989 (UK)
Plough Animal Health) Enec, Epra, Eten
ParacoxÕ -5 (Schering Eac, Emax 2, Emit, Eten Attenuated (precocious) Broilers Hatchery spray, water or 1989 (UK)
Plough Animal Health) feed spray
SupercoxÕ (Qilu Animal Eac, Emax, Eten Attenuated (precocious: Broilers Oral 2005 (China)
Pharmaceutical Eten) non-attenuated (Eac
Company) 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 feed in case chicken flocks are vaccinated with drug-
exploring the feasibility of subunit vaccines against sensitive live vaccine parasites in order to avoid
coccidiosis, no commercial products, except vaccination failures.
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. 3.2.1. Non-attenuated (or wild-type strains of
1992; Jenkins 1998; Vermeulen 1998; Jenkins 2001; Eimeria spp.) vaccines
Vermeulen et al. 2001; Dalloul and Lillehoj 2006). A Non-attenuated vaccines consist of Eimeria parasites,
major limiting factor has been that until now no which have not been modified in any way to change
antigens able to induce potent protective immune their pathogenicity and originate from laboratory or
response against Eimeria have been isolated. field strains. Examples of such vaccines are:
Systematic and detailed analysis of host–parasite CocciVacÕ , ImmucoxÕ , InovocoxÕ and ADVENTÕ .
interactions at the molecular and cellular levels includ- Some of these vaccines (CocciVacÕ and
ing studies of basic immunology need to be completed ImmucoxÕ ) are available as two different products
before successful subunit vaccine products will be and the choice of products depends on the poultry to
made available. In this regard, the E. tenella genome be vaccinated, e.g. broilers versus breeders and layers.
project may help to further understand how protective During the usage of non-attenuated coccidiosis
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immune responses against Eimeria spp. are developed vaccines, it is crucial that all birds are given the
and help to identify antigens of vital importance in required dose and the occurrence of clinical coccidiosis
coccidial immunology (Shirley et al. 2007). is avoided. Therefore, application protocols should be
followed strictly (Chapman et al. 2002). In order to
diminish the risk of coccidiosis outbreaks following
3.1.1. Maternal immunization, transmission blocking
vaccination, attenuated vaccines have been developed.
immunity
CoxAbicÕ is a vaccine against coccidiosis, which
induces maternally derived antibodies to protect 3.2.2. Attenuated vaccines
broiler chickens (Michael 2003, 2007; Finger and Attenuated vaccines consist of Eimeria spp. strains,
Michael 2005; Ziomko et al. 2005). It is an inactivated, which have been manipulated in the laboratory in
subunit vaccine (oil emulsion) containing affinity- order to decrease their virulence. Reduced virulence
purified proteins (56, 82 and 230 kDa) from the has been performed by serial passages of the parasite in
oocyst wall-forming bodies of E. maxima gametocytes. chicken embryos; e.g. E. tenella in LivacoxÕ vaccines.
Cross-protection resulting in lower oocyst shedding of Selection for precocity is the second described method
E. maxima, E. acervulina and E. tenella has been for attenuation; e.g. remaining Eimeria spp. in
described after the administration of low-dose LivacoxÕ and all lines in ParacoxÕ vaccines
challenge inocula using the aforementioned Eimeria (McDonald and Shirley 1984; Shirley and Millard
spp. (Wallach et al. 1995; Wallach 1997). This is 1986; Shirley et al. 1995; Shirley and Bedrnik 1997).
remarkable because after natural Eimeria infections, Precocity is characterized by a shortened endogenous
cross-immunity has not been described (Rose and life-cycle due to the fact that the number of generations
Long 1962). However, Crane and co-workers (1991) of schizogony is decreased because last generations of
found cross-protection against four Eimeria spp. schizogony disappear by selecting early oocysts. As a
(E. acervulina, E. maxima, E. necatrix and E. tenella) consequence, the number of oocysts produced during
after administration of a single recombinant antigen. infection is reduced. However, the immunizing poten-
Offspring originating from vaccinated parent birds tial is maintained (Jeffers 1975, 1986; McDonald et al.
are fed an anticoccidial drug-free diet in order to 1986; Shirley and Millard 1986).
ensure natural exposure to the parasites and subse- A major drawback of live coccidiosis vaccines is
quent development of active immunity after maternal their loss of infectivity with time affecting their expiry
antibodies have disappeared. (Jeston et al. 2002). Other concerns are their high
production costs and management shortcomings
during their application such as dosage errors that
3.2. Live vaccines may result in insufficient immune response or clinical
Live Eimeria vaccines consist of sporulated oocysts coccidiosis in case non-attenuated vaccines are used,
and are either non-attenuated (wild-type strains of the erroneous addition of anticoccidial drugs to the
Eimeria spp.) or attenuated. Further differentiation is feed frustrating effective vaccination of drug-sensitive
based on the Eimeria spp. included, their anticoccidial strains and vaccination of sick birds. Furthermore,
drug sensitivity profile and application. Protective reversal of virulence of live vaccines may be another
immunity can be achieved if chickens are infected point of concern. Subunit vaccines offer possibilities to
with either a single high dose or multiple low doses circumvent mentioned drawbacks and could provide a
(trickle infections) of Eimeria (vaccine) parasites sustainable solution for the coccidiosis problem in
(Joyner and Norton 1973, 1976; Long et al. 1986). It commercial poultry if with the help of new technolo-
is crucial that anticoccidial drugs are withdrawn from gies their immunogenicity can be increased.
 Veterinary Quarterly 149

A full list of anticoccidial vaccines, including, of ways. On the other hand, oocysts may already be
amongst others, their composition and route of present in the farm house if cleaning and disinfection
administration, has been given in Table 2. was not adequate.
Biosecurity measures aiming to prevent the intro-
duction of Eimeria parasites to the farm are similar to
4. Other preventive strategies against coccidiosis those applied for the prevention of other infectious
The prevention and control of coccidiosis in commer- poultry diseases and should focus on:
cial poultry and mainly broilers is largely based on the (1) Isolation. Birds should be separated from the
administration of anticoccidial drugs in feed, although environment by fencing and other animals
in some cases an anticoccidial drug administered including rodents and insects should be kept
shortly via drinking water is applied (Mathis et al. out.
2004). Moreover, biosecurity measures aiming at (2) Traffic control should not only be performed at
preventing the introduction of the parasite to the the farm, but also the traffic between farms
farm can be of additional strategic value against should be restricted.
clinical coccidiosis. During the past decade, live (3) Sanitation includes disinfection of materials,
coccidiosis vaccination has become increasingly people and equipment entering the farm and
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popular as an alternative strategy to control Eimeria poultry house.

spp. In feed, products with supposed anticoccidial
activity like herbs, essential oils, probiotics and
prebiotics have been added more recently. 4.1.2. Environmental factors
The development of resistance against all antic- In case coccidiosis infections occur, their multiplication
occidial drugs used in feed to date and a loud call for cannot be restricted by influencing the climate envi-
residue-free poultry products, which in Europe has ronment of the chicken house as Eimeria spp. thrives in
been translated first into a re-evaluation of all existing atmospheric conditions that are beneficial to the birds
anticoccidial products and regulations safeguarding also.
lower residues, have prompted the search for In order for Eimeria spp. to become infective, it
alternative control and prevention strategies. 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
4.1. Management and biosecurity the oocyst depends mainly on the following basic
Good health and hence optimal immune response are factors: temperature, humidity and aeration (access to
essential in order to minimize the impact of infectious oxygen) (Kheysin 1972).
diseases. General management measures safeguarding The best sporulation temperature is approximately
the basic requirements of poultry should therefore 24–28 C (Edgar 1955), while a temperature above 35 C
always be implemented: birds should be provided with is lethal for oocysts (Schneider et al. 1979). Due to the
proper feed and drinking water intake, adequate fact that the ideal sporulation temperature is within
bedding, temperature, humidity, lighting and the range of temperatures frequently encountered in
ventilation. the poultry environment and that high temperatures
Management and biosecurity measures for the are detrimental to the birds, temperature is not a factor
control of coccidiosis should focus on the prevention that can be used to control parasite multiplication.
of the introduction of the parasite into the premises, A general misconception, regarding humidity is the
and control of its multiplication and spread in case belief that the drier the climate, the less coccidiosis
flocks have been infected. However, strict biosecurity occurs. Research data have shown that in the field
leading to coccidiosis-free flocks is almost impossible sporulation in wet litter is suboptimal possibly due to
to attain in practice. Therefore, already in the early the occurrence of ammonia and bacteria (Williams
days of coccidiosis research gradual building up of 1995); in fact, dry litter showed better sporulation rates
immunity through repeated light (trickle) infections (Graat et al. 1994; Waldenstedt et al. 2001). However,
was advocated as a mean to control this disease increasing the litter humidity as a control measure to
(Chapman 2003). 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
4.1.1. Avoiding the introduction of the parasite essential for good performance and health of the
Eimeria parasites are ubiquitous and have enormous birds although proper aeration will also favour
reproduction capabilities leading to high contamina- sporulation.
tion levels of infected poultry houses and their Theoretically, a higher bird density will result in
surroundings. Moreover, the oocyst wall protects the greater oocyst accumulation in the litter and increase
parasite from desiccation and chemical disinfectants, the chances of clinical coccidiosis (Williams et al.
ensuring long-term survival in the environment, from 2000). Thus, reducing bird density could help to
which it may be introduced to a farm through a variety control Eimeria infections.
 150 H.W. Peek and W.J.M. Landman

4.1.3. Cleaning and disinfection body’s natural defenses. Homeopathy is often confused
Cleaning and disinfection between flocks and maxi- with herbalism also known as botanical medicine,
mizing the downtime period is important in order to medicinal botany, medical herbalism, herbal medicine,
significantly reduce the number of parasites in herbology and phytotherapy. It is based on the use of
contaminated chicken houses. However, there are plant and plant extracts for the treatment and preven-
mixed points of view regarding the use of cleaning tion of disease. Its scope is sometimes extended to
and disinfection for the control of coccidiosis. Some include fungi, bee products, minerals, shells and certain
consider that the presence of oocysts in the poultry animal parts. Aromatherapy, which is closely related to
environment enabling early establishment of immunity phytotherapy, is the treatment or prevention of disease
in order to avoid outbreaks at later age is beneficial. In by means of essential oils, and other scented
case coccidiosis vaccines are used to repopulate the compounds from plants. It involves the use of distilled
houses with drug-sensitive strains, survival of vaccine plant volatiles, a twentieth century innovation.
parasites between vaccinated and non-vaccinated Essential oils differ in chemical composition from
flocks is desired and therefore cleaning and disinfection other herbal products because the distillation process
should be skipped. Nevertheless, in case of severe only recovers lighter phytomolecules.
clinical coccidiosis outbreaks especially due to Although many papers have been published on the
efficacy of homeopathic treatment in humans, its
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anticoccidial drug-resistant strains, it is customary in

Europe, where birds are not housed on deep litter, effectiveness has remained a matter of debate to the
to clean and disinfect the chicken houses in order to scientific community. Studies assessing the methodo-
reduce infection pressure. logical quality of a large number of human homeo-
Ammonium hydroxide has been reported as a pathic experiments report a lack of evidence for
highly effective disinfectant against sporulated and efficacy of homeopathic treatments because of frequent
non-sporulated oocysts. It has been shown to be low methodological quality and publication bias
effective at a concentration of 5% in both fluid and (Kleynen et al. 1991; Linde et al. 2001). According to
vapour forms (Chroustova and Pinka 1987). Also, Velkers et al. (2005), ‘Efficacy of medicines should be
products that generate ammonia after mixing two beyond placebo effect and observation and interpreta-
components (ammonium salt and sodium hydroxide) tion should be without subjective elements. Therefore,
have shown to be oocidal (OocideÕ , Antec all medicines, including homeopathic remedies, should
International Ltd, UK). More recently, a cresol- be tested in a double blind randomized clinical trial’.
based product (NeopredisanÕ 135-1, Menno Chemie, Published studies on homeopathy in poultry are rare
Norderstedt, Germany) has been marketed in and similar to human studies, are frequently affected
Germany for the control of coccidiosis by chemical by low methodological quality (Velkers et al. 2005).
disinfection. It has been shown to be efficient against There are no scientific reports on the homeopathic
various Eimeria spp. (Daugschies et al. 2002; Houdek treatment of coccidiosis.
et al. 2002). In a recent study, the efficacy of eight Some plant products or derived pharmaceutical
drugs have been incorporated into mainstream medi-
disinfectants against E. tenella unsporulated oocysts
cine; nevertheless, most herbal treatments have been
isolated from broilers was studied in vitro. The best
developed without modern scientific assessment.
disinfection efficacy was observed for the combination
Although later on many herbs have been found
formol 37% and sodium dodecylbenzene sulphonate
efficacious in in vitro animal models and/or clinical
12% (Gumarães et al. 2007).
studies (Srinivasan 2005), there are also many studies
In practice, poultry houses in the Netherlands are
showing negative results (Pittler et al. 2000). However,
often disinfected using calcium hydroxide in
evaluation of the literature on complementary/alterna-
combination with ammonium sulphate (per 500 m2
tive therapies is difficult due to the occurrence of
40 kg calcium hydroxide is spread and subsequently
location bias in the corresponding controlled clinical
moisturized with approximately 500 L water, after
trials. More positive than negative trials are published,
which 80 kg ammonium sulphate is added).
except in high-impact mainstream medical journals.
Furthermore, in complementary/alternative medicine
journals, positive studies are of poorer quality than
4.2. Alternative coccidiosis control corresponding negative studies. The latter was not the
Various alternative methods like homeopathy, phy- case in mainstream medical journals publishing on a
totherapy and aromatherapy have been used during wider range of therapies.
the past decennia for the treatment of various poultry Pre- and probiotics have also been included within
diseases. Homeopathy is a system for treating disease alternative coccidiosis control strategies although they
based on the administration of minute doses of a drug are quite distinct from phytotherapy and aromather-
that in massive amounts produces clinical signs in apy. Probiotics consist of live bacteria or yeasts
healthy individuals similar to those of the disease itself. administered in feed, which are supposed to be
The treatment is thus based on law of similars, i.e. beneficial for the individual’s health. In contrast,
similia similibus curentur ¼ the most similar remedy prebiotics are non-digestible food ingredients, which
will cure (Saine 2000). It is thought to enhance the also have a beneficial effect on the host’s health.
 Veterinary Quarterly 151

4.2.1. Plant (herb) extracts increases intraepithelial lymphocytes in the duodenum

Many different herbal compounds have been and the functional properties of phagocytes of
investigated for their potential use as a dietary supple- Eimeria-infected chickens (Klasing et al. 2002).
ment to control coccidiosis and are reported next in
alphabetical order. The main conclusions obtained in
the research of alternative coccidiosis control have 4.2.1.3. Citric extracts. A product based on citric
been summarized in Table 3 and Figure 1. extracts and organic acids amongst others supple-
mented to broilers showed a moderate efficacy against
a challenge with various Eimeria spp. considering
4.2.1.1. Artemisinin. Artemisinin is an herbal extract, coccidiosis lesion scores and oocyst production
which can be obtained from Artemisia annua (annual (Tamasaukas et al. 1996, 1997).
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 4.2.1.4. Echinacea purpurea. The anticoccidial effect
et al. 2006) and negative results for E. maxima (Allen of E. purpurea has been attributed to its immunomo-
et al. 1997b; Arab et al. 2006). dulating properties, which have been widely docu-
mented (Stimple et al. 1984; Burger et al. 1997; See
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et al. 1997; Sun et al. 1999; Currier and Miller 2001;

4.2.1.2. Betaine. Betaine is a sweet crystalline alkaloid Goel et al. 2002). Ground root preparations of
(trimethylglycine C5H11NO2), choline analogue and E. purpurea (0.1–0.5%) supplemented to broilers
methyl donor occurring in sugar beets and other during 2 weeks reduced weight gain retardation and
plants, which is used in the treatment of certain coccidial lesions after a mixed infection at the age of 28
metabolic disorders (muscular weakness and degener- days with E. acervulina, E. maxima, E. tenella and
ation). It has been shown to protect cells against E. necatrix (Allen 2003).
osmotic stress by stabilizing cell membranes enabling
the maintenance of osmotic pressure in the cells and
ensuring normal metabolic activity (Rudolph et al. 4.2.1.5. Gentian violet. Gentian violet, also named
1986). The osmoprotective effect of betaine is not crystal violet, methyl violet and hexamethyl pararos-
restricted to the intestinal cells, but also affects the aniline chloride, is derived from coal tar and known for
developing stages of the coccidia. It protects different its antifungal and antibacterial properties. It has been
cell types against chemical and environmental stresses shown to reduce coccidiosis lesion scores in the
(Kunin and Rudy 1991), including the asexual stages duodenum and improve weight gain in Eimeria spp.
(sporozoites) of E. acervulina against the destructive challenged birds. In combination with anticoccidial
action of salinomycin (Augustine and Danforth 1999). drugs, it improved feed conversion (Sharkey 1978).
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 4.2.1.6. Mushrooms and their extracts. Mushrooms
(0.15%) and salinomycin (44 or 66 ppm) were supple- and their extracts have gained interest in medicine
mented separately, but much more if both components and as dietary supplement due to their immune
were given together suggesting a palliative effect of enhancing and antitumour properties. However, they
betaine on the coccidiosis infection. Betaine alone did should be used cautiously as mushrooms may harbour
not influence the severity of lesion scores and mortality toxic levels of metals (arsenic, lead, cadmium and
(Augustine et al. 1997). Both products alone or in mercury) and radioactive contamination with 137Cs
combination inhibited the invasion of E. acervulina and (Borchers et al. 2004).
E. tenella (sporozoites) and the development of Polysaccharide extracts originating from Lentinus
E. acervulina (second generation schizonts). edodes and Tremella fuciformes as well as the herb
The ionophore-amplifying effect of betaine was Astragalus membranaceus showed a positive effect on
only observed once and could not be found with other the cellular and humoural immunity of E. tenella
anticoccidial ionophore drugs like monensin and infected female broilers (Guo et al. 2004). In another
narasin (Matthews et al. 1997; Waldenstedt et al. study, the birds treated with the same extracts had
1999), while other scientists found contradictory results better growth during immunization in comparison with
(Fetterer et al. 2003). the non-treated vaccinated birds and had lower
The weight gain and feed conversion-promoting E. tenella oocyst countings after challenge (Guo et al.
capabilities found in some studies may be explained by 2005).
betaine’s osmoprotectant properties ensuring normal Extracted lectin from the mushroom Fomitella
metabolism of intestinal cells. This may warrant fraxinea injected in 18-day-old embryos, protected
normal development of the chicks despite the fact broilers inoculated with E. acervulina at 1 week post-
that the coccidiosis infection is not fully halted. hatch against weight loss and was associated with a
Another contributing factor to the positive effect of significant reduction in oocyst shedding compared to
betaine on coccidiosis infection may be the fact that it untreated embryos (Dalloul et al. 2006).
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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 #
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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
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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 found for both Eimeria spp. (Allen et al. 1998). A
vulgare are known for their antibacterial activity similar effect on lesion scores, oocyst shedding,
(Hammer et al. 1999) and effect against some parasites growth, and plasma NO 
2 and NO3 concentrations
(Milhau et al. 1997). Furthermore, some essential oils was found for -tocopherol. The antioxidative prop-
of oregano, mainly carvacrol and thymol, have an erties of curcumin by inhibiting NOS induction by
anticoccidial effect against E. tenella although lower macrophages stimulated with lipopolysaccharide and
than lasalocid (Giannenas et al. 2003). However, in interferon- has been shown previously (Brouet and
subsequently performed studies with diets supple- Ohshima 1995). Although NO is an important defence
mented with a mixture of the essential oils, oregano, mechanism against the invasion of different
thymol, eugenol, curcumin and piperin, a beneficial Apicomplexa parasites (Adams et al. 1990; Mellouk
effect of these oils on a coccidiosis vaccination was not et al. 1991), it was suggested more recently that NO
found (Oviedo-Rondón et al. 2006). 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 4.2.1.9. Incidental reports on the anticoccidial activity
plant C. longa, a leafy plant belonging to the ginger of other herb(s) extracts. The anticoccidial effect of a
family. Its phenolic compound curcumin has been number of herbs and extracts has been documented in
shown to have antioxidative, anti-inflammatory and single manuscripts and summarized in Table 3 for
antitumour properties (Mukhopadhyay et al. 1982; convenience. Although anticoccidial activity was
Conney et al. 1991; Ammon et al. 1993; Brouet and reported, to our knowledge, none of these studies
Ohshima 1995). was repeated and has not led to the large-scale
Eimeria maxima-infected chicks fed with diets application of any of these compounds in practice.
supplemented with 1% curcumin showed an improved
weight gain and a reduction in the lesion scores and
oocyst excretion. Nevertheless, the activity was only 4.2.2. Pre- and probiotics
shown against E. maxima and not against E. tenella. A The term prebiotic was introduced by Gibson and
significant reduction of plasma NO 2 and NO 3 Roberfroid (1995), who defined it as ‘a non-digestible
concentrations was only found in E. maxima-infected food ingredient that beneficially affects the host by
and curcumin-treated birds and provide a possible selectively stimulating the growth and/or activity of
explanation for the difference in anticoccidial activity one or a limited number of bacteria in the colon, and
 Veterinary Quarterly 155

thus improves the host’s health. The positive influence combination did not reduce the severity of a mixed
of prebiotics on the intestinal flora has been confirmed coccidiosis infection of E. acervulina, E. maxima and
by a number of studies (Van Loo et al. 1999). Recently, E. tenella given orally at clinical doses of 50,000, 15,000
the definition of the prebiotics was narrowed with the and 15,000 sporulated oocysts, respectively. These
introduction of a prebiotic index by Roberfroid (2005), contradictory results are possibly explained by the
who stated that a preparation might be called prebiotic differences in MOS concentrations in feed and the
if it is capable to produce at least 4  108 colony- magnitude of Eimeria spp. inoculation doses.
forming units of Bifidobacteria/gram faeces per daily
dose (gram) ingested. Only three large groups meet this
criterion: inulin and oliogofructose, galactose 4.2.2.2. Probiotics. Lower intestinal invasion, devel-
oligosaccharides and xylooligosaccharides. opment of coccidia and oocyst production, explained
Probiotics consist of beneficial live bacteria or by enhanced local cell-mediated immunity, were
yeasts supplemented to the diet. According to the Food observed with a Lactobacillus-based probiotic supple-
and Agriculture Organization (FAO) and WHO pro- mented diet in E. acervulina-infected broilers (Dalloul
biotics are ‘live microorganisms, which when adminis- et al. 2003a, 2003b, 2005).
trated in adequate amounts confer a health benefit on More recently, in a study performed with a
the host’ (FAO/WHO 2002). The most frequently used Pediococcus-based commercial probiotic
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probiotics in humans are species of the genera (MitoGrowÕ ) given to birds infected with either
Lactobacillus and Bifidobacteria, whereas species of E. acervulina or E. tenella, increased resistance of
Bacillus, Enterococcus and Saccharomyces yeasts have birds against coccidiosis and a partial protection
been the most commonly used organisms in livestock. against growth retardation were demonstrated (Lee
In poultry production, probiotics are known for their et al. 2007a). In another study, performed with a
capacity to restore the intestinal microflora after being Pediococcus- and Saccharomyces-based probiotic
disrupted by antibiotic treatment or enteric infections (MitoMaxÕ ), less E. acervulina and E. tenella oocyst
(Rada and Rychly 1995; Line et al. 1998; Pascual et al. shedding and a better antibody response were found
1999). They are also known for their ability to boost (Lee et al. 2007b).
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). 5. Conclusions and perspectives
A treatment with prebiotics can be easily combined To date, coccidiosis control has relied mainly on
with a probiotic in a so-called ‘synbiotic’ approach chemoprophylaxis. However, the occurrence of resis-
(Gibson and Roberfroid 1995). An advantage of this tance, consumer concerns and the increasing regula-
combination is the improved survival of probiotics tions as well as possible upcoming bans on the use of
when given in a medium of prebiotics. The use of pre- anticoccidial drugs as feed additives, have prompted
and probiotics in poultry has been reviewed by the quest for alternative control strategies, amongst
Patterson and Burkholder (2003). which vaccines, phytotherapy, aromatherapy, pre- and
probiotics have been quite extensively studied. So far,
4.2.2.1. Prebiotics. Mannan oligosaccharides (MOS) live vaccines have proved to be the most solid and
are derived from the cell wall of the yeast successful anticoccidiosis alternative approach.
Saccharomyces cerevisiae and are widely used in Although a number of drawbacks are associated with
animal feed to promote gastrointestinal health and the production and use of live coccidiosis vaccines,
performance. MOS have been described as a prebiotic, their efficacy and ability to increase the sensitivity of
but are thought to block the binding of pathogens to Eimeria spp. isolates to anticoccidial drugs, have
mannan receptors on the mucosal surface and stimu- further stimulated their use. If the immunogenicity of
late the immune response (Spring et al. 2000). subunit vaccines can be improved, they could represent
In an experiment performed with coccidia, dietary the next generation of highly efficient and low-cost
MOS (1 g/kg feed) were able to reduce the severity of a anticoccidial strategies.
single E. tenella infection with 3500 or 5000 sporulated
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